Surrogate end points: how well do they represent patient-relevant end points?

This review takes a critical look at the concept of replacing patient-relevant end points, such as morbidity or mortality, with surrogate end points in clinical trials. Surrogate end points can be measured earlier in the course of a clinical trial and so are thought to accelerate the drug development process. Furthermore, they might be beneficial to the patients themselves by allowing faster adjustment of therapeutic strategies. However, the fact that in the past several promising surrogate end points have not fulfilled their expectations emphasizes the importance of applying strict evaluation criteria. The evaluation of the candidate surrogate end point prostate-specific antigen using the Prentice criteria and a meta-analytic approach is discussed. Prostate-specific antigen is often used to replace overall or progression-free survival in prostate cancer trials testing the benefit of medical interventions.