Jointly pooling aggregated effect sizes and their standard errors from studies with continuous clinical outcomes

The DerSimonian-Laird (DL) weighted average method for aggregated data meta-analysis has been widely used for the estimation of overall effect sizes. It is criticized for its underestimation of the standard error of the overall effect size in the presence of heterogeneous effect sizes. Due to this negative property, many alternative estimation approaches have been proposed in the literature. One of the earliest alternative approaches was developed by Hardy and Thompson (HT), who implemented a profile likelihood instead of the moment-based approach of DL. Others have further extended this likelihood approach and proposed higher-order likelihood inferences (e.g., Bartlett-type corrections). In addition, corrections factors for the estimated DL standard error, like the Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustment, and the restricted maximum likelihood (REML) estimation have been suggested too. Although these improvements address the uncertainty in estimating the between-study variance better than the DL method, they all assume that the true within-study standard errors are known and equal to the observed standard errors of the effect sizes. Here, we will treat the observed standard errors as estimators for the within-study variability and we propose a bivariate likelihood approach that jointly estimates the overall effect size, the between-study variance, and the potentially heteroskedastic within-study variances. We study the performance of the proposed method by means of simulation, and compare it to DL (with and without HKSJ), HT, their higher-order likelihood methods, and REML. Our proposed approach seems to have better or similar coverages compared to the other approaches and it appears to be less biased in the case of heteroskedastic within-study variances when this heteroskedasticty is correlated with the effect size.

Automated summary

The DerSimonian-Laird weighted average method is widely used for overall effect size estimation in meta-analysis, but it underestimates the standard error when effect sizes are heterogeneous. Several alternative approaches, such as profile likelihood and corrections factors, have been proposed to improve the estimation. This study presents a bivariate likelihood approach that jointly estimates the overall effect size, between-study variance, and potentially heteroskedastic within-study variances. Simulation results show that the proposed method has better or similar performance compared to other approaches.