Citation

Silverberg ND, Crane PK, Dams-O'connor K, Holdnack J, Ivins BJ, Lange RT, Manley GT, McCrea M, Iverson GL. J. Neurotrauma 2016; 34(2): 363-371.

Affiliation

Harvard Medical School, Red Sox Foundation and Massachusetts General Hospital Home Base Program, Boston, Massachusetts, United States ; giverson@mgh.harvard.edu.

Copyright

(Copyright © 2016, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2016.4443

PMID

27188248

Abstract

Cognitive impairment is a core clinical feature of traumatic brain injury (TBI). Following TBI, cognition is a key determinant of post-injury productivity, outcome, and quality of life. As a final common pathway of diverse molecular and microstructural TBI mechanisms, cognition is an ideal endpoint in clinical trials involving many candidate drugs and non-pharmacological interventions. Cognition can be reliably measured with performance-based neuropsychological tests that have greater granularity than crude rating scales, such as the Glasgow Outcome Scale-Extended, which remain the standard for clinical trials. Remarkably, however, there is no well-defined, widely accepted, and validated cognition endpoint for TBI clinical trials. A single cognition endpoint that has excellent measurement precision across a wide functional range, and is sensitive to the detection of small improvements (and declines) in cognitive functioning, would enhance the power and precision of TBI clinical trials and accelerate drug development research. In this article, we outline methodologies for deriving a cognition composite score and a research program for validation. Finally, we discuss regulatory issues and the limitations of a cognition endpoint.

Language: en