Background: Composite outcomes are commonly used in heart failure trials. The aim of this article is to discuss the advantages and disadvantages of composite outcomes and recommend guidelines for reporting them. Examples are used to illustrate key points. Methods and Results: A workshop jointly planned by the Heart Failure Society of America and the US Food and Drug Administration was convened in April 2004. One of the panel discussions concerned the use of composite outcomes in heart failure trials. With use of composite outcomes, event rates are higher and if it is reasonable to assume that the treatment effect is similar for each component of the composite outcome, sample size will be smaller than using one of the components as the primary end point. Composites end points are difficult to interpret if effects are not similar for all components or if the effect of treatment is primarily on a more common, less serious component of the composite. Composite outcomes typically only focus on the first occurring event. This can lead to a substantial loss of information in some trials. When composite end points are used, data collection for all components should continue until the end of the trial so that each component can be separately evaluated. Conclusion: Composite end points should be used with caution. Additional research is need on optimally weighting components of composite outcomes and to better using the entire event history of patients in heart failure trials. Further analyses of completed trials could be useful in this respect.
Bibliographical noteFunding Information:
The opinions expressed in this paper are those of the authors and do not necessarily represent those of the editor or the Heart Failure Society of America (HFSA). All writing group members were required to complete and submit a Faculty Disclosure Questionnaire before the workshop was held, April 1–2, 2004. The workshop was sponsored by the HFSA. This article represents the professional opinion of the authors and is not an official document, agency guidance, or policy of the U.S. Government, the Department of Health and Human Services, or the Food and Drug Administration, nor should any official endorsment be inferred.
- Clinical trial
- Composite end point
- Heart failure
- Medical devices