Protein C as a surrogate end-point for clinical trials of sepsis

Kathleen D Liu¹ and Michael A Matthay²

¹Divisions of Nephrology and Critical Care Medicine, Department of Medicine, University of California, 521 Parnassus Ave, C443, San Francisco, CA 94143, USA

²Departments of Anesthesia and Medicine and the Cardiovascular Research Institute, University of California, 505 Parnassus Ave, Moffitt Hospital, Room M-917, San Francisco, CA 94143-0624, USA

author email corresponding author email

Critical Care 2008, 12:139doi:10.1186/cc6859


Published:	24 April 2008

See related research by Shorr et al, http://ccforum.com/content/12/2/R45

Abstract

Identification of good surrogate end-points can greatly facilitate the design of clinical trials. Using data from PROWESS and ENHANCE, Shorr and colleagues explore the potential value of several plasma biomarkers for treatment trials of activated protein C for severe sepsis. Based on the framework proposed by Vasan, they tested the utility of several factors (protein C, interleukin-6, antithrombin III, prothrombin time, protein S, and d-dimers) as type 0, 1 and 2 biomarkers. Only protein C had acceptable performance characteristics as a type 2 biomarker, or surrogate end-point. The utility of protein C as a surrogate end-point for studies of severe sepsis must be validated in future prospective studies.