Examination of overall treatment effect and the proportion attributable to contextual effect in osteoarthritis: meta-analysis of randomised controlled trials

Zou, Kun; Wong, Jean; Abdullah, Natasya; Chen, Xi; Smith, Toby; Doherty, Michael; Zhang, Weiya

Abstract

Objective: To examine the overall treatment effect and the proportion attributable to contextual effect (PCE) in randomised controlled trials (RCTs) of diverse treatments for osteoarthritis (OA).
Methods: We searched Medline, Embase, Central, Science Citation Index, AMED and CINAHL through October 2014, supplemented with manual search of reference lists, published meta-analyses and systematic reviews. Included were RCTs in OA comparing placebo with representative complementary, pharmacological, non-pharmacological and surgical treatments. The primary outcome was pain. Secondary outcomes were function and stiffness. The effect size (ES) of overall treatment effect and the PCE were pooled using random-effects model. Subgroup analyses and meta-regression were conducted to examine determinants of the PCE.
Results: In total, 215 trials (41 392 participants) were included. The overall treatment effect for pain ranged from the smallest with lavage (ES=0.46, 95% CI 0.24 to 0.68) to the largest with topical non-steroidal anti-inflammatory drugs (ES=1.37, 95% CI 1.19 to 1.55). On average, 75% (PCE=0.75, 95% CI 0.72 to 0.79) of pain reduction was attributable to contextual effect. It varied by treatment from 47% (PCE=0.47, 95% CI 0.32 to 0.70) for intra-articular corticosteroid to 91% (PCE=0.91, 95% CI 0.60 to 1.37) for joint lavage. Similar results were observed for function and stiffness. Treatment delivered by needle/injection and other means than oral medication, longer duration of treatment, large sample size (≥100 per arm) and public funding source were associated with increased PCE for pain reduction.
Conclusions: The majority (75%) of the overall treatment effect in OA RCTs is attributable to contextual effects rather than the specific effect of treatments. Reporting overall treatment effect and PCE, in addition to traditional ES, permits a more balanced, clinically meaningful interpretation of RCT results. This would help dispel the frequent discordance between conclusions from RCT evidence and clinical experience—the ‘efficacy paradox’.

Citation

Zou, K., Wong, J., Abdullah, N., Chen, X., Smith, T., Doherty, M., & Zhang, W. (2016). Examination of overall treatment effect and the proportion attributable to contextual effect in osteoarthritis: meta-analysis of randomised controlled trials. Annals of the Rheumatic Diseases, 75(11), 1964-1970. https://doi.org/10.1136/annrheumdis-2015-208387

• Journal Article Type: Article
• Acceptance Date: Jan 16, 2016
• Online Publication Date: Feb 16, 2016
• Publication Date: Nov 15, 2016
• Deposit Date: Apr 17, 2018
• Publicly Available Date: Jan 22, 2019
• Print ISSN: 0003-4967
• Electronic ISSN: 1468-2060
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 75
• Issue: 11
• Pages: 1964-1970
• DOI: https://doi.org/10.1136/annrheumdis-2015-208387
• Public URL: https://nottingham-repository.worktribe.com/output/1126437
• Publisher URL: https://ard.bmj.com/content/75/11/1964
• PMID: 26882927