The impact of blinding on trial results: A systematic review and meta-analysis

Abstract Background Blinding—the concealment of the arm to which participants have been randomized—is an important consideration for assessing risk of bias of randomized trials. A growing body of evidence has, however, yielded inconsistent results on whether trials without blinding produce biased findings. Objective To conduct a systematic review and meta-analysis of the evidence addressing whether trials with and without blinding produce different results. Methods We searched MEDLINE, EMBASE, Cochrane Reviews, JBI EBP, and Web of Science, from inception to May 2022, for studies comparing the results of trials with and without blinding. Pairs of reviewers, working independently and in duplicate, reviewed search results for eligible studies and extracted data. We pooled the results of studies comparing trials with and without blinding of patients, healthcare providers/investigators, and outcome assessors/adjudicators using frequentist random-effects meta-analyses. We coded study results such that a ratio of odds ratio (ROR) < 1 and difference in standardized mean difference (dSMD) < 0 indicate that trials without blinding overestimate treatment effects. Results We identified 47 eligible studies. For dichotomous outcomes, we found low certainty evidence that trials without blinding of patients and healthcare providers, outcome assessors/adjudicators, and patients may slightly overestimate treatment effects. For continuous outcomes, we found low certainty evidence that trials without blinding of outcome assessors/adjudicators and patients may slightly overestimate treatment effects. Conclusion Our systematic review and meta-analysis suggests that blinding may influence trial results in select situations—albeit the findings are of low certainty and the magnitude of effect is modest. In the absence of high certainty evidence suggesting that trials with and without blinding produce similar results, investigators should be cautious about interpreting the results of trials without blinding.