A-093 Clinical Performance of Biomarkers for Traumatic Brain Injury

Abstract

Abstract Background An estimated 5 million people are evaluated in emergency departments (ED) for Traumatic Brain Injury (TBI) in the United States each year. The vast majority (80%) of patients evaluated for TBI in the ED will receive head CT scans, however less than 10% of those will have any findings of acute traumatic abnormalities. This highlights the need for objective, rapid, accurate tools to help clinicians evaluate and triage TBI patients and reduce unnecessary radiation exposure. The Alinity i TBI test is a panel of in vitro diagnostic chemiluminescent microparticle immunoassays used to measure glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) in human plasma and serum. TBI performance was evaluated in a multi-center study by performing reproducibility and a pivotal study. Methods A pivotal study using prospectively collected archived (frozen) plasma specimens was conducted to establish the clinical performance of the TBI test on the Alinity i system. The testing of the archived specimens was performed at three clinical sites in the United States. The specimens tested were originally collected in a prospective, multi-center clinical study and were from individuals 18 years of age or older who presented to a health care facility or emergency department with suspected traumatic brain injury. These subjects had an initial Glasgow Coma Scale (GCS) score of 13–15 and had a computed tomography (CT) scan of the head performed per the clinical site’s standard of care. Reproducibility was assessed using multiple panel/control members for 5 days based on guidance from Clinical and Laboratory Standards Institute EP05-A3. Testing was conducted using 3 lots of GFAP and UCH-L1 reagents, and 1 Alinity i system at each of 3 testing sites. Results Of the 1899 mild TBI subjects, 120 had positive head CT scan results; 116 of the 120 specimens had a positive TBI interpretation (Sensitivity 96.7%;95%CI:91.7%,98.7%). Of the 1779 subjects with negative CT scan results, 713 had a negative TBI interpretation (Specificity 40.1%;95%CI:37.8%,42.4%). The negative predictive value (NPV) of the test was 99.4% (713/717, 95%CI:98.6%,99.8%). Within-Laboratory imprecision (includes repeatability, between-run, and between-day variance components) results ranged from 2.2% to 3.5% CV for GFAP and 1.8 to 3.2 %CV for UCH-L1. The Overall Reproducibility (includes repeatability, between-run, between-day, between-lot, between-site, and site-lot interaction variance components) results ranged from 2.5% to 4.7% CV for GFAP and 2.6 to 6.6 %CV for UCH-L1. Conclusion The Alinity i TBI clinical performance results demonstrated that the TBI test is characterized by high sensitivity and high NPV, which supports the clinical utility to assist in determining the need for a CT scan of the head in subjects presenting with suspected mild TBI. The GFAP and UCH-L1 assays demonstrated acceptable reproducibility across a wide dynamic range. These assays can report results within 18 min and be conveniently loaded into the Electronic Health Records to aid clinicians in their triage (or imaging) decisions. Funding The study was funded by Abbott Laboratories and in collaboration with the US Army Medical Materiel Development Activity, US Army Medical Research and Development Command CRADA 20-1266-CRA.