Designing p53 trials: A surgical oncologists view

Abstract

No single marker currently in use was shown to be of clinical benefit in a suitably designed clinical phase III marker trial. There is widespread agreement among experts as to how new anticancer drugs should be evaluated before they can be used in standard therapy. However, a corresponding algorithm for the clinical implementation of markers does not exist. Before designing a phase III marker trial one must know whether the marker being tested predicts relapse (prognostic marker) or response to a certain therapy (predictive marker), because relapse and response to therapy are entirely different endpoints. The endpoint is the most critical aspect of a phase III trial and is determined by the type of marker (prognostic or predictive). Knowledge of the underlying scenario is a prerequisite to decide on the optimal marker trial design. We describe a generally applicable algorithm for clinical evaluation of a marker. The algorithm is applied to current knowledge concerning the marker p53.