Clinical trial endpoints.

Whenever clinical study results are publicly announced, the endpoints are the focus; more specifically, the focus is on whether the clinical trial met or failed its primary endpoint. Clinical trial endpoints are important because they are proof that the drug does what its manufacturer claims it does for the patient. Even though clinical trial endpoints are measurements at an individual patient level, the results are extrapolated to entire populations of patients based on clinical similarities to patients in the clinical trials. The Food and Drug Administration bases approval decisions on clinical trial endpoints.

The most important requirement for a clinical trial endpoint is clinical relevance, or what the effect means to the patient. Appropriate measurement or detection of a clinical endpoint is secondary to the appropriate selection of a clinically relevant endpoint; measuring an endpoint well means nothing to the patient if the endpoint has poor clinical relevance. In addition to clinical relevance, trial endpoints should reflect the research question, the drug's mechanism (or mechanisms) of action and patient well-being. In phase I clinical studies, safety is the primary endpoint; in phase II clinical studies, a measure of efficacy is the primary endpoint. Quality of life (QOL) is becoming an increasingly important endpoint in chronic or terminal conditions, including cancer.

Clinical trials should have only one primary endpoint -- hence the "primary" designation. The primary endpoint should be the most meaningful result in a clinical trial. An example of a primary endpoint in cancer clinical trials is survival. Survival has long been considered the "gold standard" endpoint for cancer therapies, based on the importance of survival to cancer patients. Other results that contribute to the interpretation of the clinical trial are then considered "secondary endpoints." A clinical trial can have, and often does have, many secondary endpoints. Still, when a clinical trial attempts to capture too many endpoints, complications can arise that impede the critical goal of answering a primary question. If multiple endpoints yield conflicting results, the study cannot be interpreted meaningfully. Multiple endpoints also increase the chance of a Type 1 error (when a difference is shown when there is no actual difference).

Posted in: Clinical Research