title: Sepsis: time to reconsider the concept.
abstract: OBJECTIVE
  To discuss the difficulty in using the concept of sepsis for clinical trials and propose new ways for designing future trials for severe infections.
  
  
  METHODS
  Short position statement. METHODS AND MAIN RESEARCH: Using a thorough evaluation of the recent literature in the field of severe sepsis and septic shock, the authors challenge the concept of sepsis as used in the past two decades and propose new ideas for designing future trials in this setting. The two main proposals are first to use a systematic assessment of the targeted inflammatory mediators when the study intends to counteract or replace those mediators (e.g., anti-tumor necrosis factor-alpha, activated protein C) and, second, to select more homogeneous populations, coming back to "precise infectious diseases," such as severe community-acquired pneumonia, severe peritonitis, or meningitis.
  
  
  CONCLUSIONS
  The concept of sepsis has been useful to help clinicians to suspect and detect severe infections. Due to a considerable heterogeneity in the patients and type of infections included in the trials performed in the last two decades, it has not been useful in demonstrating the efficacy of new compounds. The authors propose a dramatic change in the design of future trials dealing with severe infections.
authors.affiliation: Intensive Care Unit, Infectious Diseases Department, Groupe Hospitalier Paris Saint-Joseph, Paris, France. j.carlet@has-saute.fr
authors.forename: Jean
authors.initials: J
authors.lastname: Carlet
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cohen
authors.forename: Thierry
authors.initials: T
authors.lastname: Calandra
authors.forename: Steven M
authors.initials: SM
authors.lastname: Opal
authors.forename: Henry
authors.initials: H
authors.lastname: Masur
mesh_terms: D002986:Clinical Trials as Topic / Q000592:standards*; D005544:Forecasting; D006801:Humans; D018805:Sepsis / Q000188:drug therapy*; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000188:drug therapy