Topical benzoyl peroxide for acne
Zhirong Yang
Yuan Zhang
Elvira Lazic Mosler
Jing Hu
Hang Li
Yanchang Zhang
Jia Liu
Qian Zhang
Corresponding author.
Collection date 2020.
Abstract
Background
Acne is a common, economically burdensome condition that can cause psychological harm and, potentially, scarring. Topical benzoyl peroxide (BPO) is a widely used acne treatment; however, its efficacy and safety have not been clearly evaluated.
Objectives
To assess the effects of BPO for acne.
Search methods
We searched the following databases up to February 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of relevant randomised controlled trials (RCTs) and systematic reviews.
Selection criteria
We included RCTs that compared topical BPO used alone (including different formulations and concentrations of BPO) or as part of combination treatment against placebo, no treatment, or other active topical medications for clinically diagnosed acne (used alone or in combination with other topical drugs not containing BPO) on the face or trunk.
Data collection and analysis
We used standard methodological procedures as expected by Cochrane. Primary outcome measures were 'participant global self‐assessment of acne improvement' and 'withdrawal due to adverse events in the whole course of a trial'. 'Percentage of participants experiencing any adverse event in the whole course of a trial' was a key secondary outcome.
Main results
We included 120 trials (29,592 participants randomised in 116 trials; in four trials the number of randomised participants was unclear). Ninety‐one studies included males and females. When reported, 72 trials included participants with mild to moderate acne, 26 included participants with severe acne, and the mean age of participants ranged from 18 to 30 years.
Our included trials assessed BPO as monotherapy, as add‐on treatment, or combined with other active treatments, as well as BPO of different concentrations and BPO delivered through different vehicles. Comparators included different concentrations or formulations of BPO, placebo, no treatment, or other active treatments given alone or combined. Treatment duration in 80 trials was longer than eight weeks and was only up to 12 weeks in 108 trials. Industry funded 50 trials; 63 trials did not report funding. We commonly found high or unclear risk of performance, detection, or attrition bias. Trial setting was under‐reported but included hospitals, medical centres/departments, clinics, general practices, and student health centres. We reported on outcomes assessed at the end of treatment, and we classified treatment periods as short‐term (two to four weeks), medium‐term (five to eight weeks), or long‐term (longer than eight weeks).
For 'participant‐reported acne improvement', BPO may be more effective than placebo or no treatment (risk ratio (RR) 1.27, 95% confidence interval (CI) 1.12 to 1.45; 3 RCTs; 2234 participants; treatment for 10 to 12 weeks; low‐certainty evidence). Based on low‐certainty evidence, there may be little to no difference between BPO and adapalene (RR 0.99, 95% CI 0.90 to 1.10; 5 RCTs; 1472 participants; treatment for 11 to 12 weeks) or between BPO and clindamycin (RR 0.95, 95% CI 0.68 to 1.34; 1 RCT; 240 participants; treatment for 10 weeks) (outcome not reported for BPO versus erythromycin or salicylic acid).
For 'withdrawal due to adverse effects', risk of treatment discontinuation may be higher with BPO compared with placebo or no treatment (RR 2.13, 95% CI 1.55 to 2.93; 24 RCTs; 13,744 participants; treatment for 10 to 12 weeks; low‐certainty evidence); the most common causes of withdrawal were erythema, pruritus, and skin burning. Only very low‐certainty evidence was available for the following comparisons: BPO versus adapalene (RR 1.85, 95% CI 0.94 to 3.64; 11 RCTs; 3295 participants; treatment for 11 to 24 weeks; causes of withdrawal not clear), BPO versus clindamycin (RR 1.93, 95% CI 0.90 to 4.11; 8 RCTs; 3330 participants; treatment for 10 to 12 weeks; causes of withdrawal included local hypersensitivity, pruritus, erythema, face oedema, rash, and skin burning), erythromycin (RR 1.00, 95% CI 0.07 to 15.26; 1 RCT; 60 participants; treatment for 8 weeks; withdrawal due to dermatitis), and salicylic acid (no participants had adverse event‐related withdrawal; 1 RCT; 59 participants; treatment for 12 weeks). There may be little to no difference between these groups in terms of withdrawal; however, we are unsure of the results because the evidence is of very low certainty.
For 'proportion of participants experiencing any adverse event', very low‐certainty evidence leaves us uncertain about whether BPO increased adverse events when compared with placebo or no treatment (RR 1.40, 95% CI 1.15 to 1.70; 21 RCTs; 11,028 participants; treatment for 10 to 12 weeks), with adapalene (RR 0.71, 95% CI 0.50 to 1.00; 7 RCTs; 2120 participants; treatment for 11 to 24 weeks), with erythromycin (no participants reported any adverse events; 1 RCT; 89 participants; treatment for 10 weeks), or with salicylic acid (RR 4.77, 95% CI 0.24 to 93.67; 1 RCT; 41 participants; treatment for 6 weeks). Moderate‐certainty evidence shows that the risk of adverse events may be increased for BPO versus clindamycin (RR 1.24, 95% CI 0.97 to 1.58; 6 RCTs; 3018 participants; treatment for 10 to 12 weeks); however, the 95% CI indicates that BPO might make little to no difference. Most reported adverse events were mild to moderate, and local dryness, irritation, dermatitis, erythema, application site pain, and pruritus were the most common.
Authors' conclusions
Current evidence suggests that BPO as monotherapy or add‐on treatment may be more effective than placebo or no treatment for improving acne, and there may be little to no difference between BPO and either adapalene or clindamycin. Our key efficacy evidence is based on participant self‐assessment; trials of BPO versus erythromycin or salicylic acid did not report this outcome.
For adverse effects, the evidence is very uncertain regarding BPO compared with adapalene, erythromycin, or salicylic acid. However, risk of treatment discontinuation may be higher with BPO compared with placebo or no treatment. Withdrawal may be linked to tolerability rather than to safety. Risk of mild to moderate adverse events may be higher with BPO compared with clindamycin.
Further trials should assess the comparative effects of different preparations or concentrations of BPO and combination BPO versus monotherapy. These trials should fully assess and report adverse effects and patient‐reported outcomes measured on a standardised scale.
Plain language summary
Topical benzoyl peroxide for acne
Review question
We reviewed the evidence showing effects and safety of topical benzoyl peroxide (BPO), used alone or in combination. Eligible comparisons included placebo (an identical but inactive treatment), no treatment, or other active (medical) topical medications for treating acne (used alone or in combination with other topical drugs not containing BPO) (evidence is current to February 2019).
The main outcomes of interest in this review were participant‐reported acne improvement and withdrawal from the study due to any side effects. More generally, we also considered the percentage of participants experiencing any side effects over the whole course of a trial.
Background
As a common skin disease, acne vulgaris affects the physical, mental, and social well‐being of millions of adolescents and young adults. A wide range of treatments for acne vulgaris are available, and topical BPO has been recommended as a priority therapy to be used alone or combined with other topical or oral treatments, depending on acne severity. However, the benefits and harms of BPO have yet to be evaluated.
Study characteristics
We included 120 studies (which comprised 29,592 people randomised in 116 trials; in four trials the number of randomised participants was unclear). Through our search, we found studies assessing different concentrations of BPO, BPO delivered through various means, or BPO used alone or given with other treatments that may or may not be considered as the primary treatment. These studies compared treatments against different concentrations or formulations of BPO, placebo, no treatment, or other medical treatments given alone or in combination.
Most of the studies included male and female participants with mild to moderate acne; only 67% of studies reported participant age, which ranged between 18 and 30 years. Participants were treated for over eight weeks in nearly two‐thirds of the trials. Industry financially supported approximately two‐fifths of the trials, and more than half of the trials did not report their funding sources. Few studies reported where they were set, but locations included hospitals, medical centres, national medical institutes, clinics, medical departments, and general practices.
Key results
We found low‐certainty evidence to suggest that long‐term (i.e. given for longer than eight weeks) BPO treatment may increase self‐reported treatment success compared to placebo or no BPO treatment (three studies), but there may be little to no difference when BPO treatment is compared to adapalene (five studies) or clindamycin (one study). This outcome was not reported by studies comparing BPO treatment to erythromycin or salicylic acid.
Long‐term BPO may lead to an increased chance of treatment discontinuation compared to placebo or no treatment (24 studies), with the most common causes being redness, itch, and skin burning (low‐certainty evidence). When medium‐ to long‐term BPO was compared to adapalene (11 studies), clindamycin (eight studies), erythromycin (one study), or salicylic acid (one study), we found only very low‐certainty evidence, meaning that although there may be little to no difference in withdrawal between these groups, we are not sure of the results. It should be noted that participant withdrawal may be linked to issues around treatment acceptability (dermatitis, rash, facial swelling, sensitivity) rather than to safety.
Very low‐certainty evidence means that we are uncertain if BPO leads to more side effects among participants receiving medium‐ to long‐term BPO than among those given no treatment/placebo (21 studies), adapalene (seven studies), erythromycin (one study), or salicylic acid (one study). Medium‐term treatment with BPO may lead to increased risk of side effects when compared against clindamycin, but the effects of this treatment vary, so the treatment chosen may make little to no difference (six studies; moderate‐certainty evidence). Side effects reported in these studies were usually mild to moderate, and the most common were local dryness, irritation, eczema, redness, pain at the site of application, and pruritus.
Certainty of the evidence
For our key comparisons, we rated the certainty of evidence for 'participant‐reported acne improvement' as low. For the outcomes 'withdrawal due to adverse effects' and ‘percentage of participants having any adverse events', the evidence was mainly of very low certainty.
Included trials were at high or unclear risk of bias, participant numbers were small, results were not consistent across trials, and we suspected publication bias.
Summary of findings
Summary of findings for the main comparison. Benzoyl peroxide compared to placebo or no treatment for acne.
| Benzoyl peroxide compared to placebo or no treatment for acne | ||||||
| Patient or population: acne vulgaris Setting: unspecified (probably outpatient) Intervention: benzoyl peroxide Comparison: placebo or no treatment | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with placebo or no treatmenta | Risk with benzoyl peroxide | |||||
| Participant's global self‐assessment of improvement (long‐term data) assessed with any greater improvement above the first category of improvement on a Likert or Likert‐like scale Treatment duration: range 10 weeks to 12 weeks | 550 per 1000 | 699 per 1000 (616 to 798) | RR 1.27 (1.12 to 1.45) | 2234 (3 RCTs) | ⊕⊕⊝⊝ Lowb | ‐ |
| Withdrawal due to adverse effects (long‐term data) Treatment duration: range 10 weeks to 12 weeks | 4 per 1000 | 8 per 1000 (6 to 11) | RR 2.13 (1.55 to 2.93) | 13,744 (24 RCTs) | ⊕⊕⊝⊝ Lowc | ‐ |
| Total number of participants with any adverse events (long‐term data) Treatment duration: range 10 weeks to 12 weeks | 79 per 1000 | 111 per 1000 (91 to 135) | RR 1.40 (1.15 to 1.70) | 11,028 (21 RCTs) | ⊕⊝⊝ ⊝ Very lowd | ‐ |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and therelative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio. | ||||||
| GRADE Working Group grades of evidence. High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | ||||||
aThe control group risk estimate is the median control group risk across studies.
bDowngraded by two levels to low‐quality evidence due to study limitations (risk of bias) and publication bias.Gold 2009 was classified as high risk of bias due to "incomplete outcome data". Although ITT strategy was taken, 14.3% of participants discontinued and withdrawal due to adverse events was higher in the adapalene‐BPO combination gel group. BothGold 2009 andLeyden 2001a were classified as "unclear risk of bias" for randomisation, allocation concealment, and blinding of participants and outcome assessors. InJawade 2016, the proportion of withdrawals was high and participants were excluded from analysis because of non‐compliance with the treatment regimen or duration and protocol violation. In addition, all studies were judged to be unclear for at least one risk of bias domain. There was potential risk of publication bias because we identified trials starting before 2015 but still "ongoing" as shown in the trial registries.
cDowngraded by two levels to low‐quality evidence due to study limitations (risk of bias). Ten studies were classified as “high risk of bias” for at least one risk of bias domain, includingGollnick 2009,Kawashima 2015, andXu 2016, for blinding of participants and healthcare providers;Gold 2009,Gollnick 2009,Jaffe 1989,Jawade 2016,Thiboutot 2007,Thiboutot 2008, andXu 2016 for incomplete outcome data; andChalker 1983 andJaffe 1989 for selective reporting of outcomes. In addition, all studies were judged to be unclear for at least one risk of bias domain. There was potential risk of publication bias because we identified trials starting before 2015 but still "ongoing" as shown in the trial registries.
dDowngraded by three levels to very low‐quality evidence due to study limitations (risk of bias) and inconsistency. Ten studies were classified as “high risk of bias” for at least one risk of bias domain, includingDraelos 2002,Gollnick 2009,Kawashima 2015,NCT02073461,Xu 2016, andZeichner 2013 for blinding of participants and healthcare providers;Gollnick 2009,Jaffe 1989,Kawashima 2015,Thiboutot 2007,Thiboutot 2008, andXu 2016 for incomplete outcome data; andChalker 1983 andJaffe 1989 for selective reporting of outcomes. All were classified as “unclear risk of bias” for at least one risk of bias domain. We further downgraded the evidence by one level because of inconsistency: point estimates varied, and I² was 72%. There was potential risk of publication bias because we identified trials starting before 2015 but still "ongoing" as shown in the trial registries.
Summary of findings 2. Benzoyl peroxide compared to adapalene for acne.
| Benzoyl peroxide compared to adapalene for acne | ||||||
| Patient or population: acne vulgaris Setting: unspecified (probably outpatient) Intervention: benzoyl peroxide Comparison: adapalene | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with adapalene | Risk with benzoyl peroxide | |||||
| Participant's global self‐assessment of improvement (long‐term data) assessed with any greater improvement above the first category of improvement on a Likert or Likert‐like scale Treatment duration: range 11 weeks to 12 weeks | 785 per 1000a | 777 per 1000 (707 to 864) | RR 0.99 (0.90 to 1.10) | 1472 (5 RCTs) | ⊕⊕⊝⊝ Lowb | ‐ |
| Withdrawal due to adverse effects (long‐term data) Treatment duration: range 11 weeks to 24 weeks | 2 per 1000a | 4 per 1000 (2 to 5) | RR 1.85 (0.94 to 3.64) | 3295 (11 RCTs) | ⊕⊝⊝⊝ Very lowc | ‐ |
| Total number of participants with any adverse events (long‐term data) Treatment duration: range 11 weeks to 24 weeks | 203 per 1000a | 144 per 1000 (101 to 203) | RR 0.71 (0.50 to 1.00) | 2120 (7 RCTs) | ⊕⊝⊝⊝ Very lowd | ‐ |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and therelative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio. | ||||||
| GRADE Working Group grades of evidence. High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | ||||||
aThe control group risk estimate is the median control group risk across studies.
bDowngraded by two levels to low‐quality evidence due to study limitations (risk of bias) as three studies were classified as "high risk of bias" for incomplete outcome data and one study for blinding of participants. InGold 2009, although ITT strategy was taken, 14.3% of participants discontinued and withdrawal due to adverse events was higher in the adapalene‐BPO combination gel group. Indo Nascimento 2003, comparing dropout rates between groups revealed that the adapalene group showed the higher rate of participants who withdrew from the study before completion of treatment. InJawade 2016, the proportion of withdrawal was high and participants were excluded from analysis because of non‐compliance with the treatment regimen or duration schedule and protocol violation. InHayashi 2018, only investigators, not participants, were blinded. There was potential risk of publication bias because we identified trials starting before 2015 but still "ongoing" as shown in the trial registries.
cDowngraded by three levels to very low‐quality evidence: one level due to study limitations (risk of bias) as eight included studies were classified as “high risk of bias” in at least one risk of bias domain.Hayashi 2018,Gollnick 2009,Iftikhar 2009, andKorkut 2005 were at high risk of bias due to unblinded or partially blinded design.do Nascimento 2003,Gold 2009,Gollnick 2009,Jawade 2016, andThiboutot 2007 were classified as high risk of bias for incomplete participant data. All included studies were classified as unclear for at least one risk of bias domain. Evidence was downgraded by a further one level due to imprecision as the confidence interval includes 1; could not exclude the possibility of no effect compared with adapalene. The estimate was based on a small number of events. There was potential risk of publication bias because we identified trials starting before 2015 but still "ongoing" as shown in the trial registries.
dDowngraded by three levels to very low‐quality evidence: one level due to study limitations (risk of bias) as four included studies were classified as “high risk of bias” in at least one risk of bias domain.Hayashi 2018 andGollnick 2009 were at high risk of bias due to unblinded or partially blinded design. Three trials ‐do Nascimento 2003,Gold 2009, andThiboutot 2007 ‐ were classified as high risk of bias for incomplete participant data. All included studies were classified as unclear for at least one risk of bias domain. Evidence was also downgraded by one level due to inconsistency as I² = 70% and point estimates were not similar. There was potential risk of publication bias because we identified trials starting before 2015 but still "ongoing" as shown in the trial registries.
Summary of findings 3. Benzoyl peroxide compared to clindamycin for acne.
| Benzoyl peroxide compared to clindamycin for acne | ||||||
| Patient or population: acne vulgaris Setting: unspecified (probably outpatient) Intervention: benzoyl peroxide Comparison: clindamycin | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with clindamycin | Risk with benzoyl peroxide | |||||
| Participant's global self‐assessment of improvement (long‐term data) assessed with any greater improvement above the first category of improvement on a Likert or Likert‐like scale Treatment duration: 10 weeks | 367 per 1000a | 348 per 1000 (249 to 491) | RR 0.95 (0.68 to 1.34) | 240 (1 RCT) | ⊕⊕⊝⊝ Lowb | ‐ |
| Withdrawal due to adverse effects (long‐term data) Treatment duration: range 10 weeks to 12 weeks | Low risk: 0 per 1000c | 0 per 1000 (0 to 0) | RR 1.93 (0.90 to 4.11) | 3330 (8 RCTs) | ⊕⊝⊝⊝ Very lowd | ‐ |
| High risk: 46 per 1000c | 89 per 1000 (41 to 189) | |||||
| Total number of participants with any adverse events (long‐term data) Treatment duration: range 10 weeks to 12 weeks | 73 per 1000a | 91 per 1000 (71 to 116) | RR 1.24 (0.97 to 1.58) | 3018 (6 RCTs) | ⊕⊕⊕⊝ Moderatee | ‐ |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and therelative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio. | ||||||
| GRADE Working Group grades of evidence. High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | ||||||
aThe control group risk estimate is the median control group risk across studies.
bDowngraded by two levels to low‐quality evidence: one level due to imprecision as the confidence interval is wide and includes 1; could not exclude the possibility of no effect compared with clindamycin. The estimate was based on a small number of events. One further level due to study limitations (risk of bias), asLeyden 2001a was classified as “unclear risk of bias” for most risk of bias domains because the report did not provide sufficient information to allow judgement.
cWe assume a range of risks according to risks in the control groups of included studies, where we expect different populations to experience different risks of events of interest. In this case, the lower limit of the risk is 0, and the upper limit is the highest control group risk in the included studies.
dDowngraded by three levels to very low‐quality evidence: two levels due to very serious imprecision as the confidence interval includes 1; could not exclude the possibility of no effect compared with clindamycin, and there were very few events. One further level due to study limitations (risk of bias) as seven of the included studies were classified as “unclear risk of bias” for most risk of bias domains because reports did not provide sufficient information to allow judgement. In addition, inDraelos 2002, the nurse may be aware of erythromycin/benzoyl peroxide treatment after randomisation. This study has a high proportion of withdrawal, and it is unclear whether numbers of withdrawals and corresponding reasons were balanced between groups. In addition, ITT analysis was not conducted. InThiboutot 2008, 10% of participants did not complete the treatment duration within each group and reasons were not balanced across groups. Besides, trial authors did not compare characteristics between participants who completed and discontinued treatment.
eDowngraded by one level to moderate‐quality evidence due to risk of bias as five included studies were classified as “unclear risk of bias” for most risk of bias domains because reports did not provide sufficient information to allow judgement. In addition, inDraelos 2002, the nurse may be aware of the erythromycin/benzoyl peroxide treatment after randomisation. This study has a high proportion of withdrawal, and it is unclear whether numbers of withdrawals and corresponding reasons were balanced between groups. In addition, ITT analysis was not conducted. InThiboutot 2008, 10% of participants did not complete the treatment duration within each group and reasons were not balanced across groups. Besides, trial authors did not compare characteristics between participants who completed and discontinued treatment.
Summary of findings 4. Benzoyl peroxide compared to erythromycin for acne.
| Benzoyl peroxide compared to erythromycin for acne | ||||||
| Patient or population: acne vulgaris Setting: unspecified (probably outpatient) Intervention: benzoyl peroxide Comparison: erythromycin | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with erythromycina | Risk with benzoyl peroxide | |||||
| Participant's global self‐assessment of improvement (long‐term data) ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | Neither long‐ nor medium‐term data for this outcome were reported |
| Withdrawal due to adverse effects (medium‐term data) Treatment duration: 8 weeks | 13 per 1000 | 13 per 1000 | RR 1.00 (0.07 to 15.26) | 60 (1 RCT) | ⊕⊝⊝⊝ Very lowb | ‐ |
| Total number of participants with any adverse events (long‐term data) Treatment duration: 10 weeks | See comment | See comment | Not estimable | 89 (1 RCT) | ⊕⊝⊝⊝ Very lowc | There were zero events in either group, so absolute risks and relative effect could not be calculated |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and therelative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio. | ||||||
| GRADE Working Group grades of evidence. High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | ||||||
aThe control group risk estimate is the median control group risk across studies.
bDowngraded by three levels due to serious risk of bias and very serious imprecision. We downgraded by one level due to risk of bias becauseBurke 1983 was a study without sufficient information in the report to allow judgement about risk of bias. InChalker 1983, trial authors did not provide sufficient information on randomisation and blinding, although they described this study as "randomised" and "double‐blind". We further downgraded by two levels due to very serious imprecision because of a very small number of events.
cDowngraded by three levels due to serious risk of bias and very serious imprecision. We downgraded by one level due to risk of bias because inChalker 1983, trial authors did not provide sufficient information on randomisation and blinding, although they described this study as "randomised" and "double‐blind". We further downgraded by two levels due to very serious imprecision because there were zero events in either group and the effect was not estimable.
Summary of findings 5. Benzoyl peroxide compared to salicylic acid for acne.
| Benzoyl peroxide compared to salicylic acid for acne | ||||||
| Patient or population: acne vulgaris Setting: unspecified (probably outpatient) Intervention: benzoyl peroxide Comparison: salicylic acid | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with salicylic acida | Risk with benzoyl peroxide | |||||
| Participant's global self‐assessment of improvement (long‐term data) ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | Neither long‐ nor medium‐term data for this outcome were reported |
| Withdrawal due to adverse effects (long‐term data) Treatment duration: 12 weeks | See comment | See comment | Not estimable | 59 (1 RCT) | ⊕⊝⊝⊝ Very lowb | No withdrawals in either group, so absolute risks and relative effect could not be calculated |
| Total number of participants with any adverse events (medium‐term data) Treatment duration: 6 weeks | 0 per 1000 | 0 per 1000 | RR 4.77 (0.24 to 93.67) | 41 (1 RCT) | ⊕⊝⊝⊝ Very lowc | There were zero events in the salicylic acid group and 2 events in the BPO group, so absolute risks could not be calculated |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and therelative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio. | ||||||
| GRADE Working Group grades of evidence. High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | ||||||
aThe control group risk estimate is the median control group risk across studies.
bDowngraded by three levels due to serious risk of bias and very serious imprecision. We downgraded by one level due to risk of bias because inBissonnette 2009, a high proportion (21/80) of participants withdrew from the trial. No information on comparisons of reasons for withdrawal between groups was available, with no ITT analysis being conducted. We further downgraded by two levels due to very serious imprecision because there were zero events in either group and the effect was not estimable.
cDowngraded by three levels due to serious risk of bias and very serious imprecision. We downgraded by one level due to risk of bias because the included study,Chantalat 2006, was classified as “unclear risk of bias” for most risk of bias domains because the report did not provide sufficient information to allow judgement. We further downgraded by two levels due to very serious imprecision because of the very small number of events.
Background
Description of the condition
Acne vulgaris is a common, chronic inflammatory disease of pilosebaceous units. It is characterised by increased sebum production and the formation of comedones, erythematous papules, pustules, and nodules, which may lead to scarring (Archer 2012).
For an explanation of the terminology used throughout the text, please refer to the glossary inTable 6.
1. Glossary of unfamiliar terms.
| Term | Definition |
| Acne inversa | A chronic disease of the apocrine glands occurring mainly in the axillae and in groin regions. It is caused by poral occlusion with secondary bacterial infection, evolving into abscesses that eventually rupture. The chronic phase is characterised by ulcers, sinus tracts, fistulas, fibrosis, and scarring |
| Acne vulgaris | Chronic acne involving mainly the face, chest, and shoulders, which is common among adolescents, and characterised by the intermittent formation of discrete papular and/or pustular lesions, sometimes resulting in scarring |
| Alpha‐hydroxy acids | Organic acids, such as glycolic, lactic, citric, and mandelic acids, containing a hydroxyl group bonded to the carbon atom adjacent to the carboxylic acid group. They are used in skin care preparations for their exfoliating properties |
| Androgen | A steroid hormone, such as testosterone or androsterone, that controls the development and maintenance of masculine characteristics. Androgens stimulate sebaceous glands to grow and produce sebum, and therefore cause acne |
| Azelaic acid | A natural material that kills bacteria in the skin and decreases the production of keratin. It is used to treat and prevent mild and moderate acne that is caused by bacteria |
| Bacterial resistance | The ability of bacteria to resist the effects of an antibiotic |
| Benzoyl peroxide | An organic compound in the peroxide family used for acne treatment. It works as a peeling agent. It increases skin turnover, clearing pores and reducing the bacterial count (specificallyC acnes) as well as acting directly as an anti‐microbial agent |
| Chloracne | An acneiform eruption due to exposure to chlorine compounds |
| Clindamycin | A lincosamide antibiotic, commonly used for topical treatment of acne |
| Colonisation | The presence of bacteria on a body surface (like on the skin, mouth, intestines or airway) without causing disease in the person |
| Comedolytic | The term used to describe a product or medication that inhibits the formation of comedones. Comedolytic products work by helping the skin to shed more effectively, keeping the pores from becoming plugged |
| Comedone | A blocked pore in the form of a yellow or black bump or plug on the skin |
| Corticosteroids | Any of a class of steroid hormones formed in the cortex of the adrenal gland or chemically similar synthesised hormones that have anti‐inflammatory properties |
| Cyst | A closed sac having a distinct membrane compared to nearby tissue, which may contain air, fluids, or semi‐solid material |
| Cytokines | A diverse group of soluble molecules important for cell signalling in the generation of an immune response, where they act as intercellular mediators or signalling molecules |
| Differentiation | The process by which a less specialised cell becomes a more specialised cell. |
| Drug‐induced acne | Acne caused or exacerbated by several types of drugs, such as anti‐epileptics, halogens, and steroids |
| Eczema | An acute or chronic non‐contagious inflammation of the skin, often caused by allergy and characterised by itching, scaling, and blistering |
| Erythema | Blanching reddening of the skin due to local vasodilatation |
| Erythromycin | A macrolide antibiotic, commonly used for topical treatment of acne |
| Hypercolonisation | Abnormal increase in the number of bacteria otherwise normally present on a body surface without causing disease in the person |
| Infantile acne | Acne that presents at the age of 2 to 6 months and persists until the age of 3 to 4 years |
| Keratinisation | The process of keratin production that forms an epidermal barrier in stratified squamous epithelial tissue |
| Microcomedones | Microscopic comedones, not visible to the naked eye |
| Nodule | A deep skin‐seated dome‐shaped solid lump |
| Occupational acne | Acne caused by exposure to extraneous agents or adverse conditions in a working environment. The agents and conditions that most commonly cause problems are oils, tars, and excessive humidity |
| Papule | Small, solid, raised lesion, usually dome‐shaped |
| Pilosebaceous unit | The hair follicle and sebaceous gland |
| Polycystic ovarian syndrome | A condition caused by the imbalance of female sex hormones. It is associated with absence of ovulation resulting in irregular menstrual cycles and infertility, insulin resistance causing obesity, and high levels of masculinising hormones causing excessive hair growth and acne |
| Pustule | A visible collection of pus |
| Reactive oxygen species | Chemically reactive molecules containing oxygen. Increased levels of reactive oxygen species may result in significant damage to cell structures, which is calledoxidative stress |
| Resorcinol | A dihydroxy benzene compound used in many acne treatment products. It helps prevent comedones by removing buildup of dead skin cells |
| Retinoids | A class of chemical compound related chemically to vitamin A, topically used for acne treatment due to the way they regulate epithelial cell growth |
| Rosacea | A chronic dermatitis of the face, especially of the nose and cheeks, characterised by a red or rosy colouration, caused by dilation of capillaries, and the appearance of acne‐like pimples |
| Sebaceous glands | Glands that produce sebum and deliver it to the surface of the skin. They are larger and greater in number on the face and upper parts of the trunk, which makes these the acne‐prone areas |
| Sebum | An oily substance produced by the sebaceous glands of the skin. Its main function is to protect and waterproof the hair and skin. Oily skin and acne are the result of excessive sebum production |
| Scar | The fibrous tissue replacing normal tissues destroyed by injury, disease, or surgery |
| Sodium sulphacetamide | A sulphonamid antibiotic used topically for fighting bacteria on the skin in the treatment of acne, dandruff, and seborrhoeic dermatitis |
| Tetracycline | A broad‐spectrum antibiotic synthesised from chlortetracycline or derived from certain micro‐organisms of the genusStreptomyces |
| Topical therapy | A medication in the form of a cream, foam, gel, lotion, or ointment that is applied to body surfaces to treat ailments |
Epidemiology
Acne vulgaris affects nearly all adolescents and adults at some time in their lives (Webster 2002). It is estimated that up to 40 to 50 million individuals in the USA have acne, with an 85% prevalence in those aged 12 to 24 years (Bhate 2013;White 1998). Moderate to severe acne constitutes 15% to 20% of all cases (Bhate 2013;Dréno 2010;Law 2010;Wei 2010). Girls are likely to suffer from acne earlier than boys (Archer 2012), but boys appear to be more susceptible to the disease (Halvorsen 2011). Acne may decrease with age, but 64% of people aged 20 to 29 years and 43% of people aged 30 to 39 years may still have visible acne (Bhate 2013;Schäfer 2001). Globally, acne is the second most disabling skin disease after eczema (Murray 2012).
Pathogenesis
Multiple factors are involved in the development of acne. An increased level of androgens at puberty, greater sebum production, and abnormal hyperproliferation of keratinocytes lead to the development of small microscopic lesions called microcomedones. In this lipid‐rich and anaerobic environment,Cutibacterium acnes (C acnes, formerlyPropionibacterium acnes), which is present in normal follicles, proliferates abnormally. Conventionally, it is believed that abnormal colonisation ofP acnes initiates the production of inflammatory and chemotactic mediators, which drives the inflammatory processes (Brown 1998;Burkhart 1999;Cunliffe 2000;Gollnick 2003). Evidence also suggests that involvement of inflammation at all stages of acne development (Jeremy 2003;Tanghetti 2013), as well as the exact sequence of events and the interaction between these events and other possible factors (genes, diet, smoking, sunlight, etc), remains unclear (Williams 2012).
Diagnosis and outcome measures
Clinical diagnosis of acne is usually straightforward. The condition tends to affect the face (99%), the back (60%), and the chest (15%) (Archer 2012), where the lesions are comedones (whiteheads and blackheads), which are non‐inflamed lesions (Simpson 2008). Inflammatory lesions such as papules, pustules, nodules, and cysts may develop after non‐inflamed lesions appear (Layton 2010). Papules and pustules are superficial lesions, but they may evolve into deep pustules or nodules in more severe forms of the disease. In conglobate acne, suppurative nodules can extend deeply and over larger areas, leading to exudative sinus tracts and tissue destruction, resulting in extensive and disfiguring scarring.
Classification of acne severity at the time of diagnosis is important because guidelines for subsequent treatment are based on the severity of disease (Nast 2012;Strauss 2007;Thiboutot 2009). Acne can be assessed and subsequently classified from two perspectives: as an objective disease activity based on measurement of the visible signs of acne by an investigator, or as a patient assessment of the impact of the condition on their quality of life (Nast 2012). More than 25 acne assessment scales have been described, and they are inconsistently used across different trials (Lehmann 2002). This does not allow a direct comparison of the results of separate trials (Nast 2012;Zarchi 2012). Additionally, grading is a subjective measure that may vary from one dermatologist to another (Ramli 2012). In clinical trials, assessment of the severity of acne before and after the intervention is essential to determine the therapeutic effect (Zarchi 2012). Grading and lesion counting appear to be most frequently used for this purpose (Zarchi 2012), as is described in the revised Leeds acne grading system, which includes numerical grading systems for the back and chest, as well as for the face (Lehmann 2002).
Description of the intervention
Treatments for acne target the pathophysiological processes, and a wide range of topical and systemic treatments are currently available (Katsambas 2004). Topical therapies, including benzoyl peroxide (BPO), tretinoin, antibiotics, and salicylic acid, can be used for non‐inflammatory comedones or mild to moderate inflammatory acne (Strauss 2007;Thiboutot 2009). The underlying mechanism can be action primarily against comedones (retinoids and salicylic acid) or against inflammatory lesions (antibacterials and antibiotics).
BPO is an oxidising agent that is bactericidal forC acnes. Besides its primary bactericidal effect onC acnes, BPO has mild anti‐inflammatory, as well as comedolytic, activity (Patel 2010;Strauss 2007). Treatment of acne vulgaris with BPO alone or in combination with other topical treatments (antibiotics, retinoid, salicylic acid, or zinc) at concentrations of 2% to 5% is the standard of care for mild to moderate acne (Bojar 1994;Dutil 2010;Gollnick 2003;Lookingbill 1997;Strauss 2007). The most common fixed‐combination products containing BPO are BPO with clindamycin, erythromycin, or adapalene (Layton 2009;Taylor 2004). Besides BPO, other potentially efficient over‐the‐counter agents for acne treatment include azelaic acid, alpha‐hydroxy acids, resorcinol, sulphur, and zinc, but evidence of their effectiveness from randomised controlled clinical trials and studies comparing their efficacy with other topical treatments is lacking.
An increasingly wide range of non‐drug‐based approaches have been developed for treating acne, among which low‐concentration chemical peels with glycolic, salicylic, or trichloroacetic acid are beneficial for reduction of comedones (Kempiak 2008;Rendon 2010). In addition, comedo extractions, light electrocautery, electrofulguration, and cryotherapy present other therapeutic options for comedonal acne. In addition, acne can be treated by photodynamic therapy, utilising topical 5‐aminolevulinic acid together with various light sources (e.g. blue, red, intense pulsed) or lasers (e.g. pulsed dye, 635‐nm red diode), as well as methyl aminolevulinate plus red light. Blue or intense pulsed light alone and lasers such as pulsed dye, the 1320‐nm neodymium: yttrium‐aluminum‐garnet (YAG), and especially the 1450‐nm diode may be of therapeutic benefit for inflammatory acne (Rai 2013). For deep, inflamed nodules and cysts, intralesional injections of corticosteroids, such as triamcinolone acetate, are beneficial (Levine 1983;Strauss 2007). Besides, some plant extracts (such as tea tree oil,Casuarina equisetifolia, Zimade Muhasa, green tea polyphenols, and resveratrol) and synthetic chemicals (such as isolutrol and superoxidised solution) are available for cosmetic use or as medicine for acne given their potential anti‐bacterial, anti‐inflammatory, or anti‐oxidant activities.
Commercially available over‐the‐counter preparations of BPO include gels, creams, lotions, soaps, and washes, ranging from 2.5% to 10% in concentration (Strauss 2007;Zaenglein 2006). The choice of vehicle depends largely on skin type and the patient's preference (Brown 1998). Irritant dermatitis (erythema, scaling, burning, and itching) is the primary limitation of BPO for some people; this primarily occurs within the first few days of treatment but generally subsides with continued use (Gollnick 2003;Sagransky 2009). However, when in contact with hair, clothing, and other fabrics, BPO can cause bleaching (Bojar 1995;Sagransky 2009).
How the intervention might work
BPO acts through three fundamental mechanisms: it is bactericidal toC acnes, it has mild comedolytic and anti‐inflammatory properties (Dutil 2010;Patel 2010;Strauss 2007), and it is lipophilic, concentrating inside the sebaceous follicles to produce benzoic acid and reactive oxygen species. By oxidising bacterial proteins, BPO can inhibit protein and nucleotide synthesis and mitochondrial activity (Dutil 2010;Fakhouri 2009;Krakowski 2008). The response to BPO appears to be rapid; it has been shown that significant reductions in surface and follicular micro‐organisms may be obtained after 48 hours' treatment with 5% BPO in aqueous gel (Bojar 1995), and clinical improvement has been noted as early as five days after the start of treatment (James 2005). A significant reduction inC acnes is seen within 20 hours of a single application of 5% BPO in solution, which implies that the vehicle in topical therapy is important (Ramirez 2006).
The action mechanisms of BPO are considered complementary to antibiotics (reducing inflammation andC acnes counts) and retinoids (reducing sebum production and keratinisation); their combinations may thus contribute to the synergistic activity. The combination therapy can be prescribed as separate products used together or as fixed combinations in a single product, with the former being less expensive and the latter potentially enhancing patient compliance and adherence (Gamble 2012). However, no evidence has demonstrated that combination therapy as separate products is superior or inferior to a fixed combination (Gamble 2012). Topical monotherapy with antibiotics is no longer recommended due to the risk of developing antibiotic resistance (Patel 2010).
Resistance toC acnes, which commonly develops during monotherapy with topical antibiotics, has not been reported with BPO because of its direct toxicity toC acnes, which is due to its ability to inhibit bacterial protein and nucleotide synthesis, metabolic pathways, and mitochondrial activity (Dutil 2010). This mechanism allows BPO to be used as long‐term therapy for acne, either as monotherapy or in combination with topical antibiotics, without the hazard of development of bacterial resistance. However, any relationship between skin colonisation with antibiotic‐resistantC acnes and treatment outcomes remains unclear.
Besides topical antibiotics, topical retinoids (adapalene and tazarotene) are frequently used as combination therapy with BPO. Retinoids regulate the differentiation and proliferation of keratinocytes and have an anti‐inflammatory effect (Chivot 2005;Williams 2012). Because BPO oxidises retinoids if applied simultaneously, it has been suggested that BPO should be used in the morning and the retinoid at night to minimise any possible interaction (Gollnick 2003;Kraft 2011). However, modern formulations allow the stable combination of topical retinoids and BPO (Tan 2009).
Why it is important to do this review
Effective treatment of individuals with this condition is important. Acne is a common skin disease in adolescence that can cause psychological harm to an individual and the possibility of long‐term scarring. It also involves an economic burden.
More than half of people with acne may experience shame, embarrassment, anxiety, lack of confidence, and impaired social contact (Bach 1993;Cunliffe 1986;Jowett 1985). Severe acne may increase anger and anxiety (Layton 2010). Acne itself induces stress, which may also exacerbate the condition (Archer 2012). Furthermore, acne episodes impose a financial burden on healthcare providers as well as the individuals themselves: an acne episode costs a total of USD690 on average, ranging from USD360 to USD870 (Gamble 2012;Yentzer 2010). The average cost of a 30‐day supply of a topical treatment depends on the drugs but ranges from USD21 to more than USD100, and generic BPO costs USD21 to USD60 per 30‐day course of treatment (Gamble 2012;Krakowski 2008). The annual direct cost of acne management is over USD2.5 billion, and among skin diseases, it ranks second only to the cost of treating skin ulcers and wounds (Bickers 2006).
Multiple treatments for acne have been developed, among which topical BPO has been recommended for first‐line treatment of acne and is one of the least costly acne therapies. Current evidence‐based clinical guidelines have recommended BPO as monotherapy or combined with adapalene or with clindamycin for mild to moderate acne, or in conjunction with a topical retinoid and/or systemic antibiotic therapy for moderate to severe acne (Asai 2016;Nast 2016;Oon 2019;Zaenglein 2016).
Several relevant systematic reviews (or meta‐analyses) were conducted for BPO versus placebo (Lamel 2015;Seidler 2010), BPO versus adapalene (Kolli 2019), BPO versus clindamycin (Seidler 2010), BPO/adapalene versus placebo (Dressler 2016;Gold 2016a;Kolli 2019;Zhou 2014), BPO/adapalene versus adapalene (Kolli 2019), BPO/clindamycin versus placebo (Seidler 2010), BPO/clindamycin versus adapalene (Kolli 2019), BPO plus salicylic acid versus placebo (Seidler 2010), BPO plus salicylic acid versus clindamycin (Seidler 2010), and BPO 10% versus 5% versus 2.5% (Fakhouri 2009). However, none of these reviews has provided a comprehensive picture of evidence on the comparative effects of BPO (as monotherapy or add‐on treatment) versus other topical treatments for acne. Most of these reviews had some major issues of conduct and reporting quality, including incomprehensive literature search, lack of risk of bias assessment, neglect of treatment duration, and/or incorrect method for evidence synthesis.
A comprehensive and transparent assessment of the efficacy and safety of topical BPO treatment for acne is important, and this is what we planned to do in our Cochrane Review. We did not apply any restriction on the concentration of BPO nor on the treatment duration, in the hope of providing sufficient evidence to inform physicians when treating people with this skin condition.
Plans for this review were published as a protocol titled "Topical benzoyl peroxide for acne" (Yang 2014).
Objectives
To assess the effects of benzoyl peroxide for acne.
Methods
Criteria for considering studies for this review
Types of studies
We considered randomised controlled trials (RCTs) with a parallel or cross‐over design eligible for our review. We included only the first‐phase data from cross‐over trials because of the possibility that the effects of the acne interventions may carry over to subsequent periods. For parallel design, if participants were re‐randomised to assess the maintenance effect upon completion of the first phase of a trial, the second‐phase data after re‐randomisation were excluded in light of the possibility of carry‐over effects from the first phase. Although split‐face design was also included, data from this kind of study were not combined with those from studies of parallel or cross‐over design but were only summarised narratively based on potential correlated effects within individuals in split‐face design. For studies simultaneously analysing individual participant data from two or more trials, we considered each trial as an independent study.
Types of participants
We considered participants with a clinical diagnosis by a healthcare practitioner of acne vulgaris on the face or trunk, regardless of age, gender, severity, setting, and previous treatment. We excluded studies in which individuals were diagnosed with rosacea, chloracne, acne inversa, infantile acne, occupational acne, drug‐induced acne, or acne associated with polycystic ovary syndrome. We included the study reporting the most complete data only when the same population or subsets of the same population were investigated in multiple studies.
Types of interventions
We included BPO of any treatment regimen (including wash‐off and leave‐on), dose, duration, and vehicle (e.g. gel, cream, lotion), used alone or as an ingredient in any combination treatment.
We made comparisons between BPO (used alone or in combination with other active topical treatment) versus placebo, no treatment, and other active topical pharmacological treatments (such as retinoids, antibiotics, azelaic acid, salicylic acid, etc., used alone or in combination with other topical drugs not containing BPO). We also made comparisons between different formulations and concentrations of BPO when available. We did not consider comparisons with any multi‐step regimens (usually including cleanser, toner, and moisturiser) involving multiple active ingredients with different formulations and concentrations. We also excluded comparisons between different brand products of the same formulation and concentration of BPO. We allowed other topical or oral co‐interventions if they were offered equivalently to both groups in the trial.
Types of outcome measures
We considered short‐term (two to four weeks), medium‐term (five to eight weeks), and long‐term (longer than eight weeks) treatment duration for each outcome. Besides the long‐term outcomes, we were interested in shorter treatment periods given that they can indicate early improvement, which may encourage participants to continue the treatments. As the time units used in different studies may vary from day to week to month, we stipulated that four weeks is roughly equivalent to 30 days or one month when we analysed the outcome data. When there was more than one follow‐up point within the same period, we extracted and analysed the data collected at the latest time point.
Primary outcomes
Participant global self‐assessment of acne improvement. Treatment success was defined as any greater improvement above the first category of improvement on a Likert or Likert‐like scale. For example, if there is a 5‐point Likert‐like scale ‐ much worse, worse, same, improved, much improved ‐ we counted "much improved" as treatment success. For a similar 6‐point scale, we compared everything better than "improved" versus the rest
Withdrawal due to adverse events over the whole course of a trial
Secondary outcomes
Investigator‐assessed absolute or percentage change in lesion counts (total (TL), inflamed (IL), and non‐inflamed (NIL) lesions, separately) from baseline to the last available evaluation. If the change in lesion counts with its standard deviation was not available from the publication or from liaisons with study authors, we described in the review the lesion counts at the last available evaluation
Percentage of participants rated 'clear' or 'almost clear' on the Investigator Global Assessment (IGA) scale of acne severity
Change in quality of life (assessed with a validated instrument such as Skindex‐16, Skindex‐29, or Cardiff Acne Disability Index)
Reduction inC acnes strains (total and resistant)
Percentage of participants experiencing any adverse events over the whole course of a trial
Search methods for identification of studies
We aimed to identify all relevant RCTs regardless of language or publication status (published, unpublished, in press, or in progress).
Electronic searches
The Cochrane Information Specialist searched the following databases up to 28 February 2019 using strategies based on the draft strategy for MEDLINE in our published protocol (Yang 2014).
Cochrane Skin Group Specialised Register via the search strategy inAppendix 1.
Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 2), in the Cochrane Library, via the strategy inAppendix 2.
MEDLINE via Ovid (from 1946) via the strategy inAppendix 3.
Embase via Ovid (from 1974) via the strategy inAppendix 4.
Latin American and Caribbean Health Science Information database (LILACS) (from 1982) via the strategy inAppendix 5.
Trials registers
We (ZY) searched the following trials registers up to 28 February 2019. Search strategies for each register are presented inAppendix 6.
International Standard Randomized Controlled Trials Number (ISRCTN) registry (www.isrctn.com).
ClinicalTrials.gov (www.clinicaltrials.gov).
Australian New Zealand Clinical Trials Registry (www.anzctr.org.au).
World Health Organization International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch/).
EU Clinical Trials Register (www.clinicaltrialsregister.eu).
Searching other resources
References from published studies
We checked the bibliographies of included primary studies and related systematic reviews for further references to relevant trials.
Unpublished literature
We attempted to identify unpublished studies and grey literature through correspondence with study authors and pharmaceutical companies. We also requested missing data or clarification on the primary outcomes and confirmation of duplicates.
Adverse effects
We did not perform a separate search for adverse effects of the target intervention. However, we critically examined data on adverse effects and the methods used to collect these from the included studies.
Data collection and analysis
We included 'Summary of findings' tables in our review to summarise the primary outcomes and the secondary safety outcome for the main comparisons, which included comparisons between BPO or BPO fixed combination treatments and placebo or other active treatments, and comparisons between different concentrations of BPO.
Selection of studies
Two review authors (ZY, ELM) examined the titles and abstracts of each reference retrieved through the search to determine those potentially related to our review. Based on this first assessment, we then obtained the full texts of these articles to ascertain further whether they should be included in our review. Throughout this process, we selected studies independently and resolved any disagreements by consultation with a third review author (YZ). We recorded the reasons for exclusion of each study and drew a PRISMA flow chart of study selection (Liberati 2009;Moher 2009).
Data extraction and management
We pre‐designed a data extraction form (Appendix 7). Using a piloted data extraction form, two review authors (ZY, YZ) independently extracted the data from the full text of eligible studies, with any disagreements resolved by a third review author (HL). We compiled the following information from the included studies.
Publication details (e.g. year, country, authors, registration number).
Study objectives.
Study design.
Setting, inclusion and exclusion criteria.
Population characteristics (e.g. age, gender, severity of the acne).
Details of the intervention (e.g. regimen, concentration, duration, co‐interventions).
Outcome measures and corresponding data.
Treatment duration.
Type of data analyses (e.g. intention‐to‐treat (ITT)).
When outcome data, for example, the change in acne lesions, were presented only in a figure in a published article, we extracted data from the figure using a Java programme called "Plot Digitizer" (Plot Digitizer). Although most of the trial registration numbers were not published in the journal articles, we matched the articles and the numbers from trial registries by examining the similarity in population characteristics, interventions compared, and sample sizes specified in the articles and registration records. We used all the above information to populate theCharacteristics of included studies table for each included study (Appendix 7).
Assessment of risk of bias in included studies
Independently, two review authors (ZY, JH) performed assessment of risk of bias using the Cochrane tool (Higgins 2011). If necessary, we resolved disagreements through discussion with a third review author (YCZ).
We assigned 'low', 'high', or 'unclear' risk of bias for each of the following 'Risk of bias' domains based on the judgement criteria (Appendix 7) (Higgins 2011).
Random sequence generation.
Allocation concealment.
Blinding of participants and personnel.
Blinding of outcome assessment.
Incomplete outcome data.
Selective outcome reporting.
Other sources of bias.
Measures of treatment effect
We expressed dichotomous outcomes as risk ratios (RRs), with 95% confidence intervals (CIs). We expressed continuous outcomes as mean differences (MDs), with 95% CIs. We presented RR or MD only for the outcomes of interest in this review.
Unit of analysis issues
When we included cross‐over trials, we included only the first phase of the intervention, as we expected that interventions for acne may have a lasting effect and minimal data were available on the effectiveness of wash‐out periods for the treatment. In the case of within‐participant studies (split‐face design), in which different treatments had been allocated to different body parts, we considered the body part as a unit of analysis and described the data separately.
Dealing with missing data
We contacted the authors of the included trials to attempt to acquire the missing information (Appendix 8). We conducted ITT analysis when data were available, in which case we analysed all participants in the group to which they were allocated, regardless of whether or not they received the allocated intervention. When we failed to obtain missing data for ITT analysis, we used the method of last observation carried forward for continuous data if available in the trials. For dichotomous data, we assumed that none of the missing participants experienced the outcome event. For example, when we assessed the primary outcome of participant global self‐assessment of acne improvement, those who did not provide data for this outcome would be regarded as experiencing treatment failure.
Assessment of heterogeneity
We assessed statistical heterogeneity using the I² statistic and the thresholds provided in theCochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We planned to explore potential sources of heterogeneity through pre‐specified subgroup analyses, which we had suggested underSubgroup analysis and investigation of heterogeneity.
Assessment of reporting biases
We generated funnel plots using the log of the effect measure for individual studies by its standard error to assess reporting bias for each primary outcome and for the secondary safety outcome if more than 10 studies were included in the meta‐analysis. Additionally, we performed Egger's test for assessment of publication bias using STATA (Egger 1997). Due to the limited number of included studies for most of the outcomes in all comparisons, we created a funnel plot and performed Egger's test only for the safety outcomes (long‐term data) for BPO versus placebo or no treatment and for BPO versus adapalene.
Data synthesis
We expected that clinical heterogeneity would exist across included studies, mainly because of the various tools used for grading acne and the various concentrations and vehicles of benzoyl peroxide employed, which may introduce differences in treatment effects across studies. Therefore we used a random‐effects model a priori for data synthesis for all outcomes.
For dichotomous outcomes, we pooled RRs and corresponding 95% CIs from individual studies. For continuous outcomes, we pooled MDs and corresponding 95% CIs from individual studies. When data provided in a trial were not sufficient to estimate RR or MD, we described the results only as presented by trial authors.
We made only direct comparisons; we did not perform indirect comparisons because we expected that an assumption of consistency was invalid in the current therapeutic field of acne. We did not analyse outcomes that were not considered in our review, but we described them in a narrative way in the tables (included studies) if any were reported in an included trial report.
Subgroup analysis and investigation of heterogeneity
We planned to perform exploratory subgroup meta‐analyses (if each subgroup included at least three studies) to assess whether treatment effects were different between subgroups. Possible factors for which we planned to conduct subgroup analysis included the following.
Disease factors at baseline.
Site.
Severity.
Treatment factors.
Concentration.
Vehicle.
Co‐intervention.
However, none of the comparisons met the prerequisite (each subgroup including at least three studies) for the subgroup analysis. For post hoc analysis, we conducted subgroup analyses only to explore whether the effects of BPO would differ with different co‐interventions, regardless of the number of trials included in a specific comparison. We conducted a Q test to examine the differences between subgroups.
Sensitivity analysis
If possible (i.e. if at least three studies were included in a meta‐analysis), we planned to perform exploratory sensitivity analyses to examine treatment effects by excluding studies of low methodological quality (more than three items rated as 'high risk' or 'unclear risk' based on the Cochrane tool for assessing risk of bias). As per our protocol, however, we conducted only two sensitivity analyses for the secondary safety outcome in the two main comparisons (BPO versus placebo or no treatment and BPO versus adapalene) because numbers of trials for all other outcomes were small and/or most of the included studies were rated as having low methodological quality for each comparison.
When applicable, we also conducted a sensitivity analysis post hoc for the primary outcome 'participant‐self reported acne improvement' in the main comparisons by including all studies that reported data for this outcome when applicable, regardless of the scales and criteria used in the included studies to determine improvement.
Quality of the evidence
We used the GRADE approach to assess the quality of evidence for the following outcomes: participant global self‐assessment of acne improvement, withdrawal due to adverse events, and percentage of participants experiencing any adverse event (Schünemann 2013). Long‐term outcomes were of primary interest; when long‐term data for an outcome were not available, we summarised the quality of evidence for the medium term. We developed 'Summary of findings' (SoF) tables for the most important comparisons using the GRADEpro Guideline Development Tool in consideration of five aspects (GRADEpro GDT 2015): study limitations, consistency, imprecision, indirectness, and publication bias.
We deemed the following comparisons the most important:
benzoyl peroxide compared to placebo or no treatment;
benzoyl peroxide compared to adapalene;
benzoyl peroxide compared to clindamycin;
benzoyl peroxide compared to erythromycin; and
benzoyl peroxide compared to salicylic acid.
Results
Description of studies
We summarised trial characteristics in theCharacteristics of included studies tables for eligible trials with published results; in theCharacteristics of studies awaiting classification tables for trials that were completed but with no published results, or trials whose eligibility could not be confirmed based on available abstracts; in theCharacteristics of ongoing studies tables for potentially eligible ongoing trials; and in theCharacteristics of excluded studies tables for each trial that we excluded based on the published full text.
Results of the search
Searches of the five databases (seeElectronic searches) yielded 627 records. Our searches of trial registries revealed 221 further studies, of which 87 duplicates were removed. Our searches of other resources revealed three additional studies that met the inclusion criteria. We therefore had a total of 764 records.
We excluded 381 records based on review of titles and abstracts. We obtained full texts of the remaining 383 records. We excluded 127 studies (seeCharacteristics of excluded studies), classified 43 studies reported in 46 records as awaiting classification (seeCharacteristics of studies awaiting classification), and identified 22 ongoing studies (seeCharacteristics of ongoing studies).
We included 120 studies reported in 188 references. For a further description of our screening process, please see the study flow diagram (Figure 1).
1.
Study flow diagram.
Included studies
We included a total of 120 randomised controlled trials (188 reports), with 29,592 people randomised in 116 trials; the numbers randomised in four trials were unclear (Chantalat 2005;Del 2009a;Lookingbill 1997;Makino 2015). Of these 120 included studies, 73 studies contributed to the quantitative analysis. For specific details about each study, please refer to theCharacteristics of included studies tables.
Design
Of these 120 trials, one used a cross‐over design (Shalita 1989), and nine were of split‐face (within‐individual) design (Bikowski 2006;Dreno 2016;Dréno 2018;Fyrand 1986;Goreshi 2012;NCT00787943;NCT01522456;Prince 1982;Zheng 2019). The other 110 trials employed a parallel design. The included trials consisted of 78 two‐arm trials, 24 three‐arm trials, 16 four‐arm trials, one five‐arm trial, and one six‐arm trial. Treatment duration was longer than eight weeks in 80 trials and was only up to 12 weeks in 108 trials, with a median of 12 weeks (minimum 2 weeks; maximum 52 weeks). Total trial duration was equivalent to the treatment duration.
Sample sizes
We noted a huge difference in the numbers of participants in the included studies, ranging from 8 to 2813.
Participants
Seventy‐two trials clearly reported that included participants had mild or moderate acne, or both. Severe acne was included in 26 trials (severity was unclear in the other trials). Ninety‐one trials mentioned that both male and female participants were included, and two trials included females only; the sex ratio in the remaining studies was unclear. Among 80 trials reporting age, 71 described mean age ranging from 18 to 30 years. Most trials excluded (1) pregnant or lactating females, and (2) those using topical or oral anti‐acne medication within a certain period before randomisation. Of 16 trials reporting duration of acne, 12 specified mean duration between 2.1 and 6.8 years, and the other four reported the ranges of individuals' duration (more than 6 months, 1 month to 7 years, 2 months to 17 years, and 5 to 6 years, respectively).
Interventions
BPO‐related topical treatments assessed in comparisons included the following.
BPO used as monotherapy or as add‐on treatment (21 comparisons).
BPO fixed combination treatment used as monotherapy or as add‐on treatment (19 comparisons).
Different BPO concentrations (five comparisons).
Different BPO vehicles (four comparisons).
Our included studies evaluated many different comparators. The most common comparators were different concentrations or formulations of BPO or placebo/no treatment. Antibiotics alone or in combination with other active treatment, topical retinoids, acids, and herbal medicines were comparators in our included studies, as were other miscellaneous topical treatments assessed in a few included trials, such as sulphur, chloroxylenol/salicylic acid, and viaminate.
Concentrations of BPO in included products ranged from 2.5% to 20%, with 2.5% and 5% being the most common concentrations, as assessed in 27 and 66 trials, respectively. Gel was the most common formulation and was used in 92 trials. Only six trials assessed wash‐off BPO medications. Investigational BPO products were reported to be used once or twice daily, in 64 and 45 trials, respectively. BPO/adapalene, BPO/clindamycin, and BPO/erythromycin were the most common fixed combination treatments assessed in included trials. We summarised all comparisons underEffects of interventions.
Co‐interventions
A total of 33 trials reported that co‐interventions were used across all the groups. Among these trials, 18 trials only used non‐medicated co‐interventions, which could include mild soap/cleanser or moisturiser or sunscreen or both. Active anti‐acne treatments were given as co‐interventions in 15 trials. These co‐interventions included topical treatments (adapalene, clindamycin, tretinoin, tazarotene, dapsone, and nadifloxacin) and oral treatments (doxycycline and lymecycline). In six of these 15 trials, participants additionally received non‐medicated co‐interventions.
Outcomes
Of the 120 included trials, 113 reported at least one outcome of interest in this review.
Primary outcomes
Participant global self‐assessment of acne improvement
A total of 39 trials addressed this outcome. Of these, 33 used Likert or Likert‐like scales, with categories/points ranging from 3 to 7. One trial used a 100‐mm visual analog scale (Miyachi 2016). In the other five studies, it was unclear which method was used (Chantalat 2006;Cunliffe 2002;Makino 2015;Tung 2014;Zeng 2012). This outcome was assessed at the end of treatment duration in all of these trials (ranging from 4 weeks to 16 weeks), with repeat measurements conducted in four trials (Hayashi 2018;Langner 2007;Pariser 2014;Schaller 2016). All four trials evaluated this outcome at weeks 2, 4, 8, and 12, and two trials additionally measured the outcome after the first week of treatment (Hayashi 2018;Langner 2007).
Withdrawal due to adverse events
A total of 68 trials reported how many participants withdrew due to adverse events. This outcome was monitored throughout the whole course of the trials.
Secondary outcomes
Investigator‐assessed absolute or percentage change in lesion counts
A majority of trials (97/120) provided the number of absolute or percentage change in lesion counts for at least one lesion type. All of these trials evaluated the change from baseline at the end of treatment duration (ranging from 3 weeks to 52 weeks), among which 91 trials repeatedly measured the outcome, with the intervals between two measurements ranging from one to four weeks. It was unclear whether repeated measurements were conducted in the other six studies, in which only the last measurement was reported (NCT01044264;NCT01138514;NCT01231334;NCT02073461;NCT02465632;Study 152).
Percentage of participants rated 'clear' or 'almost clear' on the Investigator Global Assessment (IGA) scale of acne severity
A total of 25 trials assessed this outcome. The outcome was assessed at the end of treatment duration in all of the trials (ranging from 6 weeks to 24 weeks). Of 22 trials reporting repeat measurements of this outcome, 15 trials provided results for each measurement (Dreno 2011;Dréno 2018;Eichenfield 2013;Gold 2009;Gold 2010;Gollnick 2009;Hayashi 2018;Jawade 2016;Kaur 2015;Kawashima 2014;Kawashima 2015;Shafiq 2014;Thiboutot 2002;Thiboutot 2007;Zeichner 2013), and the other seven only presented the results for the last measurement (Bowman 2005;Fleischer 2010;Jackson 2010;Jones 2002;NCT00713609;Pariser 2014;Thiboutot 2008).
Change in quality of life
Only eight trials reported this outcome. Instruments used in these trials varied but included the following: Skindex‐29 (Dhawan 2013;Guerra‐Tapia 2012), Skindex‐16 (Hayashi 2018), Children's Dermatology Life Quality Index (Eichenfield 2013;Schaller 2016), acne‐specific quality of life (Chantalat 2006;Pariser 2014), Dermatology Life Quality Index (Schaller 2016), and Cardiff Acne Disability Index (Tabasum 2014). All of these trials assessed this outcome at baseline and at the end of treatment duration (at 6 or 12 weeks). Two of these trials additionally measured the outcome after two‐week treatments (Chantalat 2006;Guerra‐Tapia 2012), and one repeated measurements at weeks 1, 2, 4, 8, and 12 (Hayashi 2018).
Reduction inC acnes strains
This outcome was reported in eight trials, all of which assessed the change in totalC acnes strains from baseline to the end of treatment (at week 12 or 16) (Cunliffe 2002;Eady 1996;Jackson 2010;Kawashima 2015;Langner 2007;Langner 2008;Leyden 2001b1;Leyden 2001b2). The change in clindamycin‐ and erythromycin‐resistantC acnes strains was also measured in six (Cunliffe 2002;Jackson 2010;Kawashima 2015;Langner 2007;Langner 2008;Leyden 2001b2) and four (Eady 1996;Jackson 2010;Langner 2007;Langner 2008) of these trials respectively. Five trials conducted repeat measurements with an interval varying between one and eight weeks (Cunliffe 2002;Eady 1996;Jackson 2010;Leyden 2001b1;Leyden 2001b2).
Percentage of participants experiencing any adverse event
A total of 96 trials provided the number of participants with any adverse events. This outcome was monitored throughout the whole course of the trials.
Settings
Only 26 trials mentioned the setting of the studies. Among these trials, 14 included outpatients from clinics, medical departments, general practices, or student health centres. However, the other 12 trials reported only participants from hospitals, medical centres, or national medical institutes. A total of 54 studies were described as multi‐centre trials and 26 as single‐centre trials. Among 75 trials reporting the country settings, 33 studies involved at least a trial site in North America, 14 studies involved at least a European trial site, and 16 studies involved at least an east Asian trial site.
Funding sources
Of the 120 trials, 50 were financially supported by industry, eight were supported by a non‐commercial organisation (e.g. university, government), and 63 did not report sources of funding.
Excluded studies
We excluded 119 trials described in 128 reports based on their full text. Reasons for exclusion are listed underCharacteristics of excluded studies. We excluded 58 studies because BPO treatment served as a co‐intervention for all included participants to investigate other acne medications, and we excluded 21 studies because participants did not meet the inclusion criteria for this review. We excluded 23 studies because they were not RCTs. Treatment duration was less than two weeks in ten studies. Three RCTs compared multi‐step regimens involving multiple active ingredients in different formulations. Three RCTs re‐randomised participants upon completion of the first study phase. Seven RCTs did not involve any BPO treatment. Two trials involved oral treatment in the comparison, and one involved light treatment.
Studies awaiting classification
We identified 43 trials awaiting classification and summarised their features in theCharacteristics of studies awaiting classification tables. A total of 27 studies were recorded in the trial registries as completed, but their results were not published (2004‐002272‐41;2006‐004278‐28;2008‐002359‐26;2008‐006792‐68;2013‐001716‐30;2016‐000063‐16;IRCT20181229042165N1;NCT00160394;NCT00624676;NCT00663286;NCT01106807;NCT01237821;NCT01445301;NCT01501799;NCT01742637;NCT01769235;NCT01769664;NCT01788384;NCT01796665;NCT02515305;NCT02525549;NCT02578043;NCT02595034;NCT02616614;NCT02651220;NCT02709902;NCT03393494). We found insufficient information to judge the eligibility of three conference proceedings (Ahmadi 2014;Dahl 2012;Perez 2017); six paper abstracts also provided inadequate information (Chiou 2012;Fagundes 2003;Lassus 1981;Leyden 2002;Stinco 2016;Wokalek 1989). Neither abstracts nor full‐text articles were available for seven studies (Anonymous 1985;Cunliffe 1978;Cunliffe 1980;Danto 1966;Mallol 1984;Peereboom‐Wynia 1984;Priano 1993). We attempted to contact the responsible parties for these studies via available correspondence information but were unsuccessful in obtaining further details or results.
Ongoing studies
We present the details of 22 ongoing trials underCharacteristics of ongoing studies (2005‐004708‐35;2015‐002699‐26;ACTRN12609000443291;CTRI/2012/11/003127;CTRI/2014/07/004734;CTRI/2015/11/006379;CTRI/2016/04/006875;CTRI/2017/09/009884;CTRI/2017/12/010974;CTRI/2018/05/013744;CTRI/2018/06/014684;IRCT2017072035195N1;IRCT20170806035524N5;JPRN‐UMIN000019639;JPRN‐UMIN000024874;NCT00869492;NCT00877409;NCT01422785;NCT02005666;NCT02731105;NCT03076320;NCT03563365). Among these trials, 10 were initiated before 2015, with the earliest start date of 2007. These trials were probably unpublished studies, indicating risk of publication bias. All of these trials were parallel RCTs, and their comparisons involved BPO versus adapalene, BPO versus hydrogen peroxide, BPO/adapalene versus placebo, BPO/adapalene versus Replenix (green tea polyphenols) with resveratrol, BPO/clindamycin versus placebo, BPO/clindamycin versus clindamycin, BPO/sulphur versus placebo, BPO/clindamycin versus adapalene, BPO plus clindamycin/tretinoin versus clindamycin/tretinoin, and BPO plus nadifloxacin versus placebo plus nadifloxacin, and BPO/adapalene plus Replenix with resveratrol versus Replenix with resveratrol. Treatment duration was between 10 and 12 weeks in most trials (ACTRN12609000443291;CTRI/2012/11/003127;CTRI/2014/07/004734;CTRI/2015/11/006379;CTRI/2016/04/006875;CTRI/2017/09/009884;CTRI/2018/06/014684;IRCT2017072035195N1;IRCT20170806035524N5;JPRN‐UMIN000019639;JPRN‐UMIN000024874;NCT00877409;NCT01422785;NCT02005666;NCT03076320;NCT03563365).
Risk of bias in included studies
Overall, none of the included studies were rated as having low risk of bias across all seven domains for assessment (Characteristics of included studies). We have presented each risk of bias item across all included studies inFigure 2 and a summary of risk of bias for each included study inFigure 3.
2.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Allocation
Random sequence generation
We judged the risk of bias as low in 39 studies in which an appropriate method (i.e. a random numbers table or computer software) was used to generate the random sequence. However, in the other 81 trials, study authors did not report how participants were randomly assigned to different treatment groups. We judged the risk of bias of these trials as unclear.
Allocation concealment
Only nine trials were judged as having low risk in the domain of allocation concealment, which was ensured by central assignment of treatment or use of sequentially numbered, opaque, sealed envelopes. The remaining trials did not provide sufficient information for judgement about allocation concealment.
Blinding
Blinding of participants and personnel
We decided the risk of bias as low in only six trials in which study authors specified that participants and personnel were blinded. Also complete blinding in these trials was possible as comparator preparations and usage of treatments were the same and the well‐known treatment‐related adverse events (such as dryness and erythema in BPO‐related treatments) were similar between groups. We classified 35 trials as having unclear risk, most of which were claimed to be double‐blind with no sufficient information on who was blinded when blinding was possible in these trials. We judged remaining trials (79/120) as high risk as study authors specified or indicated no blinding of participants or personnel, or treatment groups differed in comparator preparations, frequency of treatments, or well‐known treatment‐related adverse events.
Blinding of outcome assessment
For only 19 trials, we judged the risk of bias as low given that study authors specified that outcome assessors were not aware of the treatment assignment, and the balance of specific treatment‐related adverse events between groups made complete blinding possible. We assessed 50 trials as having unclear risk because information needed for the judgement was insufficient. We considered the rest of the trials (51/120) to be at high risk of bias as study authors specified or indicated no blinding in the outcome assessment, or between‐group imbalance among treatment‐related adverse events may have compromised the blinding.
Incomplete outcome data
We considered 34 trials as having low risk of attrition bias when at least 90% of participants were followed up and the reasons for withdrawal were comparable between different treatment groups. We judged 34 trials as having high risk of bias because more than 10% of study participants did not provide complete outcome data, and some trials reported imbalance in the numbers and reasons for withdrawal between groups. We considered the remaining 52 trials as having unclear risk of bias.
Selective reporting
With all outcomes planned on the trial registry reported, 26 trials were regarded as having low risk of reporting bias. We judged the risk of bias as high for 11 trials in which one or more outcomes planned in their published information on a trial registry or specified in the methods section were not reported in the results. Substantial uncertainty existed in this domain for 83 trials because no corresponding registered information or protocols were available to confirm whether all pre‐specified outcomes were reported, or because additional outcomes were reported besides those pre‐specified in a trial registry.
Other potential sources of bias
In 25 trials, the baseline characteristics of participants were similar between different treatment groups and the washout periods of previous acne treatments were long enough. Risk of bias was high in 26 trials; the main issues involved imbalance in the demographics or in acne severity between groups or the unacceptably short washout periods. Insufficient information was available for this judgement on the remaining 69 trials.
Effects of interventions
See:Table 1;Table 2;Table 3;Table 4;Table 5
We reported pre‐defined outcomes under the following 47 pair‐wise comparisons that we identified from the included studies. InData and analyses, we presented the results for five main comparisons, which included comparisons of BPO versus placebo/no treatment or four major topical active medications (adapalene, clindamycin, erythromycin, and salicylic acid). These comparisons were highlighted in our review because the treatments involved are now commonly used in clinical practice. For these comparisons, we rated the corresponding quality of evidence using GRADE. For the other 44 comparisons, we presented as many relevant details as we were able to obtain from the original reports. All comparisons involved only topical treatments and are summarised below. Results for the two primary outcomes (from studies included in and excluded from the main pooled analyses) are also presented inAppendix 9 andAppendix 10.
Main comparisons
BPO versus placebo or no treatment
BPO versus adapalene
BPO versus clindamycin
BPO versus erythromycin
BPO versus salicylic acid
Other comparisons
BPO versus tretinoin
BPO versus isotretinoin
BPO versus azelaic acid
BPO versus retinoic acid
BPO versus sulphur
BPO versus hydrogen peroxide
BPO versus superoxidised solution
BPO versusCasuarina equisetifolia bark extract
BPO versus Chinese medical mask
BPO versus meclocycline sulfosalicylate
BPO versus isolutrol
BPO versus tea tree oil
BPO versus Unani preparation (Zimade Muhasa)
BPO versus glycerin
BPO versus chloroxylenol/salicylic acid
BPO versus chloroxylenol/zinc oxide
BPO/adapalene versus placebo or no treatment
BPO/adapalene versus tretinoin
BPO/adapalene versus salicylic acid
BPO/adapalene versus clindamycin/tretinoin
BPO/clindamycin versus placebo or no treatment
BPO/clindamycin versus adapalene
BPO/clindamycin versus azelaic acid
BPO/clindamycin versus erythromycin/zinc
BPO/clindamycin versus dapsone
BPO/erythromycin versus placebo or no treatment
BPO/erythromycin versus clindamycin
BPO/erythromycin versus azelaic acid
BPO/erythromycin versus metronidazole
BPO/erythromycin versus viaminate
BPO/erythromycin versus zinc/erythromycin
BPO/sulphur versus placebo
BPO/glycolic acid/zinc lactate versus placebo
BPO/potassium hydroxyquinoline sulphate versus placebo
BPO (10%) versus BPO (5%)
BPO (10%) versus BPO (2.5%)
BPO (5%) versus BPO (2.5%)
BPO (6%) versus BPO (5.5%)
BPO (vehicle with 8% urea) versus BPO (vehicle with no urea)
BPO (vehicle with acetone) versus BPO (vehicle with alcohol/detergent)
BPO (formulation 1) versus BPO (formulation 2)
Water‐based BPO versus alcohol‐based BPO
Results for the main comparisons
BPO versus placebo or no treatment
This comparison comprises 46 parallel trials and one split‐face trial. A total of 25 parallel trials (Burke 1983;Chalker 1983;Chantalat 2005;Ede 1973;Eichenfield 2011;Gold 2009;Gollnick 2009;Hughes 1992;Jaffe 1989;Kabir 2018;Kawashima 2014;Kawashima 2017b;Leyden 2001a;Lookingbill 1997;Mills 1986;NCT02073461;Papageorgiou 2000;Smith 1980;Study 152;Study 156;Thiboutot 2007;Thiboutot 2008;Tirado‐Sanchez 2009;Tschen 2001;Vasarinsh 1969), as well as one split‐face trial (Bikowski 2006), involved the comparison between BPO monotherapy and placebo or no treatment, with treatment duration varying from 2 weeks to 14 weeks.
In all, 34 parallel trials treating participants for 2 to 24 weeks evaluated effects of BPO as an add‐on treatment (Borglund 1991;Cassano 2002;Chalker 1983;Cunliffe 2002;Del 2009a;Draelos 2002;Draelos 2010;Eady 1996;Eichenfield 2011;Fang 2002;Fleischer 2010;Fu 2003;Gold 2009;Gollnick 2009;Jawade 2016;Kabir 2018;Kawashima 2015;Korkut 2005;Leyden 2001a;Leyden 2001b1;Leyden 2001b2;Lookingbill 1997;Miyachi 2016;NCT00713609;Ozgen 2013;Shalita 2003;Study 152;Thiboutot 2007;Thiboutot 2008;Tschen 2001;Tucker 1984;Vasarinsh 1969;Xu 2016;Zeichner 2013). All outcomes of interest in this review were available except for change in quality of life. SeeTable 1, where we rated the evidence for the two primary outcomes and the secondary safety outcome.
Primary outcome: participant global self‐assessment of acne improvement
Of 16 trials that reported this outcome, 13 treated participants for the long term (Cunliffe 2002;Draelos 2002;Gold 2009;Gollnick 2009;Jawade 2016;Leyden 2001a;Miyachi 2016;Shalita 2003;Thiboutot 2007;Thiboutot 2008;Tschen 2001;Tucker 1984;Zeichner 2013), and two for the medium term (Ozgen 2013;Papageorgiou 2000). The treatment duration inVasarinsh 1969 varied from 4 to 14 weeks.
Main pooled analyses: BPO versus placebo or no treatment
Overall, the data for long‐term outcomes from three trials were complete to be pooled (Gold 2009;Jawade 2016;Leyden 2001a), and a total of 1111 participants in the BPO group and 1123 in the placebo group were included. The treatment duration was 10 weeks and 12 weeks in these trials. The outcome was assessed via a 6‐point or a 5‐point Likert‐like scale. The pooled risk ratio of treatment success was 1.27 (95% confidence interval (CI) 1.12 to 1.45; I² = 58%;Analysis 1.1), which shows some difference in this outcome between groups in favour of BPO treatment.
1.1. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 1 Participant's global self‐assessment of improvement (long‐term data).
The risk ratio of treatment success for the medium term was 2.70 (95% CI 1.68 to 4.34; I² = 0%;Analysis 1.2) from two trials (Ozgen 2013;Papageorgiou 2000). Study authors used two different 6‐point scales to assess the outcome.
1.2. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 2 Participant's global self‐assessment of improvement (medium‐term data).
Subgroup analyses: co‐intervention
ForAnalysis 1.1 andAnalysis 1.2, the test for subgroup differences was not statistically significant, with P values of 0.42 and 0.71, respectively. This suggests that effects of BPO did not differ by the co‐intervention.
Studies not included in the meta‐analysis
For the long‐term outcome, we did not include the other eight trials in the main analysis because the definitions of treatment success used were different from that in our review (Borglund 1991;Draelos 2002;Gollnick 2009;Thiboutot 2007;Thiboutot 2008;Tschen 2001;Tucker 1984;Zeichner 2013), but sensitivity analysis including these trials suggests similar results (risk ratio (RR) 1.32, 95% CI 1.20 to 1.45) to our main analysis in favour of BPO treatment (Appendix 9).
This outcome was assessed in the 10‐week trial comparing BPO plus meclocycline versus meclocycline monotherapy (Borglund 1991), but it is unclear how the outcome was assessed. It was reported that participants rating treatments as "good to excellent" accounted for 55% and 49% in the two groups, respectively, with an RR of 1.13 (95% CI 0.70 to 1.80).
This outcome was assessed via a 5‐point Likert‐like scale (from highly favourable to highly unfavourable) in one 12‐week parallel trial (Draelos 2002), with each group comprising 89 participants (BPO plus tazarotene versus tazarotene). At week 12, a significant difference was found in the proportion of participants rating the improvement as highly favourable or favourable (92% versus 73%; P < 0.05) in favour of BPO treatment.
In a 12‐week trial (Gollnick 2009), 415 participants in the BPO group, 418 in the placebo group, 419 in the BPO/adapalene group, and 418 in the adapalene group were assessed for this outcome via a 6‐point Likert‐like scale. The risk ratio for self‐reported complete or marked improvement was 1.16 (95% CI 1.01 to 1.34) in favour of BPO treatment.
A similar 6‐point Likert‐like scale was used in another 12‐week trial in which 149 participants were treated with BPO, 71 with placebo, 149 with BPO/adapalene, and 148 with adapalene (Thiboutot 2007). The risk ratio for self‐reported complete or marked improvement was 1.53 (95% CI 0.87 to 2.69) with no significant difference.
Thiboutot 2008, with 809 participants in the BPO group, 395 in the placebo group, 797 in the BPO/clindamycin group, and 812 in the clindamycin group, assessed the outcome after 12 weeks using a 7‐point Likert‐like scale. The risk ratio for self‐reported clear or almost clear was 1.58 (95% CI 1.35 to 1.86) in favour of BPO treatment.
In a 10‐week trial, a 7‐point Likert‐like scale (from 3 = much better to ‐3 = much worse) was used to assess the outcome (95 participants treated with BPO, 48 with placebo, 95 with BPO/clindamycin, and 49 with clindamycin) (Tschen 2001). The risk ratio for being "much better" on this scale was 2.58 (95% CI 1.42 to 4.68) in favour of BPO treatment.
In one 10‐week parallel trial with 24 participants on BPO plus clindamycin treatment and 29 on clindamycin alone, 96% and 95% of participants felt their acne had improved at week 10, respectively, with no statistical difference (Tucker 1984). However, it is unclear how this outcome was assessed.
Zeichner 2013 included 20 participants in each group (BPO plus tretinoin/clindamycin versus placebo plus tretinoin/clindamycin) and assessed this outcome using a 6‐point Likert‐like scale (0 = clear to 5 = severe). At week 12, no significant difference was found in the proportion of participants who scored 0 or 1 (5/20 versus 2/20; P = 0.24).
The long‐term outcome was also assessed in a 12‐week parallel trial comparing BPO plus tretinoin versus placebo plus tretinoin, with completion of follow‐up in 56 of 87 participants (Shalita 2003). No information about the criteria for the measure was available. For this outcome, study authors reported that participants in both groups rated their improvement as mild.
Vasarinsh 1969, with varied treatment duration, assessed the outcome using a 4‐point Likert‐like scale (from worse = ‐1 to greatly improved = 2). The average score was 0.66 and 0.53 for the BPO and placebo groups, respectively. This trial also compared BPO/sulphur with sulphur, and the average score was 1.15 and 0.75, respectively.
Primary outcome: withdrawal due to adverse effects
A total of 25 trials reported the long‐term outcome (Borglund 1991;Chalker 1983;Cunliffe 2002;Draelos 2002;Eichenfield 2011;Fleischer 2010;Gold 2009;Gollnick 2009;Hughes 1992;Jaffe 1989;Jawade 2016;Kawashima 2014;Kawashima 2015;Kawashima 2017b;Korkut 2005;Leyden 2001a;Lookingbill 1997;Miyachi 2016;NCT00713609;Study 156;Thiboutot 2007;Thiboutot 2008;Tirado‐Sanchez 2009;Tschen 2001;Xu 2016), four reported the medium‐term outcome (Burke 1983;Mills 1986;Ozgen 2013;Papageorgiou 2000), and one reported the short‐term outcome (Draelos 2010).
Main pooled analyses: BPO versus placebo or no treatment
For the long‐term period, risk of withdrawal due to adverse events was higher in the BPO group (RR 2.13, 95% CI 1.55 to 2.93; 13,744 participants; I² = 0%;Analysis 1.3). According to the funnel plot (Figure 4) and Egger's test (P = 0.753), no evidence suggests potential publication bias. Erythema, pruritus, and skin burning were the most common causes of withdrawal.
1.3. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 3 Withdrawal due to adverse effects (long‐term data).
4.
Funnel plot of comparison: 1 BPO versus placebo or no treatment, outcome: 1.3 Withdrawal due to adverse effects (long‐term data).
