EPSRC Centre for Predictive Modelling in Healthcare

Lead Research Organisation: University of Birmingham
Department Name: School of Mathematics

Abstract

Our Centre brings together a world leading team of mathematicians, statisticians and clinicians with a range of industrial partners, patients and other stakeholders to focus on the development of new methods for managing and treating chronic health conditions using predictive mathematical models. This unique approach is underpinned by the expertise and breadth of experience of the Centre's team and innovative approaches to both the research and translational aspects.

At present, many chronic disorders are diagnosed and managed based upon easily identifiable phenomena in clinically collected data. For example, features of the electrical activity of the heart of brain are used to diagnose arrhythmias and epilepsy. Sampling hormone levels in the blood is used for a range of endocrine conditions, and psychological testing is used in dementia and schizophrenia. However, it is becoming increasingly understood that these clinical observables are not static, but rather a reflection of a highly dynamic and evolving system at a single snapshot in time. The qualitative nature of these criteria, combined with observational data which is incomplete and changes over time, results in the potential for non-optimal decision-making.

As our population ages, the number of people living with a chronic disorder is forecast to rise dramatically, increasing an already unsustainable financial burden of healthcare costs on society and potentially a substantial reduction in quality of life for the many affected individuals. Critical to averting this are early and accurate diagnoses, optimal use of available medications, as well as new methods of surgery. Our Centre will facilitate these through developing mathematical and statistical tools necessary to inform clinical decision making on a patient-by-patient basis. The basis of this approach is patient-specific mathematical models, the parameters of which are determined directly from clinical data obtained from the patient. As an example of this, our recent research in the field of epilepsy has revealed that seizures may emerge from the interplay between the activity in specific regions of the brain, and the network structures formed between those regions. This hypothesis has been tested in a cohort of people with epilepsy and we identified differences in their brain networks, compared to healthy volunteers. Mathematical analysis of these networks demonstrated that they had a significantly increased propensity to generate seizures, in silico, which we proposed as a novel biomarker of epilepsy. To validate this, an early phase clinical trial at King's Health Partners in London has recently commenced, the success of which could ultimately lead to a revolution in diagnosis of epilepsy by enabling diagnosis from markers that are present even in the absence of seizures; reducing time spent in clinic and increasing accuracy of diagnosis. Indeed it may even make diagnosis in the GP clinic a reality.

However, epilepsy is just the tip of the iceberg! Patient-specific mathematical models have the potential to revolutionise a wide range of clinical conditions. For example, early diagnosis of dementia could enable much more effective use of existing medication and result in enhanced quality and quantity of life for millions of people. For other conditions, such as cortisolism and diabetes where a range of treatment options exist, identifying the optimal medication, and the pattern of its delivery, based upon the profile of the individual will enable us to maximise efficacy, whilst minimising unwanted side effects.

Planned Impact

Building on a substantial track-record of engagement with end-users (including patients and their carers, clinicians, device manufacturers and diagnostics companies, the pharmaceutical industry and funding agencies) we have developed a set of activities for User engagement that will build upon the research core of the Centre and form the basis of future impact. These activities include:

- bespoke training and a visitor programme (for both clinical researchers and practitioners) to introduce key concepts and to develop understanding of predictive models; a key first step to facilitate the ultimate uptake of these methods in practice
- researcher exchanges where members of the Centre and researchers from our industry partners will spend time working on projects of mutual interest
- "hot topics" workshops and sandpits where groups of scientists and clinicians spend a focused period discussing the very latest findings and challenges and suggest a roadmap for future travel
- "research incubator" retreats. Here we will bring mathematicians, clinicians and clinical scientists together with relevant industry to develop proposals for pump-priming new areas of research. This will be facilitated by our industry partner Life Sciences SouthWest and members of the Universities' Research & Knowledge Transfer teams, focused on research development, impact and commercialisation will help teams to develop bids and budgets to maximise the likelihood of substantive impact arising from these projects

