What should we learn from the failure of an activated protein C?

Abstract

A recombinant human activated protein C had been used for the treatment of severe sepsis and septic shock but was withdrawn from the global market because no survival benefit has been shown according to the findings of a recent randomized controlled trial following a decade of extensive controversy concerning its safety and effectiveness. The original large phase III trial published in 2001 was funded by Eli Lilly and Company, the manufacturer of the drug, and was criticized for a problematic protocol amendment, an early termination for benefit and interpretation of abundant subgroup analyses. The company also financially supported the Surviving Sepsis Campaign and caused those conflict-of-interest issues. Controversy remains over the successful administration in critical care in Japan and it is important to learn how to practice the evidence-based medicine from the failure of this drug.