Brian Freed1, Brian Williams2, Xiaolu Situ3, Victoria Landsman4,5, Jeehyoung Kim6, Alex Moroz7, Heejung Bang3,8,9, Jongbae J Park10. 1. Department of Pain Management, Summit Medical Group, Berkeley Heights, NJ, USA. 2. Departments of Physiatry and Orthopedic Surgery, Hospital for Special Surgery, New York, NY, USA. 3. Graduate Group of Biostatistics, Department of Statistics, University of California, Davis, CA, USA. 4. Institute for Work and Health, Toronto, ON, Canada. 5. Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. 6. Department of Orthopedic Surgery, Seoul Sacred Heart General Hospital, Seoul, Korea. 7. Department of Rehabilitation Medicine, New York University Grossman School of Medicine, New York, NY, USA. 8. Division of Biostatistics, Department of Public Health Sciences, University of California, Davis, CA, USA. 9. Center for Healthcare Policy and Research & Clinical and Translational Science Center Davis School of Medicine, University of California, Sacramento, CA, USA. 10. Department of Anesthesiology, Duke University School of Medicine, Durham, NC, USA.
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.
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.