APPENDIX B: DETAILED INFORMATION ON THE TBI WB BIOMARKER

NOTE: Information summarized from the following sources:

- Abbott Point of Care Inc., 2021, 510(k) Summary: i-STAT TBI Plasma Cartridge with the i-STAT Alinity System (K201778; Approved January 8, 2021). https://www.accessdata.fda.gov/cdrh_docs/pdf20/K201778.pdf
- Abbott Point of Care Inc. 2024, 510(k) Summary: i-STAT TBI Cartridge with the i-STAT Alinity System (K234143; Approved March 27, 2024). https://www.accessdata.fda.gov/cdrh_docs/reviews/K234143.pdf

Capability Name: Analyzer, Traumatic Brain Injury System

Device Name: i-STAT TBI Cartridge with the i-STAT Alinity System

Device and Assay Description:

- Semi-quantitative multiplex immunoassay in ethylenediaminetetraacetic acid (EDTA) anticoagulated WB for:

- Glial fibrillary acidic protein (GFAP)
- Ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1)
- Cartridge can only be used on the i-STAT Alinity.
- Test time is approximately 15 minutes

- Will give an error reading if used on i-STAT 1.
- Cartridges require refrigerated storage; calibration/verification and control fluids require freezer for storage.

Whole Blood Assay Reference Range:

- Range derived from N=150 apparently healthy individuals with no history of neurological disease: GFAP: Mean 18.7 pg/mL; Median 18.0 pg/mL; Reference Interval <47-53 pg/mL
- UCH-L1: Mean 89.3 pg/mL; Median 81.5 pg/mL; Reference Interval <87-251 pg/mL

Whole Blood Assay Cut-Off Values and Results:

- Elevated: An elevated result is given if either GFAP OR UCH-L1 is elevated

- GFAP cut-off: 65 pg/mL
- UCH-L1 cut-off: 360 pg/mL

- Not elevated: A not elevated result is given if GFAP AND UCH-L1 are below the cut-off
- Not reportable: No result is given if valid results are below the cut-off AND one or more results are not reportable

Plasma and Whole Blood Assay Performance

There were three studies performed as part of the U.S. Food and Drug Administration (FDA) licensure process; two of which were based on plasma samples and one based on whole blood samples.

Study #1: This study was conducted on stored plasma samples and demonstrated performance comparable to the Banyan Biomarkers assay with:

- Sensitivity of 95.8% [95% Confidence Interval (CI) 90.6%, 98.2%]
- Negative predictive value of 99.3% [95%CI 98.5%, 99.7%]
- Specificity of 40.4% [95%CI 38.2%, 42.7%]

(See Appendix C for additional details.)

Study #2: This study was conducted on fresh plasma samples and demonstrated comparable sensitivity but lower specificity.

- Sensitivity of 100.0 [95% CI 88.3%, 100.0%]
- Specificity of 23.7% [95%CI 14.7%, 36.0%]

(See Appendix C for additional details.)

Study #3: A prospective, multi-center, observational study was conducted to evaluate the clinical performance of the i-STAT TBI whole blood cartridge in classifying intended use population subjects with suspected mild TBI for the likely absence of acute intracranial lesions visualized by a head CT scan. Testing was performed at 20 external point of care clinical sites across the United States.

- Clinical Sensitivity 96.5% (273/283) (95% CI 93.6%, 98.1%)
- Clinical Specificity 40.3% (277/687) (95% CI 36.7%, 44.0%)
- Negative Predictive Value (NPV) 96.5% (277/287) (95% CI 93.7%, 98.1%)
- Adjusted NPV at 6% prevalence is 99.4% (95% CI: 99.0%, 99.7%)

Whole Blood TBI Assay Intended Use Statement

The i-STAT TBI test is a panel of in vitro diagnostic immunoassays for the quantitative measurements of glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L 1 (UCH-L 1) in whole blood and a semi-quantitative interpretation of test results derived from these measurements, using the i-STAT Alinity instrument. The interpretation of test results is used, in conjunction with other clinical information, to aid in the evaluation of patients, 18 years of age or older, presenting with suspected mild traumatic brain injury (Glasgow Coma Scale score 13-15), which may include one of the following four clinical criteria: 1) any period of loss of consciousness, 2) any loss of memory for events immediately before and after the accident, 3) any alteration in mental state at the time of accident, and/or 4) focal neurological deficits, within 24 hours of injury, to assist in determining the need for a CT (computed tomography) scan of the head. A 'Not Elevated' test interpretation is associated with the absence of acute traumatic intracranial lesions visualized on a head CT scan. The test is to be used with venous whole blood collected with EDTA anticoagulant in point of care or clinical laboratory settings by a healthcare professional.