New strategies for clinical trials in patients with sepsis and septic shock


ID Serval
Article: article d'un périodique ou d'un magazine.
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
New strategies for clinical trials in patients with sepsis and septic shock
Critical Care Medicine
Cohen  J., Guyatt  G., Bernard  G. R., Calandra  T., Cook  D., Elbourne  D., Marshall  J., Nunn  A., Opal  S.
0090-3493 (Print)
Statut éditorial
Date de publication
Consensus Development Conference
Journal Article
Research Support, Non-U.S. Gov't
Review --- Old month value: Apr
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.
Clinical Trials/*methods/standards Humans Outcome Assessment (Health Care) Research Design/standards *Sepsis/classification/mortality/therapy Severity of Illness Index *Shock, Septic/classification/mortality/therapy
Web of science
Création de la notice
25/01/2008 14:28
Dernière modification de la notice
20/08/2019 16:10
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