In terms of the medium‐term outcome, one trial found no withdrawals due to adverse effects (Mills 1986), another trial observed that only one participant discontinued BPO treatment (due to dermatitis) (Burke 1983), and one trial reported that only one participant on BPO plus nadifloxacin withdrew because of a severe burning sensation (Ozgen 2013). These three trials suggested no clear differences between the two groups (RR 2.92, 95% CI 0.31 to 27.44; 202 participants; 3 studies; I² = 0%;Analysis 1.4).
1.4. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 4 Withdrawal due to adverse effects (medium‐term data).
Subgroup analyses: co‐intervention
For long‐term data, the test for subgroup differences showed a borderline statistically significant difference when different co‐interventions were used (P = 0.05;Analysis 1.3). This potential difference came from the comparison between BPO plus tazarotene and tazarotene. In this comparison, BPO treatment was associated with non‐significantly decreased risk of withdrawal from the trial, but in other comparisons the association was opposite.
For medium‐term data, we did not observe significant differences between subgroups (P = 1.00;Analysis 1.4).
Studies not included in the meta‐analysis
Borglund 1991, the long‐term trial, reported that no participants discontinued BPO plus meclocycline or meclocycline monotherapy due to adverse events (Appendix 10).
Two studies, which assessed medium‐ and short‐term outcomes, respectively, were not included in the meta‐analysis.Papageorgiou 2000 reported that two participants discontinued treatments because of flare‐up. However, it is unclear what treatments the participants received previously.
The other trial was the only one that focused on the short‐term outcome. Of 61 participants enrolled (30 in the BPO plus tretinoin/clindamycin group and 31 in the placebo plus tretinoin/clindamycin group), no participants discontinued treatment because of adverse events during the four‐week period (Draelos 2010).
Secondary outcome: investigator‐assessed change in lesion counts
Although 32 included trials assessed acne lesions (Borglund 1991;Burke 1983;Cassano 2002;Chalker 1983;Cunliffe 2002;Draelos 2002;Ede 1973;Eichenfield 2011;Fang 2002;Fleischer 2010;Fu 2003;Gold 2009;Gollnick 2009;Hughes 1992;Kawashima 2014;Korkut 2005;Leyden 2001a;Lookingbill 1997;Mills 1986;Miyachi 2016;NCT02073461;Ozgen 2013;Papageorgiou 2000;Shalita 2003;Study 152;Study 156;Thiboutot 2007;Thiboutot 2008;Tirado‐Sanchez 2009;Tschen 2001;Tucker 1984;Xu 2016), only 10 trials provided sufficient data for our review to estimate effect size for the absolute or percentage change in total lesions (TLs), inflamed lesions (ILs), or non‐inflamed lesions (NILs) (Burke 1983;Cunliffe 2002;Eichenfield 2011;Fleischer 2010;Hughes 1992;Kawashima 2014;Lookingbill 1997;Mills 1986;Papageorgiou 2000;Xu 2016).
Main pooled analyses: BPO versus placebo or no treatment
For long‐term treatment duration, the absolute change in TLs pooled from the three trials was ‐10.73 (95% CI ‐15.68 to ‐5.78; 3230 participants; I² = 84%;Analysis 1.5), in favour of both BPO monotherapy and add‐on treatment (Eichenfield 2011;Kawashima 2014;Xu 2016). The three trials also suggested significant absolute change in ILs and NILs among participants on BPO treatment, with pooled mean differences of ‐3.50 (95% CI ‐6.33 to ‐0.67; 2635 participants; I² = 92%;Analysis 1.6) and ‐6.53 (95% CI ‐9.74 to ‐3.32; 2635 participants; I² = 75%;Analysis 1.7), respectively. The two studies were conducted in western and Asian populations, respectively, which may lead to heterogeneity in the reduction in acne lesions. The difference in percentage change in TLs was 10.29% (95% CI 3.39% to 17.19%; 1567 participants; 4 studies; I² = 72%;Analysis 1.8), which was pooled from four trials (Cunliffe 2002;Fleischer 2010;Miyachi 2016;Xu 2016). The counterpart in ILs and NILs from four trials was 17.22 (95% CI 4.98 to 29.45; 1588 participants; I² = 87%;Analysis 1.9) and 19.31 (95% CI 7.16 to 31.47; 1588 participants; I² = 80%;Analysis 1.10), respectively (Cunliffe 2002;Fleischer 2010;Lookingbill 1997;Xu 2016).
1.5. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 5 Investigator‐assessed absolute change in total lesions (long‐term data).
1.6. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 6 Investigator‐assessed absolute change in inflammatory lesions (long‐term data).
1.7. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 7 Investigator‐assessed absolute change in non‐inflammatory lesions (long‐term data).
1.8. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 8 Investigator‐assessed percentage change in total lesions (long‐term data).
1.9. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 9 Investigator‐assessed percentage change in inflammatory lesions (long‐term data).
1.10. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 10 Investigator‐assessed percentage change in non‐inflammatory lesions (long‐term data).
As for the medium‐term outcome, we found significant differences in percentage reduction in NILs (mean difference (MD) 18.42, 95% CI 1.39 to 35.45; 1212 participants; 3 studies; I² = 89%;Analysis 1.13) in favour of BPO treatment but not in TLs (MD 16.02, 95% CI ‐0.95 to 32.99; 252 participants; 2 studies; I² = 65%;Analysis 1.11) nor ILs (MD 13.83, 95% CI ‐0.22 to 27.88; 1212 participants; 3 studies; I² = 86%;Analysis 1.12).
1.13. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 13 Investigator‐assessed percentage change in non‐inflammatory lesions (medium‐term data).
1.11. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 11 Investigator‐assessed percentage change in total lesions (medium‐term data).
1.12. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 12 Investigator‐assessed percentage change in inflammatory lesions (medium‐term data).
These trials also reported the short‐term outcome. We found significant differences in percentage reduction in TLs (MD 10.00, 95% CI 2.26 to 17.74; 201 participants; 1 study;Analysis 1.14) and NILs (MD 24.65, 95% CI 4.23 to 45.07; 229 participants; 2 studies;Analysis 1.16) in favour of BPO treatment but not in ILs (MD 14.02, 95% CI ‐0.60 to 28.63; 1212 participants; 3 studies; I² = 91%;Analysis 1.15).
1.14. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 14 Investigator‐assessed percentage change in total lesions (short‐term data).
1.16. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 16 Investigator‐assessed percentage change in non‐inflammatory lesions (short‐term data).
1.15. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 15 Investigator‐assessed percentage change in inflammatory lesions (short‐term data).
Subgroup analyses: co‐intervention
Most subgroup analyses suggested significant differences were common for BPO monotherapy and BPO combination (Analysis 1.6;Analysis 1.7;Analysis 1.8;Analysis 1.9;Analysis 1.10;Analysis 1.12;Analysis 1.13;Analysis 1.15). Reduction in acne lesions tended to be greater with BPO monotherapy than with BPO combination therapies. On the other hand, we did not observe the subgroup difference in absolute or percentage change in TLs regardless of treatment duration (Analysis 1.5;Analysis 1.11;Analysis 1.14).
Studies not included in the meta‐analysis
In the other trials, data on the absolute or percentage change in acne lesions were insufficient to summarise the effect size.
Three trials investigated BPO monotherapy.Leyden 2001a claimed that neither TLs (‐13.8 versus ‐1.3) nor ILs (‐5.9 versus 0.7) were significantly reduced in the BPO group when compared to the placebo group at week 10. However, another two trials did not show the difference. InStudy 152, the percentage reduction in TLs, ILs, and NILs was 25.5% versus 20.6% (P value not reported), 33.5% versus 28.6% (P = 0.54), and 18.8% versus 15.4% (P = 0.49) for the BPO group (n = 70) and the placebo group (n = 37).Vasarinsh 1969 assessed the change in lesion counts for superficial (comedones and pustules) and deep (papules and cysts) lesions, respectively, using a 11‐point scoring system (decrease in lesions by 100% = 5, 76% to 99% = 4, 51% to 75% = 3, 26% to 50% = 2, < 25% = 1, no change = 0; increase by < 25% = ‐1, 26% to 50% = ‐2, 51% to 75% = ‐3, 76% to 100% = ‐4, over 100% = ‐5). The average score for superficial lesions was 0.55 and 0 for the BPO and placebo groups, respectively, and the counterpart for deep lesions was 0.69 and 0.53.
Four trials comparing BPO/adapalene with adapalene reported the percentage reduction in lesion counts (Gold 2009;Gollnick 2009;Miyachi 2016;Thiboutot 2007).Gold 2009 found a significant difference in the percentage reduction in TLs (60.7% versus 49.8%), ILs (66.0% versus 52.1%), and NILs (58.9% versus 52.9%) between groups (all P values < 0.05). InGollnick 2009, the percentage reduction in TLs, ILs, and NILs was significantly higher in the BPO/adapalene group (68.8% versus 55.7%, 72.4% versus 61.9%, and 66.4% versus 54.3%, respectively) (all P values < 0.05). InMiyachi 2016, which compared BPO/adapalene gel with adapalene in participants (212 versus 107 participants), the percentage reduction in TLs was 82.7% versus 68.6%, with a significant difference (MD 14.6%, 95% CI 8.3% to 20.8%). The average percentage reduction in ILs and NILs was 80.9% versus 66.2% (P < 0.001) and 74.6% versus 61.1% (P < 0.001), respectively. Another trial found 51.0% and 35.4% reduction in TLs, 62.9% and 45.7% in ILs, and 51.2% and 33.3% in NILs for BPO/adapalene and adapalene, respectively (all P values < 0.001) (Thiboutot 2007).
Six trials compared BPO/clindamycin with clindamycin (Leyden 2001a;Study 152;Study 156;Thiboutot 2008;Tschen 2001;Tucker 1984). For the absolute change in lesion counts, in another trial, investigators claimed that both TLs (‐18.4 versus ‐6.2; P < 0.001) and ILs (‐10.1 versus ‐3.2; P < 0.001) were significantly reduced in the BPO/clindamycin group when compared to the clindamycin group at week 10 (Leyden 2001a).Tschen 2001 found ‐16.6 versus ‐14.7 in ILs for BPO/clindamycin (95 participants) and clindamycin (49 participants) (P = 0.034). InTucker 1984, trial authors reported the absolute change in comedone, papule, pustule, and cyst lesions at week 10 separately: corresponding results were ‐21.0 versus ‐7.3, ‐11.3 versus ‐9.7, ‐8.3 versus ‐3.4, and ‐1.4 versus ‐2.3. For the percentage change in lesion counts, inStudy 152, the percentage reduction in TLs, ILs, and NILs was 32.5% versus 23.5% (P = 0.002), 43.4% versus 39.8% (0.538), the 25.7% versus 11.2% (P < 0.001) for the BPO/clindamycin group (n = 73 participants) and the clindamycin group (n = 70). InStudy 156, the percentage reduction in TLs, ILs, and NILs was 49.8% versus 33.3% (P < 0.001), 57.3% versus 48.6% (0.03), and 39.0% versus 18.0% (P < 0.001) for the BPO/clindamycin group (n = 96) and the clindamycin group (n = 96). ForThiboutot 2008, 797 participants were randomised to the BPO/clindamycin group and 812 participants to the clindamycin group. The percentage reduction was 47.9% versus 40.4% in TLs, 54.6% versus 46.2% in ILs, and 43.2% versus 36.2% in NILs at week 12 (all P values < 0.001).
Other comparisons for BPO as an add‐on treatment were limited. One 10‐week trial focusing on BPO/erythromycin versus erythromycin assessed the mean difference in the percentage reduction in lesion counts between two groups but reported only that the percentage reduction in comedone, pustule, papule, and inflammatory lesions seemed greater in the BPO/erythromycin group, with no significant difference (Chalker 1983). Two trials assessed the reduction in acne lesions for BPO plus adapalene versus adapalene (Cassano 2002;Fang 2002). Only an abstract was available forCassano 2002, in which a total of 162 participants were randomised to one of the four groups: adapalene gel; adapalene gel; adapalene gel plus BPO gel 5%; and adapalene plus erythromycin gel 4%. With no information on the absolute or percentage reduction in lesion counts, trial authors claimed that all these treatments similarly led to a significant reduction in the numbers of papules, pustules, and comedones. The results ofFang 2002 were also presented in an abstract. A total of 150 participants were randomised to one of the two groups. At week 12, there was no significant difference in the percentage reduction in TLs (81.3% versus 68.9%), despite higher reduction found in the BPO plus adapalene group. One 12‐week parallel trial comparing BPO plus tazarotene with tazarotene reported that the percentage reduction in both ILs (39.7% versus 43.7%, P > 0.05) and NILs (42.7% versus 41.6%, P > 0.05) was similar between two groups (Draelos 2002). For the medium‐ and short‐term periods, both treatments reduced NILs by about 40% and 30%, respectively, with no significant difference. Their effects on reducing ILs were also comparable (31% versus 31% for the medium‐term and 24% versus 17% for the short‐term period). In a 12‐week parallel trial (Shalita 2003), researchers investigating BPO plus tretinoin versus placebo plus tretinoin observed that the mean number of IL counts was reduced from 9.4 at baseline to 3.9 at week 12 among participants on BPO, and from 9.3 to 6.6 among participants on placebo (P < 0.01). For NILs, there were no significant differences between treatment groups, although both groups had a significant reduction from baseline. One 10‐week parallel trial with 24 participants on BPO plus clindamycin and 29 participants on clindamycin alone reported the absolute reduction in comedone, pustule, papule, and cyst lesions from baseline to week 10 (‐20.4 versus ‐7.3, ‐5.4 versus ‐3.4, ‐11.4 versus ‐9.7, and ‐1.4 versus ‐2.4, respectively) (Tucker 1984). The significance of test results was not reported. As reported in one 10‐week parallel trial for BPO plus meclocycline sulfosalicylate versus meclocycline sulfosalicylate (Borglund 1991), the difference in the absolute reduction in papules, pustules, and comedones was ‐2, ‐1.6, and ‐2.6, respectively, for long‐term data. For medium‐term outcomes, the counterpart was ‐2.9, ‐2.4, and ‐1, respectively. For short‐term outcomes, the counterpart was ‐4.8, ‐2.1, and 1.3, respectively. All results were not statistically significant (all P values > 0.05).
In an 8‐week parallel trial with 47 participants on BPO plus nadifloxacin and 46 participants on placebo plus nadifloxacin (Ozgen 2013), the mean percentage reduction in ILs and NILs was 53.5% versus 22.08% and 34.8% versus 7.6% (both P < 0.001) at week 8.Vasarinsh 1969 compared BPO/sulphur with sulphur. The change in lesion counts in this trial was assessed for superficial (comedones and pustules) and deep (papules and cysts) lesions, respectively, using a 11‐point scoring system (decrease in lesions by 100% = 5, 76% to 99%=4, 51% to 75%=3, 26% to 50%=2, < 25% = 1, and no change = 0; increase by < 25% = ‐1, 26% to 50% = ‐2, 51% to 75% = ‐3, 76% to 100% = ‐4, over 100% = ‐5). The average score for superficial lesions was 0.81 and ‐0.70 for the BPO/sulphur and sulphur groups, respectively, and the counterpart for deep lesions was 0.91 and 0.30.
We also found some trials that comparing only lesions between groups at end of treatment, rather than the absolute or percentage change in lesions.
For BPO monotherapy, three trials reported long‐term data ‐Hughes 1992 ‐ or medium‐term data (Burke 1983;Mills 1986); all supported the benefits of BPO treatment. The mean difference was ‐27.50 (95% CI ‐46.77 to ‐8.23) in ILs, and ‐28.20 (95% CI ‐45.04 to ‐11.36) in NILs (Hughes 1992). The mean difference was ‐16.00 (95% CI ‐18.25 to ‐13.75) in TLs, and ‐8.40 (95% CI ‐9.88 to ‐6.92) in NILs, as reported inBurke 1983. The pooled mean difference in ILs was ‐4.40 (95% CI ‐5.47 to ‐3.33; I² = 0%).
For BPO add‐on treatment, two trials presented long‐term data for BPO plus adapalene versus adapalene (Fu 2003;Korkut 2005). No significant difference was found for TLs (MD 0.11, 95% CI ‐4.94 to 5.17; I² = 0%), ILs (MD ‐0.52, 95% CI ‐2.15 to 1.10; I² = 0%), and NILs (MD 0.87, 95% CI ‐2.15 to 3.88; I² = 0%).
Secondary outcome: percentage of participants rated 'clear' or 'almost clear' on the IGA scale of acne severity
Overall, BPO therapy was associated with higher proportions of participants rated 'clear' or 'almost clear' on the IGA scale, regardless of the length of treatment duration.
Main pooled analyses: BPO versus placebo or no treatment
The long‐term outcome was reported in 10 trials (Eichenfield 2011;Fleischer 2010;Gold 2009;Gollnick 2009;Kawashima 2014;Kawashima 2015;Thiboutot 2007;Thiboutot 2008;Xu 2016;Zeichner 2013), with an RR of 1.55 (95% CI 1.40 to 1.70; 10,399 participants; I² = 43%;Analysis 1.17). Counterparts for medium‐ and short‐term outcomes were reported in five studies (Gold 2009;Gollnick 2009;Kawashima 2014;Kawashima 2015;Thiboutot 2007), with an RR of 1.96 (95% CI 1.58 to 2.44; 5014 participants; I² = 35%;Analysis 1.18) and 2.43 (95% CI 1.78 to 3.32; 5014 participants; I² = 19%;Analysis 1.19), respectively.
1.17. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 17 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (long‐term data).
1.18. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 18 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (medium‐term data).
1.19. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 19 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (short‐term data).
Subgroup analyses: co‐intervention
In subgroup analysis, we did not observe that the effects of BPO can differ by co‐intervention, regardless of treatment duration (Analysis 1.17;Analysis 1.18;Analysis 1.19).
Secondary outcome: reduction inC acnes strains
Studies not included in the meta‐analysis
This outcome was reported in only two trials (Eady 1996;Kawashima 2015). InKawashima 2015, 34 (6.8%) in the BPO/clindamycin group and 59 (19 7%) in the clindamycin group had a sample ofC acnes. Study authors reported that a small increase in the number of clindamycin‐resistantC acnes isolates was found across groups.Eady 1996 randomised 20 participants into the combination treatment group and 17 into the erythromycin group. BPO/erythromycin treatment was more effective in reducing total propionibacterial numbers than was erythromycin alone at week 12. Meanwhile, erythromycin‐resistant propionibacteria were found in seven participants treated with combination formulation and in 10 participants treated with erythromycin alone.
Secondary outcome: percentage of participants experiencing any adverse event
A total of 28 trials reported the outcome for long‐term treatment duration (Borglund 1991;Cassano 2002;Chalker 1983;Cunliffe 2002;Eady 1996;Eichenfield 2011;Fang 2002;Fleischer 2010;Fu 2003;Gold 2009;Gollnick 2009;Hughes 1992;Jaffe 1989;Kawashima 2014;Kawashima 2015;Korkut 2005;Leyden 2001a;Lookingbill 1997;Miyachi 2016;NCT02073461;Shalita 2003;Thiboutot 2007;Thiboutot 2008;Tirado‐Sanchez 2009;Tschen 2001;Tucker 1984;Xu 2016;Zeichner 2013), three trials for medium‐term duration (Burke 1983;Ozgen 2013;Papageorgiou 2000), and two for short‐term duration (Del 2009a;Draelos 2010); one assessed varying durations (Vasarinsh 1969).
Main pooled analyses: BPO versus placebo or no treatment
Overall, we observed that BPO treatment can potentially result in higher risk of adverse events in the long‐term treatment period, with an RR of 1.40 (95% CI 1.15 to 1.70; 11,028 participants; I² = 72%;Analysis 1.20). According to the funnel plot (Figure 5) and Egger's test (P = 0.881), no evidence suggests potential publication bias. Most adverse events were mild to moderate. The most common adverse events across trials included skin dryness, facial pain, pruritus, dermatitis, erythema, and irritation.
1.20. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 20 Percentage of participants with any adverse events (long‐term data).
5.
Funnel plot of comparison: 1 BPO versus placebo or no treatment, outcome: 1.20 Percentage of participants with any adverse events (long‐term data).
Evidence for medium‐term or short‐term treatment duration was limited, with an RR of 1.67 (95% CI 1.08 to 2.59; 93 participants; 1 study;Analysis 1.21) and 0.13 (95% CI 0.02 to 0.94; 60 participants; 1 study;Analysis 1.22), respectively.
1.21. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 21 Percentage of participants with any adverse events (medium‐term data).
1.22. Analysis.
Comparison 1 BPO versus placebo or no treatment, Outcome 22 Percentage of participants with any adverse events (short‐term data).
In the trial with varying treatment durations, excessive erythema and dryness occurred in five participants on BPO and two on placebo. One participant developed severe allergic sensitisation after BPO treatment (Vasarinsh 1969).
Subgroup analyses: co‐intervention
We did not observe that the occurrence of adverse events differed by co‐intervention (P for subgroup differences = 0.32).
Studies not included in the meta‐analysis
Two trials did not present the number of participants experiencing at least one adverse event but reported that the number was similar across study treatments (Borglund 1991;Gold 2009). Although adverse events were assessed in four trials exploring effects of BPO plus adapalene versus adapalene (Cassano 2002;Fang 2002;Fu 2003;Korkut 2005), three of them did not present the outcomes of our review interest (Cassano 2002;Fang 2002;Korkut 2005). We cannot calculate RR as the effect size for the comparison between BPO plus tretinoin and placebo plus tretinoin as investigated in one 12‐week parallel trial because the number of participants with at least one adverse event was not provided (Shalita 2003).Vasarinsh 1969 also assessed adverse events for the comparison between BPO/sulphur and sulphur, but the total number of participants with any adverse event was not reported. As mentioned inKabir 2018, adverse events were noted during the trial but were not reported.
BPO versus adapalene
This comparison comprises 13 parallel trials (Babaeinejad 2013;do Nascimento 2003;Dudhia 2015;Fleischer 2010;Gold 2009;Gollnick 2009;Hayashi 2018;Iftikhar 2009;Jawade 2016;Korkut 2005;Miyachi 2016;Stinco 2007;Thiboutot 2007). Participants in all trials except one were followed up for a long‐term period (Stinco 2007). All outcomes of interest in this review were available except the reduction inC acnes strains. SeeTable 2, where we rated the evidence for the two primary outcomes and the secondary safety outcome.
Primary outcome: participant global self‐assessment of acne improvement
Eight trials presented long‐term data for this outcome (Babaeinejad 2013;do Nascimento 2003;Gold 2009;Gollnick 2009;Hayashi 2018;Jawade 2016;Miyachi 2016;Thiboutot 2007). Treatment duration was 12 weeks in all these trials except one (do Nascimento 2003), in which participants were treated for 11 weeks.
Main pooled analyses: BPO versus adapalene
Complete data for the long‐term outcome were available in five trials (Babaeinejad 2013;do Nascimento 2003;Gold 2009;Hayashi 2018;Jawade 2016), in which the outcome was assessed with a four‐category, a 5‐point, or a 6‐point Likert‐like scale. No difference in the probability of treatment success was found (RR 0.99, 95% CI 0.90 to 1.10; 1472 participants; 5 studies; I² = 55%;Analysis 2.1).
2.1. Analysis.
Comparison 2 BPO versus adapalene, Outcome 1 Participant's global self‐assessment of improvement (long‐term data).
Subgroup analyses: co‐intervention
We found that effects of BPO versus adapalene may be altered by co‐intervention with clindamycin, with a P value of 0.03 (Analysis 2.1).
Studies not included in the meta‐analysis
We did not pool the results from the other three trials because data were insufficient to calculate the percentage of treatment success defined in our review (Appendix 9) (Gollnick 2009;Miyachi 2016;Thiboutot 2007). InGollnick 2009, 415 participants in the BPO group and 418 in the adapalene group were assessed for this outcome via a 6‐point Likert‐like scale. The risk ratio for self‐reported complete or marked improvement was 0.89 (95% CI 0.59 to 1.34). A similar 6‐point Likert‐like scale was used in another trial (Thiboutot 2007), in which 149 participants were treated with BPO and 148 with placebo. The risk ratio for self‐reported complete or marked improvement was 0.88 (95% CI 0.63 to 1.22). Sensitivity analysis including both studies revealed similar results (RR 0.99, 95% CI 0.90 to 1.08). These results consistently suggested no difference in self‐assessed improvement between the two groups. InMiyachi 2016, where self‐reported improvement was assessed via a 100‐mm visual analog scale (0 mm = not completely satisfactory, 100 mm = very satisfactory), the average (± standard deviation) score at 12 weeks was 79.6 ± 22.0 mm for BPO and 74.4 ± 19.7 mm for adapalene.
Primary outcome: withdrawal due to adverse effects
A total of 11 trials reported the long‐term outcome (Babaeinejad 2013;do Nascimento 2003;Fleischer 2010;Gold 2009;Gollnick 2009;Hayashi 2018;Iftikhar 2009;Jawade 2016;Korkut 2005;Miyachi 2016;Thiboutot 2007), and one reported the medium‐term outcome (Stinco 2007).
Main pooled analyses: BPO versus adapalene
We did not observe significant differences in the long‐term withdrawal rate between BPO and adapalene, with an RR of 1.85 (95% CI 0.94 to 3.64; 3295 participants; 11 studies; I² = 0%;Analysis 2.2). As shown in the funnel plot (Figure 6) and on Egger's test (P = 0.407), no evidence suggests potential publication bias. For medium‐term data, no participants discontinued treatment inStinco 2007.
2.2. Analysis.
Comparison 2 BPO versus adapalene, Outcome 2 Withdrawal due to adverse effects (long‐term data).
6.
Funnel plot of comparison: 2 BPO versus adapalene, outcome: 2.2 Withdrawal due to adverse effects (long‐term data).
Subgroup analyses: co‐intervention
No significant between‐group differences by co‐interventions were observed in subgroup analyses for the long‐term outcome (P = 0.60).
Secondary outcome: investigator‐assessed change in lesion counts
Although lesion counts were assessed in nine included trials (Babaeinejad 2013;do Nascimento 2003;Fleischer 2010;Hayashi 2018;Iftikhar 2009;Korkut 2005;Miyachi 2016;Shwetha 2014;Thiboutot 2007), sufficient data were available from only four trials for our review to estimate the effect size for the absolute or percentage change in TLs, ILs, or NILs (Hayashi 2018;do Nascimento 2003;Fleischer 2010;Shwetha 2014).
Main pooled analyses: BPO versus adapalene
In the trial comparing BPO/clindamycin with adapalene plus clindamycin among 349 participants (Hayashi 2018), the mean difference in absolute change in TLs, ILs, and NILs assessed after a long‐term treatment duration was ‐1.70 (95% CI ‐5.46 to 2.06;Analysis 2.3), ‐1.10 (95% CI ‐2.42 to 0.22;Analysis 2.4), and ‐0.60 (95% CI ‐3.65 to 2.45;Analysis 2.5), respectively, with no significant differences between the two groups. Counterparts reported in this trial were ‐0.70 (95% CI ‐5.09 to 3.69;Analysis 2.6), ‐1.90 (95% CI ‐3.44 to ‐0.36;Analysis 2.7), and 1.20 (95% CI ‐2.46 to 4.86;Analysis 2.8) for the medium‐term period and ‐4.70 (95% CI ‐9.39 to ‐0.01;Analysis 2.9), ‐2.60 (95% CI ‐4.29 to ‐0.91;Analysis 2.10), and ‐2.00 (95% CI ‐6.02 to 2.02;Analysis 2.11) for the short‐term period, respectively.
2.3. Analysis.
Comparison 2 BPO versus adapalene, Outcome 3 Investigator‐assessed absolute change in total lesions (long‐term data).
2.4. Analysis.
Comparison 2 BPO versus adapalene, Outcome 4 Investigator‐assessed absolute change in inflammatory lesions (long‐term data).
2.5. Analysis.
Comparison 2 BPO versus adapalene, Outcome 5 Investigator‐assessed absolute change in non‐inflammatory lesions (long‐term data).
2.6. Analysis.
Comparison 2 BPO versus adapalene, Outcome 6 Investigator‐assessed absolute change in total lesions (medium‐term data).
2.7. Analysis.
Comparison 2 BPO versus adapalene, Outcome 7 Investigator‐assessed absolute change in inflammatory lesions (medium‐term data).
2.8. Analysis.
Comparison 2 BPO versus adapalene, Outcome 8 Investigator‐assessed absolute change in non‐inflammatory lesions (medium‐term data).
2.9. Analysis.
Comparison 2 BPO versus adapalene, Outcome 9 Investigator‐assessed absolute change in total lesions (short‐term data).
2.10. Analysis.
Comparison 2 BPO versus adapalene, Outcome 10 Investigator‐assessed absolute change in inflammatory lesions (short‐term data).
2.11. Analysis.
Comparison 2 BPO versus adapalene, Outcome 11 Investigator‐assessed absolute change in non‐inflammatory lesions (short‐term data).
For the percentage change in TLs, ILs, and NILs, the mean difference was ‐2.63 (95% CI ‐18.42 to 13.15; 869 participants; 4 studies; I² = 98%;Analysis 2.12), ‐5.70 (95% CI ‐21.14 to 9.74; 806 participants; 4 studies; I² = 98%;Analysis 2.13), and ‐7.09 (95% CI ‐21.39 to 7.21; 806 participants; 4 studies; I² = 97%;Analysis 2.14). Counterparts for the medium‐term period reported in this trial were 0.56 (95% CI ‐5.04 to 6.16; 547 participants; 2 studies; I² = 33%;Analysis 2.15), 5.55 (95% CI 1.58 to 9.52; 689 participants; 3 studies; I² = 0%;Analysis 2.16), and 0.89 (95% CI ‐8.35 to 10.12; 689 participants; 3 studies; I² = 71%;Analysis 2.17), and for the short‐term period, 4.50 (95% CI 0.22 to 8.78; 547 participants; 2 studies; I² = 10%;Analysis 2.18), 9.12 (95% CI 4.98 to 13.26; 689 participants; 3 studies; I² = 3%;Analysis 2.19), and 6.18 (95% CI ‐1.80 to 14.15; 689 participants; 3 studies; I² = 64%;Analysis 2.20), respectively.
2.12. Analysis.
Comparison 2 BPO versus adapalene, Outcome 12 Investigator‐assessed percentage change in total lesions (long‐term data).
2.13. Analysis.
Comparison 2 BPO versus adapalene, Outcome 13 Investigator‐assessed percentage change in inflammatory lesions (long‐term data).
2.14. Analysis.
Comparison 2 BPO versus adapalene, Outcome 14 Investigator‐assessed percentage change in non‐inflammatory lesions (long‐term data).
2.15. Analysis.
Comparison 2 BPO versus adapalene, Outcome 15 Investigator‐assessed percentage change in total lesions (medium‐term data).
2.16. Analysis.
Comparison 2 BPO versus adapalene, Outcome 16 Investigator‐assessed percentage change in inflammatory lesions (medium‐term data).
2.17. Analysis.
Comparison 2 BPO versus adapalene, Outcome 17 Investigator‐assessed percentage change in non‐inflammatory lesions (medium‐term data).
2.18. Analysis.
Comparison 2 BPO versus adapalene, Outcome 18 Investigator‐assessed percentage change in total lesions (short‐term data).
2.19. Analysis.
Comparison 2 BPO versus adapalene, Outcome 19 Investigator‐assessed percentage change in inflammatory lesions (short‐term data).
2.20. Analysis.
Comparison 2 BPO versus adapalene, Outcome 20 Investigator‐assessed percentage change in non‐inflammatory lesions (short‐term data).
Subgroup analyses: co‐intervention
The percentage change in TLs, ILs, and NILs may differ by co‐interventions (Analysis 2.12;Analysis 2.13;Analysis 2.14;Analysis 2.17;Analysis 2.20). BPO monotherapy seemed to achieve greater reduction in TLs for the long term (Analysis 2.12) and in NILs for the medium (Analysis 2.17) and short term (Analysis 2.20) than adapalene monotherapy. On the other hand, greater reduction in ILs and NILs was observed with BPO/clindamycin versus adapalene plus clindamycin for the long term (Analysis 2.13;Analysis 2.14). We did not observe significant differences in the changes in any other acne lesions (Analysis 2.15;Analysis 2.16;Analysis 2.18;Analysis 2.19).
Studies not included in the meta‐analysis
We also found some studies that assessed the change in acne lesions but did not provide sufficient data for meta‐analysis. For the comparison between BPO monotherapy versus adapalene monotherapy, we can compare the lesions between groups at end of treatment from only two trials (Babaeinejad 2013;Korkut 2005): the mean difference was 3.62 (95% CI 2.02 to 5.22; I² = 0%) in TLs, ‐1.25 (95% CI ‐4.23 to 1.73; I² = 80%) in ILs, and 2.45 (95% CI 0.87 to 4.04; I² = 0%) in NILs. InIftikhar 2009, no significant difference in the absolute reduction in TLs was found. The percentage reduction in TLs (35.6% versus 35.4%), ILs (43.6% versus 45.7%), and NILs (36.4% versus 33.3%) was similar between trial groups (Thiboutot 2007). InMiyachi 2016, which compared BPO with adapalene in participants (104 versus 101 participants), the percentage reduction in TLs was 73.5% versus 62.7%, with a significant difference (MD 10.80%, 95% CI 3.38 to 18.22%). The average percentage reduction in ILs and NILs was 78.9% versus 66.2% and 78.8% versus 61.1% (with no significance test results available), respectively.
Secondary outcome: percentage of participants rated 'clear' or 'almost clear' on the IGA scale of acne severity
This outcome was reported in five trials (Hayashi 2018;Fleischer 2010;Gold 2009;Gollnick 2009;Thiboutot 2007).
Main pooled analyses: BPO versus adapalene
Overall, there were no significant differences in this outcome after a long‐term treatment duration (RR 1.12, 95% CI 0.95 to 1.32; 2512 participants; 5 studies; I² = 20%;Analysis 2.21), regardless of BPO used as monotherapy or add‐on treatment. A shorter treatment period seemed to find the higher probability of achieving 'clear' or 'almost clear' in the BPO group, as shown by the risk ratio for the medium term (RR 1.36, 95% CI 1.07 to 1.74; 2314 participants; 4 studies; I² = 0%;Analysis 2.22) and for the short term (RR 2.14, 95% CI 1.41 to 3.27; 2314 participants; 4 studies; I² = 0%;Analysis 2.23).
2.21. Analysis.
Comparison 2 BPO versus adapalene, Outcome 21 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (long‐term data).
2.22. Analysis.
Comparison 2 BPO versus adapalene, Outcome 22 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (medium‐term data).
2.23. Analysis.
Comparison 2 BPO versus adapalene, Outcome 23 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (short‐term data).
Subgroup analyses: co‐intervention
No evidence suggests that co‐intervention may alter the effects of BPO on this outcome for a long, medium, or short period (all P values for testing subgroup differences > 0.05;Analysis 2.21;Analysis 2.22;Analysis 2.23).
Secondary outcome: change in quality of life
Studies not included in the meta‐analysis
Only one trial assessed the outcome using Skindex‐16 for the comparison between BPO/clindamycin versus adapalene plus clindamycin among 349 participants (Hayashi 2018). Trial results suggest no significant differences between the two groups for the long‐term period, with an MD of ‐0.17 (95% CI ‐0.37 to 0.03;Analysis 2.24). For medium‐ and short‐term periods, more benefits were observed in the BPO add‐on treatment group, with an MD of ‐0.22 (95% CI ‐0.42 to ‐0.02;Analysis 2.25) and ‐0.22 (95% CI ‐0.41 to ‐0.03;Analysis 2.26), respectively.
2.24. Analysis.
Comparison 2 BPO versus adapalene, Outcome 24 Change in quality of life (long‐term data).
2.25. Analysis.
Comparison 2 BPO versus adapalene, Outcome 25 Change in quality of life (medium‐term data).
2.26. Analysis.
Comparison 2 BPO versus adapalene, Outcome 26 Change in quality of life (short‐term data).
Secondary outcome: percentage of participants experiencing any adverse event
The outcome was reported in 10 trials for a long‐term treatment duration (Babaeinejad 2013;do Nascimento 2003;Fleischer 2010;Gold 2009;Gollnick 2009;Hayashi 2018;Korkut 2005;Miyachi 2016;Shwetha 2014;Thiboutot 2007), and in two trials for a medium‐term treatment duration (Dudhia 2015;Stinco 2007).
Main pooled analyses: BPO versus adapalene
Of the ten trials, seven provided the number of participants with adverse events, and pooled results from these trials show no significant difference in the long‐term outcome between the two groups (RR 0.71, 95% CI 0.50 to 1.00; 2120 participants; I² = 70%;Analysis 2.27). One trial, conducted exclusively in Japanese people, increased the heterogeneity in this meta‐analysis (Miyachi 2016). Most adverse events were mild to moderate and included skin dryness, peeling, burning, redness, nasopharyngitis, erythema, and application site pain.
2.27. Analysis.
Comparison 2 BPO versus adapalene, Outcome 27 Percentage of participants with any adverse events (long‐term data).
The risk of adverse events for the short‐term treatment duration was substantially uncertain, with an RR of 3.00 (95% CI 0.13 to 68.26; 70 participants; 2 studies; I² = 0%;Analysis 2.28). No adverse events for the medium‐term period were reported in the trial, which included 40 participants in total (Stinco 2007). After the four‐week treatment, one of 15 participants treated with BPO plus clindamycin had hyperpigmentation, and none of 15 participants treated with adapalene plus clindamycin reported an adverse event (Dudhia 2015).
2.28. Analysis.
Comparison 2 BPO versus adapalene, Outcome 28 Percentage of participants with any adverse events (short‐term data).
Subgroup analyses: co‐intervention
We did not observe that the long‐term outcome differed by co‐intervention (P value for subgroup differences = 0.44;Analysis 2.27).
Studies not included in the meta‐analysis
Another two trials mentioned only that no statistical differences in adverse events were found between the two groups (Gold 2009;Korkut 2005).
BPO versus clindamycin
This comparison comprised eight parallel trials (Eichenfield 2011;Leyden 2001a;Lookingbill 1997;Schmidt 1988;Swinyer 1988;Thiboutot 2008;Tschen 2001;Tucker 1984). The treatment duration was long. All of the outcomes of interest in this review were available, except change in quality of life and reduction inC acne strains. SeeTable 3, where we rated the evidence for the two primary outcomes and the secondary safety outcome.
Primary outcome: participant global self‐assessment of acne improvement
Trials assessing this outcome were all long‐term trials (Draelos 2002;Leyden 2001a;Thiboutot 2008;Tschen 2001), one of which provided sufficient data to estimate the effect size (Leyden 2001a).
Main pooled analyses: BPO versus clindamycin
With 120 participants treated with BPO and 120 with clindamycin, the risk ratio of treatment success assessed via a 5‐point Likert‐like scale was 0.95 (95% CI 0.68 to 1.34;Analysis 3.1) (Leyden 2001a).
3.1. Analysis.
Comparison 3 BPO versus clindamycin, Outcome 1 Participant's global self‐assessment of improvement (long‐term data).
Studies not included in the meta‐analysis
We did not pool the results with those from the other three trials (Draelos 2002;Thiboutot 2008;Tschen 2001), given that the number of treatment successes defined in our review was not available (Appendix 9). However, sensitivity analysis including these studies showed a similar result (RR 1.05, 95% CI 0.97 to 1.15) to the main analysis.
Thiboutot 2008 randomly assigned 809 participants to the BPO group and 812 to the clindamycin group and assessed the outcome after 12 weeks using a 7‐point Likert‐like scale. The risk ratio for self‐reported clear or almost clear was 1.00 (95% CI 0.86 to 1.16).
In another 10‐week trial (Tschen 2001), a 7‐point Likert‐like scale (from 3 = much better to ‐3 = much worse) was used to assess the outcome for 95 participants treated with BPO and 49 participants treated with clindamycin. The risk ratio for achieving "much better" improvement on the scale was 1.77 (95% CI 0.82 to 3.81). These results consistently suggest similar effects of both treatments.
Draelos 2002, with 89 participants on BPO plus tazarotene and 87 participants on clindamycin plus tazarotene, assessed this outcome using a 5‐point Likert‐like scale (from highly favourable to highly unfavourable). At week 12, no significant difference was found in the proportion of participants rating improvement as highly favourable or favourable (92% versus 85%; P > 0.05). We cannot estimate RR as the effect size because data were not sufficient to calculate the number of participants with treatment success defined in our review.
Primary outcome: withdrawal due to adverse effects
Main pooled analyses: BPO versus clindamycin
Eight long‐term trials assessing this outcome suggest no clear differences in withdrawal due to adverse effects (Draelos 2002;Eichenfield 2011;Leyden 2001a;Lookingbill 1997;Study 156;Swinyer 1988;Thiboutot 2008;Tschen 2001) (RR 1.93, 95% CI 0.90 to 4.11; 3330 participants; 8 studies; I² = 0%;Analysis 3.2). Reasons for withdrawal from these trials included application site hypersensitivity, pruritus, erythema, face oedema, rash, and skin burning.
3.2. Analysis.
Comparison 3 BPO versus clindamycin, Outcome 2 Withdrawal due to adverse effects (long‐term data).
Subgroup analyses: co‐intervention
No evidence suggests that either BPO monotherapy or BPO add‐on treatment can increase the risk of withdrawal due to adverse events, with no significant differences between co‐intervention subgroups (P = 0.58).
Secondary outcome: investigator‐assessed change in lesion counts
This outcome was assessed in 10 included trials (Draelos 2002;Eichenfield 2011;Leyden 2001a;Lookingbill 1997;Study 152;Study 156;Swinyer 1988;Thiboutot 2008;Tschen 2001;Tucker 1984). Two of these trials provided sufficient long‐term data to estimate effect size in our review (Eichenfield 2011;Lookingbill 1997).
Main pooled analyses: BPO versus clindamycin
The absolute change in TLs was ‐3.50 (95% CI ‐7.54 to 0.54;Analysis 3.3), derived from a total of 323 participants treated with BPO and 318 participants treated with clindamycin (Eichenfield 2011). This trial also showed the absolute change in ILs (‐1.20, 95% CI ‐2.99 to 0.59;Analysis 3.4) and NILs (‐2.40, 95% CI ‐5.30 to 0.50;Analysis 3.5). These results did not show significant differences in absolute change for each lesion type.
3.3. Analysis.
Comparison 3 BPO versus clindamycin, Outcome 3 Investigator‐assessed absolute change in total lesions (long‐term data).
3.4. Analysis.
Comparison 3 BPO versus clindamycin, Outcome 4 Investigator‐assessed absolute change in inflammatory lesions (long‐term data).
3.5. Analysis.
Comparison 3 BPO versus clindamycin, Outcome 5 Investigator‐assessed absolute change in non‐inflammatory lesions (long‐term data).
As for the percentage change, the mean difference reported inLookingbill 1997 was in NILs (21.00, 95% CI 6.86 to 35.14;Analysis 3.7) but not in ILs (4.00, 95% CI ‐8.56 to 16.56;Analysis 3.6) (92 participants treated with BPO and 89 with clindamycin contributed to these two estimates).
3.7. Analysis.
Comparison 3 BPO versus clindamycin, Outcome 7 Investigator‐assessed percentage change in non‐inflammatory lesions (long‐term data).
3.6. Analysis.
Comparison 3 BPO versus clindamycin, Outcome 6 Investigator‐assessed percentage change in inflammatory lesions (long‐term data).
Studies not included in the meta‐analysis
For the absolute change,Leyden 2001a reported the absolute change in both TLs (‐13.8 versus ‐6.2) and ILs (‐5.9 versus ‐3.2) in the BPO group (120 participants) compared to the clindamycin group (120 participants) at week 10.Tschen 2001 found some difference (‐12.4 in ILs for BPO (95 participants) versus ‐14.7 for clindamycin (49 participants); P < 0.034). InTucker 1984, trial authors reported the absolute change in comedone, papule, pustule, and cyst lesions at week 10 separately: corresponding results were ‐6.8 versus ‐7.3, ‐9.5 versus ‐9.7, ‐5.7 versus ‐3.4, and ‐0.05 versus ‐2.3.
The percentage reduction in TLs, ILs, and NILs was 25.5% versus 23.5%, 33.5% versus 29.8%, and 18.8% versus 11.2% for the BPO group (n = 70) and the clindamycin group (n = 70) inStudy 152. InStudy 156, the percentage reduction in TLs, ILs, and NILs was 43.3% versus 33.3% (P = 0.008), 56.7% versus 48.6% (0.048), and 28.7% versus 18.0% (0.037) for the BPO group (n = 96) versus the clindamycin group (n = 96). Another trial found a significant difference in the percentage reduction in NILs (62.9% (BPO, 30 participants) versus 37.1% (clindamycin, 30 participants); P < 0.001) at week 12 (Swinyer 1988). ForThiboutot 2008, 809 participants were randomised to the BPO group and 812 to the clindamycin group. The percentage reduction was 41.6% versus 40.4% in TLs, 47.5% versus 46.2% in ILs, and 37.4% versus 36.2% in NILs at week 12. InDraelos 2002, the percentage reduction in both ILs (39.7% versus 40.2%; P > 0.05) and NILs (42.7% versus 55.4%; P > 0.05) at week 12 was similar between two groups. For the medium‐ and the short‐term period, both treatments reduced NILs by about 40% and 30%, respectively, with no significant differences. Similar effects on reducing ILs were also observed (31% versus 35% for the medium‐term period and 24% versus 22% for the short‐term period). We cannot estimate MD as the effect size because data were not sufficient to calculate standard deviation.
Secondary outcome: percentage of participants rated 'clear' or 'almost clear' on the IGA scale of acne severity
Main pooled analyses: BPO versus clindamycin
The long‐term outcome was reported in two 12‐week trials (Eichenfield 2011;Thiboutot 2008). With a total of 1137 and 1140 participants treated with BPO and clindamycin, respectively, heterogeneity was substantial, with no significant difference in this outcome (RR 1.10, 95% CI 0.83 to 1.45; 2277 participants; 2 studies; I² = 72%;Analysis 3.8).
3.8. Analysis.
Comparison 3 BPO versus clindamycin, Outcome 8 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (long‐term data).
Secondary outcome: percentage of participants experiencing any adverse event
The outcome was reported in five trials, all of which provided long‐term data (Eichenfield 2011;Leyden 2001a;Lookingbill 1997;Thiboutot 2008;Tschen 2001).
Main pooled analyses: BPO versus clindamycin
The risk of adverse events may be higher with BPO than with clindamycin (RR 1.24, 95% CI 0.97 to 1.58; 3018 participants; 6 studies; I² = 0%;Analysis 3.9). The most common adverse events reported in these trials included skin dryness, pruritus, burning, tingling, and headache.
3.9. Analysis.
Comparison 3 BPO versus clindamycin, Outcome 9 Percentage of participants with any adverse events (long‐term data).
Subgroup analyses: co‐intervention
No evidence suggests that co‐intervention affected the association between BPO and adverse events (P value for subgroup differences = 0.43;Analysis 3.9).
BPO versus erythromycin
The comparison was made in four trials (Burke 1983;Cassano 2002;Chalker 1983;Dogra 1993), which provided data for withdrawal due to adverse effects, lesion counts, and adverse events. SeeTable 4, where we rated evidence for the two primary outcomes and the secondary safety outcome.
Primary outcome: withdrawal due to adverse effects
Main pooled analyses: BPO versus erythromycin
With 30 participants equally assigned to each group, an eight‐week trial reported that one participant in each group did not complete the trial due to adverse events (both had dermatitis) (Burke 1983). Evidence suggests that the risk of withdrawal was not different between the two groups (RR 1.00, 95% CI 0.07 to 15.26; 30 participants;Analysis 4.1).
4.1. Analysis.
Comparison 4 BPO versus erythromycin, Outcome 1 Withdrawal due to adverse effects (medium‐term data).
Studies not included in the meta‐analysis
Of 44 participants treated with BPO and 45 with erythromycin, none withdrew due to adverse events during a 10‐week trial (Chalker 1983).
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
After a six‐week treatment duration, reduction of 34.8% in NILs and 73.6% in ILs was found in the erythromycin group, which consisted of 25 participants; the counterpart in NILs and ILs was 70.1% and 63.9%, respectively, in the BPO group of 24 participants (Dogra 1993).
Mean lesion counts at each follow‐up were reported in another trial (Burke 1983). At the end of the trial, the mean difference in TLs, ILs, and NILs between BPO and erythromycin groups was ‐5.60 (95% CI ‐8.03 to ‐3.17), ‐0.90 (95% CI ‐1.72 to ‐0.08), and ‐8.40 (95% CI ‐9.87 to ‐6.93), respectively.
In one 16‐week parallel trial involving BPO plus adapalene versus erythromycin plus adapalene (only abstract was available), it is unclear how many participants were randomised to each group (Cassano 2002). With no details on the absolute or percentage reduction in lesion counts, study authors claimed that all these treatments similarly led to a significant reduction in the numbers of papules, pustules, and comedones.
Secondary outcome: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
No adverse events were identified in one trial (Chalker 1983). In another trial, mild erythema and scaling were found in a small number of participants, but the exact number was not reported (Burke 1983). InCassano 2002, tolerability was satisfactory in most cases in each treatment arm. Itching and burning occurred in the early phase in both groups, but the intensity of these symptoms was gradually decreased. We cannot calculate RR for these trials as the effect size because the number of participants with at least one adverse event was not provided.
BPO versus salicylic acid
This comparison comprises three parallel trials (Bissonnette 2009;Chantalat 2005;Chantalat 2006), along with one cross‐over trial (Shalita 1989).Chantalat 2005 did not present any outcomes of interest in this review in the abstract. For the other three trials, all outcomes of interest, except the percentage of participants rated 'clear' or 'almost clear' and the reduction inC acnes strains, were reported in at least one of these trials. SeeTable 5, where we rated evidence for the two primary outcomes and the secondary safety outcome.
Primary outcome: participant global self‐assessment of acne improvement
Studies not included in the meta‐analysis
Bissonnette 2009, a 12‐week trial, andChantalat 2006, a six‐week trial, assessed this outcome; neither provided sufficient data to estimate the effect size (Appendix 9).
A total of 80 participants with mild to moderate facial acne were randomised to either BPO or salicylic acid, and no significant difference was found (P = 0.81) (Bissonnette 2009). According to the other trial, which included 21 participants treated with BPO and 20 with salicylic acid, self‐assessment results favoured salicylic acid in terms of improvements in tone and texture (Chantalat 2006).
Primary outcome: withdrawal due to adverse effects
Studies not included in the meta‐analysis
One trial reported that no participants terminated treatment due to adverse events (Appendix 10) (Bissonnette 2009).
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
Evidence inBissonnette 2009 showed no difference in ILs (P = 0.748) or NILs (P = 0.445) between two groups. With 30 participants randomised in a four‐week cross‐over trial, a significant reduction in comedones was found in those treated with salicylic acid cleanser (Shalita 1989). However, neither of the trial reports provided sufficient data to estimate the effect size.
Secondary outcome: change in quality of life
Studies not included in the meta‐analysis
As reported inChantalat 2006, participants treated with salicylic acid had a significant improvement in acne‐related quality of life (ARQL). This effect started at the second week and continued through the following four weeks. By contrast, such an effect was not found in the BPO group. Insufficient data were available from both trials to estimate the effect size.
Secondary outcome: percentage of participants experiencing any adverse event
Main pooled analyses: BPO versus salicylic acid
Although 16 of 80 participants in the trial had at least one adverse event during treatment (Bissonnette 2009), the number of participants with adverse events was not reported for each group. InChantalat 2006, two of 21 participants treated with BPO experienced an adverse event, but no adverse events occurred among 20 participants in the salicylic acid group, with an RR of 4.77 (95% CI 0.24 to 93.67;Analysis 5.1).
5.1. Analysis.
Comparison 5 BPO versus salicylic acid, Outcome 1 Percentage of participants with any adverse events (medium‐term data).
Results for the other comparisons
BPO versus tretinoin
Four long‐term trials ‐Bowman 2005;Gupta 2003;Jackson 2010;Kaur 2015 ‐ and two medium‐term trials with parallel design ‐Lyons 1978;Shahid 1996 ‐ focused on this comparison. Outcomes of interest in this review were available in these trials. Another small‐scale trial including only eight participants did not cover any outcomes of interest in this review and focused merely on changes in the microbiome after topical treatment with BPO or tretinoin (Coughlin 2017).
Primary outcome: participant global self‐assessment of acne improvement
Studies not included in the meta‐analysis
This outcome was reported only in a 12‐week trial comparing BPO (5%)/erythromycin (3%) with tretinoin (0.025%)/erythromycin (4%) among 112 participants (Gupta 2003), but the data provided were not sufficient to calculate the effect size of treatment success defined in our review. Participants rated the overall change in their facial acne using a 7‐point scale (‐1 = exacerbation, 0 = no change, 1 = modest clearing, 2 = marked change, 3 = good, 4 = almost cleared, 5 = completely cleared). Trial authors claimed that scores rated in the BPO/erythromycin group were lower than those in the tretinoin/erythromycin group, with a significant difference as early as week 2.
Primary outcome: withdrawal due to adverse effects
Main pooled analyses: BPO versus tretinoin
Three trials reported the long‐term outcome, with no statistical difference between BPO and tretinoin (RR 1.11, 95% CI 0.07 to 17.36; 200 participants; I² = 0%;Analysis 6.1) (Bowman 2005;Gupta 2003;Jackson 2010). In one 10‐week trial (Bowman 2005), in which 43 were treated with BPO/clindamycin and 45 with tretinoin plus clindamycin, no participants in each group discontinued treatments due to adverse events during the trial. In one 16‐week trial (Jackson 2010), which included 27 participants in each group (BPO/clindamycin versus tretinoin/clindamycin), no participants discontinued treatment because of adverse effects. Only two participants (2/112) inGupta 2003 did not complete the study due to severe burning or stinging, with one in each group.
6.1. Analysis.
Comparison 6 BPO versus tretinoin, Outcome 1 Withdrawal due to adverse effects (long‐term data).
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
We cannot estimate MD as the effect size for this outcome because data were not sufficient to calculate standard deviation as reported in the included studies. In an eight‐week trial analysing 54 participants treated with BPO acetone gel (Lyons 1978), 38 treated with BPO alcohol/detergent gel and 55 with tretinoin cream, trial authors reported that no statistical differences in the change in comedones, pustules, and total lesions were found between groups. However, both BPO gels reduced papules by 59% ‐ significantly higher than 29% with tretinoin cream.
In one 12‐week parallel trial with 33 participants randomised to each group (BPO plus clindamycin versus tretinoin plus clindamycin) (Kaur 2015), the mean number of ILs was reduced from 3.6 to 0 among participants on BPO plus clindamycin and from 4.9 to 0.3 among participants on tretinoin plus clindamycin. The mean number of NILs was reduced from 12.0 to 0 among participants on BPO plus clindamycin, and from 13.7 to 1.3 among participants on tretinoin plus clindamycin. It is unclear whether there was a significant difference between the two groups.
In one 10‐week trial (Bowman 2005), the percentage reduction in TLs, ILs, and NILs at week 10 in the BPO/clindamycin group was 61.4%, 65.7%, and 57.2%, respectively, compared to 49.6%, 52.5%, and 46.2% in the other group. A significant difference was found in the percentage reduction in ILs (P = 0.02). For medium‐term and short‐term treatment durations, the percentage reduction in TLs (medium term: 51.2% versus 40.9%; short term: 42.1% versus 35.3%), ILs (61.0% versus 44.9%; 53.9% versus 45.7%), and NILs (42.8% versus 37.9%; 32.0% versus 21.9%) was consistently greater in the BPO/clindamycin treatment group, but it is unclear whether significant differences existed, as no relevant information was reported.
The median percentage reduction reported inJackson 2010 was 52.4% versus 54.3% in TLs, 74.1% versus 70.7% in ILs, and 53.3% versus 52.8% in NILs at week 16. The median percentage reduction in TLs was 52.4% versus 54.3%, 51.8% versus 44.5%, and 43.8% versus 31.3% for the long‐, medium‐, and short‐term periods. Trial authors claimed that the difference between groups was comparable, except that the short‐term period favoured BPO/clindamycin treatment. No significant difference was observed in the median percentage reduction in ILs and NILs at any time points (long term: 74.1% versus 70.7% in ILs, 53.3% versus 52.8% in NILs; medium term: 61.6% versus 46.7% in ILs, 30.9% versus 36.8% in NILs; short term: 53.7% versus 32.5% in ILs, 39.9% versus 25.1% in NILs).
No significant difference was found inGupta 2003 for the absolute reduction in ILs or NILs at any time points between groups. The mean number of papules was reduced from 16.0 at baseline to 10 (short term), to 8 (medium term), and to 5.5 (long term) among participants on BPO/erythromycin The counterpart in participants on tretinoin/erythromycin was reduced from 17.7 to 12, to 8, and to 5.5, respectively. The number of pustules in BPO/erythromycin was reduced from 7.1 to 3.7, to 3, and to 2.3 for short‐, medium‐, and long‐term periods, respectively, and the counterpart in tretinoin/erythromycin was decreased from 8.3 to 3.7, to 2, and to 1.5. The mean number of comedones was reduced from 28.2 to 21.3, to 16.3, and to 9.3 in participants on BPO/erythromycin for short‐, medium‐, and long‐term periods, respectively. The counterpart was reduced from 35.5 to 21.3, to 13.1, to 11.7 in participants on tretinoin/erythromycin.
Secondary outcome: percentage of participants rated 'clear' or 'almost clear' on the IGA scale of acne severity
Main pooled analyses: BPO versus tretinoin
At week 10, the percentage of participants rated 'clear' or 'almost clear' on the IGA scale of acne severity was not significantly different between the BPO/clindamycin group and the tretinoin plus clindamycin group (RR 2.09, 95% CI 0.86 to 5.08; 88 participants;Analysis 6.2).
6.2. Analysis.
Comparison 6 BPO versus tretinoin, Outcome 2 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (long‐term data).
Secondary outcome: reduction inC acnes strains (total and resistant)
Studies not included in the meta‐analysis
This outcome was reported only inJackson 2010 for this comparison. The reduction in total, erythromycin‐resistant, and clindamycin‐resistantC acnes strains at week 16 (log10 CFU cm‐2) was ‐1.84 versus ‐0.78 (P < 0.003), ‐0.83 versus 0.3 (P < 0.002), and ‐0.73 versus 0.05 (P < 0.002).
Secondary outcome: percentage of participants experiencing any adverse event
Main pooled analyses: BPO versus tretinoin
For the long‐term treatment duration, we did not observe significant differences between the two groups, with an RR of 0.58 (95% CI 0.31 to 1.07; 166 participants; 2 studies; I² = 29%;Analysis 6.3). Trial authors did not report further information regarding what adverse events were observed inJackson 2010. The most frequently reported adverse events inGupta 2003 were facial dryness, stinging/burning, erythema, pruritus, and peeling/scaling. No significant differences were found between groups for any individual adverse events, except erythema (6% versus 19%; P = 0.047).
6.3. Analysis.
Comparison 6 BPO versus tretinoin, Outcome 3 Percentage of participants with any adverse events (long‐term data).
The outcome reported in trials for BPO monotherapy versus tretinoin was only for a medium‐term treatment duration (103 participants in BPO groups and 67 in the tretinoin group), with an RR of 0.03 (95% CI 0.00 to 0.48; 170 participants; 2 studies; I² = 0%;Analysis 6.4).Shahid 1996 specified that no participants in both groups reported any adverse events. InLyons 1978, no adverse events were reported in either of the two BPO groups, but 18.2% (10/55) of participants treated with tretinoin cream experienced at least one adverse event, including burning, erythema, peeling, and soreness.
6.4. Analysis.
Comparison 6 BPO versus tretinoin, Outcome 4 Percentage of participants with any adverse events (medium‐term data).
Subgroup analyses: co‐intervention
No evidence suggests that this association may differ by co‐intervention (P value for subgroup differences = 0.24;Analysis 6.3).
Studies not included in the meta‐analysis
We cannot calculate RR as the effect size for these trials because the number of participants with at least one adverse event was not provided (Bowman 2005;Kaur 2015).
Burning sensation and dryness were the only two adverse events that occurred during theKaur 2015. Burning sensation occurred in one participant on BPO plus clindamycin, and dryness occurred in four participants on tretinoin plus clindamycin.
Although no significance test results were provided,Bowman 2005 reported that adverse events were substantially more common among participants on BPO/clindamycin than among those on tretinoin and clindamycin. The most common adverse events were irritation (11.6% versus 17.9%), dryness (7.0% versus 15.6%), desquamation (7.0% versus 11.1%), and erythema (4.7% versus 8.9%).
BPO versus isotretinoin
Three trials of parallel design focused on this comparison ‐ one for four weeks including 16 participants treated with BPO and 13 with isotretinoin (Cunliffe 2001), one for 12 weeks including 26 participants treated with BPO and 25 with isotretinoin (Hughes 1992), and another 12‐week trial (Marazzi 2002), which included 93 participants treated with BPO/erythromycin and 95 participants with isotretinoin/erythromycin. The outcomes of interest in this review available for these trials were participant global self‐assessment, withdrawal due to adverse effects, lesion counts, and adverse events.
Primary outcome: participant global self‐assessment of acne improvement
Studies not included in the meta‐analysis
InMarazzi 2002, participants rated the overall change in their facial acne as improved, no change, or worse. There was no significant difference between the two groups in the proportion of participants rated as "improved" (P value = 0.26).
Primary outcome: withdrawal due to adverse effects
Main pooled analyses: BPO versus isotretinoin
The risk of withdrawal due to adverse effects was not significantly different (RR 1.23, 95% CI 0.53 to 2.87; 239 participants; 2 studies; I² = 0%;Analysis 7.1) inHughes 1992 andMarazzi 2002).Hughes 1992 did not specify what adverse events led to their discontinuation. Nine participants on BPO/erythromycin and eight participants on isotretinoin/erythromycin withdrew due to adverse events, with no significant differences between the two groups (Marazzi 2002). The major event leading to withdrawal was infection requiring antibiotic treatment. Besides, two participants on BPO/erythromycin and five on isotretinoin/erythromycin withdrew because of skin reactions to these products.
7.1. Analysis.
Comparison 7 BPO versus isotretinoin, Outcome 1 Withdrawal due to adverse effects (long‐term data).
Subgroup analyses: co‐intervention
No evidence suggests that this association may differ by co‐intervention (P value for subgroup differences = 0.24;Analysis 7.1).
Studies not included in the meta‐analysis
No participants inCunliffe 2001 withdrew as a result of any adverse events.
Secondary outcome: investigator‐assessed change in lesion counts
Main pooled analyses: BPO versus isotretinoin
For the comparison between BPO/erythromycin and isotretinoin/erythromycin, no significant difference was found in the absolute reduction in ILs (MD ‐4.00, 95% CI ‐9.89 to 1.89;Analysis 7.2) for the long‐term period. However, the counterpart for medium‐term and short‐term periods was significantly different, favouring BPO/erythromycin, with an MD of ‐6.10 (95% CI ‐11.27 to ‐0.93;Analysis 7.4) and ‐9.20 (95% CI ‐14.09 to ‐4.31;Analysis 7.6), respectively. In terms of the absolute change in NILs, no significant difference was observed for any time periods (long term: MD 2.30, 95% CI ‐6.07 to 10.67;Analysis 7.3; medium term: MD 4.90, 95% CI ‐1.66 to 11.46;Analysis 7.5; short‐term: MD 1.20, 95% CI ‐4.39 to 6.79;Analysis 7.7).
7.2. Analysis.
Comparison 7 BPO versus isotretinoin, Outcome 2 Investigator‐assessed absolute change in inflammatory lesions (long‐term data).
7.4. Analysis.
Comparison 7 BPO versus isotretinoin, Outcome 4 Investigator‐assessed absolute change in inflammatory lesions (medium‐term data).
7.6. Analysis.
Comparison 7 BPO versus isotretinoin, Outcome 6 Investigator‐assessed absolute change in inflammatory lesions (short‐term data).
7.3. Analysis.
Comparison 7 BPO versus isotretinoin, Outcome 3 Investigator‐assessed absolute change in non‐inflammatory lesions (long‐term data).
7.5. Analysis.
Comparison 7 BPO versus isotretinoin, Outcome 5 Investigator‐assessed absolute change in non‐inflammatory lesions (medium‐term data).
7.7. Analysis.
Comparison 7 BPO versus isotretinoin, Outcome 7 Investigator‐assessed absolute change in non‐inflammatory lesions (short‐term data).
Studies not included in the meta‐analysis
The outcome of lesion counts, rather than the change in lesion counts, was reported inHughes 1992. At the end of the trial (12 weeks), the mean difference between BPO and isotretinoin groups was ‐6.30 (95% CI ‐17.04 to 4.44). The mean difference for the medium‐term outcome (eight weeks) was ‐0.60 (95% CI ‐10.70 to 9.50). This outcome was not available forCunliffe 2001.
Percentage of participants experiencing any adverse event
Main pooled analyses: BPO versus isotretinoin
This outcome was reported in two trials (Cunliffe 2001;Marazzi 2002).
InMarazzi 2002, 53 participants in the BPO/erythromycin group and 64 participants in the isotretinoin/erythromycin group experienced at least one adverse event during the long‐term period, with no significant differences (RR 0.85, 95% CI 0.68 to 1.06; 188 participants;Analysis 7.8). The most common treatment‐related events were burning reported for three participants using BPO/erythromycin and five participants using isotretinoin/erythromycin, followed by itching or redness reported in three participants using BPO/erythromycin and four participants using isotretinoin/erythromycin.
7.8. Analysis.
Comparison 7 BPO versus isotretinoin, Outcome 8 Percentage of participants with any adverse events (long‐term data).
As reported inCunliffe 2001, the risk ratio for the short‐term outcome was 0.18 (95% CI 0.05 to 0.69;Analysis 7.9) in favour of BPO treatment.
7.9. Analysis.
Comparison 7 BPO versus isotretinoin, Outcome 9 Percentage of participants with any adverse events (short‐term data).
Studies not included in the meta‐analysis
Instead of presenting the total number, authors of theHughes 1992 trial described only the numbers of participants for individual adverse events. The most common adverse event for both groups was redness (10/26 for the BPO group and 10/25 for the isotretinoin group), followed by scaling (7/26 and 7/25, respectively).
BPO versus azelaic acid
One trial of parallel design focused on this comparison, including 20 participants treated with BPO and 20 with azelaic acid for 8 weeks (Stinco 2007). Outcomes of interest in this review that were available in these trials were withdrawal due to adverse effects, lesion counts, and adverse events.
Primary outcome: withdrawal due to adverse effects
Studies not included in the meta‐analysis
No withdrawal due to adverse events was reported inStinco 2007.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
At the end ofStinco 2007, ILs were reduced by 45% in the azelaic acid group and 44% in the BPO group. NILs were reduced by 47% for azelaic acid and 38% for BPO. Trial authors reported no significant differences between treatments.
Secondary outcome: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
Although no data on the total number of participants experiencing an adverse event were provided inStinco 2007, trial authors reported individual adverse events. For the BPO group, 12 participants reported itchiness (seven mild and five moderate) after two weeks of treatment. For the azelaic acid group, 20 participants reported itchiness (12 mild, five moderate, and three severe). Dryness occurred in 15 participants treated with BPO (one mild, nine moderate, and five severe) and in 14 treated with azelaic acid (nine mild, three moderate, and two severe). A total of 10 participants in the BPO group (eight mild and two moderate) and six in the azelaic acid group (five mild and one moderate) experienced erythema.
BPO versus retinoic acid
One six‐week trial compared BPO with retinoic acid for treating acne and assessed only the outcome change in lesion counts (Dogra 1993). A total of 24 participants in this trial were treated with BPO and 23 with retinoic acid.
Primary outcomes
No information on the primary outcomes was available.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
After six‐week treatment duration, although reduction in NILs and ILs was 75.2% and 60.7%, respectively, in the retinoic acid group, the counterpart in the BPO group was 70.1% and 63.9% (Dogra 1993).
BPO versus sulphur
In one parallel trial compared BPO and sulphur (Vasarinsh 1969), 16 participants were treated with BPO and 18 with sulphur for 4 to 14 weeks. The report of this trial covered the outcomes of participant self‐assessment of acne improvement, change in acne lesions, and adverse events.
Primary outcome: participant global self‐assessment of acne improvement
Studies not included in the meta‐analysis
This trial assessed the outcome using a 4‐point Likert‐like scale (from worse = ‐1 to greatly improved = 2). The average score was 0.66 and 0.75 for the BPO and sulphur groups, respectively.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
The change in lesion counts was assessed for superficial (comedones and pustules) and deep (papules and cysts) lesions via an 11‐point scoring system (decrease in lesions by 100% = 5, 76% to 99% = 4, 51% to 75% = 3, 26% to 50% = 2, < 25% = 1, no change = 0; increase by < 25% = ‐1, 26% to 50% = ‐2, 51% to 75% = ‐3, 76% to 100% = ‐4, over 100% = ‐5). The average score for superficial lesions was 0.55 and ‐0.70 for BPO and sulphur groups, respectively, and the counterpart for deep lesions was 0.69 and 0.30.
Secondary outcome: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
The study provided only information on individual adverse events. Excessive erythema and dryness occurred in five participants on BPO and four on sulphur. One participant developed severe allergic sensitisation after BPO treatment. We cannot calculate RR as the effect size because the number of participants with at least one adverse event was not provided.
BPO versus hydrogen peroxide
Three eight‐week parallel trials contributed to this comparison (Capizzi 2004;Milani 2003;Tung 2014). These trials covered the outcomes of our review interest including participant global self‐assessment, lesion counts, and total adverse events.
Primary outcome: participant global self‐assessment of acne improvement
Studies not included in the meta‐analysis
One trial including a total of 120 participants assessed this outcome (Tung 2014). However, the data, which were available in an abstract, were not sufficient to estimate the effect size. Study authors reported that both acne regimens were effective but found no statistical difference across arms (P = 0.70).
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
Insufficient data were available to estimate the effect size of either absolute or percentage change.Milani 2003, which included 30 participants treated with BPO and 30 with hydrogen peroxide, reported the mean counts of lesions at week 8. The mean difference in TLs, ILs, and NILs was ‐2.00 (95% CI ‐6.08 to 2.08), 0.00 (95% CI ‐1.52 to 1.52), and ‐2.00 (95% CI ‐4.09 to 0.09), respectively, with no significant difference.
Capizzi 2004, a parallel trial with 26 participants in each group (BPO plus adapalene versus hydrogen peroxide plus adapalene), suggested that BPO reduced the mean number of TLs from 40 to 5.4 and hydrogen peroxide from 44 to 3.2. ILs were decreased from 21 to 3.1 among participants on BPO, and from 25 to 2.5 among participants on hydrogen peroxide, with NILs decreasing from 19 to 2.3 and from 19 to 0.7 (P = 0.0025), respectively.
Secondary outcome: percentage of participants experiencing any adverse event
Main pooled analyses: BPO versus isotretinoin
The outcome was reported in both trials. InMilani 2003, seven of 30 participants with BPO and two of 30 participants with hydrogen peroxide had at least one adverse event, with no significant difference between the two groups (RR 3.50, 95% CI 0.79 to 15.49; 60 participants; 1 study;Analysis 8.1).
8.1. Analysis.
Comparison 8 BPO versus hydrogen peroxide, Outcome 1 Percentage of participants with any adverse events (medium‐term data).
Studies not included in the meta‐analysis
No adverse events were found in each group in the other trial (Tung 2014), where the sample size for each group was not reported. We cannot calculate RR as the effect size forCapizzi 2004 because the number of participants with at least one adverse event was not provided. Dryness, erythema, and burning were observed (19/26 versus 2/26, 5/26 versus 1/26, 4/26 versus 0/26 for BPO and hydrogen peroxide, respectively). A significant difference was found in the occurrence of dryness (P = 0.0025) and burning (P = 0.01).
BPO versus superoxidised solution
Tirado‐Sanchez 2009, a 12‐week parallel trial, focused on this comparison, in which 24 participants were randomly assigned to BPO treatment and 39 to superoxidised solution treatment. The outcomes of our review interest reported in this trial were withdrawal due to adverse effects, change in lesion counts, and occurrence of adverse events.
Primary outcome: withdrawal due to adverse effects
Studies not included in the meta‐analysis
No withdrawal due to adverse events was reported in that trial.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
At the end of the trial, the mean number of ILs was reduced from 35 to 19 in the BPO group and from 34 to 12 in the superoxidised solution group. The proportion of participants with at least 50% reduction in ILs was 17 of 24 versus 30 of 39 with no significant difference.
Secondary outcome: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
Trial authors reported that no local adverse events were noted in each group. We cannot calculate RR as the effect size because the number of participants with at least one adverse event was not provided.
BPO versusCasuarina equisetifolia bark extract
Shafiq 2014, a six‐week parallel trial, focused on this comparison with 25 participants in each group. No efficacy outcomes of interest in this review were reported. Clinical efficacy was assessed by Cook’s acne grading scale and trial authors claimed no significant differences between groups. The only outcome assessed in the trial and relevant to our review was the occurrence of adverse events.
Primary outcomes
No information was available on the primary outcomes.
Secondary outcome: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
Although no severe adverse events were observed in the group receiving treatment withCasuarina equisetifolia bark extract, 17% of participants on BPO treatment complained of irritation, redness, and swelling.
BPO versus Chinese herbal mask
One four‐week parallel trial compared BPO and Chinese medical mask (Zeng 2012). In all, 120 participants were assigned to the BPO group and 113 to the Chinese herbal mask. No efficacy outcomes of interest in this review were reported. The only outcome assessed in the trial and relevant to our review was the occurrence of adverse events.
Primary outcomes: participant global self‐assessment of acne improvement
Studies not included in the meta‐analysis
This outcome was assessed using a questionnaire (no details about the questionnaire were specified) only for the Chinese herbal mask group and not for the BPO group. Of 111 respondents in the assessment, 104 (93.7%) were very satisfied or satisfied with the treatment.
Secondary outcome: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
A total of 3 of 120 participants on BPO treatment and 2 of 112 participants on Chinese herbal mask complained of irritation and redness. We cannot calculate RR as the effect size because the number of participants with at least one adverse event was not provided.
BPO versus meclocycline sulfosalicylate
One 10‐week parallel trial compared BPO and meclocycline sulfosalicylate (Borglund 1991). A total of 36 participants treated with BPO and 33 with meclocycline were analysed. This study reported the outcomes of participant global self‐assessment of acne improvement, withdrawal due to adverse effects, change in lesion counts, and adverse events.
Primary outcomes: participant global self‐assessment of acne improvement
Studies not included in the meta‐analysis
This outcome was assessed in the trial, but it is unclear how the outcome was assessed. It was reported that participants rating treatments as "good to excellent" accounted for 63% and 49% in the two groups, respectively, with an RR of 1.32 (95% CI 0.86 to 2.02).
Primary outcomes: withdrawal due to adverse effects
Main pooled analyses: BPO versus meclocycline
It was reported that no participants discontinued meclocycline treatment due to adverse effects, but three discontinued BPO treatment for this reason, with an RR of 6.43 (95% CI 0.34 to 120.03;Analysis 10.1), Adverse events leading to withdrawal were not specified.
10.1. Analysis.
Comparison 10 BPO versus meclocycline, Outcome 1 Withdrawal due to adverse effects (long‐term data).
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
For long‐term outcomes, the difference in absolute reduction in papules, pustules, and comedones was ‐5.3, 1.1, and ‐2.7, respectively. For medium‐term outcomes, the counterpart was ‐4.7, ‐0.1, and ‐3, respectively. For short‐term outcomes, the counterpart was ‐6.7, ‐0.6, and ‐1.9, respectively. All results were statistically significant (P < 0.05) except for the reduction in pustules for long‐term data.
Secondary outcome: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
Trial authors reported that it was more common for BPO‐treated participants to have local side effects (including erythema, scaling, stinging/burning) than meclocycline‐treated participants. Yellowish decolouration was reported in one participant on BPO and in two participants on meclocycline. Allergic contact dermatitis was confirmed in one participant treated with BPO. We cannot calculate RR as the effect size because the number of participants with at least one adverse event was not provided.
BPO versus isolutrol
This comparison was made in one 12‐week parallel trial with 35 participants in each group (Dunlop 1995). Change in lesion counts and adverse events were reported.
Primary outcomes
No information was available on the primary outcomes.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
At week 12, BPO reduced the mean number of ILs from 33.3 to 12.7, and isolutrol from 23.9 to 15.7. NILs were decreased from 25.5 to 11.9 among participants on BPO and from 23.4 to 16.4 among participants on isolutrol. Trial authors presented significance test results for before‐and‐after lesion counts in each group rather than differences between the two groups.
Secondary outcome: percentage of participants experiencing any adverse event
Main pooled analyses: BPO versus isolutrol
Overall, adverse events occurred in 94% of BPO‐treated participants, whereas only 34% of isolutrol‐treated participants reported such problems, with higher risk in the BPO group (RR 2.75, 95% CI 1.73 to 4.38; 70 participants;Analysis 9.1). The most common event reported in the BPO group was dryness (83%), followed by erythema (49%). Dryness (31%) and pruritus (14%) were the most common events in the isolutrol group.
9.1. Analysis.
Comparison 9 BPO versus isolutrol, Outcome 1 Percentage of participants with any adverse events (long‐term data).
BPO versus tea tree oil
One 10‐week parallel trial compared BPO and tea tree oil (Bassett 1990). A total of 124 participants were included in the trial, where 63 participants assigned to the BPO group and 61 to the tea tree oil group were followed up for three months. Outcomes covered in the study included change in lesion counts and adverse events.
Primary outcomes
No information was available on the primary outcomes.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
Insufficient data were available in this trial to estimate the effect size of absolute or percentage change. It was reported that the mean difference in absolute reduction in ILs was ‐10.4 (P < 0.001), ‐10.8 (P < 0.001), and ‐10.2 (P < 0.05) for the long, medium, and short term, respectively. The counterpart in NILs was ‐1.2, ‐1.0, and ‐2.3, respectively (all P values > 0.05).
Secondary outcome: percentage of participants experiencing any adverse event
Main pooled analyses: BPO versus tea tree oil
Overall, 79% (50/63) of BPO‐treated participants and 44% (27/61) of tea tree oil‐treated participants reported adverse events during the trial, with an RR of 1.79 (95% CI 1.32 to 2.44;Analysis 11.1). The most common adverse events reported included skin dryness, pruritus, stinging, burning, and redness.
11.1. Analysis.
Comparison 11 BPO versus tea tree oil, Outcome 1 Percentage of participants with any adverse events (long‐term data).
BPO versus Unani preparation (Zimade Muhasa)
This comparison was made in one six‐week parallel trial with 24 participants in each group (Tabasum 2014). This trial reported outcomes of our review interest including withdrawal due to adverse effects, lesion counts, and adverse events.
Primary outcome: withdrawal due to adverse effects
Studies not included in the meta‐analysis
Four participants in each group did not complete the study; however, none of these participants withdrew from the trial due to adverse effects.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
Trial authors presented significance test results for before‐and‐after lesion counts in each group rather than the difference between the two groups based on the Global Acne Severity Scale (Tabasum 2014). At week 6, grading scores for comedones and papules were significantly different before and after both treatments (both P values < 0.001). Although significant results were found for the grading scores for pustules (P < 0.001) and nodules (P = 0.02) in the Unani preparation group, scores in the BPO group were not significantly reduced from baseline.
Secondary outcome: change in quality of life
Studies not included in the meta‐analysis
Similar to the outcome mentioned above, trial authors presented significance test results for before‐and‐after quality of life in each group rather than the difference between two groups. The mean score of the Cardiff Acne Disability Index was reduced from 12.00 to 5.80 in the BPO group (P < 0.001) and from 12.25 to 4.95 in the Unani preparation group (P < 0.001).
Secondary outcome: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
Trial authors claimed that the difference between two groups regarding adverse events was not significant. The most common events reported in both groups were itching (9/20 versus 13/20) and dryness (9/20 versus 7/20). We cannot calculate RR as the effect size because the number of participants with at least one adverse event was not provided.
BPO versus glycerin in methylated spirit
One six‐week trial made this comparison, in which the only outcome assessed was change in lesion counts (Dogra 1993).
Primary outcomes
No information on the primary outcomes was available.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
After a six‐week treatment duration, although a reduction in NILs and 1ILs was 7.4% and 11.9% in the glycerin group of 21 participants, respectively, the counterpart was 70.1% and 63.9% in the BPO group of 24 participants (Dogra 1993).
BPO versus chloroxylenol/salicylic acid
One 12‐week parallel trial compared BPO and chloroxylenol/salicylic acid (Boutli 2003). Only an abstract was available for this trial. Nineteen participants on BPO and 18 on chloroxylenol/salicylic acid were assessed for the outcomes of change in lesion counts and adverse events. Limited information on these outcomes was available in the abstract.
Primary outcomes
No information was available on the primary outcomes.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
At week 12, both groups showed marked improvement in both ILs (60% versus 62%) and NILs (54% versus 56%). With no statistically significant difference in such reduction between groups, trial authors concluded that both treatments were similarly effective in reducing lesions.
Secondary outcome: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
Trial authors mentioned that erythema and photosensitivity were significantly less in the chloroxylenol/salicylic acid group at week 12 than in the BPO group (P = 0.0002 and P = 0.05, respectively). We cannot calculate RR as the effect size because the number of participants with at least one adverse event was not provided.
BPO versus chloroxylenol/zinc oxide
One eight‐week parallel trial compared BPO and chloroxylenol/zinc oxide (Papageorgiou 2000). Thirteen participants in each group were assessed for the outcomes of change in lesion counts and adverse events.
