The U.S. Food and Drug Administration last week gave its first green light to a company that wants to start selling a blood test to evaluate for mild traumatic brain injury, or concussion. The agency lauded the blood test as an innovative tool for speeding diagnosis and avoiding radiation exposure from brain scans. But some head trauma experts worry the authorization was pushed through too hastily.
“The data aren't as conclusive as we would have hoped, so I was surprised by the rapid FDA approval,” says Henrik Zetterberg, a professor of neurochemistry at the University of Gothenburg in Sweden, who was not involved with the project. The Brain Trauma Indicator, developed by San Diego–based biotechnology company Banyan Biomarkers, was reviewed and authorized for commercialization in fewer than six months. It was cleared under the FDA's Breakthrough Devices Program—an approvals process that aims to fast-track the development of promising and relatively low-risk medical technologies, after reviewing available data. Banyan says the new test will soon be available in hospitals.
The Brain Trauma Indicator measures blood plasma levels of the UCH-L1, a protein scientists believe helps dispose of cellular waste in the brain, and GFAP, a structural protein found in non-neuronal cells called astrocytes. Both are released at elevated levels following a concussion or other injury that damages nerve fibers, and both can be detected within 20 minutes of a head injury (although it may take longer for doctors and patients to get the results from a lab).
Concussions are notoriously difficult to diagnose, and patients suspected of having them are typically assessed by a doctor using the Glasgow Coma Scale—a series of physical tests for determining the level of consciousness—followed by a computed tomography (CT) head scan for brain abnormalities. CT scans are expensive, however, and many patients suspected of having traumatic brain injuries do not exhibit signs of visible damage when scanned. The blood test would provide hospitals and clinicians with a relatively quick screening tool to help them decide whether a CT scan would be likely to pick up any brain injury.
The FDA authorized marketing the Brain Trauma Indicator after examining data from a clinical study of nearly 2,000 blood samples from patients with suspected concussions. From that data, the agency concluded the test can predict the absence of lesions on a CT scan with an accuracy of 99.5 percent, making it reliable enough to rule out the need for a scan in at least one third of the patients.
Yet Zetterberg, who has been identifying biomarkers associated with brain injury and other neurological disorders in his lab, questions the usefulness of UCH-L1 as a concussion biomarker, and says his own testing has found it unreliable. “It's very important to look at the timing of the sample,” he says. “UCH-L1 might work at early time points, but if a sample is collected two to three days after an injury, perhaps other markers would be better.”
Joseph Fins, a professor of medicine and medical ethics at Weill Cornell Medical Center, applauds the approval and says, “This test is an advance for triaging CT scans.” But he cautions it may not capture all minor concussions—like those that do not produce structural changes in the brain.“A negative blood test means that proteins were not released—not necessarily that there was not a mild concussion,” he says. “If it’s assumed that a patient did not have a concussion because the test is negative, and then the patient resumes the sporting activity, the effects of the next head injury can be augmented.”
“It's promising that the FDA has approved something,” Zetterberg says. “But much more research is needed,” he adds—especially comparisons of different biomarkers at different time points after injury—to develop a more reliable blood test for concussion. CT scan abnormalities, he says, are just one aspect of this type of injury.