Association Between Risk-of-Bias Assessments and Results of Randomized Trials in Cochrane Reviews: the ROBES Meta-Epidemiologic Study

Abstract

Flaws in trial design may bias intervention effect estimates and increase between-trial heterogeneity. Empirical evidence suggests that these problems are greatest for subjectively assessed outcomes. For the ROBES study, we extracted risk-of-bias judgements (for sequence generation, allocation concealment, blinding and incomplete data) from a large collection of meta-analyses published in the Cochrane Library, issue 4, 2011. We categorized outcome measures as mortality, other objective or subjective, and estimated associations of bias judgements with intervention effect estimates using Bayesian hierarchical models. Among 2,443 trials in 228 meta-analyses, intervention effect estimates were on average exaggerated in trials with high or unclear risk-of-bias judgements (versus low) for sequence generation (ratio of odds ratio = 0.91 (95% credible interval 0.86, 0.98)), allocation concealment (0.92 (0.86, 0.98)) and blinding (0.87 (0.80, 0.93)). In contrast to previous work, we did not observe consistently different bias for subjective outcomes compared with mortality. However, we found an increase in between-trial heterogeneity associated with lack of blinding in meta-analyses with subjective outcomes. Inconsistency in criteria for risk-of-bias judgments applied by individual reviewers is a likely limitation of routinely collected bias assessments. Inadequate randomization and lack of blinding may lead to exaggeration of intervention effect estimates in trials.