Primary outcome: participant global self‐assessment of acne improvement
Main pooled analyses: BPO versus chloroxylenol/zinc oxide
The medium‐term outcome was assessed according to the percentage of improvement (as worse, no change (0 to 9%), mild improvement (10% to 39%), moderate improvement (40% to 69%), marked improvement (70% to 89%), and clearance (> 90%)), with no significant difference in treatment success (RR 0.89, 95% CI 0.51 to 1.56; 26 participants;Analysis 12.1).
12.1. Analysis.
Comparison 12 BPO versus chloroxylenol/zinc oxide, Outcome 1 Participant's global self‐assessment of improvement (medium‐term data).
Primary outcome: withdrawal due to adverse effects
Studies not included in the meta‐analysis
Two participants discontinued treatment due to flare‐ups. However, it is unclear what treatments they received before the flare‐ups.
Secondary outcome: investigator‐assessed change in lesion counts
Main pooled analyses: BPO versus chloroxylenol/zinc oxide
This trial reported the percentage change in ILs and NILs. Compared with the chloroxylenol/zinc oxide group, mean differences in the percentage change were ‐7.70% (95% CI ‐19.36% to 3.96%) and ‐5.60% (95% CI ‐14.74% to 3.54%), respectively.
Secondary outcome: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
No significant difference in the number of flare‐ups was found (2/13 on BPO versus 1/13 on chloroxylenol/zinc oxide). Dryness and/or peeling of the skin was reported by four participants on BPO and one participant on chloroxylenol/zinc oxide (P < 0.01). We cannot calculate RR as the effect size because the number of participants with at least one adverse event was not provided.
BPO/adapalene versus placebo or no treatment
This comparison comprised eight parallel trials (Dreno 2011;Eichenfield 2013;Gold 2009;Gold 2010;Gold 2016;Gollnick 2009;Thiboutot 2007;Weiss 2015), as well as two split‐face trials (Dreno 2016;Dréno 2018), in which all participants were followed up for at least 12 weeks. All outcomes of interest in this review were available except reduction inC acnes strains.
Primary outcome: participant global self‐assessment of acne improvement
Of seven trials that reported this outcome (Dreno 2011;Eichenfield 2013;Gold 2009;Gold 2010;Gold 2016;Gollnick 2009;Thiboutot 2007), three trials presented data in accordance with the definition of treatment success in our review (Dreno 2011;Gold 2009;Gold 2016).
Main pooled analyses: BPO/adapalene versus placebo or no treatment
Overall, there was no significant difference in long‐term treatment success between the two groups (RR 1.16, 95% CI 0.97 to 1.38; 1480 participants; 3 studies; I² = 84%;Analysis 13.1).
13.1. Analysis.
Comparison 13 BPO/adapalene versus placebo or no treatment, Outcome 1 Participant's global self‐assessment of improvement (long‐term data).
Subgroup analyses: co‐intervention
Effects differed by the co‐intervention (P value for subgroup differences = 0.02), with a larger effect size in the BPO/adapalene versus the placebo or no treatment group (RR 1.25, 95% CI 1.09 to 1.44) than with the co‐intervention of lymecycline (RR 0.99, 95% CI 0.87 to 1.13) (Analysis 13.1).
Studies not included in the meta‐analysis
We did not pool results from the other four trials assessing this outcome because the number of treatment successes defined in our review was not available (Eichenfield 2013;Gold 2010;Gollnick 2009;Thiboutot 2007).
Eichenfield 2013 randomised 142 participants to the BPO/adapalene group and 143 to the placebo group and assessed the outcome using a 6‐point Likert‐like scale. The risk ratio for self‐reported complete or marked improvement was 2.93 (95% CI 2.14 to 4.01).
InGollnick 2009, 419 participants in the BPO/adapalene group and 418 in the placebo group were assessed via a 6‐point Likert‐like scale. The risk ratio for self‐reported complete or marked improvement was 1.75 (95% CI 1.46 to 2.09).
A similar 6‐point Likert‐like scale was used in another trial (Thiboutot 2007), in which 149 participants were treated with BPO/adapalene and 71 participants with placebo. The risk ratio for self‐reported complete or marked improvement was 3.00 (95% CI 1.64 to 5.49).
Gold 2010, a 12‐week trial including 232 participants in the BPO/adapalene plus doxycycline group and 227 in the placebo plus doxycycline group, assessed participant satisfaction at week 12 and found significant differences in the proportion of participants reporting "very satisfied" or "satisfied" (scale used for the assessment was not specified) in favour of the BPO/adapalene add‐on treatment group (76.3% versus 50.3%; P < 0.001).
These results consistently suggested a significant difference between the two groups in favour of BPO/adapalene. Sensitivity analysis additionally including these four trials suggests a higher probability of self‐assessed improvement in the BPO/adapalene group, with an RR of 1.55 (95% CI 1.25 to 1.91).
Primary outcome: withdrawal due to adverse effects
Ten trials reported the long‐term outcome (Dreno 2011;Dreno 2016;Dréno 2018;Eichenfield 2013;Gold 2009;Gold 2010;Gold 2016;Gollnick 2009;Thiboutot 2007;Weiss 2015).
Main pooled analyses: BPO/adapalene versus placebo or no treatment
The risk ratio of withdrawal due to adverse effects was 2.28 (95% CI 1.10 to 4.71; 3801 participants; I² = 3%;Analysis 13.2), pooled from the eight parallel‐group trials with a total of 2199 participants on BPO/adapalene and 1602 on placebo (Dreno 2011;Eichenfield 2013;Gold 2009;Gold 2010;Gold 2016;Gollnick 2009;Thiboutot 2007;Weiss 2015), suggesting higher risk of discontinuation in the BPO/adapalene group. The adverse events reported leading to withdrawal included erythema, irritation, and atopic dermatitis flare.
13.2. Analysis.
Comparison 13 BPO/adapalene versus placebo or no treatment, Outcome 2 Withdrawal due to adverse effects (long‐term data).
Subgroup analyses: co‐intervention
No evidence suggests that the association may differ by co‐intervention (P value for subgroup differences = 0.12) (Analysis 13.2).
Studies not included in the meta‐analysis
Two split‐face design trials reported that one of 38 participants discontinued BPO/adapalene because of moderate skin irritation (Dreno 2016), and that two of 67 participants had treatment‐related adverse events on the BPO/adapalene side (one with moderate pain of skin and one with mild skin irritation) that led to study discontinuation (Dréno 2018), respectively.
Secondary outcome: investigator‐assessed change in lesion counts
Six trials reported the percentage reduction in lesion counts, none of which provided sufficient data to estimate effect size (Dréno 2018;Eichenfield 2013;Gold 2009;Gollnick 2009;Thiboutot 2007;Weiss 2015). The results of these trials were consistently significant across studies.
Studies not included in the meta‐analysis
In the split‐face trial (Dréno 2018), the percentage reduction in acne lesion counts at week 24 was greater for the BPO/adapalene side than for the placebo side, with differences of 22.4% (73.3 versus 50.9%), 28.8% (86.7 versus 57.9%), and 18.1% (59.5 versus 41.4%) for total, inflammatory, and non‐inflammatory lesions, respectively.
Eichenfield 2013 found a significant difference in percentage reduction in TLs (68.6% versus 19.3%), ILs (63.2% versus 14.3%), and NILs (70.7% versus 14.6%) (all P values < 0.001).
Similar results were found inGold 2009, showing a significant difference in percentage reduction in TLs (60.7% versus 31.7%), ILs (66.0% versus 36.9%), and NILs (58.9% versus 32.9%) between groups (all P values < 0.05).
InGollnick 2009, compared with placebo groups, the percentage reductions in TLs, ILs, and NILs were significantly higher in the BPO/adapalene group (68.8% versus 41.1%, 72.4% versus 49.8%, and 66.4% versus 41.9%, respectively) (all P values < 0.05).
Thiboutot 2007 found 51.0% and 31% reduction in TLs, 62.9% and 37.8% in ILs, and 51.2% and 37.5% in NILs for BPO/adapalene and adapalene, respectively (all P values < 0.001).
InWeiss 2015, which compared BPO/adapalene gel with placebo among participants with moderate and severe acne (217 versus 69 participants), the absolute changes in ILs for each group were ‐27.0 and ‐14.4, respectively. The absolute changes in NILs were ‐40.1 and ‐18.4, respectively. This trial also reported percentage changes in ILs (‐68.7% vs. ‐39.2%) and NILs (‐68.3% vs. ‐37.3%, respectively). Trial authors claimed the P values for all changes to be less than 0.001.
As reported inDreno 2011, a significant difference was found in the percentage reduction in TLs (74.1% versus 56.8%; P < 0.001), ILs (81.7% versus 71.0%; P < 0.001), and NILs (71.7% versus 52.5%; P < 0.001) between the BPO/adapalene group and the placebo group.
Secondary outcome: percentage of participants rated 'clear' or 'almost clear' on the IGA scale of acne severity
Main pooled analyses: BPO/adapalene versus placebo or no treatment
Pooled results for the long‐term outcome support the use of BPO/adapalene (RR 2.43, 95% CI 1.80 to 3.28; 3012 participants; 6 studies; I² = 77%;Analysis 13.3). Three studies focusing on BPO/adapalene used alone reported medium‐ and short‐term outcomes, with an RR of 2.56 (95% CI 1.88 to 3.47; 2175 participants; I² = 31%;Analysis 13.4) and an RR of 2.76 (95% CI 1.84 to 4.16; 2175 participants; I² = 0%;Analysis 13.5), respectively.
13.3. Analysis.
Comparison 13 BPO/adapalene versus placebo or no treatment, Outcome 3 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (long‐term data).
13.4. Analysis.
Comparison 13 BPO/adapalene versus placebo or no treatment, Outcome 4 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (medium‐term data).
13.5. Analysis.
Comparison 13 BPO/adapalene versus placebo or no treatment, Outcome 5 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (short‐term data).
Subgroup analyses: co‐intervention
For the long‐term outcome, effects of BPO differed by the co‐intervention (P value for subgroup differences < 0.0001;Analysis 13.3). For BPO/adapalene used alone, the pooled risk ratio for the long‐term outcome was 2.45 (95% CI 2.07 to 2.90; I² = 1%) (Eichenfield 2013;Gold 2009;Gollnick 2009;Thiboutot 2007). A significant difference was found for this outcome (74/232 versus 19/227) favouring BPO/adapalene plus doxycycline treatment (RR 3.81, 95% CI 2.38 to 6.10) inGold 2010.Dreno 2011 showed a significant difference in this outcome (91/191 versus 63/187), with an RR of 1.41 (95% CI 1.10 to 1.82).
Studies not included in the meta‐analysis
In a split‐face trial (Dréno 2018), 'clear' or 'almost clear' was 45% more likely to occur with BPO/adapalene than with placebo (64.2 versus 19.4%).
Secondary outcome: percentage of participants experiencing any adverse event
Main pooled analyses: BPO/adapalene versus placebo or no treatment
Overall, BPO/adapalene tended to increase the long‐term risk of adverse events (RR 2.67, 95% CI 1.15 to 6.19; 2465 participants; 6 studies; I² = 86%;Analysis 13.6). The most common adverse events reported in these trials included burning sensation, skin irritation, dryness, and headache.
13.6. Analysis.
Comparison 13 BPO/adapalene versus placebo or no treatment, Outcome 6 Percentage of participants with any adverse events (long‐term data).
Subgroup analyses: co‐intervention
Substantial heterogeneity may be due to the co‐interventions (test for subgroup differences: P = 0.0002;Analysis 13.6). For BPO/adapalene used alone, adverse events were assessed in all five trials, four of which presented sufficient data for pooling, including 927 participants in the BPO/adapalene group and 701 in the placebo group (Eichenfield 2013;Gollnick 2009;Thiboutot 2007;Weiss 2015). The pooled RR was 4.71 (95% CI 2.36 to 9.37; I² = 36%;Analysis 13.6), suggesting the risk of adverse events was significantly higher in the BPO/adapalene treatment group. As for BPO/adapalene add‐on treatment, however, we did not find increased risk (Dreno 2011;Gold 2010).
Studies not included in the meta‐analysis
Gold 2009 did not present the number of participants experiencing at least one adverse event but reported that the number was similar across study treatments.Dréno 2018, a split‐face trial, showed that treatment‐related adverse events were reported in 25.4% of participants, with 20.9% on the BPO/adapalene side versus 9.0% on the placebo side. The most common were skin irritation (14.9% versus 6.0%) and skin pain (3.0% versus 1.5%).
BPO/adapalene versus tretinoin
One three‐week split‐face trial including 73 participants made this comparison (NCT01522456). Results about adverse events were published on the trial registry. No information regarding other outcomes was available.
Primary outcomes
No information was available on the primary outcomes.
Secondary outcomes: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
Rather than summarising the number of adverse events, trial authors reported local side effects individually during the three‐week period. The number of participants experiencing erythema, scaling, dryness, and stinging/burning was 25 versus 28, 25 versus 18, 34 versus 28, and 51 versus 57, respectively. We cannot calculate RR as the effect size because the number of participants with at least one adverse event was not provided.
BPO/adapalene versus salicylic acid
One 12‐week parallel trial compared BPO/adapalene and salicylic acid (Makino 2015). Only a conference abstract was available for this trial. The abstract reported limited information on characteristics of the trial and on outcomes, including the Investigator Global Assessment of acne severity and change in lesion counts. A four‐week split‐face trial comparing BPO plus adapalene with salicylic acid reported participant global self‐assessment of acne improvement, withdrawal due to adverse effects, change in lesion counts, and adverse events (Zheng 2019).
Primary outcome: participant global self‐assessment of acne improvement
Studies not included in the meta‐analysis
The proportion of participants rating BPO plus adapalene as better, similar, or worse than salicylic acid was 25.8%, 41.9%, and 32.2%, respectively (Zheng 2019).
Primary outcome: withdrawal due to adverse effects
Studies not included in the meta‐analysis
During the trial, 3 out of 34 participants developed irritant contact dermatitis on BPO treatment and withdrew from the study (Zheng 2019).
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
Trial authors reported no significant difference in reducing ILs and NILs between groups (Makino 2015). After four weeks, BPO plus adapalene showed similar reduction in papules/pustules (49.8% versus 47.9%), non‐inflammatory lesions (42.7% versus 43.1%), and total lesions (45.6% versus 44.1%) (Zheng 2019).
Secondary outcome: percentage of participants rated 'clear' or 'almost clear' on the IGA scale of acne severity
Studies not included in the meta‐analysis
Trial authors reported no significant difference in the mean scores of IGA between groups (Makino 2015).
Secondary outcome: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
No participants developed adverse events, except for three, who discontinued treatment due to irritant contact dermatitis at the BPO treatment site (Zheng 2019).
BPO/adapalene versus clindamycin/tretinoin
This comparison was made in one three‐week split‐face trial (Goreshi 2012), which included 24 participants, all of whom applied BPO/adapalene to one side of the face and clindamycin/tretinoin to the other side. The main purpose of this trial was to assess tolerance of treatments. This trial reported change in lesion counts and adverse events.
Primary outcomes
No information regarding the primary outcomes was reported.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
Trial authors claimed no significant change in lesion counts between groups. However, no relevant data were presented.
Secondary outcome: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
Trial authors did not present the number of adverse events but the mean score of erythema, dryness/scaling, itching, and burning/stinging on a 4‐point scale (from 0 = none to 3 = severe). Mean differences were 0.4 (P < 0.001), 0.201 (P < 0.001), 0.01 (P = 0.162), and 0.076 (P = 0.401), respectively. We cannot calculate RR as the effect size because the number of participants with at least one adverse event was not provided.
BPO/clindamycin versus placebo or no treatment
We included 12 parallel trials for this comparison (Bowman 2005;Del 2007;Eichenfield 2011;Leyden 2001a;Lookingbill 1997;NCT01044264;NCT01138514;Pariser 2014;Study 152;Tanghetti 2006;Thiboutot 2008;Tschen 2001). All trials followed up on participants for 10 to 12 weeks. All outcomes of interest in this review were available for these trials except reduction inC acnes strains.
Primary outcome: participant global self‐assessment of acne improvement
Main pooled analyses: BPO/clindamycin versus placebo or no treatment
This outcome was assessed in five trials (Leyden 2001a;Pariser 2014;Tanghetti 2006;Thiboutot 2008;Tschen 2001), only one of which presented data in accordance with the definition of the outcome in our review (Leyden 2001a). Results from these trials consistently showed significant difference between the two groups.
Leyden 2001a included 120 participants in the BPO/clindamycin group and 120 in the placebo group. The outcome was assessed with a 5‐point Likert‐like scale. The risk ratio for treatment success was 2.95 (95% CI 1.96 to 4.46;Analysis 14.1) with significant differences between the two groups.
14.1. Analysis.
Comparison 14 BPO/clindamycin versus placebo or no treatment, Outcome 1 Participant's global self‐assessment of improvement (long‐term data).
Studies not included in the meta‐analysis
We cannot pool this result with those from the other four trials because they did not present the number of treatment successes as defined in our review (Pariser 2014;Tanghetti 2006;Thiboutot 2008;Tschen 2001).Pariser 2014 randomised 253 participants to the BPO/clindamycin group and 245 to the placebo group and assessed the outcome using a 7‐point Likert‐like scale. At week 12, the risk ratio for self‐reported ‘clear’ or ‘almost clear’ was 1.98 (95% CI 1.44 to 2.73). A similar 7‐point Likert‐like scale was used inThiboutot 2008, in which 797 participants in the BPO/clindamycin group and 395 participants in the placebo group were assessed. The risk ratio for self‐reported ‘clear’ or ‘almost clear’ was 2.34 (95% CI 1.85 to 2.97). Another 7‐point Likert‐like scale was used inTschen 2001, in which 95 participants were treated with BPO/clindamycin and 48 with placebo. The risk ratio for self‐reported ‘much better’ was 4.04 (95% CI 1.52 to 10.77). In one 12‐week trial including 60 participants on BPO/clindamycin and 61 on placebo (Tanghetti 2006), all of whom received tazarotene as a co‐intervention, participants rated their overall impression of their treatment as highly favourable, favourable, unfavourable, or highly unfavourable. There was no significant difference in the proportion of participants rating improvement as highly favourable or favourable between the two groups (94% versus 90%) at week 12. Sensitivity analysis including these trials showed an RR of 2.10 (95% CI 1.25 to 3.52).
Primary outcome: withdrawal due to adverse effects
The long‐term outcome was reported in eight trials (Bowman 2005;Eichenfield 2011;Leyden 2001a;Lookingbill 1997;Pariser 2014;Tanghetti 2006;Thiboutot 2008;Tschen 2001), which included a total of 1791 participants treated with BPO/clindamycin and 1304 treated with placebo.
Main pooled analyses: BPO/clindamycin versus placebo or no treatment
No evidence suggests that participants treated with BPO/clindamycin had a higher risk of withdrawal due to adverse effects, with an RR of 1.07 (95% CI 0.38 to 3.00; 3095 participants; 8 studies; I² = 0%;Analysis 14.2). The most common adverse events leading to withdrawal included erythema, face oedema, rash, pruritus, and skin burning.
14.2. Analysis.
Comparison 14 BPO/clindamycin versus placebo or no treatment, Outcome 2 Withdrawal due to adverse effects (long‐term data).
Subgroup analyses: co‐intervention
We did not observe significant differences between different co‐intervention subgroups (test for subgroup differences: P = 0.28;Analysis 14.2).
Secondary outcome: investigator‐assessed change in lesion counts
All 12 trials reported the mean or percentage reduction in lesions counts (Bowman 2005;Del 2007;Eichenfield 2011;Leyden 2001a;Lookingbill 1997;NCT01044264;NCT01138514;Pariser 2014;Study 152;Tanghetti 2006;Thiboutot 2008;Tschen 2001). Three of them provided sufficient data to estimate effect size (Eichenfield 2011;Lookingbill 1997;NCT01138514). Results were consistently significant across studies.
Main pooled analyses: BPO/clindamycin versus placebo or no treatment
For the mean change in lesion counts,Eichenfield 2011, which included 322 participants treated with BPO/clindamycin and 329 treated with placebo, found significant differences in the reduction in TLs (MD ‐15.20; 95% CI ‐19.57 to ‐10.83;Analysis 14.3), ILs (MD ‐5.10; 95% CI ‐6.83 to ‐3.37;Analysis 14.4), and NILs (MD ‐10.00; 95% CI ‐13.20 to ‐6.80;Analysis 14.5).
14.3. Analysis.
Comparison 14 BPO/clindamycin versus placebo or no treatment, Outcome 3 Investigator‐assessed absolute change in total lesions (long‐term data).
14.4. Analysis.
Comparison 14 BPO/clindamycin versus placebo or no treatment, Outcome 4 Investigator‐assessed absolute change in inflammatory lesions (long‐term data).
14.5. Analysis.
Comparison 14 BPO/clindamycin versus placebo or no treatment, Outcome 5 Investigator‐assessed absolute change in non‐inflammatory lesions (long‐term data).
For the percentage change in lesion counts, we pooled two trials including 944 and 485 participants treated with BPO/clindamycin and placebo, respectively (Lookingbill 1997;NCT01138514). The mean difference in percentage reduction in ILs and NILs was 44.16% (95% CI 23.53 to 64.79%; 2 studies; I² = 86%;Analysis 14.6) and 37.65% (95% CI 26.04 to 49.25%; 2 studies; I² = 50%;Analysis 14.7), respectively, with substantial heterogeneity. The two trials were different in acne severity (Lookingbill 1997 covered mild acne, butNCT01138514 exclusively focused on moderate to severe acne).
14.6. Analysis.
Comparison 14 BPO/clindamycin versus placebo or no treatment, Outcome 6 Investigator‐assessed percentage change in inflammatory lesions (long‐term data).
14.7. Analysis.
Comparison 14 BPO/clindamycin versus placebo or no treatment, Outcome 7 Investigator‐assessed percentage change in non‐inflammatory lesions (long‐term data).
Studies not included in the meta‐analysis
For the following trials, we cannot estimate MD as the effect size for this outcome because data were not sufficient to calculate standard deviation.
Regarding the mean change in lesion counts,Leyden 2001a claimed that both TLs (‐18.4 versus ‐1.3) and ILs (‐10.1 versus 0.7) were significantly reduced in the BPO/clindamycin group when compared to the placebo group at week 10.Tschen 2001 found ‐16.6 versus ‐11.3 in ILs for BPO/clindamycin (95 participants) and placebo (48 participants) (P < 0.034).
As for the percentage change in lesion counts, trial data published on the registry show 63.8% reduction in ILs among 218 participants treated with BPO/clindamycin and 49.9% among 185 participants treated with placebo (NCT01044264).
InPariser 2014, BPO/clindamycin was statistically superior to placebo in terms of lesion percentage reduction in both ILs and NILs. The percent change in ILs from baseline to week 12 was 60.6% with BPO/clindamycin versus 31.4% with placebo, and 51.6% versus 27.4% in NILs (both P values < 0.001).
Similar results were found inThiboutot 2008, in which 797 participants were randomised to the BPO/clindamycin group and 395 to the placebo group. The percentage reduction was 47.9% versus 26.2% in TLs, 54.6% versus 29.0% in ILs, and 43.2% versus 24.0% in NILs at week 12 (all P values < 0.001).
InStudy 152, the percentage reduction in TLs, ILs, and NILs was 32.5% versus 20.6% (P = 0.003), 43.4% versus 28.6% (0.046), and 25.7% versus 15.4% (0.008) for the BPO/clindamycin group (n = 73) and the placebo group (n = 37).
Del 2007, a 12‐week parallel trial including 37 participants on BPO/clindamycin plus adapalene and 37 participants on adapalene, showed that there was a statistically greater percentage reduction in TLs among participants on BPO/clindamycin plus adapalene than on adapalene (71% versus 52%; P < 0.05) at week 12. A statistically greater reduction was also found in NILs (71% versus 51%; P < 0.05). Despite no significant difference, BPO/clindamycin plus adapalene led to a greater reduction in ILs (71% versus 58%).
For the comparison between BPO/clindamycin plus tazarotene versus placebo plus tazarotene (Tanghetti 2006), the number of papules and pustules was reduced by 63% among participants on BPO/clindamycin and by 58% among participants on placebo at week 12, but no significant difference was found. The percentage reduction in open and closed comedones was 70% and 60% (P < 0.01).
Bowman 2005 reported that at week 10, the percentage reduction in TLs, ILs, and NILs in the BPO/clindamycin plus tretinoin and clindamycin treatment groups was 62.6%, 69.3%, and 61.0%, respectively, compared to 49.6%, 52.5%, and 46.2% in the other group. A significant difference was found in the percentage reduction in ILs (P = 0.02). For medium‐term and short‐term treatment duration, the percentage reduction in TLs (medium‐term: 55.8% versus 40.9%; short‐term: 49.8% versus 35.3%), ILs (53.7% versus 44.9%; 52% versus 45.7%), and NILs (59.6% versus 37.9%; 48.6% versus 21.9%) was consistently greater in the BPO/clindamycin add‐on treatment group, but it is unclear whether significant differences existed, as no information about this was reported.
Secondary outcome: percentage of participants rated 'clear' or 'almost clear' on the IGA scale of acne severity
Main pooled analyses: BPO/clindamycin versus placebo or no treatment
This outcome for the long term was reported in five trials (Bowman 2005;Eichenfield 2011;NCT01138514;Pariser 2014;Thiboutot 2008), in which 2226 participants were included in the BPO/clindamycin group and 1399 in the placebo group. The pooled risk ratio showed clear differences in the outcome (RR 2.37, 95% CI 1.87 to 3.01; 3993 participants; 5 studies; I² = 65%;Analysis 14.8), with substantial heterogeneity probably induced by theBowman 2005 andNCT01138514 trials, in which the concentration of BPO was higher (5%) than in the others (2.5% or 3%).
14.8. Analysis.
Comparison 14 BPO/clindamycin versus placebo or no treatment, Outcome 8 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (long‐term data).
Subgroup analyses: co‐intervention
We did not find that the effects of BPO on this outcome can differ by co‐intervention, with a P value of 0.25 (Analysis 14.8).
Secondary outcome: change in quality of life
Studies not included in the meta‐analysis
Pariser 2014 reported this outcome as assessed by the acne‐specific quality of life (Acne‐QoL) questionnaire. There was no significant difference in the mean score for each domain at week 12, although each domain was scored higher in the BPO/clindamycin group (7.6 versus 5.9 in self‐perception, 5.5 versus 4.5 in role‐emotional, 4.7 versus 3.7 in role‐social, and 6.5 versus 4.3 in acne symptoms).
Secondary outcome: percentage of participants experiencing any adverse event
Ten trials reported adverse events (Bowman 2005;Del 2007;Eichenfield 2011;Leyden 2001a;Lookingbill 1997;NCT01044264;NCT01138514;Pariser 2014;Thiboutot 2008;Tschen 2001), all of which investigated BPO/clindamycin versus placebo or no treatment, with no additional co‐interventions.
Main pooled analyses: BPO/clindamycin versus placebo or no treatment
With sufficient data for the meta‐analysis in eight trials, the pooled risk ratio was 0.91 (95% CI 0.78 to 1.07; 5042 participants; I² = 24%;Analysis 14.9). The most common adverse events observed across included trials were skin dryness, irritation, desquamation, and erythema.
14.9. Analysis.
Comparison 14 BPO/clindamycin versus placebo or no treatment, Outcome 9 Percentage of participants with any adverse events (long‐term data).
Studies not included in the meta‐analysis
We cannot calculate RR as the effect size because the number of participants with at least one adverse event was not provided in theDel 2007 andTanghetti 2006 trials. InDel 2007, the proportion of participants experiencing erythema, dryness, burning, and pruritus was 14.8% versus 24.3%, 51.6% versus 56.8%, 11.2% versus 12.6%, and 8.5% versus 15.5%. A significant difference was found in erythema (P < 0.05).Tanghetti 2006, the other trial, found no significant difference in the incidence of peeling and dryness between groups (10% versus 18% and 8% versus 12%, respectively). Trial authors reported no significant differences in grading for erythema, burning, dryness, or pruritus.
BPO/clindamycin versus adapalene
The comparison was made in four parallel trials (Dubey 2016;Guerra‐Tapia 2012;Ko 2009;Langner 2008), which provided data for all outcomes of interest in this review except the Investigator Global Assessment. Participants were followed up to 12 weeks in these trials.
Primary outcome: participant global self‐assessment of acne improvement
This outcome was assessed in two trials (Guerra‐Tapia 2012;Langner 2008), one of which presented data in accordance with the definition of the outcome in our review (Guerra‐Tapia 2012).
Main pooled analyses: BPO/clindamycin versus adapalene
Guerra‐Tapia 2012 included 83 participants in the BPO/clindamycin group and 85 participants in the adapalene group. The outcome was assessed with a 12‐grade system. The risk ratio of self‐rated improvement was 1.12 (95% CI 0.96 to 1.31) (83% versus 74%) at week 12 (Analysis 15.1).
15.1. Analysis.
Comparison 15 BPO/clindamycin versus adapalene, Outcome 1 Participant's global self‐assessment of improvement (long‐term data).
Studies not included in the meta‐analysis
We cannot pool this result with those from the other trial ‐Langner 2008 ‐ because the outcome was assessed on a different definition. InLangner 2008, 65 participants randomised to the BPO/clindamycin group and 65 to the adapalene group rated their condition as improved, no change, or worse. Trial authors reported that the percentage of improvement increased over time to about 90% at week 12 for both treatment groups. Although the proportion of improvement was greater early in treatment with BPO/clindamycin (weeks 1, 2, 4, and 8), no significant difference was found at week 12.
Primary outcome: withdrawal due to adverse effects
Main pooled analyses: BPO/clindamycin versus adapalene
The outcome was reported in three trials (Dubey 2016;Guerra‐Tapia 2012;Langner 2008). No evidence suggests that participants treated with BPO/clindamycin had higher risk of withdrawal due to adverse effects. The risk ratio was 0.41 (95% CI 0.05 to 3.05; 398 participants; 3 studies; I² = 0%;Analysis 15.2).Guerra‐Tapia 2012 did not specify any adverse events leading to treatment discontinuation. InLangner 2008, one participant in each group experienced adverse events leading to withdrawal from the study (BPO/clindamycin: erythema, burning, and pruritus; adapalene: dermatitis). No participants discontinued treatment due to adverse events inDubey 2016.
15.2. Analysis.
Comparison 15 BPO/clindamycin versus adapalene, Outcome 2 Withdrawal due to adverse effects (long‐term data).
Secondary outcome: investigator‐assessed change in lesion counts
All the four trials assessed the mean or percentage reduction in lesion counts, none of which, however, provided sufficient data to estimate effect size (Dubey 2016;Guerra‐Tapia 2012;Ko 2009;Langner 2008).
Studies not included in the meta‐analysis
InDubey 2016, trial authors found that mean NIL, IL, and total counts were reduced from 24.74 at baseline to 5.23 at week 12, from 16.38 to 2.12 and from 27.53 to 5.59, respectively, in the BPO/clindamycin group. Counterparts in the clindamycin group were from 25.91 to 3.95, from 16.25 to 2.00, and from 28.68 to 4.29, respectively. Trial authors stated that no statistical difference was found between two groups for any type of lesion count.Guerra‐Tapia 2012 found a significant difference in the reduction in TLs (‐33.9 versus ‐27.1; P < 0.05), ILs (‐17.0 versus ‐15.1; P < 0.05), and NILs (‐20.1 versus ‐18.0; non‐significance) at week 12. In another trial ‐Ko 2009 ‐ investigators claimed that TLs (‐44.9 versus ‐34.1; P = 0.017) and ILs (‐29.7 versus ‐19.2; P = 0.026) were significantly reduced in 31 participants in the BPO/clindamycin group at week 12 compared to 38 participants in the adapalene group; however, this significant difference was not found in NILs (‐14.8 versus ‐15.0).Langner 2008 found that percentage reduction at week 12 was 70.4% versus 53.1% in TLs (P < 0.005), 81.5% versus 58.2% in ILs (P < 0.001), and 61.9% versus 50.0% in NILs (P < 0.005).
Secondary outcome: change in quality of life
Main pooled analyses: BPO/clindamycin versus adapalene
Guerra‐Tapia 2012 reported this outcome as assessed with Skindex‐29. A significant difference was found for the long‐term (MD ‐4.20, 95% CI ‐7.06 to ‐1.34; 168 participants;Analysis 15.3) and short‐term periods (MD ‐3.80, 95% CI ‐6.16 to ‐1.44; 168 participants;Analysis 15.4) in favour of BPO/clindamycin.
15.3. Analysis.
Comparison 15 BPO/clindamycin versus adapalene, Outcome 3 Change in quality of life (long‐term data).
15.4. Analysis.
Comparison 15 BPO/clindamycin versus adapalene, Outcome 4 Change in quality of life (short‐term data).
Secondary outcome: reduction inC acnes strains
Studies not included in the meta‐analysis
Twenty samples were collected from each group (BPO/clindamycin and adapalene groups) (Langner 2008). The reduction in total, erythromycin‐resistant, and clindamycin‐resistantC acnes strains at week 12 was ‐1.24 versus 0.50 versus ‐0.91 versus 0.13 and ‐0.80 versus 0.09 log10 CFU cm‐2. It is unclear whether the difference was significant.
Secondary outcome: percentage of participants experiencing any adverse event
All four trials reported adverse events (Dubey 2016;Guerra‐Tapia 2012;Ko 2009;Langner 2008), two of which presented sufficient data for the meta‐analysis (Guerra‐Tapia 2012;Langner 2008).
Main pooled analyses: BPO/clindamycin versus adapalene
With a total of 148 participants in the BPO/clindamycin group and 150 in the adapalene group, the pooled risk ratio was 0.60 (95% CI 0.36 to 1.01; 298 participants; 2 studies; I² = 0%;Analysis 15.5), and the difference between groups was not statistically significant. InGuerra‐Tapia 2012, among 83 participants treated with BPO/clindamycin, site reactions, nasopharyngitis, and nervous system disorders occurred in five, eight, and five participants, respectively. In the adapalene group of 85 participants, counterparts were 14, 27, and 8, respectively. InLangner 2008, only one (1.5%) participant in the BPO/clindamycin group was considered to have treatment‐related adverse events (burning, erythema, and dryness). In the adapalene group, seven (10.8%) participants had adverse events (application site burning, dermatitis, desquamation, dryness, erythema, pain, and pruritus).
15.5. Analysis.
Comparison 15 BPO/clindamycin versus adapalene, Outcome 5 Percentage of participants with any adverse events (long‐term data).
Studies not included in the meta‐analysis
InDubey 2016, dryness was the only adverse event reported, which was observed in 2.1% of participants treated with adapalene, but dryness (2.2%) and itching (2.2%) were found in the BPO/clindamycin group.Ko 2009 reported that both drugs were well tolerated, with most mild adverse events observed within one month of treatments, such as erythema, desquamation, stinging/burning sensation, dry skin, and pruritus.
BPO/clindamycin versus azelaic acid
The comparison was made in one parallel trial (Schaller 2016), which provided data for all outcomes of our review interest except the Investigator Global Assessment and reduction inC acnes strains. Participants were followed up to 12 weeks in this trial.
Primary outcome: participant global self‐assessment of acne improvement
Main pooled analyses: BPO/clindamycin versus azelaic acid
Schaller 2016 included 108 participants in the BPO/clindamycin group and 109 in the azelaic acid group. The outcome was assessed via a 7‐point scale. Participants treated with BPO/clindamycin were more likely to achieve treatment success (rated as "very much improved" or "much improved") throughout the trial, with an RR of 1.38 (95% CI 1.05 to 1.81;Analysis 16.1), 1.44 (95% CI 1.09 to 1.89;Analysis 16.2), and 1.37 (95% CI 1.00 to 1.88;Analysis 16.3) for long‐, medium‐, and short‐term periods, respectively.
16.1. Analysis.
Comparison 16 BPO/clindamycin versus azelaic acid, Outcome 1 Participant's global self‐assessment of improvement (long‐term data).
16.2. Analysis.
Comparison 16 BPO/clindamycin versus azelaic acid, Outcome 2 Participant's global self‐assessment of improvement (medium‐term data).
16.3. Analysis.
Comparison 16 BPO/clindamycin versus azelaic acid, Outcome 3 Participant's global self‐assessment of improvement (short‐term data).
Primary outcome: withdrawal due to adverse effects
Main pooled analyses: BPO/clindamycin versus azelaic acid
One participant in each group discontinued treatment due to adverse effects (application site erythema, dryness, pruritus and pain, and left and right eyelid oedema occurred in the participant on BPO/clindamycin, and application site pruritus and pain occurred in the participant on azelaic acid) (Schaller 2016). No significant difference was observed between the two groups, with an RR of 1.01 (95% CI 0.06 to 15.93; 217 participants;Analysis 16.4).
16.4. Analysis.
Comparison 16 BPO/clindamycin versus azelaic acid, Outcome 4 Withdrawal due to adverse effects (long‐term data).
Secondary outcome: investigator‐assessed change in lesion counts
The percentage reduction in each type of lesion was significantly different between the two groups at three time points, consistently supporting the benefits of BPO/clindamycin.
Main pooled analyses: BPO/clindamycin versus azelaic acid
For the long‐term period, the mean difference was 18.50% (95% CI 10.54 to 26.46%; 211 participants;Analysis 16.5), 17.30% (95% CI 9.87 to 24.73%; 211 participants;Analysis 16.6), and 18.50% (95% CI 8.67 to 28.33%; 211 participants;Analysis 16.7) for TLs, ILs, and NILs, respectively.
16.5. Analysis.
Comparison 16 BPO/clindamycin versus azelaic acid, Outcome 5 Investigator‐assessed percentage change in total lesions (long‐term data).
16.6. Analysis.
Comparison 16 BPO/clindamycin versus azelaic acid, Outcome 6 Investigator‐assessed percentage change in inflammatory lesions (long‐term data).
16.7. Analysis.
Comparison 16 BPO/clindamycin versus azelaic acid, Outcome 7 Investigator‐assessed percentage change in non‐inflammatory lesions (long‐term data).
For the medium‐term period, the counterpart was 15.10% (95% CI 7.19 to 23.01%; 206 participants;Analysis 16.8), 15.90% (95% CI 8.06 to 23.74%; 206 participants;Analysis 16.9), and 13.00% (95% CI 3.24 to 22.76%; 206 participants;Analysis 16.10).
16.8. Analysis.
Comparison 16 BPO/clindamycin versus azelaic acid, Outcome 8 Investigator‐assessed percentage change in total lesions (medium‐term data).
16.9. Analysis.
Comparison 16 BPO/clindamycin versus azelaic acid, Outcome 9 Investigator‐assessed percentage change in inflammatory lesions (medium‐term data).
16.10. Analysis.
Comparison 16 BPO/clindamycin versus azelaic acid, Outcome 10 Investigator‐assessed percentage change in non‐inflammatory lesions (medium‐term data).
The short‐term mean difference was 13.00% (95% CI 6.77 to 19.23%; 212 participants;Analysis 16.11), 14.10% (95% CI 6.18 to 22.02%; 212 participants;Analysis 16.12), and 11.10% (95% CI 3.56 to 18.64%; 212 participants;Analysis 16.13).
16.11. Analysis.
Comparison 16 BPO/clindamycin versus azelaic acid, Outcome 11 Investigator‐assessed percentage change in total lesions (short‐term data).
16.12. Analysis.
Comparison 16 BPO/clindamycin versus azelaic acid, Outcome 12 Investigator‐assessed percentage change in inflammatory lesions (short‐term data).
16.13. Analysis.
Comparison 16 BPO/clindamycin versus azelaic acid, Outcome 13 Investigator‐assessed percentage change in non‐inflammatory lesions (short‐term data).
Secondary outcome: percentage of participants rated 'clear' or 'almost clear' on the IGA scale of acne severity
Main pooled analyses: BPO/clindamycin versus azelaic acid
This outcome was significantly different between the two groups for long‐ and medium‐term periods, with an RR of 1.91 (95% CI 1.17 to 3.11;Analysis 16.14) and 1.88 (95% CI 1.07 to 3.32;Analysis 16.15), respectively, in favour of BPO/clindamycin treatment. We cannot observe significant differences for the short‐term period (RR 1.74, 95% CI 0.87 to 3.49;Analysis 16.16).
16.14. Analysis.
Comparison 16 BPO/clindamycin versus azelaic acid, Outcome 14 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (long‐term data).
16.15. Analysis.
Comparison 16 BPO/clindamycin versus azelaic acid, Outcome 15 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (medium‐term data).
16.16. Analysis.
Comparison 16 BPO/clindamycin versus azelaic acid, Outcome 16 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (short‐term data).
Secondary outcome: change in quality of life
Studies not included in the meta‐analysis
A greater percentage change in quality of life was reported at week 12 in the Children's Dermatology Life Quality Index (CDLQI) score (60.5% versus 36.8%) and the Dermatology Life Quality Index (DLQI) score (73.4% versus 31.9%) for BPO/clindamycin versus azelaic acid.
Secondary outcome: percentage of participants experiencing any adverse event
Main pooled analyses: BPO/clindamycin versus azelaic acid
Treatment‐related adverse events were reported in 13.9% and 33.0% of participants with BPO/clindamycin and azelaic acid treatment, respectively, with significantly lower risk in the BPO/clindamycin group (RR 0.42, 95% CI 0.24 to 0.72; 217 participants;Analysis 16.17). Local reactions occurred in 15.7% of participants treated with BPO/clindamycin (24 events in 17 participants) and 35.8% of participants with azelaic acid (60 events in 39 participants), including pruritus (7.4% versus 22.9%), pain (6.5% versus 20.2%), erythema (2.8% versus 4.6%), and dryness (1.9% versus 2.8%).
16.17. Analysis.
Comparison 16 BPO/clindamycin versus azelaic acid, Outcome 17 Percentage of participants with any adverse events (long‐term data).
BPO/clindamycin versus erythromycin/zinc
This comparison was made in one 12‐week trial (Langner 2007), which included 73 participants on BPO/clindamycin and 75 on erythromycin/zinc. This trial reported the following outcomes of our review interest: participant global self‐assessment, withdrawal due to adverse effects, change in lesion counts, reduction inC acnes strains, and adverse events.
Primary outcome: participant global self‐assessment of acne improvement
Studies not included in the meta‐analysis
Participants rated their improvement as improved, no change, or worse. There was no significant difference in the proportion of "improved" between the two groups (91.9% versus 89.3%) at week 12.
Primary outcome: withdrawal due to adverse effects
Main pooled analyses: BPO/clindamycin versus erythromycin/zinc
Two participants withdrew, with no significant differences between the two groups (RR 1.03, 95% CI 0.07 to 16.12; 148 participants;Analysis 17.1): one participant on BPO/clindamycin treatment due to rash and skin tightness and one on erythromycin/zinc treatment due to exacerbation of acne.
17.1. Analysis.
Comparison 17 BPO/clindamycin versus erythromycin/zinc, Outcome 1 Withdrawal due to adverse effects (long‐term data).
Secondary outcome: investigator‐assessed change in lesion counts
The absolute change in each type of lesion reported from the ITT analysis was not significantly different between the two groups at the three time points.
Main pooled analyses: BPO/clindamycin versus erythromycin/zinc
For the long‐term period, the mean difference was 6.10 (95% CI ‐4.65 to 16.85;Analysis 17.2), 0.10 (95% CI ‐3.85 to 4.05;Analysis 17.3), and 6.40 (95% CI ‐2.16 to 14.96;Analysis 17.4) for TLs, ILs, and NILs, respectively.
17.2. Analysis.
Comparison 17 BPO/clindamycin versus erythromycin/zinc, Outcome 2 Investigator‐assessed absolute change in total lesions (long‐term data).
17.3. Analysis.
Comparison 17 BPO/clindamycin versus erythromycin/zinc, Outcome 3 Investigator‐assessed absolute change in inflammatory lesions (long‐term data).
17.4. Analysis.
Comparison 17 BPO/clindamycin versus erythromycin/zinc, Outcome 4 Investigator‐assessed absolute change in non‐inflammatory lesions (long‐term data).
For the medium‐term period, the counterpart was 5.60 (95% CI ‐5.61 to 16.81;Analysis 17.5), ‐0.20 (95% CI ‐4.33 to 3.93;Analysis 17.6), and 6.20 (95% CI ‐2.66 to 15.06;Analysis 17.7).
17.5. Analysis.
Comparison 17 BPO/clindamycin versus erythromycin/zinc, Outcome 5 Investigator‐assessed absolute change in total lesions (medium‐term data).
17.6. Analysis.
Comparison 17 BPO/clindamycin versus erythromycin/zinc, Outcome 6 Investigator‐assessed absolute change in inflammatory lesions (medium‐term data).
17.7. Analysis.
Comparison 17 BPO/clindamycin versus erythromycin/zinc, Outcome 7 Investigator‐assessed absolute change in non‐inflammatory lesions (medium‐term data).
The short‐term mean difference was 5.80 (95% CI ‐5.96 to 17.56;Analysis 17.8), 0.10 (95% CI ‐3.91 to 4.11;Analysis 17.9), and 6.20 (95% CI ‐3.60 to 16.00;Analysis 17.10).
17.8. Analysis.
Comparison 17 BPO/clindamycin versus erythromycin/zinc, Outcome 8 Investigator‐assessed absolute change in total lesions (short‐term data).
17.9. Analysis.
Comparison 17 BPO/clindamycin versus erythromycin/zinc, Outcome 9 Investigator‐assessed absolute change in inflammatory lesions (short‐term data).
17.10. Analysis.
Comparison 17 BPO/clindamycin versus erythromycin/zinc, Outcome 10 Investigator‐assessed absolute change in non‐inflammatory lesions (short‐term data).
Secondary outcome: reduction inC acnes strains
Studies not included in the meta‐analysis
Only 14 participants treated with BPO/clindamycin and 15 treated with erythromycin/zinc contributed to the bacteriology data. At week 12, the total number ofC acnes strains (log10 CFU cm‐2) was reduced from 5.38 (standard deviation (SD), 0.82) to 3.67 (SD, 1.30) and from 4.35 (SD, 1.19) to 3.49 (SD, 2.18) for BPO/clindamycin and erythromycin/zinc groups, respectively. In the BPO/clindamycin group, the number of erythromycin‐ and clindamycin‐resistantC acnes strains was reduced from 2.71 (SD, 2.35) to 1.45 (SD, 1.86) and from 2.48 (SD, 2.30) to 1.14 (SD, 1.75), respectively. In the erythromycin/zinc group, however, there was an increase in the number of erythromycin‐ and clindamycin‐resistantC acnes strains: from 0.76 (1.64) to 2.53 (SD, 2.05) and from 0.78 (SD, 1.56) to 2.19 (SD, 2.21), respectively. With no significance test results reported, trial authors claimed that the level of resistance appeared to decline with BPO/clindamycin but appeared to increase with erythromycin/zinc. We cannot estimate MD as the effect size because data were not sufficient to calculate the standard deviation of the change inC acnes strains from baseline.
Secondary outcome: percentage of participants experiencing any adverse event
Main pooled analyses: BPO/clindamycin versus erythromycin/zinc
A total of 20.5% of participants on BPO/clindamycin and 30.7% of participants on erythromycin/zinc reported at least one adverse event, with no significant difference detected (RR 0.67, 95% CI 0.38 to 1.18; 148 participants;Analysis 17.11). Common adverse events that occurred in each group were similar, including dryness (4.1% versus 5.3%), desquamation (4.1% versus 2.7%), burning (2.7% versus 2.7%), and erythema (2.7 versus 2.7%). There were no differences between treatments.
17.11. Analysis.
Comparison 17 BPO/clindamycin versus erythromycin/zinc, Outcome 11 Percentage of participants with any adverse events (long‐term data).
BPO/clindamycin versus dapsone
One 12‐week parallel trial made this comparison (NCT01231334), including 141 participants on BPO/clindamycin plus adapalene and 145 on dapsone plus adapalene. Results about change in lesion reduction and adverse events were published on the trial registry. No information regarding other outcomes was available.
Primary outcomes
No information was available on the primary outcomes.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
The median percentage reduction was 65.0% versus 62.7% in TLs, 75.9% versus 70.7% in ILs, and 60.7% versus 55.3% in NILs at week 12. No significance test results were presented.
Secondary outcome: percentage of participants experiencing any adverse event
Main pooled analyses: BPO/clindamycin plus adapalene versus dapsone plus adapalene
No serious adverse events were found in both groups. During the 12‐week period, adverse events occurred in 15 participants on BPO/clindamycin plus adapalene (7 participants with nasopharyngitis and 8 with headache) and 23 participants on dapsone plus adapalene (15 participants with nasopharyngitis and 8 with headache), with no significant differences between the two groups (RR 0.67, 95% CI 0.37 to 1.23;Analysis 18.1).
18.1. Analysis.
Comparison 18 BPO/clindamycin versus dapsone, Outcome 1 Percentage of participants with any adverse events (long‐term data).
BPO/erythromycin versus placebo or no treatment
The comparison was made in five parallel trials (Chalker 1983;Draelos 2002;Jones 2002;Sklar 1996;Thiboutot 2002), which provided data for all the outcomes of interest in this review except quality of life and reduction inC. acnes strains.
Primary outcome: participant global self‐assessment of acne improvement
For BPO/erythromycin used alone, two 8‐week trials reported this outcome (Jones 2002;Thiboutot 2002).
Main pooled analyses: BPO/erythromycin versus placebo or no treatment
Jones 2002 presented data in accordance with the definition of treatment success in our review. The trial included 112 participants in the BPO/erythromycin group and 111 in the placebo group. The outcome was assessed with a 4‐point Likert‐like scale. The risk ratio of treatment success was 1.28 (95% CI 1.04 to 1.57;Analysis 19.1), supporting the benefits of BPO/erythromycin treatment.
19.1. Analysis.
Comparison 19 BPO/erythromycin versus placebo or no treatment, Outcome 1 Participant's global self‐assessment of improvement (medium‐term data).
Studies not included in the meta‐analysis
A similar scale was used in the other trial (Thiboutot 2002), but the proportion of treatment success defined in our review cannot be calculated based on data provided in the original report of this trial. With 245 participants treated with BPO/erythromycin and 82 with placebo, the trial found that participants receiving BPO/erythromycin had significantly greater scores at the end of treatment compared with participants receiving placebo (P < 0.001).
Another 12‐week parallel trial included 90 participants on BPO/erythromycin plus tazarotene and 89 participants on tazarotene alone (Draelos 2002). This outcome was assessed using a 5‐point Likert‐like scale (from highly favourable to highly unfavourable). At week 12, no significant difference was found in the proportion of participants rating the improvement as "highly favourable" or "favourable" (86% versus 73%).
Primary outcome: withdrawal due to adverse effects
Main pooled analyses: BPO/erythromycin versus placebo or no treatment
The long‐term trial reported that 6% of participants on BPO/erythromycin versus 11% on placebo discontinued treatments because of adverse events during the 12‐week period (Draelos 2002), with no clear differences detected (RR 0.49, 95% CI 0.18 to 1.39; 179 participants;Analysis 19.2). The trial did not specify which adverse events led to withdrawal.
19.2. Analysis.
Comparison 19 BPO/erythromycin versus placebo or no treatment, Outcome 2 Withdrawal due to adverse effects (long‐term data).
For the other two medium‐term trials (Jones 2002;Thiboutot 2002), only one of 193 participants receiving placebo withdrew because of dryness and itching, and none withdrew from the BPO/erythromycin group consisting of 357 participants, with an RR of 0.33 (95% CI 0.01 to 8.02; 550 participants; 2 studies; I² = 0%;Analysis 19.3).
19.3. Analysis.
Comparison 19 BPO/erythromycin versus placebo or no treatment, Outcome 3 Withdrawal due to adverse effects (medium‐term data).
Studies not included in the meta‐analysis
Two trials provided long‐term data for this outcome (Chalker 1983;Sklar 1996). They included an equal number of participants in each group (76 participants in each) and found that no participants discontinued treatments because of adverse effects.
Secondary outcome: investigator‐assessed change in lesion counts
All four trials reported the mean or percentage reduction in lesion counts (Chalker 1983;Jones 2002;Sklar 1996;Thiboutot 2002). Two of them provided sufficient data to estimate the effect size (Jones 2002;Sklar 1996).
Main pooled analyses: BPO/erythromycin versus placebo or no treatment
For the long‐term change in lesion counts, the mean difference in the absolute change was ‐5.20 (95% CI ‐11.74 to 1.34;Analysis 19.4), ‐6.93 (95% CI ‐11.55 to ‐2.31;Analysis 19.5), and 1.80 (95% CI ‐1.96 to 5.56;Analysis 19.6) for TLs, ILs, and NILs, respectively (Sklar 1996).
19.4. Analysis.
Comparison 19 BPO/erythromycin versus placebo or no treatment, Outcome 4 Investigator‐assessed absolute change in total lesions (long‐term data).
19.5. Analysis.
Comparison 19 BPO/erythromycin versus placebo or no treatment, Outcome 5 Investigator‐assessed absolute change in inflammatory lesions (long‐term data).
19.6. Analysis.
Comparison 19 BPO/erythromycin versus placebo or no treatment, Outcome 6 Investigator‐assessed absolute change in non‐inflammatory lesions (long‐term data).
For the medium‐term change in lesion counts, the mean difference in the absolute change pooled from two trials was ‐4.59 (95% CI ‐12.63 to 3.44; 281 participants; 2 studies; I² = 75%;Analysis 19.7), ‐3.90 (95% CI ‐8.07 to 0.27; 58 participants; 1 study;Analysis 19.8), and 0.80 (95% CI ‐4.30 to 5.89; 281 participants; 2 studies; I² = 73%;Analysis 19.9) for TLs, ILs, and NILs respectively, with no significant differences but high heterogeneity (Jones 2002;Sklar 1996).
19.7. Analysis.
Comparison 19 BPO/erythromycin versus placebo or no treatment, Outcome 7 Investigator‐assessed absolute change in total lesions (medium‐term data).
19.8. Analysis.
Comparison 19 BPO/erythromycin versus placebo or no treatment, Outcome 8 Investigator‐assessed absolute change in inflammatory lesions (medium‐term data).
19.9. Analysis.
Comparison 19 BPO/erythromycin versus placebo or no treatment, Outcome 9 Investigator‐assessed absolute change in non‐inflammatory lesions (medium‐term data).
Sklar 1996 also reported the short‐term outcome. It found no significant differences between the two groups in the absolute change in TLs (MD ‐3.60, 95% CI ‐7.92 to 0.72;Analysis 19.10) and in NILs (MD 2.40, 95% CI ‐0.71 to 5.51;Analysis 19.12). However, the change in ILs differed between groups, favouring the BPO/erythromycin group (MD ‐6.10, 95% CI ‐9.39 to ‐2.81;Analysis 19.11).
19.10. Analysis.
Comparison 19 BPO/erythromycin versus placebo or no treatment, Outcome 10 Investigator‐assessed absolute change in total lesions (short‐term data).
19.12. Analysis.
Comparison 19 BPO/erythromycin versus placebo or no treatment, Outcome 12 Investigator‐assessed absolute change in non‐inflammatory lesions (short‐term data).
19.11. Analysis.
Comparison 19 BPO/erythromycin versus placebo or no treatment, Outcome 11 Investigator‐assessed absolute change in inflammatory lesions (short‐term data).
Studies not included in the meta‐analysis
The other long‐term trial mentioned only whether the significant difference was found (Chalker 1983). As reported, BPO/erythromycin was significantly superior to placebo at week 10 in the percentage reduction in comedone, pustule, papule, and inflammatory lesions.
We cannot obtain mean difference from another medium‐term trial (Thiboutot 2002). Trial authors claimed that significant differences in the percentage reduction in TLs, ILs, and NILs were found at week 8. In the BPO/erythromycin group, TLs were reduced by 58.5%, ILs by 62.6%, and NILs by 59%, compared to 27.5%, 34.1%, and 28.0% in the placebo group.
For the comparison between BPO/erythromycin plus tazarotene and tazarotene, the percentage reduction in ILs was significantly different (65.2% versus 43.7%; P < 0.05) between two groups at week 12 but not the reduction in NILs (48.4% versus 41.6%; P > 0.05). For the medium‐ and short‐term periods, both treatments reduced NILs by about 40% and 30%, respectively, with no significant differences. On the other hand, BPO/erythromycin plus tazarotene was more effective for reducing ILs (58% versus 31% for the medium‐term period and 44% versus 17% for the short‐term period). We cannot estimate MD as the effect size because data were not sufficient to calculate standard deviation.
Secondary outcome: percentage of participants rated 'clear' or 'almost clear' on the IGA scale of acne severity
Main pooled analyses: BPO/erythromycin versus placebo or no treatment
This outcome was reported in two medium‐term trials (Jones 2002;Thiboutot 2002), in which 357 and 193 participants were randomised to BPO/adapalene and placebo groups, respectively. The pooled risk ratio was 2.84 (95% CI 1.79 to 4.52; I² = 9%;Analysis 19.13). For the short‐term outcome,Thiboutot 2002 reported the risk ratio of 6.69 (95% CI 0.91 to 49.10;Analysis 19.14), andJones 2002 mentioned significant differences (P < 0.021).
19.13. Analysis.
Comparison 19 BPO/erythromycin versus placebo or no treatment, Outcome 13 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (medium‐term data).
19.14. Analysis.
Comparison 19 BPO/erythromycin versus placebo or no treatment, Outcome 14 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (short‐term data).
Secondary outcome: percentage of participants experiencing any adverse event
Main pooled analyses: BPO/erythromycin versus placebo or no treatment
For the long‐term outcome, with no significant differences between two groups, 15 of 90 versus 14 of 89 participants had at least one treatment‐related adverse event (RR 1.06, 95% CI 0.54 to 2.06; 179 participants;Analysis 19.15). The distribution of adverse events in each group is unclear.Chalker 1983 reported no adverse events observed during a 10‐week period. The other long‐term trial did not present the total number of participants with at least one adverse event but claimed that the incidence of scaling and tightness in the BPO/erythromycin group was significantly higher (P < 0.05) than in the placebo group.
19.15. Analysis.
Comparison 19 BPO/erythromycin versus placebo or no treatment, Outcome 15 Percentage of participants with any adverse events (long‐term data).
In the two medium‐term trials (Jones 2002;Thiboutot 2002), the risk ratio was 1.88 (95% CI 0.92 to 3.87;Analysis 19.16).
19.16. Analysis.
Comparison 19 BPO/erythromycin versus placebo or no treatment, Outcome 16 Percentage of participants with any adverse events (medium‐term data).
BPO/erythromycin versus clindamycin
One 10‐week parallel trial compared BPO/erythromycin and clindamycin (Packman 1996), in which 99 participants received BPO/erythromycin and 100 received clindamycin. One 12‐week parallel trial included 90 participants on BPO/erythromycin and 87 on clindamycin, all of whom received tazarotene as a co‐intervention (Draelos 2002). This trial reported the following outcomes of our review interest: participant global self‐assessment, withdrawal due to adverse effects, change in lesion counts, and adverse events.
Primary outcome: participant global self‐assessment of acne improvement
Studies not included in the meta‐analysis
This outcome was assessed inDraelos 2002 via a 5‐point Likert‐like scale (from highly favourable to highly unfavourable). At week 12, no significant difference was found in the proportion of participants rating improvement as highly favourable or favourable (86% versus 85%). We cannot estimate RR as the effect size because data were not sufficient to calculate the number of participants with treatment success defined in our review.
Primary outcome: withdrawal due to adverse effects
Main pooled analyses: BPO/erythromycin versus clindamycin
Participants on BPO/erythromycin tended to discontinue treatments because of adverse events, with no significant differences between the two groups (RR 1.51, 95% CI 0.50 to 4.61; 376 participants; 2 studies; I² = 0%;Analysis 20.1). Both trials did not report which adverse events led to their withdrawal.
20.1. Analysis.
Comparison 20 BPO/erythromycin versus clindamycin, Outcome 1 Withdrawal due to adverse effects (long‐term data).
Subgroup analyses: co‐intervention
No evidence suggests the co‐intervention may affect the effect, with a P value of 0.49 (Analysis 20.1).
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
We cannot estimate MD as the effect size because data in both trials were not sufficient to calculate standard deviation.
InPackman 1996, the absolute change in ILs and NILs was significantly different between the two groups at any time point, in favour of BPO/erythromycin. The mean number of ILs decreased from 18.2 at baseline to 11.5 (short term), 9.0 (medium term), and 8.4 (long term) in participants on BPO/erythromycin, and the counterpart decreased from 17.4 to 12.7, 12.0, and 12.3 in participants on clindamycin. The mean number of NILs decreased from 25.6 at baseline to 15.4, 14.7, and 13.6 in participants on BPO/erythromycin, but there was almost no change in participants on clindamycin (from 23.6 to 25.5, 22.6, and 23.2).
InDraelos 2002, the percentage reduction in ILs at week 12 was significantly different (65.2% versus 40.1%; P < 0.05) but not in NILs (48.4% versus 55.7%; P > 0.05). For the medium‐ and short‐term periods, both treatments reduced NILs by about 40% and 30%, respectively, with no significant differences. On the other hand, BPO/erythromycin plus tazarotene seemed more effective for reducing ILs (58% versus 35% for the medium‐term period and 44% versus 22% for the short‐term period).
Secondary outcome: percentage of participants experiencing any adverse event
Main pooled analyses: BPO/erythromycin versus clindamycin
Non‐significantly increased risk of adverse event occurrence was observed between the two groups (RR 2.16, 95% CI 0.77 to 6.08; 378 participants; 2 studies; I² = 23%;Analysis 20.2). Adverse events reported in the trials included dryness, erythema, pruritus, stinging, burning, and unusual taste and smell.
20.2. Analysis.
Comparison 20 BPO/erythromycin versus clindamycin, Outcome 2 Percentage of participants with any adverse events (long‐term data).
Subgroup analyses: co‐intervention
No evidence suggests that the co‐intervention may affect the effect, with a P value of 0.25 (Analysis 20.2).
BPO/erythromycin versus azelaic acid
One eight‐week parallel trial compared BPO/erythromycin and azelaic acid (Dunlap 1997). Only an abstract was available for this trial. A total of 150 participants were included in the trial, but it is unclear how many participants were in each group. The abstract reported limited information on the change in lesion counts.
Primary outcomes
No information was available on the primary outcomes.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
Trial authors reported that BPO/erythromycin was superior to azelaic acid in reducing ILs at week 8, but they were not significantly different in reducing NILs. We cannot estimate RR as the effect size because insufficient data were reported in the abstract.
BPO/erythromycin versus metronidazole
One four‐week parallel trial made this comparison (Fan 1998), in which 56 participants received BPO/erythromycin and 54 received metronidazole. Trial authors reported the change in lesion counts.
Primary outcomes
No information was available on the primary outcomes.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
At week 4, the difference in TLs between the two treatment groups was not significant. The mean number of TLs decreased from of 18.1 at baseline to 3.7 in participants on BPO/erythromycin and from 17.8 to 4.2 in participants on metronidazole. We cannot estimate MD as the effect size because data were not sufficient to calculate standard deviation.
BPO/erythromycin versus viaminate
One four‐week parallel trial made this comparison (Zhao 2001), in which 100 participants received BPO/erythromycin and 87 received viaminate. The trial reported withdrawal due to adverse effects and adverse events.
Primary outcome: withdrawal due to adverse effects
Studies not included in the meta‐analysis
No participants discontinued treatments due to adverse effects.
Secondary outcome: percentage of participants experiencing any adverse event
Main pooled analyses: BPO/erythromycin versus viaminate
No adverse events occurred in the viaminate group, but 13 participants in the BPO/erythromycin group had dryness and mild peeling and redness, with significantly higher risk in the BPO/erythromycin group (RR 23.52, 95% CI 1.42 to 390.03; 187 participants;Analysis 21.1).
21.1. Analysis.
Comparison 21 BPO/erythromycin versus viaminate, Outcome 1 Percentage of participants with any adverse events (short‐term data).
BPO/erythromycin versus zinc/erythromycin
One 10‐week trial compared BPO (5%)/erythromycin (3%) and zinc (1.2%)/erythromycin (4%) (Chu 1997): a total of 72 participants were included. It is unclear how many participants were randomised to each group, so we cannot calculate the effect size for any outcomes. Trial authors reported the following outcomes of our review interest: participant global self‐assessment, withdrawal due to adverse effects, change in lesion counts, and adverse events.
Primary outcome: participant global self‐assessment of acne improvement
Studies not included in the meta‐analysis
Participants rated overall acne improvement using a 6‐point scale (0 = worse, 1 = no change, 2 = slight improvement, 3 = mild improvement, 4 = moderate improvement, 5 = excellent improvement). For this outcome, trial authors reported only that participant self‐assessment was strongly in favour of BPO/erythromycin (P < 0.001).
Primary outcome: withdrawal due to adverse effects
Studies not included in the meta‐analysis
No participants on BPO/erythromycin and three participants on zinc/erythromycin discontinued treatment due to adverse events. It is unclear what adverse events occurred in these three participants.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
A significant difference between groups was found in the percentage reduction in both ILs (86.6% versus 60.3%) and NILs (53.1% versus 26.8%) for the long‐term period (week 10) (both P values < 0.005). For the medium‐term period, significant differences were observed in both ILs (80% versus 52%) and NILs (49% versus 25%). However, the percentage reduction in ILs was significantly different for the short‐term period (69% versus 44%), but not the percentage reduction in NILs (26% versus 14%).
Secondary outcome: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
Only one participant on BPO/erythromycin reported adverse events (dryness and irritation). In the zinc/erythromycin group, four participants reported nine adverse events, including irritation, itching, dryness, redness, scratching, scaling, and soreness.
BPO/sulphur versus placebo
One parallel trial compared BPO/sulphur and placebo (Vasarinsh 1969); 19 participants were treated with BPO and 19 with placebo for 4 to 14 weeks. This trial report covered the outcomes of participant self‐assessment of acne improvement, change in acne lesions, and adverse events.
Primary outcome: participant global self‐assessment of acne improvement
Studies not included in the meta‐analysis
Researchers assessed the outcome using a 4‐point Likert‐like scale (from worse = ‐1 to greatly improved = 2). The average score was 1.15 and 0.53 for the BPO/sulphur and placebo groups, respectively. We cannot estimate RR as the effect size because data were not sufficient to calculate the number of participants with treatment success as defined in our review.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
The change in lesion counts was assessed for superficial (comedones and pustules) and deep (papules and cysts) lesions, respectively, via an 11‐point scoring system (decrease in lesions by 100% = 5, 76% to 99% = 4, 51% to 75% = 3, 26% to 50% = 2, < 25% = 1, and no change = 0; increase by < 25% = ‐1, 26% to 50% = ‐2, 51% to 75% = ‐3, 76% to 100% = ‐4, and over 100% = ‐5). The average score for superficial lesions was 0.81 and 0 for the BPO/sulphur and placebo groups, respectively, and the counterpart for deep lesions was 0.91 and 0.53. We cannot estimate MD as the effect size because data were not sufficient to calculate standard deviation.
Secondary outcome: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
Individual adverse events were reported, but the total number of participants with any adverse event was not reported. Excessive erythema and dryness occurred in two participants on placebo and in four participants taking BPO/sulphur treatment.
BPO/glycolic acid/zinc lactate versus placebo
Sklar 1996, a 12‐week trial that made this comparison, included 30 participants on BPO/glycolic acid/zinc lactate gel and 32 on placebo. Trial authors reported the following outcomes of our review interest: withdrawal due to adverse effects, change in lesion counts, and adverse events.
Primary outcome: withdrawal due to adverse effects
Studies not included in the meta‐analysis
No participants discontinued treatment because of any adverse events.
Secondary outcome: investigator‐assessed change in lesion counts
Main pooled analyses: BPO/glycolic acid/zinc lactate versus placebo
For the long‐term change in lesion counts, the absolute change in TLs and ILs was significantly different, with an MD of ‐6.50 (95% CI ‐12.56 to ‐0.44; 56 participants;Analysis 22.1) and ‐5.60 (95% CI ‐10.38 to ‐0.82; 56 participants;Analysis 22.2), respectively. No clear difference in NILs was found (MD ‐0.90, 95% CI ‐4.74 to 2.94; 56 participants;Analysis 22.3).
22.1. Analysis.
Comparison 22 BPO/glycolic acid/zinc lactate versus placebo, Outcome 1 Investigator‐assessed absolute change in total lesions (long‐term data).
22.2. Analysis.
Comparison 22 BPO/glycolic acid/zinc lactate versus placebo, Outcome 2 Investigator‐assessed absolute change in inflammatory lesions (long‐term data).
22.3. Analysis.
Comparison 22 BPO/glycolic acid/zinc lactate versus placebo, Outcome 3 Investigator‐assessed absolute change in non‐inflammatory lesions (long‐term data).
For the medium‐term absolute change in lesion counts, no significant difference was observed for any types of lesions, with an MD of ‐0.90 (95% CI ‐5.26 to 3.46; 56 participants;Analysis 22.4), ‐2.60 (95% CI ‐6.59 to 1.39; 56 participants;Analysis 22.5), and 1.70 (95% CI ‐1.95 to 5.35; 56 participants;Analysis 22.6) for TLs, ILs, and NILs, respectively.
22.4. Analysis.
Comparison 22 BPO/glycolic acid/zinc lactate versus placebo, Outcome 4 Investigator‐assessed absolute change in total lesions (medium‐term data).
22.5. Analysis.
Comparison 22 BPO/glycolic acid/zinc lactate versus placebo, Outcome 5 Investigator‐assessed absolute change in inflammatory lesions (medium‐term data).
22.6. Analysis.
Comparison 22 BPO/glycolic acid/zinc lactate versus placebo, Outcome 6 Investigator‐assessed absolute change in non‐inflammatory lesions (medium‐term data).
Trial authors also reported the short‐term outcome, noting no significant differences between the two groups in the absolute change in TLs (MD ‐4.20, 95% CI ‐9.29 to 0.89; 58 participants;Analysis 22.7) nor in NILs (MD 0.50, 95% CI ‐3.41 to 4.41; 58 participants;Analysis 22.9). However, the change in ILs differed, favouring the BPO/erythromycin group (MD ‐4.80, 95% CI ‐8.66 to ‐0.94; 58 participants;Analysis 22.8).
22.7. Analysis.
Comparison 22 BPO/glycolic acid/zinc lactate versus placebo, Outcome 7 Investigator‐assessed absolute change in total lesions (short‐term data).
22.9. Analysis.
Comparison 22 BPO/glycolic acid/zinc lactate versus placebo, Outcome 9 Investigator‐assessed absolute change in non‐inflammatory lesions (short‐term data).
22.8. Analysis.
Comparison 22 BPO/glycolic acid/zinc lactate versus placebo, Outcome 8 Investigator‐assessed absolute change in inflammatory lesions (short‐term data).
Secondary outcome: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
Trial authors reported that adverse events including mild erythema, scaling, tightness, burning, stinging, itching, or tingling were observed in both groups. However, the number of participants with any event in each group was not reported.
BPO/potassium hydroxyquinoline sulphate versus placebo
One 12‐week trial made this comparison (Jaffe 1989); 25 participants on BPO/potassium hydroxyquinoline sulphate cream and 28 on placebo were included. Trial authors reported the following outcomes of our review interest: withdrawal due to adverse effects and adverse events.
Primary outcome: withdrawal due to adverse effects
Main pooled analyses: BPO/potassium hydroxyquinoline sulphate versus placebo
Three participants on BPO/potassium hydroxyquinoline sulphate discontinued treatment because of stinging or skin irritation, with no significant differences between the two groups (RR 7.81, 95% CI 0.42 to 144.12; 53 participants;Analysis 23.1).
23.1. Analysis.
Comparison 23 BPO/potassium hydroxyquinoline sulphate versus placebo, Outcome 1 Withdrawal due to adverse effects (long‐term data).
Secondary outcome: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
Trial authors mentioned that adverse events were recorded; however, no information on specific adverse events was available in the results section, except that three participants withdrew due to adverse events.
BPO (10%) versus BPO (5%)
Two trials compared 10% BPO with 5% BPO for treating acne (Ji 2000;Wang 2003); length of treatment in both was six weeks. Both trials assessed the following outcomes: withdrawal, lesion counts, and adverse events.
Primary outcome: withdrawal due to adverse effects
Main pooled analyses: BPO (10%) versus BPO (5%)
One of 93 participants treated with 10% BPO discontinued treatment due to adverse effects, and five of 164 participants in the 5% BPO group withdrew (Ji 2000;Wang 2003). Such differences were not significant, with an RR of 0.40 (95% CI 0.06 to 2.52; I² = 0%;Analysis 24.1). It is unclear which adverse events resulted in their withdrawal.
24.1. Analysis.
Comparison 24 BPO 10% versus BPO 5%, Outcome 1 Withdrawal due to adverse effects (medium‐term data).
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
Neither of the trials reported the change in lesion counts from baseline, but trial authors reported lesion counts at the end of the study. Compared with 5% BPO, the mean difference in IL counts at week 6 was ‐0.62 (95% CI ‐1.97 to 0.73; I² = 19%), and the counterpart in NIL counts was ‐7.56 (95% CI ‐12.04 to ‐3.07; I² = 65%).
Secondary outcome: percentage of participants experiencing any adverse event
Main pooled analyses: BPO (10%) versus BPO (5%)
No evidence suggests a significant difference in the occurrence of adverse events. The risk ratio was 0.72 (95% CI 0.40 to 1.31; I² = 65%;Analysis 24.2).
24.2. Analysis.
Comparison 24 BPO 10% versus BPO 5%, Outcome 2 Percentage of participants with any adverse events (medium‐term data).
BPO (10%) versus BPO (2.5%)
Two trials compared 10% BPO with 2.5% BPO for treating acne (Mills 1986;Wang 2003); length of treatment was six or eight weeks. Researchers assessed the following outcomes: withdrawal, lesion counts, and adverse events.
Primary outcome: withdrawal due to adverse effects
Studies not included in the meta‐analysis
In total, the two trials included 58 participants treated with 10% BPO and 56 treated with 2.5% BPO. None in both groups discontinued treatment due to adverse effects.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
With 24 participants treated with 10% BPO and an equal number of participants with 2.5% BPO,Mills 1986 found similar percentage reduction in ILs (44.7% versus 46.7%) at week 8.
InWang 2003, 33 participants were included in the 10% BPO group and 124 in the 2.5% BPO group. Trial authors presented lesion counts at week 6, rather than the change in lesion counts from baseline, suggesting that both IL and NIL counts were fewer in the 10% BPO group (MD for ILs ‐3.80, 95% CI ‐5.99 to ‐1.61; MD for NILs ‐3.70, 95% CI ‐6.66 to ‐0.74).
Secondary outcome: percentage of participants experiencing any adverse event
Main pooled analyses: BPO (10%) versus BPO (2.5%)
InWang 2003, more participants in the 10% BPO group were experiencing adverse events (20/33 versus 11/31; RR 1.71, 95% CI 0.99 to 2.96;Analysis 25.1).Mills 1986 reported a significant difference in the frequency and severity of erythema, peeling, and burning between those receiving 10% BPO and those receiving 2.5% BPO at all follow‐up visits.
25.1. Analysis.
Comparison 25 BPO 10% versus BPO 2.5%, Outcome 1 Percentage of participants with any adverse events (medium‐term data).
BPO (5%) versus BPO (2.5%)
This comparison consisted of six trials assessing BPO (5%) versus BPO (2.5%) with no co‐intervention (Kawashima 2017a;Kawashima 2017b;Mills 1986;NCT02073461;Wang 2003;Yong 1979), along with one trial using clindamycin and tazarotene as co‐interventions in each group (Dhawan 2013). Researchers assessed the following outcomes: participant global self‐assessment, withdrawal due to adverse effects, change in lesion counts, change in quality of life, and adverse events.
Primary outcome: participant global self‐assessment of acne improvement
Studies not included in the meta‐analysis
The outcome was assessed inDhawan 2013 (including 20 participants in each group) via a 5‐point scale (1 = very satisfied, 2 = satisfied, 3 = neutral, 4 = unsatisfied, 5 = very unsatisfied). There was no significant difference between the two groups in the proportion of participants rating the improvement as "very satisfied" or "satisfied" (88.2% versus 85.0%) at week 12. We cannot estimate RR as the effect size because data were not sufficient to calculate the number of participants with treatment success defined in our review.
Primary outcome: withdrawal due to adverse effects
Main pooled analyses: BPO (5%) versus BPO (2.5%)
In the long‐term trials (Dhawan 2013;Kawashima 2017a;Kawashima 2017b), the pooled RR of this outcome was 1.28 (95% CI 0.65 to 2.54; 906 participants; I² = 0%;Analysis 26.1). Adverse events leading to withdrawal included application site erythema and irritation.
26.1. Analysis.
Comparison 26 BPO 5% versus BPO 2.5%, Outcome 1 Withdrawal due to adverse effects (long‐term data).
Wang 2003, a six‐week trial, andMills 1986, an eight‐week trial, reported medium‐term outcomes. Among a total of 151 participants treated with 5% BPO and 57 participants treated with 2.5% BPO, only three participants on 5% BPO treatment discontinued treatment due to adverse effects (Mills 1986;Wang 2003), with an RR of 1.79 (95% CI 0.09 to 33.82;Analysis 26.2). Trial authors did not specify which adverse events led to their withdrawal.
26.2. Analysis.
Comparison 26 BPO 5% versus BPO 2.5%, Outcome 2 Withdrawal due to adverse effects (medium‐term data).
Subgroup analyses: co‐intervention
For the long‐term outcome, no evidence suggests that the effect may be affected by the co‐intervention (P = 0.59;Analysis 26.1).
Studies not included in the meta‐analysis
InYong 1979, in which participants were treated for 4 to 18 weeks, 11 participants did not complete the trial because of desquamation and erythema, and four participants with pustulation and exacerbation of acne lesions were withdrawn. In this trial, however, it is unclear how many participants in each group withdrew.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
With 25 participants on 5% BPO and 26 on 2.5% BPO,Mills 1986 found similar percentage reduction in ILs (57.7% versus 55.9%) at week 8. A total of 124 participants were included in the 5% BPO group and 31 in the 2.5% BPO group (Wang 2003). Trial authors presented lesion counts at week 6, rather than the change in lesion counts from baseline, suggesting that IL but not NIL counts were lower in the 5% BPO group (MD for ILs ‐4.00, 95% CI ‐6.42 to ‐1.58; MD for NILs 1.80, 95% CI ‐1.69 to 5.29). In a 12‐week trial including 78 participants on 5% BPO and 79 on 2.5% BPO (NCT02073461), the reduction in TLs was 65.9% and 58.3%, respectively, with no significance test results presented. InYong 1979, 98 participants on 5% BPO and 96 on 2.5% BPO were assessed for treatment improvement based on the percentage reduction in lesion counts. At least 50% reduction was found in 74 versus 64 participants.Dhawan 2013 suggested no significant difference in the percentage reduction in TLs, ILs, and NILs at week 12 (67.7% versus 67.9%, 66.1% versus 53.8%, and 67.8% versus 75.0%, respectively). We cannot estimate MD as the effect size because data were not sufficient to calculate standard deviation.
Secondary outcome: change in quality of life
Main pooled analyses: BPO (5%) versus BPO (2.5%)
InDhawan 2013, no significant difference was found in the mean change in Skindex‐29 global scores from baseline at week 12 (MD ‐2.40, 95% CI ‐8.68 to 3.88; 40 participants;Analysis 26.3).
26.3. Analysis.
Comparison 26 BPO 5% versus BPO 2.5%, Outcome 3 Change in quality of life (long‐term data).
Secondary outcome: percentage of participants experiencing any adverse event
Main pooled analyses: BPO (5%) versus BPO (2.5%)
Three studies provided long‐term data for this outcome in a total of 1063 participants (529 in the 5% group and 534 in the 2.5% group), with no clear differences between groups (RR 1.06, 95% CI 0.95 to 1.19;Analysis 26.4) (Dhawan 2013,Kawashima 2017a;Kawashima 2017b;NCT02073461).
26.4. Analysis.
Comparison 26 BPO 5% versus BPO 2.5%, Outcome 4 Percentage of participants with any adverse events (long‐term data).
Kawashima 2017a reported that the top three adverse events were skin exfoliation (52/227 versus 42/231), application site irritation (46/227 versus 44/231), and application site erythema (41/227 versus 32/231). Similarly, the most common adverse event inKawashima 2017b was skin exfoliation (48/204 versus 39/204), followed by erythema (22/204 versus 28/204) and irritation (25/204 versus 17/204). Skin irritation (1/78 versus 3/79) was the most frequent skin or cutaneous adverse event reported inNCT02073461.Dhawan 2013 reported that 11 participants on BPO (5%)/clindamycin and seven participants on BPO (2.5%)/clindamycin had at least one adverse event, most of which were related to infections and infestations with nasopharyngitis.
Three trials reported the medium‐term outcome (Mills 1986;Wang 2003;Yong 1979); of these, onlyWang 2003 provided sufficient data for an effect estimate. More participants in the 5% BPO group experienced adverse events (82/124 versus 11/31; RR 1.86, 95% CI 1.14 to 3.05;Analysis 26.5).
26.5. Analysis.
Comparison 26 BPO 5% versus BPO 2.5%, Outcome 5 Percentage of participants with any adverse events (medium‐term data).
Subgroup analyses: co‐intervention
For the long‐term outcome, we did not find evidence suggesting this effect may differ by co‐intervention, with a P value of 0.86 (Analysis 26.4).
