Some issues with composite endpoints in clinical trials.

This article discusses some important issues that may arise in the current usage of composite endpoints as primary endpoints for demonstrating the efficacy of new drugs in clinical trials. The discussion focuses on time-to-event composite endpoints. Issues discussed include validity of a composite endpoint, the often lack of follow-up of patients beyond first event, the analysis of a composite endpoint, its sub-composite and individual component endpoints and their interpretation. Actual published examples in the literature are used to illustrate some of these problems. It is recommended that a clinical trial using a composite endpoint as the primary endpoint should be designed to include patient follow-up beyond the first event if possible. For data collected from such trials, basic formats for tabular presentation of trial data and for results of analysis of the composite endpoint, its sub-composite and individual component endpoints are proposed for transparency and ease of interpretation.