Biomarkers for Traumatic Brain Injury Proceedings of a Workshop (2023) / Chapter Skim
Currently Skimming:
4 Incorporating Biomarkers into Research and Clinical Practice
4 Incorporating Biomarkers into Research and Clinical Practice
Pages 35-46
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 35... ...
More precise language that incorporates additional clinical and biomarker information is needed to inform treat ment and improve outcomes (Manley, Okonkwo)
|
From page 36... ...
Patrick Kochanek, University of Pittsburgh, discussed efforts conducted through the preclinical consortium Operation Brain Trauma Therapy (OBTT) to identify blood-based biomarkers able to function as pharmacodynamic response biomarkers for evaluating drug candidates in several small animal injury models.
|
From page 37... ...
Serum GFAP level significantly increased at 4 hours and/or 24 hours after injury across all the tested TBI models, while the increase in UCH-L1 level in rats, unlike in humans, was too fast and transient to be of use in evaluating drug performance. Comparing levels of GFAP after different injury models (representing, for example, diffuse injury versus penetrating injury)
|
From page 38... ...
IMPROVING DIAGNOSIS AND ENVISIONING THE FUTURE OF TBI CARE2 Turning to the role of biomarkers in the future of TBI care, David Okonkwo, University of Pittsburgh, recalled the progress that has been achieved in TBI management over the past decades, and said the field is poised to move forward. A landmark paper in 1977 defined the modern management of TBI, and emphasized early diagnosis, surgical evacuation of intercranial mass lesions, use of artificial ventilation, control of 2 This section is based on a presentation by David Okonkwo, University of Pittsburgh.
|
From page 39... ...
The first blood biomarker test for concussion detection was cleared by the Food and Drug Administration (FDA) in 2018, using GFAP and UCH-L1.3 Then in 2021, a rapid test developed by Abbott in collaboration with DoD was cleared by FDA, also measuring biomarker proteins GFAP and UCH-L1 in plasma.4 Work is currently under way to develop a whole blood test that can more easily be used at the point of care, and Okonkwo noted that such a device could be a game changer.
|
From page 40... ...
Picking up on the use of pharmacodynamic response biomarkers for drug testing described by Kochanek, Okonkwo saw important future effects of biomarkers on clinical trials for new TBI therapies, using combina tions of biomarkers, testing multiple drugs simultaneously, and gauging the effects of these treatments over the weeks afterward. Having the ability to understand and monitor treatment effects using biomarkers, he said, would radically change the game for TBI clinical drug trials, as well for TBI patient evaluation and diagnosis.
|
From page 41... ...
Picking up on the issue of clinical trial design, Okonkwo noted that there have been dozens of failed phase 3 clinical trials for drugs to treat TBI, often attributable to insufficient clarity coming out of the preclinical space. Many phase 2 trials have been insufficient to identify which drugs to push forward and how, he added, and the field needs to get trial design right.
|
From page 42... ...
There are currently no FDA cleared biomarkers, she explained. Rather, the FDA Center for Devices and Radiological Health 6 This section is based on a panel discussion among Frederick Korley, University of M ichigan; Martin Schreiber, Oregon Health and Science University; Beth McQuiston, Abbott Laboratories; Allison Kumar, Arina Consulting; Carol Taylor-Burds, National Institute of Neurological Disorders and Stroke; Travis Polk, Combat Casualty Care Research Program, DoD; and Narayan Iyer, Biomedical Advanced Research and Development Authority, HHS.
|
From page 43... ...
She added that it is not only TBI patients who need to be recruited to clinical studies, but also similar patients who are negative for a TBI, so that standards for biomarker sensitivity and specificity can be optimized. Carol Taylor-Burds, National Institute of Neurological Disorders and Stroke at the National Institutes of Health, said that she was struck by the progress that has been made in TBI biomarkers but also by the number of possibilities still out there for better understanding the underlying pathophysiology of TBI, incorporating biomarkers into the system of classifying TBI, and identifying additional therapeutic targets.
|
From page 44... ...
These blunt classification terms are hurting patients on both ends of the severity spectrum, he argued, and while a classification change will not happen overnight, incorporation of additional information from available biomarkers can change the way patients receive care. Schreiber highlighted the gap between patients who have a positive CT scan and those who have a negative CT scan and are discharged without a TBI diagnosis but continue to suffer symptoms weeks or months later.
|
From page 45... ...
Another participant added that overtriage can occur in military settings, with more people evacuated to receive CT scans than necessary, and that incorporation of blood-based biomarker tests as part of diagnosis is reducing unnecessary evacuations for mild TBI. Evans added that from a health economics standpoint, extrapolating these findings into the civilian market could have a significant return on investment.
|
From page 46... ...
Kumar replied that the next phase of biomarker research should extend "aid in diagnosis" results to understand the interpretation of available data for use in prognostication. Schreiber added that blood biomarker screening tests can now start to fulfill certain aspects of the spectrum of care for a patient.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.