Studies not included in the meta‐analysis
Two medium‐term trials did not provide sufficient data for the meta‐analysis.Mills 1986 reported no significant differences in the frequency and severity of erythema, peeling, and burning between those receiving 5% BPO and those given 2.5% BPO. Adverse events were reported individually inYong 1979, with erythema the most common event (50/98 versus 45/96), followed by desquamation (28/98 versus 22/96).
BPO gel (6%) versus BPO cream (5.5%)
One 12‐week trial, which included 24 participants in each group, compared the two concentrations of BPO (Smith 2006). Trial authors reported the following outcomes of our review interest: participant global self‐assessment, withdrawal due to adverse effects, change in lesion counts, and adverse events.
Primary outcome: participant global self‐assessment of acne improvement
Studies not included in the meta‐analysis
The outcome was assessed via a 5‐point scale (from 0 = no improvement or worsening to 4 = complete clearing). With no significance test results reported, trial authors claimed that more participants on 5.5% BPO cream rated the improvement as "marked" or "better" than those on 6% BPO gel (38% versus 32%). We cannot estimate the RR because data were not sufficient to calculate the number of participants with treatment success defined in our review.
Primary outcome: withdrawal due to adverse effects
Main pooled analyses: BPO gel (6%) versus BPO cream (5.5%)
One participant on 6% BPO gel discontinued treatment due to application site irritation, with no significant differences between the two groups (RR 3.00, 95% CI 0.13 to 70.16; 48 participants;Analysis 27.1).
27.1. Analysis.
Comparison 27 BPO gel (6%) versus BPO cream (5.5%), Outcome 1 Withdrawal due to adverse effects (long‐term data).
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
No significant difference was found in the percentage reduction in TLs, ILs, and NILs at week 12 (21.2% versus 35.6%, 25.1% versus 39.3%, and 19.5% versus 33.0%, respectively). We cannot estimate MD as the effect size because data were not sufficient to calculate standard deviation.
Secondary outcome: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
As reported by trial authors, 46 adverse events were reported in 48% of participants and were more frequently observed in participants on 6% BPO. However, the number of adverse events for each group is unclear. The most common events were dryness, erythema, scaling, itching, stinging, and burning.
BPO (vehicle with 8% urea) versus BPO (vehicle with no urea)
One eight‐week split‐face trial made this comparison (Prince 1982), including 39 participants. Only an abstract was available for this trial. The abstract reported limited information on trial characteristics and on the outcome of change in lesion counts.
Primary outcomes
No information was available on the primary outcomes.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
Trial authors found no significant differences in the reduction in TLs and ILs between groups during the eight weeks. We cannot estimate MD as the effect size because data were not sufficient to calculate standard deviation.
BPO (vehicle with acetone) versus BPO (vehicle with alcohol/detergent)
This comparison was made in one 8‐week parallel trial (Lyons 1978), which included 54 participants treated with BPO acetone gel and 38 treated with BPO alcohol/detergent gel. Trial authors reported the following outcomes of our review interest: withdrawal due to adverse effects, change in lesion counts, and adverse events.
Primary outcomes
No primary outcomes of this review were reported in the trials.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
Trial authors reported that no statistical differences in the percentage change in comedones (62% versus 57%), papules (56% versus 56%), pustules (80% versus 79%), and total lesions (62% versus 59%) were found between groups at week 8. We cannot estimate MD as the effect size because data were not sufficient to calculate standard deviation.
Secondary outcome: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
No adverse events were reported in either of the BPO gel groups.
BPO (formulation 1) versus BPO (formulation 2)
One four‐week split‐face trial made this comparison (NCT00787943), including 10 participants receiving each formulation on each face side. No information was provided regarding differences between the two formulations. Results about the change in lesion reduction and about adverse events were published on the trial registry. No information regarding other outcomes was available.
Primary outcomes
No information was available on the primary outcomes.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
The trial registry published papule and pustule counts for each individual at any time point, with no statistical results available.
Secondary outcome: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
No serious adverse events were found in the 10 participants. During the four‐week period, adverse events occurred in eight participants. All experienced burning/stinging.
Water‐based BPO versus alcohol‐based BPO
This comparison was made in one 8‐week split‐face trial (Fyrand 1986), which included 45 participants treated with water‐based BPO on one side of the face and with alcohol‐based BPO on the other side. Trial authors reported the following outcomes of our review interest: withdrawal due to adverse effects, change in lesion counts, and adverse events.
Primary outcome: withdrawal due to adverse effects
Studies not included in the meta‐analysis
Six participants discontinued treatment due to local side effects. Two participants had severe dermatitis on both sides. Side effects occurred on both sides in another two participants but were worse on the side treated with alcohol‐based BPO: one participant had erythema, itching, and stinging, and the other had erythema and scaling. Another two participants stopped alcohol‐based BPO because of severe stinging.
Secondary outcome: investigator‐assessed change in lesion counts
Studies not included in the meta‐analysis
Trial authors reported no significant differences (mean difference was null) at each time point (four weeks and eight weeks) for any types of lesions including open comedones, closed comedones, pustules, papules, and cysts. We cannot estimate MD as the effect size because data were not sufficient to calculate standard deviation.
Secondary outcome: percentage of participants experiencing any adverse event
Studies not included in the meta‐analysis
No significant difference in the incidence of peeling and dryness was found between groups (10% versus 18% and 8% versus 12%, respectively). Trial authors reported no significant differences in grading for erythema, burning, dryness, or pruritus.
Discussion
Summary of main results
We included 120 randomised controlled trials (RCTs) (188 reports) in this systematic review, which consisted of 47 pair‐wise comparisons involving topical treatments. Most of the evidence centred around BPO (as monotherapy or as add‐on treatment) and benzoyl peroxide (BPO) fixed combination treatments (BPO/adapalene, BPO/clindamycin, or BPO/erythromycin). Treatment duration in most of these trials was longer than eight weeks (a long‐term period as defined in our review); we found that our included studies rarely assessed short‐term treatment. Evaluation of our outcomes was limited, with many of our included studies assessing different outcomes from those we had pre‐specified as of interest. Application vehicle and BPO concentration were treatment aspects that were under‐reviewed by our studies.
We summarise here the key results for our key treatment comparisons.
BPO versus placebo or no treatment (Table 1).
BPO versus adapalene (Table 2).
BPO versus clindamycin (Table 3).
BPO versus erythromycin (Table 4).
BPO versus salicylic acid (Table 5).
Clinical efficacy
Primary efficacy outcome: participant global self‐assessment of acne improvement
Our review suggests that BPO as monotherapy or as add‐on treatment may be more effective than placebo or no treatment in achieving self‐reported treatment success (low‐certainty evidence).
Low‐certainty evidence suggests there may be little to no difference in achieving treatment success when BPO is compared to adapalene or to clindamycin. In studies using their own definitions of self‐reported improvement, a neutral comparative effect was observed for BPO when compared with adapalene, clindamycin, or salicylic acid.
No studies evaluating BPO compared to erythromycin or salicylic acid assessed self‐reported acne improvement.
Adverse effects
Primary safety outcome: withdrawal due to adverse effects
Withdrawal from the trial due to adverse effects was generally rare in the included trials. However, low‐certainty evidence suggests that participants on BPO may be more likely than participants on placebo or no treatment to discontinue treatment. Skin burning, erythema, and pruritus were the main adverse events leading to withdrawal for this comparison.
We found very low‐certainty evidence for risk of withdrawal due to adverse events when BPO was compared to clindamycin, erythromycin, adapalene, or salicylic acid: there may be little to no difference between groups in these comparisons in terms of withdrawal; however, we are unsure of the results due to the very low certainty of the evidence. When stated, reasons given for withdrawal may be associated with tolerability and included local hypersensitivity, pruritus, dermatitis, erythema, face oedema, rash, and skin burning.
Secondary safety outcome: percentage of participants experiencing any adverse event
Adverse events were usually short term, mild to moderate, and well tolerated. The most commonly reported adverse events included skin dryness, pruritus, dermatitis, erythema, pain at the site of application, and irritation.
For BPO compared with placebo or no treatment, adapalene, erythromycin, or salicylic acid, we found only very low‐certainty evidence underlying risk of adverse events, so we are uncertain whether there was a difference between these groups.
Moderate‐certainty evidence indicates that BPO may increase risk of adverse events when compared with clindamycin; however, the 95% confidence interval (CI) indicates that BPO might make little to no difference.
Overall completeness and applicability of evidence
Evidence from our included studies was insufficient to fully address the objectives of this review: minimal assessment of key outcomes, variation in how reported outcomes were measured, and lack of evidence for key comparisons, limiting our conclusions.
Most of the participants in the included trials suffered mild to moderate facial acne. Nearly 22% had severe acne, and 18% of studies did not report acne severity. We had planned to conduct subgroup analysis of severity, but none of the comparisons met our prerequisite (each subgroup included at least three studies). The mean age of participants ranged from 18 to 30, which is a relevant target population, as 64% of people aged 20 to 29 years may still have acne. Women who were pregnant, breastfeeding, or planning pregnancy were excluded from the trials. Therefore, the results of this review might not apply to these excluded participants. Approximately 7% of the included studies assessed acne on the trunk, meaning that our evidence pertains mainly to facial acne.
Although we assessed the outcomes for different treatment duration, most evidence was derived from studies (80/120 trials) with a long‐term treatment duration (> 8 weeks). This might also restrict the results reported in this review, in that they cannot be generalised to people treated for a shorter time. However, evidence from a longer treatment duration (at least 24 weeks) was rare, with only four included trials having participants treated for at least 24 weeks. Although long‐term treatment was our primary end point of interest, we aimed to report shorter treatment periods as an indicator of early improvement; however, short‐term treatment was given in only 10% of the studies.
Despite a large number of trials included in this review, the number of trials for most outcomes of interest for a specific comparison was usually limited. This hindered investigation of heterogeneity sources (e.g. subgroup analysis), assessment of publication bias, and evaluation of the certainty of evidence. In terms of treatment, application vehicle and concentration are considered key treatment factors, but only four comparisons assessed BPO given in different vehicles, and different concentrations of BPO (10%, 6%, 5.5%, 5%, 2.5%) were assessed by only 10 studies in total, with low numbers eligible for pooling in a meta‐analysis. Combination treatment was also evaluated in relatively few trials.
The primary efficacy outcome (self‐reported improvement) was reported in only 38 trials. Moreover, assessment scales varied substantially in these studies, and data for this outcome were heterogeneous. Evidence synthesis for this outcome was thus impossible for most comparisons.
For secondary efficacy outcomes, most trials (97/120) presented results related to acne lesions (mostly as the primary outcome). However, reporting was not consistent across these trials, which was reflected in three aspects. First, different types of lesions were reported. Most trials reported only one or two types of lesions (total, inflamed, or non‐inflamed lesions). Second, different measures were used across trials, including absolute change in lesions, percentage change in lesions, and change in lesion counts. One or two measures were usually reported in a trial. Third, results were not completely reported. Most trials reported only point estimates, without standard errors, 95% confidence intervals, or specified P values. The problems with inconsistent and incomplete reporting not only hindered evidence synthesis but also implied the probability of selective reporting. The Investigator Global Assessment (IGA) scale of acne severity was used in a small portion of trials (25/120), in which the proportion or the number of participants rated as 'clear' or 'almost clear' was presented. Limited data were available on the change in quality of life and reduction inCutibacterium acnes (C acnes) strains, neither of which could be assessed for most comparisons in this review.
Regarding safety outcomes, only 68 of the 120 trials reported withdrawal due to adverse effects, but most trials (96/120) mentioned the number of participants with any adverse events.
Quality of the evidence
We summarised the certainty of evidence for five main comparisons. Certainty of the evidence was moderate in a limited number of outcomes, but most varied from low to very low certainty, depending on the outcomes and comparisons. The most common reasons for downgrading the certainty level were risk of bias, imprecision, and inconsistency of results.
Limitations in study design or execution
We considered most of the included studies as having high or unclear risk of bias in all seven risk of bias domains. We classified 65% of the included studies as having high risk of performance bias due to no blinding of participants and personnel, and nearly half as having high risk of detection bias for no blinding of outcome assessment. Blinding is likely to affect the measurement of outcomes for acne improvement, especially for the subjective measure, for the participant's self‐reported acne improvement. Even though blinding was conducted in some trials, success in blinding was difficult because treatment comparators differed in their appearance, properties, or known adverse effects (Ingram 2010). Lack of successful blinding could lead to biased results in favour of an experimental intervention due to lack of expectations in a control group, especially in placebo‐controlled trials. Because of incomplete outcome data, we judged more than a quarter of studies as having high risk of attrition bias. Most of the included studies did not provide sufficient information to determine the risk of bias in the domain of allocation concealment. Failure to conduct allocation concealment may lead investigators to include participants on the basis of their prognostic factors (such as severity and duration of acne) or to deliberately direct participants to the treatment from which they were considered to benefit more. Due to high and unclear risk of bias, we downgraded the certainty of evidence for risk of bias by one or more levels for most of the outcomes that we evaluated.
Inconsistency of results
The small number of included studies confined assessment of inconsistency for most comparisons. When inconsistency was identified, however, we downgraded the certainty of evidence by one level.
For the primary efficacy outcome, heterogeneity probably resulted from differences in the scales used to assess participant‐reported acne improvement. Heterogeneity was also common in the safety outcome probably due to different criteria used to determine adverse events. In the subgroup analysis, we found that effects of BPO may differ by co‐interventions. Acne severity, BPO concentrations, and countries in which trials were conducted (western and Asian) were also potential sources of heterogeneity.
Indirectness
We included studies that met the eligibility criteria regarding study population, intervention, comparison, and outcomes. We assessed only the two primary outcomes and adverse events related to treatment. We did not downgrade the certainty of evidence for any outcomes for indirectness.
Imprecision
The numbers of studies included were small for most comparisons. Events were rare in some outcomes, for example, withdrawal due to adverse effects and occurrence of adverse events. Consequently, imprecision was one major reason for which we downgraded the certainty of evidence.
Publication bias
In the systematic review process, we conducted a comprehensive search to minimise the risk of publication bias. ForAnalysis 1.3,Analysis 1.20, andAnalysis 2.2, when the number of included trials met the prerequisites as pre‐defined for publication bias analysis, funnel plots suggested low risk of publication bias (Figure 4;Figure 5;Figure 6). On the other hand, we identified risk of publication bias for some comparisons (BPO versus placebo or no treatment, BPO versus adapalene, BPO/adapalene versus placebo, BPO/clindamycin versus placebo, BPO/clindamycin versus adapalene, and BPO/sulphur versus placebo) that were involved in 10 trials starting before 2015 but still "ongoing" as shown in the trial registries.
Upgrading of certainty of evidence
We included only randomised trials; thus, the certainty of evidence would be high if we did not rate down due to any of the GRADE downgrading domains (risk of bias, inconsistency, indirectness, imprecision, and publication bias). If we had any concerns for rating down, we would not be confident to upgrade the certainty of evidence.
Potential biases in the review process
We made every effort to minimise potential bias in the review process. We comprehensively searched and included studies with no limits on language or publication year, so that the risk of missing eligible studies was low. Two review authors independently determined the eligibility of studies, extracted data, and assessed risk of bias, with a third review author acting as an arbiter to minimise potential bias in the review process. None of the review authors had a conflict of interest regarding any of the medications involved in this review.
However, several limitations of our review should be acknowledged. First, some potentially relevant trials were not included in our full assessment, as we could not confirm eligibility for those that were not reported in full text (listed inCharacteristics of studies awaiting classification). Second, all amendments were made to the original protocol before data extraction and were based on consideration of clinical relevance, the purpose of this review, and consistency in definitions with other acne‐related Cochrane Reviews. Third, poor reporting was very common in the included trials and may introduce some bias or incompleteness in our assessment and analysis. To clarify any ambiguity due to such poor reporting, we contacted study authors for additional data (mainly about primary outcomes and the availability of full text) but seldom received a response to our request.
Agreements and disagreements with other studies or reviews
Several relevant systematic reviews (or meta‐analyses) have been conducted for BPO versus placebo (Lamel 2015;Seidler 2010), BPO versus adapalene (Kolli 2019), BPO versus clindamycin (Seidler 2010), BPO/adapalene versus placebo (Dressler 2016;Gold 2016a;Kolli 2019;Zhou 2014), BPO/adapalene versus adapalene (Kolli 2019), BPO/clindamycin versus placebo (Seidler 2010), BPO/clindamycin versus adapalene (Kolli 2019), BPO plus salicylic acid versus placebo (Seidler 2010), BPO plus salicylic acid versus clindamycin (Seidler 2010), and BPO 10% versus 5% versus 2.5% (Fakhouri 2009). The main difference between these reviews and ours was the choice of primary efficacy outcome: those reviews assessed changes in acne lesions or used IGA as the primary outcome, but our review focused primarily on participant self‐assessment.
In the systematic review of randomised placebo‐controlled trials that aimed to assess the impact of study design and implementation on the efficacy of BPO, when compared with placebo, for treating acne (Lamel 2015), the percentage reductions in total, inflamed, and non‐inflamed lesions were inappropriately pooled for the active BPO monotherapy and placebo groups separately. The average percentage reduction in total, inflamed, and non‐inflamed lesions was 44.3 (standard deviation (SD), 9.2) versus 27.8 (SD, 21.0), 52.1 (SD, 10.4) versus 34.7 (SD, 22.7), and 41.5 (SD, 9.4) versus 27.0 (SD, 20.9) for BPO monotherapy and placebo groups, respectively. These results favouring BPO were consistent with our long‐term results. However,Lamel 2015 did not estimate the mean difference in percentage reduction in lesions but pooled the data for each arm separately, with no consideration of the difference in treatment duration between studies. Risk of bias for each included trial was not assessed.
For the comparison between BPO/adapalene and placebo, one review identified only one eligible trial supporting the use of BPO/adapalene maintenance treatment for reducing inflamed and non‐inflamed lesions (Dressler 2016). Participants on 24‐week treatment with BPO/adapalene were more likely to achieve 'clear' or 'almost clear' on the IGA scale (45.7% versus 25.6%), which was in line with our results. One meta‐analysis pooled individual participant data from three 12‐week trials, all of which were included in our review (Gold 2016a). Results on achieving 'clear' or 'almost clear' on the IGA scale were similar to ours: review authors conducted analyses for adult females and teenage females separately and concluded that once‐daily fixed‐dose BPO/adapalene was an efficacious and well‐tolerated anti‐acne treatment for both. Another systematic review including six trials supported the benefits of BPO/adapalene in terms of achieving 'clear' or 'almost clear' on the IGA and participant self‐reported improvement. These review authors also expressed some concerns about withdrawal due to BPO/adapalene‐related adverse effects (Zhou 2014). Similar results were shown in our review for the IGA outcome, but for participant‐reported improvement, we found no significant differences after long‐term treatment.
A meta‐analysis involving 23 trials tried to compare five topical treatments (Seidler 2010), including 5% BPO, clindamycin, BPO (5%)/clindamycin, BPO (5%) plus salicylic acid, and placebo. Absolute and percentage reductions in inflamed and non‐inflamed lesions were the main outcomes assessed in the review. BPO monotherapy, BPO/clindamycin, and BPO plus salicylic acid were all superior to placebo for any outcome regardless of lesion type and treatment duration. Our review found similar results for long‐term assessment of BPO monotherapy and BPO/clindamycin but did not include any studies assessing BPO plus salicylic acid. Both BPO/clindamycin and BPO plus salicylic acid seemed superior to clindamycin monotherapy for all outcomes except the absolute reduction in inflamed lesions at 10 to 12 weeks. However, these results are questionable because they were obtained from naive comparisons based on overlaps in 95% CIs estimated from the data syntheses for each arm separately. In addition, information regarding assessment of risk of bias was lacking. Our review did not include any studies assessing these comparisons.
A systematic review comparing BPO concentrations suggested that 10%, 5%, and 2.5% were equally effective in reducing inflammatory acne, but a higher concentration seemed to increase the risk of adverse effects (Fakhouri 2009). However, these results were not convincing due to the poor quality of the review: unclear inclusion criteria for studies, no assessment of risk of bias, and no attempt to combine studies (Smith 2010).
A systematic review focusing on topical retinoids in acne vulgaris included some studies involving BPO treatment (Kolli 2019), all of which were covered in our review. That review summarised individual studies on acne lesion reduction and Investigator Global Assessment success rate. Its findings were similar to ours for these comparisons: BPO versus adapalene, BPO/adapalene versus placebo, BPO/adapalene versus adapalene, and BPO/clindamycin versus adapalene.
Authors' conclusions
Implications for practice.
Our review's primary efficacy evidence is based on participant self‐assessment. Low‐certainty evidence suggests that BPO (as monotherapy or as add‐on treatment) may lead to better participant self‐reported acne improvement when compared to no treatment or placebo, and low‐certainty evidence suggests there may be little to no difference between BPO compared to clindamycin or adapalene for this outcome. This indicates that BPO could potentially be used as a replacement for clindamycin in combination treatments to reduce the risk of antibiotic resistance. Our primary efficacy outcome was not assessed by studies comparing BPO with erythromycin or salicylic acid.
Regarding safety, low‐certainty evidence suggests that compared with placebo or no treatment, BPO (as monotherapy or as add‐on treatment) may be associated with higher risk of discontinuation of treatment due to adverse events, which may negatively influence treatment adherence. However, these events may be related to tolerability, mostly cutaneous irritation, such as erythema, pruritus, and skin burning.
As we found only very low‐certainty evidence for withdrawal due to adverse effects for the comparisons BPO versus adapalene, clindamycin, erythromycin, or salicylic acid, we cannot draw conclusions regarding these treatment comparisons for that particular outcome.
More broadly, BPO may increase the risk of adverse events when compared against clindamycin, based on moderate‐certainty evidence; although the 95% confidence interval indicates that BPO might make little to no difference. Adverse events tended to be mild to moderate and well tolerated; the most common were local dryness, irritation, dermatitis, erythema, application site pain, and pruritus.
Very low‐certainty evidence regarding the risk of adverse events for BPO compared against adapalene, clindamycin, erythromycin, or salicylic acid means we cannot draw conclusions regarding these treatment comparisons for that particular outcome.
The 43 studies inStudies awaiting classification may alter the conclusions of the review if assessed.
Implications for research.
This systematic review highlights the need for large‐scale well‐conducted RCTs to assess the benefits and harms of BPO for treating acne, with focus on the comparative effects of different preparations or concentrations and combination versus monotherapy.
Design
No RCTs included in our review were regarded as being at low risk of bias in all assessment domains. To improve the quality of clinical trials in this field,FDA 2005 has presented guidelines for assessing drugs for treating acne vulgaris. However, our review suggests that further improvement of study quality is needed. Future trials need to ensure that allocation concealment and blinding are properly conducted.
Outcomes
Our review suggests three limitations in outcome assessment. First, it was uncommon to assess patient‐reported efficacy outcomes in the included trials, which could be helpful in informing both participants and clinicians (FDA 2005). Only 31% of trials reported patient self‐assessed acne improvement. These outcomes should be consistently included in future acne trials. Second, standardisation of outcome measurements needs to be improved for acne trials. Likert‐like scales used for patient self‐assessed acne improvement, for example, varied in different studies, which challenges synthesis of data for this outcome. Although the importance of standardisation of outcome measurements for acne trials has been acknowledged (Barratt 2009), substantial improvement in standardisation is still needed to facilitate comparisons between studies and to promote evidence synthesis. The work on standardisation of outcome measurement may significantly benefit from ongoing collaborative initiatives, including the Acne Core Outcomes Research Network (ACORN) (ACORN), the Core Outcome Measures in Effectiveness Trials (COMET) (COMET), and the Cochrane Skin Group Outcomes Research Initiative (Schmitt 2016). Finally, long‐term outcome assessment (at least six months) was rare, with only four included trials following participants for at least 24 weeks (Dreno 2016;Dréno 2018;Iftikhar 2009;Kawashima 2017a;Korkut 2005). Future trials need to strengthen the long‐term evidence base.
Interventions
Although BPO as monotherapy or used in combination with topical retinoid or antibiotics has been consistently recommended for first‐line treatment of acne by recent clinical guidelines (Goh 2015;Le Cleach 2017;Zaenglein 2016), available evidence supporting this recommendation is not of high quality in terms of participant self‐evaluation, as suggested in our review. BPO is available in various concentrations and vehicles; however, insufficient evidence suggests the comparative efficacy of its different formulations. The quality of evidence regarding safety (most adverse effects were cited as cutaneous intolerability) is mostly low or even very low. These findings in our review highlight the need for high‐quality evidence for comparisons between BPO monotherapy and other active topical treatments, between BPO combination and monotherapy, and between different formulations.
Reporting issues
Future trials need to enhance reporting quality by following the CONSORT statement (Schulz 2010). Incomplete reporting, which impairs risk of bias assessment, is very common in acne trials (Ingram 2010). Lack of sufficient reported information leads to substantial uncertainty in the risk of bias for most included trials. Poor reporting also challenges evidence synthesis. For example, a majority of the trials assessed change in acne lesion counts but seldom reported essential statistics for data synthesis and results interpretation, such as standard deviation, 95% confidence interval, and P value for estimates of effect size. Although adverse events were observed in most trials, the number of participants having adverse events in each group was not generally reported. These problems should be properly tackled in future research.
Acknowledgements
Many thanks to Laura Prescott, Finola Delamere, and Hywel Williams for providing us with useful suggestions on the title registration and development of the protocol. Many thanks to Information Specialist, Liz Doney, for helping us revise and establish the search strategy. Many thanks to Assistant Managing Editor, Helen Scott, for helping us retrieve full‐text articles for some of the eligible trials, and to Systematic Review methodologist, Emma Axon, for providing guidance on methods and results presentation. Many thanks also to other members of Cochrane Skin and to all peer reviewers who contributed to our protocol and review.
The Cochrane Skin editorial base wishes to thank Sue Jessop, Cochrane Dermatology Editor for this review; Matthew Grainge, Statistical Editor; Laurence Le Cleach, Methods Editor, the clinical referees, Miriam Santer, Jeremy Hugh, and Jerry Tan; and Dolores Matthews, who copy‐edited the review.
Appendices
Appendix 1. Skin Group Specialised Register/CRS search strategy
acne and (peroxide or superoxide or benzoyl or dibenzoyl or panoxyl or benzoperoxide or diphenylglyoxal)
Appendix 2. CENTRAL (Cochrane Library) search strategy
#1 MeSH descriptor: [Acne Vulgaris] explode all trees #2 acne:ti,ab #3 #1 or #2 #4 MeSH descriptor: [Benzoyl Peroxide] explode all trees #5 benzoyl peroxide*:ti,ab #6 peroxide dibenzoyl:ti,ab #7 dibenzoyl peroxide:ti,ab #8 benzoyl superoxide:ti,ab #9 panoxyl:ti,ab #10 diphenylglyoxal superoxide:ti,ab #11 benzoperoxide:ti,ab #12 {or #4‐#11} #13 #3 and #12
Appendix 3. MEDLINE (Ovid) search strategy
1. exp Acne Vulgaris/ 2. acne.mp. 3. 1 or 2 4. exp Benzoyl Peroxide/ 5. benzoyl peroxide$.ti,ab. 6. peroxide dibenzoyl.ti,ab. 7. dibenzoyl peroxide.ti,ab. 8. benzoyl superoxide.ti,ab. 9. panoxyl.ti,ab. 10. diphenylglyoxal superoxide.ti,ab. 11. benzoperoxide.ti,ab. 12. or/4‐11 13. randomized controlled trial.pt. 14. controlled clinical trial.pt. 15. randomized.ab. 16. placebo.ab. 17. clinical trials as topic.sh. 18. randomly.ab. 19. trial.ti. 20. 13 or 14 or 15 or 16 or 17 or 18 or 19 21. exp animals/ not humans.sh. 22. 20 not 21 23. 3 and 12 and 22
[Lines 13‐22: Cochrane Highly Sensitive Search Strategy for identifying randomized trials in MEDLINE: sensitivity‐ and precision‐maximizing version (2008 revision); Ovid format, from section 3.6.1 in Lefebvre C, Glanville J, Briscoe S, Littlewood A, Marshall C, Metzendorf M‐I, Noel‐Storr A, Rader T, Shokraneh F, Thomas J, Wieland LS. Technical Supplement to Chapter 4: Searching for and selecting studies. In: Higgins JPT, Thomas J, Chandler J, Cumpston MS, Li T, Page MJ, Welch VA (eds). Cochrane Handbook for Systematic Reviews of Interventions Version 6. Cochrane, 2019. Available from:www.training.cochrane.org/handbook]
Appendix 4. Embase (Ovid) search strategy
1. exp acne vulgaris/ 2. acne.ti,ab. 3. 1 or 2 4. benzoyl peroxide/ 5. benzoyl peroxide$.ti,ab. 6. peroxide dibenzoyl.ti,ab. 7. dibenzoyl peroxide.ti,ab. 8. benzoyl superoxide.ti,ab. 9. panoxyl.ti,ab. 10. diphenylglyoxal superoxide.ti,ab. 11. benzoperoxide.ti,ab. 12. or/4‐11 13. crossover procedure.sh. 14. double‐blind procedure.sh. 15. single‐blind procedure.sh. 16. (crossover$ or cross over$).tw. 17. placebo$.tw. 18. (doubl$ adj blind$).tw. 19. allocat$.tw. 20. trial.ti. 21. randomized controlled trial.sh. 22. random$.tw. 23. or/13‐22 24. exp animal/ or exp invertebrate/ or animal experiment/ or animal model/ or animal tissue/ or animal cell/ or nonhuman/ 25. human/ or normal human/ 26. 24 and 25 27. 24 not 26 28. 23 not 27 29. 3 and 12 and 28
[Lines 13‐28: Based on terms suggested for identifying RCTs in Embase (section 3.6.2) in Lefebvre C, Glanville J, Briscoe S, Littlewood A, Marshall C, Metzendorf M‐I, Noel‐Storr A, Rader T, Shokraneh F, Thomas J, Wieland LS. Technical Supplement to Chapter 4: Searching for and selecting studies. In: Higgins JPT, Thomas J, Chandler J, Cumpston MS, Li T, Page MJ, Welch VA (eds). Cochrane Handbook for Systematic Reviews of Interventions Version 6. Cochrane, 2019. Available from:www.training.cochrane.org/handbook]
Appendix 5. LILACS search strategy
acne and (benzoyl or benzoilo)
We combined these terms with the LILACS controlled clinical trials topic‐specific query filter.
Appendix 6. Search strategies for trial registers
| Search strategy | Records retrieved |
| ClinicalTrials.gov (www.clinicaltrials.gov) | |
| acne [Condition or disease] and peroxide [Other terms] | 130 |
| ISRCTN registry (www.isrctn.com) | |
| acne peroxide | 2 |
| World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch/) | |
| acne and peroxide | 192 |
| Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) | |
| acne peroxide | 8 |
| EU Clinical Trials Register (www.clinicaltrialsregister.eu/) | |
| acne and peroxide | 37 |
Appendix 7. Characteristics of included studies table
| Methods | Study design: parallel/cross‐over design Duration of follow‐up: |
| Participants | Inclusion criteria: Exclusion criteria: Diagnostic criteria: Treatment before study: Sex: [male %] Age: [mean (SD)/range years, or as reported] Sites of acne: Duration of acne: [mean/range years (SD), or as reported] Severity of acne and corresponding criteria of judgement: |
| Interventions | Topical treatment: Combination: yes (specify)/no Regimen: wash‐off/leave‐on Concentration: Vehicle: gel/cream/lotion/other (specify) Dose: Duration: Co‐interventions: |
| Control | Topical treatment: no treatment/placebo/active treatments (specify) Regimen: wash‐off/leave‐on Concentration: Vehicle: gel/cream/lotion/other (specify) Dose: Duration: Co‐interventions: |
| Outcomes | Definition: Time point of measurement: Number of event (percentage) in each group: Effect size: |
| Study details | Study period: Country: Setting: Number of study centres: Study terminated before regular end (for benefit/because of adverse events): yes/no |
| Publication details | Language of publication: Funding: commercial/non‐commercial/other funding Publication status: full article/journal supplement/conference paper/other (specify) |
| Stated aim for study | Quote from publication: "..." |
| Notes | Abbreviations: |
Risk of bias table
| Bias | Criteria for judgement | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk: any one of the following random sequence generations: a random numbers table, a computer random number generator, coin tossing, shuffling cards or envelopes, throwing dice, drawing lots, or minimisation High risk: any one of non‐random sequence generations (other methods except those suggested as low risk) Unclear risk: insufficient information to permit judgement of 'low risk' or 'high risk' | Quote from publication: "..."
Comment: ... | |
| Allocation concealment (selection bias) | Low risk: allocation based on any one of the following methods: central allocation, sequentially numbered drug containers of identical appearance, sequentially numbered, opaque, sealed envelopes High risk: allocation based on any other methods (other methods except those suggested as low risk) Unclear risk: insufficient information to permit judgement of 'low risk' or 'high risk' | Quote from publication: "..."
Comment: ... | |
| Blinding of participants and personnel (performance bias) | Low risk: blinding of participants and key study personnel, and unlikely that the blinding could be broken High risk: no blinding or incomplete blinding, or blinding of participants and key study personnel could be broken (comparator preparations were different, e.g. gel versus cream, or specific adverse events were more common in one treatment but not the other, e.g. erythema, dryness, and peeling in BPO but not in placebo) Unclear risk: insufficient information to permit judgement of 'low risk' or 'high risk' | Quote from publication: "..."
Comment: ... | |
| Blinding of outcome assessment (detection bias) | Low risk: blinding of outcome assessment and unlikely that blinding could be broken High risk: no blinding or incomplete blinding, or blinding of outcome assessment could be broken (specific adverse events were more common in one treatment but not the other, e.g. erythema, dryness, and peeling in BPO but not in placebo) Unclear risk: insufficient information to permit judgement of 'low risk' or 'high risk' | Quote from publication: "..."
Comment: ... | |
| Incomplete outcome data (attrition bias) | Low risk: any one of the following situations: no missing outcome data, missing outcome data (proportion of loss of follow‐up ≤ 10%) balanced in numbers across intervention groups with similar reasons, or missing data have been imputed using data complement High risk: any other situation except those suggested above Unclear risk: insufficient information to permit judgement of 'low risk' or 'high risk' | Quote from publication: "..."
Comment: ... | |
| Selective reporting (reporting bias) | Low risk: the study protocol is available and all of the study's pre‐specified (primary and secondary) outcomes that are of interest in the protocol have been reported in the pre‐specified way High risk: any other situation except those suggested above Unclear risk: insufficient information to permit judgement of 'low risk' or 'high risk' | Quote from publication: "..." Comment: ... | |
| Other sources of bias | We assessed the following potential sources: (1) the baseline characteristics (e.g. age, gender, duration, location, severity, previous treatment) imbalance between groups; (2) blocked randomisation (if used) in an unblinded trial; (3) no washout period before the start of a trial. Low risk: no statistical significance (P ≥ 0.05) of baseline imbalance for each characteristic, blocked randomisation (if used) in a strictly blinded trial, and at least 4‐week washout period for systemic acne treatments and at least 2 week for topical acne treatment High risk: statistical significance (P < 0.05) of baseline imbalance for each characteristic, blocked randomisation (if used) in an unblinded trial (or blinding is difficult), and less than 4‐week washout period for systemic acne treatments or less than at least 2 weeks for topical acne treatment Unclear risk: insufficient information to permit judgement of 'low risk' or 'high risk' for any sources above | Quote from publication: "..." Comment: ... |
Appendix 8. Survey of authors providing information on trials
| Study ID | Study author contacted | Study author replied | Study author asked for additional information | Study author provided data |
| To request clarification on the primary outcomes | ||||
| Cunliffe 2002 | Sharon Levy | No reply | Percentage or number of participants classified into each category on the Likert‐like scale for the primary outcome | N/A |
| Eichenfield 2013 | Lawrence Eichenfield | No reply | Percentage or number of participants classified into each category on the Likert‐like scale for the primary outcome | N/A |
| Gollnick 2009 | Harald Gollnick | Harald Gollnick | Percentage or number of participants classified into each category on the Likert‐like scale for the primary outcome | No (data had been archived) |
| Pariser 2014 | David Pariser | No reply | Percentage or number of participants classified into each category on the Likert‐like scale for the primary outcome | N/A |
| Thiboutot 2007 | Diane Thiboutot | No reply | Percentage or number of participants classified into each category on the Likert‐like scale for the primary outcome | N/A |
| Thiboutot 2008 | Diane Thiboutot | No reply | Percentage or number of participants classified into each category on the Likert‐like scale for the primary outcome | N/A |
| Tschen 2001 | Eduardo Tschen | No reply | Percentage or number of participants classified into each category on the Likert‐like scale for the primary outcome | N/A |
| To request unpublished data or full‐text reports | ||||
| Borglund 1991 | Agneta Andersson (Editorial Manager of Acta Derm Venereol) | Anna‐Maria Andersson (Editorial Assistant of Acta Derm Venereol) | Full‐text publication | Yes (a full‐text article was provided) |
| Boutli 2003 | Ioannides D | No reply | Full‐text publication | N/A |
| Cassano 2002 | Giuseppe Alessandrini, and Dario Fai | No reply | Full‐text publication | N/A |
| Ede 1973 | Editorial Office of Curr Ther Res Clin Exp | No reply | Full‐text publication | N/A |
| Miyachi 2016 | Yoshiki Miyachi | Yoshiki Miyachi | Full‐text publication | Yes (a full‐text article was provided) |
| Prince 1982 | Allegra Sparta (Assistant Managing Editor of Cutis) | No reply | Full‐text publication | N/A |
| Schmidt 1988 | Editorial Office of Zeitschrift fur Hautkrankheiten | No reply | Full‐text publication | N/A |
| Shahid 1996 | Publication Office of Biomedica | No reply | Full‐text publication | N/A |
| Shalita 1989 | Judy Pachella (Managing Editor of Clinical Therapeutics) | Judy Pachella | Full‐text publication | No (no access to online archive beyond 1996 or to archival hard copy journals) |
| NCT00713609,NCT02058628,NCT01445301,NCT02557399, 2004‐002272‐41, 2008‐002359‐26 | GSK (Sponsor) | GSK | Unpublished data and full‐text article | Yes (GSK provided a link to the trials) |
| NCT00787943 | Amy Paller | Amy Paller | Unpublished data and full‐text article | No (was unable to provide data) |
| NCT01044264,NCT01138514,NCT01796665,NCT02515305,NCT02525549,NCT03393494 | Perrigo (Sponsor) | No reply | Unpublished data and full‐text article | N/A |
| NCT01231334,NCT01788384 | Allergan (Sponsor) | No reply | Unpublished data and full‐text article | N/A |
| NCT01522456,NCT02073448NCT02073461,NCT01106807, 2006‐004278‐28, 2008‐006792‐68, 2016‐000063‐16 | Galderma (Sponsor) | No reply | Unpublished data and full‐text article | N/A |
| NCT02465632 | Glenmark (Sponsor) | No reply | Unpublished data and full‐text article | N/A |
| NCT00624676 | Robert Bissonnette | Sophie Seite | Unpublished data and full‐text article | Yes (a full‐text article was provided) |
| NCT00663286 | Dow Pharmaceutical Sciences (Sponsor) | No reply | Unpublished data and full‐text article | N/A |
| NCT01237821 | Christian Oresajo | No reply | Unpublished data and full‐text article | N/A |
| NCT01501799,NCT02616614,NCT02651220 | Actavis Mid‐Atlantic (Sponsor) | No reply | Unpublished data and full‐text article | N/A |
| NCT01742637 | Catawba Research (Sponsor) | No reply | Unpublished data and full‐text article | N/A |
| NCT01769235 | Symbio CRO (Sponsor) | No reply | Unpublished data and full‐text article | N/A |
| NCT01769664,NCT02578043,NCT02595034,NCT02709902 | Taro Pharmaceuticals USA (Sponsor) | No reply | Unpublished data and full‐text article | N/A |
| Ahmadi 2014 | Dr. Ahmadi | No reply | Unpublished data and full‐text article | N/A |
| Cunliffe 1978 , Cunliffe 1980 | Dr. Cunliffe | No reply | Unpublished data and full‐text article | N/A |
| Ellis 2001 | Dr. Ellis | No reply | Unpublished data and full‐text article | N/A |
| Peereboom‐Wynia 1984 | Dr. Bernsen | No reply | Unpublished data and full‐text article | N/A |
| To confirm duplicates | ||||
| Dubey 2016 | Anuradha Dubey | No reply | Confirmation that a published article and a trial registration related to the same study | N/A |
| Footnotes N/A: not applicable | ||||
Appendix 9. Summary of results for participant's global self‐assessment of improvement
| Comparison | Treatment duration | Evidence synthesis | Study ID | Outcome definition | RR (95% CI) | Other resultsa |
| Main comparisons | ||||||
| 1. BPO versus placebo or no treatment | Long‐term | Main pooled analysis | Gold 2009;Jawade 2016;Leyden 2001a | As defined in this review | 1.27 (1.12 to 1.45) | |
| Sensitivity analysis | Borglund 1991;Draelos 2002;Gold 2009;Gollnick 2009;Jawade 2016;Leyden 2001a;Thiboutot 2007;Thiboutot 2008;Tschen 2001;Tucker 1984;Zeichner 2013 | Based on various definitions originally reported in the studies | 1.32 (1.20 to 1.45 | |||
| Individual study not included in the main analysis | Borglund 1991 | "good to excellent" | 1.13 (0.70 to 1.80) | |||
| Draelos 2002 | "highly favourable or favourable" on a 5‐point Likert‐like scale | 1.26 (1.10 to 1.45) | ||||
| Gollnick 2009 | "complete or marked improvement" on a 6‐point Likert‐like scale | 1.16 (1.01 to 1.34) | ||||
| Shalita 2003 | Unclear | Unclear | It was reported that participants in both groups rated their improvement as mild | |||
| Thiboutot 2007 | "complete or marked improvement" on a 6‐point Likert‐like scale | 1.53 (0.87 to 2.69) | ||||
| Thiboutot 2008 | "clear or almost clear" on a 6‐point Likert‐like scale | 1.58 (1.35 to 1.86) | ||||
| Tschen 2001 | "much better" on a 7‐point scale | 2.58 (1.42 to 4.68) | ||||
| Tucker 1984 | Unclear | 1.03 (0.90 to 1.17) | ||||
| Zeichner 2013 | "0 or 1" on a 6‐point scale | 2.50 (0.55 to 11.41) | ||||
| Medium‐term | Main pooled analysis | Ozgen 2013;Papageorgiou 2000 | As defined in this review | 2.70 (1.68 to 4.34 | ||
| Varied | Individual study not included in the main analysis | Vasarinsh 1969 | Summary score on a 4‐point Likert‐like scale (the higher the better) | Unclear | 0.66 and 0.53 for the BPO and placebo groups, respectively; 1.15 and 0.75 for BPO/sulphur and sulphur groups, respectively | |
| 2. BPO versus adapalene | Long‐term | Main pooled analysis | Babaeinejad 2013;do Nascimento 2003;Gold 2009;Hayashi 2018;Jawade 2016 | As defined in this review | 0.99 (0.90 to 1.10) | |
| Sensitivity analysis | Babaeinejad 2013;do Nascimento 2003;Gold 2009;Gollnick 2009;Hayashi 2018;Jawade 2016;Thiboutot 2007 | Based on various definitions originally reported in the studies | 0.99 (0.90 to 1.08) | |||
| Individual study not included in the main analysis | Gollnick 2009 | "complete or marked improvement" on a 6‐point Likert‐like scale | 0.89 (0.59 to 1.34) | |||
| Miyachi 2016 | Summary score on a 100‐mm visual analog scale (the higher the better) | Unclear | 79.6 ± 22.0 mm for BPO and 74.4 ± 19.7 mm for adapalene, in favour of BPO | |||
| Thiboutot 2007 | "complete or marked improvement" on a 6‐point Likert‐like scale | 0.88 (0.63 to 1.22) | ||||
| 3. BPO versus clindamycin | Long‐term | Main pooled analysis | Leyden 2001a | As defined in this review | 0.95 (0.68 to 1.34) | |
| Sensitivity analysis | Draelos 2002;Leyden 2001a;Thiboutot 2008;Tschen 2001 | Based on various definitions originally reported in the study | 1.05 (0.97 to 1.15) | |||
| Individual study not included in the main analysis | Draelos 2002 | "highly favourable or favourable" on a 5‐point Likert‐like scale | 1.08 (0.97 to 1.21) | |||
| Thiboutot 2008 | "clear or almost clear" on a 7‐point Likert‐like scale | 1.00 (0.86 to 1.16) | ||||
| Tschen 2001 | "much better" on a 7‐point Likert‐like scale | 1.77 (0.82 to 3.81) | ||||
| 4. BPO versus erythromycin (outcome not reported) | ||||||
| 5. BPO versus salicylic acid | Long‐term | Individual study not included in the main analysis | Bissonnette 2009 | Unclear | Unclear | No significant difference was found (P = 0.81) |
| Chantalat 2006 | Unclear | Unclear | In favour of salicylic acid in terms of improvements in tone and texture | |||
| Other comparisons | ||||||
| 1. BPO versus tretinoin | Individual study not included in the main analysis | Gupta 2003 | Summary score on a 7‐point scale (the higher the better) | Unclear | It was reported that scores rated in the BPO/erythromycin group were significantly lower than those in the tretinoin/erythromycin group, in favour of the latter as early as week 2 | |
| 2. BPO versus isotretinoin | Long‐term | Individual study not included in the main analysis | Marazzi 2002 | "improved" on a 3‐point Likert‐like scale | Unclear | It was reported that there was no significant difference in the proportion of participants rated as "improved" between the 2 groups (P = 0.26) |
| 3. BPO versus azelaic acid (outcome not reported) | ||||||
| 4. BPO versus retinoic acid (outcome not reported) | ||||||
| 5. BPO versus sulphur | Varied | Individual study not included in the main analysis | Vasarinsh 1969 | Summary score on a 4‐point Likert‐like scale (the higher the better) | Unclear | 0.66 and 0.75 for the BPO and sulphur groups, respectively |
| 6. BPO versus hydrogen peroxide | Medium‐term | Individual study not included in the main analysis | Tung 2014 | Unclear | Unclear | It was reported that both treatments were effective but no statistical difference across arms was found (P = 0.70) |
| 7. BPO versus superoxidised solution (outcome not reported) | ||||||
| 8. BPO versusCasuarina equisetifolia bark extract (outcome not reported) | ||||||
| 9. BPO versus Chinese medical mask (outcome not reported) | ||||||
| 10. BPO versus meclocycline sulfosalicylate (outcome not reported) | ||||||
| 11. BPO versus isolutrol (outcome not reported) | ||||||
| 12. BPO versus tea tree oil (outcome not reported) | ||||||
| 13. BPO versus Unani preparation (Zimade Muhasa) (outcome not reported) | ||||||
| 14. BPO versus glycerin (outcome not reported) | ||||||
| 15. BPO versus chloroxylenol/salicylic acid (outcome not reported) | ||||||
| 16. BPO versus chloroxylenol/zinc oxide | Medium‐term | Main pooled analysis | Papageorgiou 2000 | As defined in this review | 0.89 (0.51 to 1.56) | |
| 17. BPO/adapalene versus placebo or no treatment | Long‐term | Main pooled analysis | Dreno 2011;Gold 2009;Gold 2016 | As defined in this review | 1.16 (0.97 to 1.38) | |
| Sensitivity analysis | Dreno 2011;Eichenfield 2013;Gold 2009;Gold 2010;Gold 2016;Gollnick 2009;Thiboutot 2007 | Based on various definitions originally reported in the studies | 1.55 (1.25 to 1.91) | |||
| Individual study not included in the main analysis | Eichenfield 2013 | "complete or marked improvement" on a 6‐point Likert‐like scale | 2.93 (2.14 to 4.01) | |||
| Gold 2010 | "very satisfied or satisfied" (scale not reported) | 1.52 (1.31 to 1.76) | ||||
| Gollnick 2009 | "complete or marked improvement" on a 6‐point Likert‐like scale | 1.75 (1.46 to 2.09) | ||||
| Thiboutot 2007 | "complete or marked improvement" on a 6‐point Likert‐like scale | 3.00 (1.64 to 5.49) | ||||
| 18. BPO/adapalene versus tretinoin (outcome not reported) | ||||||
| 19. BPO/adapalene versus salicylic acid | Short‐term | Individual study not included in the main analysis | Zheng 2019 | "better" on a 3‐point scale | Unclear | It was reported that the proportion of participants rating BPO plus adapalene as better, similar to, or worse than salicylic acid was 25.8%, 41.9%, and 32.2%, respectively |
| 20. BPO/adapalene versus clindamycin/tretinoin (outcome not reported) | ||||||
| 21. BPO/clindamycin versus placebo or no treatment | Long‐term | Main pooled analysis | Leyden 2001a | As defined in this review | 2.95 (1.96 to 4.46) | |
| Sensitivity analysis | Leyden 2001a;Pariser 2014;Tanghetti 2006;Thiboutot 2008;Tschen 2001 | Based on various definitions originally reported in the studies | 2.10 (1.25 to 3.52) | |||
| Individual study not included in the main analysis | Pariser 2014 | "clear" or "almost clear" on a 7‐point Likert‐like scale | 1.98 (1.44 to 2.73) | |||
| Tanghetti 2006 | "highly favourable" or "favourable" on a 4‐point Likert‐like scale | 1.04 (0.93 to 1.15) | ||||
| Thiboutot 2008 | "clear" or "almost clear" on a 7‐point Likert‐like scale | 2.34 (1.85 to 2.97) | ||||
| Tschen 2001 | "much better" on a 7‐point Likert‐like scale | 4.04 (1.52 to 10.77) | ||||
| 22. BPO/clindamycin versus adapalene | Long‐term | Main pooled analysis | Guerra‐Tapia 2012 | As defined in this review | 1.12 (0.96 to 1.31) | |
| Individual study not included in the main analysis | Langner 2008 | "improved" on a 3‐point Likert‐like scale | Unclear | It was reported that improvement was greater in treatment with BPO/clindamycin at weeks 1, 2, 4, and 8, but no significant difference was found at week 12 | ||
| 23. BPO/clindamycin versus azelaic acid | Long‐term | Main pooled analysis | Schaller 2016 | As defined in this review | 1.38 (1.05 to 1.81) | |
| Long‐term | Main pooled analysis | Schaller 2016 | As defined in this review | 1.44 (1.09 to 1.89) | ||
| Long‐term | Main pooled analysis | Schaller 2016 | As defined in this review | 1.37 (1.00 to 1.88) | ||
| 24. BPO/clindamycin versus erythromycin/zinc | Long‐term | Individual study not included in the main analysis | Langner 2007 | "improved" on a 3‐point Likert‐like scale | 1.03 (0.93 to 1.14) | |
| 25. BPO/clindamycin versus dapsone (outcome not reported) | ||||||
| 26. BPO/erythromycin versus placebo or no treatment | Medium‐term | Main pooled analysis | Jones 2002 | As defined in this review | 1.28 (1.04 to 1.57 | |
| Individual study not included in the main analysis | Thiboutot 2002 | Summary score on a 4‐point Patient's Global Improvement scale (the higher the better) | Unclear | It was reported that participants receiving BPO/erythromycin had significantly greater (P < 0.001) scores than participants receiving placebo at the end of treatment | ||
| Long‐term | Individual study not included in the main analysis | Draelos 2002 | "highly favourable" or "favourable" on a 5‐point Likert‐like scale | 1.17 (1.01 to 1.36) | ||
| 27. BPO/erythromycin versus clindamycin | Long‐term | Individual study not included in the main analysis | Draelos 2002 | "highly favourable" or "favourable" on a 5‐point Likert‐like scale | 1.01 (0.89 to 1.14) | |
| 28. BPO/erythromycin versus azelaic acid (outcome not reported) | ||||||
| 29. BPO/erythromycin versus metronidazole (outcome not reported) | ||||||
| 30. BPO/erythromycin versus viaminate (outcome not reported) | ||||||
| 31. BPO/erythromycin versus zinc/erythromycin | Long‐term | Individual study not included in the main analysis | Chu 1997 | On a 6‐point Likert‐like scale | Unclear | It was reported that participant self assessment was strongly in favour of BPO/erythromycin (P < 0.001). |
| 32. BPO/sulphur versus placebo | Varied | Individual study not included in the main analysis | Vasarinsh 1969 | Summary score on a 4‐point Likert‐like scale (the higher the better) | Unclear | It was reported that the average score was 1.15 and 0.53 for the BPO/sulphur and placebo groups, respectively |
| 33. BPO/glycolic acid/zinc lactate versus placebo (outcome not reported) | ||||||
| 34. BPO/potassium hydroxyquinoline sulphate versus placebo (outcome not reported) | ||||||
| 35. BPO (10%) versus BPO (5%) (outcome not reported) | ||||||
| 36. BPO (10%) versus BPO (2.5%) (outcome not reported) | ||||||
| 37. BPO (5%) versus BPO (2.5%) | Long‐term | Individual study not included in the main analysis | Dhawan 2013 | "very satisfied" or "satisfied" on a 5‐point Likert‐like scale | 1.06 (0.84 to 1.34) | |
| 38. BPO gel (6%) versus BPO cream (5.5%) | Long‐term | Individual study not included in the main analysis | Smith 2006 | "marked improvement" or "better" on a 5‐point Likert‐like scale | 1.13 (0.52 to 2.42) | |
| 39. BPO (vehicle with 8% urea) versus BPO (vehicle with no urea) (outcome not reported) | ||||||
| 40. BPO (vehicle with acetone) versus BPO (vehicle with alcohol/detergent) (outcome not reported) | ||||||
| 41. BPO (formulation 1) versus BPO (formulation 2) (outcome not reported) | ||||||
| 42. Water‐based BPO versus alcohol‐based BPO (outcome not reported) | ||||||
Abbreviation: BPO: benzoyl peroxide; RR: risk ratio
a If 95%CI was not reported and cannot be calculated, other results (depending on availability) were summarised, which may include effect size, P value, effect direction or other description.
Appendix 10. Summary of results for withdrawal due to adverse effects
| Comparison | Treatment duration | Evidence synthesis | Study ID | RR (95%CI) | Other resultsa | Adverse events leading to withdrawal |
| Main comparisons | ||||||
| 1. BPO versus placebo or no treatment | Long‐term | Main pooled analysis | Chalker 1983;Cunliffe 2002;Draelos 2002;Eichenfield 2011;Fleischer 2010;Gold 2009;Gollnick 2009;Hughes 1992;Jaffe 1989;Jawade 2016;Kawashima 2014;Kawashima 2015;Kawashima 2017b;Korkut 2005;Leyden 2001a;Lookingbill 1997;Miyachi 2016;NCT00713609;Study 156;Thiboutot 2007;Thiboutot 2008;Tirado‐Sanchez 2009;Tschen 2001;Xu 2016 | 2.13 (1.55 to 2.93) | erythema, pruritus, and skin burning | |
| Individual study not included in the main analysis | Borglund 1991 | No participants discontinued treatment due to adverse events | ||||
| Medium‐term | Main pooled analysis | Burke 1983;Mills 1986;Ozgen 2013 | 2.92 (0.31 to 27.44) | dermatitis and severe burning sensation | ||
| Individual study not included in the main analysis | Papageorgiou 2000 | It was reported that 2 participants discontinued treatment but it was unclear what treatment they had received | flare‐up | |||
| Short‐term | Individual study not included in the main analysis | Draelos 2010 | No participants withdrew due to adverse effects | |||
| 2. BPO versus adapalene | Long‐term | Main pooled analysis | Babaeinejad 2013;do Nascimento 2003;Fleischer 2010;Gold 2009;Gollnick 2009;Hayashi 2018;Iftikhar 2009;Jawade 2016;Korkut 2005;Miyachi 2016;Thiboutot 2007 | 1.85 (0.94 to 3.64) | ||
| Medium‐term | Individual study not included in the main analysis | Stinco 2007 | No participants discontinued treatments | |||
| 3. BPO versus clindamycin | Long‐term | Main pooled analysis | Draelos 2002;Eichenfield 2011;Leyden 2001a;Lookingbill 1997;Study 156;Swinyer 1988;Thiboutot 2008;Tschen 2001 | 1.93 (0.90 to 4.11) | local hypersensitivity, pruritus, erythema, face edema, rash, and skin burning. | |
| 4. BPO versus erythromycin | Long‐term | Individual study not included in the main analysis | Chalker 1983 | No participants withdrew due to adverse events | ||
| Medium‐term | Main pooled analysis | Burke 1983 | 1.00 (0.07 to 15.26) | dermatitis | ||
| 5. BPO versus salicylic acid | Long‐term | Individual study not included in the main analysis | Bissonnette 2009 | No participants terminated treatment due to adverse events | ||
| Other comparisons | ||||||
| 1. BPO versus tretinoin | Long‐term | Main pooled analysis | Bowman 2005;Gupta 2003;Jackson 2010 | 1.11 (0.07 to 17.36) | severe burning or stinging | |
| 2. BPO versus isotretinoin | Long‐term | Main pooled analysis | Hughes 1992;Marazzi 2002 | 1.23 (0.53 to 2.87) | skin reactions and infection | |
| Short‐term | Individual study not included in the main analysis | Cunliffe 2001 | No participants withdrew due to adverse events | |||
| 3. BPO versus azelaic acid | Medium‐term | Individual study not included in the main analysis | Stinco 2007 | There was no withdrawal due to adverse events | ||
| 4. BPO versus retinoic acid (outcome not reported) | ||||||
| 5. BPO versus sulphur (outcome not reported) | ||||||
| 6. BPO versus hydrogen peroxide (outcome not reported) | ||||||
| 7. BPO versus superoxidized solution | Long‐term | Individual study not included in the main analysis | Tirado‐Sanchez 2009 | There was no withdrawal due to adverse events | ||
| 8. BPO versus Casuarina equisetifolia bark extract (outcome not reported) | ||||||
| 9. BPO versus Chinese medical mask (outcome not reported) | ||||||
| 10. BPO versus meclocycline sulfosalicylate (outcome not reported) | ||||||
| 11. BPO versus isolutrol (outcome not reported) | ||||||
| 12. BPO versus tea tree oil (outcome not reported) | ||||||
| 13. BPO versus Unani preparation (Zimade Muhasa) | Medium‐term | Individual study not included in the main analysis | Tabasum 2014 | There was no withdrawal due to adverse events | ||
| 14. BPO versus glycerin (outcome not reported) | ||||||
| 15. BPO versus chloroxylenol/salicylic acid (outcome not reported) | ||||||
| 16. BPO versus chloroxylenol/zinc oxide | Medium‐term | Individual study not included in the main analysis | Papageorgiou 2000 | It was reported that 2 participants discontinued treatment but it was unclear what treatment they received | flare‐up | |
| 17. BPO/adapalene versus placebo or no treatment | Long‐term | Main pooled analysis | Dreno 2011;Eichenfield 2013;Gold 2009;Gold 2010;Gold 2016;Gollnick 2009;Thiboutot 2007;Weiss 2015 | 2.28 (1.10 to 4.71) | erythema, irritation and atopic dermatitis flare | |
| Individual study not included in the main analysis | Dreno 2016 | One of 38 participants discontinued BPO/adapalene | moderate skin irritation | |||
| Individual study not included in the main analysis | Dréno 2018 | Two of 67 participants discontinued BPO/adapalene | moderate pain of skin and mild skin irritation | |||
| 18. BPO/adapalene versus tretinoin (outcome not reported) | ||||||
| 19. BPO/adapalene versus salicylic acid | Short‐term | Individual study not included in the main analysis | Zheng 2019 | Three of 34 participants discontinued BPO | irritant contact dermatitis | |
| 20. BPO/adapalene versus clindamycin/tretinoin (outcome not reported) | ||||||
| 21. BPO/clindamycin versus placebo or no treatment | Long‐term | Main pooled analysis | Bowman 2005;Eichenfield 2011;Leyden 2001a;Lookingbill 1997;Pariser 2014;Tanghetti 2006;Thiboutot 2008;Tschen 2001 | 1.07 (0.38 to 3.00) | erythema, face edema, rash, pruritus, and skin burning | |
| 22. BPO/clindamycin versus adapalene | Long‐term | Main pooled analysis | Dubey 2016;Guerra‐Tapia 2012;Langner 2008 | 0.41 (0.05 to 3.05) | erythema, burning and pruritus and dermatitis | |
| 23. BPO/clindamycin versus azelaic acid | Long‐term | Main pooled analysis | Schaller 2016 | 1.01 (0.06 to 15.93) | application site erythema, dryness, pruritus and pain | |
| 24. BPO/clindamycin versus erythromycin/zinc | Long‐term | Main pooled analysis | Langner 2007 | 1.03, (0.07 to 16.12) | rash and skin tightness | |
| 25. BPO/clindamycin versus dapsone (outcome not reported) | ||||||
| 26. BPO/erythromycin versus placebo or no treatment | Long‐term | Main pooled analysis | Draelos 2002 | 0.49 (0.18 to 1.39) | Unclear | |
| Individual study not included in the main analysis | Chalker 1983 | No participants discontinued treatment because of adverse effects | ||||
| Individual study not included in the main analysis | Sklar 1996 | No participants discontinued treatment because of adverse effects | ||||
| Medium‐term | Main pooled analysis | Chalker 1983;Sklar 1996 | 0.33 (0.01 to 8.02) | dryness and itching | ||
| 27. BPO/erythromycin versus clindamycin | Long‐term | Main pooled analysis | Draelos 2002;Packman 1996 | 1.51 (0.50 to 4.61) | Unclear | |
| 28. BPO/erythromycin versus azelaic acid (outcome not reported) | ||||||
| 29. BPO/erythromycin versus metronidazole (outcome not reported) | ||||||
| 30. BPO/erythromycin versus viaminate | Short‐term | Individual study not included in the main analysis | Zhao 2001 | No participants discontinued treatment due to adverse effects | ||
| 31. BPO/erythromycin versus zinc/erythromycin | Long‐term | Individual study not included in the main analysis | Chu 1997 | No participants on BPO/erythromycin and 3 participants on zinc/erythromycin discontinued treatment due to adverse events | Unclear | |
| 32. BPO/sulphur versus placebo (outcome not reported) | ||||||
| 33. BPO/glycolic acid/zinc lactate versus placebo | Long‐term | Individual study not included in the main analysis | Sklar 1996 | No participants discontinued treatment due to adverse effects | ||
| 34. BPO/potassium hydroxyquinoline sulphate versus placebo | Long‐term | Main pooled analysis | Jaffe 1989 | 7.81 (0.42 to 144.12) | stinging or skin irritation | |
| 35. BPO (10%) versus BPO (5%) | Medium‐term | Main pooled analysis | Ji 2000;Wang 2003 | 0.40 (0.06 to 2.52) | Unclear | |
| 36. BPO (10%) versus BPO (2.5%) | Medium‐term | Individual study not included in the main analysis | Mills 1986 | No participants discontinued treatment due to adverse effects | ||
| Individual study not included in the main analysis | Wang 2003 | No participants discontinued treatment due to adverse effects | ||||
| 37. BPO (5%) versus BPO (2.5%) | Long‐term | Main pooled analysis | Dhawan 2013;Kawashima 2017a;Kawashima 2017b | 1.28 (0.65 to 2.54) | erythema and irritation | |
| Medium‐term | Main pooled analysis | Mills 1986;Wang 2003 | 1.79 (0.09 to 33.82) | Unclear | ||
| Varied | Individual study not included in the main analysis | Yong 1979 | 11 participants did not complete the trial because of adverse events; however, it was unclear how many participants in each group withdrew | desquamation and erythema | ||
| 38. BPO gel (6%) versus BPO cream (5.5%) | Long‐term | Main pooled analysis | Smith 2006 | 3.00 (0.13 to 70.16) | irritation | |
| 39. BPO (vehicle with 8% urea) versus BPO (vehicle with no urea) (outcome not reported) | ||||||
| 40. BPO (vehicle with acetone) versus BPO (vehicle with alcohol/detergent) (outcome not reported) | ||||||
| 41. BPO (formulation 1) versus BPO (formulation 2) (outcome not reported) | ||||||
| 42. Water‐based BPO versus alcohol‐based BPO | Medium‐term | Individual study not included in the main analysis | Fyrand 1986 | Six participants discontinued treatment due to local side effects | severe dermatitis, erythema, itching, stinging, and scaling |
Abbreviation: BPO: benzoyl peroxide; RR: risk ratio
a If 95%CI was not reported and cannot be calculated, other results (depending on availability) were summarised, which may include effect size, P value, effect direction or other description.
