Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study

OBJECTIVE: To examine the presence and extent of small study effects in clinical osteoarthritis research.DESIGN: Meta-epidemiological study.DATA SOURCES: 13 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' reportedpain as an outcome.METHODS: We compared estimated benefits of treatment between large trials (atleast 100 patients per arm) and small trials, explored funnel plots supplemented with lines of predicted effects and contours of significance, and used threeapproaches to estimate treatment effects: meta-analyses including all trialsirrespective of sample size, meta-analyses restricted to large trials, andtreatment effects predicted for large trials.RESULTS: On average, treatment effects were more beneficial in small than inlarge 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 estimatesuggested a clinically relevant, significant benefit of treatment, whereasanalyses restricted to large trials and predicted effects in large trials yieldedsmaller non-significant estimates.CONCLUSIONS: Small study effects can often distort results of meta-analyses. The influence of small trials on estimated treatment effects should be routinelyassessed.