The FDA announced approval of a blood test that incorporates both GFAP and UCH-L1. Approval was based on two as yet to be published studeis titled Evaluation of Biomarkers of Traumatic Brain Injury (ALERT-TBI) and Evaluation of Biomarkers of Traumatic Brain Injury Extension Study (ALERT-TBIx), and passed after less than 6 months of evaluation. Yes, more silly acronyms, I know.

The studies were designed to “evaluate the utility of the Banyan UCH-L1/GFAP Detection Assay as an aid in the evaluation of suspected traumatic brain injury (Glasgow Coma Scale score 9-15) in conjunction with other clinical information within 12 hours of injury to assist in determining the need for a CT scan of the head.”

The former study started in 2012 and involved 2011 patients! The latter had only 119 patients, starting in 2015. Now, I have no access to their data, so I can’t tell what the FDA saw.

From Banyan Biomarkers’ website:

“The CT scan is widely available to assist clinicians in the evaluation of TBI, however, CT scans do not provide a clear and objective answer and scanning may increase the risk for radiation-induced cancer. Furthermore, over 90% of patients presenting to the emergency department with mild TBI, sometimes described as “concussion”, have a negative CT scan. Despite these limitations, nearly all patients are sent for a CT, which results in increased costs to the healthcare system and unnecessary patient exposure to radiation.”

Here are the (very) few factoids that I can find:

• CT scan results were compared to the Brain Trauma Indicator (BTI) blood test (GFAP + UCH-L1)
• BTI predicted a positive CT scan 98% of the time
• It predicted a negative CT scan 99.6% of the time
• Time to process the test is currently 4 hours

Bottom line: Sounds promising, right? Based on the data summarized over the last two days, I wouldn’t be too excited about this test, but the FDA was able to look at a study that I can’t. It appears that the negative predictive value is excellent, so I can see the application.

That being said, 4 hours is way to long. We can’t have a patient sitting in the ED waiting for the results to come back to decide whether they need a head CT. And how long will it take the assay to be widely available?

The devil will be in the details. What types of intracranial lesions were detected. Are the negative predictive values the same for subarachnoid, subdural, epidural, or intraparenchymal bleeds? And finally, how expensive will it be? How does the cost for the test compare to the cost of a CT scan done in 5 minutes?

I’ll let you know more as the details emerge. But don’t look for, or plan to use, this test at your hospital any time soon. There’s more work to do!

Reference: Banyan Biomarkers (banyanbio.com)

Yesterday, I wrote about one blood biomarker, GFAP, and its possible application in detecting traumatic brain injury (TBI). Today, I’ll discuss a complementary marker called UCH-L1.

Fewer studies have been done looking at the utility of UCH-L1 in detecting TBI than of GFAP.  A review article published last month pooled existing literature to get a sense of how good this biomarker really is. It also examined the risk of bias due to the small numbers of studies involved.

Here are the factoids:

• Only 38 abstracts were eligible, but full text was available for analysis in only 13 (meaning it was only an abstract and never passed muster for publication). The authors of the published studies were contacted for additional information, which is an interesting (and helpful) practice.
• Of all of those, only 4 were selected for meta-analysis! This significantly limited the value of the analysis.
• Serum UCH-L1 has a high accuracy in predicting CT findings in mild to moderate TBI, but there is a high risk of bias affecting this result
• Plasma UCH-L1 has a moderate accuracy predicting CT findings across all GCS levels, with a low risk of bias
• Pooling all studies, this is high accuracy in predicting CT findings in patients with TBI across all GCS levels, but there is a high risk of bias affecting the results

Bottom line: UCH-L1 show promise as a predictor of CT findings in patients with TBI. However, the research papers were few and far between, and the possibility of bias was high. What does this mean? That using this test alone is better than a coin toss, but not good enough to change our practice in ordering CT scans in head injured patients. More well-designed studies are needed tell us whether this new (and undoubtedly expensive) test is worth the trouble.

Tomorrow, I’ll discuss a blood test incorporating both UCH-L1 and GFAP that was recently approved by the FDA.

Reference: The diagnostic values of UCH-L1 in traumatic brain injury: A meta-analysis. Brain Inj 32(1):1-17, 2018.

Traumatic brain injury (TBI) is an extremely common problem encountered by trauma professionals. Diagnostic and management pathways are fairly well-defined, and rely mainly on physical examination, as well as CT imaging in select cases.

In recent years, work has been done to identify markers of brain injury in the blood. The theory is that the injured brain may release substances that can be assayed with a simple blood test. The presence of these blood markers could then influence our use of CT for diagnosis, decision to admit or send home, and possibly help identify patients likely to develop post-concussive symptoms.

Two particular biomarkers are being evaluated: UCH-L1 and GFAP. A recently published review examined the current status of GFAP in diagnosis of head injury.

Here are the factoids:

• A total of 27 pertinent research papers were identified for review, and 24 of 27 demonstrated a positive association between GFAP levels and TBI
• GFAP prediction of intracranial pathology by CT scan was good to excellent
• GFAP appeared to be able to discriminate between mass lesions and diffuse injury
• There was considerable variability in the average GFAP values. This means that the cutoff value that predicts significant injury is not yet clear.
• The number of pediatric studies reviewed was low, so the results may not be generalizable to children
• GFAP may be elevated in patients with orthopedic injuries, and this was not well controlled for in the studies reviewed. It is unclear whether GFAP can be used in patients with fractures.

Bottom line: GFAP looks promising as a marker for detecting significant TBI in some trauma patients. 

Tomorrow, I’ll take a look at the other biomarker, UCH-L1, and the following day I’ll discuss the recent FDA approval of an assay for both of these by a US company, Banyan Biomarkers.

Reference: A systematic review of the usefulness of glial fibrillary acidic protein for predicting intracranial lesions following head trauma. Frontiers in Neurology 8(652):1-16.

I have no financial interest in Banyan Biomarkers.