The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials

Objective: To examine the placebo effect and its potential determinants in the treatment of osteoarthritis (OA) via a systematic literature search of Medline, EMBASE, Scientific Citation Index, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Library. Methods: Randomised placebo controlled trials in OA were included. The placebo effect was defined as the overall change from baseline in the placebo group. It was estimated as the effect size (ES; the standard mean difference between baseline and endpoint) and this was compared with the ES obtained from untreated control. ES for pain was the primary outcome. Statistical pooling was undertaken as appropriate and 95% CIs were used for comparison. Quality of trials was assessed and potential determinants of placebo effect were examined using multiple regression analysis. The partial regression coefficient (beta) was used to present the adjusted size of the association. Results: We identified 198 trials with 193 placebo groups ( 16 364 patients) and 14 untreated control groups ( 1167 patients) that met our inclusion criteria. These included a range of therapies (non-pharmacological, pharmacological and surgical treatments). Placebo was effective at relieving pain ( ES 0.51, 95% CI 0.46 to 0.55 for the placebo group and 0.03, 95% CI -0.13 to 0.18 for untreated control). Placebo was also effective at improving function and stiffness. The pain-relieving effect increased when the active treatment effect (beta = 0.38, p<0.001), baseline pain ( 0.006, p = 0.014) and sample size (0.001, p = 0.004) increased, and when placebo was given through injections/needles (0.144, p = 0.020). Conclusion: Placebo is effective in the treatment of OA, especially for pain, stiffness and self-reported function. The size of this effect is influenced by the strength of the active treatment, the baseline disease severity, the route of delivery and the sample size of the study.