Challenges to effective research in acute trauma resuscitation: consent and endpoints

Selection of study endpoints is one of the most important decisions in the design of effective clinical trials. Late mortality (e.g., 28 days) is an unambiguous endpoint, accepted by regulatory agencies, but it is viewed as problematic among researchers in the study of resuscitation for acute trauma injury with hemorrhagic shock. In February 2008, physicians, ethicists, statisticians, and research scientists from the military, academia, industry, the Federal Drug Administration, and the National Heart Lung and Blood Institute gathered to discuss the obstacles confronting the trauma community in their efforts to improve patient outcomes. The primary meeting objective was to generate preliminary suggestions for a series of follow-up meetings that will develop consensus guidelines for the design of large multicenter clinical trials. Twenty short presentations and discussions, summarized here, outlined the group's concerns and suggestions. Successful and failed, completed or ongoing, clinical studies provided insight as to endpoints that may be of value for future trauma and shock studies. In addition to the importance of appropriate endpoints in study design, other related topics were discussed, including trauma epidemiology, patient enrollment and inclusion criteria, community consultation and the difficulty of obtaining informed consent in acute trauma research, and the inclusion of quality of life in composite endpoints. The consensus was that more discussion was needed and that consideration of new endpoints for clinical trials in emergency trauma research was a worthwhile and necessary goal.