Pre-clinical testing of therapies for traumatic brain injury

Douglas Dewitt, Bridget Hawkins, C. Edward Dixon, Patrick M. Kochanek, William Armstead, Cameron R. Bass, Helen M. Bramlett, Andras Buki, W. Dalton Dietrich, Adam R. Ferguson, Edward D. Hall, Ronald L. Hayes, Sidney R. Hinds, Michelle C. Laplaca, Joseph B. Long, David F. Meaney, Stefania Mondello, Linda J. Noble-Haeusslein, Samuel M. Poloyac, Donald Prough & 8 others Claudia S. Robertson, Kathryn E. Saatman, Sandy R. Shultz, Deborah A. Shear, Douglas H. Smith, Alex B. Valadka, Pamela Vandevord, Liying Zhang

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Despite the large number of promising neuroprotective agents identified in experimental traumatic brain injury (TBI) studies, none has yet shown meaningful improvements in long-term outcome in clinical trials. To develop recommendations and guidelines for pre-clinical testing of pharmacological or biological therapies for TBI, the Moody Project for Translational Traumatic Brain Injury Research hosted a symposium attended by investigators with extensive experience in pre-clinical TBI testing. The symposium participants discussed issues related to pre-clinical TBI testing including experimental models, therapy and outcome selection, study design, data analysis, and dissemination. Consensus recommendations included the creation of a manual of standard operating procedures with sufficiently detailed descriptions of modeling and outcome measurement procedures to permit replication. The importance of the selection of clinically relevant outcome variables, especially related to behavior testing, was noted. Considering the heterogeneous nature of human TBI, evidence of therapeutic efficacy in multiple, diverse (e.g., diffuse vs. focused) rodent models and a species with a gyrencephalic brain prior to clinical testing was encouraged. Basing drug doses, times, and routes of administration on pharmacokinetic and pharmacodynamic data in the test species was recommended. Symposium participants agreed that the publication of negative results would reduce costly and unnecessary duplication of unsuccessful experiments. Although some of the recommendations are more relevant to multi-center, multi-investigator collaborations, most are applicable to pre-clinical therapy testing in general. The goal of these consensus guidelines is to increase the likelihood that therapies that improve outcomes in pre-clinical studies will also improve outcomes in TBI patients.

Original languageEnglish (US)
Pages (from-to)2737-2754
Number of pages18
JournalJournal of Neurotrauma
Volume35
Issue number23
DOIs
StatePublished - Dec 1 2018

Fingerprint

Therapeutics
Consensus
Research Personnel
Guidelines
Investigational Therapies
Biological Therapy
Neuroprotective Agents
Traumatic Brain Injury
Publications
Rodentia
Theoretical Models
Pharmacokinetics
Outcome Assessment (Health Care)
Clinical Trials
Pharmacology
Brain
Research
Pharmaceutical Preparations
Clinical Studies

Keywords

  • guidelines
  • pre-clinical
  • traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Dewitt, D., Hawkins, B., Dixon, C. E., Kochanek, P. M., Armstead, W., Bass, C. R., ... Zhang, L. (2018). Pre-clinical testing of therapies for traumatic brain injury. Journal of Neurotrauma, 35(23), 2737-2754. https://doi.org/10.1089/neu.2018.5778

Pre-clinical testing of therapies for traumatic brain injury. / Dewitt, Douglas; Hawkins, Bridget; Dixon, C. Edward; Kochanek, Patrick M.; Armstead, William; Bass, Cameron R.; Bramlett, Helen M.; Buki, Andras; Dietrich, W. Dalton; Ferguson, Adam R.; Hall, Edward D.; Hayes, Ronald L.; Hinds, Sidney R.; Laplaca, Michelle C.; Long, Joseph B.; Meaney, David F.; Mondello, Stefania; Noble-Haeusslein, Linda J.; Poloyac, Samuel M.; Prough, Donald; Robertson, Claudia S.; Saatman, Kathryn E.; Shultz, Sandy R.; Shear, Deborah A.; Smith, Douglas H.; Valadka, Alex B.; Vandevord, Pamela; Zhang, Liying.

In: Journal of Neurotrauma, Vol. 35, No. 23, 01.12.2018, p. 2737-2754.

Research output: Contribution to journalArticle

Dewitt, D, Hawkins, B, Dixon, CE, Kochanek, PM, Armstead, W, Bass, CR, Bramlett, HM, Buki, A, Dietrich, WD, Ferguson, AR, Hall, ED, Hayes, RL, Hinds, SR, Laplaca, MC, Long, JB, Meaney, DF, Mondello, S, Noble-Haeusslein, LJ, Poloyac, SM, Prough, D, Robertson, CS, Saatman, KE, Shultz, SR, Shear, DA, Smith, DH, Valadka, AB, Vandevord, P & Zhang, L 2018, 'Pre-clinical testing of therapies for traumatic brain injury', Journal of Neurotrauma, vol. 35, no. 23, pp. 2737-2754. https://doi.org/10.1089/neu.2018.5778
Dewitt, Douglas ; Hawkins, Bridget ; Dixon, C. Edward ; Kochanek, Patrick M. ; Armstead, William ; Bass, Cameron R. ; Bramlett, Helen M. ; Buki, Andras ; Dietrich, W. Dalton ; Ferguson, Adam R. ; Hall, Edward D. ; Hayes, Ronald L. ; Hinds, Sidney R. ; Laplaca, Michelle C. ; Long, Joseph B. ; Meaney, David F. ; Mondello, Stefania ; Noble-Haeusslein, Linda J. ; Poloyac, Samuel M. ; Prough, Donald ; Robertson, Claudia S. ; Saatman, Kathryn E. ; Shultz, Sandy R. ; Shear, Deborah A. ; Smith, Douglas H. ; Valadka, Alex B. ; Vandevord, Pamela ; Zhang, Liying. / Pre-clinical testing of therapies for traumatic brain injury. In: Journal of Neurotrauma. 2018 ; Vol. 35, No. 23. pp. 2737-2754.
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