Surrogate end points are widely used for the development of new therapies in cancer and many other chronic diseases. Surrogate outcomes are particularly useful because they greatly increase the efficiency of developmental clinical trials. In particular, they can shorten the time required to observe treatment effects and reduce the sample size required for some trials. As a consequence, surrogate end points can reduce costs and speed up the development time for new therapies. To be useful, a surrogate end point should be strongly associated with the definitive outcome, lie in the causal pathway for the definitive outcome, should manifest early in the course of follow-up, and should be relatively easy to measure. However, the defining characteristic is that the surrogate outcome should be affected by treatment in the same way (direction and relative magnitude) as the definitive outcome. It is this last characteristic that is difficult to verify. Even when a surrogate outcome is judged to be appropriate for a particular treatment, different therapies for the same disease could potentially invalidate a given surrogate outcome. There are numerous examples of the apparently successful application of surrogate outcomes in cancer. However, there are other circumstances in which the traditionally employed surrogate (tumor shrinkage) is not appropriate. Furthermore, for other diseases, such as cardiovascular disease and AIDS (acquired immune deficiency syndrome), the putative surrogate outcome may be wholly inadequate. All of these ideas were discussed in more depth during the presentation.
Piantadosi S. Some Statistical Issues in the Design of Cancer Clinical Trials With Surrogate End Points. Arch Neurol. 2000;57(8):1233. doi: