The need to keep Britain's ageing population economically active has prompted government policies aimed at extending working lives. However, working beyond the traditional retirement age may not be feasible for those with major health problems of ageing and, depending on occupational and personal circumstances (e.g. savings, retirement intentions, domestic responsibilities, whether work is arduous, rewarding), might be either good or bad for health. Non-medical circumstances, including the design of work and workplace policies, may also hinder or harm prospects of job retention. Better information on these questions has many potential uses - e.g. to optimise government and employer policies; to identify interventions that may help older workers with health problems to remain in work; to alert doctors to medical problems associated with poor vocation outcomes; and to inform fitness for work decisions; to improve the design of work for older people; evidence on health, ageing, and risk of occupational injury can be used to ensure older workers are placed in safe work and that, where possible, their employment opportunities are not restricted without good justification. We are being funded by the charity Arthritis Research UK to recruit and follow 6,000 men and women aged 50-64 years from some 18 general practices in England. The practices contribute to the Clinical Practice Research Datalink (CPRD), a research database maintained by the government's Medicines and Healthcare Products Regulatory Agency (MHRA). The CPRD contains a log of every medical consultation episode associated with significant events, illnesses, or medical activity (diagnosis, referral, prescription, death etc) among the patients of participating general practices. These data are pseudo-anonymised (only identifiable by an ID code) and collected by MHRA from 250 practices in England and Wales, from which we will sample practices. CPRD linkage offers compelling scientific and logistic advantages. In particular, because we will access the entire GP medical records of participants in selected areas of inquiry, we can pursue our study questions using a hugely detailed database in which many health events and their timings are objectively corroborated. This will enable us to explore the effect of health on work, and vice versa, at a level of detail that is not feasible in periodic interviewer-administered or postal surveys. Moreover, the data will be captured at very low cost relative to alternative means of acquiring the same information. ARUK has provided funding only to investigate the impact of common musculoskeletal disorders (MSDs) of ageing on work retention and the effect of deferring retirement on musculoskeletal health. This leaves us short, particularly in respect of research assistant time to develop the cohort and computing and statistical time to analyse the many non-MSD problems that the dataset offers. We hope through this bid to maximise the value of the cohort, and the efforts of participants, by extending our analysis to a much broader range of health conditions and their impact on work participation. Funding will be used to purchase more research assistant, data programmer and statistical time, but many of the other costs (eg mailing, clerical, payment to practices) are already met and many of the practical hurdles (eg ethics and governance permissions, access rights to CPRD data) have already been resolved. The MHRA's research director is a collaborator in this application. Patients from participating general practices who agree to be studied will complete questionnaires about their work and home circumstances, initially over a 3-year follow-up. With their written permission, we will access their health data via the CPRD and link this to their questionnaire data. The inter-relation of changes in employment (with reasons) and changes in health (eg major new illnesses, new treatments, mortality) will be examined statistically.

DRIVE-Health will train a minimum of 85 PhD health data scientists and engineers with the skills to deliver data-driven, personalised, sustainable healthcare for 2027 and beyond. Co-created with the NHS Trusts, healthcare providers, patients, healthtech, pharma, charities and health data stakeholders in the UK and internationally, it will build on the successes of its King's College London seed-funded and industry-leveraged pilot. Led by an established team, further growing the network of funding partners and collaborators built over the past four years, it will leverage an additional £1.45 of investment from King's and partners for every £1 invested by EPSRC. A CDT in data driven health is needed to deliver the EPSRC Priority for Transforming Health and Healthcare, EPSRC Health Technologies Strategy, and on challenges laid out in the UK Government's 2022 Plan for Digital Health and Social Care envisaging lifelong, joined-up health and care records, digitally-supported diagnoses and therapies, increasing access to NHS services through digital channels, and scaling up digital health self-help. This ambition is made possible by the increasing availability of real-world routine healthcare data (e.g. electronic health care record, prescriptions, scans) and non-healthcare sources (e.g. environmental, retail, insurance, consumer wearable devices) and the extraordinary advances in computational power and methods required to process it, which includes significant innovations in health informatics, data capture and curation, knowledge representation, machine learning and analytics. However, for these technological and data advances to deliver their full potential, we need to think imaginatively about how to re-engineer the processes, systems, and organisations that currently underpin the delivery of healthcare. We need to address challenges including transformation of the quality, speed and scale of multidisciplinary collaborations, and trusted systems that will facilitate adoption by people. This will require a new generation of scientists and engineers who combine technical knowledge with an understanding of how to design effective solutions and how to work with patients and professionals to deliver transformational change. DRIVE-Health's unique cohort-based doctoral research and training ecosystem, embedded across partner organisations, will equip students with specialist skills in five scientific themes co-produced with our partners and current students: (T1) Sustainable Healthcare Data Systems Engineering investigates methods and frameworks for developing scalable, integrated and secure data-driven software systems (T2) Multimodal Patient Data Streams will enable the vision of a highly heterogeneous data environment where device data from wearables, patient-generated content and structured/unstructured information from electronic health records can combine seamlessly (T3) Complex Simulations and Digital Twins focuses on the paradigm of building simulated environments, including healthcare settings or virtual patients, to make step-change advances in individual predictive models and to inform clinical and organisational decision-making. (T4) Trusted Next-Generation Clinical User Interfaces will place usability front and centre to ensure health data science applications are usable in clinical settings and are aligned with users' workflows (T5) Co-designing Impactful Healthcare Solutions, is a cross-cutting theme that ensures co-production and co-design in the context of health data science, engagement with stakeholders, evaluation techniques and achieving maximum impact. The theme training will be complemented with a cohort and programme-wide approach to personal, career, professional and leadership development. Students will be trained by an expert pool of 60+ supervisors from KCL and across partners, delivering outstanding supervision, student mentoring, opportunities, research quality and impact.

Thanks to the development of drugs known as antiretrovirals, people living with HIV (PLHIV) can live long, healthy lives. Unfortunately, PLHIV need to take antiretrovirals for the rest of their lives. Antiretrovirals are generally safe but can cause serious side effects in some people, particularly with long-term use. Common side effects are discovered in clinical trials. If a drug causes side effects that are too severe or too common it will fail the trial. It isn't possible to test enough people in a clinical trial to discover less common side effects. These are found by monitoring people taking the drug in the real world. It is also essential that the safety of a drug is monitored in people of all ethnicities because some side effects are more common in people belonging to a particular ethnic group. Our work focuses on the 3.5% of the Ugandan population - 1.5 million people - who live with HIV. At the moment we have very little information about how many PLHIV suffer side effects due to antiretrovirals. The importance of encouraging and enabling healthcare professionals to report drug-related side effects is recognised by the Ugandan government. However, systems for monitoring drug-related side effects have only recently been developed in Uganda and the number of reports is very low. Only 400 reports on side effects due to antiretrovirals were made during the 12-months from October 2018 to September 2019. We urgently need to improve reporting of drug-related side effects due to recent changes in the treatment offered to PLHIV in Uganda. In 2018, Uganda began a programme to rapidly roll-out antiretroviral combinations including