On Assessing Surrogacy in a Single Trial Setting Using a Semicompeting Risks Paradigm
Article first published online: 27 AUG 2008
© 2008, The International Biometric Society
Volume 65, Issue 2, pages 521–529, June 2009
How to Cite
Ghosh, D. (2009), On Assessing Surrogacy in a Single Trial Setting Using a Semicompeting Risks Paradigm. Biometrics, 65: 521–529. doi: 10.1111/j.1541-0420.2008.01109.x
- Issue published online: 28 MAY 2009
- Article first published online: 27 AUG 2008
- Received November 2007. Revised March 2008. Accepted May 2008.
- Bivariate survival data;
- Copula model;
- Dependent censoring;
- Multivariate failure time data;
- Prentice criterion
Summary There has been a recent emphasis on the identification of biomarkers and other biologic measures that may be potentially used as surrogate endpoints in clinical trials. We focus on the setting of data from a single clinical trial. In this article, we consider a framework in which the surrogate must occur before the true endpoint. This suggests viewing the surrogate and true endpoints as semicompeting risks data; this approach is new to the literature on surrogate endpoints and leads to an asymmetrical treatment of the surrogate and true endpoints. However, such a data structure also conceptually complicates many of the previously considered measures of surrogacy in the literature. We propose novel estimation and inferential procedures for the relative effect and adjusted association quantities proposed by Buyse and Molenberghs (1998, Biometrics54, 1014–1029). The proposed methodology is illustrated with application to simulated data, as well as to data from a leukemia study.