When and How Can Endpoints Be Changed after Initiation of a Randomized Clinical Trial?

Introduction Endpoints are outcome measures used to address the objectives of a clinical trial. The primary endpoint is the most important outcome and is used to assess the primary objective of a trial (e.g., the variable used to compare the effect difference of two treatment groups). A fundamental principle in the design of randomized trials involves setting out in advance the endpoints that will be assessed in the trial [1], as failure to prespecify endpoints can introduce bias into a trial and creates opportunities for manipulation. However, sometimes new information may come to light that could merit changes to endpoints during the course of a trial. This new information might include, for example, results from other trials or identification of better biomarkers or surrogate outcome measures. Such changes can allow incorporation of up-to-date knowledge into the trial design. However, changes to endpoints can also compromise the scientific integrity of a trial. Here I discuss some of the issues and decisionmaking processes that should be considered when evaluating whether to make changes to endpoints, and discuss the documentation and reporting of clinical trials that have revised endpoints.