Protein C as a surrogate end-point for clinical trials of sepsis.
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.
Liu
Kathleen D
KD
Divisions of Nephrology and Critical Care Medicine, Department of Medicine, University of California, 521 Parnassus Ave, C443, San Francisco, CA 94143, USA.
Matthay
Michael A
MA
D000890:Anti-Infective Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D006801:Humans; D011486:Protein C / Q000378:metabolism* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality
D000890:Anti-Infective Agents; D015415:Biomarkers; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated