TBI Endpoints Development Initiative

TBI Endpoints Development Initiative

TBI is a multifaceted condition, and as of 2015, no drug or device has been approved by the U.S. Food and Drug Administration (FDA) to treat acute TBI.  In collaboration with the FDA, TBI Endpoints Development (TED) researchers will examine existing datasets from thousands of athletes, soldiers and the broader population to identify which current measures are most effective, and validate these measures or “endpoints” of brain injury and recovery. The TED team is comprised of leading academic clinician-scientists, industry leaders in biotechnology and imaging technology, patient advocacy organizations, and philanthropies.The lead site is the University of California, San Francisco.

First among TED’s objectives (Stage I) is to establish a TED Metadataset consisting of integrated clinical outcomes, and imaging, proteomic, and genomic data, from ongoing and legacy TBI studies across civilian, military, and sports cohorts. This highly detailed and multi-scalar repository will be continuously curated and analyzed using conventional and novel methodologies. TED researchers aim to identify and validate meaningful TBI endpoints, as well as structural abnormalities that may be predictive of outcomes, making strides toward a new taxonomy for TBI.

Among other objectives (Stage II) TED will support the selection, funding, and oversight of four Seed Projects focused on validation of clinical outcome assessments (COAs) and blood-based and neuroimaging biomarkers. Creating a range of validated COAs, biomarkers, and devices will:

  • Permit more accurate disease/condition diagnosis
  • Identify patient subpopulations likely to benefit from therapy/intervention
  • Provide refined outcome assessments to confirm efficacy

Evidence-Based Clinical Outcome Assessment Platform (EB-COP)

The TED Government Steering Committee selected Spaulding Rehabilitation Hospital’s proposal for Evidence-Based Clinical Outcome Assessment Platform (EB-COP) as one of four awardees to receive funding for 1-year projects commencing in 2016.

The primary aim of EB-COP was to design, build, and pilot-test a semi-automated assessment platform to enable the efficient, transparent, systematic and context of use (COU)-specific grading of COAs to inform selection of suitable candidate measures for submission to the FDA. The Platform will also be disseminated to Investigators as a tool to help foster validation of existing COAs.

The EB-COP evaluates the strength of COAs using a six-step process that begins with the guided specification of the COU. The COA is ultimately graded using a four-tiered recommendation scheme based on the number of mandatory quality indicators appraised as adequate.

The team has pilot tested the EB-COP on the Glasgow Outcome Scale-Extended for the detection of treatment effects in patients with moderate/severe TBI of subacute duration. Results from this pilot test were presented to the Government Steering Committee on March 17, 2017 and at the Second TED Consensus Conference held on the NIH campus on April 4-5th, 2017. In collaboration with the American Academy of Neurology, the investigators are finalizing a Qualtrics software platform designed to semi-automate the COA review and grading process.

Read a complete description of the methodology, development, and evaluation of the findings from the EB-COP pilot-testing published here. Funded by the Department of Defense.

Primary Investigator: Dr. Joseph Giacino, PhD

For more information about the TED Initiative, click here.