학술논문
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.
Document Type
Academic Journal
Author
Balsby IM; Section for Biostatistics and Evidence-Based Research, The Parker Institute, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address: ida.maria.balsby@regionh.dk.; Nielsen SM; Section for Biostatistics and Evidence-Based Research, The Parker Institute, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark; Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark. Electronic address: sabrina.mai.nielsen@regionh.dk.; Christensen R; Section for Biostatistics and Evidence-Based Research, The Parker Institute, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark; Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark. Electronic address: Robin.Christensen@Regionh.dk.; Henriksen M; The Parker Institute, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address: marius.henriksen@regionh.dk.; Dahl LU; The Parker Institute, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address: louise.ulff-moeller.nielsen@regionh.dk.; Berg JI; The Parker Institute, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address: Johanneskib@gmail.com.; Tarp S; The Parker Institute, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address: simon.tarp@regionh.dk.; Kroon F; Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; Department of Rheumatology, Zuyderland Medical Center, Heerlen, The Netherlands. Electronic address: fpbkroon@gmail.com.; Kloppenburg M; Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: G.Kloppenburg@lumc.nl.; Zhang W; Academic Rheumatology, University of Nottingham, City Hospital, Nottingham, UK. Electronic address: weiya.zhang@nottingham.ac.uk.; Hunter DJ; Sydney Musculoskeletal Health, University of Sydney, Faculty of Medicine and Health, Sydney, Australia. Electronic address: David.Hunter@sydney.edu.au.; Bliddal H; The Parker Institute, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address: Henning.Bliddal@regionh.dk.; Døssing A; The Parker Institute, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address: anna.dossing@gmail.com.
Source
Publisher: W.B. Saunders For The Osteoarthritis Research Society Country of Publication: England NLM ID: 9305697 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-9653 (Electronic) Linking ISSN: 10634584 NLM ISO Abbreviation: Osteoarthritis Cartilage Subsets: MEDLINE
Subject
Language
English
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.
(Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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.
(Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)