CHIMERA: Collaborative Healthcare Innovation through Mathematics, EngineeRing and AI

Lead Research Organisation: University College London
Department Name: Mechanical Engineering

Abstract

Hospitals collect a wealth of physiological data that provide information on patient health. Full use of this data is significantly limited by its complexity and by a limited mechanistic understanding of the relationship between internal physiology and external measurement. Addressing this challenge requires multidisciplinary collaboration between mathematicians developing new biomechanical models, clinicians who measure and interpret the data to treat patients, and statistical and computational scientists to bridge the two-way translation between model output and real-life data. CHIMERA is designed to foster such collaboration to generate new understanding of physiology, new methods for relating physiology to real time data, and, finally, to translate these into practice, improving outcomes for patients by supporting clinical decision making.

CHIMERA will start by focusing on the most critically ill patients within hospital intensive care units: such patients have by far the most monitoring data and are most likely to benefit from improved understanding of what that data can tell us about their underlying physical state. Each year about 20,000 children and 300,000 adults in the UK need intensive care. These critically ill patients are continuously monitored at the bedside, including measurements of heart rate, breathing rate, blood pressure and other vital sign data. However, the wealth of these physiological data are not currently used to inform clinical decision making and clinicians can only really use real-time snapshots of the physiology to guide their decisions.

CHIMERA will address this unmet opportunity to use individual patient physiological data to support clinical decision making, with the potential to impact on patient management across the UK and beyond. This will be achieved through a multidisciplinary Hub which brings together experts in mathematics, statistics, data science and machine learning, with unique, high volume and rich data sets from both adult and paediatric Intensive Care Units provided through embedded Project Partnerships with Great Ormond Street Hospital (GOSH) and University College London Hospital (UCLH). CHIMERA will deliver new mathematical frameworks to learn the biophysical relationships that govern the interdependencies between physiological variables, based on data sets for thousands of patients through these project partners. Clinical impact will be achieved through an extensive series of clinically-led, multidisciplinary workshops themed around specific opportunities to improve care, for example identifying deteriorating patients in advance of an adverse event such as heart attack or stroke, or advance warning systems to diagnose sepsis. These workshops will include partnering with the Alan Turing Institute (the national centre for AI and Data Science), will be open to national participation, and will provide a mechanism to fund new projects by making available seed corn funding, PhD studentships and researcher resource for new interdisciplinary teams and partnerships. CHIMERA will build new links with clinical centres, companies and academic units across the UK and internationally, expand to work with a variety of patient monitoring data, and provide dedicated support to nurture new projects, funding bids and collaborations. In this way, we will build CHIMERA to a self-sustaining, multidisciplinary and vibrant Centre for the application of mathematical and data sciences tools in patient care.

Planned Impact

CLINICAL AND ECONOMIC IMPACT

Intensive care units (ICUs) treat the country's most critically ill patients. Intensive care is characterised by high resource use (both in equipment and staff), uncertainty in outcome and length of stay; and high levels of stress for patients and their families. Patients are intensively monitored, with almost all patients receiving continuous bedside monitoring for their heart rate, blood pressure, temperature, and how Oxygen and Carbon Dioxide are being used by the body. Such vital signs provide doctors and nurses crucial information about how well the patient's body is recovering from critical illness, particularly given patients are usually sedated and cannot provide direct feedback. Currently, clinicians can only really use real-time snapshots of the physiology to guide their decisions, with existing automatic monitor alarms being generally crude and unsophisticated.

CHIMERA's main clinical impact will be new mathematical and data science techniques that can support the decisions of the clinical team. Our models will provide clinicians with a better idea of how well the patient's body is recovering by using clues hidden in the wealth of physiological data collected for that patient since their admission to ICU. The possibilities for improving care in this way are practically endless but some of our foci include:
- ensuring that patients are weaned off organ support only when their bodies are ready to support themselves, but not longer than necessary;
- spotting deterioration before it becomes obvious through some adverse event such as a heart attack or stroke.
- diagnosing sepsis (a treatable but very dangerous condition) more quickly than can be done currently
- enabling better treatment for rare or complex conditions where a patient's physiology is very different from the norm making the monitor data harder to interpret (e.g. a severe heart defect).

In the longer term our work should lead to new clinical tools that could increase survival after ICU and reduce the time needed for patients to recover. With ICU stays typically costing £2000 - £5000 a day, any systematic reductions in length of stay could generate significant savings for the NHS. Meanwhile, we will be leveraging the enormous amount of data currently collected for each patient in ICU but that is currently not used in decision making.

