Informed choice of composite end points in cardiovascular trials

Abstract

A composite end point is often used as the primary end point to assess the efficacy of a new treatment in randomized clinical trials. In cardiovascular trials, the often rare event of the relevant primary end point (individual or composite), such as cardiovascular death, myocardial infarction, or both, is combined with a more common secondary end point, such as target lesion revascularization, with the aim to increase the statistical power of the study. Gómez and Lagakos developed statistical methodology to be used at the design stage of a randomized clinical trial for deciding whether to expand a study-relevant primary end point to the composite of the relevant end point and a secondary end point. The method uses the asymptotic relative efficiency of the logrank test for comparing treatment groups based on the relevant end point versus the logrank test based on the composite end point. The method is used to assess, in the cardiovascular research area, the characteristics of the candidate individual end points that should govern the choice of using a composite end point as the primary end point in a clinical trial. A set of recommendations is provided based on the reported values of the frequencies of observing each candidate end point and on the magnitude of the effect of treatment as expressed by the hazard ratio, supported by cardiovascular randomized clinical trials published in 2008.

Keywords: asymptotic relative efficiency; cardiovascular drugs; clinical trials, randomized; composite end point; logrank test.