A-090 Performance of GFAP and UCH-L1 Biomarkers for Traumatic Brain Injury in the ARCHITECT i1000SR TBI Test
Authors: Al Sahouri Z , Datwyler S A , Moore M K , West D R , Syed H N , Grasso K B , Yen J L , Chandran R L , Marino J A , Caudle K L , McQuiston B 
Published: October 2024

Abstract

Background
Traumatic Brain Injury (TBI) has been recognized as an important cause of death and disability and is a growing public health problem. An estimated 69 million people globally experience a TBI annually. The vast majority (80%) of patients evaluated for TBI in the Emergency Department will receive head CT scans, however less than 10% will have findings of acute traumatic abnormalities. This highlights the need for objective, rapid, accurate tools to help clinicians evaluate and triage patients with suspected TBI and reduce unnecessary radiation exposure. Blood based biomarkers such as glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) have shown utility to predict acute traumatic intracranial injury on CT scan after TBI.

Methods
The ARCHITECT TBI test is a panel of in vitro diagnostic chemiluminescent microparticle immunoassays for the measurement of GFAP and UCH-L1 in plasma and serum. A method comparison study was performed to compare the GFAP and UCH-L1 assays on ARCHITECT i1000SR to the FDA cleared Alinity i assays. Performance characteristics such as detection limits, imprecision, linearity, and measuring interval were established following CLSI guidance.

Results
The analytical measuring interval (AMI) extends from the limit of quantitation (LoQ) to the upper LoQ and is determined by the range that demonstrates acceptable performance for linearity, imprecision, and bias. The AMI is 6.1 to 42,000 pg/mL for GFAP and 26.3 to 25,000 pg/mL for UCH-L1. Within-laboratory imprecision ranged from 2.2 to 6.2% CV for GFAP and 2.2 to 4.5% CV for UCH-L1. The Overall Reproducibility (includes repeatability, between-run, between-day, between-instrument variance components) results ranged from 2.7 to 6.8% CV for GFAP and 2.4 to 3.9 %CV for UCH-L1. The method comparison study evaluated 123 specimens across the range of 6.5-32,548.6 pg/mL for GFAP, and 51.5-24,127.7 for UCH-L1. The correlation coefficients were 1.0, with a slope of 1.03 and 1.06, an intercept of -0.6 and -6.0, for GFAP and UCH-L1, respectively. The results support use of the established GFAP and UCH-L1 cutoffs and clinical performance findings in a multi-site pivotal study which enrolled 1899 mild TBI (Glasgow Coma Scale score 13 to 15) subjects. 116 of the 120 specimens with a positive CT scan had a positive TBI interpretation (Sensitivity 96.7%). Of the 1779 subjects with negative CT scan results, 713 had a negative TBI interpretation (Specificity 40.1%). The negative predictive value (NPV) of the test was 99.4% (713/717).

Conclusions
The ARCHITECT TBI test performance was evaluated compared to the Alinity i TBI test across a broad concentration range of GFAP and UCH-L1. The results support equivalence of the ARCHITECT TBI test to the Alinity i TBI test. The established cutoffs were evaluated in a prospective cohort of mild TBI subjects and demonstrated high sensitivity and NPV relative to head CT scan results, supporting the utility to rule out the need for CT scan in mild TBI subjects presenting to the emergency department.

Funding
This work is in collaboration with the US Army Medical Materiel Development Activity, US Army Medical Research and Development Command CRADA 20-1266-CRA.