Document Detail

New strategies for clinical trials in patients with sepsis and septic shock.
MedLine Citation:
PMID:  11373487     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: The difficulty in identifying new treatment modalities that significantly reduce the mortality and morbidity rates associated with sepsis has highlighted the need to reevaluate the approach to clinical trial design. The United Kingdom Medical Research Council convened an International Working Party to address these issues. DATA SOURCES: The subject areas that were to be the focus of discussion were identified by the co-chairs, and group leaders were nominated. Preconference reading material was circulated to group members. STUDY SELECTION AND DATA EXTRACTION: Small-group discussion fed into an iterative process of feedback from plenary sessions, followed by the formulation of recommendations. Finally, each working group prepared a summary of its recommendations and these are reported herein. DATA SYNTHESIS: There were five key recommendations. First, investigators should no longer rely solely on the American College of Chest Physicians/Society of Critical Care Medicine definitions of sepsis or sepsis syndrome as the basis of trial entry. Entry criteria should be based on three principles: a) All patients should have infection; b) there should be evidence of a pathologic process that represents a biologically plausible target for the proposed intervention, for example, an abnormal circulating level of a biological marker pertinent to the study drug; and c) patients should fall into an appropriate category of severity (usually severe sepsis). Second, investigators should use a scoring system for organ dysfunctions that has been validated and that can be incorporated into all sepsis studies; agreement on the use of a single system would simplify comparisons between studies. Third, the primary outcome measure generally should be mortality rates, but under appropriate circumstances major morbidities could be considered as primary end points. Regardless of choice of the duration to primary end point, patients should be followed for > or =90 days. Fourth, sample size needs to be based on a realistic assessment of achievable effect size based on knowledge of the at-risk population. Fifth, subgroups should be few in number and should be defined a priori on the basis of variables present before randomization. CONCLUSIONS: Important changes in several aspects of trial design may improve the quality of clinical studies in sepsis and maximize the chance of identifying effective therapeutic agents.
J Cohen; G Guyatt; G R Bernard; T Calandra; D Cook; D Elbourne; J Marshall; A Nunn; S Opal;
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Publication Detail:
Type:  Consensus Development Conference; Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Critical care medicine     Volume:  29     ISSN:  0090-3493     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2001 Apr 
Date Detail:
Created Date:  2001-05-24     Completed Date:  2001-06-14     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  880-6     Citation Subset:  AIM; IM    
Department of Infectious Diseases, Imperial College School of Medicine, London, England.
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MeSH Terms
Clinical Trials as Topic / methods*,  standards
Outcome Assessment (Health Care)
Research Design / standards
Sepsis* / classification,  mortality,  therapy
Severity of Illness Index
Shock, Septic* / classification,  mortality,  therapy

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