Improving clinical trials in the critically ill: Unique challenge-Sepsis

Objective: This article aimed at providing suggestions to improve the success rate of future sepsis trials. Design: Systematic review. Intervention: None. Measurements and main results: CENTRAL (The Cochrane Library Issue 2, 2007) was searched using "sepsis" OR "severe sepsis" OR "septic shock" as search terms. The search was restricted to studies designed and conducted in adults with severe sepsis or septic shock after June 1992, published before September 2007, and powered for survival analysis. Twenty-seven trials were included and analyzed. The author suggested six key points for the design and conduct of future sepsis trials: 1) avoid mixing patients with severe sepsis and septic shock; 2) restrict time window to less than 24 hrs from onset of the first organ dysfunction or shock; 3) include only undisputable sepsis; 4) use the Sepsis-related Organ Failure Assessment score for eligibility; 5) include a first interim analysis after enrollment of 25% of the planned sample size to check the actual basal risk of death and to recalculate the number of patients needed; 6) strictly control for concomitant treatments on the basis of the Surviving Sepsis Campaign. Conclusions: There is a need to limit the sources of heterogeneity in sepsis trials by a better definition of target populations, by a better estimation of basal risk of death, and by controlling cointerventions. (Crit Care Med 2009; 37[Suppl.]:S117-S128)