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Keywords:

  • surrogate endpoint;
  • validation;
  • meta-analysis;
  • two-stage model;
  • prediction

Abstract

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 Rmath image 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 Rmath image 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.