• Patrick M Kochanek, C Edward Dixon, Stefania Mondello, WangKevin K KKKKProgram for Neuroproteomics and Biomarkers Research, Departments of Psychiatry, Neuroscience, and Chemistry, University of Florida, Gainesville, FL, United States., Audrey Lafrenaye, Helen M Bramlett, W Dalton Dietrich, Ronald L Hayes, Deborah A Shear, Janice S Gilsdorf, Michael Catania, Samuel M Poloyac, Philip E Empey, Travis C Jackson, and John T Povlishock.
• Safar Center for Resuscitation Research, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
• Front Neurol. 2018 Jan 1; 9: 640.

AbstractCurrent approaches have failed to yield success in the translation of neuroprotective therapies from the pre-clinical to the clinical arena for traumatic brain injury (TBI). Numerous explanations have been put forth in both the pre-clinical and clinical arenas. Operation Brain Trauma Therapy (OBTT), a pre-clinical therapy and biomarker screening consortium has, to date, evaluated 10 therapies and assessed three serum biomarkers in nearly 1,500 animals across three rat models and a micro pig model of TBI. OBTT provides a unique platform to exploit heterogeneity of TBI and execute the research needed to identify effective injury specific therapies toward precision medicine. It also represents one of the first multi-center pre-clinical consortia for TBI, and through its work has yielded insight into the challenges and opportunities of this approach. In this review, important concepts related to consortium infrastructure, modeling, therapy selection, dosing and target engagement, outcomes, analytical approaches, reproducibility, and standardization will be discussed, with a focus on strategies to embellish and improve the chances for future success. We also address issues spanning the continuum of care. Linking the findings of optimized pre-clinical consortia to novel clinical trial designs has great potential to help address the barriers in translation and produce successes in both therapy and biomarker development across the field of TBI and beyond.

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