Data and analyses
Comparison 1. BPO versus placebo or no treatment.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Participant's global self‐assessment of improvement (long‐term data) | 3 | 2234 | Risk Ratio (IV, Random, 95% CI) | 1.27 [1.12, 1.45] |
| 1.1 BPO monotherapy versus placebo or no treatment | 2 | 1073 | Risk Ratio (IV, Random, 95% CI) | 1.44 [0.94, 2.22] |
| 1.2 BPO/adapalene versus adapalene | 2 | 921 | Risk Ratio (IV, Random, 95% CI) | 1.19 [0.98, 1.45] |
| 1.3 BPO/clindamycin versus clindamycin | 1 | 240 | Risk Ratio (IV, Random, 95% CI) | 1.48 [1.11, 1.97] |
| 2 Participant's global self‐assessment of improvement (medium‐term data) | 2 | 121 | Risk Ratio (IV, Random, 95% CI) | 2.70 [1.68, 4.34] |
| 2.1 BPO monotherapy versus placebo or no treatment | 1 | 28 | Risk Ratio (IV, Random, 95% CI) | 2.31 [0.90, 5.92] |
| 2.2 BPO plus nadifloxacin versus placebo plus nadifloxacin | 1 | 93 | Risk Ratio (IV, Random, 95% CI) | 2.85 [1.64, 4.94] |
| 3 Withdrawal due to adverse effects (long‐term data) | 24 | 13744 | Risk Ratio (IV, Random, 95% CI) | 2.13 [1.55, 2.93] |
| 3.1 BPO monotherapy versus placebo or no treatment | 14 | 5493 | Risk Ratio (IV, Random, 95% CI) | 2.10 [1.22, 3.64] |
| 3.2 BPO/adapalene versus adapalene | 5 | 2368 | Risk Ratio (IV, Random, 95% CI) | 3.45 [1.47, 8.07] |
| 3.3 BPO/clindamycin versus clindamycin | 9 | 4918 | Risk Ratio (IV, Random, 95% CI) | 2.91 [1.68, 5.04] |
| 3.4 BPO/erythromycin versus erythromycin | 1 | 89 | Risk Ratio (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 3.5 BPO plus adapalene versus adapalene | 1 | 70 | Risk Ratio (IV, Random, 95% CI) | 5.0 [0.25, 100.53] |
| 3.6 BPO plus tazarotene versus tazarotene | 2 | 391 | Risk Ratio (IV, Random, 95% CI) | 0.61 [0.26, 1.43] |
| 3.7 BPO/clindamycin plus tazarotene versus clindamycin plus tazarotene | 1 | 214 | Risk Ratio (IV, Random, 95% CI) | 1.02 [0.15, 7.10] |
| 3.8 BPO plus dapsone versus placebo plus dapsone | 1 | 201 | Risk Ratio (IV, Random, 95% CI) | 9.45 [0.52, 173.34] |
| 4 Withdrawal due to adverse effects (medium‐term data) | 3 | 202 | Risk Ratio (IV, Random, 95% CI) | 2.92 [0.31, 27.44] |
| 4.1 BPO monotherapy versus placebo or no treatment | 2 | 109 | Risk Ratio (IV, Random, 95% CI) | 2.90 [0.12, 68.50] |
| 4.2 BPO plus nadifloxacin versus placebo plus nadifloxacin | 1 | 93 | Risk Ratio (IV, Random, 95% CI) | 2.94 [0.12, 70.30] |
| 5 Investigator‐assessed absolute change in total lesions (long‐term data) | 4 | 3230 | Mean Difference (IV, Random, 95% CI) | ‐10.73 [‐15.68, ‐5.78] |
| 5.1 BPO monotherapy versus placebo or no treatment | 2 | 1012 | Mean Difference (IV, Random, 95% CI) | ‐16.14 [‐26.51, ‐5.78] |
| 5.2 BPO/clindmycin versus clindamycin | 3 | 2218 | Mean Difference (IV, Random, 95% CI) | ‐7.25 [‐11.05, ‐3.45] |
| 6 Investigator‐assessed absolute change in inflammatory lesions (long‐term data) | 3 | 2635 | Mean Difference (IV, Random, 95% CI) | ‐3.50 [‐6.33, ‐0.67] |
| 6.1 BPO monotherapy versus placebo or no treatment | 2 | 1012 | Mean Difference (IV, Random, 95% CI) | ‐6.12 [‐11.02, ‐1.22] |
| 6.2 BPO/clindamycin versus clindamycin | 2 | 1623 | Mean Difference (IV, Random, 95% CI) | ‐1.03 [‐1.88, ‐0.18] |
| 7 Investigator‐assessed absolute change in non‐inflammatory lesions (long‐term data) | 3 | 2635 | Mean Difference (IV, Random, 95% CI) | ‐6.53 [‐9.74, ‐3.32] |
| 7.1 BPO monotherapy versus placebo or no treatment | 2 | 1012 | Mean Difference (IV, Random, 95% CI) | ‐9.69 [‐15.08, ‐4.29] |
| 7.2 BPO/clindamycin versus clindamycin | 2 | 1623 | Mean Difference (IV, Random, 95% CI) | ‐3.97 [‐5.81, ‐2.13] |
| 8 Investigator‐assessed percentage change in total lesions (long‐term data) | 4 | 1567 | Mean Difference (IV, Random, 95% CI) | 10.29 [3.39, 17.19] |
| 8.1 BPO/adapalene versus adapalene | 1 | 313 | Mean Difference (IV, Random, 95% CI) | 14.60 [8.35, 20.85] |
| 8.2 BPO/clindamycin versus clindamycin | 2 | 1053 | Mean Difference (IV, Random, 95% CI) | 12.74 [‐6.51, 31.99] |
| 8.3 BPO plus dapsone versus placebo plus dapsone | 1 | 201 | Mean Difference (IV, Random, 95% CI) | 7.00 [‐2.06, 16.06] |
| 9 Investigator‐assessed percentage change in inflammatory lesions (long‐term data) | 4 | 1588 | Mean Difference (IV, Random, 95% CI) | 17.22 [4.98, 29.45] |
| 9.1 BPO monotherapy versus placebo or no treatment | 1 | 150 | Mean Difference (IV, Random, 95% CI) | 34.0 [18.20, 49.80] |
| 9.2 BPO/clindamycin versus clindamycin | 3 | 1237 | Mean Difference (IV, Random, 95% CI) | 15.51 [‐2.02, 33.04] |
| 9.3 BPO plus dapsone versus placebo plus dapsone | 1 | 201 | Mean Difference (IV, Random, 95% CI) | 9.0 [‐0.82, 18.82] |
| 10 Investigator‐assessed percentage change in non‐inflammatory lesions (long‐term data) | 4 | 1588 | Mean Difference (IV, Random, 95% CI) | 19.31 [7.16, 31.47] |
| 10.1 BPO monotherapy versus placebo or no treatment | 1 | 150 | Mean Difference (IV, Random, 95% CI) | 41.0 [23.47, 58.53] |
| 10.2 BPO/clindamycin versus clindamycin | 3 | 1237 | Mean Difference (IV, Random, 95% CI) | 17.07 [2.15, 32.00] |
| 10.3 BPO plus dapsone versus placebo plus dapsone | 1 | 201 | Mean Difference (IV, Random, 95% CI) | 8.0 [‐3.24, 19.24] |
| 11 Investigator‐assessed percentage change in total lesions (medium‐term data) | 2 | 262 | Mean Difference (IV, Random, 95% CI) | 16.02 [‐0.95, 32.99] |
| 11.1 BPO/clindamycin versus clindamycin | 1 | 61 | Mean Difference (IV, Random, 95% CI) | 26.70 [8.33, 45.07] |
| 11.2 BPO plus dapsone versus placebo plus dapsone | 1 | 201 | Mean Difference (IV, Random, 95% CI) | 9.0 [‐0.43, 18.43] |
| 12 Investigator‐assessed percentage change in inflammatory lesions (medium‐term data) | 3 | 1212 | Mean Difference (IV, Random, 95% CI) | 13.83 [‐0.22, 27.88] |
| 12.1 BPO monotherapy versus placebo or no treatment | 1 | 28 | Mean Difference (IV, Random, 95% CI) | 33.80 [19.68, 47.92] |
| 12.2 BPO/clindamycin versus clindamycin | 1 | 983 | Mean Difference (IV, Random, 95% CI) | 5.0 [0.82, 9.18] |
| 12.3 BPO plus dapsone versus placebo plus dapsone | 1 | 201 | Mean Difference (IV, Random, 95% CI) | 7.00 [‐2.86, 16.86] |
| 13 Investigator‐assessed percentage change in non‐inflammatory lesions (medium‐term data) | 3 | 1212 | Mean Difference (IV, Random, 95% CI) | 18.42 [1.39, 35.45] |
| 13.1 BPO monotherapy versus placebo or no treatment | 1 | 28 | Mean Difference (IV, Random, 95% CI) | 40.2 [26.10, 54.30] |
| 13.2 BPO/clindamycin versus clindamycin | 1 | 983 | Mean Difference (IV, Random, 95% CI) | 8.0 [2.56, 13.44] |
| 13.3 BPO plus dapsone versus placebo plus dapsone | 1 | 201 | Mean Difference (IV, Random, 95% CI) | 10.0 [‐1.18, 21.18] |
| 14 Investigator‐assessed percentage change in total lesions (short‐term data) | 1 | 201 | Mean Difference (IV, Random, 95% CI) | 10.0 [2.26, 17.74] |
| 14.1 BPO plus dapsone versus placebo plus dapsone | 1 | 201 | Mean Difference (IV, Random, 95% CI) | 10.0 [2.26, 17.74] |
| 15 Investigator‐assessed percentage change in inflammatory lesions (short‐term data) | 3 | 1212 | Mean Difference (IV, Random, 95% CI) | 14.02 [‐0.60, 28.63] |
| 15.1 BPO monotherapy versus placebo or no treatment | 1 | 28 | Mean Difference (IV, Random, 95% CI) | 32.9 [22.22, 43.58] |
| 15.2 BPO/clindamycin versus clindamycin | 1 | 983 | Mean Difference (IV, Random, 95% CI) | 6.00 [1.65, 10.35] |
| 15.3 BPO plus dapsone versus placebo plus dapsone | 1 | 201 | Mean Difference (IV, Random, 95% CI) | 5.0 [‐3.57, 13.57] |
| 16 Investigator‐assessed percentage change in non‐inflammatory lesions (short‐term data) | 2 | 229 | Mean Difference (IV, Random, 95% CI) | 24.65 [4.23, 45.07] |
| 16.1 BPO monotherapy versus placebo or no treatment | 1 | 28 | Mean Difference (IV, Random, 95% CI) | 35.90 [21.00, 50.80] |
| 16.2 BPO plus dapsone versus placebo plus dapsone | 1 | 201 | Mean Difference (IV, Random, 95% CI) | 15.0 [5.32, 24.68] |
| 17 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (long‐term data) | 10 | 10399 | Risk Ratio (IV, Random, 95% CI) | 1.55 [1.40, 1.70] |
| 17.1 BPO monotherapy versus placebo or no treatment | 6 | 4110 | Risk Ratio (IV, Random, 95% CI) | 1.77 [1.37, 2.28] |
| 17.2 BPO/adapalene versus adapalene | 3 | 1969 | Risk Ratio (IV, Random, 95% CI) | 1.65 [1.42, 1.93] |
| 17.3 BPO/clindamycin versus clindamycin | 4 | 4079 | Risk Ratio (IV, Random, 95% CI) | 1.45 [1.31, 1.61] |
| 17.4 BPO plus tretinoin/clindamycin versus placebo plus tretinoin/clindamycin | 1 | 40 | Risk Ratio (IV, Random, 95% CI) | 1.08 [0.67, 1.75] |
| 17.5 BPO plus dapsone versus placebo plus dapsone | 1 | 201 | Risk Ratio (IV, Random, 95% CI) | 1.23 [0.82, 1.83] |
| 18 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (medium‐term data) | 5 | 5014 | Risk Ratio (IV, Random, 95% CI) | 1.96 [1.58, 2.44] |
| 18.1 BPO monotherapy versus placebo or no treatment | 4 | 2246 | Risk Ratio (IV, Random, 95% CI) | 1.95 [1.22, 3.11] |
| 18.2 BPO/adapalene versus adapalene | 3 | 1969 | Risk Ratio (IV, Random, 95% CI) | 1.98 [1.43, 2.73] |
| 18.3 BPO/clindamycin versus clindamycin | 1 | 799 | Risk Ratio (IV, Random, 95% CI) | 2.30 [1.55, 3.43] |
| 19 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (short‐term data) | 5 | 5014 | Risk Ratio (IV, Random, 95% CI) | 2.43 [1.78, 3.32] |
| 19.1 BPO monotherapy versus placebo or no treatment | 4 | 2246 | Risk Ratio (IV, Random, 95% CI) | 2.57 [1.28, 5.15] |
| 19.2 BPO/adapalene versus adapalene | 3 | 1969 | Risk Ratio (IV, Random, 95% CI) | 3.16 [2.05, 4.87] |
| 19.3 BPO/clindamycin versus clindamycin | 1 | 799 | Risk Ratio (IV, Random, 95% CI) | 1.74 [1.08, 2.79] |
| 20 Percentage of participants with any adverse events (long‐term data) | 21 | 11028 | Risk Ratio (IV, Random, 95% CI) | 1.40 [1.15, 1.70] |
| 20.1 BPO monotherapy versus placebo or no treatment | 13 | 4287 | Risk Ratio (IV, Random, 95% CI) | 1.46 [1.01, 2.11] |
| 20.2 BPO/adapalene versus adapalene | 3 | 1447 | Risk Ratio (IV, Random, 95% CI) | 1.38 [0.98, 1.95] |
| 20.3 BPO/clindamycin versus clindamycin | 8 | 4726 | Risk Ratio (IV, Random, 95% CI) | 1.48 [1.02, 2.16] |
| 20.4 BPO plus adapalene versus adapalene | 1 | 149 | Risk Ratio (IV, Random, 95% CI) | 1.08 [0.67, 1.74] |
| 20.5 BPO plus tazarotene versus tazarotene | 1 | 178 | Risk Ratio (IV, Random, 95% CI) | 0.57 [0.25, 1.29] |
| 20.6 BPO plus tretinoin/clindamycin versus placebo plus tretinoin/clindamycin | 1 | 40 | Risk Ratio (IV, Random, 95% CI) | 3.0 [0.34, 26.45] |
| 20.7 BPO plus dapsone versus placebo plus dapsone | 1 | 201 | Risk Ratio (IV, Random, 95% CI) | 2.36 [0.75, 7.43] |
| 21 Percentage of participants with any adverse events (medium‐term data) | 1 | 93 | Risk Ratio (IV, Random, 95% CI) | 1.67 [1.08, 2.59] |
| 21.1 BPO plus nadifloxacin versus placebo plus nadifloxacin | 1 | 93 | Risk Ratio (IV, Random, 95% CI) | 1.67 [1.08, 2.59] |
| 22 Percentage of participants with any adverse events (short‐term data) | 1 | 60 | Risk Ratio (IV, Random, 95% CI) | 0.13 [0.02, 0.94] |
| 22.1 BPO plus tretinoin/clindamycin versus placebo plus tretinoin/clindamycin | 1 | 60 | Risk Ratio (IV, Random, 95% CI) | 0.13 [0.02, 0.94] |
Comparison 2. BPO versus adapalene.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Participant's global self‐assessment of improvement (long‐term data) | 5 | 1472 | Risk Ratio (IV, Random, 95% CI) | 0.99 [0.90, 1.10] |
| 1.1 BPO monotherapy versus adapalene monotherapy | 4 | 1123 | Risk Ratio (IV, Random, 95% CI) | 0.96 [0.86, 1.06] |
| 1.2 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Risk Ratio (IV, Random, 95% CI) | 1.11 [1.01, 1.22] |
| 2 Withdrawal due to adverse effects (long‐term data) | 11 | 3295 | Risk Ratio (IV, Random, 95% CI) | 1.85 [0.94, 3.64] |
| 2.1 BPO monotherapy versus adapalene monotherapy | 9 | 2748 | Risk Ratio (IV, Random, 95% CI) | 2.05 [0.83, 5.06] |
| 2.2 BPO plus dapsone versus adapalene plus dapsone | 1 | 198 | Risk Ratio (IV, Random, 95% CI) | 4.08 [0.46, 35.87] |
| 2.3 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Risk Ratio (IV, Random, 95% CI) | 1.23 [0.38, 3.97] |
| 3 Investigator‐assessed absolute change in total lesions (long‐term data) | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐1.70 [‐5.46, 2.06] |
| 3.1 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐1.70 [‐5.46, 2.06] |
| 4 Investigator‐assessed absolute change in inflammatory lesions (long‐term data) | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐1.10 [‐2.42, 0.22] |
| 4.1 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐1.10 [‐2.42, 0.22] |
| 5 Investigator‐assessed absolute change in non‐inflammatory lesions (long‐term data) | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐0.60 [‐3.65, 2.45] |
| 5.1 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐0.60 [‐3.65, 2.45] |
| 6 Investigator‐assessed absolute change in total lesions (medium‐term data) | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐0.70 [‐5.09, 3.69] |
| 6.1 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐0.70 [‐5.09, 3.69] |
| 7 Investigator‐assessed absolute change in inflammatory lesions (medium‐term data) | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐1.90 [‐3.44, ‐0.36] |
| 7.1 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐1.90 [‐3.44, ‐0.36] |
| 8 Investigator‐assessed absolute change in non‐inflammatory lesions (medium‐term data) | 1 | 349 | Mean Difference (IV, Random, 95% CI) | 1.20 [‐2.46, 4.86] |
| 8.1 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | 1.20 [‐2.46, 4.86] |
| 9 Investigator‐assessed absolute change in total lesions (short‐term data) | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐4.70 [‐9.39, ‐0.01] |
| 9.1 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐4.70 [‐9.39, ‐0.01] |
| 10 Investigator‐assessed absolute change in inflammatory lesions (short‐term data) | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐2.60 [‐4.29, ‐0.91] |
| 10.1 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐2.60 [‐4.29, ‐0.91] |
| 11 Investigator‐assessed absolute change in non‐inflammatory lesions (short‐term data) | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐2.0 [‐6.02, 2.02] |
| 11.1 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐2.0 [‐6.02, 2.02] |
| 12 Investigator‐assessed percentage change in total lesions (long‐term data) | 4 | 869 | Mean Difference (IV, Random, 95% CI) | ‐2.63 [‐18.42, 13.15] |
| 12.1 BPO monotherapy versus adapalene monotherapy | 1 | 205 | Mean Difference (IV, Random, 95% CI) | 10.80 [3.38, 18.22] |
| 12.2 BPO plus clindamycin versus adapalene plus clindamycin | 1 | 117 | Mean Difference (IV, Random, 95% CI) | ‐19.0 [‐20.49, ‐17.51] |
| 12.3 BPO plus dapsone versus adapalene plus dapsone | 1 | 198 | Mean Difference (IV, Random, 95% CI) | ‐5.0 [‐14.37, 4.37] |
| 12.4 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | 3.24 [‐0.36, 6.84] |
| 13 Investigator‐assessed percentage change in inflammatory lesions (long‐term data) | 4 | 806 | Mean Difference (IV, Random, 95% CI) | ‐5.70 [‐21.14, 9.74] |
| 13.1 BPO monotherapy versus adapalene monotherapy | 1 | 142 | Mean Difference (IV, Random, 95% CI) | ‐7.70 [‐16.46, 1.06] |
| 13.2 BPO plus clindamycin versus adapalene plus clindamycin | 1 | 117 | Mean Difference (IV, Random, 95% CI) | ‐20.0 [‐22.17, ‐17.83] |
| 13.3 BPO plus dapsone versus adapalene plus dapsone | 1 | 198 | Mean Difference (IV, Random, 95% CI) | 1.0 [‐9.03, 11.03] |
| 13.4 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | 4.49 [0.64, 8.34] |
| 14 Investigator‐assessed percentage change in non‐inflammatory lesions (long‐term data) | 4 | 806 | Mean Difference (IV, Random, 95% CI) | ‐7.09 [‐21.39, 7.21] |
| 14.1 BPO monotherapy versus adapalene monotherapy | 1 | 142 | Mean Difference (IV, Random, 95% CI) | ‐3.90 [‐13.31, 5.51] |
| 14.2 BPO plus clindamycin versus adapalene plus clindamycin | 1 | 117 | Mean Difference (IV, Random, 95% CI) | ‐19.0 [‐20.95, ‐17.05] |
| 14.3 BPO plus dapsone versus adapalene plus dapsone | 1 | 198 | Mean Difference (IV, Random, 95% CI) | ‐9.0 [‐20.31, 2.31] |
| 14.4 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | 3.81 [‐0.59, 8.21] |
| 15 Investigator‐assessed percentage change in total lesions (medium‐term data) | 2 | 547 | Mean Difference (IV, Random, 95% CI) | 0.56 [‐5.04, 6.16] |
| 15.1 BPO plus dapsone versus adapalene plus dapsone | 1 | 198 | Mean Difference (IV, Random, 95% CI) | ‐4.0 [‐13.25, 5.25] |
| 15.2 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | 2.35 [‐1.89, 6.59] |
| 16 Investigator‐assessed percentage change in inflammatory lesions (medium‐term data) | 3 | 689 | Mean Difference (IV, Random, 95% CI) | 5.55 [1.58, 9.52] |
| 16.1 BPO monotherapy versus adapalene monotherapy | 1 | 142 | Mean Difference (IV, Random, 95% CI) | 2.40 [‐9.01, 13.81] |
| 16.2 BPO plus dapsone versus adapalene plus dapsone | 1 | 198 | Mean Difference (IV, Random, 95% CI) | 3.0 [‐6.67, 12.67] |
| 16.3 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | 6.69 [1.98, 11.40] |
| 17 Investigator‐assessed percentage change in non‐inflammatory lesions (medium‐term data) | 3 | 689 | Mean Difference (IV, Random, 95% CI) | 0.89 [‐8.35, 10.12] |
| 17.1 BPO monotherapy versus adapalene monotherapy | 1 | 142 | Mean Difference (IV, Random, 95% CI) | 10.90 [0.52, 21.28] |
| 17.2 BPO plus dapsone versus adapalene plus dapsone | 1 | 198 | Mean Difference (IV, Random, 95% CI) | ‐9.0 [‐19.78, 1.78] |
| 17.3 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | 0.59 [‐4.65, 5.83] |
| 18 Investigator‐assessed percentage change in total lesions (short‐term data) | 2 | 547 | Mean Difference (IV, Random, 95% CI) | 4.50 [0.22, 8.78] |
| 18.1 BPO plus dapsone versus adapalene plus dapsone | 1 | 198 | Mean Difference (IV, Random, 95% CI) | 1.0 [‐6.80, 8.80] |
| 18.2 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | 5.86 [1.28, 10.44] |
| 19 Investigator‐assessed percentage change in inflammatory lesions (short‐term data) | 3 | 689 | Mean Difference (IV, Random, 95% CI) | 9.12 [4.98, 13.26] |
| 19.1 BPO monotherapy versus adapalene monotherapy | 1 | 142 | Mean Difference (IV, Random, 95% CI) | 14.60 [4.28, 24.92] |
| 19.2 BPO plus dapsone versus adapalene plus dapsone | 1 | 198 | Mean Difference (IV, Random, 95% CI) | 5.0 [‐3.22, 13.22] |
| 19.3 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | 9.38 [4.17, 14.59] |
| 20 Investigator‐assessed percentage change in non‐inflammatory lesions (short‐term data) | 3 | 689 | Mean Difference (IV, Random, 95% CI) | 6.18 [‐1.80, 14.15] |
| 20.1 BPO monotherapy versus adapalene monotherapy | 1 | 142 | Mean Difference (IV, Random, 95% CI) | 15.30 [5.71, 24.89] |
| 20.2 BPO plus dapsone versus adapalene plus dapsone | 1 | 198 | Mean Difference (IV, Random, 95% CI) | 0.0 [‐9.75, 9.75] |
| 20.3 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | 3.94 [‐2.02, 9.90] |
| 21 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (long‐term data) | 5 | 2512 | Risk Ratio (IV, Random, 95% CI) | 1.12 [0.95, 1.32] |
| 21.1 BPO monotherapy versus adapalene monotherapy | 3 | 1965 | Risk Ratio (IV, Random, 95% CI) | 1.16 [0.98, 1.37] |
| 21.2 BPO plus dapsone versus adapalene plus dapsone | 1 | 198 | Risk Ratio (IV, Random, 95% CI) | 0.83 [0.59, 1.18] |
| 21.3 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Risk Ratio (IV, Random, 95% CI) | 1.45 [0.95, 2.23] |
| 22 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (medium‐term data) | 4 | 2314 | Risk Ratio (IV, Random, 95% CI) | 1.36 [1.07, 1.74] |
| 22.1 BPO monotherapy versus adapalene monotherapy | 3 | 1965 | Risk Ratio (IV, Random, 95% CI) | 1.32 [1.01, 1.73] |
| 22.2 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Risk Ratio (IV, Random, 95% CI) | 1.72 [0.87, 3.40] |
| 23 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (short‐term data) | 4 | 2314 | Risk Ratio (IV, Random, 95% CI) | 2.14 [1.41, 3.27] |
| 23.1 BPO monotherapy versus adapalene monotherapy | 3 | 1965 | Risk Ratio (IV, Random, 95% CI) | 2.14 [1.30, 3.51] |
| 23.2 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Risk Ratio (IV, Random, 95% CI) | 2.23 [0.87, 5.73] |
| 24 Change in quality of life (long‐term data) | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐0.17 [‐0.37, 0.03] |
| 24.1 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐0.17 [‐0.37, 0.03] |
| 25 Change in quality of life (medium‐term data) | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐0.22 [‐0.42, ‐0.02] |
| 25.1 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐0.22 [‐0.42, ‐0.02] |
| 26 Change in quality of life (short‐term data) | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐0.22 [‐0.41, ‐0.03] |
| 26.1 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Mean Difference (IV, Random, 95% CI) | ‐0.22 [‐0.41, ‐0.03] |
| 27 Percentage of participants with any adverse events (long‐term data) | 7 | 2120 | Risk Ratio (IV, Random, 95% CI) | 0.71 [0.50, 1.00] |
| 27.1 BPO monotherapy versus adapalene monotherapy | 5 | 1573 | Risk Ratio (IV, Random, 95% CI) | 0.77 [0.48, 1.25] |
| 27.2 BPO plus dapsone versus adapalene plus dapsone | 1 | 198 | Risk Ratio (IV, Random, 95% CI) | 0.66 [0.30, 1.44] |
| 27.3 BPO/clindamycin versus adapalene plus clindamycin | 1 | 349 | Risk Ratio (IV, Random, 95% CI) | 0.55 [0.42, 0.71] |
| 28 Percentage of participants with any adverse events (short‐term data) | 2 | 70 | Risk Ratio (IV, Random, 95% CI) | 3.0 [0.13, 68.26] |
| 28.1 BPO monotherapy versus adapalene monotherapy | 1 | 40 | Risk Ratio (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 28.2 BPO plus clindamycin versus adapalene plus clindamycin | 1 | 30 | Risk Ratio (IV, Random, 95% CI) | 3.0 [0.13, 68.26] |
Comparison 3. BPO versus clindamycin.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Participant's global self‐assessment of improvement (long‐term data) | 1 | 240 | Risk Ratio (IV, Random, 95% CI) | 0.95 [0.68, 1.34] |
| 1.1 BPO monotherapy versus clindamycin monotherapy | 1 | 240 | Risk Ratio (IV, Random, 95% CI) | 0.95 [0.68, 1.34] |
| 2 Withdrawal due to adverse effects (long‐term data) | 8 | 3330 | Risk Ratio (IV, Random, 95% CI) | 1.93 [0.90, 4.11] |
| 2.1 BPO monotherapy versus clindamycin monotherapy | 7 | 3154 | Risk Ratio (IV, Random, 95% CI) | 2.27 [0.87, 5.95] |
| 2.2 BPO plus tazarotene versus clindamycin plus tazarotene | 1 | 176 | Risk Ratio (IV, Random, 95% CI) | 1.47 [0.43, 5.02] |
| 3 Investigator‐assessed absolute change in total lesions (long‐term data) | 1 | 641 | Mean Difference (IV, Random, 95% CI) | ‐3.5 [‐7.54, 0.54] |
| 3.1 BPO monotherapy versus clindamycin monotherapy | 1 | 641 | Mean Difference (IV, Random, 95% CI) | ‐3.5 [‐7.54, 0.54] |
| 4 Investigator‐assessed absolute change in inflammatory lesions (long‐term data) | 1 | 641 | Mean Difference (IV, Random, 95% CI) | ‐1.20 [‐2.99, 0.59] |
| 4.1 BPO monotherapy versus clindamycin monotherapy | 1 | 641 | Mean Difference (IV, Random, 95% CI) | ‐1.20 [‐2.99, 0.59] |
| 5 Investigator‐assessed absolute change in non‐inflammatory lesions (long‐term data) | 1 | 641 | Mean Difference (IV, Random, 95% CI) | ‐2.40 [‐5.30, 0.50] |
| 5.1 BPO monotherapy versus clindamycin monotherapy | 1 | 641 | Mean Difference (IV, Random, 95% CI) | ‐2.40 [‐5.30, 0.50] |
| 6 Investigator‐assessed percentage change in inflammatory lesions (long‐term data) | 1 | 181 | Mean Difference (IV, Random, 95% CI) | 4.0 [‐8.56, 16.56] |
| 6.1 BPO monotherapy versus clindamycin monotherapy | 1 | 181 | Mean Difference (IV, Random, 95% CI) | 4.0 [‐8.56, 16.56] |
| 7 Investigator‐assessed percentage change in non‐inflammatory lesions (long‐term data) | 1 | 181 | Mean Difference (IV, Random, 95% CI) | 21.0 [6.86, 35.14] |
| 7.1 BPO monotherapy versus clindamycin monotherapy | 1 | 181 | Mean Difference (IV, Random, 95% CI) | 21.0 [6.86, 35.14] |
| 8 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (long‐term data) | 2 | 2277 | Risk Ratio (IV, Random, 95% CI) | 1.10 [0.83, 1.45] |
| 8.1 BPO monotherapy versus clindamycin monotherapy | 2 | 2277 | Risk Ratio (IV, Random, 95% CI) | 1.10 [0.83, 1.45] |
| 9 Percentage of participants with any adverse events (long‐term data) | 6 | 3018 | Risk Ratio (IV, Random, 95% CI) | 1.24 [0.97, 1.58] |
| 9.1 BPO monotherapy versus clindamycin monotherapy | 5 | 2842 | Risk Ratio (IV, Random, 95% CI) | 1.27 [0.98, 1.64] |
| 9.2 BPO plus tazarotene versus clindamycin plus tazarotene | 1 | 176 | Risk Ratio (IV, Random, 95% CI) | 0.87 [0.35, 2.15] |
Comparison 4. BPO versus erythromycin.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Withdrawal due to adverse effects (medium‐term data) | 1 | 60 | Risk Ratio (IV, Random, 95% CI) | 1.0 [0.07, 15.26] |
| 1.1 BPO monotherapy versus erythromycin monotherapy | 1 | 60 | Risk Ratio (IV, Random, 95% CI) | 1.0 [0.07, 15.26] |
Comparison 5. BPO versus salicylic acid.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Percentage of participants with any adverse events (medium‐term data) | 1 | 41 | Risk Ratio (IV, Random, 95% CI) | 4.77 [0.24, 93.67] |
| 1.1 BPO monotherapy versus salicylic acid monotherapy | 1 | 41 | Risk Ratio (IV, Random, 95% CI) | 4.77 [0.24, 93.67] |
Comparison 6. BPO versus tretinoin.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Withdrawal due to adverse effects (long‐term data) | 3 | 254 | Risk Ratio (IV, Random, 95% CI) | 1.11 [0.07, 17.36] |
| 1.1 BPO/clindamycin versus tretinoin plus clindamycin | 1 | 88 | Risk Ratio (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 1.2 BPO/clindamycin versus tretinoin/clindamycin | 1 | 54 | Risk Ratio (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 1.3 BPO/erythromycin versus tretinoin/erythromycin | 1 | 112 | Risk Ratio (IV, Random, 95% CI) | 1.11 [0.07, 17.36] |
| 2 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (long‐term data) | 1 | 88 | Risk Ratio (IV, Random, 95% CI) | 2.09 [0.86, 5.08] |
| 2.1 BPO/clindamycin versus tretinoin plus clindamycin | 1 | 88 | Risk Ratio (IV, Random, 95% CI) | 2.09 [0.86, 5.08] |
| 3 Percentage of participants with any adverse events (long‐term data) | 2 | 166 | Risk Ratio (IV, Random, 95% CI) | 0.58 [0.31, 1.07] |
| 3.1 BPO/clindamycin versus tretinoin/clindamycin | 1 | 54 | Risk Ratio (IV, Random, 95% CI) | 1.0 [0.33, 3.06] |
| 3.2 BPO/erythromycin versus tretinoin/erythromycin | 1 | 112 | Risk Ratio (IV, Random, 95% CI) | 0.48 [0.31, 0.76] |
| 4 Percentage of participants with any adverse events (medium‐term data) | 2 | 170 | Risk Ratio (IV, Random, 95% CI) | 0.03 [0.00, 0.48] |
| 4.1 BPO monotherapy versus tretinoin monotherapy | 2 | 170 | Risk Ratio (IV, Random, 95% CI) | 0.03 [0.00, 0.48] |
Comparison 7. BPO versus isotretinoin.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Withdrawal due to adverse effects (long‐term data) | 2 | 239 | Risk Ratio (IV, Random, 95% CI) | 1.23 [0.53, 2.87] |
| 1.1 BPO monotherapy versus isotretinoin monotherapy | 1 | 51 | Risk Ratio (IV, Random, 95% CI) | 1.92 [0.19, 19.90] |
| 1.2 BPO/erythromycin versus isotretinoin/erythromycin | 1 | 188 | Risk Ratio (IV, Random, 95% CI) | 1.15 [0.46, 2.85] |
| 2 Investigator‐assessed absolute change in inflammatory lesions (long‐term data) | 1 | 188 | Mean Difference (IV, Random, 95% CI) | ‐4.0 [‐9.89, 1.89] |
| 2.1 BPO/erythromycin versus isotretinoin/erythromycin | 1 | 188 | Mean Difference (IV, Random, 95% CI) | ‐4.0 [‐9.89, 1.89] |
| 3 Investigator‐assessed absolute change in non‐inflammatory lesions (long‐term data) | 1 | 188 | Mean Difference (IV, Random, 95% CI) | 2.30 [‐6.07, 10.67] |
| 3.1 BPO/erythromycin versus isotretinoin/erythromycin | 1 | 188 | Mean Difference (IV, Random, 95% CI) | 2.30 [‐6.07, 10.67] |
| 4 Investigator‐assessed absolute change in inflammatory lesions (medium‐term data) | 1 | 188 | Mean Difference (IV, Random, 95% CI) | ‐6.10 [‐11.27, ‐0.93] |
| 4.1 BPO/erythromycin versus isotretinoin/erythromycin | 1 | 188 | Mean Difference (IV, Random, 95% CI) | ‐6.10 [‐11.27, ‐0.93] |
| 5 Investigator‐assessed absolute change in non‐inflammatory lesions (medium‐term data) | 1 | 188 | Mean Difference (IV, Random, 95% CI) | 4.90 [‐1.66, 11.46] |
| 5.1 BPO/erythromycin versus isotretinoin/erythromycin | 1 | 188 | Mean Difference (IV, Random, 95% CI) | 4.90 [‐1.66, 11.46] |
| 6 Investigator‐assessed absolute change in inflammatory lesions (short‐term data) | 1 | 188 | Mean Difference (IV, Random, 95% CI) | ‐9.20 [‐14.09, ‐4.31] |
| 6.1 BPO/erythromycin versus isotretinoin/erythromycin | 1 | 188 | Mean Difference (IV, Random, 95% CI) | ‐9.20 [‐14.09, ‐4.31] |
| 7 Investigator‐assessed absolute change in non‐inflammatory lesions (short‐term data) | 1 | 188 | Mean Difference (IV, Random, 95% CI) | 1.20 [‐4.39, 6.79] |
| 7.1 BPO/erythromycin versus isotretinoin/erythromycin | 1 | 188 | Mean Difference (IV, Random, 95% CI) | 1.20 [‐4.39, 6.79] |
| 8 Percentage of participants with any adverse events (long‐term data) | 1 | 188 | Risk Ratio (IV, Random, 95% CI) | 0.85 [0.68, 1.06] |
| 8.1 BPO/erythromycin versus isotretinoin/erythromycin | 1 | 188 | Risk Ratio (IV, Random, 95% CI) | 0.85 [0.68, 1.06] |
| 9 Percentage of participants with any adverse events (short‐term data) | 1 | 29 | Risk Ratio (IV, Random, 95% CI) | 0.18 [0.05, 0.69] |
| 9.1 BPO monotherapy versus isotretinoin monotherapy | 1 | 29 | Risk Ratio (IV, Random, 95% CI) | 0.18 [0.05, 0.69] |
Comparison 8. BPO versus hydrogen peroxide.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Percentage of participants with any adverse events (medium‐term data) | 1 | 60 | Risk Ratio (IV, Random, 95% CI) | 3.5 [0.79, 15.49] |
| 1.1 BPO monotherapy versus hydrogen peroxide monotherapy | 1 | 60 | Risk Ratio (IV, Random, 95% CI) | 3.5 [0.79, 15.49] |
Comparison 9. BPO versus isolutrol.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Percentage of participants with any adverse events (long‐term data) | 1 | 70 | Risk Ratio (IV, Random, 95% CI) | 2.75 [1.73, 4.38] |
Comparison 10. BPO versus meclocycline.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Withdrawal due to adverse effects (long‐term data) | 1 | 69 | Risk Ratio (M‐H, Random, 95% CI) | 6.43 [0.34, 120.03] |
| 1.1 BPO monotherapy versus meclocycline monotherapy | 1 | 69 | Risk Ratio (M‐H, Random, 95% CI) | 6.43 [0.34, 120.03] |
Comparison 11. BPO versus tea tree oil.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Percentage of participants with any adverse events (long‐term data) | 1 | 124 | Risk Ratio (M‐H, Random, 95% CI) | 1.79 [1.32, 2.44] |
| 1.1 BPO monotherapy versus tea tree oil monotherapy | 1 | 124 | Risk Ratio (M‐H, Random, 95% CI) | 1.79 [1.32, 2.44] |
Comparison 12. BPO versus chloroxylenol/zinc oxide.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Participant's global self‐assessment of improvement (medium‐term data) | 1 | 26 | Risk Ratio (IV, Random, 95% CI) | 0.89 [0.51, 1.56] |
| 1.1 BPO monotherapy versus chloroxylenol/salicylic acid | 1 | 26 | Risk Ratio (IV, Random, 95% CI) | 0.89 [0.51, 1.56] |
Comparison 13. BPO/adapalene versus placebo or no treatment.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Participant's global self‐assessment of improvement (long‐term data) | 3 | 1480 | Risk Ratio (IV, Random, 95% CI) | 1.16 [0.97, 1.38] |
| 1.1 BPO/adapalene monotherapy versus placebo or no treatment | 2 | 1102 | Risk Ratio (IV, Random, 95% CI) | 1.25 [1.09, 1.44] |
| 1.2 BPO/adapalene plus lymecycline versus placebo plus lymecycline | 1 | 378 | Risk Ratio (IV, Random, 95% CI) | 0.99 [0.87, 1.13] |
| 2 Withdrawal due to adverse effects (long‐term data) | 8 | 3801 | Risk Ratio (IV, Random, 95% CI) | 2.28 [1.10, 4.71] |
| 2.1 BPO/adapalene monotherapy versus placebo or no treatment | 6 | 2964 | Risk Ratio (IV, Random, 95% CI) | 3.01 [1.34, 6.74] |
| 2.2 BPO/adapalene plus doxycycline versus placebo plus doxycycline | 1 | 459 | Risk Ratio (IV, Random, 95% CI) | 0.49 [0.09, 2.64] |
| 2.3 BPO/adapalene plus lymecycline versus placebo plus lymecycline | 1 | 378 | Risk Ratio (IV, Random, 95% CI) | 6.85 [0.36, 131.79] |
| 3 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (long‐term data) | 6 | 3012 | Risk Ratio (IV, Random, 95% CI) | 2.43 [1.80, 3.28] |
| 3.1 BPO/adapalene monotherapy versus placebo or no treatment | 4 | 2175 | Risk Ratio (IV, Random, 95% CI) | 2.45 [2.07, 2.90] |
| 3.2 BPO/adapalene plus doxycycline versus placebo plus doxycycline | 1 | 459 | Risk Ratio (IV, Random, 95% CI) | 3.81 [2.38, 6.10] |
| 3.3 BPO/adapalene plus lymecycline versus placebo plus lymecycline | 1 | 378 | Risk Ratio (IV, Random, 95% CI) | 1.41 [1.10, 1.82] |
| 4 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (medium‐term data) | 4 | 2175 | Risk Ratio (IV, Random, 95% CI) | 2.56 [1.88, 3.47] |
| 4.1 BPO/adapalene monotherapy versus placebo or no treatment | 4 | 2175 | Risk Ratio (IV, Random, 95% CI) | 2.56 [1.88, 3.47] |
| 5 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (short‐term data) | 4 | 2175 | Risk Ratio (IV, Random, 95% CI) | 2.76 [1.84, 4.16] |
| 5.1 BPO/adapalene monotherapy versus placebo or no treatment | 4 | 2175 | Risk Ratio (IV, Random, 95% CI) | 2.76 [1.84, 4.16] |
| 6 Percentage of participants with any adverse events (long‐term data) | 6 | 2465 | Risk Ratio (IV, Random, 95% CI) | 2.67 [1.15, 6.19] |
| 6.1 BPO/adapalene monotherapy versus placebo or no treatment | 4 | 1628 | Risk Ratio (IV, Random, 95% CI) | 4.60 [2.42, 8.75] |
| 6.2 BPO/adapalene plus doxycycline versus placebo plus doxycycline | 1 | 459 | Risk Ratio (IV, Random, 95% CI) | 0.91 [0.55, 1.50] |
| 6.3 BPO/adapalene plus lymecycline versus placebo plus lymecycline | 1 | 378 | Risk Ratio (IV, Random, 95% CI) | 1.04 [0.53, 2.05] |
Comparison 14. BPO/clindamycin versus placebo or no treatment.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Participant's global self‐assessment of improvement (long‐term data) | 1 | 240 | Risk Ratio (IV, Random, 95% CI) | 2.95 [1.96, 4.46] |
| 1.1 BPO/clindamycin monotherapy versus placebo or no treatment | 1 | 240 | Risk Ratio (IV, Random, 95% CI) | 2.95 [1.96, 4.46] |
| 2 Withdrawal due to adverse effects (long‐term data) | 8 | 3095 | Risk Ratio (IV, Random, 95% CI) | 1.07 [0.38, 3.00] |
| 2.1 BPO/clindamycin monotherapy versus placebo or no treatment | 6 | 2885 | Risk Ratio (IV, Random, 95% CI) | 0.87 [0.29, 2.60] |
| 2.2 BPO/clindamycin plus tretinoin and clindamycin versus tretinoin and clindamycin | 1 | 89 | Risk Ratio (IV, Random, 95% CI) | 5.11 [0.25, 103.53] |
| 2.3 BPO/clindamycin plus tazarotene versus placebo plus tazarotene | 1 | 121 | Risk Ratio (IV, Random, 95% CI) | 0.0 [0.0, 0.0] |
| 3 Investigator‐assessed absolute change in total lesions (long‐term data) | 1 | 651 | Mean Difference (IV, Random, 95% CI) | ‐15.2 [‐19.57, ‐10.83] |
| 3.1 BPO/clindamycin monotherapy versus placebo or no treatment | 1 | 651 | Mean Difference (IV, Random, 95% CI) | ‐15.2 [‐19.57, ‐10.83] |
| 4 Investigator‐assessed absolute change in inflammatory lesions (long‐term data) | 1 | 651 | Mean Difference (IV, Fixed, 95% CI) | ‐5.1 [‐6.83, ‐3.37] |
| 4.1 BPO/clindamycin monotherapy versus placebo or no treatment | 1 | 651 | Mean Difference (IV, Fixed, 95% CI) | ‐5.1 [‐6.83, ‐3.37] |
| 5 Investigator‐assessed absolute change in non‐inflammatory lesions (long‐term data) | 1 | 651 | Mean Difference (IV, Random, 95% CI) | ‐10.0 [‐13.20, ‐6.80] |
| 5.1 BPO/clindamycin monotherapy versus placebo or no treatment | 1 | 651 | Mean Difference (IV, Random, 95% CI) | ‐10.0 [‐13.20, ‐6.80] |
| 6 Investigator‐assessed percentage change in inflammatory lesions (long‐term data) | 2 | 1429 | Mean Difference (IV, Random, 95% CI) | 44.16 [23.53, 64.79] |
| 6.1 BPO/clindamycin monotherapy versus placebo or no treatment | 2 | 1429 | Mean Difference (IV, Random, 95% CI) | 44.16 [23.53, 64.79] |
| 7 Investigator‐assessed percentage change in non‐inflammatory lesions (long‐term data) | 2 | 1429 | Mean Difference (IV, Random, 95% CI) | 37.65 [26.04, 49.25] |
| 7.1 BPO/clindamycin monotherapy versus placebo or no treatment | 2 | 1429 | Mean Difference (IV, Random, 95% CI) | 37.65 [26.04, 49.25] |
| 8 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (long‐term data) | 5 | 3993 | Risk Ratio (IV, Random, 95% CI) | 2.37 [1.87, 3.01] |
| 8.1 BPO/clindamycin monotherapy versus placebo or no treatment | 4 | 3904 | Risk Ratio (IV, Random, 95% CI) | 2.29 [1.79, 2.93] |
| 8.2 BPO/clindamycin plus tretinoin and clindamycin versus tretinoin and clindamycin | 1 | 89 | Risk Ratio (IV, Random, 95% CI) | 3.75 [1.68, 8.36] |
| 9 Percentage of participants with any adverse events (long‐term data) | 8 | 5042 | Risk Ratio (IV, Random, 95% CI) | 0.91 [0.78, 1.07] |
| 9.1 BPO/clindamycin monotherapy versus placebo or no treatment | 8 | 5042 | Risk Ratio (IV, Random, 95% CI) | 0.91 [0.78, 1.07] |
Comparison 15. BPO/clindamycin versus adapalene.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Participant's global self‐assessment of improvement (long‐term data) | 1 | 168 | Risk Ratio (IV, Random, 95% CI) | 1.12 [0.96, 1.31] |
| 1.1 BPO/clindamycin versus adapalene monotherapy | 1 | 168 | Risk Ratio (IV, Random, 95% CI) | 1.12 [0.96, 1.31] |
| 2 Withdrawal due to adverse effects (long‐term data) | 3 | 398 | Risk Ratio (IV, Random, 95% CI) | 0.41 [0.05, 3.05] |
| 2.1 BPO/clindamycin versus adapalene monotherapy | 3 | 398 | Risk Ratio (IV, Random, 95% CI) | 0.41 [0.05, 3.05] |
| 3 Change in quality of life (long‐term data) | 1 | 168 | Mean Difference (IV, Random, 95% CI) | ‐4.20 [‐7.06, ‐1.34] |
| 3.1 BPO/clindamycin versus adapalene monotherapy | 1 | 168 | Mean Difference (IV, Random, 95% CI) | ‐4.20 [‐7.06, ‐1.34] |
| 4 Change in quality of life (short‐term data) | 1 | 168 | Mean Difference (IV, Random, 95% CI) | ‐3.8 [‐6.16, ‐1.44] |
| 4.1 BPO/clindamycin versus adapalene monotherapy | 1 | 168 | Mean Difference (IV, Random, 95% CI) | ‐3.8 [‐6.16, ‐1.44] |
| 5 Percentage of participants with any adverse events (long‐term data) | 2 | 298 | Risk Ratio (IV, Random, 95% CI) | 0.60 [0.36, 1.01] |
| 5.1 BPO/clindamycin versus adapalene monotherapy | 2 | 298 | Risk Ratio (IV, Random, 95% CI) | 0.60 [0.36, 1.01] |
Comparison 16. BPO/clindamycin versus azelaic acid.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Participant's global self‐assessment of improvement (long‐term data) | 1 | 217 | Risk Ratio (IV, Random, 95% CI) | 1.38 [1.05, 1.81] |
| 1.1 BPO/clindamycin versus azelaic acid monotherapy | 1 | 217 | Risk Ratio (IV, Random, 95% CI) | 1.38 [1.05, 1.81] |
| 2 Participant's global self‐assessment of improvement (medium‐term data) | 1 | 217 | Risk Ratio (IV, Random, 95% CI) | 1.44 [1.09, 1.89] |
| 2.1 BPO/clindamycin versus azelaic acid monotherapy | 1 | 217 | Risk Ratio (IV, Random, 95% CI) | 1.44 [1.09, 1.89] |
| 3 Participant's global self‐assessment of improvement (short‐term data) | 1 | 217 | Risk Ratio (IV, Random, 95% CI) | 1.37 [1.00, 1.88] |
| 3.1 BPO/clindamycin versus azelaic acid monotherapy | 1 | 217 | Risk Ratio (IV, Random, 95% CI) | 1.37 [1.00, 1.88] |
| 4 Withdrawal due to adverse effects (long‐term data) | 1 | 217 | Risk Ratio (IV, Random, 95% CI) | 1.01 [0.06, 15.93] |
| 4.1 BPO/clindamycin versus azelaic acid monotherapy | 1 | 217 | Risk Ratio (IV, Random, 95% CI) | 1.01 [0.06, 15.93] |
| 5 Investigator‐assessed percentage change in total lesions (long‐term data) | 1 | 211 | Mean Difference (IV, Random, 95% CI) | 18.50 [10.54, 26.46] |
| 5.1 BPO/clindamycin versus azelaic acid monotherapy | 1 | 211 | Mean Difference (IV, Random, 95% CI) | 18.50 [10.54, 26.46] |
| 6 Investigator‐assessed percentage change in inflammatory lesions (long‐term data) | 1 | 211 | Mean Difference (IV, Random, 95% CI) | 17.30 [9.87, 24.73] |
| 6.1 BPO/clindamycin versus azelaic acid monotherapy | 1 | 211 | Mean Difference (IV, Random, 95% CI) | 17.30 [9.87, 24.73] |
| 7 Investigator‐assessed percentage change in non‐inflammatory lesions (long‐term data) | 1 | 211 | Mean Difference (IV, Random, 95% CI) | 18.5 [8.67, 28.33] |
| 7.1 BPO/clindamycin versus azelaic acid monotherapy | 1 | 211 | Mean Difference (IV, Random, 95% CI) | 18.5 [8.67, 28.33] |
| 8 Investigator‐assessed percentage change in total lesions (medium‐term data) | 1 | 206 | Mean Difference (IV, Random, 95% CI) | 15.10 [7.19, 23.01] |
| 8.1 BPO/clindamycin versus azelaic acid monotherapy | 1 | 206 | Mean Difference (IV, Random, 95% CI) | 15.10 [7.19, 23.01] |
| 9 Investigator‐assessed percentage change in inflammatory lesions (medium‐term data) | 1 | 206 | Mean Difference (IV, Random, 95% CI) | 15.90 [8.06, 23.74] |
| 9.1 BPO/clindamycin versus azelaic acid monotherapy | 1 | 206 | Mean Difference (IV, Random, 95% CI) | 15.90 [8.06, 23.74] |
| 10 Investigator‐assessed percentage change in non‐inflammatory lesions (medium‐term data) | 1 | 206 | Mean Difference (IV, Random, 95% CI) | 13.00 [3.24, 22.76] |
| 10.1 BPO/clindamycin versus azelaic acid monotherapy | 1 | 206 | Mean Difference (IV, Random, 95% CI) | 13.00 [3.24, 22.76] |
| 11 Investigator‐assessed percentage change in total lesions (short‐term data) | 1 | 212 | Mean Difference (IV, Random, 95% CI) | 13.00 [6.77, 19.23] |
| 11.1 BPO/clindamycin versus azelaic acid monotherapy | 1 | 212 | Mean Difference (IV, Random, 95% CI) | 13.00 [6.77, 19.23] |
| 12 Investigator‐assessed percentage change in inflammatory lesions (short‐term data) | 1 | 212 | Mean Difference (IV, Random, 95% CI) | 14.10 [6.18, 22.02] |
| 12.1 BPO/clindamycin versus azelaic acid monotherapy | 1 | 212 | Mean Difference (IV, Random, 95% CI) | 14.10 [6.18, 22.02] |
| 13 Investigator‐assessed percentage change in non‐inflammatory lesions (short‐term data) | 1 | 212 | Mean Difference (IV, Random, 95% CI) | 11.10 [3.56, 18.64] |
| 13.1 BPO/clindamycin versus azelaic acid monotherapy | 1 | 212 | Mean Difference (IV, Random, 95% CI) | 11.10 [3.56, 18.64] |
| 14 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (long‐term data) | 1 | 217 | Risk Ratio (IV, Random, 95% CI) | 1.91 [1.17, 3.11] |
| 14.1 BPO/clindamycin versus azelaic acid monotherapy | 1 | 217 | Risk Ratio (IV, Random, 95% CI) | 1.91 [1.17, 3.11] |
| 15 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (medium‐term data) | 1 | 217 | Risk Ratio (IV, Random, 95% CI) | 1.88 [1.07, 3.32] |
| 15.1 BPO/clindamycin versus azelaic acid monotherapy | 1 | 217 | Risk Ratio (IV, Random, 95% CI) | 1.88 [1.07, 3.32] |
| 16 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (short‐term data) | 1 | 217 | Risk Ratio (IV, Random, 95% CI) | 1.74 [0.87, 3.49] |
| 16.1 BPO/clindamycin versus azelaic acid monotherapy | 1 | 217 | Risk Ratio (IV, Random, 95% CI) | 1.74 [0.87, 3.49] |
| 17 Percentage of participants with any adverse events (long‐term data) | 1 | 217 | Risk Ratio (IV, Random, 95% CI) | 0.42 [0.24, 0.72] |
| 17.1 BPO/clindamycin versus azelaic acid monotherapy | 1 | 217 | Risk Ratio (IV, Random, 95% CI) | 0.42 [0.24, 0.72] |
Comparison 17. BPO/clindamycin versus erythromycin/zinc.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Withdrawal due to adverse effects (long‐term data) | 1 | 148 | Risk Ratio (IV, Random, 95% CI) | 1.03 [0.07, 16.12] |
| 1.1 BPO/clindamycin monotherapy versus erythromycin/zinc monotherapy | 1 | 148 | Risk Ratio (IV, Random, 95% CI) | 1.03 [0.07, 16.12] |
| 2 Investigator‐assessed absolute change in total lesions (long‐term data) | 1 | 148 | Mean Difference (IV, Random, 95% CI) | 6.10 [‐4.65, 16.85] |
| 2.1 BPO/clindamycin monotherapy versus erythromycin/zinc monotherapy | 1 | 148 | Mean Difference (IV, Random, 95% CI) | 6.10 [‐4.65, 16.85] |
| 3 Investigator‐assessed absolute change in inflammatory lesions (long‐term data) | 1 | 148 | Mean Difference (IV, Random, 95% CI) | 0.10 [‐3.85, 4.05] |
| 3.1 BPO/clindamycin monotherapy versus erythromycin/zinc monotherapy | 1 | 148 | Mean Difference (IV, Random, 95% CI) | 0.10 [‐3.85, 4.05] |
| 4 Investigator‐assessed absolute change in non‐inflammatory lesions (long‐term data) | 1 | 148 | Mean Difference (IV, Random, 95% CI) | 6.40 [‐2.16, 14.96] |
| 4.1 BPO/clindamycin monotherapy versus erythromycin/zinc monotherapy | 1 | 148 | Mean Difference (IV, Random, 95% CI) | 6.40 [‐2.16, 14.96] |
| 5 Investigator‐assessed absolute change in total lesions (medium‐term data) | 1 | 148 | Mean Difference (IV, Random, 95% CI) | 5.60 [‐5.61, 16.81] |
| 5.1 BPO/clindamycin monotherapy versus erythromycin/zinc monotherapy | 1 | 148 | Mean Difference (IV, Random, 95% CI) | 5.60 [‐5.61, 16.81] |
| 6 Investigator‐assessed absolute change in inflammatory lesions (medium‐term data) | 1 | 148 | Mean Difference (IV, Random, 95% CI) | ‐0.20 [‐4.33, 3.93] |
| 6.1 BPO/clindamycin monotherapy versus erythromycin/zinc monotherapy | 1 | 148 | Mean Difference (IV, Random, 95% CI) | ‐0.20 [‐4.33, 3.93] |
| 7 Investigator‐assessed absolute change in non‐inflammatory lesions (medium‐term data) | 1 | 148 | Mean Difference (IV, Random, 95% CI) | 6.20 [‐2.66, 15.06] |
| 7.1 BPO/clindamycin monotherapy versus erythromycin/zinc monotherapy | 1 | 148 | Mean Difference (IV, Random, 95% CI) | 6.20 [‐2.66, 15.06] |
| 8 Investigator‐assessed absolute change in total lesions (short‐term data) | 1 | 148 | Mean Difference (IV, Random, 95% CI) | 5.80 [‐5.96, 17.56] |
| 8.1 BPO/clindamycin monotherapy versus erythromycin/zinc monotherapy | 1 | 148 | Mean Difference (IV, Random, 95% CI) | 5.80 [‐5.96, 17.56] |
| 9 Investigator‐assessed absolute change in inflammatory lesions (short‐term data) | 1 | 148 | Mean Difference (IV, Random, 95% CI) | 0.10 [‐3.91, 4.11] |
| 9.1 BPO/clindamycin monotherapy versus erythromycin/zinc monotherapy | 1 | 148 | Mean Difference (IV, Random, 95% CI) | 0.10 [‐3.91, 4.11] |
| 10 Investigator‐assessed absolute change in non‐inflammatory lesions (short‐term data) | 1 | 148 | Mean Difference (IV, Random, 95% CI) | 6.20 [‐3.60, 16.00] |
| 10.1 BPO/clindamycin monotherapy versus erythromycin/zinc monotherapy | 1 | 148 | Mean Difference (IV, Random, 95% CI) | 6.20 [‐3.60, 16.00] |
| 11 Percentage of participants with any adverse events (long‐term data) | 1 | 148 | Risk Ratio (IV, Random, 95% CI) | 0.67 [0.38, 1.18] |
| 11.1 BPO/clindamycin monotherapy versus erythromycin/zinc monotherapy | 1 | 148 | Risk Ratio (IV, Random, 95% CI) | 0.67 [0.38, 1.18] |
Comparison 18. BPO/clindamycin versus dapsone.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Percentage of participants with any adverse events (long‐term data) | 1 | 286 | Risk Ratio (IV, Random, 95% CI) | 0.67 [0.37, 1.23] |
| 1.1 BPO/clindamycin plus adapalene versus dapsone plus adapalene | 1 | 286 | Risk Ratio (IV, Random, 95% CI) | 0.67 [0.37, 1.23] |
Comparison 19. BPO/erythromycin versus placebo or no treatment.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Participant's global self‐assessment of improvement (medium‐term data) | 1 | 223 | Risk Ratio (IV, Random, 95% CI) | 1.28 [1.04, 1.57] |
| 1.1 BPO/erythromycin monotherapy versus placebo or no treatment | 1 | 223 | Risk Ratio (IV, Random, 95% CI) | 1.28 [1.04, 1.57] |
| 2 Withdrawal due to adverse effects (long‐term data) | 1 | 179 | Risk Ratio (IV, Random, 95% CI) | 0.49 [0.18, 1.39] |
| 2.1 BPO/erythromycin plus tazarotene versus tazarotene | 1 | 179 | Risk Ratio (IV, Random, 95% CI) | 0.49 [0.18, 1.39] |
| 3 Withdrawal due to adverse effects (medium‐term data) | 2 | 550 | Risk Ratio (IV, Random, 95% CI) | 0.33 [0.01, 8.02] |
| 3.1 BPO/erythromycin monotherapy versus placebo or no treatment | 2 | 550 | Risk Ratio (IV, Random, 95% CI) | 0.33 [0.01, 8.02] |
| 4 Investigator‐assessed absolute change in total lesions (long‐term data) | 1 | 58 | Mean Difference (IV, Random, 95% CI) | ‐5.20 [‐11.74, 1.34] |
| 4.1 BPO/erythromycin monotherapy versus placebo or no treatment | 1 | 58 | Mean Difference (IV, Random, 95% CI) | ‐5.20 [‐11.74, 1.34] |
| 5 Investigator‐assessed absolute change in inflammatory lesions (long‐term data) | 1 | 58 | Mean Difference (IV, Random, 95% CI) | ‐6.9 [‐11.52, ‐2.28] |
| 5.1 BPO/erythromycin monotherapy versus placebo or no treatment | 1 | 58 | Mean Difference (IV, Random, 95% CI) | ‐6.9 [‐11.52, ‐2.28] |
| 6 Investigator‐assessed absolute change in non‐inflammatory lesions (long‐term data) | 1 | 58 | Mean Difference (IV, Random, 95% CI) | 1.80 [‐1.96, 5.56] |
| 6.1 BPO/erythromycin monotherapy versus placebo or no treatment | 1 | 58 | Mean Difference (IV, Random, 95% CI) | 1.80 [‐1.96, 5.56] |
| 7 Investigator‐assessed absolute change in total lesions (medium‐term data) | 2 | 281 | Mean Difference (IV, Random, 95% CI) | ‐4.59 [‐12.63, 3.44] |
| 7.1 BPO/erythromycin monotherapy versus placebo or no treatment | 2 | 281 | Mean Difference (IV, Random, 95% CI) | ‐4.59 [‐12.63, 3.44] |
| 8 Investigator‐assessed absolute change in inflammatory lesions (medium‐term data) | 1 | 58 | Mean Difference (IV, Random, 95% CI) | ‐3.90 [‐8.07, 0.27] |
| 8.1 BPO/erythromycin monotherapy versus placebo or no treatment | 1 | 58 | Mean Difference (IV, Random, 95% CI) | ‐3.90 [‐8.07, 0.27] |
| 9 Investigator‐assessed absolute change in non‐inflammatory lesions (medium‐term data) | 2 | 281 | Mean Difference (IV, Random, 95% CI) | 0.80 [‐4.30, 5.89] |
| 9.1 BPO/erythromycin monotherapy versus placebo or no treatment | 2 | 281 | Mean Difference (IV, Random, 95% CI) | 0.80 [‐4.30, 5.89] |
| 10 Investigator‐assessed absolute change in total lesions (short‐term data) | 1 | 59 | Mean Difference (IV, Random, 95% CI) | ‐3.60 [‐7.92, 0.72] |
| 10.1 BPO/erythromycin monotherapy versus placebo or no treatment | 1 | 59 | Mean Difference (IV, Random, 95% CI) | ‐3.60 [‐7.92, 0.72] |
| 11 Investigator‐assessed absolute change in inflammatory lesions (short‐term data) | 1 | 59 | Mean Difference (IV, Random, 95% CI) | ‐6.10 [‐9.39, ‐2.81] |
| 11.1 BPO/erythromycin monotherapy versus placebo or no treatment | 1 | 59 | Mean Difference (IV, Random, 95% CI) | ‐6.10 [‐9.39, ‐2.81] |
| 12 Investigator‐assessed absolute change in non‐inflammatory lesions (short‐term data) | 1 | 59 | Mean Difference (IV, Random, 95% CI) | 2.4 [‐0.71, 5.51] |
| 12.1 BPO/erythromycin monotherapy versus placebo or no treatment | 1 | 59 | Mean Difference (IV, Random, 95% CI) | 2.4 [‐0.71, 5.51] |
| 13 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (medium‐term data) | 2 | 550 | Risk Ratio (IV, Random, 95% CI) | 2.84 [1.79, 4.52] |
| 13.1 BPO/erythromycin monotherapy versus placebo or no treatment | 2 | 550 | Risk Ratio (IV, Random, 95% CI) | 2.84 [1.79, 4.52] |
| 14 'Clear' or 'Almost clear' rated on the IGA scale of acne severity (short‐term data) | 1 | 327 | Risk Ratio (IV, Random, 95% CI) | 6.69 [0.91, 49.10] |
| 14.1 BPO/erythromycin monotherapy versus placebo or no treatment | 1 | 327 | Risk Ratio (IV, Random, 95% CI) | 6.69 [0.91, 49.10] |
| 15 Percentage of participants with any adverse events (long‐term data) | 1 | 179 | Risk Ratio (IV, Random, 95% CI) | 1.06 [0.54, 2.06] |
| 15.1 BPO/erythromycin plus tazarotene versus tazarotene | 1 | 179 | Risk Ratio (IV, Random, 95% CI) | 1.06 [0.54, 2.06] |
| 16 Percentage of participants with any adverse events (medium‐term data) | 2 | 550 | Risk Ratio (IV, Random, 95% CI) | 1.88 [0.92, 3.87] |
| 16.1 BPO/erythromycin monotherapy versus placebo or no treatment | 2 | 550 | Risk Ratio (IV, Random, 95% CI) | 1.88 [0.92, 3.87] |
Comparison 20. BPO/erythromycin versus clindamycin.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Withdrawal due to adverse effects (long‐term data) | 2 | 376 | Risk Ratio (IV, Random, 95% CI) | 1.51 [0.50, 4.61] |
| 1.1 BPO/erythromycin monotherapy versus clindamycin monotherapy | 1 | 199 | Risk Ratio (IV, Random, 95% CI) | 3.03 [0.32, 28.64] |
| 1.2 BPO/erythromycin plus tazarotene versus clindamycin plus tazarotene | 1 | 177 | Risk Ratio (IV, Random, 95% CI) | 1.21 [0.34, 4.35] |
| 2 Percentage of participants with any adverse events (long‐term data) | 2 | 378 | Risk Ratio (IV, Random, 95% CI) | 2.16 [0.77, 6.08] |
| 2.1 BPO/erythromycin monotherapy versus clindamycin monotherapy | 1 | 199 | Risk Ratio (IV, Random, 95% CI) | 6.06 [0.74, 49.43] |
| 2.2 BPO/erythromycin plus tazarotene versus clindamycin plus tazarotene | 1 | 179 | Risk Ratio (IV, Random, 95% CI) | 1.65 [0.76, 3.57] |
Comparison 21. BPO/erythromycin versus viaminate.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Percentage of participants with any adverse events (short‐term data) | 1 | 187 | Risk Ratio (IV, Random, 95% CI) | 23.52 [1.42, 390.03] |
| 1.1 BPO/erythromycin versus viaminate monotherapy | 1 | 187 | Risk Ratio (IV, Random, 95% CI) | 23.52 [1.42, 390.03] |
Comparison 22. BPO/glycolic acid/zinc lactate versus placebo.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Investigator‐assessed absolute change in total lesions (long‐term data) | 1 | 56 | Mean Difference (IV, Random, 95% CI) | ‐6.5 [‐12.56, ‐0.44] |
| 1.1 BPO/glycolic acid/zinc lactate versus placebo | 1 | 56 | Mean Difference (IV, Random, 95% CI) | ‐6.5 [‐12.56, ‐0.44] |
| 2 Investigator‐assessed absolute change in inflammatory lesions (long‐term data) | 1 | 56 | Mean Difference (IV, Random, 95% CI) | ‐5.6 [‐10.38, ‐0.82] |
| 2.1 BPO/glycolic acid/zinc lactate versus placebo | 1 | 56 | Mean Difference (IV, Random, 95% CI) | ‐5.6 [‐10.38, ‐0.82] |
| 3 Investigator‐assessed absolute change in non‐inflammatory lesions (long‐term data) | 1 | 56 | Mean Difference (IV, Random, 95% CI) | ‐0.90 [‐4.74, 2.94] |
| 3.1 BPO/glycolic acid/zinc lactate versus placebo | 1 | 56 | Mean Difference (IV, Random, 95% CI) | ‐0.90 [‐4.74, 2.94] |
| 4 Investigator‐assessed absolute change in total lesions (medium‐term data) | 1 | 56 | Mean Difference (IV, Random, 95% CI) | ‐0.90 [‐5.26, 3.46] |
| 4.1 BPO/glycolic acid/zinc lactate versus placebo | 1 | 56 | Mean Difference (IV, Random, 95% CI) | ‐0.90 [‐5.26, 3.46] |
| 5 Investigator‐assessed absolute change in inflammatory lesions (medium‐term data) | 1 | 56 | Mean Difference (IV, Random, 95% CI) | ‐2.60 [‐6.59, 1.39] |
| 5.1 BPO/glycolic acid/zinc lactate versus placebo | 1 | 56 | Mean Difference (IV, Random, 95% CI) | ‐2.60 [‐6.59, 1.39] |
| 6 Investigator‐assessed absolute change in non‐inflammatory lesions (medium‐term data) | 1 | 56 | Mean Difference (IV, Random, 95% CI) | 1.70 [‐1.95, 5.35] |
| 6.1 BPO/glycolic acid/zinc lactate versus placebo | 1 | 56 | Mean Difference (IV, Random, 95% CI) | 1.70 [‐1.95, 5.35] |
| 7 Investigator‐assessed absolute change in total lesions (short‐term data) | 1 | 58 | Mean Difference (IV, Random, 95% CI) | ‐4.20 [‐9.29, 0.89] |
| 7.1 BPO/glycolic acid/zinc lactate versus placebo | 1 | 58 | Mean Difference (IV, Random, 95% CI) | ‐4.20 [‐9.29, 0.89] |
| 8 Investigator‐assessed absolute change in inflammatory lesions (short‐term data) | 1 | 58 | Mean Difference (IV, Random, 95% CI) | ‐4.8 [‐8.66, ‐0.94] |
| 8.1 BPO/glycolic acid/zinc lactate versus placebo | 1 | 58 | Mean Difference (IV, Random, 95% CI) | ‐4.8 [‐8.66, ‐0.94] |
| 9 Investigator‐assessed absolute change in non‐inflammatory lesions (short‐term data) | 1 | 58 | Mean Difference (IV, Random, 95% CI) | 0.5 [‐3.41, 4.41] |
| 9.1 BPO/glycolic acid/zinc lactate versus placebo | 1 | 58 | Mean Difference (IV, Random, 95% CI) | 0.5 [‐3.41, 4.41] |
Comparison 23. BPO/potassium hydroxyquinoline sulphate versus placebo.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Withdrawal due to adverse effects (long‐term data) | 1 | 53 | Risk Ratio (IV, Random, 95% CI) | 7.81 [0.42, 144.12] |
| 1.1 BPO/potassium hydroxyquinoline sulphate versus placebo | 1 | 53 | Risk Ratio (IV, Random, 95% CI) | 7.81 [0.42, 144.12] |
Comparison 24. BPO 10% versus BPO 5%.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Withdrawal due to adverse effects (medium‐term data) | 2 | 257 | Risk Ratio (IV, Random, 95% CI) | 0.40 [0.06, 2.52] |
| 1.1 BPO 10% monotherapy versus BPO 5% monotherapy | 2 | 257 | Risk Ratio (IV, Random, 95% CI) | 0.40 [0.06, 2.52] |
| 2 Percentage of participants with any adverse events (medium‐term data) | 2 | 257 | Risk Ratio (IV, Random, 95% CI) | 0.72 [0.40, 1.31] |
| 2.1 BPO 10% monotherapy versus BPO 5% monotherapy | 2 | 257 | Risk Ratio (IV, Random, 95% CI) | 0.72 [0.40, 1.31] |
Comparison 25. BPO 10% versus BPO 2.5%.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Percentage of participants with any adverse events (medium‐term data) | 1 | 64 | Risk Ratio (IV, Random, 95% CI) | 1.71 [0.99, 2.96] |
| 1.1 BPO 10% monotherapy versus BPO 2.5% monotherapy | 1 | 64 | Risk Ratio (IV, Random, 95% CI) | 1.71 [0.99, 2.96] |
Comparison 26. BPO 5% versus BPO 2.5%.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Withdrawal due to adverse effects (long‐term data) | 3 | 906 | Risk Ratio (IV, Random, 95% CI) | 1.28 [0.65, 2.54] |
| 1.1 BPO 5% monotherapy versus BPO 2.5% monotherapy | 2 | 866 | Risk Ratio (IV, Random, 95% CI) | 1.23 [0.61, 2.48] |
| 1.2 BPO (5%)/clindamycin plus tazarotene versus BPO (2.5%)/clindamycin plus tazarotene | 1 | 40 | Risk Ratio (IV, Random, 95% CI) | 3.0 [0.13, 69.52] |
| 2 Withdrawal due to adverse effects (medium‐term data) | 2 | 208 | Risk Ratio (IV, Random, 95% CI) | 1.79 [0.09, 33.82] |
| 2.1 BPO 5% monotherapy versus BPO 2.5% monotherapy | 2 | 208 | Risk Ratio (IV, Random, 95% CI) | 1.79 [0.09, 33.82] |
| 3 Change in quality of life (long‐term data) | 1 | 40 | Mean Difference (IV, Random, 95% CI) | ‐2.40 [‐8.68, 3.88] |
| 3.1 BPO (5%)/clindamycin plus tazarotene versus BPO (2.5%)/clindamycin plus tazarotene | 1 | 40 | Mean Difference (IV, Random, 95% CI) | ‐2.40 [‐8.68, 3.88] |
| 4 Percentage of participants with any adverse events (long‐term data) | 4 | 1063 | Risk Ratio (IV, Random, 95% CI) | 1.06 [0.95, 1.19] |
| 4.1 BPO 5% monotherapy versus BPO 2.5% monotherapy | 3 | 1023 | Risk Ratio (IV, Random, 95% CI) | 1.06 [0.95, 1.19] |
| 4.2 BPO (5%)/clindamycin plus tazarotene versus BPO (2.5%)/clindamycin plus tazarotene | 1 | 40 | Risk Ratio (IV, Random, 95% CI) | 1.14 [0.51, 2.55] |
| 5 Percentage of participants with any adverse events (medium‐term data) | 1 | 155 | Risk Ratio (IV, Random, 95% CI) | 1.86 [1.14, 3.05] |
| 5.1 BPO 5% monotherapy versus BPO 2.5% monotherapy | 1 | 155 | Risk Ratio (IV, Random, 95% CI) | 1.86 [1.14, 3.05] |
Comparison 27. BPO gel (6%) versus BPO cream (5.5%).
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Withdrawal due to adverse effects (long‐term data) | 1 | 48 | Risk Ratio (IV, Random, 95% CI) | 3.0 [0.13, 70.16] |
| 1.1 BPO gel (6%) monotherapy versus BPO cream (5.5%) monotherapy | 1 | 48 | Risk Ratio (IV, Random, 95% CI) | 3.0 [0.13, 70.16] |
Characteristics of studies
Characteristics of included studies [ordered by study ID]
Babaeinejad 2013.
| Methods | Study design: parallel design Duration of follow‐up: 3 months | |
| Participants | Total number of participants randomised: N = 60 Inclusion criteria: patients with mild acne vulgaris Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Evaluator Global Severity Score (EGSS) of 2 Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 6/24; B = 7/23 Age (years): A = 20.93 (3.77); B = 21.27 (3.57) Duration of acne (years): A = 6.07 (2.77); B = 6.20 (2.94) | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: wash with a gentle cleanser | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at months 1, 2, and 3 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: January 2011 to April 2012 Country: Iran Setting: a teaching clinic Number of study centres: 1 Washout period: at least 2 weeks of topical antibiotics and corticosteroid, 1 month of oral antibiotics and corticosteroid, and 6 months of oral retinoid agent Registered number: ACTRN12612001006831 ITT analysis: yes | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: none Publication status: full article | |
| Stated aim for study | Quote from publication: "the present clinical trial aims to compare the efficacy and safety profile of topical adapalene 0.1% and BPO 2.5% gels in patients with mild acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "randomization was conducted using standard computer randomization software" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Low risk | Quote: "both medications were filled into identical tubes by a third party other than the investigator/evaluator. The tubes were marked as 'A' or 'B', and the coding was not disclosed only after the data were analyzed" Comment: the method of allocation concealment was specified |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote: "both medications were filled into identical tubes by a third party other than the investigator/evaluator. The tubes were marked as 'A' or 'B', and the coding was not disclosed only after the data were analyzed" Comment: treatment groups were marked during the trial, by which participants and personnel were probably unaware of treatments (the vehicle was the same for each treatment and adverse events were similar in each group) |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "both medications were filled into identical tubes by a third party other than the investigator/evaluator. The tubes were marked as 'A' or 'B', and the coding was not disclosed only after the data were analyzed" Comment: treatment groups were marked during the trial, by which outcome assessors were probably unaware of treatments (adverse events were similar in each group) |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "all the patients completed the study, with no case of discontinuation or unavailability for follow‐up" Comment: no data for outcomes were missing |
| Selective reporting (reporting bias) | Unclear risk | Comment: according to relevant information on the trial registry, the trial was retrospectively registered. Concerns were about whether outcomes reported in the article were all pre‐defined, although all outcomes listed in the methods section were reported |
| Other bias | Low risk | Quote: "the two treatment groups were well matched with respect to demography (Table 1), as well as for the number of different acne lesions on the face at baseline (Table 2)" Comment: baseline characteristics were similar between groups, and the washout period was long enough |
Bassett 1990.
| Methods | Study design: parallel design Duration of follow‐up: 3 months | |
| Participants | Total number of participants randomised: N = 124 Inclusion criteria
Exclusion criterion: pregnancy Sites of acne: face Severity of acne and corresponding criteria of judgement: "the counting technique" as described by Burke and Cunliffe Treatment before study: unclear Participants' baseline data presented as mean (SD) for all participants Sex ratio (male/female): 64/60 Age (years): mean 19.7 (range 12 to 35) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: unclear | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at months 1, 2, and 3 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: Australia Setting: unclear Number of study centres: unclear Washout period: 30 days for systemic antibiotics, corticosteroids, retinoids, anti‐convulsants, or androgens; 2 weeks for topical acne therapy Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "we have performed a single‐blind, randomised clinical trial on 124 patients to evaluate the efficacy and skin tolerance of 5% tea‐tree oil gel in the treatment of mild to moderate acne when compared with 5% benzoyl peroxide lotion" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "the patients were randomly assigned to either of two treatment groups: tea‐tree oil 5% (n = 61) and benzoyl peroxide 5% (n = 63)" Comment: methods of randomisation are unclear |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information was provided on the method of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "because of the difference in consistency and colour between the two treatments, this study was technically a single blind study (the investigator being "blind"); however, none of the patients was officially informed as to which treatment he or she had received" Comment: participants were likely to know what treatments they received |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: although insufficient information on blinding of outcome assessment was reported, blinding is difficult as risk of dryness was significantly higher in the BPO group |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: 5 of 124 participants (< 10%) withdrew for reasons unrelated to treatments; baseline characteristics were balanced in 119 participants between the 2 groups |
| Selective reporting (reporting bias) | Unclear risk | Comment: without a protocol or relevant information on a trial registry, it is unclear whether outcomes reported in the article included all pre‐defined, although all outcomes listed in the methods section were reported |
| Other bias | Low risk | Quote: "there was no significant difference between the two study groups with respect to age, sex, duration of acne condition, baseline counts of inflamed and non‐inflamed lesions, or baseline assessments of skin oiliness, scaling and dryness" Comment: participant characteristics at baseline were similar between groups, and the washout period was long enough |
Bikowski 2006.
| Methods | Study design: split‐face design Duration of follow‐up: 2 weeks | |
| Participants | Total number of participants randomised: N = 45 Inclusion criteria: patients with acne who did not have previous treatment for acne vulgaris or topical retinoid therapy for at least 4 months Exclusion criteria: unclear Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for all participants Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: unclear | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at week 2 Not enough information to determine which outcome was assessed as the primary outcome | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: conference abstract | |
| Stated aim for study | Quote from publication: "this poster reports results from a double‐blind, randomised, split‐face study assessing skin tolerability on the face in patients using BP 4% creamy wash once daily or a synthetic detergent cleanser once daily (N = 45)" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: although trial authors claimed that the trial was double‐blind, it is unclear who was blinded |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: although trial authors claimed that the trial was double‐blind, it is unclear who was blinded |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on incomplete outcome data was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | Unclear risk | Comment: insufficient information on comparability of participant characteristics at baseline between groups and length of washout period was provided |
Bissonnette 2009.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 80 Inclusion criteria: patients with mild to moderate acne (< 50 non‐inflammatory and 15 to 50 inflammatory lesions) Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: numbers of non‐inflammatory and inflammatory lesions Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): overall = 28/52 Age (years): overall = 25.7 Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: unclear | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and on days 28, 56, and 87 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: January 2006 to August 2006 Country: unclear Setting: unclear Number of study centres: 2 Washout period: 15 days for topical acne treatment, 4 weeks for systemic antibiotic treatment, 8 weeks for cyproterone acetate/ethinyl oestradiol, and 12 months for isotretinoin Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: commercial (La Roche‐Posay Laboratoire Pharmaceutique) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "to compare the efficacy and tolerance of a lipophilic derivative of salicylic acid (lipo hydroxy acid or LHA) containing formulation and 5% benzoyl peroxide in subjects with acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "randomization list was prepared manually by the sponsor" Comment: trial authors did not specify the method used to generate the random sequence |
| Allocation concealment (selection bias) | Low risk | Quote: "subjects were assigned to treatment using sealed envelopes containing the name of the study product" Comment: the method of allocation concealment used was specified |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: although no information on the method of blinding of participants and personnel was reported, blinding is difficult as the vehicles were different (gel for BPO and cream for 2‐hydroxy 5‐octanoyl benzoic acid) and desquamation and pruritus were more common in the BPO group |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "investigators who performed efficacy and tolerance evaluations were kept blinded to treatment assignment throughout the study" Comment: outcome assessors were blinded but assessors may be aware because desquamation and pruritus were more common in the BPO group |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Quote: "sixteen subjects were lost to follow‐up (eight in each group) and five subjects had an early termination visit (four in the LHA formulation group and one in the benzoyl peroxide group)" Comment: a high proportion (21/80) of participants withdrew from the trial. No information on comparisons of reasons for withdrawal between groups was available with no ITT analysis conducted |
| Selective reporting (reporting bias) | Unclear risk | Comment: without a protocol or relevant information on a trial registry, it is unclear whether outcomes reported in the article included all pre‐defined, although all outcomes listed in the methods section were reported |
| Other bias | Unclear risk | Comment: no information was provided on the comparability of baseline characteristics between groups |
Borglund 1991.
| Methods | Study design: parallel design Duration of follow‐up: 10 weeks | |
| Participants | Total number of participants randomised: N = 106 (4 participants withdrew for reasons unrelated to treatments and only data for 102 participants were reported) Inclusion criteria: male or female patients with more than 10 papules and pustules in the face Exclusion criteria: unclear Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for all participants Sex ratio (male/female): 48/54 Age (years): median 19 (range 12 to 37) Duration of acne (years): 2 months to 17 years | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: unclear | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Outcomes were assessed at weeks 2, 6, and 10 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: Sweden Setting: unclear Number of study centres: 6 Washout period: 1 month for systemic antibiotics and 2 weeks for topical acne treatments Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "in this study the three topical treatments of acne vulgaris: 1) meclocycline sulfosalicyate, 2) benzoyl peroxide, and 3) the combination of the two were compared" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "a randomized, double‐blind parallel group study was used"; "Treatment allocation was based upon block randomization" Comment: insufficient information on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "however, blinding was difficult due to differences in colour, odour, viscosity, and side effects of the drugs that could not be masked without changing their properties" Comment: complete blinding of participants and personnel is not possible |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "however, blinding was difficult due to differences in colour, odour, viscosity, and side effects of the drugs that could not be masked without changing their properties" Comment: complete blinding of outcome assessors is not possible |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: less than 10% of participants withdrew from the trial and reasons for withdrawal seem comparable |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all of the outcomes listed in the methods section were reported, we could not identify the corresponding protocol or information on a trial registry to confirm selective reporting was avoided |
| Other bias | High risk | Comment: block randomisation was conducted in this unblinded trial |
Boutli 2003.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 37 Inclusion criteria: unclear Exclusion criteria: unclear Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: unclear | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 0, 3, 6, 9, and 12 Not enough information to determine which outcome was assessed as the primary outcome | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article (we can access only the abstract) | |
| Stated aim for study | Quote from publication: "a 12‐week double‐blind randomized study was performed to compare benzoyl peroxide 5% (BP) gel and chloroxylenol 0.5% plus salicylic acid 2% (PCMX + SA) cream (Nisal cream) for efficacy and adverse reactions" | |
| Notes | Information extracted based only on abstract because the full text was not available | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "a 12‐week double‐blind randomized study was performed" Comment: insufficient information on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on incomplete outcome data was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | Unclear risk | Comment: insufficient information on comparability of participant characteristics at baseline between groups was provided |
Bowman 2005.
| Methods | Study design: parallel design Duration of follow‐up: 10 weeks | |
| Participants | Total number of participants randomised: N = 132 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Global Acne Severity score of 1.5 to 3.0 Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 19/24; B = 18/27; C = 15/29 Age (years): A = 18.6 (5.4); B = 18.8 (4.6); C = 19.3 (5.7) Duration of acne (years): A = 2.1 (0.5); B = 2.2 (0.5); C = 2.1 (0.5) | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Clinical assessments were conducted at baseline and at weeks 2, 4, 7, and 10 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: USA Setting: unclear Number of study centres: 3 Washout period: 2‐week washout for acne topical medications; 4 weeks for systemic antibiotics, systemic anti‐acne drugs, or topical retinoids; 6 weeks for laser therapy or electrodesiccation; 6 months for oral retinoids Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: commercial (Dermik Laboratories) Conflicts of interest: "Dr. Gold has received honoraria for speaking on behalf of Dermik Laboratories. Dr. Bowman and Dr. Nasir have nothing to disclose. Mr. Vamvakias is an employee of Dermik Laboratories" Publication status: full article | |
| Stated aim for study | Quote from publication: "a randomized, evaluator‐blind, multicenter study was conducted to compare the efficacy and safety of treatment regimens combining the daily use of a clindamycin/benzoyl peroxide gel, a tretinoin gel, and a clindamycin gel in acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "treatment allocation was completed by PRACS Institute, Ltd., using a computer‐generated randomization schedule" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "study medication was dispensed by an independent third‐party dispenser to nullify any differences in product packaging and was packaged as individual patient and patting dry......Patients randomized to clindamycin/benzoyl peroxide were instructed to apply the study medication once daily in the morning; those randomized to tretinoin + clindamycin were instructed to apply both products in the evening (tretinoin first, followed by clindamycin); and those randomized to clindamycin/benzoyl peroxide + tretinoin + clindamycin were instructed to apply each study drug as outlined above" Comment: despite no differences in the packaging, regimens differed across the 3 treatments. It is likely that participants and personnel could realise what the treatment was |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "this was a multicenter (3 sites), randomized, evaluator‐blind, parallel‐group study" Comment: although outcome assessors were blinded, they may have been aware because dryness, erythema, and peeling were more common in patients treated with clindamycin/BPO plus tretinoin and clindamycin |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Quote: "of 132 enrolled patients who received at least 1 dose of study drug (ITT population), 109 patients completed the study. Reasons for discontinuation included lost to follow‐up (n = 14), consent withdrawn (n = 3), noncompliance or protocol violation (n = 2), adverse event (n = 2), use of prohibited concomitant medication (n = 1), and other (n = 1). A total of 26 patients who completed the study were excluded from the efficacy population due to a failure to appear for the final assessment within the 4‐day assessment window (n = 16), use of prohibited medication (n = 6 [with 1 patient also outside of the 4‐day assessment window]), and incomplete compliance (n = 5)" Comment: more than 10% of participants discontinued treatment |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all of the outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor information on a trial registry to confirm that selective reporting was avoided |
| Other bias | High risk | Quote: "at baseline, patients in the 3 groups had similar numbers of papules, although patients in Group 2 (tretinoin + clindamycin) had significantly higher numbers of comedones compared with Groups 1 and 3 and patients in Group 1 (clindamycin/benzoyl peroxide) had significantly lower numbers of pustules compared with Groups 2 and 3. The mean Investigator's Global Acne Severity score was 2.1 to 2.2 in all groups" Comment: severity of acne was not comparable between groups |
Burke 1983.
| Methods | Study design: parallel design Duration of follow‐up: 8 weeks | |
| Participants | Total number of participants randomised: N = 94 Inclusion criteria: local students with mild or moderate acne Exclusion criteria: unclear Sites of acne: unclear Severity of acne and corresponding criteria of judgement: subjective scoring system that involved both inspection and palpation of the skin Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 22/8; B = 25/5; C = 23/6 Age (years): A = 19.0; B = 18.8; C = 18.8 Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: unclear | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 4 and 8 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "this paper reports the findings of a double‐blind clinical trial of 1.5% (w/v) erythromycin versus 5% (w/v) benzoyl peroxide" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient data on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient data on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "this study was a double‐blind comparative group assessment of three test formulae" Comment: although trial authors stated that the trial was double‐blind, blinding was difficult as the vehicles of treatments assigned were different |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "this study was a double‐blind comparative group assessment of three test formulae" Comment: although trial authors stated that the trial was double‐blind, blinding was difficult because adverse events were more common in the BPO and erythromycin groups |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "ninety‐four subjects with mild or moderate acne were recruited from the local student population, all but five of whom completed the trial" Comment: despite a low proportion of withdrawal, it is unclear about the reasons for withdrawal and whether withdrawal numbers and reasons were balanced between groups. ITT analysis was not conducted |
| Selective reporting (reporting bias) | Unclear risk | Comment: without relevant information on a trial registry or protocol, it is unclear whether outcomes reported in the article included all that were pre‐defined, although all outcomes listed in the methods section were reported |
| Other bias | Unclear risk | Comment: according to Tables 1 and 2, no significant difference in demographics and severity of acne at baseline between groups is apparent, but information on the washout period was not reported |
Capizzi 2004.
| Methods | Study design: parallel design Duration of follow‐up: 8 weeks | |
| Participants | Total number of participants randomised: N = 52 Inclusion criteria
Exclusion criteria: acne conglobata, severe acne, requiring more than topical treatment Sites of acne: mainly the face Severity of acne and corresponding criteria of judgement: mild to moderate AV according to Lehmann et al and defined as at least 10 and < 50 inflammatory lesions (ILs), at least 10 and < 100 non‐inflammatory lesions (NILs), and no more than 2 nodulo‐cystic lesions Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 9/17; B = 10/16 Age (years): A = 25 (7); B = 25 (6) Duration of acne (years): A = 2.1 (0.5); B = 2.2 (0.5) | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: adapalene gel 0.1% (Differin gel; Galderma, Italy) once daily in the evening | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Efficacy was assessed at each visit (baseline, week 4, and week 8) and tolerability was assessed at weeks 4 and 8 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: October 2002 and April 2003 Country: unclear Setting: unclear Number of study centres: unclear Washout period: at least 4 weeks washout for topical anti‐acne treatments or oral antibiotics Registered number: unclear ITT analysis: yes | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "to evaluate the tolerability and the efficacy of combination therapy with HP cream and adapalene 0.1% gel in comparison with the combination of BP 4% cream and adapalene 0.1% gel in the treatment of mild to moderate AV" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "randomization was performed using a computer‐generated randomization list (Arcus Quickstat, Cambridge, U.K.) with a block of six in a 1:1 ratio" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: trial authors did not report whether and how participants and personnel were blinded, but blinding was difficult as dryness, burning, and erythema were much more common in the BPO group |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "to assure the blinded characteristics of the trial, an investigator unaware of the treatment allocation (F.L.) performed the efficacy and tolerability evaluations" Comment: the outcome assessor was blinded but blinding was difficult as dryness, burning, and erythema were much more common in the BPO group |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "all patients completed the study" Comment: no data for outcomes were missing |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all of the outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | Low risk | Comment: Table 1 shows similarity between the 2 groups in gender, age, and acne severity and the washout period was long enough |
Cassano 2002.
| Methods | Study design: parallel design Duration of follow‐up: 16 weeks | |
| Participants | Total number of participants randomised: N = 162 Inclusion criteria: patients with mild to moderate acne vulgaris Exclusion criteria: unclear Sites of acne: unclear Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Interventions in Group D
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 8 and 16 There was not enough information to determine which outcome was assessed as the primary outcome | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: Italian Funding: unclear Conflicts of interest: unclear Publication status: full article (we can access only the abstract) | |
| Stated aim for study | Quote from publication: "we have carried out an open randomized trial to assess the efficacy and tolerability of adapalene 0.1% gel, alone or in combination with other topical anti‐acne treatments, in mild to moderate acne vulgaris" | |
| Notes | No full text; published in Italian | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "we have carried out an open randomized trial..." Comment: insufficient information on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "we have carried out an open randomized trial..." Comment: described as "open" |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "we have carried out an open randomized trial..." Comment: described as "open" |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on incomplete outcome data was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability of participant characteristics between groups was provided |
Chalker 1983.
| Methods | Study design: parallel design Duration of follow‐up: 10 weeks | |
| Participants | Total number of participants randomised: N = 177 Inclusion criteria: at least grade 3 acne severity as described by Cook et al and > 10 inflammatory lesions on the face Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Cook's grading system Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 27/21; B = 30/19; C = 33/17; D = 25/24 Age (years): ranging from 15 to 30 years Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Interventions in Group D
Co‐interventions: unclear | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 2, 4, 6, 8, and 10 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: USA Setting: medical centres Number of study centres: 2 Washout period: as specified in exclusion criteria Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "the purpose of the present study was to determine if a product containing both erythromycin and benzoyl peroxide is effective in the treatment of acne vulgaris. The study aIso compared this combination to erythromycin gel, benzoyl peroxide gel, and the vehicle" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "the subjects were randomly assigned to one of four groups" Comment: trial authors did not specify methods of randomisation used |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Quote: "both were double‐blind controlled studies" Comment: although trial authors mentioned that the trial was double‐blind, it is unclear who was blinded. The vehicle for all treatments was the same and no adverse events were reported |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: trial authors did not report whether outcome assessors were blinded. No adverse events were reported |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "seven patients voluntarily left the study and five were lost to follow‐up. The number of subjects in the four groups were comparable (see Table I)" Comment: it is unclear whether reasons for missing outcomes were similar between groups |
| Selective reporting (reporting bias) | High risk | Comments: the outcome of grading specified in the Methods section was not reported in the Results, as was the response to therapy measured by comparing acne severity to baseline severity |
| Other bias | Unclear risk | Comments: washout periods were long enough but information on the comparison of age and severity of acne between groups was not available |
Chantalat 2005.
| Methods | Study design: parallel design Duration of follow‐up: unclear | |
| Participants | Total number of participants randomised: unclear (39 completed) Inclusion criteria: patients with mild to moderate acne Exclusion criteria: unclear Sites of acne: unclear Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: unclear | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Outcomes at days 1 and 7 were reported in the abstract. It is unclear how long participants were followed up There was not enough information to determine which outcome was assessed as the primary outcome | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: conference abstract | |
| Stated aim for study | Quote from publication: "a double‐blind, randomized controlled study was conducted to evaluate the efficacy of twice daily application of the novel 2% salicylic acid acne treatment compared to twice daily application of 10% BPO treatment or untreated (control)" | |
| Notes | Conference abstract | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on incomplete outcome data was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability of participant characteristics between groups was provided |
Chantalat 2006.
| Methods | Study design: parallel design Duration of follow‐up: 6 weeks | |
| Participants | Total number of participants randomised: N = 41 Inclusion criteria: patients with mild to moderate acne. Exclusion criteria: unclear Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): overall = 12 to 30 (range) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: unclear | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 2 and 6 There was not enough information to determine which outcome was assessed as the primary outcome | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: commercial (Johnson & Johnson Consumer and Personal Products Worldwide) Conflicts of interest: not specified Publication status: conference abstract | |
| Stated aim for study | Quote from publication: "a 6‐week, double‐blind, randomized, controlled clinical study was conducted to evaluate the clinical efficacy of a formulation containing the microgel complex with 2% salicylic acid (n = 20) versus a 10% BPO cream (n = 21)" | |
| Notes | Conference abstract | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on incomplete outcome data was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | Unclear risk | Comment: insufficient information on comparability of participant characteristics at baseline between groups was provided |
Chu 1997.
| Methods | Study design: parallel design Duration of follow‐up: 10 weeks | |
| Participants | Total number of participants randomised: N = 72 Inclusion criteria
Exclusion criteria: systematic antibiotics for 4 weeks and topical antibiotics and/or acne treatments for 2 weeks before the study Sites of acne: face and forehead Severity of acne and corresponding criteria of judgement: Pillsbury classification Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): overall = 24 Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Outcomes were assessed at baseline and at weeks 2, 4, 6, 8, and 10 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: at least 4 weeks washout for oral antibiotics and 2 weeks washout for topical antibiotics and acne medications Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: commercial (Dermic Laboratories, Inc.) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "this randomized 10‐week study compared the efficacy of benzoyl peroxide 5%/erythromycin 3% gel with erythromycin 4%/zinc 1.2% solution in 72 acne vulgaris patients" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "this was an evaluator‐blinded, randomized parallel comparison study" Comment: trial authors did not specify how the random sequence was generated |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "this was an evaluator‐blinded, randomized parallel comparison study" Comment: trial authors did not specify whether participants and personnel were blinded but blinding was difficult as vehicles for the 2 treatments were different |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "this was an evaluator‐blinded, randomized parallel comparison study" Comment: outcome assessors were blinded and blinding was possible because adverse events were comparable between the 2 groups |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: trial authors did not specify how many participants were randomised to each group and how many completed the trial |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | Low risk | Quote: "statistical treatment group baseline contrasts indicated no treatment group differences in baseline scores (all P > 0.20) or lesion counts (both P > 0.05)" Comment: baseline characteristics were similar between groups and washout periods were long enough |
Coughlin 2017.
