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
Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
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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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Osteoarthritis and Cartilage |
| Vol/bind | 32 |
| Udgave nummer | 7 |
| Sider (fra-til) | 848-857 |
| Antal sider | 10 |
| ISSN | 1063-4584 |
| DOI | |
| Status | Udgivet - 2024 |
| Eksternt udgivet | Ja |
Bibliografisk note
Funding Information:
Interests disclosed in the International Committee of Medical Journal Editors (ICMJE) conflict of interest forms are as follows: MH is supported by a core grant to his institution from the Oak Foundation (OCAY-18\u2013774-OFIL); has received travel support for conference participation from Contura International A/S; is on the advisory board for Thuasne Group; and is associate editor of Osteoarthritis & Cartilage. MK has received grants from IMI-APPROACH and the Dutch Arthritis Society; royalties or licenses from Wolters Kluwer and Springer Verlag; consulting fees for consultancy/advisory boards by Pfizer, Galapagos, CHDR, Novartis, and UCB; payment or honoraria from Galapagos and Jansen; and is an OARSI board member (2017-2022), EULAR council, and president of the Dutch Society for Rheumatology. DJH is supported by an NHMRC Investigator Grant Leadership 2 (#1194737); received consulting fees for consulting advice on the scientific advisory boards for Pfizer, Lilly, TLCBio and Novartis; is editor in chief of Osteoarthritis and Cartilage; is section editor of osteoarthritis, UpToDate; is on data safety monitoring board for Success trial for spinal stenosis (ACTRN12617000884303) and ICM-203 for knee OA (NCT04875754); and is an Osteoarthritis Research Society International Board Member. AD has received support for congress attendance from the Danish Rheumatism Organization; and is president of the Danish Association of Junior Rheumatologists. IMB, SMN, RC, LUD, JJB, ST, FK, WZ, and HB have no conflicts of interest.
Funding Information:
The Parker Institute, Bispebjerg and Frederiksberg Hospital is supported by a core grant and would like to acknowledge the Oak Foundation (OCAY-18-774-OFIL). The Oak Foundation had no role in study design, data collection, data synthesis, data interpretation, writing the report or decision to submit the manuscript.
Funding Information:
We would like to thank both patient research partners for contributing valuable points to the design of this study, and Kirsten Lomholt for contributing to the discussion of this publication. Furthermore, we would like to thank J\u00FCrgen Rech for sharing data from the ACCOST study (EudraCT Number 2008-005365-61), Jonathan Vela for sharing data from the NordCan study, and Eva Ekvall Hansson for sharing data from the study 'Effects of an education programme for patients with osteoarthritis in primary care \u2013 a randomized controlled trial' BMC Musculoskeletal. Disord. 2010. IMB, AD and RC conceived and designed the study and contributed to the development of the protocol. AD developed the search strategy. AD and IMB sorted the references. AD, IMB, JIB, and LUD extracted all data. IMB and SMN conducted statistical analyses. All authors assisted in the final manuscript and agreed to its final approval before submission. Interests disclosed in the International Committee of Medical Journal Editors (ICMJE) conflict of interest forms are as follows: MH is supported by a core grant to his institution from the Oak Foundation (OCAY-18-774-OFIL); has received travel support for conference participation from Contura International A/S; is on the advisory board for Thuasne Group; and is associate editor of Osteoarthritis & Cartilage. MK has received grants from IMI-APPROACH and the Dutch Arthritis Society; royalties or licences from Wolters Kluwer and Springer Verlag; consulting fees for consultancy/advisory boards by Pfizer, Galapagos, CHDR, Novartis, and UCB; payment or honoraria from Galapagos and Jansen; and is an OARSI board member (2017\u20132022), EULAR council, and president of the Dutch Society for Rheumatology. DJH is supported by an NHMRC Investigator Grant Leadership 2 (#1194737); received consulting fees for consulting advice on the scientific advisory boards for Pfizer, Lilly, TLCBio and Novartis; is editor in chief of Osteoarthritis and Cartilage; is section editor of osteoarthritis, UpToDate; is on data safety monitoring board for Success trial for spinal stenosis (ACTRN12617000884303) and ICM-203 for knee OA (NCT04875754); and is an Osteoarthritis Research Society International Board Member. AD has received support for congress attendance from the Danish Rheumatism Organization; and is president of the Danish Association of Junior Rheumatologists. IMB, SMN, RC, LUD, JIB, ST, FK, WZ, and HB have no conflicts of interest. Template data collection forms, extracted data, data used for analysis, and analytic code are not publicly available. Extracted data that underlie the results reported in this article and analytic code will be available from Robin Christensen ( robin.christensen@regionh.dk) once all planned analyses have been completed and published. We will consider the request on an individual basis. We will not share unpublished data explicitly provided for this study. In these cases, we recommend contacting the authors of the original work. The corresponding author (AD) and first author (IMB) affirm that the manuscript is an honest, accurate, and transparent account of the reported study. No aspects of the study have been omitted, and discrepancies from the study as initially planned have been explained.
Funding Information:
The Parker Institute is supported by a core grant from the Oak Foundation (OCAY-18-774-OFIL).
Publisher Copyright:
© 2024 The Author(s)
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