Surrogate Markers

Abstract

The validation of surrogate endpoints has been studied by Prentice. He presented a definition as well as a set of criteria that are equivalent if the surrogate and true endpoints are binary. Freedman and colleagues supplemented these criteria with the so‐called proportion explained . Buyse and Molenberghs proposed to replace the proportion explained by two quantities: (i) the relative effect linking the effect of treatment on both endpoints and (ii) the adjusted association , an individual‐level measure of agreement between both endpoints. Later, a number of proposals have been made to replace the single‐unit validation measures by multiunit (e.g., meta‐analytic) counterparts.