Composite Endpoints in Clinical Trials

Composite endpoints have become increasingly useful as a measure of a patient's disease status. They have been found useful in both clinical practice and medical research. This chapter examines the usefulness of composite endpoints as a primary endpoint in clinical trials. The basic rationale for their use is discussed and illustrated with examples, followed by a variety of procedures for forming composites including how they should be interpreted. The chapter considers alternate approaches to conducting a primary analysis with multiple endpoints, and compares these methods with the use of composite endpoints. It focuses on the outcome measures used in the typical phase III clinical trial for efficacy, for simplicity assuming that an experimental therapy is being compared with a placebo. Some useful methods for defining a composite endpoint for use as a primary endpoint in a clinical trial are considered.