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Meta-Analysis
. 2016 Nov;75(11):1964-1970.
doi: 10.1136/annrheumdis-2015-208387. Epub 2016 Feb 16.

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

Kun Zou  1 , Jean Wong  2 , Natasya Abdullah  3 , Xi Chen  3 , Toby Smith  4 , Michael Doherty  3 , Weiya Zhang  3
Affiliations
Meta-Analysis

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

Kun Zou et al. Ann Rheum Dis. 2016 Nov.

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'.

Keywords: Epidemiology; Osteoarthritis; Treatment.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Flow chart of study selection.
Figure 2
Figure 2
Funnel plot of LnPCE for pain in osteoarthritis. PCE, proportion attributable to contextual effect, Egger test p<0.001.
Figure 3
Figure 3
The overall treatment effect and the proportion attributable to contextual effect (PCE) for pain in osteoarthritis. The overall length of the bar represents the effect size (ES) of overall treatment effect; the blue component of the bar and the label represents the PCE of each treatment (measured by ratio of the ESs between contextual effect and overall treatment effect, ranging from no contribution from contextual effect (=0) to 100% contribution from contextual effect (=1); the red component represent the proportion attributable to specific effect of each treatment). CS, chondroitin sulfate; GS, glucosamine sulfate; IACS, intra-articular corticosteroid; IAHA, intra-articular hyaluronic acid; NSAID, non-steroidal anti-inflammatory drug; PEMF, pulsed-electromagnetic field therapy.
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