Translational Outcomes Project in Neurotrauma (TOP-NT) Pre-Clinical Consortium Study: A Synopsis.

Traumatic brain injury (TBI) has long been a leading cause of death and disability, yet research has failed to successfully translate findings from the pre-clinical, animal setting into the clinic. One factor that contributes significantly to this struggle is the heterogeneity observed in the clinical setting where patients present with injuries of varying types, severities, and comorbidities. Modeling this highly varied population in the laboratory remains challenging. Given feasibility constraints, individual laboratories often focus on single injury types and are limited to an abridged set of outcome measures. Furthermore, laboratories tend to use different injury or outcome methodologies from one another, making it difficult to compare studies and identify which pre-clinical findings may be best suited for clinical translation. The NINDS-funded Translational Outcomes Project in Neurotrauma (TOP-NT) is a multi-site consortium designed to address the reproducibility, rigor, and transparency of pre-clinical development and validation of clinically relevant biomarkers for TBI. The current overview article provides a detailed description of the infrastructure and strategic approach undertaken by the consortium. We outline the TOP-NT strategy to address three goals: (1) selection and cross-center validation of biomarker tools, (2) development and population of a data infrastructure to allow for the sharing and reuse of pre-clinical, animal research following findable, accessible, interoperable, and reusable data guidelines, and (3) demonstration of feasibility, reproducibility, and transparency in conducting a multi-center, pre-clinical research trial for TBI biomarker development. The synthesized scientific analysis and results of the TOP-NT efforts will be the topic of future articles.