Critical Care

official impact factor 4.60

Commentary

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

Kathleen D Liu1 and Michael A Matthay2*

Author Affiliations

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

2 Departments 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

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

Published: 24 April 2008

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.