Research Article
Open access
Published Online: 8 June 2009

Combination Therapies for Traumatic Brain Injury: Prospective Considerations

Authors: Susan Margulies and Ramona Hicks on behalf of The Combination Therapies for Traumatic Brain Injury Workshop LeadersAuthors Info & Affiliations
Publication: Journal of Neurotrauma
Volume 26, Issue Number 6

Abstract

Traumatic brain injury (TBI) initiates a cascade of numerous pathophysiological events that evolve over time. Despite the complexity of TBI, research aimed at therapy development has almost exclusively focused on single therapies, all of which have failed in multicenter clinical trials. Therefore, in February 2008 the National Institute of Neurological Disorders and Stroke, with support from the National Institute of Child Health and Development, the National Heart, Lung, and Blood Institute, and the Department of Veterans Affairs, convened a workshop to discuss the opportunities and challenges of testing combination therapies for TBI. Workshop participants included clinicians and scientists from a variety of disciplines, institutions, and agencies. The objectives of the workshop were to: (1) identify the most promising combinations of therapies for TBI; (2) identify challenges of testing combination therapies in clinical and pre-clinical studies; and (3) propose research methodologies and study designs to overcome these challenges. Several promising combination therapies were discussed, but no one combination was identified as being the most promising. Rather, the general recommendation was to combine agents with complementary targets and effects (e.g., mechanisms and time-points), rather than focusing on a single target with multiple agents. In addition, it was recommended that clinical management guidelines be carefully considered when designing pre-clinical studies for therapeutic development. To overcome the challenges of testing combination therapies it was recommended that statisticians and the U.S. Food and Drug Administration be included in early discussions of experimental design. Furthermore, it was agreed that an efficient and validated screening platform for candidate therapeutics, sensitive and clinically relevant biomarkers and outcome measures, and standardization and data sharing across centers would greatly facilitate the development of successful combination therapies for TBI. Overall there was great enthusiasm for working collaboratively to act on these recommendations.

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Published In

cover image Journal of Neurotrauma
Journal of Neurotrauma
Volume 26Issue Number 6June 2009
Pages: 925 - 939
PubMed: 19331514

History

Published online: 8 June 2009
Published in print: June 2009
Published ahead of print: 20 May 2009

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Affiliations

Susan Margulies
University of Pennsylvania, Philadelphia, Pennsylvania.
Ramona Hicks on behalf of The Combination Therapies for Traumatic Brain Injury Workshop Leaders
National Institute of Neurological Disorders and Stroke, Bethesda, Maryland.

Notes

Address reprint requests to:
Susan Margulies, Ph.D.
Professor of Bioengineering
School of Engineering and Applied Science
Department of Bioengineering
University of Pennsylvania
240 Skirkanich Hall
210 S. 33rd Street
Philadelphia, PA 19104-6321
E-mail: [email protected]

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