| Methods | Study design: parallel design; a pilot study Duration of follow‐up: 10 weeks | |
| Participants | Total number of participants randomised: N = 8 Inclusion criteria: children aged 7 to 10 years with acne Exclusion criteria: recent (within 1 month) oral or topical antibiotic, any acne treatment, significant immunosuppression Sites of acne: face Severity of acne and corresponding criteria of judgement: Comprehensive Acne Severity Scale (CASS) Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 2/3; B = 0/3 Age (years, range): A = 9 (7 to 10); B = 9 (7 to 10) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Outcomes were assessed at baseline and at the end of treatment *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: USA Setting: unclear Number of study centres: unclear Washout period: at least 1 month washout for treatment with an oral or topical antibiotic, any acne treatment, or significant immunosuppression Registered number: unclear ITT analysis: yes | |
| Publication details | Language of publication: English Funding: non‐commercial (American Acne and Rosacea Society) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "in this pilot study we aimed to characterize the preadolescent acne microbiome, compare the microbiome in preadolescents with and without acne, and investigate changes in the microbiome after topical treatment with benzoyl peroxide or a retinoid in a small cohort of preadolescents" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "blocks of patients were randomized and assignments were concealed until group assignment at the baseline visit" Comment: trial authors did not specify how the random sequence was generated |
| Allocation concealment (selection bias) | Low risk | Quote: "blocks of patients were randomized and assignments were concealed until group assignment at the baseline visit" Comment: allocation concealment was conducted |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: trial authors did not specify whether participants and personnel were blinded but blinding was difficult because vehicles of the 2 treatments were different |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: trial authors did not specify whether outcome assessors were blinded and treatment‐related adverse events were not reported |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Quote: "we collected post‐treatment data on three children treated with BP and two treated with tretinoin an average of 8.6 weeks (range 7‐10 weeks) after their baseline visits" Comment: outcome data were available for only 5 of the 8 participants |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | High risk | Comment: despite insufficient information on baseline characteristics between groups, block randomisation was conducted in this possibly unblinded trial |
Cunliffe 2001.
| Methods | Study design: parallel design Duration of follow‐up: 4 weeks | |
| Participants | Total number of participants randomised: N = 31 Inclusion criteria
Exclusion criteria
Sites of acne: face and trunk Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 8/5; B = 9/7 Age (years): A = 22.9 (7.6); B = 23.4 (7.5) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Outcomes were assessed at weeks 1, 2, 3, and 4 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: UK Setting: hospital Number of study centres: 1 Washout period: at least 1 year washout for oral retinoids and 1 week for other acne treatments Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "this study assessed the systemic absorption of isotretinoin and its metabolites, during a 4‐week application of a cream containing 0.1% isotretinoin and chemical sunscreens, compared with a 4% benzoyl peroxide cream, in patients with acne on the face and trunk" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: no information about randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: no information about allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: trial authors claim the study was double‐blinded, but it is unclear who was blinded. The vehicles of treatment were the same and adverse event profiles were similar between the 2 groups |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: trial authors claims the study was double‐blinded, but it is unclear who was blinded. Adverse event profiles were similar between the 2 groups |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: no information about incomplete data was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | High risk | Comment: the comparability of baseline severity of acne between groups was unclear, but according to Table 1, the amount of medication applied was not similar between groups, which may indicate that severity of acne in the 2 groups was different. The 1‐week washout period for topical acne treatment was short |
Cunliffe 2002.
| Methods | Study design: parallel design Duration of follow‐up: 16 weeks | |
| Participants | Total number of participants randomised: N = 79 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 25/9; B = 25/11 Age (years): A = 18.1 (1.8); B = 18.3 (1.7) Duration of acne (years): A = 5.4 (3.3); B = 5.6 (2.7) | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: a moisturiser if needed | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Efficacy was assessed at baseline and at weeks 4, 8, 12, and 16 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: UK Setting: unclear Number of study centres: 1 Washout period: at least 12 weeks washout for oral antibiotics, topical antibiotics, or systemic hormones; 2 weeks for topical steroids; 4 weeks for topical retinoids; and 6 weeks for oral retinoids Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: "support for the preparation of this article was provided by Dermik Laboratories" Publication status: full article | |
| Stated aim for study | Quote from publication: "the purpose of this study was to compare the anti‐microbial and clinical efficacy and tolerability of clindamycin phosphate 1%/benzoyl peroxide 5% gel formulation with matching clindamycin 1% gel in the treatment of acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method used to generate random sequence was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote: "to preserve the blinding of the study, all treatment assignments were made by a statistician who was not involved in data collection, management, or analysis. Furthermore, blinded medication was dispensed by a pharmacist and not an evaluator" |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "to preserve the blinding of the study, all treatment assignments were made by a statistician who was not involved in data collection, management, or analysis. Furthermore, blinded medication was dispensed by a pharmacist and not an evaluator" Comments: this blinding was difficult because dryness and application site reaction were more common in the BPO/clindamycin group |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "seventy of these 79 patients (50 males, 20 females; mean age, 18.2 years) had at least 1 post baseline assessment and were included in the ITT analyses (Figure 1)" Comment: despite ITT analysis being conducted, according to Figure 1, the number of withdrawals was not similar in the 2 groups and reasons for withdrawal were not clearly presented |
| Selective reporting (reporting bias) | Unclear risk | Comment: without a protocol or relevant information on a trial registry, it is difficult to confirm that all pre‐planned outcomes were reported |
| Other bias | Low risk | Quote: "demographic and baseline characteristics were similar between the 2 treatment groups (Table 1)" Comment: baseline characteristics were similar between groups and washout periods were long enough |
Del 2007.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 73 Inclusion criteria: unclear Exclusion criteria: unclear Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 15/22; B = 14/22 Age (years): 17.7 Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 2, 4, 8, and 12 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: multiple but unclear Washout period: unclear Registered number: unclear ITT analysis: yes | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "the primary study objective was to compare the efficacy and safety of BP/C gel monotherapy to 0.1% AP gel monotherapy and the combination of BP/C gel plus 0.1% AP gel for 4 weeks of treatment. The secondary objective was to compare the efficacy and safety of BP/C gel in combination with 0.1% AP gel versus that of 0.1% AP gel alone during 8 weeks of treatment" | |
| Notes | The trial randomised participants to 3 groups. We did not extract information for a group in which participants were treated with BPO/clindamycin for the first 4 weeks and then with both BPO/clindamycin and adapalene for the next 8 weeks. Comparisons between this regimen and the other 2 regimens are not the intent of this review | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information about randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: no information about allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: it seems impossible to blind participants because participants in the BPO/clindamycin plus adapalene group received treatments twice daily but participants in the adapalene group received treatment once daily |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information on blinding and occurrence of adverse events was similar between the 2 groups |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: all 109 participants randomised were analysed |
| Selective reporting (reporting bias) | Unclear risk | Comment: without a protocol or relevant information on a trial registry, it is difficult to confirm that all pre‐planned outcomes were reported |
| Other bias | Unclear risk | Comment: insufficient information on comparability of baseline characteristics between groups or on washout periods was provided |
Del 2009a.
| Methods | Study design: parallel design Duration of follow‐up: 3 weeks | |
| Participants | Total number of participants randomised: N = unclear Inclusion criteria: patients aged at least 12 years with mild to moderate facial acne Exclusion criteria: unclear Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): 12 to 46 Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: clindamycin and tretinoin gel, clindamycin: 1.2%; tretinoin: 0.025% | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 2 and 3 | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: conference abstract | |
| Stated aim for study | Quote from publication: "the focus of this investigation is to evaluate the tolerability of benzoyl peroxide microsphere (BPM) wash 5.5% in combination with a clindamycin and tretinoin gel versus a gentle cleanser and a clindamycin and tretinoin gel in acne vulgaris" | |
| Notes | There was not enough information to determine which outcome was assessed as the primary outcome | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "a multicenter, investigator‐blind, randomized study" Comment: participants were not blinded |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Quote: "a multicenter, investigator‐blind, randomized study" Comment: it is unclear whether the investigator was referred to the outcome assessor |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on numbers of and reasons for withdrawal for all groups was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability of participant characteristics between groups was provided |
Dhawan 2013.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 40 Inclusion criteria
Exclusion criteria: unclear Sites of acne: face Severity of acne and corresponding criteria of judgement: ISGA (0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe, 5 = very severe) Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 7/13; B = 11/9 Age (years): A = 22.2 (9.0); B = 22.6 (7.8) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: a gentle cleanser was used to wash participants' faces before any interventions and a retinoid cream 0.1% (tazarotene) was applied to the entire affected area of the face in the evenings | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 1, 2, 4, 8, and 12 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: October 2009 to April 2010 Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number:NCT01016977 ITT analysis: most analyses were ITT analyses | |
| Publication details | Language of publication: English Funding: commercial (Stiefel, a GSK company) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "the aim of our study was to compare the tolerability and efficacy of 2 adjunctive therapies combining CLNP 1.2%–BPO 5% (CLNP‐BPO5) (Duac Gel, Stiefel, a GSK company) or CLNP 1.2%–BPO 2.5% (CLNP‐BPO2.5) (Acanya Gel, Valeant Dermatology, a division of Valeant Pharmaceuticals North America LLC) fixed‐dose gel formulations with TZ cream 0.1% (Tazorac Cream, Allergan, Inc) when applied topically once daily for 12 weeks in participants with moderate to severe facial acne. Our study also evaluated the influence of acne on quality of life (QOL) and how changes in QOL may influence clinical severity indices used to assess the treatment of acne" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "eligible participants were randomly assigned to receive CLNP‐BPO5/TZ or CLNP‐BPO2.5/TZ formulations in a 1:1 ratio using a computer‐generated randomization schedule" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: trial authors claimed that the trial was single‐blind, but it is unclear who was blinded. The vehicles of treatments were the same and treatment‐related adverse events were similar between groups |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: trial authors claimed that the trial was single‐blind, but it is unclear who was blinded. Treatment‐related adverse events were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "of the 40 participants who were initially included in the intention‐to‐treat analysis set (20 participants in each group), 35 (87.5%) completed the study. Five participants discontinued due to withdrawal of consent or lost to follow‐up" Comment: despite ITT analysis being used, it is unclear whether the numbers of withdrawals and the corresponding reasons were balanced between groups |
| Selective reporting (reporting bias) | Unclear risk | Comment: all outcomes listed on the trial registry were reported |
| Other bias | Unclear risk | Quote: "there were no significant differences between the 2 study groups for any demographic or disease characteristics at baseline" Comment: baseline characteristics were similar between groups. Washout periods were not reported |
do Nascimento 2003.
| Methods | Study design: parallel design Duration of follow‐up: 11 weeks | |
| Participants | Total number of participants randomised: N = 178 Inclusion criteria: unclear Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 49/40; B = 40/49 Age (years): A = 17.3; B = 17.7 Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B:
Co‐interventions: not reported | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 2, 5, 8, and 11 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: October 2009 to April 2010 Country: Brazil Setting: hospital Number of study centres: 2 Washout period: 1 week washout for shampoos and cleanser agents; 6 months for oral retinoid agents; 1 month for oral acne therapy, including antibiotics and corticosteroids; 2 weeks for topical acne therapy, including antibiotics and corticosteroids Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "the aim of this study was to compare the efficacy and tolerability of a gel containing benzoyl peroxide 4%, to be used twice daily, with a gel containing adapalene 0.1%, to be used once daily, in patients with acne vulgaris, over 11 weeks" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "178 patients of both sexes, aged 13–30 years were included, and received BP 4% gel twice daily or Adapalene 0.1% once a day for 11 weeks, according to a previously generated random list" Comment: the method used to generate random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: trial authors claimed that the trial was single‐blind, but it is unclear who was blinded. However, blinding was difficult as the frequency of treatments was different |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: trial authors claimed that the trial was single‐blind, but it is unclear who was blinded. The occurrence of treatment‐related adverse events was similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Quote: "of the 178 included patients, 142 were deemed to have completed the study, and of the 36 who did not, 17 were female and 19 male. The main reason for drop‐outs was loss to follow‐up (Table I). Comparing the drop‐out rates between the groups, it was noticed that the adapalene group showed the higher rate of patients who withdrew from the study before completion of the treatment" Comment: more than 10% of participants did not complete the trial. The proportion of withdrawal was not similar between groups |
| Selective reporting (reporting bias) | Unclear risk | Comment: without a protocol or relevant information on a trial registry, it is difficult to confirm that all pre‐planned outcomes were reported |
| Other bias | High risk | Quote: "at the baseline, the number of non‐inflammatory lesions was higher in patients of the BP group when compared with those included in the adapalene group, with significance level of 5%" Comment: baseline severity of acne was not similar between groups |
Dogra 1993.
| Methods | Study design: parallel design Duration of follow‐up: 6 weeks | |
| Participants | Total number of participants randomised: N = 93 Inclusion criteria: unclear Exclusion criteria: pregnancy or hirsutism, menstrual dysfunction or adrenal dysfunction, taking drugs or contraceptives Sites of acne: face and trunk Severity of acne and corresponding criteria of judgement: spot counting of noninflammatory (NI) and inflammatory (I) acne lesions Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): overall = 37/63 Age (years): overall = 13 to 32 (range) Duration of acne (years): varying from 1 month to 7 years | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Interventions in Group D
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 2, 4, and 6 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "the present study was undertaken to study the relative efficacy of 0.05% retinoic acid cream, 2% erythromycin lotion and 10% benzoyl peroxide in comparison with glycerin in methylated spirit used as control, in the management of acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method used to generate random sequence was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: participants were likely to be aware of differences in the frequency and vehicle of assigned treatments |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information on blinding of outcome assessors was provided. Information on treatment‐related adverse events was not reported |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: although less than 10% of participants were lost to follow‐up, it is unclear whether reasons for withdrawal were comparable and ITT analysis was not reported |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, without a protocol or relevant information on a trial registry, it is difficult to judge whether selective reporting existed |
| Other bias | Unclear risk | Comment: insufficient information on baseline characteristics between groups and washout periods was provided |
Draelos 2002.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 440 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 42/47; B = 33/52; C = 38/51; D = 42/48; E = 39/48 Age (years): A = 20 (9); B = 21 (9); C = 21 (9); D = 22 (10); E = 22 (9) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Interventions in Group D
Interventions in Group E
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 2, 4, 8, and 12 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: multiple but unclear Washout period: 2 weeks washout for topical anti‐acne medication, 4 weeks for oral anti‐acne medication, 1 month for investigational drug or device Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "a multicenter, investigator‐marked, randomized, parallel‐group study was performed to evaluate whether the adjunctive use of benzoyl peroxide gel, erythromycin/benzoyl peroxide gel, or clindamycin phosphate lotion could further enhance the efficacy and tolerability of tazarotene monotherapy" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "subject medication kits containing sufficient study medication for the 12‐week duration of the study were prepared using an electronic randomization scheme" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Low risk | Quote: "two sealed and coded kits for each of the 5 study regimens were sent to each study site (a total of 10 kits per site). Each patient was assessed by the investigator and then assigned a sealed kit by the study nurse" Comment: allocation concealment was conducted through sealed and coded kits |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "the nurse checked the contents of the kit and, if the assigned treatment regimen included erythromycin/benzoyl peroxide, the nurse mixed the formulation before dispensing it to the patient" Comment: the nurse may be aware of the erythromycin/BPO treatment after randomisation |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "a multcenter, investigator‐marked, randomized, parallel‐group study was performed..."; "the investigators evaluated the patients for noninflammatory lesion count..." Comment: investigators (outcome assessors) were marked but they may be aware of treatment groups because the occurrence of treatment‐related adverse events differed by treatments |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: only 311 of 440 participants (71%) completed the whole trial; besides the high proportion of withdrawal, it is unclear whether numbers of withdrawals and corresponding reasons were balanced between groups. ITT analysis was not conducted |
| Selective reporting (reporting bias) | Unclear risk | Comment: without a protocol or relevant information on a trial registry, it is difficult to confirm that all pre‐planned outcomes were reported |
| Other bias | High risk | Quote: "generally, baseline demographics were comparable among treatment groups, though the evaluation of facial acne vulgaris was significantly lower in the clindamycin monotherapy group than in all of the other groups, and the comedo count was significantly lower in the clindamycin group than in the tazarotene monotherapy and tazarotene plus clindamycin groups" Comment: despite the similarity of demographics among groups, baseline severity of acne was not comparable |
Draelos 2010.
| Methods | Study design: parallel design Duration of follow‐up: 4 weeks | |
| Participants | Total number of participants randomised: N = 61 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: investigator static global assessment score ≥ 2 (grade 0 = normal, clear skin; grade 5 = highly inflammatory lesions predominant) Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 12/18; B = 11/20 Age (years): A = 17.9 (5.0); B = 19.2 (5.3) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: soap‐free cleanser and clindamycin phosphate 1.2%/tretinoin 0.025% gel in the evening daily | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 1, 2, and 4 *These outcomes were assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: USA Setting: dermatology clinics Number of study centres: 5 Washout period: 4 weeks washout for any investigational product; 2 weeks for topical acne agents; 4 weeks for systemic agents (6 months for systematic retinoids); 4 weeks for facial procedure (peel, dermabrasion, or UV light therapy) Registered number:NCT00891982 ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial (Stiefel, a GSK company) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "the current trial was designed to evaluate the local tolerability, irritation potential, and safety of CT gel in a solubilized aqueous‐based gel formulation (Veltin™) when used in conjunction with BPO wash 4% in a hydrophase base formulation (Brevoxyl®‐4) in participants with mild to moderate acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "participants were randomized (1:1 ratio) using a computer‐generated random assignment schedule from the study sponsor to treatment with either BPO wash 4% or nonmedicated soap‐free cleaner lotion (SFC) (Impruv) once daily in the morning" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: study authors did not specify the method of allocation concealment |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "investigators were blinded to treatment assignment but participants, study nurse, and co‐ordinators were not" Comment: neither participants nor personnel were blinded |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "investigators were blinded to treatment assignment but participants, study nurse, and co‐ordinators were not" Comment: investigators (outcome assessors) were blinded, and the occurrence of treatment‐related adverse events was similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "of the 61 participants who were enrolled (30 participants in the CT gel BPO wash group; 31 participants in the CT gel SFC group) and comprised the intention‐to‐treat population, 58 participants completed the study (28 [93%] and 30 [97%], respectively)" Comment: A low proportion of withdrawals from each group was reported and ITT analysis was conducted |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes listed on the trial registry and in the methods section were reported |
| Other bias | Low risk | Quote: "demographic characteristics were similar in both treatment groups at baseline (Table 2) and exposure to the study products was comparable between the groups throughout the study" Comment: baseline characteristics were similar between groups and washout periods were long enough |
Dreno 2011.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 378 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Investigator Global Assessment (IGA; score of 3 or 4 on a scale from 0 to 5) Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 100/91; B = 109/78 Age (years): A = 18.6 (4.7); B = 19.1 (4.6) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: oral lymecycline 300 mg; gentle skin cleanser used before study medication was applied; moisturising lotion in the morning for symptomatic relief of skin dryness and irritation; sun protection factor (SPF) 50 sunscreen | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 2, 4, 8, and 12 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: January 2009 to December 2009 Country: France, Italy, Belgium, Sweden, Germany, Poland, Mexico, Brazil, and Australia Setting: unclear Number of study centres: 32 Washout period: unclear Registered number: 2008‐006792‐68 (EudraCT number) andNCT01014689 ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial Conflicts of interest: "all investigators received fees for conducting this study. N.K. and F.P. are current employees of Galderma R&D" Publication status: full article | |
| Stated aim for study | Quote from publication: "to evaluate the efficacy and safety of oral lymecycline 300 mg with adapalene 0.1%–BPO 2.5% (A/BPO) fixed‐dose gel in comparison with oral lymecycline 300 mg with a vehicle gel in subjects with moderate to severe acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "subjects were randomized in a 1:1 ratio by a designated statistician (using a computed randomization list that generated treatment numbers in a block size of four) to receive either oral lymecycline with A ⁄BPO gel (Epiduo; Galderma SA, Lausanne, Switzerland) or lymecycline (Tetralysal; Galderma) with a vehicle gel" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Low risk | Quote: "the randomization list and the electronic file were secured in a locked cabinet and in an electronic file with restricted access to only the designated personnel directly responsible for labelling and handling the study medications, until the study database was locked and ready to be unblinded for statistical analyses. The investigators could not access the randomization list" Comment: allocation concealment was likely concealed via this method |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Quote: "integrity of the blinding was ensured by packaging the topical medication in identical tubes and requiring a third party other than the investigator/evaluator to dispense the medications" Comment: it is unclear whether participants were blinded. The vehicles of the 2 treatments were the same and the occurrence of treatment‐related adverse events was similar between groups |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Comment: outcome assessors (i.e. investigators/evaluators) were blinded. The occurrence of treatment‐related adverse events was similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "overall, 93.2% of subjects completed the study. The early discontinuation rate was low (6.8%) and similar between the two groups. The main reasons for study discontinuation in both groups were ‘subject’s request’ and ‘lost to follow‐up’. Only three subjects (1.6%) in the lymecycline with A/BPO group discontinued due to an AE"; "The primary endpoint was median percentage change from baseline in total lesion counts at week 12 in the intent‐to‐treat (ITT) population composed of all enrolled and randomized subjects. The last‐observation‐carried‐forward method was used to impute efficacy missing values" Comment: the proportion of withdrawal was low in each group. Numbers of and reasons for withdrawal were similar between groups. ITT analysis was conducted |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes listed on the trial registry and in the methods section were reported |
| Other bias | Unclear risk | Quote: "demographics were similar between the two groups in terms of age, sex and ethnicity"; "Overall, the two groups had comparable IGA severity scores and similarly high numbers of inflammatory, noninflammatory and total lesions at baseline" Comment: baseline characteristics were similar between groups. Information on washout periods was not reported |
Dreno 2016.
| Methods | Study design: split‐face design Duration of follow‐up: 24 weeks | |
| Participants | Total number of participants randomised: N = 38 Inclusion criteria
Exclusion criteria: unspecified Sites of acne: face Severity of acne and corresponding criteria of judgement: unspecified Treatment before study: unclear Participants' baseline data presented as mean (SD) for all participants Sex ratio (male/female): 24/14 Age (years): 23.4 (3.6) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: unspecified | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 4, 8, 12, 16, 20, and 24 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: August 2012 to September 2013 Country: France and Canada Setting: unclear Number of study centres: 3 Washout period: unclear Registered number:NCT01688531 ITT analysis: no | |
| Publication details | Language of publication: English Funding: commercial (Galderma R&D) Conflicts of interest: "JT, BD and RB have received honoraria and grants and served as advisors, clinical trialists, consultants and speakers for Galderma R&D. MR and PM are employees of Galderma R&D" Publication status: full article | |
| Stated aim for study | Quote: "this study had two objectives, to determine the effect of topical treatment with A/BPO compared to its vehicle on acne scarring (the focus of the current communication), and to investigate acne lesion filiation on the half‐face treated with vehicle only (the focus of another manuscript in preparation)" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "prior to the start of the study, the randomization list was generated by a statistician" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Low risk | Quote: "investigators did not have access to the randomization list, and study treatments were dispensed by a designated study drug dispenser" Comment: allocation concealment was probably conducted |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: the trial was single‐blinded and only investigators were blinded |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: the trial was single‐blinded and only investigators were blinded; treatment‐related adverse events were more common on the face treated with BPO/adapalene |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: 33 of 38 participants completed the trial |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes specified on the trial registry were reported |
| Other bias | Unclear risk | Comment: the split‐face trial ensured that baseline characteristics were comparable within individuals. Information on washout periods was not reported |
Dréno 2018.
| Methods | Study design: split‐face, investigator‐blind design Duration of follow‐up: 24 weeks | |
| Participants | Total number of participants randomised: N = 67 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Investigator Global Assessment Treatment before study: unclear Participants' baseline data presented as mean (SD) for all participants Sex ratio (male/female): 23/44 Age (years): 21.5 (4.2) Duration of acne (years): 6.8 (4.2) | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: foam wash and moisturiser | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 1, 4, 8, 12, 16, 20, and 24 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: August 2012 to September 2013 Country: France and Canada Setting: unclear Number of study centres: 5 Washout period: 2 weeks for topical corticosteroids, antibiotics, BPO, azelaic acid, hydroxy acids, and other anti‐inflammatory drugs; 4 weeks for topical retinoids; 1 month for oral corticosteroids or antibiotics; 3 months for spironolactone/drospirenone or immunomodulators; 6 months for oral retinoids or cyproterone acetate/chlormadinone acetate Registered number:NCT02735421 ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial (Galderma R&D/Nestle Skin Health) Conflicts of interest: investigators (JT, RB, AGH, BB, CL, BD) received financial support for conducting the study. NK is an employee of Galderma R&D Publication status: full article | |
| Stated aim for study | Quote: "the objective of this study was to evaluate whether using a higher concentration of retinoid in A0.3/BPO2.5 would also demonstrate efficacy in atrophic acne scars, specifically in subjects with moderate and severe acne" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "prior to the start of the study, the randomization list was generated by a statistician" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: no information about the methods used for allocation concealment was available |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: the trial was single‐blinded and only investigators were blinded; treatment‐related adverse events were more common at the BPO/adapalene site |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: the trial was single‐blinded and only investigators were blinded; treatment‐related adverse events were more common at the BPO/adapalene site |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Quote: "in total, 54 (80.6%) of the 67 subjects randomized completed the study" Comment: more than 10% of participants did not complete the trial |
| Selective reporting (reporting bias) | Unclear risk | Comment: not all outcomes reported in the publication were specified on the trial registry |
| Other bias | Low risk | Comment: the split‐face trial ensured that baseline characteristics were comparable within individuals and washout periods were long enough |
Dubey 2016.
| Methods | Study design: parallel, open‐label design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 100 Inclusion criteria
Exclusion criteria
Sites of acne: face, chest, and back Severity of acne and corresponding criteria of judgement: simple grading system (4 grades) Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): overall = 38/55 Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: not specified | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 4, 8, and 12 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: November 2012 to April 2014 Country: India Setting: hospital Number of study centres: 1 Washout period: 1 month for any other drugs for acne treatment Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: none Conflicts of interest: none Publication status: full article | |
| Stated aim for study | Quote from publication: "the main objective of the present study was to assess the efficacy and safety of adapalene in comparison to benzoyl peroxide‐clindamycin combination for the treatment of mild to moderate acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "a prospective and randomized study was conducted ...... It was an observational, comparative and open‐label study...... "; "A total of 100 patients who attended dermatology OPD for acne treatment were selected and randomly divided into two groups" Comment: trial authors stated that the study was an RCT but on the other hand it was referred to as an observational study |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "it was an observational, comparative and open‐label study in which male and female patients in the age group of 12 to 30 years were enrolled" Comment: trial authors specified that the study was open‐label |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "it was an observational, comparative and open‐label study in which male and female patients in the age group of 12 to 30 years were enrolled" Comment: trial authors specified that the study was open‐label |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "a total of 100 patients were enrolled in this study, out of which 47 patients completed the treatment in group A whereas 46 completed it in group B, during the study period" Comment: it is unclear whether reasons for discontinuation were similar between the 2 groups and ITT analysis was not performed |
| Selective reporting (reporting bias) | High risk | Comment: safety outcomes specified in the Methods section were not fully reported in the Results section |
| Other bias | Unclear risk | Comment: insufficient information was available regarding the similarity in baseline characteristics between groups |
Dudhia 2015.
| Methods | Study design: parallel design Duration of follow‐up: 1 month | |
| Participants | Total number of participants randomised: N = 30 Inclusion criteria: patients aged 15 to 30 years with diagnosis of mild to moderate acne Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Grade 1 (mild): comedones, occasional papules; Grade 2 (moderate): papules, comedones, few pustules; Grade 3 (severe): predominant pustules, nodules, and abscesses; Grade 4 (very severe): mainly cysts, abscesses, widespread scarring Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 9/6; B = 11/4 Age (years): 20.9 (3.14) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at month 1 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: India Setting: hospital Number of study centres: 1 Washout period: unclear Registered number: unclear ITT analysis: yes | |
| Publication details | Language of publication: English Funding: none Conflicts of interest: none Publication status: full article | |
| Stated aim for study | Quote from publication: "the aim of this study was to compare the efficacy and safety of clindamycin gel + benzoyl peroxide gel and clindamycin gel + adapalene gel in the treatment of mild to moderate acne" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "all the included patients were randomly divided into two groups, A and B, using a computer‐generated random number table" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: this trial is an open‐label study |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: this trial is an open‐label study |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: all eligible participants were followed up at the end of the trial |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, without a protocol or relevant information on a trial registry, it is difficult to judge whether selective reporting existed |
| Other bias | Unclear risk | Comment: according to Table 1, demographic parameters and baseline grading of acne were comparable between groups. Washout periods were not reported |
Dunlap 1997.
| Methods | Study design: parallel design Duration of follow‐up: 8 weeks | |
| Participants | Total number of participants randomised: N = 150 Inclusion criteria: male and female participants with acne vulgaris (Grade II or III, Pillsbury classification) Exclusion criteria: unclear Sites of acne: face Severity of acne and corresponding criteria of judgement: Pillsbury classification Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): overall = 13 to 30 (range) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 2, 4, and 8 There was not enough information to determine which outcome was assessed as the primary outcome | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: conference abstract | |
| Stated aim for study | Quote from publication: not available | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on numbers and reasons for withdrawal for each group was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability of participant characteristics between groups was provided |
Dunlop 1995.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 70 Inclusion criteria
Exclusion criteria: female participants who commenced or ceased the oral contraceptive pill in the 6 months before the trial Sites of acne: face Severity of acne and corresponding criteria of judgement: Burke and Cunliffe criteria Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): overall = 44/26 Age (years): overall = 18.6 (range 13 to 35) Duration of acne (year): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 2, 4, 8, and 12 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear but trial authors acknowledge support from McFarlane Marketing (Aust.) Pty Ltd. Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "the aim of this study was thus to compare the efficacy and skin tolerance of topical isolutrol with 5% benzoyl peroxide in the treatment of mild to moderate acne" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "the patients were randomized into two treatment arms: 5% benzoyl peroxide (n = 35) and isolutrol (n = 35)" Comment: trial authors did not specify the method used to generate the random sequence |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient related information was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "the trial was designed as a double‐blind study and patients were instructed not to describe to the investigator any characteristics of the product such as colour, smell or consistency" Comment: trial authors stated that the trial was double‐blind, but it seems that participants could tell the differences between products |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "the trial was designed as a double‐blind study and patients were instructed not to describe to the investigator any characteristics of the product such as colour, smell or consistency" Comment: insufficient information was provided on whether the outcome assessor was blinded but the assessor may be aware of treatments given because treatment‐related adverse events were more common in the BPO group |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on incomplete outcome data was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: without a protocol or relevant information on a trial registry, it is difficult to confirm that all pre‐planned outcomes were reported |
| Other bias | Unclear risk | Quote: "there was no significant difference between the two study groups with respect to age, sex, duration of acne or baseline assessment of facial erythema, pruritus, burning and stinging, dryness and scaling" Comment: baseline characteristics were similar between groups but no information on washout periods was reported |
Eady 1996.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 44 Inclusion criteria: mild to moderate acne vulgaris and ≥ 10 inflamed lesions Exclusion criteria: receiving any oral or topical anti‐acne therapy in the 4 weeks before the study Sites of acne: face Severity of acne and corresponding criteria of judgement: grade 0.3 to 2.5 on the scale of Burke and Cunliffe Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 13/7; B = 7/10 Age (years): A = 22 (range 14 to 54); B = 19.9 (range 12 to 34) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 6 and 12 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: 12 weeks Country: unclear Setting: unclear Number of study centres: unclear Washout period: 4‐week washout for any oral or topical anti‐acne therapy Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: commercial (Dermik Laboratories) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "the purpose of the present study was to examine the ability of the same therapeutic combination to prevent the emergence of erythromycin‐resistant propionibacteria and to inhibit (he growth of pre‐existing resistant strains during a standard 12‐week course of therapy" | |
| Notes | Only information from the first study was extracted because the second study reported in this article was not an RCT | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "patients were randomly allocated to treatment with either 3% w/w erythromycin alone or 3% w/w erythromycin plus 5% w/w benzoyl peroxide (Benzamycin") in a gel base" Comment: trial authors did not specify the method used to generate the random sequence |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: although trial authors claimed that the trial was double‐blinded, there is no information about who was blinded. The vehicles and frequency of treatments were the same and no information on treatment‐related adverse events was reported |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: although trial authors claimed that the trial was double‐blinded, there is no information on who was blinded. No information on treatment‐related adverse events was reported |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Quote: "initial bacteriology results showed that seven patients (five in the group receiving erythromycin alone and two in the group receiving the combination) had low propionibacterlal counts pretreatment (<103 c,f.u./cm2). These patients were excluded from the data analysis" Comment: the exclusion of different numbers of participants for different groups may lead to bias |
| Selective reporting (reporting bias) | Unclear risk | Comment: a protocol or relevant information on a trial registry is not available to confirm no selective reporting |
| Other bias | Unclear risk | Comment: no information on baseline comparability of participant characteristics between groups was provided |
Ede 1973.
| Methods | Study design: parallel design Duration of follow‐up: 4 weeks | |
| Participants | Total number of participants randomised: N = 96 Inclusion criteria: patients with Grade II or III acne Exclusion criteria: unclear Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | .Interventions in Group A
Interventions in Group B
Co‐interventions: unclear | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 2 and 4 There was not enough information to determine which outcome was assessed as the primary outcome | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article (we can access only the abstract) | |
| Stated aim for study | Quote from publication: not available | |
| Notes | No full text available; only information from the 2 relevant groups was extracted | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on numbers of and reasons for withdrawal for each group was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability of participant characteristics between groups was provided |
Eichenfield 2011.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 1315 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Investigator's Static Global Assessment Treatment before study: unclear Participants' baseline data presented as mean for each group Sex ratio (male/female): A = 125/202; B = 148/180; C = 125/203; D = 122/210 Age (years): A = 20.0 (7.0); B = 20.2 (6.9); C = 20.6 (7.1); D = 20.7 (7.4) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Interventions in Group D
Co‐interventions: use of a mild non‐anti‐microbial soap or a soap‐free cleanser to wash the whole face before applying the intervention | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 2, 4, 8, and 12 or at early termination *These outcomes were assessed as the primary outcome in the trial | |
| Study details | Study period: September 2008 to March 2009 Country: USA, Canada, Belize Setting: unclear Number of study centres: 24 Washout period: unclear Registered number:NCT00776919 ITT analysis: most analyses were ITT analyses | |
| Publication details | Language of publication: English Funding: commercial (Stiefel, GSK) Conflicts of interest: "Dr. Eichefield served as a study investigator without compensation and has been a prior consultant to Stiefel. He has also served as an investigator and consultant for Coria/Valeant, Galderma and Johnson & Johnson, Dr. Alio is an employee of Stiefel and medical monitor of this study" Publication status: full article | |
| Stated aim for study | Quote from publication: "to demonstrate that the combination of 1.2% CLNP with lower strength BPO (CLNP 1.2%‐BPO 3%) in a gel formulation if superior to each individual ingredient, CLNP 1.2% and BPO 3%, and vehicle gel" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: trial authors did not specify the method used to generate the random sequence |
| Allocation concealment (selection bias) | Unclear risk | Comment: no information on allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: trial authors claimed that the trial was double‐blinded; there is no information on who was blinded. The vehicles and frequency of treatments were the same and the occurrence of treatment‐related adverse events was similar between groups |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: trial authors claimed that the trial was double‐blinded; there is no information on who was blinded. The occurrence of treatment‐related adverse events was similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: although 27 to 39 participants withdrew from each group, numbers of and reasons for withdrawal were similar between groups and ITT analysis was conducted |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes pre‐planned on the trial registry were reported |
| Other bias | Unclear risk | Comment: Table 1 shows that baseline characteristics were comparable between groups. No information on washout periods was provided |
Eichenfield 2013.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 285 Inclusion criteria
Exclusion criteria
Sites of acne: face and trunk Severity of acne and corresponding criteria of judgement: Investigator Global Assessment (IGA) scale Treatment before study: unclear Participants' baseline data presented as mean for each group Sex ratio (male/female): A = 33/109; B = 35/108 Age (years): A = 10.3 (0.76); B = 10.4 (0.68) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: using a moisturiser | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 1, 2, 4, 8, and 12 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: June 2010 to August 2011 Country: USA and Canada Setting: unclear Number of study centres: 25 Washout period: unclear Registered number:NCT01138735 ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial (Galderma R&D) Conflicts of interest: "the sponsor participated in the study design, collection, analysis, and interpretation of data, writing of the first draft of the manuscript, and the decision to submit the manuscript for publication. Galdariel Bonne, an employee of the sponsor, wrote the first draft of this manuscript. Dr. Eichenfield is an investigator and has served as an advisor, consultant, and speaker for Galderma. Dr. Draelos is an investigator for Galderma. Dr. Lucky is a consultant and investigator for Galderma. Dr. Sugarman is a consultant and investigator for Galderma. Dr. Stein Gold has served as an advisor (advisory board), speaker, and investigator for Galderma. Ms. Rudisill is an employee of Galderma. Ms. Liu is an employee of Galderma. Dr. Manna is an employee of Galderma" Publication status: full article | |
| Stated aim for study | Quote from publication: "evaluate the efficacy and safety of adapalene 0.1%‐benzoyl peroxide 2.5% (adapalene‐BPO) in patients 9‐11 years old with acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: trial authors did not specify the method used to generate the random sequence |
| Allocation concealment (selection bias) | Unclear risk | Comment: no information on allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: although trial authors claimed the trial was double‐blind, there is no information on who was blinded. However, blinding was difficult as treatment‐related adverse events were more common in the BPO/adapalene group |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: although trial authors claimed the trial was double‐blind, there is no information on who was blinded. However, blinding was difficult as treatment‐related adverse events were more common in the BPO/adapalene group |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: according to Figure 1, the numbers of participants who withdrew and the corresponding reasons were not comparable between groups |
| Selective reporting (reporting bias) | Low risk | Comment: without relevant information on a trial registry or a protocol, we cannot confirm there was no selective reporting bias |
| Other bias | High risk | Quote: "there was a higher total lesion count for vehicle than adapalene‐BPO (56.4 vs 50.5, respectively, P = .015)" Comment: baseline severity of acne was not comparable between groups |
Fan 1998.
| Methods | Study design: parallel design Duration of follow‐up: 4 weeks | |
| Participants | Total number of participants randomised: N = 110 Inclusion criteria: those with papulae and comedos Exclusion criteria: unclear Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean for each group Sex ratio (male/female): overall = 40/70 Age (years): overall = 17 to 41 (range) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: using a special anti‐acne mask once or twice per week | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 2 and 4 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: China Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: Chinese Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: not specified | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on numbers and reasons for withdrawal for each group was provided |
| Selective reporting (reporting bias) | High risk | Comment: investigator‐assessed global acne improvement was mentioned in the methods section but the result was not reported |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability of participant characteristics between groups and on washout periods |
Fang 2002.
| Methods | Study design: randomised, open, and parallel comparison trial Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 150 Inclusion criteria: mild to moderate acne vulgaris Exclusion criteria: unclear Sites of acne: unclear Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐intervention: not reported | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 8 and 12 There was not enough information to determine which outcome was assessed as the primary outcome | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: 3 Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language: English Funding: unclear Conflicts of interest: not specified Publication status: conference abstract | |
| Stated aim for study | Quote from publication: "to assess the safety and efficacy of the combination therapy of benzoyl peroxide gel 5% plus adapalene gel 0.1% in patients with mild to moderate acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "randomized, open and parallel comparison trial" Comment: not blinded |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "randomized, open and parallel comparison trial" Comment: not blinded |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on numbers of and reasons for withdrawal for each group was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability of participant characteristics between groups and on washout periods was provided |
Fleischer 2010.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 301 Inclusion criteria
Exclusion criteria
Sites of acne: above the mandibular line Severity of acne and corresponding criteria of judgement: Global Acne Assessment Score (GAAS) Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 52/51; B = 48/52; C = 47/51 Age (years): A = 18; B = 20; C = 18 Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐intervention: dapsone 5% gel twice daily | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 2, 4, 8, and 12 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: February 2005 to July 2005 Country: USA Setting: unclear Number of study centres: 22 Washout period: 2 weeks washout for topical drugs or treatments (retinoids, antibiotics, and anti‐inflammatory agents); 4 weeks for systemic immunosuppressive drugs or systemic medications or therapy known to affect acne or inflammatory response; 3 months for isotretinoin Registered number:NCT00151541 ITT analysis: yes | |
| Publication details | Language: English Funding: commercial (QLT USA, Inc., Fort Collins, Colorado) Conflicts of interest: all trial authors declared that they were consultants or advisors for pharmaceutical companies supporting BPO‐related trials Publication status: full article | |
| Stated aim for study | Quote from publication: "to evaluate the safety and efficacy of dapsone gel 5% in the treatment of acne when used in combination with adapalene gel 0.1%, benzoyl peroxide gel 4% or moisturizer" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "all eligible patients applied dapsone gel and were also randomly assigned in a 1:1:1 ratio, according to a computer‐generated randomization table, to one of three additional treatment groups: adapalene gel, benzoyl peroxide gel or moisturizer" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Quote: "all eligible patients applied dapsone gel and were also randomly assigned in a 1:1:1 ratio, according to a computer‐generated randomization table, to one of three additional treatment groups: adapalene gel, benzoyl peroxide gel or moisturizer" Comment: information about the allocation concealment process is unclear |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "the investigators, patients and sponsor personnel were blinded to the treatment assignment. To maintain blinding, personnel who were not involved in efficacy or safety assessments conducted the drug accountability and test‐article‐weight assessments" Comment: blinding was undertaken but blinding was difficult as treatment‐related adverse events were more common in adapalene and BPO groups |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "the investigators, patients and sponsor personnel were blinded to the treatment assignment. To maintain blinding, personnel who were not involved in efficacy or safety assessments conducted the drug accountability and test‐article‐weight assessments" Comment: blinding was undertaken but blinding was difficult as treatment‐related adverse events were more common in adapalene and BPO groups |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "efficacy results are presented for the intent‐to‐treat (ITT) population and were summarized for each treatment group at weeks 2, 4, 8 and 12. Missing values for the ITT data set were analyzed with a last‐observation‐carried forward method" Comment: this study used ITT strategy for data analysis. It is unclear how many participants were randomised originally |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes planned on the trial registry were reported |
| Other bias | Low risk | Quote: "at baseline, all three treatment groups were balanced with respect to demographics (i.e. age, race and sex), inflammatory and total acne lesion counts and GAAS (Table 1)" Comment: baseline characteristics were similar between groups and washout periods were long enough |
Fu 2003.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 150 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: classified as grade of I, Ⅱ, or Ⅲ Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 49/26; B = 55/19 Age (years): A = 22.2 (5.04); B = 21.3 (4.46) Duration of acne (years): A = 4.2 (4.00); B = 3.6 (2.66) | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 8 and 12 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: March to September 2001 Country: China Setting: unclear Number of study centres: multiple Washout period: 1 day washout for topical alpha‐hydroxy acid or alcohol medication; 2 weeks for a topical retinoid, antibiotic, steroid, topical, or oral anti‐inflammatory medication; 4 weeks for oral antibiotic or steroid; 30 days for any other intervention that may influence effects in this trial Registered number: unclear ITT analysis: no (but only 1 participant was excluded) | |
| Publication details | Language of publication: Chinese Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "to assess the clinical efficacy and safety of the combination therapy of 5% benzoyl peroxide (BPO) gel with 0.1% adapalene gel in patients with mild to moderate acne vulgaris" | |
| Notes | *It is unclear from which group one participant was excluded after randomisation. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "a random number table with 1:1 allocation ratio was generated by a statistician before the trial" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: information on allocation concealment was unavailable |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: information on blinding was unavailable but blinding was difficult as the frequency of the 2 treatments was different |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: information on blinding and treatment‐related adverse events was unavailable |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: only 1 participant was lost to follow‐up |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | High risk | Quote: "there was significant difference in the severity of acne" Comment: baseline characteristics were not similar between groups |
Fyrand 1986.
| Methods | Study design: split‐face design Duration of follow‐up: 8 weeks | |
| Participants | Total number of participants randomised: N = 49 Inclusion criteria: symmetrically distributed acne vulgaris in the face Exclusion criteria: allergy to 1 or more ingredients of tested drugs Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for all participants Sex ratio (male/female): 17/32 Age (years): median 24 (range 14 to 44) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 1, 2, 4, and 8 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: at least 3 weeks washout for any acne treatment Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "the aim of the present study was to evaluate the role of the alcohol‐based vehicle, comparing two different benzoyl peroxide preparations" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information for judgement was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information for judgement was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: although trial authors claimed that the trial was double‐blind, it is unclear who was blinded. However, blinding was difficult because the vehicles of treatments were different |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: although trial authors claimed that the trial was double‐blind, it is unclear who was blinded |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: 6 of 49 participants were lost to follow‐up and ITT analysis was not conducted |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, without a protocol or relevant information on a trial registry it is difficult to determine the presence of selective reporting |
| Other bias | High risk | Comment: baseline characteristics were controlled within participants in the split‐face design. The washout period for systemic acne treatment was not long enough |
Gold 2009.
| Methods | Study design: multi‐centre, randomised, double‐blind, parallel‐group study Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 1668 Inclusion criteria
Exclusion criteria: acne conglobata, acne fulminans, secondary acne, severe acne requiring systemic treatment Sites of acne: face and trunk Severity of acne and corresponding criteria of judgement: Investigator Global Assessment (IGA) scale Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 205/210; B = 203/217; C = 208/207; D = 196/222 Age (years): A = 18.7; B = 17.9; C = 18.4; D = 18.0 Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Interventions in Group D
Co‐intervention: not reported | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at screening, at baseline, and at weeks 1, 2, 4, 8, and 12 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: USA, Puerto Rico, Canada Setting: unclear Number of study centres: 60 Washout period: unclear Registered number:NCT00422240 ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial (Galderma R&D Inc) Conflicts of interest: "LP. Dr. Tan is an advisory board member and speaker and has received research grants from Galderma Laboratories, LP. Drs. Cruz‐Santana and Papp report no conflict of interest. Dr. Poulin has received research grants from GaldermaLaboratories, LP. Dr. Schlessinger is an advisory board member for Galderma Laboratories, LP. Mrs. Gidner and Drs. Liu and Graeber are employees of Galderma Laboratories, LP" Publication status: full text | |
| Stated aim for study | Quote from publication: "to assess the efficacy and safety of a unique, once‐daily, fixed‐dose combination gel containing adapalene 0.1% and benzoyl peroxide (BPO) 2.5% in comparison to the monads (adapalene gel and BPO gel) and the vehicle in patients with acne vulgaris for up to 12 weeks" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "participants were randomized in a 1:1:1:1 ratio to adapalene‐BPO combination gel, adapalene gel monotherapy, BPO gel monotherapy, or gel vehicle" Comment: the method used to generate the random sequence was not specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: described as "double‐blind", but it is unclear who was blinded. However, blinding was difficult because treatment‐related adverse events were more common in the BPO/adapalene and adapalene groups |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: described as "double‐blind", but it is unclear who was blinded. However, blinding was difficult because treatment‐related adverse events were more common in the BPO/adapalene and adapalene groups |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Quote: "the primary end point efficacy analyses were evaluated at week 12 using the intention‐to‐treat (ITT) population and the last observation carried forward (LOCF) imputation for missing data points... Among the 1668 enrolled participants, 1429 (85.7%) completed the study and 239 (14.3%) discontinued early, with only 22 (1.3%) discontinuing because of AEs. Although the rates for discontinuation due to AEs were higher in the adapalene‐BPO combination gel group (2.7%) compared with the other groups (adapalene, BPO, and vehicle), they were low for all of the treatment groups (1.0%, 1.2%, and 0.5% of participants, respectively)" Comment: although ITT strategy was taken, 14.3% of participants discontinued and withdrawal due to adverse events was higher in the adapalene‐BPO combination gel group |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes planned on the trial registry were reported |
| Other bias | Unclear risk | Quote: "the baseline characteristics of the ITT population are summarized in the Table. Participant disposition was similar between groups" Comment: baseline characteristics were similar between groups. No information on the washout period was reported |
Gold 2010.
| Methods | Study design: randomised, controlled, multi‐centre, double‐blinded, parallel trial Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 459 Inclusion criteria
Exclusion criteria
Sites of acne: unclear Severity of acne and corresponding criteria of judgement: Investigator Global Assessment (IGA) scale Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 124/108; B = 130/97 Age (years): A = 18.6 (5.84); B = 18.1 (4.92) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐intervention: doxycycline hyclate 100 mg once daily; daily use of facial moisturiser with sun protection factor 15 and gentle skin cleanser was encouraged | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 2, 4, 8, and 12 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: USA and Canada Setting: unclear Number of study centres: 35 (30 in the United States and 5 in Canada) Washout period: unclear Registered number:NCT00688064 ITT analysis: yes | |
| Publication details | Language: English Funding: commercial (Galderma R&D.) Conflicts of interest: "LP. Dr. Cruz reports no additional conflicts of interest. Dr. Eichenfield is on the advisory board for and has received grants from Galderma Laboratories, LP. Dr. Tan is an advisory board member and speaker for and has received research grants from Galderma R&D. Dr. Jorizzo is a speaker for and has received honoraria from Dermik Laboratories and Graceway Pharmaceuticals, LLC. Mr. Kerrouche and Mr. Dhuin are employees of Galderma R&D and hold a patent related to the study medication" Publication status: full article | |
| Stated aim for study | Quote from publication: "to evaluate the efficacy and safety of adapalene 0.1%/benzoyl peroxide 2.5% gel with doxycycline hyclate 100 mg tablets, QD compared to vehicle gel with doxycycline hyclate 100 mg tablets, QD in patients with severe acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "participants were randomized in a 1:1 ratio to receive oral doxycycline hyclate 100 mg once daily in the morning and either A/BPO or vehicle once daily in the evening for 12 weeks" Comment: trial authors did not report methods used to generate the random sequence |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: trial authors described the trial as "double‐blind", but it is unclear who was blinded. The vehicles and frequency of treatments were the same and treatment‐related adverse events were similar between groups |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: trial authors described the trial as "double‐blind", but it is unclear who was blinded. Treatment‐related adverse events were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "overall, 89.8% of participants completed the study and participant disposition was similar between the 2 groups" Comment: ITT strategy was taken. Although 10.2% of participants discontinued, numbers of and reasons for withdrawal were similar between groups |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes planned on the trial registry were reported |
| Other bias | Unclear risk | Quote: "the characteristics of the ITT population are summarized in Table 1. They were similar in the 2 groups" Comment: baseline characteristics were similar between groups. No information on washout periods was reported |
Gold 2016.
| Methods | Study design: multi‐centre, randomised, double‐blind, parallel‐group study Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 503 Inclusion criteria
Exclusion criteria: acne conglobata, acne fulminans, nodulo‐cystic acne, or acne requiring systemic treatment Sites of acne: face and trunk Severity of acne and corresponding criteria of judgement: Investigator Global Assessment (IGA) scale Treatment before study: unspecified Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 104/113; B = 103/114; C = 33/36 Age (years, SD): A = 20.1 (7.6); B = 19.4 (6.8); C = 18.5 (5.7) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐intervention: using cleanser twice daily and moisturiser at least once daily | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at screening, at baseline, and at weeks 1, 2, 4, 8, and 12 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: July 2013 to March 2014 Country: USA and Canada Setting: unclear Number of study centres: 31 Washout period: unclear Registered number:NCT01880320 ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial (Galderma R&D Inc) Conflicts of interest: "the investigators received grants for conducting the studies. Dr. Stein Gold is an investigator, consultant, and a member of the speaker’s bureau for Galderma, and is also a consultant and/or investigator for Allergan, Valeant and Ranbaxy. Dr. Weiss is an investigator and has served on advisory boards for Galderma, and also has received grants and/or honoraria from AbbVie, Allergan, Amgen, Celgene, Galderma, Leo, Neothetics, Promius, Sebacia, Valeant, and Xenoport. Dr. Tanghetti has served on advisory boards for Galderma. Dr. Rueda and Ms. Liu are employees of Galderma" Publication status: full text | |
| Stated aim for study | Quote from publication: "the current study aimed to evaluate the efficacy and safety of adapalene 0.3%/benzoyl peroxide 2.5% (0.3% A/BPO) gel as single‐agent therapy in subjects with moderate and severe inflammatory acne" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "prior to the start of the study, a randomization list was generated by a statistician" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Low risk | Quote: "the study design was considered double‐blind based on the following: the topical medication was packaged in identical tubes, medication was dispensed by a third party, and the randomization list was locked, with access restricted to designated personnel" Comment: allocation concealment was conducted |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "the study design was considered double‐blind based on the following: the topical medication was packaged in identical tubes, medication was dispensed by a third party, and the randomization list was locked, with access restricted to designated personnel" Comment: it seems that participants were blinded but not personnel. It is unclear whether access to designated personnel influenced the results. However, blinding was difficult as treatment‐related adverse events were more common in the BPO/adapalene groups |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: described as "double‐blind", but trial authors did not clearly specify that outcome assessors were blinded. However, blinding was difficult as treatment‐related adverse events were more common in the BPO/adapalene groups |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: most participants completed the trial (90.8%, 88.5%, and 88.4% for each group, respectively). Reasons for discontinuation were similar between groups. ITT strategy was taken |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes planned on the trial registry were reported |
| Other bias | Unclear risk | Quote: "baseline demographics and clinical characteristics were similar between groups (Table 1)" Comment: baseline characteristics were similar between groups. No information on the washout period was reported |
Gollnick 2009.
| Methods | Study design: randomised, double‐blind, controlled, parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 1670 Inclusion criteria
Exclusion criteria
Sites of acne: face (excluding nose) Severity of acne and corresponding criteria of judgement: Investigator Global Assessment (IGA) scale Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 183/236; B = 189/229; C = 185/230; D = 174/244 Age (years): A = 19.5 (range 12 to 48); B = 18.5 (12 to 50); C = 18.9 (12 to 55); D = 19.2 (12 to 51) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Interventions in Group D
Co‐interventions: not specified | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 1, 2, 4, 8, and 12 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: USA, Canada, and Europe Setting: unclear Number of study centres: 61 Washout period: unclear Registered number:NCT00421993 ITT analysis: yes | |
| Publication details | Language of publication: English Funding: private for profit (Galderma R&D) Conflicts of interest: "the investigating authors received payments for this research project. B.G.,Y.L. and M.G. are employees of Galderma R&D. H.P.M.G. has served as a speaker for Galderma Laboratories" Publication status: full article | |
| Stated aim for study | Quote from publication: "to evaluate the efficacy and safety of adapalene 0.1%–BPO 2.5% fixed‐dose combination gel (adapalene–BPO) relative to adapalene 0.1% monotherapy (adapalene), BPO 2.5% monotherapy (BPO), and the gel vehicle (vehicle) in a large population for the treatment of acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "subjects were randomized consecutively in a 1:1:1:1 ratio to receive either adapalene–BPO gel, adapalene gel, BPO gel, or gel vehicle, once daily in the evening for 12 weeks" Comment: trial authors did not report the method used to generate the random sequence |
| Allocation concealment (selection bias) | Unclear risk | Comment: no information about allocation concealment was available |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "blinding integrity was ensured by packaging the topical medication in identical tubes. A third party other than the investigator ⁄evaluator was required to dispense the medication" Comment: it is unclear whether participants were blinded. However, complete blinding was difficult because treatment‐related adverse events were more common in the BPO/adapalene and adapalene groups |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "a third party other than the investigator/evaluator was required to dispense the medication" Comments: complete blinding was difficult because treatment‐related adverse events were more common in the BPO/adapalene and adapalene groups |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Quote: "in total, 1670 subjects were randomized and included in the ITT population... 87.4% of subjects completed the study" Comment: although ITT strategy was taken for data analysis, 87.4% of participants completed the study and reasons for withdrawal were not similar between groups according to Figure 1 |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes listed in the methods section and on the trial registry were reported |
| Other bias | Unclear risk | Comment: Table 2 shows comparability of baseline demographic and clinical characteristics between groups. No information on washout periods was reported |
Goreshi 2012.
| Methods | Study design: split‐face design Duration of follow‐up: 3 weeks | |
| Participants | Total number of participants randomised: N = 24 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for all participants Sex ratio (male/female): 7/11 Age (years): 26.1 (5.7) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐intervention: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Follow‐up visits were conducted on days 0, 7, 14, and 21 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: USA Setting: unclear Number of study centres: 1 Washout period: 1 week washout for topical retinoids, steroids, antibiotics, keratolytics (BPO, α‐ or β‐hydroxyl acids) and other topical medications, oral antibiotics, or steroids; 6 months for oral retinoids Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: commercial (Medicis Pharmaceutical Corporation) Conflicts of interest: none Publication status: full article | |
| Stated aim for study | Quote from publication: "we sought to compare the tolerability of 2 combination topical acne products, clindamycin 1.2%‐tretinoin 0.025% (CLIN/RA) gel and benzoyl peroxide 2.5%‐adapalene 0.1% (BPO/ADA) gel" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "a randomized, bilateral (split face), double‐blind, dual‐therapy, single‐center clinical study" Comment: trial authors did not specify methods of randomisation used |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "double‐blind" Comment: it is unclear whether participants and personnel were blinded. However, complete blinding was difficult as treatment‐related adverse events were more common in the BPO/adapalene group |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "double‐blind" Comment: it is unclear whether participants and personnel were blinded. However, complete blinding was difficult as treatment‐related adverse events were more common in the BPO/adapalene group |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "24 subjects ultimately entered and started the study. 23 subjects completed the study" Comment: only 1 participant withdrew |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all of the outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | High risk | Comment: baseline characteristics were controlled within participants in the split‐face design. However, washout periods were not long enough |
Guerra‐Tapia 2012.
| Methods | Study design: parallel study, multi‐centre, single‐blind Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 168 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Leeds Revised Acne Grading System Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 24/59; B = 20/65 Age (years): A = 18.9 (5.3); B = 19.2 (5.3) Duration of acne (months): A = 50.3 (35.7); B = 50.8 (42.3) | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: not specified | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 1, 2, 4, 8, and 12 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: November 2006 to July 2008 Country: Spain Setting: unclear Number of study centres: 1 Washout period: 2 weeks washout for any form of topical treatment for acne (including natural or UV light); 30 days washout for any significant medicinal product that may have affected a participant's acne; 6 months for oral isotretinoin Registered number:NCT00807014,NCT00688519,NCT00689481 ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial (Stiefel, GSK) Conflicts of interest: editorial support provided by Catherine Rees and Medisys Health Communications Publication status: full article | |
| Stated aim for study | Quote from publication: "to compare BPO/C and AP with regard to the early effect on QOL, efficacy and tolerability in patients with mild to moderate acne vulgaris" | |
| Notes | The 2 registration numbers cited in the publication are not relevant to the acne condition but to psoriasis. We identified the correct record from ClnicalTrials.gov | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "patients were randomized in a 1:1 ratio to either BPP/C or AP, using a computer‐generated table of random subject numbers provided by a clinical research organization. Each study product was correlated with a subject number and individually labelled with that number" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "because of differences in the appearance of the products and size of the tubes, patients were not blinded to their treatment allocation" Comment: participants were not blinded |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "assessors remained blinded throughout the study and subjects were instructed to keep study product information confidential" Comment: outcome assessors were blinded. However, complete blinding was difficult as treatment‐related adverse events were more common in the adapalene group |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: although trial authors used the ITT strategy, 27 of 83 participants in the BPO/C group and 27 of 85 participants in the AP group did not complete the study. Besides, reasons for withdrawal were not similar between groups |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes listed on the trial registry were reported |
| Other bias | Low risk | Comment: according to Table 1, baseline characteristics were similar between groups. Washout periods were long enough |
Gupta 2003.
| Methods | Study design: randomised, double‐blind. multi‐centre, parallel‐group study Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 112 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): A = 18.5 (range 13.7 to 29.6); B = 18.7 (range 13.1 to 37.1) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 2, 4, 8, and 12 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: Canada Setting: unclear Number of study centres: 6 Washout period: 4 weeks for use of oral or systemic antibiotics; 2 weeks for use of topical antibiotics, retinoids, or BPO derivatives Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: commercial (Dermik Laboratories Canada, Inc.) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "to compare the effectiveness of 3% erythromycin/5% benzoyl peroxide and 0.025% tretinoin/erythromycin 4%, each applied twice daily in patients with moderate acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "randomization was performed centrally, and each investigator was provided with medication kits" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Low risk | Quote: "randomization was performed centrally, and each investigator was provided with medication kits. These kits were numbered sequentially, and, following enrollment, each patient was assigned to a medication in this sequential order" Comment: allocation concealment was probably conducted |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "neither the evaluating physician nor the patient was informed as to which treatment was received" Comment: participants and personnel were probably blinded. However, complete blinding was difficult as treatment‐related adverse events were more common in the tretinoin/erythromycin group |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "neither the evaluating physician nor the patient was informed as to which treatment was received" Comment: outcome assessors were probably blinded. However, complete blinding was difficult as treatment‐related adverse events were more common in the tretinoin/erythromycin group |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Quote: "the six sites randomized a total of 112 subjects for treatment... At the final analysis, 81 subjects had completed the study" Comment: a high proportion of participants did not complete the trial and ITT analysis was not conducted |
| Selective reporting (reporting bias) | High risk | Comment: trial authors reported in the Methods section that the outcome of participant global self‐assessment of acne improvement was assessed; however, this outcome was not reported in the results section |
| Other bias | Low risk | Comment: demographics and acne severity at baseline were similar between groups. Washout periods were long enough |
Hayashi 2018.
| Methods | Study design: parallel, investigator‐blinded design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 351 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Investigator’s Static Global Assessments Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 75/97; B = 67/110 Age (years): A = 20.3 (5.9); B = 19.8 (4.9) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 1, 2, 4, 8, and 12, or at study end **This outcome was assessed as the primary outcome in the trial (percentage change from baseline in TLs at week 2) | |
| Study details | Study period: October 2015 to February 2016 Country: Japan Setting: unclear Number of study centres: 15 Washout period: 2 weeks for topical facial antibiotics and systemic antibiotics, topical anti‐acne medications, non‐mild facial cleansers, or products containing glycolic or other acids Registered number:NCT02557399; 2017‐001575‐23 ITT analysis: no | |
| Publication details | Language of publication: English Funding: commercial (GlaxoSmithKline) Conflicts of interest: "A. E., T. H. and M. Y. are employees of GSK, Tokyo, Japan. O. S. is an employee of GSK, London, UK. N. H., I. K. and M. K. served as coordinating investigators in the current study, for which they received compensation. N. H. has served as a consultant to GSK, Galderma, Shionogi Pharmaceutical, Maruho, Rohto Pharmaceutical, Sato Pharmaceutical, POLA Pharma and Otsuka Pharmaceutical. I. K .has served as a consultant to GSK, Galderma, Shionogi Pharmaceutical, Maruho and Rohto Pharmaceutical. M. K. has served as a consultant to GlaxoSmithKline, Galderma, Shionogi Pharmaceutical, Maruho, Nippon Zoki Pharmaceutical, Mochida Pharmaceutical, Rohto Pharmaceutical, Mitsubishi Tanabe Pharma, Allergan, Nippon Shinyaku and Sato Pharmaceutical" Publication status: full article | |
| Stated aim for study | Quote from publication: "this study aims to evaluate the early efficacy (at week 2) and the safety (throughout the study) of CLNP/BPO 3% in comparison with ADA + CLNP for the treatment of acne vulgaris in Japanese patients" | |
| Notes | *Two participants randomised to the clindamycin/BPO group were excluded from ITT analysis due to withdrawal of consent | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "patients who provided written informed consent were randomized (using validated internal software) in a 1:1 ratio to receive either CLNP/BPO 3% or ADA + CLNP for 12 weeks" Comment: random sequence was generated via validated internal software |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information was available regarding allocation concealment |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: only investigators were blinded but complete blinding was difficult because the frequency of treatments differed by treatment group and treatment‐related adverse events were more common among participants treated with adapalene |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "investigators responsible for end‐point assessments did not have access to or administrate the study products and were prohibited from collecting information regarding the investigational products or compliance records" Comment: attempts were made to blind outcome assessors but complete blinding was difficult as treatment‐related adverse events were more common among participants treated with adapalene |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: as shown in Figure 1, less than 10% of participants in each group did not complete the trial, with similar numbers of and reasons for withdrawal, and ITT analysis was conducted |
| Selective reporting (reporting bias) | Unclear risk | Comment: not all outcomes reported in the publication were specified in the trial registry |
| Other bias | High risk | Quote: "patient demographics and baseline characteristics were similar between the groups" Comment: demographics and acne severity at baseline were similar between groups. Washout periods were not long enough |
Hughes 1992.
| Methods | Study design: double‐blind, parallel studies Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 77 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: method of Burke and Cunliffe Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): overall = 46/31 Age (years): overall = 18.7 (range 14 to 29) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 4, 8, and 12 It was not reported which outcome was the primary outcome assessed in the trial | |
| Study details | Study period: September to May Country: UK Setting: outpatient Number of study centres: 1 Washout period: 4 weeks washout for any acne therapy; 2 years for oral isotretinoin Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "to confirm the effect of isotretinoin and compare it with an established topical treatment of acne ‐ 5% benzoyl peroxide gel (Panozyl aquagel 5%)" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "study medication was assigned by randomized allocation, stratified for sex, age, duration and severity of acne" Comment: the method used to generate the random sequence was not specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "the study was conducted according to a double‐blind, parallel group format involving the three treatments" Comment: it is unclear who was blinded. However, complete blinding was difficult because the frequency of treatments differed by treatment group and treatment‐related adverse events were more common among participants treated with BPO or isotretinoin |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "the study was conducted according to a double‐blind, parallel group format involving the three treatments" Comment: it is unclear who was blinded. However, complete blinding was difficult because the frequency of treatments differed by treatment group and treatment‐related adverse events were more common among participants treated with BPO or isotretinoin |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "four patients dropped out from the study" Comment: only about 5% of participants withdrew from the trial and the number of withdrawals was similar between groups |
| Selective reporting (reporting bias) | Unclear risk | Comment: all outcomes listed in the methods section were reported, including adverse events, but without a protocol or relevant information on a trial registry, it is difficult to determine whether there was selective reporting |
| Other bias | Unclear risk | Comment: insufficient information about the similarity in baseline characteristics between groups was provided |
Iftikhar 2009.
| Methods | Study design: parallel design Duration of follow‐up: 24 weeks | |
| Participants | Total number of participants randomised: N = 220 Inclusion criteria
Exclusion criteria
Sites of acne: unclear Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 1/1.8; B = 1/2.1 Age (years): A = 20.35 (4.40); B = 21.44 (4.20) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and every 2 weeks until week 24 It was not reported which outcome was the primary outcome assessed in the trial | |
| Study details | Study period: January 2007 to June 2007 Country: Pakistan Setting: hospital Number of study centres: 1 Washout period: 2 weeks washout for any other topical medication and 4 weeks for oral medications Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "to compare the efficacy and safety of topical 0.1% adapalene and 4% benzoyl peroxide in mild to moderate acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: participants "who fulfilled the inclusion and exclusion criteria were randomly divided into two groups by using random number tables" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: this is an "open trial"; its open nature could influence the validity of the outcomes |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: this is an "open trial"; its open nature could influence the validity of the outcomes |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "a total of 220 patients were enrolled in the study, out of which 200 patients completed the study. There were 10 delayed exclusions while 10 patients were lost to follow‐up" Comment: the number of participants lost to follow‐up in each group and the reasons for their withdrawal remain unclear |
| Selective reporting (reporting bias) | Unclear risk | Comment: all outcomes listed in the methods section were reported, including adverse events, but without a protocol or relevant information on a trial registry, it is difficult to determine whether there was selective reporting |
| Other bias | Unclear risk | Comment: insufficient information about similarity in baseline characteristics between groups was provided |
Jackson 2010.
| Methods | Study design: randomised, investigator‐blinded, parallel‐group trial Duration of follow‐up: 16 weeks | |
| Participants | Total number of participants randomised: N = 54 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Investigator Global Assessment (IGA) and Investigator Assessment of Overall Disease Severity Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 13/14; B = 12/15 Age (years): A = 17.6 (6.9); B = 16.2 (4.9) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions If necessary, a supplied moisturiser could be used after washing and drying the face provided that participants waited 10 minutes before applying the study medication | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 2, 4, 8, 12, and 16 It was not reported which outcome was the primary one assessed in the trial | |
| Study details | Study period: unclear Country: USA Setting: unclear Number of study centres: 2 Washout period: topical facial treatments, including retinoids, anti‐acne products, and corticosteroids (2 weeks); topical antibiotics and systemic corticosteroids (4 weeks); systemic antibiotics (6 weeks); and systemic retinoids (6 months) Registered number:NCT00841776 ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial (GSK) Conflicts of interest: all trial authors declared that they were consultants or employees for the sponsor of this study Publication status: full article | |
| Stated aim for study | Quote from publication: "to compare the anti‐microbial efficacy of benzoyl peroxide 5%/clindamycin phosphate 1% gel with a clindamycin phosphate 1.2%/ tretinoin 0.025% gel over 16 weeks of treatment in subjects with moderate to moderately severe acne" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: the method used to generate the random sequence was unclear |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: only investigators were blinded |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information about whether outcome assessors were blinded was provided. The occurrence of treatment‐related adverse events was similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "analysis of efficacy and tolerability endpoints were performed on the intent‐to‐treat population, which include all subjects who were enrolled"; "forty‐nine subjects completed the study" Comment: ITT analysis was conducted and a low proportion of incomplete follow‐up was reported |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes listed on the trial registry were reported |
| Other bias | Low risk | Comment: according to Table 1, demographics and characteristics at baseline were similar between groups. Washout periods were long enough |
Jaffe 1989.
| Methods | Study design: double‐blind, multi‐centre study Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 107 Inclusion criteria: patients with acne vulgaris Exclusion criteria: unclear Sites of acne: unclear Severity of acne and corresponding criteria of judgement: unclear Treatment before study: antibiotics alone or combined with topical steroids most commonly used, with poor or fair responses Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 15/9 (1 unclear); B = 19/8; C = 17/11; D = 15/12 Age (years): A = 18.6 (1.2); B = 20.4 (1.2); C = 20.6 (1.1); D = 19.3(0.9) Duration of acne (months): A = 19.0; B = 24.0; C = 12.0; D = 13.5 | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Interventions in Group D
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 2, 4, 8, and 12 It was not reported which outcome was the primary one assessed in the trial | |
| Study details | Study period: 12 weeks Country: UK Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: private for profit (Quinoderm Limited) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "to investigate the clinical effectiveness of the 10% benzoyl peroxide/potassium hydroxyquinoline combination preparation with or without hydrocortisone and to compare them with their aqueous astringent cream base alone and with a proprietary 10% benzoyl peroxide only alcoholic gel formulation" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "allocated at random to one of four treatment groups" Comment: insufficient details about the method used to generate the random sequence were available |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information about allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "to ensure the double‐blind nature of the study, all the preparations were supplied in plain tubes of identical appearance" Comment: although trial authors described the trial as double‐blind, it is unclear who was blinded. However, complete blinding was difficult as the vehicle of BPO treatment was different from that of other treatments |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: although trial authors described the trial as double‐blind, it is unclear who was blinded. Treatment‐related adverse events were not significantly different between groups |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Quote: "thirteen patients were withdrawn from the trial before completing the 12‐week course of treatment" Comment: according to Table II, reasons for withdrawal were not similar among groups |
| Selective reporting (reporting bias) | High risk | Comment: trial authors mentioned in the methods section that participants were evaluated at baseline and at weeks 2, 4, 8, and 12. However, they reported the efficacy results only for week 12. Trial authors mentioned that adverse events were recorded; however, no information on specific adverse events was available in the results section, except that some participants withdrew due to adverse events |
| Other bias | High risk | Quote: "the overall sex ratio was 66:40 male:female (1 not stated) there were proportionately less males in Group 4 and more in Group 2. The duration of the condition also varied between the groups, with Group 4 having a mean value of 13.5 months compared with 19 months for Group 1 and 24 months for Group 2. This was statistically significant (p<0.05, Mann‐Whitney test)" Comment: baseline characteristics were not comparable between groups |
Jawade 2016.
| Methods | Study design: parallel‐group study Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 132 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Investigator's Global Assessment scale Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 19/22; B = 18/27; C = 17/29 Age (years): A = 20.1 (3.9); B = 18.6 (3.5); C = 19.2 (3.3) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: applying moisturising cream daily in case of dryness | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 1, 2, 4, 8, and 12 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: September 2014 to September 2015 Country: India Setting: outpatient dermatology department Number of study centres: 1 Washout period: at least 3 months washout for study medications before inclusion Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full text | |
| Stated aim for study | Quote: "the aim of this study was to evaluate the efficacy and tolerability of adapalene 0.1%‐benzoyl peroxide 2.5% combination gel compared to adapalene 0.1% gel monotherapy and benzoyl peroxide 2.5% gel monotherapy in treatment of acne vulgaris in Indian patients" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "prior to the start of the study, a randomization list was generated via simple randomization by a statistician using the Random Allocation software version 1.0.0. The randomization list was secured in a locked cabinet and electronic file to which the investigator/outcome assessor had restricted access" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Low risk | Quote: "the allocation sequence was concealed from the investigator and outcome assessor using sequentially numbered, sealed, opaque envelops to enroll patients in the allocated groups" Comment: the method of allocation concealment was specified |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "the investigator and outcome assessor did not have access to the randomization list and the study treatment was provided to the patients by a designated study drug dispenser" Comment: it is unclear whether participants were blinded. However, complete blinding was difficult because treatment‐related adverse events were more common among participants treated with BPO/adapalene |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "to ensure the blinded design of the study, an investigator unaware of the treatment allocation performed the efficacy and tolerability evaluations" Comment: the outcome assessor was blinded. However, complete blinding was difficult because treatment‐related adverse events were more common among participants treated with BPO/adapalene |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Quote: "among 132 enrolled patients, 90 (68.2 %) completed the study. Forty‐two (31.8%) patients were excluded because of non compliance with the treatment regimen or the follow‐up schedule and protocol violation. Thirty patients in each group who completed study were analyzed after 12 weeks of treatment (Figure 1)" Comment: the proportion of withdrawal was high and complete case analysis was conducted |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, without a protocol or relevant information on a trial registry, it is unclear about the risk of selective reporting |
| Other bias | Unclear risk | Comment: demographic and participant characteristics at baseline were similar according to Table 1. Washout periods for other acne treatments were not reported |
Ji 2000.
| Methods | Study design: randomised, controlled, parallel‐group study Duration of follow‐up: 6 weeks | |
| Participants | Total number of participants randomised: N = 118 Inclusion criteria
Exclusion criteria
Sites of acne: face, neck, and chest Severity of acne and corresponding criteria of judgement: adapted Pillsbury grade system
Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 38/20; B = 28/15 Age (years): A = 17.4 (4.16); B = 16.23 (2.15) Duration of acne (years): A = 3.59 (2.78); B = 2.85 (1.32) | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐intervention: not specified | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 2, 4, and 6 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: 6 weeks Country: China Setting: unclear Number of study centres: 1 Washout period: topical antibiotic or anti‐acne treatment (2 weeks); systematic antibiotics (4 weeks) Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: Chinese Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "to evaluate the efficacy and safety of 10% benzoyl peroxide cream in the treatment of acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: described as "randomly assigned" but no information on how to generate the random sequence |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: trial authors did not report methods of blinding. However, complete blinding was difficult as the vehicle of BPO treatment was different from that of the other treatments |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: trial authors did not report the methods of blinding used. The number of participants having adverse events was similar between groups (what the adverse events were was not reported) |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: of all 118 participants, 67 were assigned to the treatment group and 51 to the control group. More than 10% of participants discontinued treatment. One in the treatment group and 2 in the control group withdrew from the study due to adverse events, and 10 due to non‐adverse event‐related reasons. Whether the reasons for withdrawal of 10 participants were similar between groups was not reported |
| Selective reporting (reporting bias) | High risk | Comment: trial authors mentioned in the methods section that participants were evaluated every 2 weeks. However, they reported efficacy results only for week 6 |
| Other bias | Unclear risk | Comment: insufficient information on the similarity in baseline characteristics between groups was provided |
Jones 2002.
| Methods | Study design: multi‐centre, randomised, double‐blind, parallel‐group study Duration of follow‐up: 8 weeks | |
| Participants | Total number of participants randomised: N = 223 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Physician’s Global Acne Severity Scale Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 55/57; B = 57/54 Age (years): A = 18.7 (6.2); B = 18.2 (5.4) Duration of acne (years): A = 4.9 (4.8); B = 4.6 (4.6) | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 2, 4, 6, and 8 *These outcomes were assessed as the primary outcome in the trial | |
| Study details | Study period: 8 weeks Country: USA Setting: unclear Number of study centres: 4 Washout period: 2 weeks washout period for topical antibiotics and/or anti‐acne medication, topical corticosteroids, and topical retinoids; 4 weeks for systemic antibiotics known to affect acne and systemic corticosteroids; and 5 months for oral retinoids Registered number: unclear ITT analysis: yes | |
| Publication details | Language of publication: English Funding: private for profit (Dermik Laboratories, Berwyn, Pennsylvania, USA) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "to assess the tolerability and efficacy of this formulation in participants with acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "patients were randomised to treatment regimens in a ratio of 1:1" Comment: the method of randomisation used is unclear |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: although trial authors described the trial as double‐blind, who was blinded is unclear. However, complete blinding was difficult as dryness was more common in the BPO/erythromycin group |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: although trial authors described the trial as double‐blind, who was blinded is unclear. However, complete blinding was difficult as dryness was more common in the BPO/erythromycin group |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "the intent‐to‐treat population included all participants randomised to active treatment or VC" Comment: no information was provided about how many participants discontinued during the trial for any reason |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, neither the protocol nor relevant information on a trial registry was available to determine whether selective reporting existed |
| Other bias | Low risk | Comment: demographic and participant characteristics at baseline were similar according to Table 1 |
Kabir 2018.
| Methods | Study design: parallel, single‐blind design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 128 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for all participants Sex ratio (male/female): 52/76 Age (years): 25.1 (3.1) Duration of acne (years): longer than 6 months | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: washing face with a mild soap | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and every 4 weeks *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: July 2016 to December 2016 Country: Multan Setting: outpatient dermatology department Number of study centres: 1 Washout period: at least 1 month washout for anti‐acne treatment Registered number: unclear ITT analysis: yes | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full text | |
| Stated aim for study | Quote: "to compare the efficacy of adapalene (0.1% gel) monotherapy versus adapalene (0.1%) plus benzyl peroxide (2.5%) combination therapy for treatment of mild to moderate acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "patients were randomly allocated into two groups by lottery method" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: no relevant information was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "it was a randomized controlled single blind study carried out at Dermatology OPD of NHM" Comment: no relevant information was provided regarding who was blinded. However, complete blinding was difficult because frequency differed by treatment group |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Quote: "it was a randomized controlled single blind study carried out at Dermatology OPD of NHM" Comment: no relevant information was provided regarding who was blinded. No information on treatment‐related adverse events was reported |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: it seems that all 128 participants enrolled in the trial provided outcome data |
| Selective reporting (reporting bias) | High risk | Quote: "patients were followed up on every 4th week and any side effects were noted" Comment: side effects were mentioned in the methods section but not in the results |
| Other bias | Unclear risk | Comment: no relevant information regarding demographic and participant characteristics at baseline between the 2 groups was available |
Kaur 2015.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 100 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Investigator’s Global Assessment score Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 4, 8, and 12 weeks *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: 30 days washout for any anti‑acne medications Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: none Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "the present study was undertaken with the aim of comparing the efficacy and safety of topical benzoyl peroxide and clindamycin versus topical benzoyl peroxide and nadifloxacin versus topical tretinoin and clindamycin in patients of acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "group A received benzoyl peroxide 2.5% gel once daily at bedtime and clindamycin 1% gel once daily topically. Group B received benzoyl peroxide 2.5% gel once daily at bedtime and nadifloxacin 1% cream once daily topically. Group C received tretinoin 0.025% and clindamycin 1% gel once daily at bedtime topically" Comment: insufficient information on blinding was provided. However, complete blinding was difficult as vehicles and treatment timing differed by treatment group |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "during the study period, three patients from Group A, four patients from Group B and three patients from Group C did not come for follow‑up, so data of these ten patients were not included in the statistical analysis" Comment: insufficient information on the reasons for withdrawal for each group was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability of participant characteristics between groups was provided |
Kawashima 2014.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 360 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Investigator’s Static Global Assessment (ISGA) Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 60/118; B = 66/116 Age (years): A = 21.3 (5.93); B = 22.4 (6.76) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 1, 2, 4, 8, and 12 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: Japan Setting: unclear Number of study centres: 19 Washout period: 2 weeks washout for topical/systemic antibiotics or anti‐acne medications; facials or peels containing acids; BPO‐containing products; non‐mild facial cleansers; moisturisers containing retinol, salicylic acid, or α‐ or β‐hydroxy acids; or changed astringents and toners; 4 weeks for topical corticosteroids or having undergone facial procedures; 6 months for systemic retinoids; 6 weeks for topical retinoids; 12 weeks for oestrogens, androgens, or anti‐androgenic agents Registered number:NCT01400932 ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial Conflicts of interest: "Professor Makoto Kawashima served as a study investigator, coordinator and a third‐party reviewer of facial photographs with compensation, and served as a consultant for other pharmaceutical companies. Mr Masahiro Yamada, Mr Hirofumi Hashimoto and Mr Makoto Ono are employees of GlaxoSmithKline, Tokyo, Japan. Dr Alessandra B Alio Saenz is a dermatologist and an employee of Stiefel, a GSK company" Publication status: full article | |
| Stated aim for study | Quote from publication: "this multicenter, randomized, vehicle‐controlled study evaluated the efficacy, safety and topical tolerability of BPO 3% gel when applied once daily for 12 weeks in Japanese acne patients" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "enrolled patients were randomized (1:1) by a computer randomization system to receive BPO 3% or matching vehicle" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment used was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: trial authors stated that the trial was double‐blind, but it is unclear who was blinded. However, complete blinding was difficult as treatment‐related adverse events were more common in the BPO group |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: trial authors stated that the trial was double‐blind, but it is unclear who was blinded. However, complete blinding was difficult as treatment‐related adverse events were more common in the BPO group |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: less than 10% of participants in each group withdrew from the trial, reasons for withdrawal were comparable, and ITT analysis was conducted |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes planned on the trial registry have been reported |
| Other bias | Low risk | Quote: "demographics and baseline disease characteristics, including TL, IL and non‐IL counts, were similar across both groups (Table 1)" Comment: baseline characteristics were similar between groups. Washout periods were long enough |
Kawashima 2015.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 800 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Investigator’s Static Global Assessment (ISGA) Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 65/139; B = 109/187; C = 97/202 Age (years): A = 20.4 (6.1); B = 20.7 (6.3); C = 21.1 (6.5) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A*
Interventions in Group B*
Interventions in Group C
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 1, 2, 4, 8, and 12 **This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: Japan Setting: unclear Number of study centres: 26 Washout period: 2 weeks for topical anti‐acne medications (e.g. BPO, azelaic acid, resorcinol, salicylates, antibiotics); 4 weeks for topical corticosteroids, facial procedure; 12 weeks for oestrogens, androgens, or anti‐androgenic agents; 6 months for systemic or topical retinoids Registered number:NCT01445301 ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial Conflicts of interest: "M.K. served as a coordinating investigator and a third‐party reviewer of facial photographs, for which he received compensation, and has served as a consultant for other pharmaceutical companies. M.Y., H.H. and M.O. are employees of GSK, Tokyo, Japan. A.B.A.S. is a dermatologist and an employee of Stiefel, a GSK company" Publication status: full article | |
| Stated aim for study | Quote from publication: "this multicentre study was conducted to evaluate the efficacy and safety of CLNP/BPO 3.0% gel applied once daily or twice daily relative to CLNP twice daily when applied topically for 12 weeks in Japanese patients with acne" | |
| Notes | *Data from group A and group B were combined for the meta‐analysis in this review | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "using a computer randomization system, eligible patients were randomized (2:3:3) to receive CLNP/BPO 3 0% once daily, CLNP/BPO 3 0% twice daily, or CLNP twice daily" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment used was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: the trial was single‐blind and investigators were blinded, indicating that participants were not blinded |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "to keep the single blinding, investigators were not permitted to ask about or collect any information related to the dose regimen, colour of the gel, external appearance or weight of the tubes, or to access patient compliance records" Comment: although blinding was conducted, complete blinding was difficult as it was reported that treatment‐related adverse events were more common in the 2 BPO/clindamycin groups |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: the proportion of withdrawals and corresponding reasons were not similar between the 3 groups |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes planned on the trial registry have been reported |
| Other bias | Low risk | Comment: according to Table 1, demographics and baseline disease characteristics were similar across both groups. Washout periods were long enough |
Kawashima 2017a.