Having utilised similar activities to establish a strong track-record of partnering with clinicians and industry already, we foresee substantial impact in the areas of epilepsy diagnostics and dynamic treatments for cortisolism arising during the initial period of EPSRC funding. In epilepsy, we have already taken steps to protect intellectual property through patenting the concept that time-varying changes in a network model of electroencephalography can predict clinical outcomes (joint patent between the University of Exeter and King's College London). We are currently undertaking an early phase clinical trial to validate this hypothesis. From here there is the opportunity for commercialisation, either linking with our project partner MentisCura or through a University spin-out company. To explore this latter option, we have recently secured SetSquared funding through their innovation to commercialisation scheme. Similarly, we have also patented a device for the dynamic delivery of hormone replacement with our project partner DesignWorks. Here we are exploring whether dynamic delivery of steroids - that mimic the natural secretory patterns in healthy humans - will optimise therapeutic benefit, whilst reducing significant side effects associated with long-term steroid use. Building closed loop systems based upon sensing precursor hormones offers significant potential for a dramatic impact for people with adrenal dysfunction. Building on this experience we also foresee impact in the areas of cardiology (notably arrhythmias), dementia and diabetes where we have developing collaborations with internationally leading clinical partners.

Research arising in our Centre will present the opportunity for impact for other commercial sector R&D. For example, parameter evolution of a patient-specific models extracted from clinical data brings the ability to characterise the effect of a drug or neuromodulation device. Similarly, it may be possible to develop biomarkers for response to newly developed compounds in early-stage trials, based upon parameter evolution of a patient-specific model. Based on our track-record to date, there will also be opportunities for industries focussed on device development and technologies for aiding clinical decision making. Our approach to co-develop the research focus and design of methodologies will ensure the development of mathematical and statistical methodologies that are challenge led and readily translatable.

Publications

10 25 50

Related Projects

Project Reference Relationship Related To Start End Award Value
EP/N014391/1 01/01/2016 29/09/2019 £2,008,955
EP/N014391/2 Transfer EP/N014391/1 01/01/2020 31/01/2021 £242,649
 
Title Artist in Residence Programme 
Description Four Artists in Residence were appointed to work with our researchers to develop artistic outputs as part of a multidisciplinary research team in this Sci-Art collaboration 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2021 
Impact Showcasing event held March 2021 
 
Description This Centre award has enabled key findings in several areas of non-communicable disease. Members of the Centre were particularly interested in neurology (especially epilepsy and dementia), neuroendocrinology (especially the stress-response and reproduction), as well as cardiology and cardiovascular dynamics.

Within neurology several papers were published that revealed new understanding of how pathological brain activity emerges from the interplay between brain dynamics and brain networks was revealed. These findings have had direct clinical impact through additional research that has developed techniques for bringing together clinical data (used in the diagnosis and prognosis of disease) with fundamental mathematical models.

Within neuroendocrinology several papers were published that have shown a key role for networks at different scales of description in generating hormone dynamics. This knowledge has been used to understand how these dynamics breakdown in certain medical conditions, and how treatment may optimally impact on the regeneration of healthy hormone levels.

A key mechanism for establishing novel collaborations between mathematicians and clinicians, was the research incubator. This activity enabled new collaborations to be established, supported by post-doctoral members of the Centre, or seconded PhDs. Projects supported through the incubator secured several million in follow-on funding, resulted in over 20 papers (and counting) and contributed to the establishment of a spin-out company.

In October 2019, the Centre Director was recruited by the University of Birmingham to establish the Centre for Systems Modelling and Quantitative Biomedicine through a strategic investment by the University of over £7.5M. The Centre became a core node for the last 14 months of the award. Following on from the funding of this Centre, researchers from Exeter were successful in a bid for a mathematics hub in healthcare that has broadened the focus to include diabetes and anti-microbial resistance.
Exploitation Route There are several routes by which the outcomes of this funding may be taken forward. The aforementioned Hub for Quantitative Modelling in Healthcare is already achieving this in the context of diabetes and AMR. Investigators funded through the Centre continue to build clinical networks that enable results from this award to be tested in the context of diagnosis and prognosis of disease.
Sectors Healthcare

URL https://gow.epsrc.ukri.org/NGBOViewGrant.aspx?GrantRef=EP/T017856/1
 
Description Through the establishment of a spin-out - Neuronostics - findings related to how brain networks are disrupted in conditions such as epilepsy and dementia are being trialled in a number of clinical contexts. These studies continue to receive substantial grant support (including ~£900K from NIHR and ~£500K from Innovate UK), as well as investment from venture capital. Neuronostics currently (03/22) employs 12 people.
First Year Of Impact 2021
Sector Healthcare
Impact Types Societal,Economic

