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December 4, 1996

Why Sepsis Trials Fail

Author Affiliations

University of South Florida Tampa

JAMA. 1996;276(21):1723. doi:10.1001/jama.1996.03540210031024

To the Editor.  —Dr Bone's Commentary concerning the failure of clinical trials evaluating new therapies in the treatment of sepsis was timely and thoughtful.1 However, there are a few points that we would like to address that undoubtedly contributed to these disappointing clinical trials. Sepsis is difficult to diagnose early in its course prior to the development of end-organ dysfunction. In fact, end-organ dysfunction was an entry criterion in each sepsis study cited by Bone. This study design dictates that the major endpoints used to determine efficacy of anti-inflammatory therapy are the resolution of this dysfunction and (primarily) 28-day mortality. The prevention of end-organ failure, which would most likely have an impact on nearly all of the clinical features of sepsis, including survival, morbidity, and cost, is essentially not amenable to investigation using these trial protocols. Since mortality is directly attributable to the incidence and severity of multiple organ