Biomarkers for Traumatic Brain Injury: Data Standards and Statistical Considerations
J. Russell Huie, Stefania Mondello, Christopher J. Lindsell, Luca Antiga, Esther L. Yuh, Elisa R. Zanier, Serge Masson, Bedda L. Rosario, Adam R. Ferguson, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Yelena G. Bodien, M. Ross Bullock, Randall M. Chesnut, John D. Corrigan, Karen Crawford, Ramon Diaz‐Arrastia, Sureyya Dikmen, Ann-Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Brandon Foreman, Raquel C. Gardner, Etienne Gaudette, Joseph T. Giacino, Dana P. Goldman, Luis González, Shankar P. Gopinath, Rao P. Gullapalli, J. Claude Hemphill, Gillian Hotz, Sonia Jain, Frederick K. Korley, Joel H. Kramer, Natalie Kreitzer, Harvey S. Levin, Joan Machamer, Christopher Madden, Geoffrey T. Manley, Alastair J. Martin, Thomas W. McAllister, Michael McCrea, Randall E. Merchant, Pratik Mukherjee, Lindsay D. Nelson, Laura B. Ngwenya, Florence Noël, David O. Okonkwo, Eva, Daniel P. Perl, Ava M. Puccio, Miri Rabinowitz, Claudia S. Robertson, Jonathan Rosand, Angelle M. Sander, Gabriella, David M. Schnyer, Seth A. Seabury, Murray B. Stein, Sabrina R. Taylor, Nancy Temkin, Arthur W. Toga, Alex B. Valadka, Mary J. Vassar, Paul Vespa, Kevin Wang, John K. Yue, Ross Zafonte, Cecilia Ackerlund, Hadie Adams, Vanni Agnoletti, Judith Allanson, Krisztina Amrein, Norberto Andaluz, Nada Anđelić, Lasse Andreassen, Audny Anke, Azasevac Antun, Anna Antoni, Hilko Ardon, Kaspars Auslands, Philippe Azouvi, Maria Luisa Azzolini, Camelia Baciu, Rafael Badenes, Ronald Bartels, Pál Barzó, Ursula Bauerfeind, Romuald Beauvais, Ronny Beer, F. J. Belda, Bo Michael Bellander, Antonio Belli, Rémy Bellier, Habib Benali, Thierry Bénard, Maurizio Berardino, Luigi Beretta, Christopher Beynon
Abstract
Recent biomarker innovations hold potential for transforming diagnosis, prognostic modeling, and precision therapeutic targeting of traumatic brain injury (TBI). However, many biomarkers, including brain imaging, genomics, and proteomics, involve vast quantities of high-throughput and high-content data. Management, curation, analysis, and evidence synthesis of these data are not trivial tasks. In this review, we discuss data management concepts and statistical and data sharing strategies when dealing with biomarker data in the context of TBI research. We propose that application of biomarkers involves three distinct steps-discovery, evaluation, and evidence synthesis. First, complex/big data has to be reduced to useful data elements at the stage of biomarker discovery. Second, inferential statistical approaches must be applied to these biomarker data elements for assessment of biomarker clinical utility and validity. Last, synthesis of relevant research is required to support practice guidelines and enable health decisions informed by the highest quality, up-to-date evidence available. We focus our discussion around recent experiences from the International Traumatic Brain Injury Research (InTBIR) initiative, with a specific focus on four major clinical projects (Transforming Research and Clinical Knowledge in TBI, Collaborative European NeuroTrauma Effectiveness Research in TBI, Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe, and Approaches and Decisions in Acute Pediatric TBI Trial), which are currently enrolling subjects in North America and Europe. We discuss common data elements, data collection efforts, data-sharing opportunities, and challenges, as well as examine the statistical techniques required to realize successful adoption and use of biomarkers in the clinic as a foundation for precision medicine in TBI.