The Traumatic Brain Injury Endpoints Development (TED) Initiative: Progress on a Public-Private Regulatory Collaboration To Accelerate Diagnosis and Treatment of Traumatic Brain Injury

Abstract

The Traumatic Brain Injury Endpoints Development (TED) Initiative is a 5-year, Department of Defense (DoD) funded project that is working toward the ultimate goal of developing better designed clinical trials, leading to more precise diagnosis, and effective treatments for traumatic brain injury (TBI). TED is comprised of leading academic clinician-scientists, along with innovative industry leaders in biotechnology and imaging technology, patient advocacy organizations, and philanthropists, working collaboratively with regulatory authorities, specifically the US Food and Drug Administration (FDA). The goals of the TED Initiative are to gain consensus and validation of TBI clinical outcome assessment measures and biomarkers for endorsement by global regulatory agencies for use in drug and device development processes. This manuscript summarizes the Initiative's Stage 1 progress over the first 18 months, including intensive engagement with a number of FDA divisions responsible for review and validation of biomarkers and clinical outcome assessments, progression into the prequalification phase of FDA's Medical Device Development Tool program for a candidate set of neuroimaging biomarkers, and receipt of FDA's Recognition of Research Importance Letter regarding TBI. Other signal achievements relate to the creation of the TED Metadataset, harmonizing study measures across eight major TBI studies, and the leadership role played by TED investigators in the conversion of the NINDS TBI Common Data Elements (CDEs) to Clinical Data Interchange Standards Consortium (CDISC) standards. This paper frames both the near-term expectations and the Initiative's long-term vision to accelerate approval of treatments for patients affected by TBI in urgent need of effective therapies.

Structural neuroimaging in mild traumatic brain injury: A chronic effects of neurotrauma consortium study

“…The fact that TIV and TBV did vary by site implies that measurement differences were influenced by the MR platform, yet the age and TIV or TBV relations showed similar relationships regardless of site. Hence, for correlational analyses, minor site differences likely have minimal to no effect on the correlation, and where site differences do exist, such differences likely represent a constant that could be statistically computed for harmonization of volumetric differences across sites (Manley et al, ; Nencka et al, ).…”

“…Colour online, B&W in print do exist, such differences likely represent a constant that could be statistically computed for harmonization of volumetric differences across sites (Manley et al, 2017;Nencka et al, 2017).…”

Outcome assessment after traumatic brain injury – Authors' reply

“…In the years following the discovery, similar phenotypes were mapped in patients with Parkinson's disease. 5 These phenotypes might correspond to different patterns of underlying neuronal loss, 6 which might also be the case in MPTPinduced parkinsonism. Alternatively, MPTP-induced brain lesions might be more or less the same, but the degree of compensation could differ between individuals.…”

“…However, we believe that the challenges need to be addressed if the field is to progress. 5 A 29% success rate in trials using the GOS or the GOSE is not a good track record, and the absence of positive findings is a widely recognised problem in clinical trials of TBI. Global outcome scales are likely to continue to have a central role, but there is a need for work on how multiple assessments can be included in clinical trials and combined to give a multidimensional description of outcome.…”

Editorial: Developing Successful Neuroprotective Treatments for TBI: Translational Approaches, Novel Directions, Opportunities and Challenges

“…As a consequence, investigations on mitochondrial dysfunction (14). Imaging and biofluid markers can, in fact, be instrumental in identifying and characterizing pathophysiologic mechanisms leading to more accurate and finer-grained disease classification which, in turn, may be used to enrich or stratify patient groups, to demonstrate target engagement, and/or as proof of treatment efficacy (14)(15)(16). These factors can play a transformative role in designing effective clinical trials, increasing treatment effectiveness as well as reducing healthcare costs (16)(17)(18).…”