• Eveline Nüesch, Sven Trelle, Stephan Reichenbach, Anne W S Rutjes, Beatrice Tschannen, Douglas G Altman, Matthias Egger, and Peter Jüni.
• Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland.
• BMJ. 2010 Jan 1;341:c3515.

ObjectiveTo examine the presence and extent of small study effects in clinical osteoarthritis research.DesignMeta-epidemiological study.Data Sources13 meta-analyses including 153 randomised trials (41 605 patients) that compared therapeutic interventions with placebo or non-intervention control in patients with osteoarthritis of the hip or knee and used patients' reported pain as an outcome.MethodsWe compared estimated benefits of treatment between large trials (at least 100 patients per arm) and small trials, explored funnel plots supplemented with lines of predicted effects and contours of significance, and used three approaches to estimate treatment effects: meta-analyses including all trials irrespective of sample size, meta-analyses restricted to large trials, and treatment effects predicted for large trials.ResultsOn average, treatment effects were more beneficial in small than in large trials (difference in effect sizes -0.21, 95% confidence interval -0.34 to -0.08, P=0.001). Depending on criteria used, six to eight funnel plots indicated small study effects. In six of 13 meta-analyses, the overall pooled estimate suggested a clinically relevant, significant benefit of treatment, whereas analyses restricted to large trials and predicted effects in large trials yielded smaller non-significant estimates.ConclusionsSmall study effects can often distort results of meta-analyses. The influence of small trials on estimated treatment effects should be routinely assessed.

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