Abstract

Drs. Manyara, Ciani, and Taylor make the important point that randomized controlled trials (RCTs) using a primary surrogate endpoint should be more transparent in their reporting details of biomarkers in trials. They suggest a clear statement concerning use of a surrogate primary endpoint and providing information on validity and limitations of the surrogate. They announce a new project to develop SPIRIT and CONSORT extensions specific to surrogate endpoints SPIRIT‐SURROGATE and CONSORT‐SURROGATE.There are no fully qualified and validated surrogate biomarkers for Alzheimer's disease (AD) RCTs and none that could serve as a primary RCT endpoint. As described by the US Food and Drug Administration (FDA) a surrogate endpoint is a clinical trial endpoint used as a substitute for a direct measure of how a patient feels, functions, or survives.1 A surrogate endpoint does not measure the clinical benefit of primary interest in and of itself, but rather is expected to predict clinical benefit. Epidemiologic, therapeutic, pathophysiologic, or other scientific data provide the evidentiary basis for establishing a biomarker as a surrogate. A surrogate must change in response to multiple therapies across multiple RCTs and must explain the change in clinical outcome as well as correlate with it.2 Designation as a