TY - JOUR
T1 - Blinding, sham, and treatment effects in randomized controlled trials for back pain in 2000–2019
T2 - A review and meta-analytic approach
AU - Freed, Brian
AU - Williams, Brian
AU - Situ, Xiaolu
AU - Landsman, Victoria
AU - Kim, Jeehyoung
AU - Moroz, Alex
AU - Bang, Heejung
AU - Park, Jongbae J.
N1 - Publisher Copyright:
© The Author(s) 2021.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021
Y1 - 2021
N2 - Background: Blinding aims to minimize biases from what participants and investigators know or believe. Randomized controlled trials, despite being the gold standard to evaluate treatment effect, do not generally assess the success of blinding. We investigated the extent of blinding in back pain trials and the associations between participant guesses and treatment effects. Methods: We did a review with PubMed/OvidMedline, 2000–2019. Eligibility criteria were back pain trials with data available on treatment effect and participants’ guess of treatment. For blinding, blinding index was used as chance-corrected measure of excessive correct guess (0 for random guess). For treatment effects, within- or between-arm effect sizes were used. Analyses of investigators’ guess/blinding or by treatment modality were performed exploratorily. Results: Forty trials (3899 participants) were included. Active and sham treatment groups had mean blinding index of 0.26 (95% confidence interval: 0.12, 0.41) and 0.01 (−0.11, 0.14), respectively, meaning 26% of participants in active treatment believed they received active treatment, whereas only 1% in sham believed they received sham treatment, beyond chance, that is, random guess. A greater belief of receiving active treatment was associated with a larger within-arm effect size in both arms, and ideal blinding (namely, “random guess,” and “wishful thinking” that signifies both groups believing they received active treatment) showed smaller effect sizes, with correlation of effect size and summary blinding indexes of 0.35 (p = 0.028) for between-arm comparison. We observed uniformly large sham treatment effects for all modalities, and larger correlation for investigator’s (un)blinding, 0.53 (p = 0.046). Conclusion: Participants in active treatments in back pain trials guessed treatment identity more correctly, while those in sham treatments tended to display successful blinding. Excessive correct guesses (that could reflect weaker blinding and/or noticeable effects) by participants and investigators demonstrated larger effect sizes. Blinding and sham treatment effects on back pain need due consideration in individual trials and meta-analyses.
AB - Background: Blinding aims to minimize biases from what participants and investigators know or believe. Randomized controlled trials, despite being the gold standard to evaluate treatment effect, do not generally assess the success of blinding. We investigated the extent of blinding in back pain trials and the associations between participant guesses and treatment effects. Methods: We did a review with PubMed/OvidMedline, 2000–2019. Eligibility criteria were back pain trials with data available on treatment effect and participants’ guess of treatment. For blinding, blinding index was used as chance-corrected measure of excessive correct guess (0 for random guess). For treatment effects, within- or between-arm effect sizes were used. Analyses of investigators’ guess/blinding or by treatment modality were performed exploratorily. Results: Forty trials (3899 participants) were included. Active and sham treatment groups had mean blinding index of 0.26 (95% confidence interval: 0.12, 0.41) and 0.01 (−0.11, 0.14), respectively, meaning 26% of participants in active treatment believed they received active treatment, whereas only 1% in sham believed they received sham treatment, beyond chance, that is, random guess. A greater belief of receiving active treatment was associated with a larger within-arm effect size in both arms, and ideal blinding (namely, “random guess,” and “wishful thinking” that signifies both groups believing they received active treatment) showed smaller effect sizes, with correlation of effect size and summary blinding indexes of 0.35 (p = 0.028) for between-arm comparison. We observed uniformly large sham treatment effects for all modalities, and larger correlation for investigator’s (un)blinding, 0.53 (p = 0.046). Conclusion: Participants in active treatments in back pain trials guessed treatment identity more correctly, while those in sham treatments tended to display successful blinding. Excessive correct guesses (that could reflect weaker blinding and/or noticeable effects) by participants and investigators demonstrated larger effect sizes. Blinding and sham treatment effects on back pain need due consideration in individual trials and meta-analyses.
KW - Back pain
KW - blinding
KW - clinical trial
KW - guess
KW - meta-analysis
KW - placebo
KW - systematic review
UR - http://www.scopus.com/inward/record.url?scp=85100032614&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85100032614&partnerID=8YFLogxK
U2 - 10.1177/1740774520984870
DO - 10.1177/1740774520984870
M3 - Review article
C2 - 33478258
AN - SCOPUS:85100032614
JO - Clinical Trials
JF - Clinical Trials
SN - 1740-7745
ER -