Posted December 22, 2015
Geoffrey Manley, M.D., Ph.D., University of California, San Francisco
In the past twenty years, there have been no new drugs or devices approved by the Food and Drug Administration (FDA) that facilitate the diagnosis or treatment of acute traumatic brain injuries (TBIs). The DoD's Combat Casualty Care Research Program (CCCRP)/JPC-6 has long been focused on furthering research with an emphasis on preventing and treating TBI, and has recently turned its focus toward the most effective means of advancing research that will generate successful endpoints in the battle against TBI. In 2013, the program offered the TBI Endpoints Development (TED) Award mechanism, with the intent of fostering collaborative and multidisciplinary research to improve diagnosis and treatment of mild to moderate TBI.
The project, directed by Dr. Geoffrey Manley, of UCSF, aims to identify clinical outcome assessments (COAs) and biomarkers that may eventually be accepted as endpoints by FDA for clinical trials of therapeutic drugs or devices, and potentially be qualified by the FDA as drug development tools (DDTs) for future TBI trials. A multidisciplinary team has begun to employ its diverse areas of expertise to closely evaluate metrics of TBI diagnosis and how the condition progresses, with the aim of improving the design of clinical trials that will ultimately yield the first successful treatments of acute TBI.
The TED team is currently compiling a Metadataset of TBI COA and biomarker databases by bringing together existing TBI consortia, including the NINDS-funded TRACK-TBI Consortium (Transforming Research and Clinical Knowledge in TBI, U01 NS086090), TRACK's Pilot study, and the Concussion Research Consortium, to name several. Since the start of funding one year ago, the group has also successfully established Expert Working Groups (EWGs), which will organize the analyses of the TED Metadataset, independent TBI studies, review existing TBI COA and biomarker literature, and create review processes to assess existing COAs and biomarkers for FDA regulatory readiness guidelines.
In early 2016, the TED project will award "seed projects" meant to identify and validate endpoints for diagnostic and therapeutic trials of TBI. The team then plans to use the Metadataset to validate the most promising candidate COAs and biomarkers identified by these seed projects. The validated COAs and biomarkers that appear most likely to progress will be collaboratively evaluated with FDA.
By the time the TED project draws to completion in 2019, it will have validated diagnostic endpoints that could improve diagnosis of TBI at the point of injury and will impact decision making on fitness and recovery post-injury. The identification of new therapeutic endpoints may facilitate ongoing trials working to improve outcome of individuals suffering from TBI and its after-effects. This application of expert knowledge and use of data generated by such a broad, multidisciplinary range of TBI research projects and investigators is the most promising opportunity thus far to develop tools that can be used to diagnose and treat TBI-improving the outcomes for the millions of military and civilian personnel who suffer TBIs annually.