The Problem

Traumatic Brain Injury (TBI) is a condition, not a one-time event. Effective treatment of TBI represents a great unmet need in public health. In 2013, approximately 2.8 million TBI-related emergency department visits, hospitalizations, and deaths occurred in the United States. TBI is a contributing factor in a third of all injury-related US deaths. An estimated 3.2 to 5.3 million people live with the long-term physical, cognitive, and psychological health disabilities of TBI, with annual direct and indirect costs estimated at over $76 billion. Although we are gaining ground in our understanding of the pathophysiology of TBI, these advances have failed to translate into a single successful clinical trial or treatment for acute TBI.

Effective treatment options to reduce mortality and prevent long-term morbidity caused by TBI are lacking in both military and civilian medicine. Over 30 clinical trials for TBI have failed, due in part to inadequate patient phenotyping for targeted therapy, lack of objective diagnostic and prognostic TBI biomarkers, and blunt approaches to outcome measurement. This has prompted the call for a paradigm shift in the design of TBI Phase 2 trials. Specifically, Department of Defense (DOD) and NIH workshops advise that Phase 2 TBI trials should: 1) target specific mechanisms of injury, 2) include validated prognostic and predictive biomarkers to stratify patients to enrich trial cohorts, and 3) utilize more precise outcome measures to capture relevant endpoints of pharmacologic targets.