According to the CDC, in the U.S. over 2.8M emergency department visits are associated with Traumatic Brain Injury (TBI) each year, and over 288,000 result in patients' hospitalization. TBI ranges in degree, with over 75% of these injuries classified as mild TBI (mTBI), also referred to as concussions. The clinical diagnosis of TBI and its severity remains challenging. Physicians often resort to Computed Tomography (CT) scans to detect brain tissue damage or intracranial lesions, and diagnose TBI. However, the majority of these scans are negative, as mTBI rarely results in detectable lesions. As such, of the 1.5 million head CT scans performed every year on possible TBI patients, as many as 80% are unnecessary. CT scans carry significant radiation exposure, increasing the risk of radiation-induced cancer and economic burden. The prompt and accurate triage of patients that should or should not receive a CT scan remains a major medical challenge. This SBIR Phase I proposal aims to develop and validate a point-of-care blood based diagnostic device for triaging and managing patients presenting with head injury. The device, the pScreen- TBI, leverages Accel Diagnostics' innovative and patented detection technology to accurately quantify the level of two key biomarkers, known as UCH-L1 and GFAP. The use of these biomarkers were recently cleared by the FDA to aid the evaluation of which patients affected by head injuries should be CT scanned. The FDA decision is supported by numerous studies that showed that elevated levels of these biomarkers have 99.7% sensitivity in determining which patients have lesions visible on a CT scans and those which not with a 99.6% NPV (negative predictive value). The pScreen-TBI incorporates, for the first time, the predictive power of these biomarkers in a disposable, easy to use, and economic tool that delivers a rapid and sensitive readout in an emergency and Point-of-Care setting. The device has clear utility for athletic and battlefield injuries and motor vehicle accidents. First responders can use the device to make decisions on patient need to be CT scanned, routing critical information to clinicians while en route to the hospital via the connected smart-phone application. Phase I efforts will focus on developing, optimizing, and validating a functional prototype for the parallel quantification of UCH-L1 and GFAP from a single finger-stick blood sample. Specifically, we will completed two Specific Aims: Aim 1) design and fabricate the dual-plex platform, select the optimal pair of capture and detection antibodies, and optimize reaction components for each biomarker; and Aim 2) conduct a comparative pre-clinical validation study against a gold- standard, high-sensitivity lab-assay (ELISA) using human blood samples. The proposed project is supported by extensive preliminary data, and a multi-disciplinary team bringing industry and academia together, and including a biochemist, a physicist, two assay development scientist, a neurosurgeon, a TBI biomarker discovery expert, a neuroscientist, and the support of two of the Nation's leading TBI experts, Dr. B. Omalu (inspiration for the movie Concussion), and Dr. J. Maroon (team neurosurgeon of the Pittsburgh Steelers). In summary this Phase I addresses an unmet clinical need with significant commercial opportunity. The successful development of this technology could minimize diagnostic uncertainty and eliminating unnecessary procedures, leading directly to better overall health outcomes and reduce costs.
Public Health Relevance Statement: Project Narrative Accel Diagnostics is proposing the development of an innovative blood diagnostic test to aid the triage of patients presenting with head injury. Accel Diagnostics' technology could transform how such injuries are handled in an emergency setting, resulting in significantly improved short- and long- term health outcomes. Furthermore, this easy use, rapid, and affordable device would eliminate millions of unnecessary Computed Tomography (CT) scans, reducing the risk of radiation-induced cancers for million of patients and saving hundred of millions of dollars each year in avoidable medical expenses. !
Project Terms: Academia; Accident and Emergency department; Accounting; Address; Affect; Antibodies; assay development; Athletic; base; Biological Assay; Biological Markers; biomarker discovery; Blood; Blood specimen; Blood Tests; Brain; Brain Concussion; brain tissue; Breathing; Cancer Burden; Caring; Centers for Disease Control and Prevention (U.S.); Cessation of life; Clinical; clinical Diagnosis; clinical implementation; Code; Collaborations; comparative; Complex; cost; Craniocerebral Trauma; Data; Decision Making; design; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic tests; Drops; Economic Burden; Economics; Elements; Emergency Department Physician; Emergency department visit; emergency settings; Emergency Situation; Enzyme-Linked Immunosorbent Assay; Evaluation; Fingers; first responder; Glial Fibrillary Acidic Protein; Gold; Head; Health; Healthcare; Home environment; Hospitalization; Hospitals; Hour; Human; Image; improved; In Vitro; Industry; Injury; innovation; Intuition; Laboratories; Legal patent; Lesion; Light; Location; Marketing; Medical; microfluidic technology; mid-career faculty; mild traumatic brain injury; mobile application; motor vehicle injury; movie; Multi-Institutional Clinical Trial; multidisciplinary; Neurobiology; Neurology; Neurosurgeon; Outcome; Patient Triage; Patients; Phase; Physicians; point of care; pre-clinical; Predictive Value; professor; programs; prototype; Radiation exposure; radiation risk; Radiation-Induced Cancer; Reaction; Recommendation; Recording of previous events; Resort; Risk; Route; Savings; Scanning; Scientist; Severities; Small Business Innovation Research Grant; smartphone Application; Sports; Steel; Stream; System; Technology; technology development; Test Result; Testing; Time; tool; Traumatic Brain Injury; Triage; Uncertainty; Universities; Unnecessary Procedures; Validation; validation studies; Work; X-Ray Computed Tomography