| Methods | Study design: parallel design Duration of follow‐up: 52 weeks | |
| Participants | Total number of participants randomised: N = 459 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: lesion count Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 72/159; B = 72/155 Age (years): A = 22.9 (7.3); B = 23.0 (7.5) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline, at weeks 2 and 4, and then every 4 weeks It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: May 2012 to September 2013 Country: Japan Setting: outpatient settings Number of study centres: 25 Washout period: 4 weeks for topical use of retinoids Registered number: JapicCTI‐121909 ITT analysis: no | |
| Publication details | Language of publication: English Funding: commercial (Maruho Co.,Ltd) Conflicts of interest: "Maruho covered all expenses of this study. All drugs used for this study were provided by Maruho (Kyoto, Japan). M. K. received fees for consultation, lectures and writing from Maruho. T. N. and T. K. are employees of Maruho" Publication status: full article | |
| Stated aim for study | Quote from publication: "aiming to evaluate the safety and efficacy of long‐term BPO use, we performed an open‐label, randomized, multicenter study by administration of 2.5% or 5% BPO gel once daily for 52 weeks to patients with acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "enrolled patients were randomized (1:1) by a computer randomization system (four patients within each block) to receive BPO 2.5% gel or BPO 5% gel" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not mention the method of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: this was an open‐label trial |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: this was an open‐label trial |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: more than 14% of participants (65/458) did not complete the trial. ITT analysis was not conducted for efficacy outcomes |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes planned on the trial registry have been reported |
| Other bias | Unclear risk | Comment: as shown in Table 1, baseline demographic and disease characteristics of participants were similar between groups. Washout periods for acne treatments except topical use of retinoids were unclear |
Kawashima 2017b.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 609 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: lesion count Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 84/119; B = 79/124; C = 91/110 Age (years): A = 19.5 (5.7); B = 20.0 (5.6); C = 19.2 (5.5) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: not reported | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 2, 4, 6, 8, 10, and 12 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: February 2012 to October 2012 Country: Japan Setting: unclear Number of study centres: 30 Washout period: 12 weeks washout for systemic or topical retinoids, or systemic antibiotics; 4 weeks washout for chemical peeling, laser ray treatment, or systemic use of anti‐acne medications (excluding vitamins B2 and B6), steroids, or antibiotics; 2 weeks washout for topical use of anti‐acne medications (excluding vitamins B2 and B6), steroids, or antibiotics Registered number: JapicCTI‐121784 ITT analysis: yes | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: "Maruho Co. Ltd covered all expenses for this study. All drugs used for this study were provided by the company. M. K. was the medical advisor of the study and S. S., F. F., K. M., H. A., A. I., Y. T., N. H. and Y. Y. were coordinating investigators of the study. M. K. and Y. T. received fees for consultation, lectures and writing from the company. S. S .received fees for lectures and research grants from the company. A. I. received fees for consultation, lectures and writing, and research grants from the company. N. H. received fees for lectures and writing from the company. T. N. and T. K. are employees of the company" Publication status: full article | |
| Stated aim for study | Quote from publication: "this study was a multicenter, placebo‐controlled, randomized, double‐blind, parallel‐group, comparative study to confirm the efficacy and safety of 2.5% and 5% BPO gel in Japanese patients with acne vulgaris and identify the recommended clinical dose of BPO" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "patients who enrolled in this study were first treated with placebo during the 2‐week observation period, and then randomized (1:1:1) by a computer randomization system (six patients in each block) to receive BPO 2.5%, BPO 5% or placebo" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not mention the method of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: trial authors mentioned that in this double‐blind trial, participants were blinded. However, it is unclear whether personnel were blinded. Complete blinding was difficult as treatment‐related adverse events were more common in the BPO groups |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: it is unclear whether outcome assessors were blinded. However, complete blinding was difficult as treatment‐related adverse events were more common in the BPO groups |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: more than 94% of participants in each group completed the trial |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes planned on the trial registry have been reported |
| Other bias | Low risk | Comment: as shown in Table 1, baseline demographic and disease characteristics of participants were similar between groups. Washout periods were long enough |
Ko 2009.
| Methods | Study design: prospective, open‐label, parallel comparative study Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 69 Inclusion criteria
Exclusion criteria
Sites of acne: unclear Severity of acne and corresponding criteria of judgement: Leeds Revised Acne Grading System and KAGS‐2 Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 7/24; B = 13/25 Age (years): A = 24.5; B = 21.1 Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 1, 2, 4, 8, and 12 It was unclear which outcome was assessed as the primary one in the trial | |
| Study details | Study period: unclear Country: South Korean Setting: hospital Number of study centres: 1 Washout period: a washout period of at least 2 weeks of topical antibiotics and corticosteroid, 1 month of oral antibiotics and corticosteroid, and 6 months of oral retinoid agent before the start of treatment Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: non‐commercial (Medical Research Grant (2003–32) Pusan National University) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "to compare the efficacy and tolerability in combination of CDP/BPO in comparison with ADA in Asian patients with mild to moderate acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "patients were randomly assigned to one of the two groups" Comment: the method of randomisation used is unclear |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: trial was described as "open‐label" |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: trial was described as "open‐label" |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on follow‐up was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: all outcomes listed in the methods section were reported, but without a protocol or relevant information on a trial registry, it is hard to judge whether selective reporting existed |
| Other bias | Low risk | Comment: according to Table 1, baseline characteristics were similar between groups. Washout periods were long enough |
Korkut 2005.
| Methods | Study design: open‐label, prospective, parallel‐group study Duration of follow‐up: 6 months | |
| Participants | Total number of participants randomised: N = 105 Inclusion criteria: diagnosis of acne vulgaris Exclusion criteria
Sites of acne: unclear Severity of acne and corresponding criteria of judgement: the acne grading system of the American Academy of Dermatology Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 8/24; B = 7/22; C = 8/24 Age (years): overall = 18.44 (3.75) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and each month It is unclear which outcome was assessed as the primary one in the trial | |
| Study details | Study period: unclear Country: Turkey Setting: outpatient clinics Number of study centres: unclear Washout period: 2 weeks washout for topical agents, 1 month for systemic antibiotics, and 6 months for isotretinoin Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "to compare the effects and side effects of these two drugs alone and in combination in the treatment of acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "the patients were randomly divided into three groups with 35 patients in each" Comment: randomisation method used is unclear |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: trial is described as "open‐label" |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: trial is described as "open‐label" |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "two patients in group BP and two patients in group ABP discontinued the therapy due to acute contact dermatitis" Comment: only a low proportion of participants were lost to follow‐up, with numbers and reasons similar between groups |
| Selective reporting (reporting bias) | High risk | Comment: trial authors mentioned in the methods section that participants were evaluated every month. However, they reported efficacy results only for month 6 |
| Other bias | High risk | Comment: according to Table 1, the severity of acne at baseline was not similar between groups |
Langner 2007.
| Methods | Study design: randomised, single‐blind controlled trial, parallel group Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 148 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Leeds Revised Acne Grading System Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 26/47; B = 24/51 Age (years): A = 21.2 (5.9); B = 19.5 (4.5) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 1, 2, 4, 8, and 12 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: Poland and the UK Setting: unclear Number of study centres: 4 Washout period: "patients who were using anti‐androgen‐containing contraceptives, who had received oral or topical steroids, oral or topical antibiotics, or acne treatment of any kind, including natural or artificial UV therapy, or did so at any stage of their participation in the trial were excluded", but the time window for these treatments was not reported Registered number: unclear ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial (Stiefel International R&D) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "to compare the clinical effectiveness of two combination treatments for facial acne: a ready mixed, once daily gel containing clindamycin phosphate (1%) plus benzoyl peroxide (5%) (CDP + BPO) and a twice daily solution of erythromycin (4%) plus zinc acetate (1.2%) (ERY + Zn)" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "patients were assigned to treatment groups in a 1:1 ratio using a computer‐generated randomization schedule with a block size of 6" Comment: the method used to generate random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "to maintain blinding, the physician did not inform the patient as to whether application was once or twice daily (and vice versa). A separate study nurse or pharmacist was responsible for dispensing study medication and for instructing the patient on the proper method of application" Comment: the study was described as an "assessor‐blinded study"; however, complete blinding was difficult as the vehicle differed by treatment group |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "all assessors were blinded to the treatment received. Pre‐study training was used to standardize assessments. To optimize consistency of subjective evaluations, the same staff saw the same patients at each of their visits, whenever possible" Comment: blinding was possible and may not be broken by treatment‐related adverse events, which were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: 5 in the CDP + BPO group and 8 in the ERY + Zn group did not complete the study but numbers of and reasons for withdrawal were comparable between groups |
| Selective reporting (reporting bias) | Unclear risk | Comment: all outcomes listed in the methods section were reported, but without a protocol or relevant information on a trial registry, risk of bias in selective reporting is unclear |
| Other bias | Unclear risk | Comment: according to Table 1, the severity of acne at baseline was not similar between groups. The washout period was not reported |
Langner 2008.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 130 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Leeds Revised Acne Grading System Treatment before study: most participants (80%) had been treated previously for acne vulgaris Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 27/38; B = 27/38 Age (years): A = 21.4 (4.50); B = 21.8 (4.75) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 1, 2, 4, 8, and 12 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: Poland and the UK Setting: unclear Number of study centres: 2 Washout period: 1 month washout for oral or topical steroids, oral or topical antibiotics, or acne treatment of any kind Registered number: unclear ITT analysis: yes | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: "this study was supported by Stiefel International R&D. The investigating authors received payments for this research study. None of the authors is an employee and/or consultant for Stiefel Laboratories Inc. V.G. has acted as the coordinator for the Leeds Stiefel Forum meeting which is an educational meeting for general practitioners" Publication status: full article | |
| Stated aim for study | Quote from publication: "to compare the clinical effectiveness of two treatments for facial acne: a ready‐mixed once‐daily gel containing clindamycin phosphate 10 mg mL‐1+ benzoyl peroxide 50 mg mL‐1 (CDP + BPO; Duac®; Stiefel, High Wycombe, U.K.) and a once‐daily gel containing adapalene 0.1% (ADA; Differin®; Galderma, Watford, U.K.)" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "patients were assigned to treatment groups in a 1:1 ratio using a predetermined computer‐generated randomization schedule with a block size of six. Within each country, patients were randomized to each treatment in equal numbers" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: trial authors did not report whether participants/study personnel were blinded. Blinding was possible as the vehicles and frequency of treatments were similar and treatment‐related adverse events were similar between groups |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "all assessors were blinded to the treatment received" Comment: outcome assessors were blinded. Blinding was possible as treatment‐related adverse events were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "one hundred and twenty patients (92.3%) completed the study, with the main reasons for discontinuation being noncompliance and unavailability for follow‐up" Comment: it is unclear whether the reasons for discontinuation were similar between the 2 groups |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | Low risk | Quote: "the two treatment groups were well matched with respect to demography" Comment: baseline characteristics were similar between groups. Washout periods were long enough |
Leyden 2001a.
| Methods | Study design: randomised, double‐blind, parallel‐group study Duration of follow‐up: 10 weeks | |
| Participants | Total number of participants randomised: N = 480 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Pillsbury classification system Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 52/68; B = 58/62; C = 64/56; D = 48/72 Age (years): A = 19 (4); B = 19 (4); C = 19 (4); D = 19 (5) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Interventions in Group D
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 2, 4, 6, 8, and 10 of treatment It was not reported which outcome was assessed as the primary one in the trial | |
| Study details | Study period: October 1991 to April 1992 Country: USA Setting: unclear Number of study centres: 4 Washout period: 2 weeks washout for topical anti‐acne preparations and 4 weeks for systemic anti‐bacterials Registered number: unclear ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial (Dermik Laboratories, Inc.) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "to determine the efficacy and safety of a combination benzoyl peroxide plus clindamycin in a gel formulation compared with each of its 2 active constituents in gel vehicle, and gel vehicle given alone in the treatment of acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: the method used to generate the random sequence was not specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: trial is described as "double‐blind". It is unclear whether participants and personnel were blinded. Blinding was possible as the vehicles and frequency of treatments were similar and treatment‐related adverse events were similar between groups |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: trial is described as "double‐blind". It is unclear whether outcome assessors were blinded. Blinding was possible as treatment‐related adverse events were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "all 480 patients who were enrolled and randomized were included in the intent‐to‐treat analysis, and 461 had at least one follow‐up visit. A total of 43 patients (9%) did not complete the study. Rates of discontinuation were similar among all 4 treatment groups, and were primarily because of missing 2 or more clinic visits (13 patients, 2.7%) and voluntary withdrawal (11 patients, 2.3%)" Comment: numbers of and reasons for withdrawal were similar between groups and researchers used the intent‐to‐treat analysis strategy |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | Low risk | Quote: "no significant differences in demographic characteristics were detected among treatment groups (table 1)" Comment: baseline characteristics were similar between groups. Washout periods were long enough |
Leyden 2001b1.
| Methods | Study design: randomised, double‐blind, parallel‐group study Duration of follow‐up: 2 weeks | |
| Participants | Total number of participants randomised: N = 80 Inclusion criteria: unclear Exclusion criteria: unclear Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Interventions in Group D
Co‐interventions: not reported | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 1 and 2 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "in the first study (Table 1), the combination gel was compared with 3 topical formulations of 1% clindamycin phosphate (gel, lotion, and solution) in 80% individuals..." | |
| Notes | This is 1 of 2 trials reported in Leyden 2001b | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "randomized study treatments were applied topically to the face by the study staff twice daily for 2 weeks" Comment: the method of randomisation used is unclear |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: complete blinding was difficult as the vehicle differed by treatment group |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "cultures were assessed quantitatively in a blinded manner from plate samples" Comment: outcome assessment was blinded |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on follow‐up was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information for judgement was provided |
| Other bias | Unclear risk | Comment: it is unclear whether baseline characteristics were similar between groups |
Leyden 2001b2.
| Methods | Study design: randomised, double‐blind, parallel‐group study Duration of follow‐up: 16 weeks | |
| Participants | Total number of participants randomised: N = 62 Inclusion criteria: mild to moderate acne Exclusion criteria: unclear Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: not reported | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 4, 8, 12, and 16 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "the second study compared the combination gel of benzoyl peroxide and clindamycin with 1% clindamycin in 79 patients (62 patients evaluable) with mild to moderate acne" | |
| Notes | This is 1 of 2 trials reported in Leyden 2001b | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "again, randomized treatment was applied to the face twice daily" Comment: the method of randomisation used is unclear |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: insufficient information for judgement was provided |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information for judgement was provided |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on follow‐up was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information for judgement was provided |
| Other bias | Unclear risk | Comment: it is unclear whether baseline characteristics were similar between groups |
Lookingbill 1997.
| Methods | Study design: 2 double‐blind, randomised, parallel, vehicle‐controlled studies Duration of follow‐up: 11 weeks | |
| Participants | Total number of participants randomised: N = 334 (the study reported only the number of participants who completed the study) Inclusion criteria
Exclusion criteria
Sites of acne: unclear Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): overall = 191/202 Age (years): overall = 18.5 Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Interventions in Group D
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 2, 5, 8, and 11 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: fall of 1994 through spring of 1995 Country: USA Setting: unclear Number of study centres: multiple Washout period: 1 week washout for medicated shampoos or cleansers; 1 month for acne treatment of any type, systemic or topical antibiotics or corticosteroids, or any medication that would interfere with study results; and 6 months for oral isotretinoin Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: commercial (Stiefel Laboratories, Inc.) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "to determine the efficacy and safety of a combination clindamycin/benzoyl peroxide gel when compared with benzoyl peroxide, clindamycin, or vehicle gels" | |
| Notes | This report mixed results from 2 trials and did not report baseline characteristics for each study and each group | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: trial authors did not report the methods of randomisation used |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: trial authors did not specify who was blinded, despite claiming double‐blind. However, complete blinding was difficult as treatment‐related peeling and erythema were more common in the BPO and BPO/clindamycin groups |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: trial authors did not specify who was blinded, despite claiming double‐blind. However, complete blinding was difficult as treatment‐related peeling and erythema were more common in the BPO and BPO/clindamycin groups |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "a total of 334 patients (85%) completed the study without protocol violations. The completion rate for each group was as follows: combination gel (CLX), 88%; benzoyl peroxide (BPO), 85%; clindamycin (CDM), 82%; and vehicle (VEH), 84%" Comment: despite similar incomplete rates between groups, reasons for withdrawal in each group are unclear |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability of participant characteristics was provided |
Lyons 1978.
| Methods | Study design: controlled, randomised clinical study Duration of follow‐up: 8 weeks | |
| Participants | Total number of participants randomised: N = 159 Inclusion criteria: grades I to III acne vulgaris Exclusion criteria: unclear Sites of acne: unclear Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 16/38; B = 7/31; C = 17/38 Age (years): A = 18.9; B = 17.7; C = 18.6 Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: non‐medicated soap and water was allowed for cleansing. No other medication thought to have an effect on acne was allowed | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated every 2 weeks It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: USA Setting: unclear Number of study centres: 3 Washout period: unclear Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "to compare the clinical effect of benzoyl peroxide and tretinoin on acne lesions" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "the allocation of patients to treatment groups was randomly determined by the use of pre‐numbered patient report forms which specified medication to be dispensed" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: this is an open‐label study |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: this is an open‐label study |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: results for 147 of 159 participants were provided. The number of withdrawals was not similar between groups and reasons for withdrawal were not reported |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all of the outcomes listed in the methods section were reported, we could not identify the corresponding protocol to confirm that selective reporting was avoided |
| Other bias | High risk | Comment: according to Table 1, the sex ratio was not similar between groups |
Makino 2015.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 73 (the abstract mentioned only the number of participants who completed the study) Inclusion criteria: unclear Exclusion criteria: unclear Sites of acne: face Severity of acne and corresponding criteria of judgement: Investigator's Global Assessment of acne severity Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 4, 8, and 12 There was not enough information to determine which outcome was assessed as the primary outcome | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: commercial (SkinMedica, an Allergan Company) Conflicts of interest: not specified Publication status: conference abstract | |
| Stated aim for study | Quote from publication: "a randomized, investigator‐blind, 12 week comparison study was conducted to compare three topical regimens (R1, R2, and R3) in the treatment of moderate facial acne (R1‐SA 2%, retinol 0.5%; R2‐SA 2%; and R3‐adapalene, BPO 0.1%/2.5% gel)" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: the trial was investigator‐blinded, indicating that participants and personnel were not blinded. Also, the frequency of treatment differed by treatment group |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: this trial is described as "investigator‐blinded". Based only on information from the abstract, it is unclear whether treatment‐related adverse events were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on numbers of and reasons for withdrawal for each group was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability of participant characteristics between groups was provided |
Marazzi 2002.
| Methods | Study design: multi‐centre, randomised, single‐blind, parallel‐group study Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 188 Inclusion criteria: 15 to 100 acne inflammatory lesions and/or 15 to 100 non‐inflammatory lesions, ≤ 3 nodulo‐cystic lesions Exclusion criteria: unclear Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 45/50; B = 37/56 Age (years): A = 17.1 (5.0); B = 16.9 (3.6) Duration of acne (years): A = 3.7; B = 2.9 | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 2, 4, 8, and 12 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: 19 October 1998 to 17 June 1999 Country: UK Setting: primary care centre Number of study centres: 11 Washout period: unclear Registered number: unclear ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial (Profiad Limited) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "to assess the efficacy and safety of the test product, isotretinoin/erythromycin gel, with a currently used and effective treatment for mild to moderate acne vulgaris, benzoyl peroxide/erythromycin gel" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "patients recruited for the study were assigned according to a pre‐determined randomisation schedule to receive either isotretinoin/erythromycin gel or benzoyl peroxide/erythromycin gel" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "this multi‐centre, single‐blind (investigator blind), parallel group study compared the efficacy and safety..." Comment: this trial was described as "single blind (investigator blind)", which indicated participants and personnel were not blinded. Also, the frequency of treatments differed by group |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "this multi‐centre, single‐blind (investigator blind), parallel group study compared the efficacy and safety..."; "For each patient, the investigator subjectively assessed the overall facial acne condition as a global change score" Comment: the trial was described as "single blind (investigator blind)", and the investigator was referred to the outcome assessor according to trial authors Treatment‐related adverse events were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Quote: "patients were excluded from the per‐protocol population from the visit at which the major violation was recorded, if applicable... Major protocol violations at visits 1 or 2 occurred in three patients in the isotretinoin/erythromycin group and seven patients in the benzoyl peroxide/erythromycin group, leaving 178 efficacy‐evaluable patients (per‐protocol population)" Comment: the number of withdrawals was not similar between groups and trial authors did not take intention‐to‐treat analysis strategy |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol to confirm that selective reporting was avoided |
| Other bias | Unclear risk | Comment: according to Table 1, the sex ratio was not similar between groups. Washout periods were not reported |
Milani 2003.
| Methods | Study design: double‐blind, parallel‐group study Duration of follow‐up: 8 weeks | |
| Participants | Total number of participants randomised: N = 60 Inclusion criteria
Exclusion criteria: acne conglobata, severe acne, or requiring more than topical treatment Sites of acne: mainly the face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 10/20; B = 14/16 Age (years): A = 23.8 (7); B = 25.9 (6) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐intervention: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 4 and 8 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: October 2001 to March 2002 Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial (Mipharm Spa) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "to evaluate efficacy and local tolerability of HPS in mild‐to‐moderate AV in comparison with BP gel" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: trial authors did not report the methods of randomisation used |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "the study was a randomised, prospective, investigator‐masked parallel‐group, 8‐week trial" Comment: trial authors indicated that participants and personnel were not blinded. Also, the vehicle of treatment differed by treatment group |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "the study was a randomised, prospective, investigator‐masked parallel‐group, 8‐week trial" and "TL, NIL, and IL were assessed by an investigator, unaware of treatment allocation, at baseline, and week 8" Comment: the trial was described as "single blind (investigator blind)", where the investigator was referred to the outcome assessor. However, complete blinding was difficult as treatment‐related adverse events were more common in the BPO group |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "the efficacy and tolerability evaluations were performed on an intention‐to‐treat basis" Comment: although ITT analysis was conducted, no information on withdrawal was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, without a protocol or relevant information on a trial registry, it is difficult to confirm whether there was selective reporting |
| Other bias | Unclear risk | Comment: according to Table 1, baseline characteristics between groups were similar. Washout periods were not reported |
Mills 1986.
| Methods | Study design: double‐blind, parallel‐group study Duration of follow‐up: 8 weeks | |
| Participants | Total number of participants randomised: N = 153 Inclusion criteria: mild to moderate inflammatory acne vulgaris (≥ 10 inflammatory lesions) Exclusion criteria: unclear Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): overall = 74/79 Age (years): overall = 20 (average) Duration of acne (years): unclear | |
| Interventions | TRIAL 1 Interventions in Group A
Interventions in Group B
TRIAL 2 Interventions in Group A
Interventions in Group B
TRIAL 3 Interventions in Group A
Interventions in Group B
Co‐intervention: washing with a non‐medicated soap before the interventions in all 3 trials | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 2, 4, 6, and 8 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "this paper describes clinical trials of a 2.5% benzoyl peroxide gel, which was compared with 5% and 10% benzoyl peroxide gels in groups of patients with inflammatory acne vulgaris" | |
| Notes | This paper described 3 trials, in which 2.5% BPO gel was compared with placebo, 5% BPO gel, and 10% BPO gel, respectively | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method of random sequence generation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: trial authors claimed that the trial was double‐blind; however, no information on who was blinded was provided |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: trial authors claimed that the trial was double‐blind; however, no information on who was blinded was provided |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: the proportion of withdrawal was low in these trials: no participants withdrew in Trial 1, 2 participants in the 5% BPO group in Trial 2, and 2 participants (1 in each group) in Trial 3 |
| Selective reporting (reporting bias) | High risk | Quote: "a global assessment of improvement was also made by the investigator at each visit" Comment: trial authors reported only whether or not a significant difference was found, rather than presenting all results for each visit |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability between groups and on washout periods was provided |
Miyachi 2016.
| Methods | Study design: double‐blind, parallel‐group study Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 417 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: specified Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 71/141; B = 34/67; C = 30/74 Age (years): A = 19.7 (6.5); B = 19.6 (6.0); C = 19.3 (5.4) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐intervention: moisturiser and sunscreen | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at screening, at baseline, and at weeks 1, 2, 4, 6, 8, and 12 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: March 2014 to October 2014 Country: Japan Setting: medical institutions Number of study centres: 21 Washout period: 1 week for treatment with eyebrows, adhesive tape‐type cleansing agent, other cosmetic treatments; 2 weeks for topical corticosteroids, antibiotics (including antibiotics), zinc, anti‐inflammatory agents, salicylic acid; 4 weeks for retinoid (including vitamin A), other topical treatments on the face (peeling, laser, photodynamic therapy, astringent), systemic corticosteroids, immunomodulators, biological preparations, antibiotics; and 24 weeks for isotretinoin, anti‐androgen, oral contraceptive Registered number:NCT02073448 ITT analysis: yes | |
| Publication details | Language of publication: Japanese Funding: commercial (Garderma) Conflicts of interest: "Yoshiki Miyaji was a Contract Medical Specialist at Garderma at the time of the study. Fabienne Mizzi, Tetsuya Mita, Shiratiwa, and Ikuko Yoshihiko are employees of Garderma" Publication status: full text | |
| Stated aim for study | Quote from publication: "this study was conducted in Japanese patients with acne vulgaris to assess the efficacy of the fixed dose combination gel of adapalene 0.1% and benzoyl peroxide 2.5% in comparison with each monad gel as well as the safety and tolerability prole of this fixed dose combination gel in a 12‐week treatment" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "an allocation table was created before the start of the trial. The allocation ratio was adapalene 0.1%/BPO 2.5% combination gel: adapalene 0.1%: BPO 2.5% 2:1:1, and 8 cases were divided into 1 block and distributed to each medical institution" Comment: the method used to generate the random sequence was not specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: the trial was double‐blinded (participants and investigators). However, complete blinding was difficult as treatment‐related adverse events were more common in the BPO/adapalene group |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: this trial is described as "double‐blind", but it is unclear whether outcome assessors were blinded. Complete blinding was difficult as treatment‐related adverse events were more common in the BPO/adapalene group |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: according to the flow chart, less than 10% of participants withdrew from the trial and ITT analysis was conducted |
| Selective reporting (reporting bias) | Unclear risk | Comment: not all outcomes reported in the publication were specified on the trial registry |
| Other bias | Low risk | Quote: "overall, gender, age and skin phototype at baseline were similar among treatment groups" Comment: baseline characteristics were similar between groups as shown in Table 2. Washout periods were long enough |
NCT00713609.
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 587 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 48/58; B = 49/56; C = 47/60; D = 48/60; E = 41/65; F = 20/35 Age (years): A = 19.7 (6.6); B = 19.7 (6.9); C = 20.2 (7.3); D = 19.2 (6.2); E = 21.7 (8.4); F = 19.8 (6.6) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Interventions in Group D
Interventions in Group E
Interventions in Group F
Co‐interventions: not specified | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Outcomes were assessed at weeks 2, 4, 8, and 12 *These were the primary outcomes assessed in the trial | |
| Study details | Study period: June 2008 to March 2009 Country: USA Setting: unclear Number of study centres: 16 Washout period: 4 weeks for topical antibiotics or topical steroids on the face, facial procedures, or any investigational therapy; and 6 months for systemic retinoids Registered number:NCT00713609 ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial (Stiefel, a GSK Company) Conflicts of interest: not specified Publication status: results published on ClinicalTrials.gov | |
| Stated aim for study | Quote from publication: "benzoyl peroxide, clindamycin and tazarotene are known to be effective treatment alternative for acne vulgaris. The purpose of this study is to assess the safety and efficacy of a combination product including these actives for the treatment of acne vulgaris" | |
| Notes | We attempted to contact the study sponsor, Stiefel, a GSK Company (GSKClinicalSupportHD@gsk.com), to request related information but were unsuccessful | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method used to generate the random sequence was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote: "masking: quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)". Also, the vehicles and frequency of treatments and treatment‐related adverse events were similar between groups |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "masking: quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)". Also, treatment‐related adverse events were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: about 15% of participants did not complete the trial |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes planned on the trial registry were reported |
| Other bias | Unclear risk | Comment: insufficient information on baseline acne severity was provided |
NCT00787943.
| Methods | Study design: split‐face design Duration of follow‐up: 4 weeks | |
| Participants | Total number of participants randomised: N = 10 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for all participants Sex ratio (male/female): 4/6 Age (years): range 18 to 65 Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at days 2, 7, and 28 *This was the primary outcome assessed in the trial | |
| Study details | Study period: May 2008 to January 2009 Country: USA Setting: hospital Number of study centres: 1 Washout period: 2 weeks for topical or systemic acne medication Registered number:NCT00787943 ITT analysis: yes | |
| Publication details | Language of publication: English Funding: non‐commercial (Northwestern University) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "benzoyl peroxide 10.0% creams (Formulation #1 and Formulation #2) will be evaluated to detect any differences in their response for safety and efficacy" | |
| Notes | The difference between the 2 formulations is unclear. We attempted to contact the investigator, Amy Paller (apaller@northwestern.edu), to request related information but were unsuccessful | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method used to generate the random sequence was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: insufficient information on the method of blinding was provided |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information on the method of blinding was provided |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: no participants were lost to follow‐up |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes planned on the trial registry were reported |
| Other bias | High risk | Comment: the split‐face design made baseline characteristics similar between the 2 sides of faces in the within‐person comparison. However, the washout period for systemic acne treatments was not long enough |
NCT01044264.
| Methods | Study design: parallel design Duration of follow‐up: 11 weeks | |
| Participants | Total number of participants randomised: N = 602 Inclusion criteria
Exclusion criteria
Sites of acne: face Criteria for judgement of acne severity: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 97/103; B = 101/101; C = 87/113 Age (years): A = 19.2 (7.3); B = 19.5 (7.1); C = 20.1(8.3) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐intervention: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at week 11 *This was the primary outcome assessed in the trial | |
| Study details | Study period: December 2007 to September 2008 Country: unclear Setting: unclear Number of study centres: multiple Washout period: 30 days for BPO/clindamycin Registered number:NCT01044264 ITT analysis: no | |
| Publication details | Language of publication: English Funding: commercial (Perrigo Company) Conflicts of interest: not specified Publication status: results published on ClinicalTrials.gov | |
| Stated aim for study | Quote from publication: "a randomized, double‐blind, multiple‐site, placebo‐controlled, parallel‐group clinical study conducted to evaluate the bioequivalence of two 1% Clindamycin/5% Benzoyl Peroxide Topical Gel formulations" | |
| Notes | The difference between the 2 formulations is unclear. We attempted to contact the sponsor, Perrigo Company (https://www.perrigo.com/contact/email.aspx?subject=Rx), to request related information but were unsuccessful. Data from Groups A and B were combined into 1 group in comparison with Group C in meta‐analysis for the comparison between BPO/clindamycin and placebo | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method used to generate the random sequence was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: trial authors claimed that the trial was double‐blind; it is unclear who was blinded. The vehicle and frequency of treatments and treatment‐related adverse events were similar between groups |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: trial authors claimed that the trial was double‐blind; it is unclear who was blinded. Treatment‐related adverse events were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: about 46% participants did not complete the trial and ITT analysis was not conducted |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes planned on the trial registry were reported |
| Other bias | Unclear risk | Comment: insufficient information on baseline acne severity and on washout periods for acne treatment other than BPO/clindamycin was not provided |
NCT01138514.
| Methods | Study design: parallel design Duration of follow‐up: 10 weeks | |
| Participants | Total number of participants randomised: N = 1555 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 238/284; B = 234/282; C = 238/279 Age (years): A = 20.2 (7.6); B = 20.1 (7.4); C = 20.7 (8.1) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐intervention: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at week 10 *This was the primary outcome assessed in the trial | |
| Study details | Study period: October 2009 to October 2010 Country: unclear Setting: unclear Number of study centres: multiple Washout period: 30 days for BPO/clindamycin Registered number:NCT01138514 ITT analysis: no | |
| Publication details | Language of publication: English Funding: commercial (Perrigo Company) Conflicts of interest: not specified Publication status: results published on ClinicalTrials.gov | |
| Stated aim for study | Quote from publication: "the purpose of this study is to compare the efficacy and safety profiles of Perrigo Israel Pharmaceuticals, Ltd. Clindamycin 1%/Benzoyl Peroxide 5% Topical Gel and Benzaclin® Topical Gel (Clindamycin‐ Benzoyl Peroxide Gel)" | |
| Notes | The difference between the 2 formulations is unclear. We attempted to contact the sponsor, Perrigo Company (https://www.perrigo.com/contact/email.aspx?subject=Rx), to request related information but were unsuccessful. Data from Groups A and B were combined into 1 group in comparison with Group C in meta‐analysis for the comparison between BPO/clindamycin and placebo | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method used to generate the random sequence was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "double (participant, investigator)" Comment: even though double‐blinding was conducted, complete blinding was difficult as treatment‐related adverse events were more common in the BPO/clindamycin groups |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "double (participant, investigator)" Comment: even though double‐blinding was conducted, complete blinding was difficult as treatment‐related adverse events were more common in the BPO/clindamycin groups |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: about 12.5% of participants did not complete the trial and ITT analysis was not conducted |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes planned on the trial registry were reported |
| Other bias | Unclear risk | Comment: insufficient information on baseline acne severity was provided |
NCT01231334.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 186 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 0/145; B = 0/141 Age (years): A = 27.2 (6.5); B = 27.9 (7.1) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐intervention: adapalene 0.1% once daily for 12 weeks | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at week 12 *This was the primary outcome assessed in the trial | |
| Study details | Study period: August 2010 to June 2011 Country: USA Setting: unclear Number of study centres: 1 Washout period: unclear Registered number:NCT01231334 ITT analysis: no | |
| Publication details | Language of publication: English Funding: commercial (Allergan) Conflicts of interest: not specified Publication status: results published on ClinicalTrials.gov | |
| Stated aim for study | Quote from publication: "a study comparing the topical application of Aczone® plus Differin® versus Duac® plus Differin® in patients with severe facial acne (facial acne vulgaris)" | |
| Notes | We attempted to contact the sponsor, Allergan (IR‐Medicalaffairsresearch@allergan.com), to request clarification for unclear information published on the registry but were unsuccessful | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method used to generate the random sequence was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: the trial was single‐blinded (investigator) |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Comment: investigators were blinded. Complete blinding was possible as treatment‐related adverse events were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: about 14% of participants were lost to follow‐up without reasons for withdrawal being specified and ITT analysis was not conducted |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes planned on the trial registry were reported |
| Other bias | Unclear risk | Comment: insufficient information on baseline acne severity and on washout periods was reported |
NCT01522456.
| Methods | Study design: split‐face design Duration of follow‐up: 3 weeks | |
| Participants | Total number of participants randomised: N = 73 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for all participants Sex ratio (male/female): 20/53 Age (years): 30.8 (5.97) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐intervention: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated every day from baseline until the 22nd day *This was the primary outcome assessed in the trial | |
| Study details | Study period: April 2012 to May 2012 Country: USA Setting: unclear Number of study centres: 1 Washout period: 1 week washout for topical corticosteroids and any oral medications that may have increased photosensitivity; 4 weeks for topical retinoids and oral corticosteroids; 24 weeks for oral retinoids Registered number:NCT01522456 ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial (Galderma Laboratories, L.P.) Conflicts of interest: not specified Publication status: results published on ClinicalTrials.gov | |
| Stated aim for study | Quote from publication: "to compare the tolerability of Epiduo® (adapalene and benzoyl peroxide) Gel 0.1%/2.5% to Retin‐A Micro® (tretinoin gel) microsphere when used by subjects with acne vulgaris for 3 weeks in terms of local tolerability parameters (erythema, dryness, scaling, stinging/burning) and preference" | |
| Notes | We attempted to contact the sponsor, Galderma (clinicaltrials@galderma.com), to request clarification for unclear information published on the registry but were unsuccessful | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method used to generate the random sequence was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: the trial was single‐blinded (investigator) |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Comment: investigators were blinded. Complete blinding was possible as treatment‐related adverse events were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: although 11% of participants were lost to follow‐up, ITT analysis was conducted and split‐face design still made baseline characteristics comparable within participants |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes planned on the trial registry were reported |
| Other bias | High risk | Comment: baseline characteristics were controlled within participants in the split‐face design. However, washout periods for systemic treatments were not long enough |
NCT02073461.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 236 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 27/51; B = 22/57; C = 34/45 Age (years): A = 21.1 (5.6); B = 22.1 (7.0); C = 21.4 (6.3) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at week 12 *This was the primary outcome assessed in the trial | |
| Study details | Study period: March 2014 to October 2014 Country: Japan Setting: unclear Number of study centres: 6 Washout period: unclear Registered number:NCT02073461 ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial (Galderma R&D) Conflicts of interest: not specified Publication status: results published on ClinicalTrials.gov | |
| Stated aim for study | Quote from publication: "this study is to assess the efficacy and safety of two concentrations of CD1579 (2.5% and 5%) versus vehicle in the treatment of acne vulgaris in the Japanese patients" | |
| Notes | We attempted to contact the sponsor, Galderma (clinicaltrials@galderma.com), to request clarification for unclear information published on the registry but were unsuccessful | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method used to generate the random sequence was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Comment: the trial was double‐blinded (participants and investigators). Complete blinding was possible as treatment‐related adverse events were similar between groups |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Comment: investigators were blinded. Complete blinding was possible as treatment‐related adverse events were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: only 2.5% of participants were lost to follow‐up and ITT analysis was conducted |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes planned on the trial registry were reported |
| Other bias | Unclear risk | Comment: insufficient information on baseline acne severity was provided |
NCT02465632.
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 10 weeks | |
| Participants | Total number of participants randomised: N = 1073 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 158/274; B = 171/259; C = 84/127 Age (years): A = 22.8 (7.7); B = 22.3 (7.6); C = 22.6 (7.5) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: not reported | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at week 10 *This was the primary outcome assessed in the trial | |
| Study details | Study period: April 2015 to December 2015 Country: USA Setting: unclear Number of study centres: 15 Washout period: unclear Registered number:NCT02465632 ITT analysis: no | |
| Publication details | Language of publication: English Funding: commercial (Glenmark Pharmaceuticals Ltd. India) Conflicts of interest: not specified Publication status: results published on ClinicalTrials.gov | |
| Stated aim for study | Quote from publication: "this is a randomized, double‐blind, multiple‐site, placebo‐controlled, parallel‐group study, designed to compare the efficacy and safety of generic Clindamycin 1%/ Benzoyl peroxide 5% topical gel (Glenmark Generics, Ltd), and the marketed product BenzaClin® Topical Gel, Clindamycin 1%/ Benzoyl peroxide 5% (Valeant Pharmaceuticals, US) in the treatment of acne vulgaris" | |
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, Glenmark Pharmaceuticals (GlobalPV@glenmarkpharma.com), with enquiry about availability of the full text but were unsuccessful | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method used to generate the random sequence was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Comment: the trial was triple‐blinded (participants, care providers, and investigators). Complete blinding was possible as the vehicle and frequency of treatments and treatment‐related adverse events were similar between groups |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Comment: investigators were blinded. Complete blinding was possible as treatment‐related adverse events were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: less than 10% of participants were lost to follow‐up but ITT analysis was not conducted |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes planned on the trial registry were reported |
| Other bias | Unclear risk | Comment: insufficient information on baseline acne severity was provided |
Ozgen 2013.
| Methods | Study design: parallel design Duration of follow‐up: 8 weeks | |
| Participants | Total number of participants randomised: N = 93 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 20/27; B = 16/30 Age (years): A = 19.1; B = 19.7 (SD was not available) Duration of acne (years): A = 4.6; B = 4.4 | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: nadifloxacin 1% cream twice daily | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 2, 4, and 8 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: Turkey Setting: dermatology outpatient clinic of a university‐affiliated hospital Number of study centres: 1 Washout period: at least 2 weeks for topical acne therapies; 4 weeks for oral antibiotics and laser or chemical peelings; 3 months for oestrogens or birth control pills; and 6 months for oral retinoids Registered number: unclear ITT analysis: yes | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "the primary purpose of this study was to compare the efficacies of nadifloxacin alone and with benzoyl peroxide in the treatment of mild to moderate facial acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "patients were randomized consecutively in a 1:1 ratio to apply either nadifloxacin 1% cream (Nadixa 1% cream; Adeka) twice daily and benzoyl peroxide 5% lotion (Aknefug BP5 lotion; Orva) once daily (5 minutes after nadifloxacin) or nadifloxacin 1% cream twice daily and vehicle of benzoyl peroxide once daily for 8 weeks according to a computer generated list" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information about allocation concealment was presented |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Quote: "randomized, double‐blind, parallel group study, in which the patients were randomly assigned to use either nadifloxacin 1% cream alone or with benzoyl peroxide 5% lotion during an 8‐week treatment period......The integrity of the blinding was ensured by packaging the benzoyl peroxide lotion and its vehicle in identical bottles and allocating a different person to dispense the medications" Comment: it seems that personnel were blinded, but trial authors did not report whether participants were blinded. Adverse events were reported to be higher in the BPO plus nadifloxacin group but it is unclear whether events were treatment‐related |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: trial authors did not report whether outcome assessors were blinded. Adverse events were reported to be higher in the BPO plus nadifloxacin group but it is unclear whether events were treatment‐related |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "fourteen patients were dropped due to follow‐up failure (3 patients), incompliance (10 patients), and side effects (1 patient)" Comment: trial authors did not compare the number of withdrawals and corresponding reasons between the 2 groups |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | High risk | Quote: "the baseline characteristics of the patients are summarized in Table І. The treatment groups were comparable in respect to the demographic characteristics and baseline number of inflammatory lesions, but not in respect to the noninflammatory lesions. The mean number of noninflammatory lesions were higher in the nadifloxacin + benzoyl peroxide group" Comment: baseline severity of acne was not similar between groups |
Packman 1996.
| Methods | Study design: parallel design Duration of follow‐up: 10 weeks | |
| Participants | Total number of participants randomised: N = 205 (199 were analysed) Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Pillsbury classification Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 0/99; B = 0/100 Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 2, 4, 7, and 10 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: 2 Washout period: 4 weeks for a systemic antibiotic treatment; and 2 weeks for a topical acne medication Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: not specified | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method used to generate the random sequence was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "two hundred and five women between the ages of 23 and 50 years with Grade II or III acne vulgaris (Pillsbury classification) and between 10 and 80 inflammatory lesions, were enrolled in the investigator‐blinded, randomized, multicenter study" Comment: trial authors described the trial as investigator‐blinded (i.e. outcome assessor was blinded), which indicates that participants and personnel were not blinded |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "the evaluating physician, who was not aware of the assigned medication, counted all comedones, papules, and pustules on the patient's face"; "Six patients (6%) in the erythromycin/benzoyl peroxide group had adverse experiences that were considered to be probably or definitely related to treatment, as did one patient (1%) in the clindamycin phosphate group" Comment: complete blinding was possible as treatment‐related adverse events were not significantly different between the 2 groups |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "six patients were not included in the efficacy analysis because they discontinued the study before their first follow‐up visit" Comment: numbers of and reasons for withdrawal for each group were unclear |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | Unclear risk | Comment: insufficient information on the comparability of baseline characteristics was provided |
Papageorgiou 2000.
| Methods | Study design: parallel design Duration of follow‐up: 8 weeks | |
| Participants | Total number of participants randomised: N = 45 Inclusion criteria: grade I acne severity and ≥ 5 inflammatory lesions Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 4/9; B = 3/10; C = 4/11 Age (years): A = 29.5 (range 19 to 50); B = 26.2 (range 14 to 43); C = 27.5 (range 14 to 50) Duration of acne (year): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at 4 and 8 weeks of treatment *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: multiple but unclear Washout period: 2 weeks washout for any systemic or topical acne therapy Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "the purpose of this trial was to evaluate this new product and compare its efficacy and safety with a more traditional acne therapy, 5% benzoyl peroxide cream" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: no information on the method used to generate the random sequence was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information about allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "this trial was a double‐blind controlled randomized parallel group comparison..." Comment: who was blinded remains unclear. However, complete blinding was difficult as treatment‐related adverse events were more common in the BPO group |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "this trial was a double‐blind controlled randomized parallel group comparison..." Comment: who was blinded remains unclear. However, complete blinding was difficult as treatment‐related adverse events were more common in the BPO group |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "four patients either voluntarily left the study or were lost to follow‐up" Comment: numbers of and reasons for withdrawal for each group were unclear |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | High risk | Quote: "the three groups were well matched in terms of number of patients, age, sex distribution and severity of acne (Table 1)" Comment: baseline characteristics were similar between groups. The washout period for systemic acne treatments was not long enough |
Pariser 2014.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 498 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Evaluator Global Severity Score (EGSS) Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 130/123; B = 126/119 Age (years): A = 18.2 (5.6); B = 19.3 (6.0) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 2, 4, 8, and 12 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: multiple but unclear Washout period: 1 week washout for topical astringents and abrasives; 2 weeks for topical anti‐acne products, including soaps containing anti‐microbials, and known comedogenic products; 4 weeks for topical retinoids, retinol, and systemic acne treatments; and 6 months for systemic retinoids. Registered number: unclear ITT analysis: yes | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "to evaluate efficacy, safety, and tolerability of a fixed combination clindamycin phosphate 1.2% and benzoyl peroxide 3.75% (clindamycin‐BP 3.75%) aqueous gel in moderate to severe acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "following the established stratification scheme, eligible patients were randomized (1:1) into one of 2 treatment groups: clindamycin‐BP 3.75% gel or vehicle. All patients applied study medication to the face once daily for 12 weeks" Comment: insufficient information on the method used to generate the random sequence was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: trial authors claimed that the trial was double‐blind, but it is unclear who was blinded. Complete blinding was possible as the vehicles and frequency of treatments and treatment‐related adverse events were similar between groups |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: trial authors claimed that the trial was double‐blind, but it is unclear who was blinded. Complete blinding was possible as treatment‐related adverse events were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: as shown in Figure 1, the proportion of withdrawal and corresponding reasons were not similar between groups |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | Low risk | Comment: as shown in Table 2, demographics and acne severity at baseline were similar between groups. Washout periods were long enough |
Prince 1982.
| Methods | Study design: split‐face design Duration of follow‐up: 8 weeks | |
| Participants | Total number of participants randomised: N = 39 Inclusion criteria: patients with grade II or III acne as described by Pillsbury Exclusion criteria: unclear Sites of acne: face Severity of acne and corresponding criteria of judgement: Pillsbury grading method Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed biweekly during the 8 weeks There was not enough information to determine which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article (we can access only the abstract) | |
| Stated aim for study | Quote from publication: "a clinical trial was performed to evaluate an improved vehicle for topical benzoyl peroxide" | |
| Notes | No full text available | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information for judgement was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information for judgement was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: insufficient information for judgement was provided |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information for judgement was provided |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information for judgement was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information for judgement was provided |
| Other bias | Unclear risk | Comment: insufficient information for judgement was provided |
Schaller 2016.
| Methods | Study design: parallel, single‐blind design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 217 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Investigator’s Static Global Assessment Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 47/61; B = 51/58 Age (years): A = 20.1 (7.1); B = 20.0 (6.9) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 1, 2, 4, 8, and 12 *This outcome was assessed as the primary outcome (at week 4) assessed in the trial | |
| Study details | Study period: unclear Country: Germany Setting: unclear Number of study centres: 11 Washout period: 6‐month washout for antibiotics, corticosteroids, or retinoids Registered number:NCT02058628, 2013‐004158‐81 ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial (GlaxoSmithKline) Conflicts of interest: "MSch has been a member of the advisory board of Bayer Healthcare and Galderma for the past 2 years and has received lecture fees from AbbVie, Bayer Healthcare, Galderma and La Roche‐Posay. MSeb has been an advisor or investigator for AbbVie, Novartis, Janssen‐Cilag, Lilly, Amgen, Celgene, Galderma, Leo Pharma, GSK, and Pfizer. CR, DS and MH are employees of GSK and hold stocks/shares in GSK" Publication status: full article | |
| Stated aim for study | Quote from publication: "to compare the efficacy, tolerability and safety of a combination of benzoyl peroxide 3% and clindamycin 1% (BPO + CLN) with azelaic acid 20% (AzA) for the topical treatment of mild‐to‐moderate acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "randomization (1:1) to treatments was performed using a computer‐generated schedule" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not mention the method of allocation concealment |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: trial authors specified that the trial was an assessor‐blinded trial. Participants were likely aware of their treatment because the 2 treatments differed in frequency |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Comment: trial authors specified that the trial was an assessor‐blinded trial. Complete blinding was possible as treatment‐related adverse events were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "the drop‐out rate was low, with only 15 out of 221 (6.8%) patients leaving the study post‐randomization" |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes defined on the trial registry were reported |
| Other bias | Low risk | Quote from publication: "patient demographics and baseline characteristics were similar between the treatment groups and are shown in Table 1" Comment: baseline characteristics were similar between groups. Washout periods were long enough |
Schmidt 1988.
| Methods | Study design: parallel design Duration of follow‐up: 9 weeks | |
| Participants | Total number of participants randomised: N = 60 Inclusion criteria: moderate papulopustular acne Exclusion criteria: unclear Sites of acne: unclear Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: not specified | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Outcome assessments were performed at baseline and at weeks 3, 6, and 9 There was not enough information to determine which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: multiple but unclear Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: German Funding: unclear Conflicts of interest: not specified Publication status: full text (we can access only the abstract) | |
| Stated aim for study | Quote from publication: not specified | |
| Notes | No full text available | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on numbers of and reasons for withdrawal for each group was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability of participant characteristics between groups was provided |
Shafiq 2014.
| Methods | Study design: parallel design Duration of follow‐up: 6 weeks | |
| Participants | Total number of participants randomised: N = 50 Inclusion criteria: male and non‐pregnant or non‐nursing females aged ≥ 17 years with acne vulgaris Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Cook’s acne grading system Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): overall = 18/32 Age (years): overall = 17 to 34 (range) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 1, 2, 3, 4, 5, and 6 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: from 2013 to 2014 Country: Pakistan Setting: clinic Number of study centres: 2 Washout period: 2 months washout for any anti‐acne medication like isotretinoin acid, clindamycin gel, or any oral antibiotic for acne treatment or any hormonal preparations Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: none Publication status: full article | |
| Stated aim for study | Quote from publication: "the objective of this study was to evaluate the clinical efficacy ofCasuarina equisetifolia bark extract (5% cream) in comparison with benzoyl peroxide as the standard drug for acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "the patients were randomly allocated into 5% cream ofC equisetifolia bark extract and benzoyl peroxide groups by using the lottery method" Comment: the random sequence generation method was described |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: participants were likely to know the treatment they received as the frequencies of treatment in each group were different |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: insufficient information on blinding of outcome assessors was provided. However, complete blinding was difficult as treatment‐related adverse events were more common in the BPO group |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "seventy patients were included in the study from both sexes, in the age group between 17 to 34 years. Out of these 20 patients were dropped out from study, finally 50 patients were randomly divided into two groups, 25 patients in each group" Comment: it seemed that 20 participants withdrew before randomisation. However, insufficient information on numbers of and reasons for withdrawal for each group was provided. It is also unclear whether there were participants withdrawing from the trial after randomisation |
| Selective reporting (reporting bias) | Unclear risk | Comment: no specific outcomes were listed in the methods section and we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability of demographics and acne severity between groups was provided |
Shahid 1996.
| Methods | Study design: parallel design Duration of follow‐up: 6 weeks | |
| Participants | Total number of participants randomised: N = 30 Inclusion criteria: mild acne vulgaris Exclusion criteria: any topical therapy for 2 weeks and systemic therapy for 4 weeks before this study Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: not specified | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 2, 4, and 6 There was not enough information to determine which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: Pakistan Setting: teaching hospital Number of study centres: 1 Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full text (we can access only the abstract) | |
| Stated aim for study | Quote from publication: "to compare the efficacy of commonly used topical preparation for acne (Benzoyl Peroxide and Tretinoin)" | |
| Notes | No full text is available | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on numbers of and reasons for withdrawal for each group was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability of participant characteristics between groups was provided |
Shalita 1989.
| Methods | Study design: cross‐over design Duration of follow‐up: 4 weeks (2 weeks for the first phase and 2 weeks for the second phase) | |
| Participants | Total number of participants randomised: N = 30 Inclusion criteria: unclear Exclusion criteria: unclear Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: not specified | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 2 and 4 There was not enough information to determine which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full text (we can access only the abstract) | |
| Stated aim for study | Quote from publication: "a four‐week crossover study to compare the efficacy of an acne cleanser containing 2% salicylic acid with that of a 10% benzoyl peroxide wash was conducted in 30 patients with acne vulgaris" | |
| Notes | No full text available | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on numbers of and reasons for withdrawal for each group was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability of participant characteristics between groups was provided |
Shalita 2003.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 87 Inclusion criteria
Exclusion criteria: using any acne treatment within a specified period (as specified below) Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: tretinoin 0.1% microsphere gel once in the evening and provided with a non‐comedogenic, broad‐spectrum sunscreen | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 2, 6, and 12 *These were the primary outcomes assessed in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: 6 months washout for systemic retinoids and/or anabolic steroids before enrolment; 4 weeks for systemic anti‐microbials, topical retinoids, or systemic steroids other than anabolic steroids; and 2 weeks for topical antibiotics, BPO, salicylic acid, medicated or anti‐bacterial washes, α‐hydroxy acids, and/or β‐hydroxy acids Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full text | |
| Stated aim for study | Quote from publication: "our purpose was to evaluate the efficacy and safety of a combination of benzoyl peroxide 6% cleanser and tretinoin 0.1% microsphere gel versus monotherapy with tretinoin 0.1% microsphere gel" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "the subjects were randomized to one of 2 treatment groups using a computer‐generated randomization schedule" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: no information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: trial authors described the trial as investigator‐blinded (i.e. outcome assessor was blinded), which indicates that participants and personnel were not blinded |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "this 12‐week study, conducted at 2 investigational sites, was a randomized controlled, investigator‐blind, parallel group study"; "The investigators conducted the following clinical evaluations..." Comment: trial authors claimed that the trial was investigator‐blind (outcome assessors). Complete blinding was possible as treatment‐related adverse events were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Quote: "eighty‐seven subjects were enrolled in the study and 56 completed the entire 12‐week protocol, 30 from the combination group and 26 from the monotherapy group. Only those subjects who completed the 12‐week protocol were included in outcome measures" Comment: a high proportion of participants did not complete the trial. Those who withdrew were not included in the analysis and reasons for their withdrawal for each group were unclear. ITT analysis was not performed |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability of participant characteristics between groups was provided |
Shwetha 2014.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 120 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Indian Acne Alliance Grading for Severity of Acne Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: topical 1% clindamycin once daily | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 4, 8, and 12 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: November 2011 to May 2013 Country: India Setting: dermatology outpatient department at Victoria Hospital Number of study centres: 1 Washout period: unclear Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full text | |
| Stated aim for study | Quote from publication: "the objective of this study was to compare the efficacy and safety of combination of topical 1% clindamycin and 0.1% adapalene with combination of topical 1% clindamycin and 2.5% benzoyl peroxide in mild to moderate acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "a randomization list was prepared by using table of random numbers" Comment: random sequence generation method was described |
| Allocation concealment (selection bias) | Unclear risk | Comment: no information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: no information on the method of blinding was provided |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: no information on the method of blinding was provided |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "out of 120 patients, 117 patients completed the study. 1 patient in group A and 2 patients in group B did not report for 4th week and further follow up" Comment: a low proportion of participants in each group did not complete the trial |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | Unclear risk | Quote: "both the treatment groups were comparable for their demographic characteristics and baseline disease characteristics with a similar mean number of non‐inflammatory, inflammatory and total acne lesions in each group [P=0.819, 0.294 and 0.586 respectively] [Table‐1]" Comment: despite similarity in baseline characteristics, washout periods were not reported |
Sklar 1996.
| Methods | Study design: parallel design Duration of follow‐up: 3 months | |
| Participants | Total number of participants randomised: N = 94 Inclusion criteria
Exclusion criteria: participants with interfering medical and dermatological conditions and medications, pregnancy, or oral contraceptives Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: not specified | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline, at weeks 1 and 2, and at months 1, 2, and 3 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full text | |
| Stated aim for study | Quote from publication: "its goal was to evaluate and compare the efficacy and patient tolerability of benzoyl peroxide special gel, benzoyl peroxide‐erythromycin and a placebo base, each applied twice a day for 3 months, in the treatment of moderate to moderately severe acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: trial authors did not specify the method used to generate the random sequence |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information was presented about allocation concealment |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: study authors described the trial as investigator‐blinded (i.e. outcome assessor was blinded), which indicates that participants and personnel were not blinded |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "this was a single‐blind, investigator‐masked, randomized, 3‐month clinical trial conducted during the winter months at an experienced single site" Comment: trial authors claimed that the trial was investigator‐blind (outcome assessors). However, complete blinding was difficult as treatment‐related adverse events were more common in the BPO groups |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Quote: "a total of 94 subjects were enrolled (30 benzoyl peroxide special gel, 32 benzoyl peroxide‐erythromycin, and 32 placebo base)"; "After 3 months, 86 subjects had completed the study (28 benzoyl peroxide special gel, 30 benzoyl peroxide‐erythromycin, 28 placebo base)" Comment: ITT analysis was not conducted and reasons for withdrawal for each group are unclear |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | Unclear risk | Quote: "there were no significant differences in total lesions and in total inflammatory and non‐inflammatory lesions between the three groups at baseline" Comment: despite no difference in the severity of acne at baseline, information on the similarity in demographics between groups and on washout periods is unclear |
Smith 1980.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 59 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 9/17; B = 7/18 Age (years): A = 22.3; B = 23.8 Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: washing with a non‐anti‐bacterial soap | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and every 2 weeks It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: late spring and early summer of 1978 Country: USA Setting: Student Health Centre Number of study centres: 1 Washout period: 1 week for anti‐acne topical medication and 1 month for oral antibiotics, oral contraceptives, or systemic corticosteroids Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "we carried out a controlled study designed to evaluate the effectiveness of this newer, higher concentration preparation in the management of mild to moderate inflammatory acne" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "after informed consent was obtained, the subjects were randomly assigned to one of two treatment groups" Comment: insufficient information on the method used to generate the random sequence was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote: "the preparations were packaged in identical containers so that neither the subjects nor the investigators could identify the one containing the active ingredient" Comment: the trial was double‐blinded (participants and investigators). Complete blinding was possible as vehicles and frequency of treatments and treatment‐related adverse events were similar between groups |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information for judgement was provided. Complete blinding was possible as treatment‐related adverse events were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: although 51 of 59 participants completed the trial (4 in each group), it is unclear whether reasons for withdrawal were similar |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | High risk | Comment: insufficient information on baseline acne severity was provided. The washout period for topical acne treatments was not long enough |
Smith 2006.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 48 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: acne severity scores based on a 6‐point scale Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): overall = 26/22 Age (years): overall = 17.1 (range 12 to 37 years) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐intervention: "concomitant treatments were recorded throughout the study period" but were unclear | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at weeks 4 and 12 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: 2 Washout period: 2 weeks washout for topical antibiotics; 12 weeks for oral or topical retinoids; 8 weeks for light treatment, photodynamic therapy, or chemical peels; 4 weeks for oral antibiotics; 8 weeks for oral anti‐androgens Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full text | |
| Stated aim for study | Quote from publication: "a pilot study was conducted to demonstrate the efficacy of this novel formulation compared with a 6% BP gel" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: trial authors did not specify the method used to generate the random sequence |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not specify the method of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "subjects were required to have mild to moderate facial acne vulgaris with defined lesion counts and were randomized and blinded" Comment: participants were blinded, but it is unclear whether personnel were also blinded. Complete blinding was difficult as the vehicles differed by treatment |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "on enrollment and at each visit thereafter, acne lesions were counted and acne severity scores assigned by a blinded investigator"; "the investigator remained blinded to treatment assignment throughout the trial" Comment: the investigator was referred to outcome assessors according to trial authors. Complete blinding was possible as treatment‐related adverse events were not expected to differ by treatment group in priori |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "four subjects withdrew from the study before week 12 ‐ 1 from facial attributable to the 6% BP gel and 3 for administrative reasons" Comment: a low proportion of participants did not complete the trial, but numbers of and reasons for withdrawal in each group were unclear |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | Unclear risk | Quote: "the treatment groups had similar average baseline lesion counts (table 2)" Comment: despite no difference in the severity of acne at baseline, similarity in demographics between groups is unclear |
Stinco 2007.
| Methods | Study design: parallel design Duration of follow‐up: 8 weeks | |
| Participants | Total number of participants randomised: N = 65 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: acne severity scores based on a 6‐point scale Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 7/18; B = 5/15; C = 11/9 Age (years): A = 16.8 (range 12 to 23); B = 19.3 (range 13 to 24); C = 17.7 (range 13 to 23) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: washing with the same mild detergent | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Efficacy and safety evaluations were performed at baseline and at weeks 2, 4, 6, and 8 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: 8 weeks washout for oral or topical anti‐acne therapy Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full text | |
| Stated aim for study | Quote from publication: "to evaluate the sebostatic effect of three anti‐acneic ingredients (azelaic acid, adapalene, and benzoyl peroxide) conveyed in cream and to determine whether there is a correlation with the therapeutic results" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "patients were randomly allocated to one of three groups of treatment" Comment: trial authors did not specify the method used to generate the random sequence |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided. Blinding was possible as the vehicles and frequency of treatments were similar and treatment‐related adverse events were reported to be similar between groups |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided. Blinding was possible as treatment‐related adverse events were reported to be similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: of 61 participants included in the 3 groups, 1 participant treated with azelaic acid, two treated with benzoyl peroxide, and one treated with adapalene did not complete the trial. There was a low proportion of withdrawals, and numbers of withdrawals in each group were similar |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability of participant characteristics between groups was provided |
Study 152.
| Methods | Study design: parallel design Duration of follow‐up: 11 weeks | |
| Participants | Total number of participants randomised: N = 280 Inclusion criteria: unclear Exclusion criteria: unclear Sites of acne: unclear Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (year; SD): unclear Duration of acne (year): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Interventions in Group D
Co‐interventions: unclear | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at week 11 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: USA Setting: unclear Number of study centres: multiple Washout period: unclear Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: FDA re‐submission report | |
| Stated aim for study | Not specified | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "all the analyses were done on the 'Preferred Data Set', which was the Per Protocol population" Comment: although ITT analysis was not performed, it is unclear how many participants withdrew from each group and what the reasons were |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability of participants' characteristics between groups and insufficient information on washout periods was provided |
Study 156.
| Methods | Study design: parallel, double‐blinded design Duration of follow‐up: 11 weeks | |
| Participants | Total number of participants randomised: N = 288 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 57/39; B = 57/39; C = 50/46 Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: unclear | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 2, 5, 8, and 11 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: USA Setting: unclear Number of study centres: multiple Washout period: 1 week washout for medicated cleansers, 2 weeks for topical acne treatments, and 6 months for oral retinoids Registered number: unclear ITT analysis: yes | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: FDA re‐submission report | |
| Stated aim for study | Quote from publication: "this was to compare the efficacy of Clindoxyl Gel to Clindamycin gel and Benzoyl peroxide gel in the topical treatment of acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: although trial authors claimed that the trial was double‐blind, it is unclear who was blinded. Blinding was possible as the vehicles and frequency of treatments were similar and treatment‐related adverse events were reported to be similar between the groups |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: although trial authors claimed that the trial was double‐blind, it is unclear who was blinded. Blinding was possible as treatment‐related adverse events were reported to be similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: the proportion of withdrawal was low and similar for each group and ITT analysis was performed |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | Low risk | Comment: as shown in the table of the report, participant characteristics were similar at baseline between groups. Washout periods were long enough |
Swinyer 1988.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 60 Inclusion criteria
Exclusion criteria: not specified Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean for each group Sex ratio (male/female): overall = 26/34 Age (years): overall = 19.8 Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: use of a non‐medicated lipid‐free cleanser for cleansing the face | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 2, 4, 8, and 12 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: September to December in a year Country: USA Setting: unclear Number of study centres: unclear Washout period: 14 days washout for systemic or topical acne treatment and 1 month for care of a dermatologist for acne Registered number: unclear ITT analysis: yes | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "the present study was undertaken to assess and compare the efficacy of benzoyl peroxide and the most popular topical antibiotic, clindamycin phosphate, in the treatment of acne vulgaris and to compare the skin surface parameters of oiliness, erythema, peeling and dryness" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "they were randomly assigned to one of two treatment groups, benzoyl peroxide or clindamycin phosphate, consisting of 30 patients each" Comment: trial authors did not specify the method used to generate the random sequence |
| Allocation concealment (selection bias) | Unclear risk | Comment: no information on allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "the investigator was blind as to which treatment group the patients belonged to and the patients were instructed not to discuss with the investigator, any aspect of the treatment to which they were assigned" Comment: even though blinding was conducted, complete blinding was difficult as treatment‐related adverse events were more common in the BPO group |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: no information on blinding of the outcome assessor was provided. However, complete blinding was difficult as treatment‐related adverse events were more common in the BPO group |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "all 60 patients completed the 12‐week study, none dropped out or missed any visits" Comment: no participants had incomplete outcome data |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | High risk | Comment: no information is available about whether baseline characteristics were comparable between groups. The washout period for systemic acne treatment was not long enough |
Tabasum 2014.
| Methods | Study design: parallel design Duration of follow‐up: 6 weeks | |
| Participants | Total number of participants randomised: N = 48 Inclusion criteria: male and non‐pregnant or non‐nursing females aged 13 to 40 years with acne vulgaris Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: global acne severity scale Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 8/12; B = 9/11 Age (years): A = 21.65 (4.95); B = 20.65 (5.12) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 2, 4, and 6 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: from February 2012 to January 2013 Country: India Setting: national institute Number of study centres: 1 Washout period: unclear Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: non‐commercial (Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore) Conflicts of interest: none Publication status: full article | |
| Stated aim for study | Quote from publication: "to evaluate clinically the efficacy ofZimade Muhasa, a Unani anti acne formulation, forBusoore labaniya (Acne vulgaris) against 5% benzoyl peroxide" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "the subjects were randomly assigned in the test group (n=24) and the control group (n=24) using a computer generated randomization table" |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information about allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: trial authors claimed that the trial was single‐blind, but it is unclear who was blinded |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: trial authors claimed that the trial was single‐blind, but it is unclear who was blinded. Blinding was possible as treatment‐related adverse events were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: more than 10% of participants in each group did not complete the trial and ITT analysis was not conducted |
| Selective reporting (reporting bias) | High risk | Comment: trial authors claimed that participants were assessed in 3 follow‐up visits of 15 days each. However, they presented only the results for week 6 |
| Other bias | High risk | Quote: "no significant difference was observed between the two groups regarding the basic demographic data (Table 1)" Comment: however, according to Table 2, baseline acne severity was not similar between groups, such as numbers of nodules and scores on global acne severity scale |
Tanghetti 2006.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 121 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: tazarotene 0.1% cream once daily in the evening; washing face with a non‐soap cleanser before applying tested medications | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and after 4, 8, and 12 weeks of treatment It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: multiple but unclear Washout period: 2 weeks washout for topical ance medications; 30 days for systematic antibiotics and investigational drugs; 12 weeks for oestrogens/birth control pills; 6 months for oral retinoids Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: 4 of the 5 trial authors declared that they were consultants for the companies supporting BPO‐related trials Publication status: full article | |
| Stated aim for study | Quote from publication: "a multicenter, double‐blind, randomized, parallel‐group trial has been performed to evaluate whether the adjunctive use of clindamycin/benzoyl peroxide could enhance the efficacy of tazarotene still further" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: trial authors did not specify the method used to generate the random sequence |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: although trial authors claimed that the trial was double‐blind, it is unclear who was blinded. Blinding was possible as most treatment‐related adverse events were reported to be similar between groups |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: although trial authors claimed that the trial was double‐blind, it is unclear who was blinded. Blinding was possible as most treatment‐related adverse events were reported to be similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Quote: "of 121 patients evaluated, 50/61 (82%) in the tazarotene group and 52/60 (87%) in the tazarotene/clindamycin/benzoyl peroxide group completed" Comment: a high proportion of participants withdrew with insufficient information on the reasons for incomplete outcome data. ITT analysis was not conducted |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability of participant between groups was reported |
Thiboutot 2002.
| Methods | Study design: parallel design Duration of follow‐up: 8 weeks | |
| Participants | Total number of participants randomised: N = 327 Inclusion criteria
Exclusion criteria: unclear Sites of acne: face Severity of acne and corresponding criteria of judgement: Pillsbury classification Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 59/65; B = 18/24; C = 64/57; D = 18/22 Age (years): A = 19.6; B = 19.6; C = 20.4; D = 19.8 (SD was not available) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Interventions in Group D
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and after 2, 4, 6, and 8 weeks of treatment *These outcomes were assessed as the primary outcomes in the trial | |
| Study details | Study period: unclear Country: USA Setting: unclear Number of study centres: 6 Washout period: unclear Registered number: unclear ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial (Dermik Laboratories, Berwyn, Pennsylvania) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "this trial compared the efficacy and tolerability of a single‐use EBP combination package (EBP Pak) with those of its matching vehicle control (VC Pak) and the original, reconstituted formulation packaged in a jar (EBP Jar)" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "patients were randomly assigned 3:3:1:1 to twice‐daily treatment with EBP Pak, EBP Jar, VC Pak, and VC Jar, respectively, for 8 weeks" Comment: trial authors did not specify how to generate the random sequence |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information about methods of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "qualified participants were assigned a patient number that corresponded to a randomized treatment, and each received a box of double‐blinded study medication" Comment: although describing the trial as double‐blinded, trial authors did not specify blinding of both participants and personnel. However, complete blinding was difficult as treatment‐related adverse events were more common in the BPO groups |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: trial authors did not specify blinding of outcome assessment. However, complete blinding was difficult as treatment‐related adverse events were more common in the BPO groups |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "most of the patients were evaluable for efficacy: EBP Pak, 116 (93.5%); EBP Jar, 113 (93.4%); VC Pak, 36 (85.7%); VC Jar, 35 (87.5%)" Comment: about 15% of participants did not complete follow‐up within each group and corresponding reasons were not reported. Besides, trial authors did not compare characteristics between participants who completed and discontinued treatment |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | Unclear risk | Quote: "no significant differences in patient demographic or baseline characteristics were noted among the 4 groups in the ITT population (Table I)" Comment: despite similarity in baseline characteristics, washout periods were not reported |
Thiboutot 2007.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 517 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 87/62; B = 86/62; C = 96/53; D = 40/31 Age (years): A = 16.2; B = 16.5; C = 16.5; D = 16.6 (SD was not available) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Interventions in Group D
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and after 1, 2, 4, 8, and 12 weeks of treatment *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: from February 17, 2004 to December 21, 2004 Country: USA Setting: unclear Number of study centres: 36 Washout period: unclear Registered number: unclear ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial (Galderma R&D, Princeton, NJ) Conflicts of interest: "the investigating authors received payments for this research project. Drs Liu and Graeber are employees of Galderma R&D. Drs Thiboutot, Weiss, and Kang have served as a consultants and speakers for Galderma Laboratories. Drs Bucko, Jones, and Eichenfield have served as consultants for Galderma" Publication status: full article | |
| Stated aim for study | Quote from publication: "to evaluate the efficacy and safety of adapalene 0.1% ‐BPO 2.5% fixed combination gel (adapalene‐BPO) for the treatment of acne" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "subjects were randomized consecutively in a 2:2:2:1 ratio to receive either adapalene‐BPO gel, adapalene gel, BPO gel, or gel vehicle for 12 weeks" Comment: trial authors did not specify how to generate the random sequence |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information about allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "the integrity of blinding was ensured by packaging the topical medication in identical tubes and requiring a third party other than the investigator/evaluator to dispense the medication" Comment: It is unclear whether participants were blinded. However, complete blinding was difficult as treatment‐related adverse events were more common in the BPO groups |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "the integrity of the blinding was ensured by packaging the topical medication in identical tubes and requiring a third party other than the investigator/evaluator to dispense the medication" Comment: the outcome evaluator was probably blinded. However, complete blinding was difficult as treatment‐related adverse events were more common in the BPO groups |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: Figure 1 in the article shows the number of the treatment discontinuation and the corresponding reasons. About 15% of participants did not complete the treatment within each group and the reasons were not balanced across groups. Besides, trial authors did not compare characteristics between participants who completed and discontinued treatments |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | Unclear risk | Quote: "the treatment groups were comparable with respect to the demographic characteristics and baseline dermatological scores. Baseline acne severity was moderate for more than 75% of the subjects, for all groups"; "Specified washout periods were required for subjects taking certain topical and systemic treatments" Comment: washout periods were not specified |
Thiboutot 2008.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 2813 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: EGSS Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 389/408; B = 392/420; C = 354/455; D = 203/192 Age (years): A = 19.2; B = 19.6; C = 19.1; D = 19.4 (SD was not available) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Interventions in Group D
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and after 4, 8, and 12 weeks of treatment *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: 1 week washout for topical astringents and abrasives; 2 weeks for topical anti‐acne products, including soaps containing anti‐microbials, and known comedogenic products; 4 weeks for topical retinoids, retinol, and systemic acne treatments; and 6 months for systemic retinoids Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: commercial (Arcutis Pharmaceuticals) Conflicts of interest: all trial authors declared that they were consultants or employees for the companies supporting BPO‐related trials Publication status: full article | |
| Stated aim for study | Quote from publication: "two identical phase III clinical studies were conducted to evaluate the efficacy, safety, and cutaneous tolerability of a clindamycin‐BPO 2.5% aqueous gel in the treatment of moderate to severe acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "patient treatments were randomized using permuted blocks within strata to ensure not only an appropriate distribution of patients across treatment groups, but also a relatively equal balance of patients by acne severity and skin phototype within treatment groups" Comment: trial authors detailed stratified blocked randomisation, but how to generate the random sequence was not mentioned |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not specify the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Quote: "both studies were 12‐week, multicenter, randomized, double‐blind, active‐ and vehicle‐controlled, parallel‐group, comparative studies using identical protocols in a total of 2813 patients..." Comment: although the trial was described as double‐blinded, trial authors did not specify blinding of participants and personnel. Blinding was possible as the vehicles and frequency of treatments and treatment‐related adverse events were similar between groups |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Quote: "both studies were 12‐week, multicenter, randomized, double‐blind, active‐ and vehicle‐controlled, parallel‐group, comparative studies using identical protocols in a total of 2813 patients..." Comment: although the trial was described as double‐blinded, trial authors did not specify blinding of outcome assessment. Blinding was possible as treatment‐related adverse events were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: Figure 1 in the article shows the number of treatment discontinuations and corresponding reasons. About 10% of participants within each group did not complete treatment and reasons were not balanced across groups. Besides, trial authors did not compare characteristics between participants who completed and discontinued treatments |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | Low risk | Quote: "demographic data (Table II) were not statistically different across all 4 treatment groups" Comment: baseline characteristics were comparable and washout periods were long enough |
Tirado‐Sanchez 2009.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 87 Inclusion criteria: 10 to 50 inflammatory lesions (papules and pustules) with an absence of nodulo‐cystic lesions or other inflammatory cutaneous disease on the face. Exclusion criteria: receiving acne treatment within a specified period (as specified below) Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 22/17; B = 14/10; C = 10/12 Age (years): A = 19 (2.9); B = 18 (3.3); C = 19 (2.5) Duration of acne (year): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and after 4, 8, and 12 weeks of treatment It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: México Setting: unclear Number of study centres: unclear Washout period: 14 days washout for any other topical treatment; 30 days for systemic antibiotics; and 6 months for systemic retinoid Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: none Publication status: full article | |
| Stated aim for study | Quote from publication: "in summary, our study is the first clinical trial to compare the effectiveness and tolerance of SOS in the treatment of acne" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "patients were randomly assigned to treatment A, B or C using a balanced blocks method (columns of 10 patients), followed by random numbers generated by a computer and assigned to the patients by the second investigator" |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not specify the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Quote: "a total of 87 patients were enrolled in this randomized, double‐blinded, placebo‐controlled, clinical trial..." Comment: although the trial was described as double‐blinded, trial authors did not specify blinding of participants and personnel. Blinding was possible as treatment‐related adverse events were reported to be similar between groups |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Quote: "a total of 87 patients were enrolled in this randomized, double‐blinded, placebo‐controlled, clinical trial..." Comment: although the trial was described as double‐blinded, trial authors did not specify blinding of outcome assessment. Blinding was possible as treatment‐related adverse events were reported to be similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "almost all patients included completed the study, 39 in the SOS group and 24 patients in the benzoyl peroxide (BP) and in the placebo group (two patients of the last group were lost on follow‐up, the reasons were personal ones, not related to the study product)" Comment: the number of losses to follow‐up was small and reasons were not related to study treatments |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | Unclear risk | Comment: trial authors did not adequately report comparisons of baseline demographic characteristics between groups |
Tschen 2001.
| Methods | Study design: parallel design Duration of follow‐up: 10 weeks | |
| Participants | Total number of participants randomised: N = 287 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Pillsbury classification system Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): overall = 5 to 6 years | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Interventions in Group D
Co‐interventions: supplied mild soap, moisturiser, and sunscreen on treatment area | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and after 2, 4, 6, 8, and 10 weeks of treatment It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: from September 1996 to January 1997 Country: USA Setting: unclear Number of study centres: 5 Washout period: 2 weeks washout for topical antibiotics, anti‐acne medication, steroids, or retinoids; 4 weeks for systemic antibiotics or steroids; and 6 months for oral retinoids Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: commercial (Dermik Laboratories, Inc., Berwyn, Pennsylvania) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "this study compares the efficacy and safety of this combination agent with that of its constituents, benzoyl peroxide, clindamycin, and gel vehicle" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "287 patients between 13‐ and 30‐years‐old were enrolled and randomly selected to receive 10 weeks of twice‐daily treatment..." Comment: trial authors did not specify methods of randomisation used |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not specify methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "this randomized, double‐blind, parallel‐group study was conducted according to the principles of Good Clinical Practice..." Comment: although the trial was described as double‐blind, trial authors did not specify blinding of participants and personnel. Complete blinding was difficult as treatment‐related dryness was reported to be significantly higher in the BPO/clindamycin and BPO groups |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "this randomized, double‐blind, parallel‐group study was conducted according to the principles of Good Clinical Practice..." Comment: although the trial was described as double‐blind, trial authors did not specify blinding of outcome assessment. Complete blinding was difficult as treatment‐related dryness was reported to be significantly higher in the BPO/clindamycin and BPO groups |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "of the 287 patients who were enrolled in the study, 278 had at least 1 follow‐up visit and were included in the efficacy analysis. " Comment: in case of missing data, trial authors reported neither missing numbers for each group nor corresponding reasons |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | Unclear risk | Comment: trial authors did not adequately report comparisons of baseline demographic characteristics between groups |
Tucker 1984.
