Abstract

Statistical challenges in the evaluation of surrogate endpoints in randomized trials

Molenberghs, G., Buyse, M., Geys, H., Renard, D., Burzykowski, T. and Alonso, A.

The validation of surrogate endpoints has been studied by Prentice, who presented a definition as well as a set of criteria that are equivalent if the surrogate and true endpoints are binary. Freedman et al. supplemented these criteria with the so-called proportion explained. Buyse and Molenberghs proposed to replace the proportion explained by two quantities: (1) the relative effect linking the effect of treatment on both endpoints and (2) the adjusted association, an individual-level measure of agreement between both endpoints. In a multi-unit setting, these quantities can be generalized to a trial-level measure of surrogacy and an individual-level of surrogacy. In this paper, we argue that such a multi-unit approach should be adopted because it overcomes difficulties that necessarily surround validation efforts based on a single trial. These difficulties are highlighted.

  Last update: February, 5, 2003  - Contact : S. Malali