A Unifying Approach for Surrogate Marker Validation Based on Prentice's Criteria

• Activity Number: 163
• Type: Contributed
• Date/Time: Monday, August 9, 2004 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Helena M. Geys*+ and Ariel Alonso and Geert Molenberghs
• Companies: Limburgs Universitair Centrum and Limburgs Universitair Centrum and Limburgs Universitair Centrum
• Keywords: hierarchical models ; surrogate markers ; likelihood reduction factor ; Prentice criteria

Abstract

Part of the recent literature on the evaluation of surrogate endpoints starts from a multitrial context which leads to a definition of validity in terms of the quality of both trial-level and individual-level association. Those authors proposed their methodology based on the simplest cross-sectional case in which both the surrogate and the true endpoint, are continuous and normally distributed. Different variations to the theme have been implemented for binary responses, times to event, combinations of binary and continuous endpoints, etc. However, a drawback of this methodology is that different settings have led to different definitions to quantify the association at the individual level. In the longitudinal setting, Alonso (2003b) defined a class of canonical correlation functions that can be used to study surrogacy at the trial and individual level. We propose a new approach to evaluate surrogacy in the repeated measurements framework, we also show the connection between this proposal and the previous ones reported in the literature and finally we extend this concept to the non-normal case using some of the criteria defined by Prentice.