During the lifetime of this hub, the impact will be more indirect as we increase our understanding of what the physiological data is telling us about how well someone's body is working, and discover promising avenues for new larger projects to develop clinical support tools. However, we will explore relationships with private sector partners (e.g. Microsoft, Google DeepMind) alongside our clinical partners in years 3 and 4 on how to translate our research into practice.

WIDER SOCIAL IMPACT

There has been a great deal of media coverage about the potential of data science and AI to improve health services, both in the UK and abroad. This has led to unrealistic expectations for what data science can actually achieve, and a public debate over how sensitive patient data should be used by researchers and by whom - particularly whether private companies such as Google, DeepMind should have access to NHS data.

CHIMERA will address both issues. Firstly, through our programme of public and patient engagement we will explain what we are researching, its potential to improve care as well as its limitations and what it cannot do. Secondly, we will engage the public and patients on how such new large datasets should be managed and governed - for instance, how do we balance the opportunities from private sector partners with risks to patient data and patient trust? How can we safely scale up the Hub's activities while ensuring transparent governance and accountability? Who owns the data and its anonymised derivatives, how should they be used and how will we communicate their use?

Publications

10 25 50
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Grigorian G (2024) A hybrid neural ordinary differential equation model of the cardiovascular system. in Journal of the Royal Society, Interface

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Jackson SE (2020) Understanding hormonal crosstalk in Arabidopsis root development via emulation and history matching. in Statistical applications in genetics and molecular biology

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Peters MJ (2020) Clinical Classification of Cold and Warm Shock: Is There a Signal in the Noise? in Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

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Peters MJ (2022) The United Kingdom Paediatric Critical Care Society Study Group: The 20-Year Journey Toward Pragmatic, Randomized Clinical Trials. in Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

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Schlapbach LJ (2023) Pragmatic trials for critical illness in neonates and children. in The Lancet. Child & adolescent health

 
Description We have developed a platform of mathematical models linked to physiology of patients in intensive care. Previous models have been predominantly based on animal experiments (for example pigs), whereas we have developed frameworks that can be baselined from patient data, and have begun this process.

Our approaches have primarily focused on describing the heart and lungs, and have involved statistical and machine learning to cope with the reality of working with real-world data (for example, data noise and missingness). We have also developed the data infrastructure to make patient monitoring data from intensive care units (such as heart rate, respiration rate, oxygen saturations, temperature) available for research purposes. Now this is in place, we are exploring clinical use cases where we use the data and models alongside each other - for example, prediction patient deterioration, when to extubate, airway clearance in physiotherapy within ICUs).
Exploitation Route - (Anonymised) patient data and all models are being made available as an open-source resource for the research community
- Programme of workshops (including a Data Study Group with the Alan Turing Institute, patient and public involvement and clinical-academic workshops framed around specific clinical questions)
- Further funding has been achieved to take forward the CHIMERA models and patient data access for specific clinical use cases - for example, to explore wearables monitoring with algorithms to risk stratify patients undergoing immunotherapy treatment for blood cancers.
Sectors Healthcare

URL https://www.ucl.ac.uk/chimera/chimera-0
 
Description We have established data ethics and set up a research database for sharing anonymised patient monitoring data with the wider researcher community.
First Year Of Impact 2023
Sector Digital/Communication/Information Technologies (including Software)
Impact Types Societal

 
Description Digital Health: A Digital Twin to improve holistic community-based diagnosis of heart disease
Amount £503,424 (GBP)
Funding ID EP/X000257/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 08/2022 
End 08/2024
 
Description National Institute of Health and Social Care Research Platform Development Grants
Amount £199,179 (GBP)
Funding ID NIHR155476 
Organisation National Institute for Health Research 
Department Health Technology Assessment Programme (HTA)
Sector Public
Country United Kingdom
Start 03/2023 
End 02/2024
 
Description Patient Monitoring Technologies (including CHIMERA funding for sepsis-prediction modelling, ICU physiology bed)
Amount £173,000 (GBP)
Organisation National Institute for Health Research 
Department UCLH/UCL Biomedical Research Centre
Sector Academic/University
Country United Kingdom
Start 08/2023 
End 12/2024
 
Description Pre-Symptomatic Detection of Deterioration in CAR-T Patients
Amount £40,850 (GBP)
Organisation National Institute for Health Research 
Department UCLH/UCL Biomedical Research Centre
Sector Academic/University
Country United Kingdom
Start 01/2024 
End 12/2025
 
Title CHIMERA research database 
Description A research database of de-identified high-resolution physiology measurements for the purpose of building mechanistic models of human health and disease from cradle to grave with the following secondary aims - To validate the robustness of the mathematical platforms we develop through their application and testing on data sets acquired from new hospital partners. - To engage the national community of mathematical, statistical and computational scientists to tackle unmet clinical needs and deliver new insights into patient health as well as clinical decision-making support tools. - To deliver Data Study Groups and workshops with the national community in data sciences, artificial intelligence and healthcare. - To deliver a programme of public and patient involvement, integrating patient input into the programme of research, providing researcher training, and delivering workshops around data use and sharing 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? Yes  
Impact The research governance is complete, and during 2022 we will start populating the data. 
 
