The effects of excluding patients from the analysis in randomised controlled trials: meta-epidemiological study

OBJECTIVE: To examine whether excluding patients from the analysis of randomised trials are associated with biased estimates of treatment effects and higherheterogeneity between trials.DESIGN: Meta-epidemiological study based on a collection of meta-analyses ofrandomised trials.DATA SOURCES: 14 meta-analyses including 167 trials that compared therapeuticinterventions with placebo or non-intervention control in patients withosteoarthritis of the hip or knee and used patient reported pain as an outcome.METHODS: Effect sizes were calculated from differences in means of pain intensitybetween groups at the end of follow-up, divided by the pooled standard deviation.Trials were combined by using random effects meta-analysis. Estimates oftreatment effects were compared between trials with and trials without exclusionsfrom the analysis, and the impact of restricting meta-analyses to trials without exclusions was assessed.RESULTS: 39 trials (23%) had included all patients in the analysis. In 128 trials(77%) some patients were excluded from the analysis. Effect sizes from trialswith exclusions tended to be more beneficial than those from trials withoutexclusions (difference -0.13, 95% confidence interval -0.29 to 0.04). However,estimates of bias between individual meta-analyses varied considerably(tau(2)=0.07). Tests of interaction between exclusions from the analysis andestimates of treatment effects were positive in five meta-analyses. Stratifiedanalyses indicated that differences in effect sizes between trials with andtrials without exclusions were more pronounced in meta-analyses with high betweentrial heterogeneity, in meta-analyses with large estimated treatment benefits,and in meta-analyses of complementary medicine. Restriction of meta-analyses totrials without exclusions resulted in smaller estimated treatment benefits,larger P values, and considerable decreases in between trial heterogeneity.CONCLUSION: Excluding patients from the analysis in randomised trials oftenresults in biased estimates of treatment effects, but the extent and direction ofbias is unpredictable. Results from intention to treat analyses should always be described in reports of randomised trials. In systematic reviews, the influenceof exclusions from the analysis on estimated treatment effects should routinelybe assessed.