Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Oct 1;49(10):1800-1811.
doi: 10.1097/CCM.0000000000005065.

Association Between Lack of Blinding and Mortality Results in Critical Care Randomized Controlled Trials: A Meta-Epidemiological Study

Guillaume L Martin  1 , Théo Trioux  1 , Stéphane Gaudry  2   3 , Florence Tubach  1 , David Hajage  1 , Agnès Dechartres  1
Affiliations
Free article

Association Between Lack of Blinding and Mortality Results in Critical Care Randomized Controlled Trials: A Meta-Epidemiological Study

Guillaume L Martin et al. Crit Care Med. .
Free article

Abstract

Objectives: To 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 sources: Systematic 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 extraction: For 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 synthesis: Within 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.

Conclusions: Intervention 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.

PubMed Disclaimer

Conflict of interest statement

Dr. Tubach disclosed that she is the head of the Centre de Pharmacoépidémiologie (Cephepi) of the Assistance Publique-Hôpitaux de Paris and of the Clinical Research Unit of Pitié-Salpêtrière Hospital, both these structures have received research funding, grants, and fees for consultant activities from a large number of pharmaceutical companies that have contributed indiscriminately to the salaries of its employees. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Comment in

References

    1. Wood L, Egger M, Gluud LL, et al.: Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: Meta-epidemiological study. BMJ. 2008; 336:601–605
    1. Savović J, Jones HE, Altman DG, et al.: Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials. Ann Intern Med. 2012; 157:429–438
    1. Savovic J, Turner RM, Mawdsley D, et al.: Association between risk-of-bias assessments and results of randomized trials in cochrane reviews: The ROBES meta-epidemiologic study. Am J Epidemiol. 2018; 187:1113–1122
    1. Moustgaard H, Clayton GL, Jones HE, et al.: Impact of blinding on estimated treatment effects in randomised clinical trials: Meta-epidemiological study. BMJ. 2020; 368:l6802
    1. Drucker AM, Chan AW: Blindsided: Challenging the dogma of masking in clinical trials. BMJ. 2020; 368:m229

MeSH terms