Why have recent trials of neuroprotective agents in head injury failed to show convincing efficacy? A pragmatic analysis and theoretical considerations.

An overview of the results of recent trials of neuroprotective agents in head injury is presented. None of the trials showed efficacy in the general population of patients with a severe head injury. A critical analysis of the possible reasons for this failure is given. Specific attention is focused on the heterogeneity of the patient population, the importance of baseline prognostic indicators, and the problems caused by the distribution of outcome and the dichotomization of these outcomes in the Glasgow Outcome Scale. Recommendations are presented for consideration in the design and analysis of future trials in head injury.