Three studies were conducted in support of the FDA licensure request.1-4 The first study used frozen plasma samples obtained from the study conducted in support of the Banyan Biomarkers TBI Assay.2,3 This study (n=1901) demonstrated comparable performance to the Banyan Biomarkers assay with a sensitivity of 95.8%, negative predictive value of 99.3%, and specificity of 40.4% [95%CI 38.2%, 42.7%]. There were n=5 false negative test results; none of these were abnormalities requiring surgical intervention.2
The second study used a small sample of fresh plasma samples (n=88) obtained from a small subset of patients a study of TBI at Level 1 Trauma Centers who had head CT performed.3 In this sample the sensitivity and negative predictive value were 100%, but the specificity was lower - 23.7%. The reason for the lower specificity in this population is not clear but may have been due to the small sample size or due to differences in the study population. For example, only 6% of the population in the first study had findings on head CT as compared to this study where 33% had findings on head CT. The positive predictive values for the two studies were comparable after adjustment for the prevalence of positive head CT.
The third study used venous whole blood specimens collected within 24 hours of head injury. The study (n=970) demonstrated comparable performance to the earlier plasma studies, with a sensitivity of 96.5%, negative predictive value of 96.5% (adjusted NPV at 6% prevalence of CT+ was 99.4%), and specificity was 40.3%. There were n=10 false negative results and none of these required surgical intervention.
While the specificity of the assay is low to moderate for brain injury and hemorrhage visible on CT, additional research suggests that many individuals with elevated Glial Fibrillary Acidic Protein using a prototype of the assay have evidence of brain injury on MRI.5 It is important to note the assay is not FDA approved for this purpose.
Stored frozen plasma samples were obtained from Bazarian, et al study used for approval of Banyan Biomarkers TBI assay, an early version of this assay.1,2
There were five individuals with false negative results (i.e. not elevated biomarker result and findings on head CT). None of these individuals required surgical intervention. Findings included a small sub-arachnoid hemorrhage, a small subdural hemorrhage and a venous angioma thought to be a congenital anomaly. See Figure 1 for the 5 head CT scans from false negative subjects.
Fresh plasma samples were obtained from four clinical sites of the Transforming Research and Clinical Knowledge in
Traumatic Brain Injury (TRACK-TBI) study in the United States.3
A prospective, multi-center, observational study was conducted to evaluate the clinical performance of the i-STAT TBI 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. Venous whole blood specimens were collected in K2EDTA within 24 hours of the head injury.4
Yue JK, Yuh EL, Korley FK, et al. Association between plasma GFAP concentrations and MRI abnormalities in patients with CT-negative traumatic brain injury in the TRACK-TBI cohort: a prospective multicentre study. Lancet Neurol. 2019;18(10): 953-961. https://doi.org/10.1016/s1474-4422(19)30282-0
The study enrolled adults with GCS 13-15 between 2014-2018 at 18 participating Level 1 U.S. trauma centers who presented within 24 hours of injury and had a head CT as well as an MRI within 7-18 days post injury.5