Piecing together the true picture of TBI with Professor David Menon and James Piercy
Professor David Menon talks to NR Times editor Stephanie Price about the ambitious TBI-REPORTER project and its mission to harness data for better outcomes.
Advancements in traumatic brain injury (TBI) treatment have been somewhat sluggish in recent decades, in part due to a lack of the hard evidence needed to drive innovation. The TBI-REPORTER project, however, is working to change this using a novel approach to data collection and collaboration.
TBI care costs over £10bn each year in the UK, and more than US$400bn globally. But the development of treatments that can address this burden – and transform patient lives and outcomes – is hindered by a dearth of meaningful data. Launched in 2023 and led by the University of Cambridge, the UK-TBI REpository and data PORTal Enabling discovERy (TBI-REPORTER) platform is aiming to transform TBI research and care by reusing existing clinical data, creating a national ‘bioresource’, and establishing an experimental medicine network.
The project is a multidisciplinary, multi-centre, UK-wide collaboration of over 50 investigators with experience in a range of clinical areas. With £10.5m in funding behind the scheme, it is hoped that the platform could be a catalyst for new treatments and care pathways.
Having brought together leading experts from across the UK, TBI-REPORTER also aims to facilitate patient and public engagement in its activities to ensure the voices of those with lived experience shape the future of TBI care.
NR Times spoke to principal investigator for TBI-REPORTER, Professor David Menon, and co-chair of the project’s Patient and Public Involvement and Engagement (PPIE) Committee James Piercy, to find out more.
Advancing research with data collection
It is hoped that the project will help to address a current flaw in TBI-focused clinical trials. While such trials are a crucial resource for data, cohorts of patients may, at times, be as small as 10 people, or as large as a few thousand.
But this data often stays with the trial researchers, rather than informing new treatment development more widely. Having access to large volumes of such data could be hugely useful for researchers looking to understand where resources would be best invested, or what treatments to advance.
“Drug trials have often failed and progress in clinical care has been slow”
As part of its “data hub”, TBI-REPORTER is bringing together data from multiple TBI clinical trials to create a large resource of valuable and accessible clinical data for researchers.
“While we have gained some understanding of the underlying processes driving TBI related health outcomes, drug trials have often failed and progress in clinical care has been slow,” says Menon.
“Over the years, however, each of the individual studies investigating TBI and its outcomes has gathered potentially very informative data that, to date, has not been widely available to researchers outside of the original studies.
“We currently have no specific treatments. All of the treatments are trying to modulate physiology, and there have been lots of experimental preclinical studies in traumatic brain injury models and a variety of animal models, but they’ve not translated into benefit in clinical studies.
“So, new drug development has been really halted.
“All of these previous studies and clinical trials have huge amounts of valuable data, but they are never reused.
“They get used for initial analysis and then they sit in silos.”
Professor David Menon
Alongside this data hub approach, TBI-REPORTER is also hosting a biorepository, encouraging researchers to collect biological samples in a uniform fashion that can be submitted to the database to contribute to bigger studies in the future.
“If studies undertook sample collections such as blood or biofluid, they would collect samples for their study, but they would also collect one serum sample at admission and one EDTA sample [a blood sample containing the anticoagulent EDTA], so that if we wanted to do legacy studies, we could actually bring all of these together and do very large studies,” says Menon.
“So even though there may be only 500 or 1000 patients in each study, if each one collects data in a similar fashion, then we can bring all the studies together for a very large genome-wide association study.
“That’s important because we know now that if you look at patients with traumatic brain injury, their outcomes are very variable.”
Identifying genes that influence brain injury may give an insight into a patient’s injury outcome, and the bioresource will also enable researchers to investigate blood biomarkers, says Menon.
“With those three things, the DNA studies, bringing information together for protein biomarkers of brain injury, and looking at the mechanisms by looking at blood tests, we now have a lot of information to characterise patients quite early.”
