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Recent:   

Impact of blinding on estimated treatment effects in randomised clinical trials: meta-epidemiological study

Moustgaard et al., BMJ, doi:10.1136/bmj.l6802
Jan 2020  
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Meta-analysis of 142 meta-analyses (1,153 trials) finding no evidence that lack of blinding of patients, healthcare providers, or outcome assessors influenced effect estimates in randomized clinical trials on average.
Moustgaard et al., 21 Jan 2020, peer-reviewed, 13 authors.
This PaperMiscellaneousAll
Impact of blinding on estimated treatment effects in randomised clinical trials: meta-epidemiological study
Helene Moustgaard, Gemma L Clayton, Hayley E Jones, Isabelle Boutron, Lars Jørgensen, David R T Laursen, Mette F Olsen, Asger Paludan-Müller, Philippe Ravaud, Jelena Savović, Jonathan A C Sterne, Julian P T Higgins, Asbjørn Hróbjartsson
BMJ, doi:10.1136/bmj.l6802
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 metaanalyses 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 metaepidemiological 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.
Contributors: AH and HM conceived and organised the study, interpreted the results, and drafted the manuscript. HM also extracted data. GLC analysed the data, interpreted results, and drafted the manuscript. HEJ, JS, IB, PR, JPTH, and JACS conceived the study, interpreted the results, and drafted the manuscript. LJ, DRTL, AP-M, and MFO extracted data and drafted the manuscript. HM is guarantor. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Ethical approval: Not required. Data sharing: Dataset available from the corresponding author after a post-publication period of 1 year allowing time for follow-up projects. The lead author affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained. Dissemination to participants and related patient and public..
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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.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Conclusion</jats:title>\n' ' <jats:p>No evidence was found for an average difference in estimated treatment ' 'effect between trials with and without blinded patients, healthcare providers, or outcome ' 'assessors. 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