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

Abstract

ObjectiveTo examine the overall treatment effect and the proportion attributable to contextual effect (PCE) in randomised controlled trials (RCTs) of diverse treatments for osteoarthritis (OA).MethodsWe 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.ResultsIn 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.ConclusionsThe 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’.

Mindfulness-Based Stress Reduction for Adolescents with Functional Somatic Syndromes: A Pilot Cohort Study

“…Indeed, a recent meta-analysis found that nonspecific and contextual effects were responsible for 75% of treatment effects in clinical trials in patients with osteoarthritis. 70 To minimize recall bias, subjects received daily text message reminders to record amount of home practice. We doubt that these messages affected adherence to the home practice, because most subjects (80%) reported at least one full week without any home practice, despite having received the daily text reminders.…”

Exercise therapy versus arthroscopic partial meniscectomy for degenerative meniscal tear in middle aged patients: randomised controlled trial with two year follow-up

“…Although placebo effects are greater after invasive interventions such as surgery,31 32 they are also present from non-invasive passive treatments such as inactive ultrasonography and inert gel 33. In exercise studies, where the patient, not the therapist, performs the intervention, placebo effects are less obvious, although attention effects cannot be excluded.…”

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“…An effect size of 0.5, or thereabouts, is of considerable clinical value, and comparable to that of many of our commonly used interventions [16]. The same group published a further analysis, in which they used random-effects modelling to calculate the amount of pain relief that could be attributed to placebo (contextual) effects, and how much to the treatment being tested for its effects on pain in OA [17]. They report that on average 75% of the overall treatment effect is due to the contextual factors rather than the specific intervention.…”