 
Description Artificial Intelligence in Health and Care Award Phase 1
Amount £720,000 (GBP)
Funding ID AI_AWARD01646 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 01/2021 
End 12/2022
 
Description Characterisation Of The Stress Response In Children Undergoing Heart Surgery - A Mathematical And Machine Learning Approach
Amount £29,999 (GBP)
Organisation University of Bristol 
Sector Academic/University
Country United Kingdom
Start 01/2022 
End 03/2022
 
Description Emerging Leader Fellowship: Wessel Woldman
Amount £298,775 (GBP)
Funding ID F2002 Woldman 
Organisation Epilepsy Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2020 
End 06/2024
 
Description FAST - Flagellar Analysis and Sperm Tracking
Amount £35,000 (GBP)
Funding ID 38-18 / 520954125 
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 09/2021 
End 03/2022
 
Description Military Traumatic Brain Injury Biomarker Study, a prospective cohort biomarker study of military and civilian participants with mTBI
Amount £1,551,109 (GBP)
Funding ID MoD Predict 
Organisation Ministry of Defence (MOD) 
Sector Public
Country United Kingdom
Start 12/2021 
End 11/2029
 
Description Seizures and the Brain: The Role of Perturbed Dynamic Networks
Amount £1,911,878 (GBP)
Funding ID EP/T027703/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 07/2021 
End 07/2026
 
Description University of Birmingham Dynamic Investment Fund
Amount £16,000 (GBP)
Organisation University of Birmingham 
Sector Academic/University
Country United Kingdom
Start 02/2020 
End 03/2021
 
Description Utilising a glucagon-like peptide 1 receptor agonist to treat Space flight-Associated Neuro-ocular Syndrome
Amount £93,703 (GBP)
Funding ID ST/W004976/1 
Organisation UK Space Agency 
Sector Public
Country United Kingdom
Start 09/2021 
End 03/2022
 
Description Birmingham Women's and Children's NHS Foundation Trust 
Organisation Birmingham Women's and Children's NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Meurig Gallagher's application of fluid dynamic modelling to investigating problems in male fertility. Examining how mathematical modelling can be used to extract informative and accurate information from biomedical and clinical imaging data sets, with the aim of creating tools for researchers and clinicians to use.
Collaborator Contribution Dr Jackson Kirkman-Brown MBE, HFEA Person Responsible, Birmingham Women's Fertility Centre; Qamar Walayat, Senior Clinical Embryologist, Birmingham Women's Fertility Centre. JKB provides clinical and biological expertise to the partnership in the field of assisted reproductive technology and access to donor samples for data analysis and experiments, as well as driving the clinically focussed areas of the research partnership. JKB, QW and the embryology team provide access to clinical linked imaging and outcome datasets.
Impact Multidisciplinary: mathematics, clinical medicine
Start Year 2009
 
Description University Hospital Birmingham (UHB) Precision Antithyroid Therapy 
Organisation University Hospitals Birmingham NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Meurig Gallagher's analysis of patient data to better characterise the variations seen in people with hyperthyroidism, with the aim of developing an app to enable clinicians to predict the best dose of antithyroid drugs.
Collaborator Contribution Dr Zaki Hassan-Smith, Consultant Endocrinologist, Queen Elizabeth Hospitals Birmingham. ZHS provides clinical expertise and access to clinical datasets surrounding the treatment of thyroid disease, and drives the formulation of clinically relevant research questions.
Impact Multidisciplinary collaboration: mathematicians, clinical researchers, patients with lived experience
Start Year 2019
 
Description University Hospital Birmingham (UHB) Predicting, with Optical Coherence Tomography, Papilloedema - the POP study group 
Organisation University Hospitals Birmingham NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution John Terry/Wessel Woldman/Leandro Junges using a computer assisted analysis of eye scans and statistical modelling to predict those who have papilloedema and those who do not.
Collaborator Contribution Dr Susan Mollan (UHB): Clinical expertise
Impact Multidisciplinary collaboration. Mathematicians and clinicians
Start Year 2020
 
Description Midlands Digital Health Debate 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Online public debate event exploring what digital and data health sciences can and ought to be now and in the future.
Year(s) Of Engagement Activity 2020
 
Description Purple Day 2020 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact Panel discussion around how technologies could be utilised to make managing epilepsy at home easier.
Year(s) Of Engagement Activity 2020