Comparative effectiveness of different placebos and comparator groups for hand osteoarthritis exploring the impact of contextual factors: A systematic review and meta-analysis of randomised trials

Balsby, Ida Maria; Nielsen, Sabrina M.; Christensen, Robin; Henriksen, Marius; Dahl, Louise Ulff-Møller; Berg, Johannes Iuel; Tarp, Simon; Kroon, Féline; Kloppenburg, Margreet; Zhang, Weiya; Hunter, David J.; Bliddal, Henning; Døssing, Anna

Abstract

Objective: To examine the pain relief effects of comparators (placebos and untreated control groups) in hand osteoarthritis trials and the impact of contextual factors. Methods: We systematically searched PubMed, EMBASE and CENTRAL from inception to December 26, 2021. We included randomised controlled trials of people with hand osteoarthritis with a placebo or an untreated control group. We assessed the Risk of Bias with Cochrane Risk-of-Bias tool version 2. Each comparator was contrasted with a null-arm, imputed as having a zero change from baseline with the same standard deviation as the comparator. We combined the standardised mean differences with a random effects meta-analysis. The contextual factors’ effect was explored in meta-regression and stratified models with pain as the dependent variable. Results: 84 trials (7262 participants) were eligible for quantitative synthesis, of which 76 (6462 participants) were eligible for the stratified analyses. Placebos were superior to their matched null-arms in relieving pain with an effect size of −0.51 (95% confidence interval −0.61 to −0.42), while untreated control groups were not. When analysing all comparators, blinded trial designs and low risk of bias were associated with higher pain relief compared to an open-label trial design and some concern or high risk of bias. Conclusion: The placebo response on pain for people with hand osteoarthritis was increased by appropriate blinding and a lower risk of bias assessment. Placebos were superior to a null-arm, while untreated control groups were not. Results emphasise the importance of using appropriate comparators in clinical trials. PROSPERO registration ID: CRD42022298984

Citation

Balsby, I. M., Nielsen, S. M., Christensen, R., Henriksen, M., Dahl, L. U.-M., Berg, J. I., …Døssing, A. (2024). Comparative effectiveness of different placebos and comparator groups for hand osteoarthritis exploring the impact of contextual factors: A systematic review and meta-analysis of randomised trials. Osteoarthritis and Cartilage, 32(7), 848-857. https://doi.org/10.1016/j.joca.2024.02.947

• Journal Article Type: Review
• Acceptance Date: Feb 27, 2024
• Online Publication Date: Apr 26, 2024
• Publication Date: 2024-07
• Deposit Date: May 13, 2024
• Publicly Available Date: May 30, 2024
• Journal: Osteoarthritis and Cartilage
• Print ISSN: 1063-4584
• Electronic ISSN: 1522-9653
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 32
• Issue: 7
• Pages: 848-857
• DOI: https://doi.org/10.1016/j.joca.2024.02.947
• Keywords: Hand, Comparator, Placebo, Osteoarthritis, Sham
• Public URL: https://nottingham-repository.worktribe.com/output/34849835
• Publisher URL: https://www.oarsijournal.com/article/S1063-4584(24)01162-2/fulltext
• Related Public URLs: https://www.sciencedirect.com/science/article/pii/S1063458424011622
• Additional Information: This article is maintained by: Elsevier; Article Title: Comparative effectiveness of different placebos and comparator groups for hand osteoarthritis exploring the impact of contextual factors: A systematic review and meta-analysis of randomised trials; Journal Title: Osteoarthritis and Cartilage; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.joca.2024.02.947; Content Type: article; Copyright: © 2024 The Author(s). Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.