Prospective Harmonization, Common Data Elements, and Sharing Strategies for Multicenter Pre-Clinical Traumatic Brain Injury Research in the Translational Outcomes Project in Neurotrauma Consortium.

Abstract

Effective team science requires procedural harmonization for rigor and reproducibility. Multicenter studies across experimental modalities (domains) can help accelerate translation. The Translational Outcomes Project in NeuroTrauma (TOP-NT) is a pre-clinical traumatic brain injury (TBI) consortium charged with establishing and validating noninvasive TBI assessment tools through team science. Here, we present practical approaches for harmonization of TBI research across five centers providing needed vocabulary and structure to achieve centralized data organization and use. This includes data sharing as an essential step that enables validating data between domains, evaluating reproducibility between sites, and performing multimodal analyses. As part of this process, TOP-NT (1) produced a library of TBI-relevant standard operating procedures to coordinate workflow, (2) aligned 481 pre-clinical and clinical common data elements (CDEs), and (3) generated 272 new pre-clinical TBI CDEs. This consortium then (4) connected diverse data types to validate assessments across domains and to allow multivariable TBI phenotyping. Lastly, TOP-NT (5) specified technical quality controls for pre-clinical studies. These harmonization tools can facilitate reproducibility in team science, help distinguish a wide injury spectrum from technical variability, apply quality-controls, and ease higher level data analyses. TOP-NT uses three rat TBI models across four sites. Each site collects primary outcome measures, including magnetic resonance imaging (MRI) protocols and blood biomarkers of neuronal and glial injury, validated by histopathology and behavioral outcomes. Collected data are organized using the 481 TOP-NT pre-clinical CDEs, covering surgical, behavioral, biomarker, MRI, and quantitative histopathological methods. We report data curation steps suited for data storage using the Open Data Commons for TBI as a centralized data repository, allowing unbiased cross-site analysis. This approach leads to introducing a higher level, syndromic understanding of TBI signatures. TOP-NT authors outline a semantic and structural framework suggesting strategies for robust pre-clinical research in multicenter trials to improve translatability for TBI assessments. [Figure: see text].