Decision instruments be damned. Clinical judgment be damned. We need a test! We need a biomarker test to tell us whether we should perform a CT in traumatic brain injury!
Thus enter ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), mated together in loving embrace by Banyan Biomarkers in a prospective, observational trial – ALERT-TBI. The aim of this study was to validate these biomarkers, each with their pre-set cut-off thresholds, as accurate predictors of intracranial injuries on CT. Specifically, as accurate predictors in a convenience sample of patients presenting to one of 22 investigational sites with a GCS between 9 and 15.
These trialists collected samples on 1,977 patients, 125 of whom were “CT-positive” – meaning intracranial blood, as typical, but also “bland sheer injury … brain oedema, brain herniation, non-haemorrhagic contusion, ventricular compression, ventricular trapping, cranial fractures, depressed skull fractures, facial fractures, scalp injury, or skull base fractures.” Only 8 of these patients ultimately underwent neurosurgical intervention.
The good news: these assays were 100% sensitive for neurosurgical lesions. The bad news: the lower bound of the 95% confidence interval is 63%. The other bad news: the specificity of the test is only ~35%, meaning it recommends CTs in two-thirds of your TBI patients. And, also: median time from injury to blood draw was 3.2 hours, meaning we can’t actually generalize these findings to potential phlebotomy in the the acute peri-injury trauma evaluation. And, we could keep going on with the bad news, to be certain, but I think we’ll stop there.
The final point to make is to note this study concluded in 2014. It is now, of course, past the midpoint of 2018. It probably goes without saying study findings with obvious advantages to their funding sponsor are not neglected for several years, nor shuffled into Lancet Neurology absent any fanfare.
Chalk this study up as yet another failed dalliance into potential biomarker use for TBI.
“Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study”
https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(18)30231-X/fulltext