Combination therapies for traumatic brain injury: prospective considerations

Abstract

Traumatic brain injury (TBI) initiates a cascade of numerous pathophysiological events that evolve over time.Despite the complexity of TBI, research aimed at therapy development has almost exclusively focused on single therapies, all of which have failed in multicenter clinical trials.Therefore, in February 2008 the National Institute of Neurological Disorders and Stroke, with support from the National Institute of Child Health and Development, the National Heart, Lung, and Blood Institute, and the Department of Veterans Affairs, convened a workshop to discuss the opportunities and challenges of testing combination therapies for TBI.Workshop participants included clinicians and scientists from a variety of disciplines, institutions, and agencies.The objectives of the workshop were to: (1) identify the most promising combinations of therapies for TBI; (2) identify challenges of testing combination therapies in clinical and pre-clinical studies; and (3) propose research methodologies and study designs to overcome these challenges.Several promising combination therapies were discussed, but no one combination was identified as being the most promising.Rather, the general recommendation was to combine agents with complementary targets and effects (e.g., mechanisms and time-points), rather than focusing on a single target with multiple agents.In addition, it was recommended that clinical management guidelines be carefully considered when designing pre-clinical studies for therapeut…