Composite Outcomes in Randomized Trials

Composite outcomes, in which multiple end points are combined, are frequently used as primary outcome measures in randomized trials and are often associated with increased statistical efficiency. However, such measures may prove challenging for the interpretation of results. In this article, we examine the use of composite outcomes in major clinical trials, assess the arguments for and against them, and provide guidance on their application and reporting. To assess incidence and quality of reporting, we systematically reviewed the use of composite end points in clinical trials in Annals of Internal Medicine, BMJ, Circulation, Clinical Infectious Diseases, Journal of the American College of Cardiology, JAMA, Lancet, New England Journal of Medicine, and Stroke from 1997 through 2001 using a sensitive search strategy. We selected for review 167 original reports of randomized trials (with a total of 300 276 patients) that included a composite primary outcome that incorporated all-cause mortality. Sixty-three trials (38%) were neutral both for the primary end point and the mortality component. Sixty trials (36%) reported significant results for the primary outcome measure but not for the mortality component. Only 6 trials (4%) were significant for the mortality component but not for the primary composite outcome, whereas 19 trials (11%) were significant for both. Twenty-two trials (13%) were inadequately reported. Our review suggests that reporting of composite outcomes is generally inadequate, implying that the results apply to the individual components of the composite outcome rather than only to the overall composite. Current guidelines for the undertaking and reporting of clinical trials could be revised to reflect the common use of composite outcomes in clinical trials.