Overall Summary of Evidence

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.

Summary of Study #1

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

- Inclusion/Exclusion Criteria: Adults ≥18 years, presenting to Emergency Department with non-penetrating TBI and GCS 13-15, where the referring provider felt a head CT was indicated, with blood test within 24 hours of injury at 22 sites in the U.S. and Europe
- The study population (n=1901) had a median age of 49.0 years and ranged from 18 to 98 years. Over half (56.6%) were male and 70.6% were white and 26.2% were African American.
- Nearly all had a GCS of 15 (94.1%) and around half had Loss of Consciousness (42.2%), Alteration of Consciousness (56.3%), or visible trauma above the clavicle (63.3%). Around one-third reported post-traumatic amnesia (33.0%).
- The median time between injury and blood draw was 3.2 hours with a range of 0.3 to 11.9 hours.