| Methods | Study design: parallel design Duration of follow‐up: 10 weeks | |
| Participants | Total number of participants randomised: N = 79 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Pillsbury classification system Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 15/14; B = 10/16; C = 9/15 Age (years): overall = 12 to 30 (range) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: not specified | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and after 2, 4, 6, 8, and 10 weeks of treatment It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: 30 days washout for systemic antibiotics, steroids, or androgenic drugs; 14 days for topical medication for acne Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: commercial (Upjohn Company) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "in this study, three regimens were randomly assigned and compared to assess the benefit of therapy with benzoyl peroxide (5%, gel), topical clindamycin phosphate (1% solution), and a combination of these products in patients with acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "in this study, three regimens were randomly assigned" Comment: trial authors did not specify the method used to generate the random sequence |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not specify the method of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: trial authors did not specify who was blinded. However, complete blinding was difficult as the vehicles and frequency of treatments differed by treatment groups |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: trial authors did not specify who was blinded. There was not enough information on treatment‐related adverse events to determine the possibility of blinding |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Quote: "fifty‐six of the patients completed the full course of therapy. Three patients withdrew due to a lack of efficacy. The overall rate of dropout across the three treatment groups was comparable, therefore comparisons were made only on patients who actually completed the full investigation"; "The rate of dropout in the three treatment groups was comparable, although only in the benzoyl peroxide group did three participants withdraw due to treatment failure" Comment: 23 of 79 participants (29.1%) did not complete the full course of therapy with no reasons reported for each group. ITT analysis was not conducted |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | High risk | Comment: trial authors did not adequately report comparisons of baseline demographic characteristics between groups. But according to Table 1, it seems different in the sex ratios between groups |
Tung 2014.
| Methods | Study design: parallel design Duration of follow‐up: 8 weeks | |
| Participants | Total number of participants randomised: N = 120 Inclusion criteria: aged 14 years or older with mild to moderate acne vulgaris Exclusion criteria: unclear Sites of acne: unclear Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: not specified | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Outcomes were assessed at baseline and at weeks 4 and 8 There was not enough information to determine which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: conference abstract | |
| Stated aim for study | Quote from publication: "in this 8 week pilot study, 120 subjects (aged 14 years or older) with mild to moderate acne vulgaris were enrolled to compare the safety and efficacy of a hydrogen peroxide‐based acne regimen (Acnekit, BMG Pharma) to a benzoyl peroxide based regimen, (Proactiv, Gunthy Renker)" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method used to generate the random sequence was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: insufficient information on blinding of participants and personnel was provided |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "the primary outcome measure of clinical response was documented with standardized digital photography and was assessed using the Global Acne Grading System (GAGS) by blinded dermatologist raters at baseline, 4 weeks and 8 weeks" |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: 120 participants were enrolled but only 102 completed the trial. The number of withdrawals and reasons in each group are unclear |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | Unclear risk | Comment: insufficient information on comparability of baseline characteristics between groups was reported |
Vasarinsh 1969.
| Methods | Study design: parallel‐group study Duration of follow‐up: average 6.2 weeks (4 to 14 weeks) | |
| Participants | Total number of participants randomised: N = 72 Inclusion criteria: unclear Exclusion criteria: unclear Sites of acne: unclear Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Interventions in Group D
Co‐interventions: not reported | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed every 2 weeks It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: September 1966 to May 1967 Country: USA Setting: unclear Number of study centres: 1 Washout period: at least 2 weeks for any systemic and topic anti‐acne treatment Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: non‐commercial (NIH) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "in this study an attempt has been made to evaluate the efficacy of benzoyl peroxide preparations strictly on the merits of medication per se" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "medications were assigned in a double‐blind randomized manner with instructions..." Comment: the method of randomisation is unclear |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not report the methods of allocation concealment |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "medications were assigned in a double‐blind randomized manner with instructions..." Comment: it is unclear who was blinded. However, complete blinding was difficult as treatment‐related dryness and erythema were reported to be more common in the BPO/sulphur and BPO groups |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Quote: "medications were assigned in a double‐blind randomized manner with instructions..." Comment: it is unclear who was blinded. However, complete blinding was difficult as treatment‐related dryness and erythema were reported to be more common in the BPO/sulphur and BPO groups |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: more than 20% of participants (18/72) did not complete the trial and ITT analysis was not conducted |
| Selective reporting (reporting bias) | High risk | Quote: "patients were observed every two weeks" Comment: trial authors did not report the outcome for each visit |
| Other bias | High risk | Comment: it is unclear whether baseline characteristics were similar between groups. The washout period for systemic acne treatments was not long enough |
Wang 2003.
| Methods | Study design: parallel design Duration of follow‐up: 6 weeks | |
| Participants | Total number of participants randomised: N = 103 Inclusion criteria
Exclusion criteria
Sites of acne: face, neck, chest, and back Severity of acne and corresponding criteria of judgement: grade Ⅰ: 10 to 25 inflammatory lesions, comedos, or pustules in the face; grade Ⅱ: 26 to 50 inflammatory lesions, comedos, or pustules in the face; grade Ⅲ: > 50 inflammatory lesions, comedos, or pustules in the face, < 5 nodular‐cystic lesions in the face, neck, chest, and back Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 17/14; B = 16/15; C = 9/24 Age (years): A = 17.7 (2.0); B = 18.1 (3.4); C = 18.0 (3.3) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 2, 4, and 6 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: China Setting: unclear Number of study centres: unclear Washout period: 2 weeks washout for any topical acne medication; and 4 weeks for oral antibiotics Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: Chinese Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "to assess the clinical efficacy and safety of benzoyl peroxide gel (BPG) with different concentrations in the treatment of acne vulgaris and to compare the quality between the domestic products with imported products" | |
| Notes | Data from a group of 93 participants treated with 2.5% BPO produced in China were not extracted. Only per‐protocol analysis was available | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method used to generate the random sequence was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: trial authors claimed that the trial was open‐label |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: trial authors claimed that the trial was open‐label |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: 3/34, 3/35, and 1/34 participants did not complete the whole course of treatment in 2.5%, 5%, and 10% BPO groups, respectively. Despite the proportions of withdrawal being low, reasons for withdrawal for each group are unclear and ITT analysis was not conducted |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol relevant information nor a trial registry to confirm that selective reporting was avoided |
| Other bias | Low risk | Comment: according to Table 1, the 3 groups had similar demographics and acne severity. Washout periods were long enough |
Weiss 2015.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 252 Inclusion criteria: moderate (Investigator Global Assessment (IGA) = 3) and severe (IGA = 4) acne Exclusion criteria: unclear Sites of acne: unclear Severity of acne and corresponding criteria of judgement: investigator global assessment Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): unclear Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: not specified | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated weekly for the first 2 weeks and then every 2 weeks There was not enough information to determine which outcome was assessed as the primary outcome | |
| Study details | Study period: unclear Country: unclear Setting: unclear Number of study centres: multiple but unclear Washout period: unclear Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: conference abstract | |
| Stated aim for study | Quote from publication: "this study compared the efficacy and safety of adapalene 0.3%/benzoyl peroxide 2.5% (0.3% A/BPO) topical gel vs vehicle in subjects with moderate and severe acne (overall population [OP]), and in a subpopulation of the OP (severe acne subjects only) (severe population [SP]). The study also compared 0.3% A/BPO vs adapalene 0.1%/benzoyl peroxide 2.5% (0.1% A/BPO) topical gel in the SP" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was reported |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on numbers of and reasons for withdrawal for each group was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability of participant characteristics between groups was provided |
Xu 2016.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 1020 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: ISGA score Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 118/382; B = 133/383 Age (years): A = 23.4 (4.64); B = 23.3 (4.29) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: not reported | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 1, 2, 4, 8, and 12 *These outcomes were assessed as the primary outcome in the trial | |
| Study details | Study period: April 2013 to April 2014 Country: China Setting: unclear Number of study centres: 24 Washout period: 4 weeks washout for traditional remedies known to affect acne vulgaris and for any investigative drugs Registered number:NCT01915732 ITT analysis: yes for most analyses | |
| Publication details | Language of publication: English Funding: commercial (GlaxoSmithKline) Conflicts of interest: "J. Li is an employee of GlaxoSmithKline (China) R&D Company Limited, Shanghai, China. A.G. Hamedani was formerly an employee of GlaxoSmithKline, he is currently working at Prosoft Clinical (996 Old Eagle School Rd. Suite 1106, Wayne, PA 19087, USA) and he owns stock options in GlaxoSmithKline. None of the other authors have any potential conflict of interest. The investigators’ institutes received compensation from GlaxoSmithKline (China) to support carrying out the study at the site" Publication status: full text | |
| Stated aim for study | Quote from publication: "the aim of this study was to compare the efficacy and safety of clindamycin (1%) and benzoyl peroxide (5%) (CDP/BPO) gel once daily vs. clindamycin (1%) (CDP) monotherapy gel twice daily in Chinese patients with mild to moderate acne" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "patients were randomly assigned (1:1) using a computer‐generated randomization schedule to receive either CDP/BPO gel or CDP gel" Comment: the method used to generate the random sequence was specified |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: the trial was single‐blinded (assessor), suggesting that participants may be aware of the treatment they received |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: assessors were blinded. However, complete blinding was difficult as treatment‐related adverse events were reported to be more common in the BPO/clindamycin group |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: although ITT analysis was conducted for most analyses, about 14% of participants were lost to follow‐up and reasons for withdrawal were not comparable between groups |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes planned on the trial registry were reported |
| Other bias | Low risk | Quote: "overall, patient demographics and disease characteristics were well balanced between treatment groups" Comment: baseline characteristics were similar between groups. Washout period was long enough |
Yong 1979.
| Methods | Study design: parallel design Duration of follow‐up: ranging from 4 to 18 weeks | |
| Participants | Total number of participants randomised: N = 200 Inclusion criteria: outpatients attending a private skin clinic Exclusion criteria: unclear Sites of acne: unclear Severity of acne and corresponding criteria of judgement: lesion count Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): overall = 60/140 Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: wash with a soap before using BPO | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated weekly for the first 2 weeks and then every 2 weeks It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: Singapore Setting: outpatients from a private clinic Number of study centres: 1 Washout period: unclear Registered number: unclear ITT analysis: no | |
| Publication details | Language of publication: English Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "a clinical trial was therefore undertaken to assess its efficacy and possible side effects in acne patients in Singapore" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "two strengths of benzoyl peroxide (2.5% and 5%) in a stable gel formulation were used and were supplied at random to the patients" Comment: trial authors did not specify the methods of randomisation used |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not specify the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: trial authors did not specify blinding of participants and personnel. Blinding was possible as the vehicles and frequency of treatments were the same and treatment‐related adverse events were similar between groups |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Quote: "the patients were seen weekly for the first two weeks, and then every two weeks by the same physician who evaluated the results on a point system..." Comment: trial authors did not specify blinding of outcome assessment. Blinding was possible as treatment‐related adverse events were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "six patients did not return for assessment" Comment: in case of missing data, trial authors report neither the missing number for each group nor the corresponding reasons |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | Unclear risk | Comment: trial authors did not report comparisons of baseline demographic characteristics between groups nor washout periods |
Zeichner 2013.
| Methods | Study design: parallel design Duration of follow‐up: 12 weeks | |
| Participants | Total number of participants randomised: N = 40 Inclusion criteria
Exclusion criteria: female who was pregnant, attempting to conceive, breastfeeding, or of childbearing potential Sites of acne: face Severity of acne and corresponding criteria of judgement: 6‐point PGA Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 3/17; B = 4/16 Age (years): A = 23.25 (5.98); B = 28.95 (9.74) Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: tretinoin 0.025%/clindamycin phosphate 1.2% gel | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at weeks 2, 4, 8, and 12 *This outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: USA Setting: unclear Number of study centres: 1 Washout period: 1 week for topical acne medications and 2 weeks for systematic antibiotics Registered number: unclear ITT analysis: yes | |
| Publication details | Language of publication: English Funding: commercial (Medicis) Conflicts of interest: "Dr. Zeichner has served as an investigator for Medicis and an investigator and advisory board member for Valeant" Publication status: full article | |
| Stated aim for study | Quote from publication: "in this report, we review the results of a single‐blinded investigation to evaluate the safety and efficacy of combination therapy using a fixed‐dose combination tretinoin 0.025%/clindamycin phosphate 1.2% (T/CP) gel (ZIANA® Gel; Medicis Pharmaceutial corporation, Scottsdale, AZ) in the evening compared with the same fixed‐dose combination T/CP gel in combination with a BPO 6% cleansing cloth (TRIAZ® 6% Cleansing Cloths; Medicis)" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "study co‐ordinators randomized parents in a 1:1 ratio to 1 of 2 treatment groups" Comment: trial authors did not specify the methods of randomisation used |
| Allocation concealment (selection bias) | Unclear risk | Comment: trial authors did not specify the methods of allocation concealment used |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "the study was a single‐blinded investigation, so participants knew into which arm they had been randomized" |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "study co‐ordinator dispensed all study medications, so investigators remained blind to subjects' randomization"; "Investigators assessed dryness, scaling and erythema using a 4‐point scale..." Comment: outcome assessors were blinded. Complete blinding was possible as treatment‐related adverse events were similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "analysis was performed using the intention‐to‐treat population (ITT)..."; "The last observation carried forward (LOCF) method of imputation was used for missing observations" Comment: although trial authors stated the strategies used for dealing with missing data, extent of incomplete outcome data and corresponding reasons were not specified |
| Selective reporting (reporting bias) | Unclear risk | Comment: although all outcomes listed in the methods section were reported, we could not identify the corresponding protocol nor relevant information on a trial registry to confirm that selective reporting was avoided |
| Other bias | High risk | Comment: baseline demographic characteristics were summarised in a table and were probably similar between groups. Washout periods were not long enough |
Zeng 2012.
| Methods | Study design: parallel design Duration of follow‐up: 4 weeks | |
| Participants | Total number of participants randomised: N = 233 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean (SD) for each group Sex ratio (male/female): A = 19/94; B = 30/90 Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: none | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at weeks 1, 2, and 4 after treatment It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: from September 2009 to April 2010 Country: China Setting: dermatological outpatient departments of tertiary hospitals Number of study centres: 3 Washout period: 4 weeks washout for oral treatments for acne; and 1 week for topical treatments Registered number: unclear ITT analysis: yes | |
| Publication details | Language of publication: Chinese Funding: non‐commercial (State Administration of Traditional Chinese Medicine) Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: "to evaluate the clinicaI effectiveness and safety of Chinese medicaI faciaI mask comprehensive therapy in treating acne vulgaris" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Comment: random sequence was generated by the central randomisation system |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: insufficient information on blinding was provided. Blinding was difficult as the vehicles and frequency of treatments differ by group |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: insufficient information on blinding was provided. Blinding was possible as treatment‐related adverse events were reported to be similar between groups |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on numbers of and reasons for withdrawal for each group was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | High risk | Comment: insufficient information on baseline comparability of participant characteristics between groups was provided. The washout period for topical acne treatments was not long enough |
Zhao 2001.
| Methods | Study design: parallel design Duration of follow‐up: 4 weeks | |
| Participants | Total number of participants randomised: N = 187 Inclusion criteria: those with papules, pustules, or nodule‐cyst lesions Exclusion criteria: unclear Sites of acne: face Severity of acne and corresponding criteria of judgement: unclear Treatment before study: unclear Participants' baseline data presented as mean for each group Sex ratio (male/female): overall = 90/97 Age (years): overall = 22.7 (range 14 to 33) Duration of acne (years): overall = 2.3 (range 2 weeks to 6 years) | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: washing with a cleanser before applying tested medications | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and at week 4 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: China Setting: unclear Number of study centres: unclear Washout period: unclear Registered number: unclear ITT analysis: yes | |
| Publication details | Language of publication: Chinese Funding: unclear Conflicts of interest: not specified Publication status: full article | |
| Stated aim for study | Quote from publication: not specified | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: insufficient information on the method of randomisation was provided |
| Allocation concealment (selection bias) | Unclear risk | Comment: insufficient information on the method of allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: insufficient information on blinding was provided. Blinding was difficult as the vehicles of treatments differed by group |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: insufficient information on blinding was provided. Complete blinding was difficult as all treatment‐related adverse events occurred in the BPO/erythromycin group |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Comment: insufficient information on numbers of and reasons for withdrawal for each group was provided |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting was provided |
| Other bias | Unclear risk | Comment: insufficient information on baseline comparability of participant characteristics between groups and on washout periods was provided |
Zheng 2019.
| Methods | Study design: split‐face, open‐label design Duration of follow‐up: 4 weeks | |
| Participants | Total number of participants randomised: N = 34 Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: Investigator Global Assessment Treatment before study: unclear Participants' baseline data presented as mean (SD) for all participants Sex ratio (male/female): 11/23 Age (years): unclear Duration of acne (years): unclear | |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐intervention: not reported | |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and on days 14 and 28 It was not reported which outcome was assessed as the primary outcome in the trial | |
| Study details | Study period: unclear Country: China Setting: hospital Number of study centres: 1 Washout period: 2 weeks for consumed antibiotics, hormonal drugs, isotretinoin, or photoallergic drugs Registered number: unclear ITT analysis: unclear | |
| Publication details | Language of publication: English Funding: commercial (Broda Technologies Co., Ltd., China, and Shanghai Rui Zhi Medical Science and Technology Co., Ltd., China) Conflicts of interest: "no potential conflict of interest was reported by the authors" Publication status: full article | |
| Stated aim for study | Quote from publication: "we conducted a clinical trial to compare the safety and efficacy of 2% supramolecular SA with that of BPO plus adapalene gel on mild to moderate acne" | |
| Notes | ‐ | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "prior to the start of the study, a randomization list was generated by a statistician via SPSS software" Comment: random sequence was generated by a statistician via SPSS software |
| Allocation concealment (selection bias) | Unclear risk | Quote: "the funder, investigators, patients, and research staff remained masked to the randomization list" Comment: no information on the methods used for allocation concealment was provided |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Comment: this was an open‐label study |
| Blinding of outcome assessment (detection bias) All outcomes | High risk | Comment: this was an open‐label study |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "a total of 34 patients were enrolled and 31 of them completed the trial" Comment: less than 10% of participants did not complete the trial but it is unclear whether ITT analysis was conducted |
| Selective reporting (reporting bias) | Unclear risk | Comment: insufficient information on selective reporting as a protocol or relevant information on a trial registry was not available |
| Other bias | Unclear risk | Comment: the split‐face trial ensured baseline characteristics were comparable within individuals. Washout periods for topical and systemic treatments were not specified |
A/BPO: adapalene/benzoyl peroxide. ADA: adapalene. AV: acne vulgaris. AZA: azelaic acid. BP or BPO: benzoyl peroxide. C acnes: Cutibacterium acnes. CDP, CLIN, or CLNP: clindamycin phosphate. CLN: clindamycin. CT: clindamycin/tretinoin. EBP: erythromycin/benzoyl peroxide. HP: hydrogen peroxide. HPS: hydrogen peroxide stabilised. IL: inflamed lesion. ISGA: Investigator Static Global Assessment. ITT: intention‐to‐treat. LHA: lipo‐hydroxyacid. N/A: not applicable. NIL: non‐inflamed lesion. SA: salicylic acid. SD: standard deviation. SOS: superoxidised solution. T/CP: tretinoin/clindamycin phosphate. TL: total lesion. VC: vehicle control.
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
|---|---|
| 2009‐011212‐37 | BPO was used as co‐intervention in comparison groups: the trial compared adapalene/BPO 0.1%/2.5% with BPO 2.5% gel for treating acne vulgaris |
| 2009‐016240‐40 | BPO was used as co‐intervention in comparison groups: the trial compared 2 products from different brands, both containing 5% BPO and 3% erythromycin |
| 2010‐020796‐24 | BPO was used as co‐intervention in comparison groups: the trial compared clindamycin/BPO 1%/2.5% with adapalene/BPO 0.1%/2.5% |
| 2013‐001753‐26 | No BPO treatments were involved in the trial: the trial compared a tretinoin‐treated zone with an untreated zone |
| 2016‐000616‐15 | Not an RCT: a single‐group study |
| 2017‐002975‐25 | Not an RCT: an observational study |
| 2017‐003105‐18 | No BPO treatments were involved in the trial: the trial compared erythromycin with clindamycin |
| ACTRN12617000498392 | Not an RCT: a single‐group study |
| ACTRN12617000642381 | Not an RCT: a non‐randomised trial |
| ACTRN12617001127392 | Not an RCT: a non‐randomised trial |
| Andres 2008 | Not matching our inclusion criteria for participants: study on tolerance in healthy individuals without acne |
| Bhatia 2015 | Less than 2 weeks: outcomes were assessed at hour 6 |
| Bouloc 2017 | BPO was used as co‐intervention in comparison groups: fixed‐combination adapalene/benzoyl peroxide was applied to all groups |
| Bourdes 2015a | Not matching our inclusion criteria for participants: study on atrophic acne scars |
| Bourdes 2015b | Not matching our inclusion criteria for participants: study on atrophic acne scars |
| Bucknall 1977 | Not matching our inclusion criteria for participants: of 88 participants included, 7 had drug‐induced acne ‐ 5 attributed to oral contraceptives and 2 to phenytoin |
| Burkhart 2007 | BPO was used as co‐intervention in comparison groups: the trial compared BPO/allylamine with BPO |
| Callender 2012 | BPO was used as co‐intervention in comparison groups: the trial compared the difference in effects of BPO/clindamycin between participants with Fitzpatrick skin types I to III and IV to VI |
| Caron 1997 | Not matching our inclusion criteria for participants: healthy individuals with no acne were included |
| Cavicchini 1989 | Not an RCT: a review |
| Choudhury 2011 | BPO was used as co‐intervention in comparison groups: the trial compared clindamycin plus BPO with nadifloxacin plus BPO |
| Coret 2006 | Less than 2 weeks: a 1‐week study |
| CTRI/2017/07/009004 | Oral treatment involved in the comparison: the trial compared topical Unani formulation plus oral Shahtra with topical BPO plus oral azithromycin |
| CTRI/2017/08/009299 | No BPO treatments were involved in the trial: the trial compared Vatapallava with no treatment |
| CTRI/2017/09/009855 | BPO was used as co‐intervention in comparison groups: the trial compared zinc oxide plus BPO with BPO |
| CTRI/2017/12/010963 | BPO was used as co‐intervention in comparison groups: the trial compared metformin plus BPO with doxycycline plus BPO |
| Cunliffe 1981 | BPO was used as co‐intervention in comparison groups: the trial compared 2 BPO (5%)‐containing preparations |
| de Souza Sittart 2015 | Not an RCT: a single‐group study |
| Degreef 1982 | BPO was used as co‐intervention in comparison groups: the trial compared BPO/miconazole with BPO |
| Del Rosso 2006b | BPO was used as co‐intervention in comparison groups: the trial compared (1) BPO 8% wash once daily, (2) BPO 8% wash in combination with clindamycin phosphate 1% foam once daily, and (3) BPO 8% wash once daily in combination with doxycycline monohydrate 100 mg twice daily |
| Del Rosso 2009b | Less than 2 weeks: a survey about satisfaction was conducted after BPO wash interventions |
| Del Rosso 2010 | Less than 2 weeks: the same study as Del 2009b |
| Del Rosso 2016 | Not an RCT: a review |
| Dhawan 2009 | BPO was used as co‐intervention in comparison groups: the trial compared BPO/clindamycin topical gel with the hydrating excipients dimethicone and glycerin (C/BPO HE) and BPO/clindamycin topical gel that does not contain hydrating excipients (C/BPO) |
| Dosik 2006 | Not matching our inclusion criteria for participants: healthy individuals with no acne were included |
| Dosik 2008 | Not matching our inclusion criteria for participants: healthy individuals with no acne were included |
| Draelos 2006 | BPO was used as co‐intervention in comparison groups: BPO/clindamycin was applied to all participants |
| Draelos 2012 | BPO was used as co‐intervention in comparison groups: the trial compared BPO/lipohydroxy acid plus tretinoin versus BPO/clindamycin plus tretinoin |
| Draelos 2015 | BPO was used as co‐intervention in comparison groups: this trial compared a 3‐step botanical treatment containing BPO with BPO |
| DRKS00010222 | Not an RCT: a single‐group study |
| Eichenfield 2009 | BPO was used as co‐intervention in comparison groups: the trial compared salicylic acid cleanser plus salicylic acid toner plus solubilised benzoyl peroxide gel with control cleanser plus benzoyl peroxide/clindamycin gel |
| Eichenfield 2010b | BPO was used as co‐intervention in comparison groups: the same study as Eichenfield 2009 |
| Ergin 1999 | BPO was used as co‐intervention in comparison groups: the trial compared erythromycin plus BPO with BPO monotherapy |
| Ergin 2001 | BPO was used as co‐intervention in comparison groups: the same study as Ergin 1999 |
| Fanta 1984 | BPO was used as co‐intervention in comparison groups: the trial compared BPO/miconazole with BPO |
| Fernandez‐Obregon 2003 | Not an RCT: an observational study |
| Fluckiger 1988 | BPO was used as co‐intervention in comparison groups: the trial compared BPO/miconazole with BPO |
| Ghosh 2018 | BPO was used as co‐intervention in comparison groups: the trial compared adapalene and BPO (2.5%) with nadifloxacin and BPO (2.5%) |
| Gonzalez 2012 | BPO was used as co‐intervention in comparison groups: the trial compared BPO/clindamycin with BPO/adapalene |
| Green 2008 | BPO was used as co‐intervention in comparison groups: the trial compared a 3‐step acne system containing a solubilised BPO lotion with BPO/clindamycin |
| Green 2012 | BPO was used as co‐intervention in comparison groups: the trial compared BPO/clindamycin with BPO/adapalene |
| Green 2013 | BPO was used as co‐intervention in comparison groups: the trial compared an anti‐acne system containing BPO cleanser, BPO foam treatment, and salicylic acid with 2 control systems: 1 consisted of BPO cleanser, revitalising toner, and repairing lotion; the other consisted of salicylic acid cleanser, salicylic acid gel, and a perfecting lotion |
| Grove 2013 | Not matching our inclusion criteria for participants: study on tolerance in healthy individuals |
| IRCT2016051727947N1 | BPO was used as co‐intervention in comparison groups: the trial compared light treatment plus BPO with BPO |
| ISRCTN21526350 | BPO was used as co‐intervention in comparison groups: the same study as Ozolins 2004 |
| ISRCTN38383374 | No BPO treatments were involved in the trial: the trial compared 3 products, each containing multiple active ingredients but BPO |
| Jain 1998 | BPO was used as co‐intervention in comparison groups: the trial compared BPO/metronidazole with BPO/clindamycin |
| Jeanmougin 1987 | Not an RCT: this was an uncontrolled study of BPO combination therapy with minocycline |
| JPRN‐UMIN000025358 | Not an RCT: a non‐randomised trial |
| KCT0002259 | No BPO treatments were involved in the trial: the trial compared herbal medicine treatment with placebo |
| Kellett 2006 | Less than 2 weeks: the study was done to determine patient acceptability of 4 topical antibiotic products (clindamycin gel, clindamycin lotion, BPO/erythromycin gel, and erythromycin/zinc solution) used for 1 week to treat acne vulgaris |
| Kircik 2006 | BPO was used as co‐intervention in comparison groups: BPO (5%)/clindamycin (1%) was applied to all participants |
| Kircik 2007 | BPO was used as co‐intervention in comparison groups: BPO/clindamycin topical gel was the same intervention given to the 3 groups treated with tretinoin gel 0.04% or 0.1%, or adapalene gel 0.1%, respectively |
| Kircik 2009a | BPO was used as co‐intervention in comparison groups: the trial compared BPO/clindamycin with BPO |
| Kircik 2009b | BPO was used as co‐intervention in comparison groups: the trial compared BPO/clindamycin gel plus tretinoin gel with a regimen of clindamycin/tretinoin gel plus a BPO wash |
| Leyden 1997a | Not matching our inclusion criteria for participants: healthy participants with no acne were included |
| Leyden 1997b | Not an RCT: a single‐group study |
| Leyden 2010 | Not matching our inclusion criteria for participants: participants included in the study were free of acne |
| Mareledwane 2006 | Oral treatment involved in the comparison: the intervention compared with BPO was an oral treatment (doxycycline) rather than a topical treatment |
| Mesquita 1989 | BPO was used as co‐intervention in comparison groups: the trial compared BPO/miconazole with BPO |
| Miller 2005 | Less than 2 weeks: only 4‐hour and 1‐day data were available |
| Miller 2006a | Not matching our inclusion criteria for participants: the trial compared 2 topical BPO preparations in 25 individuals colonised byP acnes |
| Miller 2006b | Less than 2 weeks: the study was a 3‐day study |
| NCT00441415 | BPO was used as co‐intervention in comparison groups: the trial compared adapalene/BPO with clindamycin/BPO |
| NCT00687908 | Second‐phase data of an RCT: this analysis focused on maintenance treatment with BPO/adapalene among participants who were previously treated with BPO/adapalene or placebo. Effects of maintenance BPO/adapalene were likely to be influenced by the previous treatment (adapalene‐BPO gel or vehicle gel, both with doxycycline hyclate 100 mg) |
| NCT00757523 | BPO was used as co‐intervention in comparison groups: the same study as Zouboulis 2009a |
| NCT00919191 | Not matching our inclusion criteria for participants: the same study as Leyden 2010, which included participants with no acne |
| NCT00926367 | Not matching our inclusion criteria for participants: the study included only healthy participants with no acne |
| NCT00952523 | Not matching our inclusion criteria for participants: the study included only healthy participants with no acne |
| NCT00964223 | BPO was used as co‐intervention in comparison groups: the same study as Gonzalez 2012 |
| NCT00964366 | Not matching our inclusion criteria for participants: the study included only healthy participants with no acne |
| NCT01015638 | Not matching our inclusion criteria for participants: the study included only healthy participants with no acne |
| NCT01188538 | BPO was used as co‐intervention in comparison groups: the trial compared BPO/adapalene with BPO |
| NCT01613924 | Not matching our inclusion criteria for participants: the trial did not recruit participants before it was withdrawn |
| NCT01706250 | BPO was used as co‐intervention in comparison groups: 2 BPO product systems including cleanser, lotion, and toner were compared |
| NCT01818167 | Not matching our inclusion criteria for participants: the target condition in the trial was hidradenitis suppurativa rather than acne |
| NCT02052752 | Less than 2 weeks: a 5‐day study |
| NCT02524665 | Comparison between 2 multi‐step regimens: the trial compared two 3‐step systems (i.e. foam cleanser (2.5% BPO), foam treatment (2.5% BPO) plus toner foam (0.5% salicylic acid), and cleanser (1.5% SA), exfoliating acne treatment gel (1% SA) plus skin perfecting lotion) |
| NCT02589405 | Not an RCT: a single‐group study |
| NCT02698436 | Light treatment is involved in the comparison: BPO vs light treatment |
| NCT02899000 | Not an RCT: a single‐group study |
| NCT02932267 | Not an RCT: a single‐group study |
| NCT03057821 | Not an RCT: a non‐randomised trial |
| NCT03122457 | Not an RCT: a single‐group study |
| NCT03128723 | Not an RCT: a single‐group study |
| NCT03257202 | Not matching our inclusion criteria for participants: the trial focused on healthy volunteers with no active acne |
| NCT03334682 | BPO was used as co‐intervention in comparison groups: the trial compared spironolactone plus BPO with doxycycline plus BPO |
| Ozdemir 2005 | BPO was used as co‐intervention in comparison groups: the trial compared BPO/clindamycin with BPO/glycolic acid |
| Ozolins 2002a | BPO was used as co‐intervention in comparison groups: the same study as Ozolins 2004 |
| Ozolins 2002b | BPO was used as co‐intervention in comparison groups: the same study as Ozolins 2004 |
| Ozolins 2004 | BPO was used as co‐intervention in comparison groups: the trial compared BPO/erythromycin with BPO |
| Ozolins 2005 | BPO was used as co‐intervention in comparison groups: the same study as Ozolins 2004 |
| Pariser 2010 | BPO was used as co‐intervention in comparison groups: the trial compared BPO wash plus a tretinoin gel applied in the morning with BPO wash in the morning plus a tretinoin in the evening |
| Patel 2001 | Not an RCT: a single‐group study |
| Poulin 2010 | Second‐phase data of an RCT: participants completing the previous study (Gold 2010a) were re‐randomised for this study. Results from this study were probably influenced by the previous treatments investigated in Gold 2010a |
| Richter 2016 | BPO was used as co‐intervention in comparison groups: the trial compared BPO/clindamycin with BPO |
| Rodriguez 2003 | Not an RCT: an observational study |
| Rueda 2014 | Less than 2 weeks: the study was done to determine patient preference for 2 different containers of BPO/adapalene gel (tube vs pump) used for 1 week |
| Schlesinger 2010 | BPO was used as co‐intervention in comparison groups: the trial compared 1% salicylic acid plus 4% BPO with 2% salicylic acid plus 8% BPO (concentrations for both BPO and salicylic acid were different between 2 groups) |
| Schutte 1982 | Less than 2 weeks: a 5‐day study |
| Shemer 2009 | BPO was used as co‐intervention in comparison groups: different encapsulations for BPO were compared |
| Tanghetti 2008 | BPO was used as co‐intervention in comparison groups: the trial compared BPO/clindamycin with BPO |
| TCTR20160216002 | BPO was used as co‐intervention in comparison groups: the trial compared ProACNE solution (containing multiple active ingredients) plus BPO with placebo plus BPO |
| TCTR20170603001 | No BPO treatments were involved in the trial: the trial compared adapalene with tretinoin |
| TCTR20171104001 | BPO was used as co‐intervention in comparison groups: the trial compared ProACNE solution (containing multiple active ingredients) plus BPO with placebo plus BPO |
| Touitou 2008 | No BPO treatments were involved in the trial: the trial compared clindamycin/salicylic acid with placebo |
| Veraldi 2016 | Comparison between 2 multi‐step regimens: the trial compared 2 multi‐step systems involving multiple active ingredients |
| Weiss 2003a | Not an RCT: an observational study |
| Weiss 2003b | Not an RCT: an observational study |
| Weiss 2011 | Second‐phase data of an RCT: the analysis included participants who had obtained at least good improvement from the first phase of the RCT |
| Wilhelm 2011 | Not matching our inclusion criteria for participants: study on tolerance in healthy individuals |
| Wilson 2007 | BPO was used as co‐intervention in comparison groups: the trial compared BPO plus salicylic acid with BPO/clindamycin |
| Woodruff 2009 | Comparison between 2 multi‐step regimens: the trial compared a regimen consisting of a retinoid‐based acne treatment cream, ancillary cleanser, and moisturising lotion with an acne treatment regimen based on BPO and salicylic acid |
| Zhen 2006 | Not matching our inclusion criteria for participants: the trial included women aged 40 to 65 years with visible signs of dry and scaly skin |
| Zouboulis 2009a | BPO was used as co‐intervention in comparison groups: the trial compared BPO/clindamycin with BPO/adapalene |
| Zouboulis 2009b | BPO was used as co‐intervention in comparison groups: the same study as Zouboulis 2009a |
| Zouboulis 2010 | BPO was used as co‐intervention in comparison groups: the same study as Zouboulis 2009a |
BPO: benzoyl peroxide. P acnes: Propionibacterium acnes. RCT: randomised controlled trial. SA: salicylic acid.
Characteristics of studies awaiting assessment [ordered by study ID]
2004‐002272‐41.
| Methods | Study design: parallel, single‐blind design Duration of follow‐up: 2 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, Stiefel, a GSK company (GSKClinicalSupportHD@gsk.com), with enquiry about the availability of the full text but were unsuccessful |
2006‐004278‐28.
| Methods | Study design: parallel, single‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, Galderma (clinicaltrials@galderma.com), with enquiry about the availability of the full text but were unsuccessful |
2008‐002359‐26.
| Methods | Study design: parallel, single‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, Stiefel, a GSK company (GSKClinicalSupportHD@gsk.com), with enquiry about the availability of the full text but were unsuccessful |
2008‐006792‐68.
| Methods | Study design: parallel, single‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face, excluding the nose |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐intervention: lymecycline 300 mg capsules |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, Galderma (clinicaltrials@galderma.com), with enquiry about the availability of the full text but were unsuccessful |
2013‐001716‐30.
| Methods | Study design: split‐face design Duration of follow‐up: unclear |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study investigator (sabine.fimmel@charite.de) with enquiry about the availability of the full text but were unsuccessful |
2016‐000063‐16.
| Methods | Study design: parallel, single‐blind design Duration of follow‐up: 6 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Interventions in Group D
Co‐intervention: not specified |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, Galderma (clinicaltrials@galderma.com), with enquiry about the availability of the full text but were unsuccessful |
Ahmadi 2014.
| Methods | Study design: parallel design, 119 participants in total Duration of follow‐up: 3 months |
| Participants | Inclusion criteria: mild to moderate acne Exclusion criteria: unclear Sites of acne: unclear |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐interventions: unclear |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This is a conference proceeding. We attempted to contact the study author (ahmadi@iaups.ac.ir) with the enquiry about availability of the full text but were unsuccessful |
Anonymous 1985.
| Methods | Unclear |
| Participants | Unclear |
| Interventions | Unclear |
| Outcomes | Unclear |
| Notes | Neither abstract nor full text was available. No contact information for the study authors was available |
Chiou 2012.
| Methods | Study design: unclear Duration of follow‐up: 10 to 12 weeks |
| Participants | Unclear |
| Interventions | The study evaluated the percentage contribution of vehicle for 8 commonly prescribed topical preparations including 0.1% tretinoin, 0.1% adapalene, 5% dapsone, 1% clindamycin, a combination of benzoyl peroxide with adapalene or clindamycin, and a clindamycin‐tretinoin combination |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | Full text was not retrieved. We attempted to contact the study author (win@chiouconsulting.com) to request the full text but were unsuccessful |
Cunliffe 1978.
| Methods | Unclear |
| Participants | Unclear |
| Interventions | Unclear |
| Outcomes | Unclear |
| Notes | Neither abstract nor full text was available. We attempted to contact the study author (mail.cunliffe@virgin.net) to request the full text but were unsuccessful |
Cunliffe 1980.
| Methods | Unclear |
| Participants | Unclear |
| Interventions | Unclear |
| Outcomes | Unclear |
| Notes | Neither abstract nor full text was available. We attempted to contact the study author (mail.cunliffe@virgin.net) to request the full text but were unsuccessful |
Dahl 2012.
| Methods | Study design: split‐face study Duration of follow‐up: 8 weeks |
| Participants | Inclusion criteria: female individuals aged 18 to 40 who presented with mild to moderate acne (no cysts, > 4 inflammatory lesions, > 7 non‐inflammatory lesions on each side of the face) Exclusion criteria: unclear Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐intervention: not specified |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and after 2 days and 1, 4, and 8 weeks |
| Notes | This is a conference proceeding. It is unclear whether the study is a randomised controlled trial. We attempted to contact the study author via Linkedin (https://www.linkedin.com/in/dahlamanda/) but were unsuccessful |
Danto 1966.
| Methods | Unclear |
| Participants | Unclear |
| Interventions | Unclear |
| Outcomes | Unclear |
| Notes | Neither abstract nor full text was available. It is unclear whether the study is a randomised controlled trial. No contact information for the study authors was available |
Fagundes 2003.
| Methods | Unclear |
| Participants | Unclear |
| Interventions | Unclear |
| Outcomes | Unclear |
| Notes | According to a meta‐analysis (Seidler 2010), which included this study, this study is a randomised controlled trial. However, we cannot assess its eligibility based on the abstract, which is the only report available to us |
IRCT20181229042165N1.
| Methods | Study design: split‐face design Duration of follow‐up: 3 months |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study investigator (dr_shajari@yahoo.com) with enquiry about availability of the full text but were unsuccessful |
Lassus 1981.
| Methods | Study design: unclear Duration of follow‐up: 4 weeks |
| Participants | Inclusion criteria: moderately severe acne Exclusion criteria: unclear Sites of acne: unclear |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐intervention: not specified |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | Full text was not retrieved. It is unclear whether this study is an RCT. No contact information for the study authors was available |
Leyden 2002.
| Methods | Study design: open‐label, single‐centre study Duration of follow‐up: 2 weeks |
| Participants | Inclusion criteria: aged 18 to 50 years withC acnes (10,000 colonies/cm²) Exclusion criteria: unclear Sites of acne: unclear |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Co‐interventions: none |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were evaluated at baseline and on days 2, 4, 8, and 15 |
| Notes | Without available full text, we cannot determine the eligibility of this study as to whether the included participants suffered acne |
Mallol 1984.
| Methods | Unclear |
| Participants | Unclear |
| Interventions | Unclear |
| Outcomes | Unclear |
| Notes | The language is Spanish. Neither abstract nor full text was available. No contact information for the study authors was available |
NCT00160394.
| Methods | Study design: parallel, single‐blind design, 130 participants Duration of follow‐up: 12 weeks Sample size: 130 participants |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed (probably the same as Langner 2008) and is likely eligible for our review. We attempted to contact the principal investigator, Langner A (langnera@silesia.top.pl), with enquiry about availability of the full text but were unsuccessful |
NCT00624676.
| Methods | Study design: parallel, single‐blind design; 80 participants in total Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the principal investigator, Robert Bissonnette (rbissonnette@innovaderm.ca), with enquiry about availability of the full text but were unsuccessful |
NCT00663286.
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 12 weeks Sample size: 1399 participants |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
Interventions in Group D
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, Dow Pharmaceutical Sciences (https://www.dow.com/en‐us/contact‐us‐cig), with enquiry about availability of the full text but were unsuccessful |
NCT01106807.
| Methods | Study design: split‐face design Duration of follow‐up: 6 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face, excluding the nose |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, Galderma (clinicaltrials@galderma.com), with enquiry about availability of the full text but were unsuccessful |
NCT01237821.
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 16 weeks Sample size: 80 participants |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the principal investigator, Christian Oresajo (coresajo@rd.us.loreal.com), with enquiry about availability of the full text but were unsuccessful |
NCT01445301.
| Methods | Study design: parallel, single‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, GlaxoSmithKline (GSKClinicalSupportHD@gsk.com), with enquiry about availability of the full text but were unsuccessful |
NCT01501799.
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, Actavis Mid‐Atlantic, with enquiry about availability of the full text but were unsuccessful |
NCT01742637.
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study investigator, Catawba Research (http://catawbaresearch.com/contact/), with enquiry about availability of the full text but were unsuccessful |
NCT01769235.
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
Participants were assessed at baseline and at week 12 |
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study investigator, Symbio CRO (http://symbioresearch.com/investigators/), with enquiry about availability of the full text but were unsuccessful |
NCT01769664.
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 11 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, Taro Pharmaceuticals USA (Businessdevelopment@taro.com), with enquiry about availability of the full text but were unsuccessful |
NCT01788384.
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, Watson Laboratories, a division of Allergan (IR‐Medicalaffairsresearch@allergan.com), with enquiry about availability of the full text but were unsuccessful |
NCT01796665.
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, Perrigo Company (https://www.perrigo.com/contact/email.aspx?subject=Rx), with enquiry about availability of the full text but were unsuccessful |
NCT02515305.
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 84 days |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face Severity of acne and corresponding criteria of judgement: baseline IGA score of 3 or 4 on a scale of 0 to 4 |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, Perrigo Company (https://www.perrigo.com/contact/email.aspx?subject=Rx), with enquiry about availability of the full text but were unsuccessful |
NCT02525549.
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 84 days |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, Perrigo Company (https://www.perrigo.com/contact/email.aspx?subject=Rx), with enquiry about availability of the full text but were unsuccessful |
NCT02578043.
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, Taro Pharmaceuticals (Businessdevelopment@taro.com), with enquiry about availability of the full text but were unsuccessful |
NCT02595034.
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 10 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, Taro Pharmaceuticals (Businessdevelopment@taro.com), with enquiry about availability of the full text but were unsuccessful |
NCT02616614.
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, Actavis Inc., with enquiry about availability of the full text but were unsuccessful |
NCT02651220.
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, Actavis Inc., with enquiry about availability of the full text but were unsuccessful |
NCT02709902.
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, Taro Pharmaceuticals (Businessdevelopment@taro.com), with enquiry about availability of the full text but were unsuccessful |
NCT03393494.
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | This trial has been completed and is likely eligible for our review. We attempted to contact the study sponsor, Perrigo Company (https://www.perrigo.com/contact/email.aspx?subject=Rx), with enquiry about availability of the full text but were unsuccessful |
Peereboom‐Wynia 1984.
| Methods | Unclear |
| Participants | Unclear |
| Interventions | Unclear |
| Outcomes | Unclear |
| Notes | Neither abstract nor full text was available. We attempted to contact the study author (roos.bernsen@uaeu.ac.ae) to request the full text but were unsuccessful |
Perez 2017.
| Methods | Unclear |
| Participants | Unclear |
| Interventions | Unclear |
| Outcomes | Unclear |
| Notes | This is a conference proceeding. It is unclear whether the study is a randomised controlled trial. Information available in the report is limited in terms of participants, interventions, and outcomes |
Priano 1993.
| Methods | Unclear |
| Participants | Unclear |
| Interventions | Unclear |
| Outcomes | Unclear |
| Notes | The language is Italian. Neither abstract nor full text was available. No contact information for the study authors was available |
Stinco 2016.
| Methods | Study design: parallel RCT Duration of follow‐up: 8 weeks |
| Participants | Unclear |
| Interventions | Three anti‐microbial preparations were compared, including BPO, clindamycin, and BPO/clindamycin |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Notes | Full text was not retrieved. No contact information for the study authors was available |
Wokalek 1989.
| Methods | Unclear |
| Participants | Unclear |
| Interventions | Unclear |
| Outcomes | Unclear |
| Notes | The language is German. Full text was not available. It is unclear whether the study is an RCT. No contact information for the study authors was available |
BP or BPO: benzoyl peroxide. C acnes: Cutibacterium acnes. IGA: Investigator Global Assessment. IL: inflamed lesion. ISGA: Investigator Static Global Assessment. ITT: intention‐to‐treat. N/A: not applicable. NIL: non‐inflamed lesion. RCT: randomised controlled trial. SD: standard deviation. TL: total lesion.
Characteristics of ongoing studies [ordered by study ID]
2005‐004708‐35.
| Trial name or title | A multi‐centre, comparative, randomized, single‐blind, parallel‐group clinical trial in phase IV for the evaluation of the subject's quality of life, the efficacy and the tolerance of Duac® gel (a gel containing clindamycin phosphate (equivalent to 1% clindamycin) and 5% benzoyl peroxide) and Differin® Gel (a gel containing 0.1% adapalene) in the topical treatment of mild to moderate acne vulgaris |
| Methods | Study design: parallel, single‐blind design Duration of follow‐up: 2 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | July 2007 |
| Contact information | Not provided but sponsored by Laboratorios Stiefel (España), S.A. |
| Notes | ‐ |
2015‐002699‐26.
| Trial name or title | Pilot study of tolerability and effectivity following application of two combination topical acne products clindamycin 1% and 0.025% tretinoin gel (Acnatac® Gel), adapalene 0.1% and benzoyl peroxide 2.5% gel (Epiduo® Gel) |
| Methods | Study design: parallel, single‐blind design Duration of follow‐up: 3 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | Unclear |
| Contact information | Not provided but sponsored by GWT‐TUD GmbH (non‐commercial) |
| Notes | ‐ |
ACTRN12609000443291.
| Trial name or title | Efficacy and safety comparison of two different topical gels (one active and one vehicle) in combination with an oral antibiotic in the treatment of moderate to severe acne vulgaris |
| Methods | Study design: parallel, single‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Co‐intervention: lymecycline 300 mg capsules |
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | August 2009 |
| Contact information | George Tiong, Galderma Australia, 13B Narabang way Belrose 2085 NSW, george.tiong@galderma.com |
| Notes | ‐ |
CTRI/2012/11/003127.
| Trial name or title | A randomized, open label, active controlled, parallel group trial to compare the safety and efficacy of adapalene, benzoyl peroxide, and benzoyl peroxide‐clindamycin combination in participants with acne vulgaris |
| Methods | Study design: parallel, open‐label design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | November 2012 |
| Contact information | Hanmant Amane Department of Pharmacology, Peoples College of Medical Sciences and Research Centre drhsamane25@gmail.com |
| Notes | Probably the same study as Dubey 2016, but trial authors contacted have not confirmed this |
CTRI/2014/07/004734.
| Trial name or title | A multicenter, double‐blind, randomized, parallel‐group, placebo‐controlled bioequivalence study with clinical endpoint to evaluate the bioequivalence of clindamycin 1% and benzoyl peroxide 5% gel of Watson Pharma Pvt Ltd and the reference listed Benzaclin® (clindamycin 1% and benzoyl peroxide 5%) gel of Dermik Laboratories, Business of Sanofi Aventis US LLC, in treatment of subjects with acne vulgaris |
| Methods | Study design: parallel, triple‐blind design Duration of follow‐up: 10 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | November 2012 |
| Contact information | Sumit Arora Clinical Development Dept., Lotus Labs Pvt. Ltd. sumit.arora@lotuslabs.com |
| Notes | ‐ |
CTRI/2015/11/006379.
| Trial name or title | A randomized, double‐blind, multicentric, parallel‐group, active and placebo controlled, three arm clinical study to compare the efficacy and safety of clindamycin phosphate 1.2%/benzoyl peroxide 5% gel (of Cadila Healthcare Limited, India) versus DUAC® gel (of Stiefel Laboratories, USA) versus placebo (vehicle gel) in the ratio of 2:2:1 respectively, in patients with acne vulgaris |
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 11 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | November 2013 |
| Contact information | Dr. Charu Gautam Cliantha Research Limited cgautam@cliantha.in |
| Notes | ‐ |
CTRI/2016/04/006875.
| Trial name or title | A comparative study of benzoyl peroxide 2.5% gel, adapalene 0.1% gel and their combination in treatment of acne vulgaris |
| Methods | Study design: parallel, single‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | September 2014 |
| Contact information | Dr. Sugat Jawade Department of Dermatology, Venereology and Leprosy, Jawaharlal Nehru Medical College, DMIMS, Sawangi (Meghe), Wardha, Maharashtra drsugat09@gmail.com |
| Notes | ‐ |
CTRI/2017/09/009884.
| Trial name or title | A multicenter, randomized, double blind, parallel, placebo controlled clinical endpoint study to determine the therapeutic equivalence of test product benzoyl peroxide 5% and clindamycin phosphate 1% gel and reference product BenzaClin Topical Gel in patients with acne vulgaris |
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 10 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | November 2017 |
| Contact information | Sajitha Sakthidharan Clinical Trial Department, Clinical operations division, 147/F , 8th Main, 3rd Block, Koramangala Bangalore ‐ 560 034. Karnataka. INDIA rajeev.siddaraj@norwichclinical.com |
| Notes | ‐ |
CTRI/2017/12/010974.
| Trial name or title | A clinical study to evaluate the efficacy and safety of Tila‐i Muhasa in the management of Busur Labaniyya (acne vulgaris) |
| Methods | Study design: parallel, open‐label design Duration of follow‐up: 6 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | Unclear |
| Contact information | Dr. Mohammad Nawab Central Research Institute of Unani Medicine, Hyderabad ccrumhqrsnd58@gmail.com |
| Notes | ‐ |
CTRI/2018/05/013744.
| Trial name or title | Evaluation of safety and efficacy of hydrogen peroxide stabilized cream for treatment of mild to moderate acne vulgaris in comparison with benzoyl peroxide (BP) gel, double‐blinded randomised controlled study |
| Methods | Study design: parallel, double‐blinded design Duration of follow‐up: 8 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: unclear |
| Interventions | Interventions in Group A
Interventions in Group B
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | Unclear |
| Contact information | Aditi Tripathi Peoples College of Medical Sciences and Research Centre, India sweetadi.tr@gmail.com |
| Notes | ‐ |
CTRI/2018/06/014684.
| Trial name or title | A randomized, double blind, multicenter, three‐arm, parallel, placebo‐controlled, clinical study to evaluate the bioequivalence using clinical endpoint of clindamycin phosphate 1.2% and benzoyl peroxide 5% gel (Encube Ethicals Private Limited, India) to DUAC® Gel (clindamycin phosphate 1.2% and benzoyl peroxide 5% gel) (Stiefel Laboratories, Inc., Research Triangle Park, NC 27709) in subjects with acne vulgaris |
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 11 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | July 2018 |
| Contact information | Mr. Vidhu Shekhar Mishra Cliantha Research Limited, Garden View Corporate House No.7, Opposite AUDA Garden, Bodakdev, Ahmedabad‐380054, Gujarat, India abarnwal@cliantha.in |
| Notes | ‐ |
IRCT2017072035195N1.
| Trial name or title | Comparison of the efficacy of dapsone 5% gel plus oral doxycycline versus benzoyl peroxide 5% gel plus oral doxycycline in patients with moderate acne vulgaris referred to Rasht Razi hospital during 2017‐2018 |
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | August 2017 |
| Contact information | Dr. Hojat Eftekhari Razi Hospital EFTEKHARI@GUMS.AC.IR |
| Notes | ‐ |
IRCT20170806035524N5.
| Trial name or title | Comparing efficacy of combination therapy with niosomal benzoyl peroxide 1% ‐ clindamycin 1% versus niosomal clindamycin 1% in acne vulgaris: a randomized clinical trial |
| Methods | Study design: parallel, triple‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | June 2018 |
| Contact information | Mahin Aflatoonian Kerman University of Medical Sciences maaflatoonian@gmail.com |
| Notes | ‐ |
JPRN‐UMIN000019639.
| Trial name or title | Study of the utility of acute‐phase and remission maintenance therapy with 2.5% benzoyl peroxide gel for moderate or severe acne vulgaris |
| Methods | Study design: parallel, open‐label design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | December 2015 |
| Contact information | Makoto Kawashima Department of Dermatology, Tokyo Woman's Medical University m‐kawash@derm.twmu.ac.jp |
| Notes | This trial has 2 phases. Only information about the first phase was extracted |
JPRN‐UMIN000024874.
| Trial name or title | Study of the utility of combination therapy 2.5% benzoyl peroxide gel and 2% ozenoxacin lotion for moderate or severe acne vulgaris |
| Methods | Study design: parallel, open‐label design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | February 2017 |
| Contact information | Makoto Kawashima Department of Dermatology, Tokyo Woman's Medical University m‐kawash@derm.twmu.ac.jp |
| Notes | ‐ |
NCT00869492.
| Trial name or title | NCT00869492 |
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 8 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | August 2008 |
| Contact information | Züleyha Yazıcı, Marmara University |
| Notes | ‐ |
NCT00877409.
| Trial name or title | NCT00877409 |
| Methods | Study design: parallel, single‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Site of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | April 2009 |
| Contact information | Sérgio Schalka, Medcin Instituto da Pele Ltda |
| Notes | ‐ |
NCT01422785.
| Trial name or title | NCT01422785 |
| Methods | Study design: parallel, single‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Site of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | August 2011 |
| Contact information | Joshua Zeichner, Mount Sinai School of Medicine |
| Notes | ‐ |
NCT02005666.
| Trial name or title | NCT02005666 |
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 11 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Site of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | November 2013 |
| Contact information | Nilendu Sen nilendu.sen@zyduscadila.com |
| Notes | ‐ |
NCT02731105.
| Trial name or title | NCT02731105 |
| Methods | Study design: split‐face, single‐blind design Duration of follow‐up: 3 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | February 2015 |
| Contact information | Roland Aschoff Uniklinikum Dresden |
| Notes | ‐ |
NCT03076320.
| Trial name or title | NCT03076320 |
| Methods | Study design: parallel, double‐blind design Duration of follow‐up: 6 months |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face and back |
| Interventions | Interventions in Group A
Interventions in Group B
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | March 2017 |
| Contact information | Yocasta Martínez‐Alvarado Hospital Civil de Guadalajara Fray Antonio Alcalde yocastadermatologia@gmail.com |
| Notes | ‐ |
NCT03563365.
| Trial name or title | NCT03563365 |
| Methods | Study design: parallel, single‐blind design Duration of follow‐up: 12 weeks |
| Participants | Inclusion criteria
Exclusion criteria
Sites of acne: face |
| Interventions | Interventions in Group A
Interventions in Group B
Interventions in Group C
|
| Outcomes | Primary outcomes of review interest
Secondary outcomes of review interest
Other outcomes reported in the study
|
| Starting date | June 2018 |
| Contact information | Suzanne Withrow swithrow@yardleyderm.com |
| Notes | ‐ |
BP or BPO: benzoyl peroxide. C acnes: Cutibacterium acnes. CDLQI: Children's Dermatology Life Quality Index. DLQI: Dermatology Life Quality Index. GAAS: Global Acne Assessment Score. GAGS: Global Acne Grading System. IGA: Investigator Global Assessment. IL: inflamed lesion. ISGA: Investigator Static Global Assessment. ITT: intention‐to‐treat. N/A: not applicable. NIL: non‐inflamed lesion. PCOD: polycystic ovary disease. PGA: Physician Global Assessment. RCT: randomised controlled trial. SD: standard deviation. TL: total lesion. VAS: visual analog scale.
Differences between protocol and review
The protocol for this study was published in 2014 (Yang 2014). We made the following changes to the Methods section when conducting this review.
Types of studies: in the protocol, we did not mention the split‐face (paired) design. We included split‐face trials in our review, but their data were summarised narratively and were not pooled with data from parallel or cross‐over trials, given the potential correlated effects within individuals in the split‐face design. We further specified that, if participants were re‐randomised upon completion of the first phase of a parallel trial, second‐phase data after re‐randomisation would be excluded, given the possibility of carry‐over effects from the first phase.
Types of interventions: there were four changes to this section. First, we expanded benzoyl peroxide (BPO) fixed combination treatments to any BPO add‐on treatment. Second, we clearly specified that any pharmacological treatment in comparisons should be applied topically (i.e. comparisons between BPO‐related treatments versus oral treatments were excluded). Third, we clearly specified that we did not consider comparisons with any multi‐step regimens involving multiple active ingredients. Finally, we excluded comparisons between different brand products of the same formulation and concentration of BPO, which is beyond our research purpose.
Types of outcome measures: in the protocol, we defined short‐term treatment duration as less than four weeks, medium‐term as four or more weeks and less than eight weeks, and long‐term as eight weeks or longer for each outcome. These definitions were changed slightly in our review (i.e. short term (two to four weeks), medium term (five to eight weeks), and long term (more than eight weeks)). In the review, we further clearly specified the methods used to address problems with multiple time scales and multiple measurements, which may occur in the trials.
Primary outcomes: in the protocol, we did not specify the measure of participant global self‐assessment of acne improvement. To make this outcome measure clinically relevant and consistent with other recent Cochrane Reviews on acne treatments (Barbaric 2016), we clarified that this outcome was measured as the proportion of participants expressing any greater improvement above the first category of improvement on a Likert or Likert‐like scale. We pre‐defined this outcome before data extraction. However, most of the trials did not provide sufficient data to allow for data pooling, in which case we described the results as reported in those trials and conducted sensitivity analyses.
Secondary outcomes: we did not initially mention in the protocol the measure of change in lesions, but we pre‐specified this before data extraction, which consists of absolute and percentage reduction in three types of lesions (total, inflamed, and non‐inflamed lesions). When neither absolute nor percentage reduction was presented in the trial, we reported comparisons of lesion number at the end of treatment if available.
For the outcome of adverse events, we clarified in the review that the unit of analysis for this outcome was an individual participant, rather than an adverse event.
Data collection and analysis: we did not specify in the protocol for what comparisons we would create 'Summary of findings' tables. This was further clarified in the review. In line with MECIR Reporting, we assessed and presented the quality of evidence for the secondary safety outcome as well as for the primary outcomes, which was not planned in the protocol.
Data extraction and management: we slightly simplified the pre‐designed extraction form after a pilot by removing some items, for which we examined data in the risk of bias assessment and data analysis stages. We provided more details about how outcome data were extracted from a graph and how a trial was linked to its registration record.
Assessment of risk of bias in included studies: we attended to the importance of intention‐to‐treat (ITT) analysis in the assessment domain of incomplete outcome data.
Measures of treatment effect: we neither used SMD in data synthesis for continuous outcomes measured via different scales nor treated ordinal outcomes as continuous variables because our review did not find any outcomes of this kind.
Unit of analysis issues: we further specified in our review that data from the split‐face design were only narratively presented.
Dealing with missing data: we planned to conduct sensitivity analysis based on consideration of 'best case' and 'worst case' scenarios for participants who dropped out or were lost to follow‐up. However, we considered only the 'worst case' in our analysis, thereby providing a conservative effect estimate. For example, when we assessed the primary outcome of participant global self‐assessment of acne improvement, those who did not provide data for this outcome would be regarded as experiencing treatment failure.
Assessment of heterogeneity: we did not use any cut‐offs of I² to guide our analysis, but we tried to explore potential sources of heterogeneity via narrative description. Subgroup analysis by pre‐specified variables was not feasible when the trials included were limited.
Assessment of reporting biases: due to the limited number of included studies for most outcomes in a specific comparison, we created a funnel plot and performed Egger's test only for the safety outcomes (long‐term data) for BPO versus placebo or no treatment and BPO versus adapalene.
Data synthesis: we deleted a sentence about pooling standardised mean difference (SMD) because this effect measure was not applicable to the outcome data in our review.
Subgroup analysis and investigation of heterogeneity: due to the scarcity of data for most outcomes across all comparisons, we did not conduct subgroup analysis as planned but separated the analysis by co‐intervention, given that this may represent different comparisons if the co‐interventions have modification effects. We conducted a Q test to examine the differences between subgroups. This analysis did not meet the prerequisite for subgroup analysis pre‐specified in our protocol (each subgroup should include at least three studies) and was performed post hoc to explore whether effects of BPO would differ with different co‐interventions.
Sensitivity analysis: we planned to conduct sensitivity analyses to examine the effects of excluding studies with high risk of bias. However, we did not undertake these analyses due to the scarcity of data. When applicable, we also conducted a sensitivity analysis post hoc for the primary outcome 'participant‐self reported acne improvement' in the main comparisons by including all studies that reported data for this outcome, regardless of the scales and criteria used in the included studies to determine improvement.
Quality of the evidence: we further described how to use the GRADE approach to assess the quality of evidence.
Contributions of authors
ZY was the contact person with the editorial base. ZY co‐ordinated contributions from co‐authors and wrote the final draft of the review. ZY, ELM, and YZ screened papers against eligibility criteria. ZY obtained data on ongoing and unpublished studies. ZY, JH, and YCZ appraised the quality of papers. ZY, YZ, and HL extracted data for the review and sought additional information about papers. ZY, YZ, and JH entered data into RevMan. ZY, YZ, and ELM analysed and interpreted data. ZY, YZ, JH, and JL worked on the methods sections. ZY, ELM, and HL drafted the clinical sections of the background and responded to the clinical comments of referees. ZY, YZ, JH, and JL responded to the methodology and statistics comments of the referees. QZ was the consumer co‐author who checked the review for readability and clarity, as well as to ensure that outcomes are relevant to consumers. ZY is the guarantor of the update.
All review authors reviewed the final draft.
Disclaimer
This project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Skin Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS, or the Department of Health.
Sources of support
Internal sources
Peking University Health Science Center, China.
University of Cambridge, UK.
McMaster University, Canada.
External sources
Cochrane Skin Group, UK.
The National Institute for Health Research (NIHR), UK.
The NIHR, UK, is the largest single funder of the Cochrane Skin Group.
Declarations of interest
Zhirong Yang: nothing to declare.
Yuan Zhang: nothing to declare.
Elvira Lazic Mosler: nothing to declare.
Jing Hu: nothing to declare.
Hang Li: nothing to declare.
Yanchang Zhang: nothing to declare.
Jia Liu: nothing to declare.
Qian Zhang: nothing to declare.
New
References
References to studies included in this review
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References to studies excluded from this review
2009‐011212‐37 {published data only}
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2009‐016240‐40 {published data only}
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2010‐020796‐24 {published data only}
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2013‐001753‐26 {published data only}
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2016‐000616‐15 {published data only}
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2017‐002975‐25 {published data only}
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2017‐003105‐18 {published data only}
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ACTRN12617000498392 {published data only}
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ACTRN12617000642381 {published data only}
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ACTRN12617001127392 {published data only}
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CTRI/2017/08/009299 {published data only}
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CTRI/2017/09/009855 {published data only}
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CTRI/2017/12/010963 {published data only}
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NCT00687908 {published data only}
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NCT00757523 {published data only}
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NCT00919191 {published data only}
- NCT00919191. Evaluation of irritation by two facial gels applied to opposite sides of the face. www.clinicaltrials.gov/ct2/show/NCT00919191 (first received 10 June 2009).
NCT00926367 {published data only}
- NCT00926367. Two‐week study to compare the tolerance and irritation potential of two combination topical gel acne medications. clinicaltrials.gov/ct2/show/NCT00926367 (first received 21 June 2009).
NCT00952523 {published data only}
- NCT00952523. Evaluation of irritation that potentially could be caused by two facial gels applied to opposite sides of the face. www.clinicaltrials.gov/ct2/show/NCT00952523 (first received 4 August 2009).
NCT00964223 {published data only}
- NCT00964223. A study to evaluate tolerability of two topical drug products in the treatment of facial acne. www.clinicaltrials.gov/ct2/show/NCT00964223 (first received 20 August 2009).
NCT00964366 {published data only}
- NCT00964366. Study to determine and compare the tolerance and irritation potential of topical acne medications. clinicaltrials.gov/ct2/show/NCT00964366 (first received 20 August 2009).
NCT01015638 {published data only}
- NCT01015638. Compare the tolerance of clindamycin 1%/benzoyl peroxide (BPO) 5% gel to clindamycin 1.2%/BPO 2.5% topical medications. clinicaltrials.gov/ct2/show/NCT01015638 (first received 17 November 2009).
NCT01188538 {published data only}
- NCT01188538. Anti Propionibacterium (P) acnes activity of Epiduo® gel compared to benzoyl peroxide (BPO) 2.5% gel. clinicaltrials.gov/ct2/show/NCT01188538 (first received 24 August 2010).
NCT01613924 {published data only}
- NCT01613924. Efficacy of handheld acne heat device. www.clinicaltrials.gov/ct2/show/NCT01613924 (first received 30 May 2012).
NCT01706250 {published data only}
- NCT01706250. U0289‐401: eight week, split‐face study to determine and compare the efficacy and tolerability of MAXCLARITY™ II to PROACTIV™. www.clinicaltrials.gov/ct2/show/NCT01706250 (first received 11 October 2012).
NCT01818167 {published data only}
- NCT01818167. An investigation Into the efficacy of povidone topical cream as compared to 10% benzoyl peroxide wash for the treatment of hidradenitis suppurativa. clinicaltrials.gov/ct2/show/NCT01818167 (first received 20 March 2013).
NCT02052752 {published data only}
- NCT02052752. A five day clinical study to examine the effects of a benzoyl peroxide treatment on facial acne lesions. clinicaltrials.gov/ct2/show/NCT02052752 (first received 30 January 2014).
NCT02524665 {published data only}
- NCT02524665. 8 week study to evaluate and compare the efficacy and tolerability of MAXCLARITY II and MURAD to treat acne. clinicaltrials.gov/ct2/show/NCT02524665 (first received 13 August 2015).
NCT02589405 {published data only}
- NCT02589405. Benzac 5% gel in combination with cosmetic products in acne vulgaris (Benzac). clinicaltrials.gov/ct2/show/NCT02589405 (first received 23 October 2015).
NCT02698436 {published data only}
- NCT02698436. A study to evaluate the effectiveness and tolerance of two acne treatments on subjects with mild to moderate acne (TIGER). clinicaltrials.gov/ct2/show/NCT02698436 (first received 26 February 2016).
NCT02899000 {published data only}
- NCT02899000. A treatment for severe inflammatory acne subjects. clinicaltrials.gov/ct2/show/NCT02899000 (first received 8 September 2016).
NCT02932267 {published data only}
- NCT02932267. Subject reported outcomes with use of adapalene 0.3% ‐ benzoyl peroxide (BPO) 2.5% in dark skin acne (EDeN). clinicaltrials.gov/ct2/show/NCT02932267 (first received 11 October 2016).
NCT03057821 {published data only}
- NCT03057821. Propionibacterium acnes in shoulder arthroplasty. clinicaltrials.gov/ct2/show/NCT03057821 (first received 14 February 2017).
NCT03122457 {published data only}
- NCT03122457. Perimenstrual acne with clindamycin phosphate and benzoyl peroxide. clinicaltrials.gov/ct2/show/NCT03122457 (first received 17 April 2017).
NCT03128723 {published data only}
- NCT03128723. A study to evaluate the tolerance of an acne treatment in sensitive skin subjects with mild to moderate acne vulgaris. clinicaltrials.gov/ct2/show/NCT03128723 (first received 20 April 2017).
NCT03257202 {published data only}
- NCT03257202. Topical treatment and prevalence of P. acnes. clinicaltrials.gov/ct2/show/NCT03257202 (first received 1 August 2017).
NCT03334682 {published data only}
- NCT03334682. Randomized double‐blind study on the benefit of spironolactone for treating acne of adult woman (FASCE). clinicaltrials.gov/ct2/show/NCT03334682 (first received 30 October 2017).
Ozdemir 2005 {published data only}
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TCTR20170603001 {published data only}
- TCTR20170603001. A comparison of the efficacy and safety of 0.1% adapalene gel and 0.025% tretinoin cream in the treatment of childhood acanthosis nigricans. apps.who.int/trialsearch/Trial2.aspx?TrialID=TCTR20170603001 (first received 3 June 2017).
TCTR20171104001 {published data only}
- TCTR20171104001. A randomized, controlled, split‐face clinical trial comparing combination of ProACNE SOLUTION ACTIVE CLEAR with 2.5% benzoyl peroxide versus 2.5% benzoyl peroxide with placebo in the treatment of mild to moderate degree of acne vulgaris. apps.who.int/trialsearch/Trial2.aspx?TrialID=TCTR20171104001 (first received 3 November 2017).
Touitou 2008 {published data only}
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NCT00624676 {published data only}
- NCT00624676. Efficacy and tolerance of a derivative of salicylic acid and 5% benzoyl peroxide in facial acne vulgaris. clinicaltrials.gov/ct2/show/NCT00624676 (first received 27 February 2008).
NCT00663286 {published data only}
- NCT00663286. A clinical trial evaluating the safety and efficacy of IDP‐110 in patients with acne vulgaris. clinicaltrials.gov/ct2/show/NCT00663286 (first received 22 April 2008).
- NCT00664248. A clinical study evaluating the safety and efficacy of IDP‐110 in patients with acne vulgaris. clinicaltrials.gov/ct2/show/NCT00664248 (first received 22 April 2008).
NCT01106807 {published data only}
- NCT01106807. Exploratory study to evaluate the efficacy and safety of CD07223 gel in subjects with acne. clinicaltrials.gov/ct2/show/NCT01106807 (first received 20 April 2010).
NCT01237821 {published data only}
- NCT01237821. Comparing OTC acne treatment to prescription regimen. clinicaltrials.gov/ct2/show/NCT01237821 (first received 10 November 2010).
NCT01445301 {published data only}
- NCT01445301. Study STF115287, a clinical confirmation study of GSK2585823 in the treatment of acne vulgaris in Japanese subjects. clinicaltrials.gov/ct2/show/NCT01445301 (first received 3 October 2011).
NCT01501799 {published data only}
- CTRI/2011/05/001762. A clinical trial to compare adapalene and benzoyl peroxide combination local application gel to Epiduo of Galderma Laboratories, L.P., and both these to an inactive local application gel in patients with mild to severe pimple. apps.who.int/trialsearch/Trial2.aspx?TrialID=CTRI/2011/05/001762 (first received 26 May 2011).
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NCT01742637 {published data only}
- NCT01742637. Study comparing adapalene and benzoyl peroxide gel 0.1%/2.5% to Epiduo® and both to a placebo control in the treatment of acne vulgaris. clinicaltrials.gov/ct2/show/NCT01742637 (first received 5 December 2012).
NCT01769235 {published data only}
- NCT01769235. Study comparing clindamycin phosphate and benzoyl peroxide gel to Acanya® Gel and both to a vehicle control in the treatment of acne vulgaris. clinicaltrials.gov/ct2/show/NCT01769235 (first received 16 January 2013).
NCT01769664 {published data only}
- NCT01769664. A study comparing clindamycin 1%/benzoyl peroxide 5% topical gel to Duac® topical gel in the treatment of acne vulgaris. https://clinicaltrials.gov/ct2/show/NCT01769664 (first received 17 January 2013).
NCT01788384 {published data only}
- NCT01788384. Evaluate therapeutic equivalence and safety of two clindamycin phosphate and benzoyl peroxide gels in acne vulgaris. clinicaltrials.gov/ct2/show/NCT01788384 (first received 11 February 2013).
NCT01796665 {published data only}
- NCT01796665. A study to compare clindamycin phosphate and benzoyl peroxide topical gel 1.2%/2.5% to Acanya® topical gel in the treatment of acne vulgaris. clinicaltrials.gov/ct2/show/NCT01796665 (first received 22 February 2013).
NCT02515305 {published data only}
- NCT02515305. Comparative safety and efficacy of two treatments in the treatment of acne vulgaris. clinicaltrials.gov/ct2/show/NCT02515305 (first received 4 August 2015).
NCT02525549 {published data only}
- NCT02525549. Comparative safety and bioequivalence of two treatments in the treatment of acne vulgaris. clinicaltrials.gov/ct2/show/NCT02525549 (first received 17 August 2015).
NCT02578043 {published data only}
- NCT02578043. A study comparing clindamycin and benzoyl peroxide gel 1.2%/3.75% to Onexton™ Gel in the treatment of acne vulgaris. clinicaltrials.gov/ct2/show/NCT02578043 (first received 14 October 2015).
NCT02595034 {published data only}
- NCT02595034. A study CLBG and benzoyl peroxide gel 1%/5% to BenzaClin® Gel in the treatment of acne vulgaris. clinicaltrials.gov/ct2/show/NCT02595034 (first received 1 November 2015).
NCT02616614 {published data only}
- NCT02616614. Double‐blind placebo‐controlled trial of generic clindamycin/benzoyl peroxide gel versus Onexton Gel in acne vulgaris. clinicaltrials.gov/ct2/show/NCT02616614 (first received 25 November 2015).
NCT02651220 {published data only}
- NCT02651220. Clinical end point study of generic adapalene and benzoyl peroxide gel versus Epiduo® Forte Gel in treatment of acne vulgaris. clinicaltrials.gov/ct2/show/NCT02651220 (first received 5 January 2016).
NCT02709902 {published data only}
- NCT02709902. Study comparing adapalene/BP gel to EPIDUO® FORTE and both to a placebo control in treatment of acne vulgaris. clinicaltrials.gov/ct2/show/NCT02709902 (first received 8 March 2016).
NCT03393494 {published data only}
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Peereboom‐Wynia 1984 {published data only}
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References to ongoing studies
2005‐004708‐35 {published data only}
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2015‐002699‐26 {published data only}
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ACTRN12609000443291 {published data only}
- ACTRN12609000443291. Efficacy and safety comparison of adapalene 0.1%/benzoyl peroxide 2.5% gel associated with lymecycline 300mg capsules versus adapalene 0.1%/benzoyl peroxide 2.5% vehicle gel associated with lymecycline 300mg capsules in the treatment of moderate to severe acne vulgaris. apps.who.int/trialsearch/Trial2.aspx?TrialID=ACTRN12609000443291 (first received 12 June 2009).
CTRI/2012/11/003127 {published data only}
- CTRI/2012/11/003127. A randomized, open label, active controlled, parallel group trial to compare the safety and efficacy of adapalene, benzoyl peroxide, and benzoyl peroxide‐clindamycin combination in patients with acne vulgaris. apps.who.int/trialsearch/Trial2.aspx?TrialID=CTRI/2012/11/003127 (first received 21 November 2012).
CTRI/2014/07/004734 {published data only}
- CTRI/2014/07/004734. A multiple center, parallel group study to evaluate the bioequivalence of test drug clindamycin 1% and benzoyl peroxide 5% gel of Watson and reference drug Benzaclin® (clindamycin 1% and benzoyl peroxide 5%) Gel of Dermik Labs, in treatment of subjects with acne vulgaris. apps.who.int/trialsearch/Trial2.aspx?TrialID=CTRI/2014/07/004734 (first received 14 July 2014).
CTRI/2015/11/006379 {published data only}
- CTRI/2015/11/006379. A randomized, double‐blind, multicentric, parallel‐group, active and placebo controlled, three arm clinical study to compare the efficacy and safety of clindamycin phosphate 1.2%/benzoyl peroxide 5% gel (of Cadila Healthcare Limited, India) versus DUAC® Gel (of Stiefel Laboratories, USA) versus placebo (vehicle gel) in the ratio of 2:2:1 respectively, in patients with acne vulgaris. apps.who.int/trialsearch/Trial2.aspx?TrialID=CTRI/2015/11/006379 (first received 26 November 2015).
CTRI/2016/04/006875 {published data only}
- CTRI/2016/04/006875. A comparative study of benzoyl peroxide 2.5% gel, adapalene 0.1% gel and their combination in treatment of acne vulgaris. apps.who.int/trialsearch/Trial2.aspx?TrialID=CTRI/2016/04/006875 (first received 27 April 2016).
CTRI/2017/09/009884 {published data only}
- CTRI/2017/09/009884. A multicenter, randomized, double blind, parallel, placebo controlled clinical endpoint study to determine the therapeutic equivalence of test product benzoyl peroxide 5% and clindamycin phosphate 1% gel and reference product BenzaClin Topical Gel in patients with acne vulgaris. apps.who.int/trialsearch/Trial2.aspx?TrialID=CTRI/2017/09/009884 (first received 22 September 2017).
CTRI/2017/12/010974 {published data only}
- CTRI/2017/12/010974. A clinical study to evaluate the efficacy and safety of Tila‐i Muhasa in the management of Busur Labaniyya (acne vulgaris). apps.who.int/trialsearch/Trial2.aspx?TrialID=CTRI/2017/12/010974 (first received 26 December 2017).
CTRI/2018/05/013744 {published data only}
- CTRI/2018/05/013744. Evaluation of safety and efficacy of hydrogen peroxide stabilized cream for treatment of mild to moderate acne vulgaris in comparison with benzoyl peroxide (BP) gel, double blinded randomized control study. apps.who.int/trialsearch/Trial2.aspx?TrialID=CTRI/2018/05/013744 (first received 7 May 2018).
CTRI/2018/06/014684 {published data only}
- CTRI/2018/05/013744. A randomized, double blind, multicenter, three‐arm, parallel, placebo‐controlled clinical study to evaluate the bioequivalence using clinical endpoint of clindamycin phosphate 1.2% and benzoyl peroxide 5% gel (Encube Ethicals Private Limited, India) to DUAC® Gel (clindamycin phosphate 1.2% and benzoyl peroxide 5% gel) (Stiefel Laboratories, Inc., Research Triangle Park, NC 27709) in subjects with acne vulgaris. apps.who.int/trialsearch/Trial2.aspx?TrialID=CTRI/2018/06/014684 (first received 29 June 2018).
IRCT2017072035195N1 {published data only}
- IRCT2017072035195N1. Comparison of the efficacy of dapsone 5% gel plus oral doxycycline versus benzoyl peroxide 5% gel plus oral doxycycline in patients with moderate acne vulgaris referred to Rasht Razi hospital during 2017‐2018. apps.who.int/trialsearch/Trial2.aspx?TrialID=IRCT2017072035195N1 (first received 23 October 2017).
IRCT20170806035524N5 {published data only}
- IRCT20170806035524N5. Comparing efficacy of combination therapy with niosomal benzoyl peroxide 1% ‐ clindamycin 1% versus niosomal clindamycin 1% in acne vulgaris: a randomized clinical trial. apps.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20170806035524N5 (first received 15 August 2018).
JPRN‐UMIN000019639 {published data only}
- JPRN‐UMIN000019639. Study of the utility of acute‐phase and remission maintenance therapy with 2.5% benzoyl peroxide gel for moderate or severe acne vulgaris. apps.who.int/trialsearch/Trial2.aspx?TrialID=JPRN‐UMIN000019639 (first received 1 December 2015).
JPRN‐UMIN000024874 {published data only}
- JPRN‐UMIN000024874. Study of the utility of combination therapy 2.5% benzoyl peroxide gel and 2% ozenoxacin lotion for moderate or severe acne vulgaris. apps.who.int/trialsearch/Trial2.aspx?TrialID=JPRN‐UMIN000024874 (first received 15 February 2017).
NCT00869492 {published data only}
- NCT00869492. Comparison of nadifloxacin cream alone and with benzoyl peroxide solution in the treatment of acne. clinicaltrials.gov/ct2/show/NCT00869492 (first received 26 March 2009).
NCT00877409 {published data only}
- NCT00877409. A monocentric, single‐blind, randomized, placebo‐controlled study of the safety and efficacy of the topical drug Acnase creme in the treatment of acne vulgaris I and II. clinicaltrials.gov/ct2/show/NCT00877409 (first received 7 April 2009).
NCT01422785 {published data only}
- NCT01422785. A study comparing combination clindamycin phosphate/tretinoin gel alone versus with benzoyl peroxide foaming cloths for facial acne. clinicaltrials.gov/ct2/show/NCT01422785 (first received 24 August 2011).
NCT02005666 {published data only}
- NCT02005666. To compare the efficacy and safety of clindamycin phosphate 1.2%/benzoyl peroxide 5% gel of CHL versus DUAC® gel. clinicaltrials.gov/ct2/show/NCT02005666 (first received 9 December 2013).
NCT02731105 {published data only}
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NCT03076320 {published data only}
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NCT03563365 {published data only}
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