Exploring experimental medicine
The platform also supports an experimental medicine network, consisting of research-ready sites which will provide a resource for both academic and industry-led endeavours. These studies will aim to characterise clinical TBI pathophysiology using biomarkers, including those from clinical data, neuroimaging, biofluid analysis and genomics.
Menon says: “For small experimental medicine studies, which are maybe at the most 100 or 200 patients, we put the intervention in, which has good preclinical evidence, and we know
that they’re safe, and we see that it does what it says on the tin.
“If it’s an anti-inflammatory intervention, we ask whether it changes the cytokines, the inflammatory mediators, downstream. And if it doesn’t do that, the chances that it will produce clinical benefit are going to be very low indeed, and it certainly won’t produce clinical benefit by that mechanism.
“These experimental medicine studies are an approach to fail fast or progress soon, and we can identify drugs that are likely to be helpful at an early stage in humans in small studies.”
Medicine studies in the network will be available to academics and pharmaceutical partners, says Menon.
“We will look to repurpose drugs that are being used for other indications, and the dialogue with pharmaceutical partners will allow us to identify which drugs are important as candidates, and we can evaluate them more before we do any studies at all.”
Championing patient engagement
A vital component of TBI-REPORTER is the Patient and Public Involvement and Engagement (PPIE) Committee, led by the United Kingdom Acquired Brain Injury Forum (UKABIF).
This brings patient perspectives into the research to ensure relevant questions are being asked; and exposes the platform’s research to the public to encourage engagement.
For example, at the recent International Neurotrauma Society Symposium in Cambridge, TBI-REPORTER held an open session for the public to educate on TBI in sport – holding a football match in conjunction with the charity Head Safe Football.
James Piercy
Co-chair of the PPIE Committee James Piercy (pictured above), says that its aim is to integrate patient and lived experience perspectives into TBI research, ensuring transparency in data storage and use, and prioritising research areas based on patient needs.
“We really want to make sure that patient voices and people with lived experience input into everything that TBI-REPORTER does,” he says.
“That means that when new research comes along it reflects unmet needs, so we don’t spend loads of time and money trying to research and develop things that nobody has any interest in and don’t have any value to patients.”
Equally important, Piercy explains, is ensuring that diverse and underserved groups such as prisoners, children and homeless people are involved.
“We’re trying to go talk to those people, and some of those groups that are hard to connect with,” says Piercy, “using other organisations that work with these people to build bridges.
“We really want to make sure that when we’re talking about patient involvement and lived experiences, it is not just the lived experience of people like me, middle aged, middle class folks.
“We really need to reach out into those different communities, because we know that the outcome of traumatic brain injury is different depending on who you are and where you live.
“We’re going to try to connect with partners at the NIHR HealthTech Research Centre in Brain Injury, because that organisation is building up a big database for a lot of patients who are willing to get involved and to provide that kind of input. Hopefully that partnership will really open the doors so we get a much broader range of people involved.”
Qualitative research will also be a focus of the PPIE Committee, in order to capture broader experiences of those living with TBI, particularly in the area of mental health.
“One of the things that our patient platform is already pushing for is to get qualitative research projects into TBI- REPORTER. Social science will come into this database, as well as collecting those stories and those experiences from wider groups on things like mental health.
“We know there is a huge correlation between TBI and mental health conditions, but how do we map that? How do we make it so it’s not just anecdotal, and how can we understand the experiences people have been through so that we can hopefully improve services? Let’s show best practice across the whole of the UK, and let’s build the evidence base for that. I think that could be a really important outcome of this project – that we get some change happening.
“There’s huge potential. We know the benefits of having bigger datasets for research. It’s going to be much more reliable. We’ve got to hope that these first few years are a springboard for a big, global initiative. We know that if you have a brain injury in India, for example, you’re not going to have the same outcome as you do if you have it in West London – they are different health systems, completely different environments.
“We really need to build that learning and pull all of this data together from all over the world. It would be really interesting to see studies with 70 million people in them.”
TBI-REPORTER has already begun a number of academic studies, and expects its first pharmaceutical collaboration before the end of 2025. •
