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.

To examine the pain relief effects of comparators (placebos and untreated control groups) in hand osteoarthritis trials and the impact of contextual factors. 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. 84 trials (7,262 participants) were eligible for quantitative synthesis, of which 76 (6,462 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. 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. CRD42022298984.

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