Empirical evaluation of which trial characteristics are associated with treatment effect estimates

Objective: Meta-epidemiological studies provide empirical evidence of trial characteristics associated with treatment effects. We aimed to evaluate methods used and characteristics associated with treatment effect in these studies. Study Design and Setting: For this systematic review, we searched MEDLINE, Embase, Cochrane Methodology Register, Web of Science, and PROSPERO up to April 2015. We particularly assessed four key methodological components: constitution of the collection, clustering of trials within meta-analyses, heterogeneity assessment, and adjustment on meta-confounders. We also assessed trial characteristics evaluated and their association with treatment effect. Results: We included 56 meta-epidemiological studies with data from 3,199 meta-analyses, 32 networks, and 21,468 trials. Thirty-two (58%) were published since 2010. Only 13 (23%) included all key methodological components. Overall, 58 trial characteristics were assessed. Allocation concealment and sequence generation were assessed in 22 (39%) and 17 (30%) meta-epidemiological studies, respectively, and trial size in 9 (16%). These characteristics were consistently associated with treatment effect estimates with larger effects in trials with inadequate sequence generation or allocation concealment or smaller trials. Conclusions: Key methodological components (e.g., constitution of the collection) were frequently missing. Concerning trial characteristics evaluated, there was consistent evidence that allocation concealment, sequence generation, and trial size were associated with treatment effect. (C) 2016 Elsevier Inc. All rights reserved.