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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..
References
Akl, Sun, Busse, Specific instructions for estimating unclearly reported blinding status in randomized trials were reliable and valid, J Clin Epidemiol, doi:10.1016/j.jclinepi.2011.04.015
Armijo-Olivo, Fuentes, Da Costa, Saltaji, Ha et al., Blinding in physical therapy trials and its association with treatment effects: a meta-epidemiological study, Am J Phys Med Rehabil, doi:10.1097/PHM.0000000000000521
Bello, Moustgaard, Hróbjartsson, Unreported formal assessment of unblinding occurred in 4 of 10 randomized clinical trials, unreported loss of blinding in 1 of 10 trials, J Clin Epidemiol, doi:10.1016/j.jclinepi.2016.08.002
Berlin, Golub, Meta-analysis as evidence: building a better pyramid, JAMA, doi:10.1001/jama.2014.8167
Chan, Altman, Epidemiology and reporting of randomised trials published in PubMed journals, Lancet, doi:10.1016/S0140-6736(05)71879-1
Chinn, A simple method for converting an odds ratio to effect size for use in meta-analysis, Stat Med, doi:10.1002/1097-0258(20001130)19:22<3127::AID-SIM784>3.0.CO;2-M16
Claessen, Mellema, Stoop, Lubberts, Ring et al., Influence of priming on patient-reported outcome measures: a randomized controlled trial, Psychosomatics, doi:10.1016/j.psym.2015.09.005
Dechartres, Trinquart, Faber, Ravaud, Empirical evaluation of which trial characteristics are associated with treatment effect estimates, J Clin Epidemiol, doi:10.1016/j.jclinepi.2016.04.005
Devereaux, Manns, Ghali, Physician interpretations and textbook definitions of blinding terminology in randomized controlled trials, JAMA, doi:10.1001/jama.285.15.2000
Ghimire, Hasegawa, Kalyal, Hurwitz, Ashkan, Patient-reported outcome measures in neurosurgery: a review of the current literature, Neurosurgery, doi:10.1093/neuros/nyx547
Giraudeau, Higgins, Tavernier, Trinquart, Sample size calculation for meta-epidemiological studies, Stat Med, doi:10.1002/sim.6627
Haahr, Hróbjartsson, Who is blinded in randomized clinical trials? A study of 200 trials and a survey of authors, Clin Trials, doi:10.1177/1740774506069153
Higgins, Altman, Gøtzsche, The Cochrane Collaboration's tool for assessing risk of bias in randomised trials, BMJ, doi:10.1136/bmj.d5928
Higgins, Ramsay, Reeves, Issues relating to study design and risk of bias when including non-randomized studies in systematic reviews on the effects of interventions, Res Synth Methods, doi:10.1002/jrsm.1056
Hróbjartsson, Emanuelsson, Thomsen, Hilden, Brorson, Bias due to lack of patient blinding in clinical trials. A systematic review of trials randomizing patients to blind and nonblind substudies, Int J Epidemiol, doi:10.1093/ije/dyu115
Hróbjartsson, Thomsen, Emanuelsson, Observer bias in randomised clinical trials with binary outcomes: systematic review of trials with both blinded and non-blinded outcome assessors, BMJ, doi:10.1136/bmj.e1119
Hróbjartsson, Thomsen, Emanuelsson, Observer bias in randomized clinical trials with measurement scale outcomes: a systematic review of trials with both blinded and nonblinded assessors, CMAJ, doi:10.1503/cmaj.120744
Hróbjartsson, Thomsen, Emanuelsson, Observer bias in randomized clinical trials with time-to-event outcomes: systematic review of trials with both blinded and non-blinded outcome assessors, Int J Epidemiol, doi:10.1093/ije/dyt270
Kaptchuk, Intentional ignorance: a history of blind assessment and placebo controls in medicine, Bull Hist Med, doi:10.1353/bhm.1998.0159
Moustgaard, Bello, Miller, Hróbjartsson, Subjective and objective outcomes in randomized clinical trials: definitions differed in methods publications and were often absent from trial reports, J Clin Epidemiol, doi:10.1016/j.jclinepi.2014.06.020
Moustgaard, Jones, Savović, Ten questions to consider when interpreting results of a meta-epidemiological studythe MetaBLIND study as a case, Res Synth Meth, doi:10.1002/jrsm.1392
Nickerson, Confirmation bias: a ubiquitous phenomenon in many guises, Rev Gen Psychol, doi:10.1037/1089-2680.2.2.175
Nüesch, Reichenbach, Trelle, The importance of allocation concealment and patient blinding in osteoarthritis trials: a meta-epidemiologic study, Arthritis Rheum, doi:10.1002/art.24894
Page, Higgins, Clayton, Sterne, Hróbjartsson et al., Empirical evidence of study design biases in randomized trials: systematic review of meta-epidemiological studies, PLoS One, doi:10.1371/journal.pone.0159267
Rhodes, Mawdsley, Turner, Jones, Savović et al., Label-invariant models for the analysis of meta-epidemiological data, Stat Med, doi:10.1002/sim.7491
Rosenthal, On the social psychology of the psychological experiment: the experimenter's hypothesis as unintended determinant of experimental results, Am Sci
Saltaji, Armijo-Olivo, Cummings, Amin, Da Costa et al., Influence of blinding on treatment effect size estimate in randomized controlled trials of oral health interventions, BMC Med Res Methodol, doi:10.1186/s12874-018-0491-0on6
Savović, Jones, Altman, Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials, Ann Intern Med, doi:10.7326/0003-4819-157-6-201209180-00537
Savović, Turner, Mawdsley, Association between risk-of-bias assessments and results of randomized trials in Cochrane reviews: the ROBES meta-epidemiologic study, Am J Epidemiol, doi:10.1093/aje/kwx344
Schulz, Chalmers, Hayes, Altman, Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials, JAMA, doi:10.1001/jama.1995.03520290060030
Sterne, Jüni, Schulz, Altman, Bartlett et al., Statistical methods for assessing the influence of study characteristics on treatment effects in 'meta-epidemiological' research, Stat Med, doi:10.1002/sim.1184
Sterne, Savović, Page, RoB 2: a revised tool for assessing risk of bias in randomised trials, BMJ, doi:10.1136/bmj.l4898
Ware, Hamel, Pragmatic trials--guides to better patient care?, N Engl J Med, doi:10.1056/NEJMp110350230
Welton, Ades, Carlin, Altman, Sterne, Models for potentially biased evidence in meta-analysis using empirically based priors, J R Stat Soc Ser A Stat Soc, doi:10.1111/j.1467-985X.2008.00548.x
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