Article Text

Extended report
Examination of overall treatment effect and the proportion attributable to contextual effect in osteoarthritis: meta-analysis of randomised controlled trials
  1. Kun Zou1,2,
  2. Jean Wong3,
  3. Natasya Abdullah1,
  4. Xi Chen1,
  5. Toby Smith4,
  6. Michael Doherty1,
  7. Weiya Zhang1
  1. 1Division of Rheumatology, Orthopaedics and Dermatology, University of Nottingham, Nottingham, UK
  2. 2Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Affiliated Hospital of University of Electronic Science and Technology, Chengdu, China
  3. 3Pinfold Medical Practice, Loughborough, UK
  4. 4School of Health Sciences, University of East Anglia, Norwich, UK
  1. Correspondence to Dr Weiya Zhang, Academic Rheumatology, Division of Rheumatology, Orthopaedics and Dermatology, Clinical Sciences Building, University of Nottingham, Nottingham NG5 1PB, UK; weiya.zhang{at}


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’.

  • Osteoarthritis
  • Treatment
  • Epidemiology

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See:

Statistics from

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.


  • Handling editor Tore K Kvien

  • Twitter Follow Toby Smith at @tobyosmith

  • Contributors MD and WZ are joint senior authors. WZ and MD conceptualised the study. KZ, WZ and MD contributed to the design of the study. KZ conducted the analysis. All authors contributed to data collection, interpretation of research findings and manuscript writing.

  • Funding KZ was supported by the International Scholarship for Research Excellence from the University of Nottingham. XC was funded by the Nottingham Arthritis Research UK Pain Centre, which was funded by the Arthritis Research UK (grant number RGB4887).

  • Competing interests WZ had grants from Nottingham-China Scholarship, during the conduct of the study; MD reports personal fees from Ad hoc advisory boards for osteoarthritis and gout for AstraZeneca, Menarini, Nordic Biosciences, Pfizer, outside the submitted work; no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.