title: Examination of overall treatment effect and the proportion attributable to contextual effect in osteoarthritis: meta-analysis of randomised controlled trials.
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'.
authors.affiliation: Division of Rheumatology, Orthopaedics and Dermatology, University of Nottingham, Nottingham, UK Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Affiliated Hospital of University of Electronic Science and Technology, Chengdu, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zou
authors.affiliation: Pinfold Medical Practice, Loughborough, UK.
authors.forename: Jean
authors.initials: J
authors.lastname: Wong
authors.affiliation: Division of Rheumatology, Orthopaedics and Dermatology, University of Nottingham, Nottingham, UK.
authors.forename: Natasya
authors.initials: N
authors.lastname: Abdullah
authors.affiliation: Division of Rheumatology, Orthopaedics and Dermatology, University of Nottingham, Nottingham, UK.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Health Sciences, University of East Anglia, Norwich, UK.
authors.forename: Toby
authors.initials: T
authors.lastname: Smith
authors.affiliation: Division of Rheumatology, Orthopaedics and Dermatology, University of Nottingham, Nottingham, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Doherty
authors.affiliation: Division of Rheumatology, Orthopaedics and Dermatology, University of Nottingham, Nottingham, UK.
authors.forename: Weiya
authors.initials: W
authors.lastname: Zhang
mesh_terms: D018771:Arthralgia / Q000209:etiology / Q000628:therapy*; D005260:Female; D006801:Humans; D007270:Injections, Intra-Articular; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000150:complications / Q000628:therapy*; D059408:Pain Management; D016032:Randomized Controlled Trials as Topic; D007507:Therapeutic Irrigation; D016896:Treatment Outcome
keywords: Epidemiology; Osteoarthritis; Treatment