The use of surrogate endpoints in clinical trials: focus on clinical trials in cardiovascular diseases

Surrogate endpoints include a wide range of laboratory or physical measurements used in clinical trials as a substitute for meaningful clinical endpoints that directly assess effects of the intervention(s) tested on mortality and/or morbidity. These surrogate endpoints are frequently employed in clinical trials and when used judiciously, can accelerate and focus the study of new therapies and can greatly enhance our understanding of their mechanisms of action. The current review provides a definition of surrogate endpoints, proposes practical criteria for establishing their validity, outlines some of the advantages, disadvantages and specific statistical considerations associated with their use in clinical trials and attempts also to highlight drug approval issues associated with the use of these endpoints. A number of examples are also provided related to the use of surrogate endpoints in clinical trials with special emphasis on their use in cardiovascular medicine. Copyright (C) 2001 John Wiley Sons, Ltd.