Surrogate threshold effect: an alternative measure for meta-analytic surrogate endpoint validation
Article first published online: 10 MAY 2006
Copyright © 2006 John Wiley & Sons, Ltd.
Volume 5, Issue 3, pages 173–186, July/September 2006
How to Cite
Burzykowski, T. and Buyse, M. (2006), Surrogate threshold effect: an alternative measure for meta-analytic surrogate endpoint validation. Pharmaceut. Statist., 5: 173–186. doi: 10.1002/pst.207
- Issue published online: 21 AUG 2006
- Article first published online: 10 MAY 2006
- surrogate endpoint;
- two-stage model;
In many therapeutic areas, the identification and validation of surrogate endpoints is of prime interest to reduce the duration and/or size of clinical trials. Buyse et al. [Biostatistics 2000; 1:49–67] proposed a meta-analytic approach to the validation. In this approach, the validity of a surrogate is quantified by the coefficient of determination R obtained from a model, which allows for prediction of the treatment effect on the endpoint of interest (‘true’ endpoint) from the effect on the surrogate. One problem related to the use of R is the difficulty in interpreting its value. To address this difficulty, in this paper we introduce a new concept, the so-called surrogate threshold effect (STE), defined as the minimum treatment effect on the surrogate necessary to predict a non-zero effect on the true endpoint. One of its interesting features, apart from providing information relevant to the practical use of a surrogate endpoint, is its natural interpretation from a clinical point of view. Copyright © 2006 John Wiley & Sons, Ltd.