Impact of blinding on estimated treatment effects in randomised clinical trials: Meta-epidemiological study
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Impact of blinding on estimated treatment effects in randomised clinical trials : Meta-epidemiological study. / Moustgaard, Helene; Clayton, Gemma L; Jones, Hayley E; Boutron, Isabelle; Jørgensen, Lars; Laursen, David Ruben Teindl; Olsen, Mette Frahm; Paludan-Müller, Asger; Ravaud, Philippe; Savović, Jelena; Sterne, Jonathan A C; Higgins, Julian P T; Hróbjartsson, Asbjørn.
I: B M J, Bind 368, l6802, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Impact of blinding on estimated treatment effects in randomised clinical trials
T2 - Meta-epidemiological study
AU - Moustgaard, Helene
AU - Clayton, Gemma L
AU - Jones, Hayley E
AU - Boutron, Isabelle
AU - Jørgensen, Lars
AU - Laursen, David Ruben Teindl
AU - Olsen, Mette Frahm
AU - Paludan-Müller, Asger
AU - Ravaud, Philippe
AU - Savović, Jelena
AU - Sterne, Jonathan A C
AU - Higgins, Julian P T
AU - Hróbjartsson, Asbjørn
N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
PY - 2020
Y1 - 2020
N2 - Objectives: To study the impact of blinding on estimated treatment effects, and their variation between trials; differentiating between blinding of patients, healthcare providers, and observers; detection bias and performance bias; and types of outcome (the MetaBLIND study).Design: Meta-epidemiological study.Data source: Cochrane Database of Systematic Reviews (2013-14).Eligibility criteria for selecting studies: Meta-analyses with both blinded and non-blinded trials on any topic.Review methods: Blinding status was retrieved from trial publications and authors, and results retrieved automatically from the Cochrane Database of Systematic Reviews. Bayesian hierarchical models estimated the average ratio of odds ratios (ROR), and estimated the increases in heterogeneity between trials, for non-blinded trials (or of unclear status) versus blinded trials. Secondary analyses adjusted for adequacy of concealment of allocation, attrition, and trial size, and explored the association between outcome subjectivity (high, moderate, low) and average bias. An ROR lower than 1 indicated exaggerated effect estimates in trials without blinding.Results: The study included 142 meta-analyses (1153 trials). The ROR for lack of blinding of patients was 0.91 (95% credible interval 0.61 to 1.34) in 18 meta-analyses with patient reported outcomes, and 0.98 (0.69 to 1.39) in 14 meta-analyses with outcomes reported by blinded observers. The ROR for lack of blinding of healthcare providers was 1.01 (0.84 to 1.19) in 29 meta-analyses with healthcare provider decision outcomes (eg, readmissions), and 0.97 (0.64 to 1.45) in 13 meta-analyses with outcomes reported by blinded patients or observers. The ROR for lack of blinding of observers was 1.01 (0.86 to 1.18) in 46 meta-analyses with subjective observer reported outcomes, with no clear impact of degree of subjectivity. Information was insufficient to determine whether lack of blinding was associated with increased heterogeneity between trials. The ROR for trials not reported as double blind versus those that were double blind was 1.02 (0.90 to 1.13) in 74 meta-analyses.Conclusion: No evidence was found for an average difference in estimated treatment effect between trials with and without blinded patients, healthcare providers, or outcome assessors. These results could reflect that blinding is less important than often believed or meta-epidemiological study limitations, such as residual confounding or imprecision. At this stage, replication of this study is suggested and blinding should remain a methodological safeguard in trials.
AB - Objectives: To study the impact of blinding on estimated treatment effects, and their variation between trials; differentiating between blinding of patients, healthcare providers, and observers; detection bias and performance bias; and types of outcome (the MetaBLIND study).Design: Meta-epidemiological study.Data source: Cochrane Database of Systematic Reviews (2013-14).Eligibility criteria for selecting studies: Meta-analyses with both blinded and non-blinded trials on any topic.Review methods: Blinding status was retrieved from trial publications and authors, and results retrieved automatically from the Cochrane Database of Systematic Reviews. Bayesian hierarchical models estimated the average ratio of odds ratios (ROR), and estimated the increases in heterogeneity between trials, for non-blinded trials (or of unclear status) versus blinded trials. Secondary analyses adjusted for adequacy of concealment of allocation, attrition, and trial size, and explored the association between outcome subjectivity (high, moderate, low) and average bias. An ROR lower than 1 indicated exaggerated effect estimates in trials without blinding.Results: The study included 142 meta-analyses (1153 trials). The ROR for lack of blinding of patients was 0.91 (95% credible interval 0.61 to 1.34) in 18 meta-analyses with patient reported outcomes, and 0.98 (0.69 to 1.39) in 14 meta-analyses with outcomes reported by blinded observers. The ROR for lack of blinding of healthcare providers was 1.01 (0.84 to 1.19) in 29 meta-analyses with healthcare provider decision outcomes (eg, readmissions), and 0.97 (0.64 to 1.45) in 13 meta-analyses with outcomes reported by blinded patients or observers. The ROR for lack of blinding of observers was 1.01 (0.86 to 1.18) in 46 meta-analyses with subjective observer reported outcomes, with no clear impact of degree of subjectivity. Information was insufficient to determine whether lack of blinding was associated with increased heterogeneity between trials. The ROR for trials not reported as double blind versus those that were double blind was 1.02 (0.90 to 1.13) in 74 meta-analyses.Conclusion: No evidence was found for an average difference in estimated treatment effect between trials with and without blinded patients, healthcare providers, or outcome assessors. These results could reflect that blinding is less important than often believed or meta-epidemiological study limitations, such as residual confounding or imprecision. At this stage, replication of this study is suggested and blinding should remain a methodological safeguard in trials.
KW - Clinical Trials as Topic/methods
KW - Epidemiologic Research Design
KW - Humans
KW - Observer Variation
KW - Outcome Assessment, Health Care/methods
KW - Research Design/standards
U2 - 10.1136/bmj.l6802
DO - 10.1136/bmj.l6802
M3 - Journal article
C2 - 31964641
VL - 368
JO - The BMJ
JF - The BMJ
SN - 0959-8146
M1 - l6802
ER -
ID: 237764325