Description Collaboration with Great Ormond Street Hospital Trust 
Organisation Great Ormond Street Hospital (GOSH)
Country United Kingdom 
Sector Hospitals 
PI Contribution Developed models of children's physiology in paediatric intensive care units.
Collaborator Contribution Part-funded the time of two clinical academic Co-Investigators on CHIMERA, as well as providing vital signs monitoring data for patients on the paediatric intensive care unit.
Impact See 'engagement' and 'publications'.
Start Year 2020
 
Description Collaboration with University College London Hospital Adult Intensive Care Unit 
Organisation National Institute for Health Research
Department UCLH/UCL Biomedical Research Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution Developing models of patient cardio physiology for ICU patients.
Collaborator Contribution UCLH Biomedical Research Centre have funded the time of numerous clinical academics to work in CHIMERA, as well as provided access to patient vital signs monitoring data from the ICU. Also provides PPIE training to all the CHIMERA academics and ECRs.
Impact See "Engagement", "Publications".
Start Year 2020
 
Description Effects of prone positioning on patient outcome 
Organisation University of Galway
Country Ireland 
Sector Academic/University 
PI Contribution Ongoing biomechanical model development to model the effects of body position on ventilation/perfusion ratio
Collaborator Contribution Data collected from ICU in Galway to investigate the impacts of prone positioning on patient outcome. Data recorded directly from the ventilator as well as medical staff, for both Covid and non-Covid patients.
Impact Mathematics, Engineering, Critical Care
Start Year 2021
 
Description Effects of prone positioning on patient outcome 
Organisation University of Warwick
Department Warwick Integrative Synthetic Biology Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution Ongoing biomechanical model development to model the effects of body position on ventilation/perfusion ratio
Collaborator Contribution Data collected from ICU in Galway to investigate the impacts of prone positioning on patient outcome. Data recorded directly from the ventilator as well as medical staff, for both Covid and non-Covid patients.
Impact Mathematics, Engineering, Critical Care
Start Year 2021
 
Description A presentation at the SIAM-UQ Minisymposium on Gaussian Process Modelling for Inverse Problems 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A presentation on : "Redefining model discrepancy in calibration: learning missing components from observations", SIAM-UQ Minisymposium on Gaussian Process Modelling for Inverse Problems
Year(s) Of Engagement Activity 2024
 
Description Acid Base Balance in Critical Care Medicine. CHIMERA ECR Conference. Septiandri. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Early Career Researcher Conference organised by CHIMERA for the EPSRC Maths in Healthcare Hubs (UCL, Cambridge, Exeter, Glasgow).
Year(s) Of Engagement Activity 2022
 
Description Bayesian updating with reliability methods: stopping conditions. European Conference on Safety and Reliability. Diaz. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact European Conference on Safety and Reliability
Year(s) Of Engagement Activity 2022
 
Description Branching Subset Simulation. European Conference on Safety and Reliability. Kinnear 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact European Conference on Safety and Reliability.
Year(s) Of Engagement Activity 2022
 
Description CHIMERA Early Career Researcher Conference - Volodina - Dynamic Linear Modelling for ICU Data 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Early Career Researcher Conference organised by UCL for the EPSRC Maths in Healthcare Hubs (UCL, Cambridge, Glasgow, Exeter).
Year(s) Of Engagement Activity 2022
 
Description CHIMERA Launch 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact We held a launch on the 20th January to celebrate the first year of CHIMERA, and to provide insight into what the hub is doing. We had discussions with our workstream leads and a virtual poster session, followed by closed discussions with the other EPSRC hubs. As a result we are working on ideas for hub integration, and have received positive feedback regarding the launch.
Year(s) Of Engagement Activity 2022
URL https://www.ucl.ac.uk/chimera/news/2022/feb/chimera-launch-celebration-watch-now
 
Description CHIMERA Workshops during BIOMEDENG'22 (September 2022) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The BioMedEng is a national conference which was hosted at UCL in September 2022. CHIMERA organised a workshop on integrating biomechanical modelling, statistical and machine learning from patient data, including 5 talks from CHIMERA ECRs.
Year(s) Of Engagement Activity 2022
 
Description CHIMERA/ Alan Turing Institute Workshop (lead Sina Saffron) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact A joint workshop organised by CHIMERA and the Alan Turing Institute, available to UCL researchers to work on clinical problems and healthcare data.
Year(s) Of Engagement Activity 2022
 
