James D. Neaton, Ph.D.
Professor of Biostatistics
School of Public Health
University of Minnesota
Heart Failure 2006
Session 405001, Monday 19/06/2006, 8:30
Composite end points are common in heart failure trials. A composite end point refers to an outcome that is considered to have occurred if any of several different events is observed.
For example, death from cardiovascular disease or hospitalization for heart failure is a composite outcome with two components. Some patients may experience both outcomes, but the typical primary analysis would be based on the time to the first event.
Use of this composite outcome in a trial as the primary end point is different from using CVD mortality as the primary end point and specifying hospitalization for heart failure as a secondary end point.
Composites are attractive outcomes because if the expected treatment effect is similar for each component of the composite end point, sample size will be smaller than using one of the components as the primary end point. That is a big “IF”. If the treatment effect is different for the components, there could be a loss of power. Thus, the journey to the dark side begins at the design stage.
Composite 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. In order to fully understand the effects of the treatment on the composite end point, treatment differences for each component of the composite end point should be reported. If data for all components of the composite end point are not collected on all patients through the end of the trial so that each component can be separately evaluated, the journey to the dark side continues at interim and final analyses.