Decision tool and Sample Size Calculator for Composite Endpoints

Summary points:

  • This article considers the combination of two binary or two time-to-event endpoints to form the primary composite endpoint for leading a trial.
  • It discusses the relative efficiency of choosing a composite endpoint over one of its components in terms of: the frequencies of observing each component; the relative treatment effect of the tested therapy; and the association between both components.
  • We highlight the very important role of the association between components in choosing the most efficient endpoint to use as primary.
  • For better grounded future trials, we recommend trialists to always reporting the association between components of the composite endpoint.
  • Common fallacies to note when using composite endpoints: i) composite endpoints always imply higher power; ii) treatment effect on the composite endpoint is similar to the average effects of its components; and iii) the probability of observing the primary endpoint increases significantly.