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Conducting a Bayesian RegularizedMeta-analysis

Packages

First, load in the necessary packages. In addition, if you arerunning the model locally on a multi-core machine, you can setoptions(mc.cores = 4). This ensures the different MCMCchains will be run in parallel, making estimation faster.

library(pema)library(tidySEM)library(ggplot2)options(mc.cores =4)

Data

In this application, we will work with the bonapersona data(Bonapersona et al., 2019). The data and codebook can be foundhere. First,we read in the data and make sure all relevant variables are of thecorrect type.

descriptives(bonapersona)[,c("name","type","n","unique","mean","sd","v")]
#>                    name      type   n unique     mean     sd     v#> 1                   exp   integer 734    411  222.644 111.88    NA#> 2                    id   integer 734    212   99.402  60.03    NA#> 3                author character 734    209       NA     NA 0.990#> 4                  year   integer 734     21 2011.014   4.45    NA#> 5               journal character 734     69       NA     NA 0.945#> 6               species    factor 734      3       NA     NA 0.433#> 7         strainGrouped    factor 734     15       NA     NA 0.762#> 8                origin    factor 734      4       NA     NA 0.617#> 9                   sex    factor 734      3       NA     NA 0.373#> 10              ageWeek   numeric 721     25   13.333   5.75    NA#> 11                model    factor 734      6       NA     NA 0.667#> 12           mTimeStart   integer 734     12    2.357   2.51    NA#> 13             mTimeEnd   integer 734     18   12.802   4.39    NA#> 14            mHoursAve   numeric 734     33   54.076  47.73    NA#> 15         mCageGrouped    factor 734      4       NA     NA 0.485#> 16           mLDGrouped    factor 734      5       NA     NA 0.469#> 17          mRepetition    factor 734      7       NA     NA 0.446#> 18      mControlGrouped    factor 734      4       NA     NA 0.069#> 19          hit2Grouped    factor 734      3       NA     NA 0.493#> 20    testAuthorGrouped    factor 734     27       NA     NA 0.894#> 21        testLDGrouped    factor 734      4       NA     NA 0.295#> 22     varAuthorGrouped    factor 734     47       NA     NA 0.914#> 23               waterT    factor 734      9       NA     NA 0.125#> 24           waterTcate    factor 734      5       NA     NA 0.123#> 25         freezingType    factor 734     10       NA     NA 0.221#> 26     retentionGrouped    factor 734      5       NA     NA 0.520#> 27     directionGrouped    factor 734      5       NA     NA 0.648#> 28 effectSizeCorrection   integer   5      2    1.000   0.00    NA#> 29               cut_nC   integer  37      2    1.000   0.00    NA#> 30         n_notRetriev   integer   5      2    1.000   0.00    NA#> 31                   nC   numeric 734     25   10.719   4.07    NA#> 32                meanC   numeric 734    412  167.110 112.13    NA#> 33                  sdC   numeric 734    499   73.919  62.43    NA#> 34                  seC   numeric 734    209   23.314  19.61    NA#> 35                   nE   numeric 734     25   11.200   4.15    NA#> 36                meanE   numeric 734    430  163.209 114.28    NA#> 37                  sdE   numeric 734    500   76.684  62.99    NA#> 38                  seE   numeric 734    206   23.554  19.54    NA#> 39             dataFrom    factor 734      4       NA     NA 0.288#> 40        seqGeneration    factor 734      3       NA     NA 0.487#> 41             baseline    factor 734      4       NA     NA 0.412#> 42           allocation    factor 734      3       NA     NA 0.170#> 43              housing    factor 734      2       NA     NA 0.000#> 44             blindExp    factor 734      4       NA     NA 0.429#> 45              control    factor 734      4       NA     NA 0.043#> 46               outAss    factor 734      4       NA     NA 0.456#> 47             outBlind    factor 734      5       NA     NA 0.654#> 48              incData    factor 734      3       NA     NA 0.219#> 49            waterTNum   numeric  48      8   22.292   1.37    NA#> 50                 each   integer 734    734  367.500 212.03    NA#> 51          mTimeLength   integer 734     19   10.446   5.61    NA#> 52 speciesStrainGrouped    factor 734     16       NA     NA 0.762#> 53            blindRand    factor 734      3       NA     NA 0.317#> 54                 bias   numeric 734      9    2.884   0.75    NA#> 55                   tV    factor 734     60       NA     NA 0.929#> 56              anxiety   integer 734      2    0.486   0.50    NA#> 57            sLearning   numeric 734      2    0.277   0.45    NA#> 58           nsLearning   numeric 734      2    0.143   0.35    NA#> 59               social   integer 734      2    0.063   0.24    NA#> 60             multiply   integer 734      2   -0.272   0.96    NA#> 61               noMeta   numeric 734      2    0.031   0.17    NA#> 62               domain    factor 734      6       NA     NA 0.662#> 63        directionQual   numeric 617      4    0.183   0.58    NA#> 64                   yi   numeric 734    726    0.243   1.34    NA#> 65                   vi   numeric 734    728    0.263   0.36    NA

