Blinding, sham, and treatment effects in randomized controlled trials for back pain in 2000–2019: A review and meta-analytic approach

Abstract

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.

Effect of Partial vs Full Disclosure of Potential Assignment to Placebo on Participant Blinding, Perceptions of Group Assignment, and Trial Outcomes

“…The blinding scenario under FD of placebo information might be interpreted as possibly problematic (RA: correct guess; PA: random guess) and that of PD ideal (RA: correct guess; PA: opposite guess), resulting in a summed BI value of −0.01 ≈ 0 (Table ). 5 There were no significant between-group differences in pain and discomfort at any time point (all P Ն .26). After debriefing, most participants accepted the study hypothesis, design, and overall procedures.…”

“…The blinding scenario under FD of placebo information might be interpreted as possibly problematic (RA: correct guess; PA: random guess) and that of PD ideal (RA: correct guess; PA: opposite guess), resulting in a summed BI value of −0.01 ≈ 0 ( Table ). 5 …”

“… c A value of 0 for either BI in both active and placebo groups or summed BI indicates the 2 most ideal blinding scenarios, implying a random guess or wishful thinking (as a metaphor for common representative scenarios), respectively. 4 , 5 If both groups guessed they were receiving active treatment in equal proportions, blinding could be a success. …”

Blinding and sham control methods in trials of physical, psychological, and self-management interventions for pain (article I): a systematic review and description of methods

“…On the other hand, emerging conflicting evidence regarding the impact of blinding status and blinding success warrants further scientific attention. 12 , 66 , 117 …”

A randomised, pragmatic clinical trial of ACUpuncture plus standard care versus standard care alone FOr Chemotherapy Induced peripheral Neuropathy (ACUFOCIN)

“…From a clinical perspective, there were concerns regarding unmasking, given the complexity of delivering a sham treatment in a clinical setting, as well as the constraints of limited resource of acupuncturists, whose time was not funded within the trial. Finally, there are criticisms of various sham acupuncture methods in the literature, with debate as to whether they can elicit therapeutic responses, thus compromising interpretation of results ( Franconi et al, 2013 ; Freed et al, 2021 , Molassiotis et al, 2019b ). The decision about whether to include sham acupuncture in future studies will be revisited.…”