Division of Critical Care, University of Toronto, Toronto, Ontario, Canada Care and Medicine Departments, St Michael’s Hospital, 30 Bond Street, Toronto, Ontario, Canada M5B 1W8 3Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5 4Department of Medicine and Clinical Epidemiology & Biostatistics, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5 Corresponding author: Jan O Friedrich, Published: 2 June 2006 This article is online at © 2006 BioMed Central Ltd Critical Care 2006, 10:145 (doi:) Abstract Two international multicentre randomised. | Available online http content 10 3 145 Commentary Drotrecogin alfa activated does current evidence support treatment for any patients with severe sepsis Jan O Friedrich1 2 Neill KJ Adhikari1 3 and Maureen O Meade4 interdepartmental Division of Critical Care University of Toronto Toronto Ontario Canada 2Critical Care and Medicine Departments St Michael s Hospital 30 Bond Street Toronto Ontario Canada M5B 1W8 3Department of Critical Care Medicine Sunnybrook Health Sciences Centre 2075 Bayview Avenue Toronto Ontario Canada M4N 3M5 4Department of Medicine and Clinical Epidemiology Biostatistics McMaster University 1200 Main Street West Hamilton Ontario Canada L8N 3Z5 Corresponding author Jan O Friedrich Published 2 June 2006 Critical Care 2006 10 145 doi cc4947 This article is online at http content 10 3 145 2006 BioMed Central Ltd Abstract Two international multicentre randomised controlled trials of drotrecogin alfa activated DrotAA the Recombinant Human Activated Protein C Worldwide Evaluation of Severe Sepsis PROWESS and Administration of Drotrecogin Alfa Activated in Early Stage Severe Sepsis ADDRESS trials have produced inconsistent results. When 28-day mortality data from these trials for patients with severe sepsis and at high risk of death are pooled using a standard random-effects meta-analysis technique there is no statistically significant survival benefit for patients with Acute Physiology and Chronic Health Evaluation APACHE II scores of 25 or more or a borderline significant benefit for patients with multiorgan failure . We argue that two important methodological issues might explain the disparate results between the two trials. These issues centre on early trial stopping which exaggerates treatment effects and reliance on subgroup analyses which for DrotAA yields inconsistent results across different definitions of high risk. These concerns call into question the effectiveness of DrotAA in any .
