Drotrecogin alfa (activated) in patients with severe sepsis and a high risk of death

doi:10.1186/cc5117

Critical Care

Volume 10
Issue 6

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Letter

Drotrecogin alfa (activated) in patients with severe sepsis and a high risk of death

Jan O Friedrich¹ , Neill KJ Adhikari² and Maureen O Meade³

¹Critical Care and Medicine Departments, St. Michael's Hospital, Interdepartmental Division of Critical Care, University of Toronto, Bond Street, Toronto, Ontario, Canada M5B 1W8

²Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Interdepartmental Division of Critical Care, University of Toronto, Bayview Avenue, Toronto, Ontario, Canada M4N 3M5

³Departments of Medicine and Clinical Epidemiology & Biostatistics, McMaster University, Department of Critical Care, Hamilton Health Sciences, Main Street West, Hamilton, Ontario, Canada L8N 3Z5

author email corresponding author email

Critical Care 2006, 10:427doi:10.1186/cc5117


Published:	20 December 2006

See related letter by Williams et al., http://ccforum.com/content/10/5/424, related commentary by Friedrich et al., http://ccforum.com/content/10/3/145, related letter by Agarwal and Nath, http://ccforum.com/content/10/4/416, related reply by Friedrich et al., http://ccforum.com/content/10/4/420 and related letter by Saxena and Williams, http://ccforum.com/content/10/5/422

First paragraph (this article has no abstract)

We are pleased that Williams and coworkers [1] confirmed our random effects analysis [2], which relied on publicly available data. This analysis pooled the results from patients with Acute Physiology and Chronic Health Evaluation (APACHE) II scores of 25 or greater from the PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation of Severe Sepsis) [3] and ADDRESS (Administration of Drotrecogin Alfa [Activated] in Early Stage Severe Sepsis) [4] trials. As we discussed previously [5], this analysis demonstrates a surprising degree of statistical heterogeneity, which remains despite minimal methodologic differences between the two trials and further minimization of clinical heterogeneity by selecting a more uniform subgroup of patients with severe sepsis and a high risk for death. This heterogeneity is illustrated in Figure 1 presented by Williams and coworkers [1], in which I²(the percentage of total variation in results across studies that is due to heterogeneity rather than chance [6]), is more than 80% for each of the methods presented. Given this degree of unexplained heterogeneity, the use of a fixed effects model, as suggested by Williams and coworkers [1], would be highly unconventional [7].