New Test for Brain Injury on Horizon

Does the story adequately quantify the benefits of the treatment/test/product/procedure?

Not Satisfactory

Although it’s too early to quantify the technique’s benefits, this story does that. We’re told that the study of 66 patients found that those with the most severe brain injury had 16 times the level of UCH-L1 as those without brain injury. What is the true clinical significance of that result?

The benefits of using biomarkers wouldn’t be just they can detect brain injury but they can do so better and more usefully than the methods we have now. Otherwise, how does it benefit us? What’s the clinical meaning of the 16x difference for this one biomarker? What about the other biomarkers in the panel alluded? Could the researchers use this result to distinguish mild from severe, or mild from normal, or cases that are hard-to-catch vs those that are obvious? (Dr. Hall suggests there are questions about mild cases.)

We’re given the analogy to troponin tests for heart attacks, which is "more precise than having a patient describe symptoms." The implication, thus, is that this 16x difference is a hugely superior signal to the standard cues we use to diagnose severe brain injury. But the researchers didn’t compare this new technique to current diagnostic ones. In short, the story does a poor job of describing how such a test will lead to improved care. The analogy to troponin is a good point, because early identification of a heart attack leads to treatments that have been shown to be lifesaving. A similar evidence base would be needed for biomarker identification of brain injuries.

That’s a big problem with reporting on laboratory research like it’s clinical research: we don’t have hard outcomes to look at, only surrogate ones. The true benefits would be the test’s specificity, sensitivity, and speed, and its effects on actual people’s lives comparative to the standard approach.

Does the story seem to grasp the quality of the evidence?

Not Satisfactory

On a fact-by-fact basis, the article states several good points about the evidence. The major, "first-of-its-kind" study with 1000 patients hasn’t been funded yet. If it is funded, it would start next year and take 18 months from then to bear results. Most of the evidence is in rats. The study of 66 humans involved (in part) people already known to have brain injuries. FDA approval of the test is conditional on the completion (and funding) of the Defense Department study, which implies that the study is a late-stage, pivotal investigation of the technique in a clinical setting.

The trouble is, the article doesn’t evaluate any of these points. Laboratory studies in rats and humans don’t prove ideas but generate ideas. We don’t know whether some future blood test will reliably identify serious cases that are missed by conventional techniques, change treatment plans, save lives, reduce long-term rehabilitation, or prevent what happened to Natasha Richardson. No one can say this technique will be better than what doctors already do, which is why the FDA won’t touch it yet. Not only do we not know the answer, we’ve yet to ask the question. None of the evidence mentioned has tested a diagnostic technique prospectively or compared it to another approach.

That context won’t be clear for a lay reader, who won’t see that the claims are remarkably premature.

The presumably independent source, Dr. Hall, explains that "the Banyan work" does show that these biomarkers can reliably track brain injury and are copious enough to be reliably detected. That statement, which seems to be about a panel of multiple biomarkers, comes before we learn about UCH-L1 and its particular evidence base. So we’re not sure whether Dr. Hall’s contextual explanation applies to the specific, quantitative evidence we’re given later, such as the 16-fold increase in UCH-L1. In other words, we’re not told what that number means.

The article is also vague about evidence from "more than 300 human brain-injury patients" regarding "certain biomarkers." On its face, in a sea of rat research, that could be the highest-quality aspect of this evidence…if we know anything about them. We presume from the detail about the study of 66 people that the 300 are all laboratory research. But of what biomarkers? All UCH-L1? Several other biomarkers of brain injury have been studied in the past. Which biomarkers would the DOD study look at — is it all about UCH-L1? Maybe no one knows because the study hasn’t even been funded — which is the point. The tone doesn’t match the facts, and pale inks were used to draw a very bold picture.

The narrative of the story is that many cases of brain injury go undiagnosed. If the laboratory research only involved people who were already diagnosed, what does that tell us about the technique’s ability to identify people who often aren’t currently diagnosed? In other words, does any of the evidence, including the UCH-L1 signal that’s quantified for us, address the problem posed by the story at the outset, the one that is blamed for Natasha Richardson’s death?

Of course, the story’s ebullient tone makes these caveats seem moot.

Does the story commit disease-mongering?

Not Satisfactory

We think this article does engage in disease-mongering. The statistical sidebar cites some grim outcomes of head trauma. These numbers cloud the point of the story, which is about undiagnosed or slow-to-diagnose cases. How many of the 3 million people who need long-term care and the 52,000 who died had undiagnosed severe brain injuries? How many died on contact? How often does the current diagnostic approach fail? In other words, who exactly might this new technique benefit? While perhaps no one knows those answers, we think the overly general sidebar inflates the expectations balloon too much.

1. In someone who has suffered serious brain injury — say, a concussion with prolonged loss of consciousness — you don’t need a test to say that the patient has had a brain injury. In theory, the test may help identify subclasses of individuals for specific treatments or monitoring. There are no data provided that supports such a use for this proposed test.
2. In someone who has suffered what appears to be minor brain trauma — with brief loss of consciousness and now looking fine or with no loss of consciousness — the test could theoretically identify the rare individuals who have had a more serious injury. Such individuals could be more carefully monitored or treated. Again, there is no data provided that supports such a use for this proposed test.

Another point that was easy to miss: the tests in humans measured UHC-L1 in spinal fluid. That requires a spinal tap. While it’s something one might consider in the first scenario, it’s unlikely to be practical for the second. One would expect that the test characteristics of a CSF level are different from a blood level. 

Does the story establish the availability of the treatment/test/product/procedure?

Not Satisfactory

The article is clear that these tests aren’t available in your local hospital, and that the FDA hasn’t approved a blood test. But the overall tone is so unchecked that it seems like a foregone conclusion that it will be available "soon."

• "researchers are close" 
• "[these biomarkers] could end up determining the future treatment" 
• "I think this will revolutionize brain-injury care"
• "the Army’s goal is to one day have a portable blood-test device"
• "biomarkers could do the same for brain injury [as troponin did for heart attacks]"

If researchers are close, why does the article lead with the evidence from rats? Again, the article is clear that the technique is not available, but we think it needed context about how preliminary this research is. Many readers would be shocked to learn how many techniques with promising preliminary results in the lab fail when tested in clinical trials.

The story is also unclear about the pivotal DOD trial. Will it specifically study UCH-L1, the biomarker investigated by Banyan Labs, or is it about a panel of biomarkers? Are they all Banyan biomarkers? Is UCH-L1 even in there? We don’t know how much of the research discussed in this article will even be investigated in the future study and, thus, potentially available.