Blood-based traumatic brain injury biomarkers – Clinical utilities and regulatory pathways in the United States, Europe and Canada

ABSTRACT

Introduction

Traumatic brain injury (TBI) is a major global health issue, resulting in debilitating consequences to families, communities, and health-care systems. Prior research has found that biomarkers aid in the pathophysiological characterization and diagnosis of TBI. Significantly, the FDA has recently cleared both a bench-top assay and a rapid point-of-care assays of tandem biomarker (UCH-L1/GFAP)-based blood test to aid in the diagnosis mTBI patients. With the global necessity of TBI biomarkers research, several major consortium multicenter observational studies with biosample collection and biomarker analysis have been created in the USA, Europe, and Canada. As each geographical region regulates its data and findings, the International Initiative for Traumatic Brain Injury Research (InTBIR) was formed to facilitate data integration and dissemination across these consortia.

Areas Covered

This paper covers heavily investigated TBI biomarkers and emerging non-protein markers. Finally, we analyze the regulatory pathways for converting promising TBI biomarkers into approved in-vitro diagnostic tests in the United States, European Union, and Canada.

Expert Opinion

TBI biomarker research has significantly advanced in the last decade. The recent approval of an iSTAT point of care test to detect mild TBI has paved the way for future biomarker clearance and appropriate clinical use across the globe.

KEYWORDS:

• Biomarkers
• regulatory pathways
• traumatic brain injury
• point of care
• consortiums

Article Highlights

• Surveys the major multicenter TBI consortia observational studies with biofluid collection and biomarker analysis component, including key studies in The United States, Europe, and Canada.

• Discusses the complexities and differences among the regulatory pathways in The United States, Europe, and Canada, for second-generation TBI-biomarker-based in vitro-diagnostics.

• Reviews the recent FDA approvals of UCH-L1/GFAP-based blood-test for TBI in accurately detecting Computerized Cranial Tomography (CCT) abnormalities and highlights an iSTAT Point of Care (POC) test and its clinical utilities.

• Establishes the various context of use of TBI biomarkers as POC diagnostic to predict clinical outcome, identify disease sequela, guide patient management, and therapy development.

Acknowledgments

The authors also thank One-Mind for supporting the InTBIR and Ramona Hicks of One-Mind for reviewing this manuscript and making helpful suggestions.

Declaration of interest

KK Wang is a shareholder of Gryphon Bio Inc. and Banyan Biomarkers Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary materials

Supplemental data for this article can be accessed here.

Additional information

Funding

This study is supported in part by NIH 1U01 NS086090-01 (KKW, RDA), DOD Grant W81XWH-14-2-0176 (KKW, RDA), DOD Grant W81XWH-13-1-04 (KKW, RDA), European Commission Framework Program 7, FP7-HEALTH-2013-INNOVATION-1 grant # 602150-2; (KKW). This material is also based upon work supported by the U.S. Army Medical Research and Material Command, from the U.S. Department of Veterans Affairs Long-term Impact of Military-related Brain Injury Consortium/Chronic Effects of Neurotrauma Consortium under Award No. 1I01CX002097-01 and the U.S Department of Defense under Award No. W81XWH-18-PH/TBIRP-LIMBIC. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick Md 21702-5014 is the awarding and administering acquisition office.