Pre-Clinical Testing of Therapies for Traumatic Brain Injury.

{"article_title":"Pre-Clinical Testing of Therapies for Traumatic Brain Injury.","author":"DeWitt DS, Hawkins BE, 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 DS, Robertson CS, Saatman KE, Shultz SR, Shear DA, Smith DH, Valadka AB, VandeVord P, Zhang L","journal_title":"Journal of neurotrauma","issn":"1557-9042","isbn":"","publication_date":"2018-12-01","volume":"35","issue":"23","first_page":"2737","page_count":"","accession_number":"29756522","doi":"10.1089\/neu.2018.5778","publisher":"Mary Ann Liebert","doctype":"Consensus Development Conference","subjects":"Brain Injuries, Traumatic therapy; Disease Models, Animal; Animals; Humans","interest_area":["Neurology"," Emergency Medicine"],"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.","url":"https:\/\/search.ebscohost.com\/login.aspx?direct=true&db=mdl&AN=29756522","isPdfLink":false,"isSAML":false,"an":"29756522","number_other":"","type_pub":"","issn_electronic":"1557-9042","languages":"English","language":"eng","date_entry":"Date Created: 20180515 Date Completed: 20191112 Latest Revision: 20220716","date_update":"20240104","titleSource":"Journal of neurotrauma [J Neurotrauma] 2018 Dec 01; Vol. 35 (23), pp. 2737-2754. Date of Electronic Publication: 2018 Aug 30.","date_pub_cy":"","type_document":"","contract_publisher":"","authored_on":"2018-12-01","description":"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.","upload_link":"https:\/\/search.ebscohost.com\/login.aspx?direct=true&site=eds-live&scope=site&db=mdl&AN=29756522&authtype=shib&custid=ns346513&group=main&profile=eds","no_of_pages":"","authored_by":"DeWitt DS, Hawkins BE, 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 DS, Robertson CS, Saatman KE, Shultz SR, Shear DA, Smith DH, Valadka AB, VandeVord P, Zhang L"}