Impute missings

bonapersona$ageWeek[is.na(bonapersona$ageWeek)]<-median(bonapersona$ageWeek,na.rm =TRUE)

Moderators

For this application, we use a smaller selection of moderators thanin Bonapersona et al. (2019).

datsel<- bonapersona[ ,c("yi","vi","author","mTimeLength","year","model","ageWeek","strainGrouped","bias","species","domain","sex")]

Two-level model

First, for simplicity, we run a two-level model ignoring the factthat certain effect sizes come from the same study.

dat2l<- datseldat2l[["author"]]<-NULL

Two-level model with the lasso prior

We start with running a penalized meta-analysis using the lassoprior. Compared to the horseshoe prior, the lasso is easier to usebecause it has only two hyperparameters to set. However, the lightertails of the lasso can result in large coefficients being shrunken toomuch towards zero thereby leading to potentially more bias compared tothe regularized horseshoe prior.

For the lasso prior, we need to specify the degrees of freedomdf and thescale. Both default to 1. Thedegrees of freedom determines the chi-square prior that is specified forthe inverse-tuning parameter. Increasing the degrees of freedom willallow larger values for the inverse-tuning parameter, leading to lessshrinkage. Increasing the scale parameter will also result in lessshrinkage. The influence of these hyperparameters can be visualizedthrough the implemented shiny app, which can be called viashiny_prior().

fit_lasso<-brma(yi~ .,data = dat2l,vi ="vi",method ="lasso",prior =c(df =1,scale =1),mute_stan =FALSE)

Assessing convergence and interpreting the results

We can request the results using thesummary function.Before we interpret the results, we need to ensure that the MCMC chainshave converged to the posterior distribution. Two helpful diagnosticsprovided in the summary are the number of effective posterior samplesn_eff and the potential scale reduction factorRhat.n_eff is an estimate of the number ofindependent samples from the posterior. Ideally, the ration_eff to total samples is as close to 1 as possible.Rhat compares the between- and within-chain estimates andis ideally close to 1 (indicating the chains have mixed well). Shouldany values forn_eff orRhat be far from theseideal values, you can try increasing the number of iterations throughtheiter argument. By default, thebrmafunction runs four MCMC chains with 2000 iterations each, half of whichis discarded as burn-in. As a result, a total of 4000 iterations isavailable on which posterior summaries are based. If this does not help,non-convergence might indicate a problem with the modelspecification.

