Controversies in sepsis clinical trials: proceedings of a meeting of the International Sepsis Forum, Lausanne, Switzerland, September 29, 2001.
Despite some recent success with clinical trials studying innovative therapies in sepsis, the field remains predominantly one of failure despite compounds with significant preclinical activity. Preclinical animal experimentation remains an important component of drug development, and a portfolio approach is recommended. Failure in animals is more likely to predict failure in humans; however, success in animals often does not predict success in humans. Because the signal with innovative therapy of sepsis is likely to be low, an oncology model clinical trial approach, in which studies start with a high-risk homogeneous population and look for a large treatment effect with smaller numbers of patients, is likely to be more relevant than the commonly used cardiology model, in which studies search for a small treatment effect using large, heterogeneous, low-risk populations. With certain rules in place, improvement in organ function may be a worthwhile alternative to mortality as a clinical end point. Once a therapy is approved, adopting less stringent but still appropriate criteria for the use of that therapy in clinical practice may be appropriate.
Dellinger
R Phillip
RP
Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08854, USA.
Abraham
Edward
E
Bernard
Gordon
G
Marshall
John C
JC
Vincent
Jean-Louis
JL
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D006801:Humans; D016015:Logistic Models; D018805:Sepsis / Q000188:drug therapy*; D013557:Switzerland; D035703:Therapies, Investigational
D000890:Anti-Infective Agents