Clinical endpoint

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

In a research trial, a clinical endpoint refers to a disease, symptom, or sign that constitutes one of the target outcomes of the trial. The results of a clinical trial generally indicate the number of people enrolled who reached the pre-determined clinical endpoint during the study interval, compared with the overall number of people who were enrolled. Once a patient reaches the endpoint, he or she is generally excluded from further experimental intervention (the origin of the term endpoint).

For example, a clinical trial investigating the ability of a medication to prevent heart attack might use chest pain as a clinical endpoint. Any patient enrolled in the trial who develops chest pain over the course of the trial, then, would be counted as having reached that clinical endpoint. The results would ultimately reflect the fraction of patients who reached the endpoint of having developed chest pain, compared with the overall number of people enrolled.

When an experiment involves a control group, the fraction of individuals who reach the clinical endpoint after an intervention is compared with the fraction of individuals in the control group who reached the same clinical endpoint, thus reflecting the ability of the intervention to prevent the endpoint in question.

Primary Endpoint

The primary endpoint is defined as the main result measured at the end of a study to see if a given treatment has worked. For example, researchers might look at survival or risk of recurrence as primary endpoints. The study then compares these factors in the treatment group and the control group. The primary endpoints need to be determined before the study begins.

Secondary Endpoint

The secondary endpoint is defined as an endpoint other than the primary endpoint that is of interest in a clinical trial. If the difference between treatment groups in the primary endpoint is not significant, the interpretation of significant differences in secondary endpoints may be difficult to interpret because of the multiple comparisons made. It has been proposed that the comparison in the primary endpoint use a significance level of alpha and that the secondary endpoints be evaluated using a significance level alpha/(k + 1), where k is the number of secondary outcomes to be evaluated. Similar to the primary endpoint, the secondary endpoints should also be pre-specified.

Composite Endpoint

Some studies will examine the incidence of a combined endpoint, which can merge a variety of outcomes into one group. For example, the heart attack study above may report the incidence of the combined endpoint of chest pain, myocardial infarction, or death.