sum<-summary(fit_lasso)sum$coefficients[,c("mean","sd","2.5%","97.5%","n_eff","Rhat")]
#>                                  mean      sd     2.5%   97.5% n_eff Rhat#> Intercept                    -20.7265 14.4136 -50.9609  3.6187  1657    1#> mTimeLength                   -0.0032  0.0048  -0.0143  0.0049  2070    1#> year                           0.0104  0.0072  -0.0017  0.0254  1660    1#> modelLG                        0.0855  0.1438  -0.1759  0.4025  2283    1#> modelLNB                       0.1430  0.1059  -0.0270  0.3721  1210    1#> modelM                         0.0213  0.0496  -0.0695  0.1329  2208    1#> modelMD                        0.0229  0.0773  -0.1253  0.1856  2320    1#> ageWeek                       -0.0073  0.0053  -0.0187  0.0015  1364    1#> strainGroupedC57Bl6           -0.0189  0.0662  -0.1587  0.1117  2193    1#> strainGroupedCD1              -0.1158  0.1813  -0.5305  0.2004  2074    1#> strainGroupedDBA              -0.0253  0.1625  -0.3563  0.3059  1591    1#> strainGroupedlisterHooded     -0.0540  0.3135  -0.7133  0.5434  2062    1#> strainGroupedlongEvans         0.0712  0.1205  -0.1421  0.3397  2253    1#> strainGroupedlongEvansHooded   0.1790  0.2181  -0.1823  0.6557  2302    1#> strainGroupedNMRI              0.1200  0.2423  -0.3336  0.6518  2225    1#> strainGroupedNS                0.0289  0.1497  -0.2674  0.3448  2842    1#> strainGroupedother            -0.0227  0.1263  -0.2832  0.2302  2079    1#> strainGroupedspragueDawley    -0.0041  0.0615  -0.1343  0.1176  1921    1#> strainGroupedswissWebster      0.5557  0.4900  -0.2266  1.6393  2230    1#> strainGroupedwistar            0.0236  0.0567  -0.0807  0.1512  2078    1#> strainGroupedwistarKyoto       0.0295  0.2698  -0.5350  0.5813  2392    1#> bias                          -0.0086  0.0290  -0.0716  0.0473  2087    1#> speciesrat                     0.1191  0.0877  -0.0203  0.3179  1380    1#> domainsLearning                0.0017  0.0501  -0.1012  0.1072  1986    1#> domainnsLearning               0.1159  0.0815  -0.0215  0.2892  1553    1#> domainsocial                   0.1702  0.1183  -0.0249  0.4232  1600    1#> domainnoMeta                  -0.3615  0.1843  -0.7299 -0.0184  1212    1#> sexM                           0.1205  0.0689  -0.0017  0.2605  1602    1#> tau2                           0.4291  0.0394   0.3524  0.5098  1112    1

If we are satisfied with the convergence, we can continue looking atthe posterior summary statistics. Thesummary functionprovides the posterior mean estimate for the effect of each moderator.Since Bayesian penalization does not automatically shrink estimatesexactly to zero, some additional criterion is needed to determine whichmoderators should be selected in the model. Currently, this is doneusing the 95% credible intervals, with a moderator being selected ifzero is excluded in this interval. In thesummary this isdenoted by an asterisk for that moderator. In this model, the onlysignificant moderator is the dummy variable for sex. All othercoefficients are not significant after being shrunken towards zero bythe lasso prior.

Also note the summary statistics fortau2, the(unexplained) residual between-studies heterogeneity. The 95% credibleinterval for this coefficient excludes zero, indicating that there is anon-zero amount of unexplained heterogeneity. It is customary to expressthis heterogeneity in terms of\(I^2\),the percentage of variation across studies that is due to heterogeneityrather than chance (Higgins and Thompson, 2002; Higgins et al., 2003).The helper functionI2() computes the posteriordistribution of\(I^2\) based on theMCMC draws oftau2:

I2(fit_lasso)
#>    mean sd 2.5% 25% 50% 75% 97.5%#> I2   68  2   64  67  68  69    72

Two-level model with the horseshoe prior

Next, we look into the regularized horseshoe prior. The horseshoeprior has five hyperparameters that can be set. Three parameters aredegrees of freedom parameters which influence the tails of thedistributions in the prior. Generally, it is not needed to specifydifferent values for these hyperparameters. Here, we focus instead onthe global scale parameter and the scale of the slab.

