FDA-Approved TBI Blood Biomarker Devices Exist but Face Systemic Barriers to Clinical Adoption

In April 2024, the FDA approved the first whole-blood traumatic brain injury (TBI) biomarker device capable of producing results at a patient's bedside — on ambulances, sports sidelines, or battlefields. This should have been a breakthrough: blood-based biomarkers can detect TBI presence and severity, potentially replacing or reducing reliance on expensive CT scans. But the devices are not being adopted in clinical practice. Medicare requires clinical utility studies demonstrating improved health outcomes that don't yet exist. Commercial insurers apply even more rigorous standards. "Mild TBI" lacks a single diagnostic code, making payer navigation difficult. And the biomarkers themselves have reduced specificity in older adults — the fastest-growing TBI population — because age-specific and sex-specific reference ranges have not been established. The result is a technology that works, has regulatory approval, but cannot reach patients.

TBI is a leading cause of morbidity and mortality in the United States, with over 2.8 million emergency department visits annually. The current diagnostic standard — the Glasgow Coma Scale plus CT imaging — is decades old, misses many injuries, and provides no biological information about injury severity or recovery trajectory. Point-of-care blood biomarkers could enable faster triage (critical in military and sports settings), reduce unnecessary CT scans (each costing $1,000–3,000 and exposing patients to radiation), and inform treatment decisions in real time. The Department of Defense specifically highlighted the need to close the 17-year average gap between scientific advance and clinical integration. For a country investing heavily in TBI research through DoD and NIH, having approved devices sitting unused represents a failure of the innovation pipeline at the last mile.

The biomarker science itself was successful — two protein markers (UCH-L1 and GFAP) were developed into commercially available devices with FDA clearance. But clinical utility studies (demonstrating that using the biomarker actually improves patient outcomes, not just that it detects a condition) have not been completed because they require large, multi-site, prospective trials that are expensive and logistically complex. Payer engagement was not built into the development process, so the evidence that insurers require was not generated alongside the device approval. Older adults were systematically excluded from clinical trials, leaving the age group most vulnerable to TBI without validated reference values. Meanwhile, research on multimodal integration — combining biomarkers with neuroimaging and clinical assessment — remains siloed: biomarker developers, imaging researchers, and clinicians operate in separate communities with different methods and publication venues. The diagnostic coding problem persists because "mild TBI" encompasses a heterogeneous range of injuries that the current coding system cannot differentiate.

A clinical utility framework designed for diagnostic biomarkers that satisfies both FDA and payer requirements simultaneously — preventing the current gap where devices are approved but uncovered. Age- and sex-specific biomarker reference ranges established through inclusive clinical trials. A multimodal data integration framework that combines blood biomarkers, advanced neuroimaging, wearable sensor data, and clinical assessment into a unified TBI classification system (the NINDS has convened working groups for this but work is early). Streamlined diagnostic codes that capture TBI subtypes with enough granularity for targeted treatment and payer navigation. The adjacent field of cardiac biomarkers (troponin adoption for heart attack diagnosis) offers a model for how point-of-care blood tests can transform emergency diagnosis — but that transition took decades.

A team could design a decision-support tool that maps existing TBI biomarker evidence against specific payer coverage criteria, identifying exactly which clinical utility data is missing and proposing a minimum viable study design to fill those gaps. This would be a health systems/policy design project. Alternatively, a team with biomedical engineering skills could prototype a low-cost microfluidic reader for TBI biomarkers aimed at resource-limited settings (rural emergency departments, military field hospitals) where CT scanners are unavailable, focusing on the interface design and workflow integration challenges rather than the assay chemistry itself.