Drotrecogin alfa (activated) a sad final fizzle to a roller-coaster party.docVIP

Angus Critical Care 2012,16:107 /content/16/1/107 CO MMENTA RY Drotrecogin alfa (activated) … a sad ? nal ? zzle to a roller-coaster party Derek C Angus* failure of PROWESS-SHOCK, a large international study, Following the failure of PROWESS-SHOCK to demonstrate e?cacy, Eli Lilly and Company withdrew drotrecogin alfa (activated) from the worldwide market. Drotrecogin was initially approved after the original trial, PROWESS, was stopped early for overwhelming e?cacy. These events prompt consideration of both the initial approval decision and the later decision to withdraw. It is regrettable that the initial decision to con? rm the bene? t reported from the original trial, PROWESS (Protein C Worldwide Evaluation in Severe Sepsis), 10 years ago. In the aftermath, many questions will be raised. Here, I discuss two initial questions. Before proceeding, I should declare that I led the long-term follow-up and cost-e? ectiveness studies accompanying PROWESS and served on the Data Safety and Monitoring Board of PROWESS-SHOCK (see Acknowledgments for was made largely on a single trial that was stopped early. However, the decision to approve was within full disclosure). the bounds of normal regulatory practice and was made by many approval bodies around the world. Furthermore, the overall withdrawal rate of approved drugs remains very low. The decision to withdraw was a voluntary decision by Eli Lilly and Company and likely re?ected key business considerations. Drotrecogin does have important biologic e?ects, and it is probable that we do not know how best to select patients who would bene?t. Overall, there may still be a small advantage to drotrecogin alfa, even used non- selectively, but the costs of determining such an e?ect with adequate certainty are likely prohibitive, and the point is now moot. In the future, we should consider ways to make clinical trials easier and quicker so that more information can be available in a tim