# use the default settingsfit_hs1<-brma(yi~ .,data = dat2l,vi ="vi",method ="hs",prior =c(df =1,df_global =1,df_slab =4,scale_global =1,scale_slab =1,relevant_pars =NULL),mute_stan =FALSE)# reduce the global scalefit_hs2<-brma(yi~ .,data = dat2l,vi ="vi",method ="hs",prior =c(df =1,df_global =1,df_slab =4,scale_global =0.1,scale_slab =1,relevant_pars =NULL),mute_stan =FALSE)# increase the scale of the slabfit_hs3<-brma(yi~ .,data = dat2l,vi ="vi",method ="hs",prior =c(df =1,df_global =1,df_slab =4,scale_global =1,scale_slab =5,relevant_pars =NULL),mute_stan =FALSE)

Note that the horseshoe prior results in some divergent transitions.This can be an indication of non-convergence. However, these divergencesarise often when using the horseshoe prior and as long as there are nottoo many of them, the results can still beused.

Next, we plot the posterior mean estimates for a selection ofmoderators for the different priors.

make_plotdat<-function(fit, prior){  plotdat<-data.frame(fit$coefficients)  plotdat$par<-rownames(plotdat)  plotdat$Prior<- priorreturn(plotdat)}df0<-make_plotdat(fit_lasso,prior ="lasso")df1<-make_plotdat(fit_hs1,prior ="hs default")df2<-make_plotdat(fit_hs2,prior ="hs reduced global scale")df3<-make_plotdat(fit_hs3,prior ="hs increased slab scale")df<-rbind.data.frame(df0, df1, df2, df3)df<- df[!df$par%in%c("Intercept","tau2"), ]pd<-0.5ggplot(df,aes(x=mean,y=par,group = Prior))+geom_errorbar(aes(xmin=X2.5.,xmax=X97.5.,colour = Prior),width=.1,position =position_dodge(width = pd))+geom_point(aes(colour = Prior),position =position_dodge(width = pd))+geom_vline(xintercept =0)+theme_bw()+xlab("Posterior mean")+ylab("")

We can see that, in general, the different priors give quite similarresults in this application. A notable exception is the estimate for thedummy variabletestAuthorGrouped_stepDownAvoidance which ismuch smaller for the lasso compared to the horseshoe specification. Thisindicates that the lasso can shrink large coefficients more towards zerowhereas the horseshoe is better at keeping them large.

Three-level model

Finally, we can also take into account the fact that some effectsizes might come from the same study by fitting a three-level model asfollows:

fit_3l<-brma(yi~ .,data = datsel,vi ="vi",study ="author",method ="lasso",standardize =FALSE,prior =c(df =1,scale =1),mute_stan =FALSE)

Standardization

It is possible to override the default standardization, whichstandardizes all variables (including dummies). To do so, first manuallystandardize any variables that must be standardized. Then, in the calltobrma(), provide a named list with elementslist(center = ..., scale = ...). For variables that arenot to be standardized, usecenter = 0, scale = 1. This retains their original scale.For variables that are to be standardized, use their originalcenter andscale to restore the coefficientsto their original scale.

In the example below, we standardize a continuous predictor, but wedo not standardize the dummies:

moderators<-model.matrix(yi~ageWeek+ strainGrouped,data = datsel)[,-1]scale_age<-scale(moderators[,1])stdz<-list(center =c(attr(scale_age,"scaled:center"),rep(0,length(levels(datsel$strainGrouped))-1)),scale =c(attr(scale_age,"scaled:scale"),rep(1,length(levels(datsel$strainGrouped))-1)))moderators<-data.frame(datsel[c("yi","vi","author")], moderators)fit_std<-brma(yi~ .,data = moderators,vi ="vi",study ="author",method ="lasso",prior =c(df =1,scale =1),standardize = stdz,mute_stan =FALSE)

Note that, in this example, onlyageWeek isstandardized; the remaining (dummy) variables are untouched. The objectstdz provides the original center and scale forageWeek, which allowsbrma() to properlyrescale the coefficient for this moderator. As the center and scale forall remaining (dummy) variables are 0 and 1, these coefficients arenot rescaled. See thepema paper for adiscussion of standardization and further references.


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