Description Calibration of a respiratory model at CHIMERA. BIOREME Webinar Series (online). Diaz 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact BIOREME is an EPSRC-funded network with complementary interests to CHIMERA - this talk was part of their webinar series, and initiated a new research collaboration on respiratory physiology modelling and statistical learning.
Year(s) Of Engagement Activity 2022
 
Description Calibration of models for clinical research. Department of Statistical Science, UCL. Diaz. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Internal research seminar at UCL, developing collaboration with the Statistics Department.
Year(s) Of Engagement Activity 2022
 
Description ECR Conference for the EPSRC Maths in Healthcare Hubs, Summer 2022, UCL. Christina Pagel and Becky Shipley Leads. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact We held an Early Career Researcher conference for the 4 national EPSRC Mathematics in Healthcare Hubs (UCL, Cambridge, Essex, Glasgow) including talks by the researchers, talks on building resilience from the academics, and training/ fellowship advice from EPSRC.
Year(s) Of Engagement Activity 2022
 
Description INI Gateway Cambridge Mathematics Of Information in Healthcare Hub (CMIH) Academic Engagement Event (Cambridge, 26th July 2022) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Talk on the CHIMERA Hub at the event - diverse audience of academics, practitioners and students.
Year(s) Of Engagement Activity 2022
 
Description Invited public lecture at the Institute of Physics and Engineering in Medicine 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact An invited public lecture by Rebecca Shipley at the Institute of Physics and Engineering in Medicine on "Hiding in Plain Sight: The Unseen Impact of Engineering in Healthcare".
Year(s) Of Engagement Activity 2023
 
Description Invited public lecture, Institute of Physics and Engineering in Medicine, Hiding in Plain Sight: The Unseen Impact of Engineering in Healthcare 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Invited talk for flagship event through IPEM, reaching ~150 people from diverse backgrounds - school children, healthcare professionals, engineering.
Year(s) Of Engagement Activity 2023
 
Description Invited talk, Australian and New Zealand Intensive Care Society Paediatric Study Group (ANZICS PSG) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Australian and New Zealand Intensive Care Society Paediatric Study Group (ANZICS PSG) - invited talk
Year(s) Of Engagement Activity 2022
 
Description Joint RRes-Exeter Digital Twin Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact A workshop between research hubs on Calibration of a digital twin. Learning model discrepancy
Year(s) Of Engagement Activity 2023
 
Description Poster presentation at Conference on Complex systems, Mallorca 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Poster presentation on Using complexity details of ICU monitor data to study extubation outcome
Year(s) Of Engagement Activity 2022
 
Description Poster presentation at a Conference on Deep Learning for Computational Physics, UCL 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact A poster presentation on "Application of Scientific Machine Learning for Time-Series Predictions of Biomedical Signals" presented at the Conference on Deep Learning for Computational Physics, UCL
Year(s) Of Engagement Activity 2023
 
Description Poster presentation at the SIAM UQ Conference 2024, Trieste, Italy 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A poster presentation by Jun Cheng, at the SIAM UQ Conference 2024, Trieste, Italy, on "Dynamic History Matching for a cardiorespiratory model".
Year(s) Of Engagement Activity 2024
 
Description Presentation at the SIAM UQ Conference 2024, Trieste, Italy. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A presentation by Alejandro Diaz, SIAM UQ Conference 2024, Trieste, Italy on "Calibration of a high-dimensional simulator through linked Gaussian processes".
Year(s) Of Engagement Activity 2024
 
Description Presentation at the SIAM UQ Conference 2024, Trieste, Italy. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A presentation by Hugh Kinnear at the SIAM UQ Conference 2024, Trieste, Italy on "Branching subset simulation for uncertainty quantification".
Year(s) Of Engagement Activity 2024
 
Description Presentation at the University of Birmingham. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact A presentation by Alejandro Diaz at the University of Birmingham on "Branching subset simulation for unconstrained optimisation".
Year(s) Of Engagement Activity 2024
 
Description Seminar on CHIMERA at Glasgow University 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact We held a seminar for the EPSRC hub at Glasgow University in ....... , where we presented the idea behind CHIMERA, details of the workstreams, our progress, and the next steps.
Year(s) Of Engagement Activity 2021
 
Description The CHIMERA Hub. Cambridge Center for AI in Medicine Summer School (online). Diaz. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Cambridge Center for AI in Medicine Summer School - around 50 people.
Year(s) Of Engagement Activity 2022
 
Description Workshop competition attendance, Glasgow 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Attendance by early career researchers at the SeCRET Competition on cardiac modelling organised by Glasgow Hub
Year(s) Of Engagement Activity 2023