• Guillaume L Martin, Théo Trioux, Stéphane Gaudry, Florence Tubach, David Hajage, and Agnès Dechartres.
• Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Pitié Salpêtrière, Département de Santé Publique, Paris, France.
• Crit. Care Med. 2021 Oct 1; 49 (10): 180018111800-1811.

ObjectivesTo investigate whether intervention effect estimates for mortality differ between blinded and nonblinded randomized controlled trials conducted in critical care. We used a meta-epidemiological approach, comparing effect estimates between blinded and nonblinded randomized controlled trials for the same research question.Data SourcesSystematic reviews and meta-analyses of randomized controlled trials evaluating a therapeutic intervention on mortality in critical care, published between January 2009 and March 2019 in high impact factor general medical or critical care journals and by Cochrane.Data ExtractionFor each randomized controlled trial included in eligible meta-analyses, we evaluated whether the trial was blinded (i.e., double-blinded and/or reporting adequate methods) or not (i.e., open-label, single-blinded, or unclear). We collected risk of bias evaluated by the review authors and extracted trial results.Data SynthesisWithin each meta-analysis, we compared intervention effect estimates between blinded and nonblinded randomized controlled trials by using a ratio of odds ratio (< 1 indicates larger estimates in nonblinded than blinded randomized controlled trials). We then combined ratio of odds ratios across meta-analyses to obtain the average relative difference between nonblinded and blinded trials. Among 467 randomized controlled trials included in 36 meta-analyses, 267 (57%) were considered blinded and 200 (43%) nonblinded. Intervention effect estimates were statistically significantly larger in nonblinded than blinded trials (combined ratio of odds ratio, 0.91; 95% CI, 0.84-0.99). We found no heterogeneity across meta-analyses (p = 0.72; I2 = 0%; τ2 = 0). Sensitivity analyses adjusting the main analysis on risk of bias items yielded consistent results.ConclusionsIntervention effect estimates of mortality were slightly larger in nonblinded than blinded randomized controlled trials conducted in critical care, but confounding cannot be excluded. Blinding of both patients and personnel is important to consider when possible in critical care trials, even when evaluating mortality.Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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