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Body fluid-based biomarkers in traumatic brain injury


Published: 23 March 2023

Version: 1.0

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This is a brief of a broader scope from which the participating programmes may be interested in funding more than one proposal. Applications should be within remit of either the:

We are interested in proposals which aim to utilise body fluid-based (blood, saliva or cerebrospinal fluid) biomarkers to improve the diagnosis, prognosis and/or management of traumatic brain injury. Applicants should clearly define and justify their choice of marker(s), patient group(s), study design and outcome measures.

Primary research including randomised and observational studies will be considered by either programme and evidence syntheses will be considered by HTA. Developmental or biomarker discovery studies are not included within the scope of this call. We are seeking studies of biomarkers with a sufficient prior evidence base in a clinical setting and in humans, with the potential to positively impact clinical practice.

Studies investigating the role of biomarkers in non-trauma related acquired brain injuries are outside the scope of this this current call. The NIHR programmes welcome applications for these conditions through their regular researcher-led funding streams, details of which are available through our funding opportunities page.

This call is intended to align with and complement other commitments to traumatic brain injury research, such as the NIHR co-funded call for a UK Traumatic Brain Injury Platform. Proposals must therefore seek to complement and build on existing research activity, resources and infrastructure as appropriate, without duplication.


Traumatic brain injury (TBI), a form of acquired brain injury, occurs when an external force impacts the head causing immediate or secondary damage to the brain. TBI can be a medical emergency as secondary injury can worsen rapidly without treatment. TBI severity depends on several factors including but not limited to the nature of injury and force of impact as well as patient characteristics and subsequent timing and quality of care. The spectrum of TBI severity ranges from concussion/mild TBI at one end to severe TBI which may result in death or permanent disability at the other.

Given the potential significant consequences of such injuries, identifying and managing the right people at the right time and in the right way is critical. Equally as important as identifying those patients with injuries who do need treatment or other intervention is identifying those cases where it is safe to do nothing, and where intervening, what ever that may be, may do more harm.

Because TBI is a heterogenous condition that can occur in a variety of different ways it can be difficult to accurately assess the level of trauma and predict the clinical outcome for individual patients. Clinical assessment of TBI often has limitations due to the non-specific clinical observations or self-reported symptoms required, together with the commonly available imaging modalities which can lack sufficient sensitivity.

Interest is growing in the potential to use body fluid derived biomarkers (in blood, saliva or cerebrospinal fluid (CSF)) as surrogate markers of brain injury to aid in the diagnosis, prognosis, and/or subsequent management of patients with TBI. A variety of such biomarkers have been identified and show promise (including but not limited to S100 calcium-binding protein B [S100B], glial fibrillary acid protein [GFAP], ubiquitin carboxyl-terminal hydrolase isozyme L1 [UCH-L1,] neuron-specific enolase [NSE] and neurofilament protein-light [NFL]) but if and how these could or should be used in routine care remains uncertain.

Most current guidelines on brain or head injury do not yet recommend the use of such biomarkers but advocate for additional high-quality research to expand the evidence base. This includes the recent NICE Head injury guideline update, which includes a number of research recommendations related to the potential role of brain injury biomarkers.

We are interested in applications which aim to provide robust evidence as to the clinical performance (efficacy) of these tests and whether such biomarkers can be routinely, easily, effectively and cost-efficiently used to improve the diagnosis, prognosis, and/or management across the spectrum of TBI severity.