Question

You are designing a randomized clinical trial of a new anti-hypertensive medication. The goal is to lower the incidence of stroke, but a surrogate endpoint will be used instead of stroke as the primary endpoint of the trial.

(1) Give an example of a surrogate endpoint that makes sense for the context of this clinical trial.

(2) In the context of this trial, give a rationale for why an investigator might decide to use a surrogate endpoint.

Answer 1

A surrogate endpoint of a clinical trial would be a laboratory value or biomarker used as a substitute for a clinically meaningful endpoint. The clinically meaningful endpoint measures directly how a patient feels, functions, or survives. Changes induced by a clinical trial are believed to reflect changes of a clinically meaningful endpoint. Usually, the validated surrogate endpoint might be a biomarker.

1. Blood pressure reduction can be used as the surrogate endpoint in this clinical trial. Blood pressure reduction is a validated surrogate endpoint for a reduction in rates of stroke and has been used as the basis for the approval of drugs and in pivotal trials of medical devices intended to treat hypertension.

2. A validated surrogate endpoint can be used without the need for additional studies to demonstrate the clinical benefit directly to support marketing approval of a medical product in a defined context. The long-term effect of a drug on stroke reduction can be assessed only after waiting for a long period. In this context the use of a surrogate endpoint is useful.