Methodologic discussions for using and interpreting composite endpoints are limited, but still identify major concerns

Abstract

Objective: To investigate the rationale, potential problems and solutions of using composite endpoints (CEPs) for the assessment of intervention effects.

Study design and setting: This study is a systematic review. We searched MEDLINE, EMBASE, and the Science Citation Index, for publications appearing between 1980 and September 2005, and reviewed potentially informative textbooks. Eligible articles provided a commentary, analysis, or discussion of CEPs for any of the following areas: (1) rationale, (2) interpretation or meaning, (3) advantages, (4) limitations or conceptual problems, and (5) recommendations for use.

Results: Seventeen articles and one textbook proved eligible. Decreases in sample size requirements and ability to assess the net effect of an intervention were the most commonly cited advantages. Authors noted the risk of misinterpretation when heterogeneity among components with respect to either patient importance or magnitude of treatment effects as the most salient disadvantage. There were discrepancies between authors concerning the usefulness of CEPs to avoid bias from competing risks and when the direction of the effect of therapy differs across components.

Conclusion: Methodologists have given limited attention to CEPs and their views are sometimes contradictory. Further work is needed to establish the role of CEPs in research and in guiding clinical practice.