dolutegravir (DTG), the new drug recommended by the World Health Organisation (WHO), to PLHIV. Uganda is also rolling-out Isoniazid Preventive Therapy (IPT) to prevent active tuberculosis - the main cause of death in PLHIV. Although DTG has some important advantages over other antiretrovirals, we know that in some people it can cause liver damage, high blood sugar, anxiety, insomnia or depression. In addition, the risk of side effects is likely to be higher when DTG and IPT are taken together. We aim to test whether reporting via a mobile application is effective at increasing reporting of antiretroviral-related side effects by healthcare professionals. If successful, our project will also improve our understanding of which side effects are most common in Ugandan PLHIV and how many people they affect. These are essential first steps in our work to make sure that every PLHIV is treated with the right antiretrovirals at the right dose in the future. The mobile application that we will test is called Med Safety(R). Med Safety(R) was developed by a European drug safety project and adapted for Uganda's National Drug Authority (NDA) by the UK's Medicines and Healthcare products Regulatory Agency (MHRA) but isn't yet widely used. We will recruit 3820 healthcare professionals from 382 HIV treatment centres to: 1) investigate factors that affect the success of rolling out Med Safety(R) among healthcare professionals and how healthcare providers feel about using the application; 2) discover whether using Med Safety(R) leads to more reports of drug-related side effects than the traditional web- and paper-based forms; and 3) whether using Med Safety(R) saves money for healthcare providers. We will also train researchers in drug safety. This project will show whether Med Safety is effective at improving the reporting of drug-related side effects by healthcare professionals. Our learning from deploying the Med Safety(R) application across a population that encompasses large, developed cities and isolated rural areas will be invaluable for wider global efforts in drug safety monitoring. Our strong links with National and International agencies including the NDA, MHRA and WHO will help to ensure that our work improves the safety of PLHIV.

Our vision is to develop enabling organ-chip technology to accelerate the time from medicines discovery to deployment supporting therapeutic innovation. This will be achieved through 3D bioprinting and micro-manufacturing techniques developed specifically for use within the complex environment of microfluidic organ-chips. Our vision and approach are supported by partnership with major biopharma, Organ-chip technology providers and by the UK regulators as well as wider community engagement with over 50 companies and other stake holders via Queen Mary's Centre for Predictive in vitro Models. The development pipeline for new therapeutics is failing due to inadequate pre-clinical testing methodologies and a reliance on in vivo animal testing. This has a significant environmental and sustainability impact with wasted energy and resources as well as associated time and money. It is estimated that over 90% of drugs entering clinical trials ultimate fail, wasting 10-15 years and over £1billion for each failed therapeutic. Furthermore, adverse drug reactions are estimated to kill 10,000 people a year in the UK alone. Unless we solve this challenge, industry will not be able to deliver on the exciting promise of new therapeutics. An organ-chip is a bioengineered system containing living cells in which key physical, chemical and biological aspects of a living organ are recreated in the laboratory to recapitulate in vivo behaviour. This technology has the potential to address the attrition in the medicine development pipeline by providing the analytical platforms that are essential for testing new therapeutics and predicting scale up performance in the clinic. In the USA, the FDA Modernisation Act in 2022 mandated that organs-chips can now be used to evaluate drug safety and efficacy as an alternative to animal testing. However, micro-manufacturing techniques are urgently needed to recreate the essential tissue/organ heterogeneity. This research programme will develop innovative micro-manufacturing approaches to spatially pattern tissues within organ-chips, producing models that replicate the complex intra- and inter- tissue heterogeneity, gradients and interfaces. Building on emerging technologies of light-based patterning, buoyancy/diffusion fabrication and 3D bioprinting, we will spatially pattern matrix niche environments, cell populations and mechanical and biochemical differentiation cues to create tissue patterning. Our novel approaches will overcome complex technical challenges including accessibility, scalability, size limitations, microfluidic boundary conditions, 3D spatial control, in situ cross linking, biological compatibility and sterility. We will therefore provide a toolbox of validated, industry-ready methodologies which will facilitate models that more accurately represent their in vivo homologues, increasing predictive power for pre-clinical testing. This in turn will stimulate a more efficient, affordable and sustainable therapeutic pipeline with accelerated delivery of safer and more effective medicines from bench to bedside. As demonstrator exemplars of this spatial tissue patterning technology, we will deliver a suite of musculoskeletal (MSK) organ-chip models aligned with partner needs. By developing micro-manufacturing spatial tissue patterning methodologies, we will enable next generation organ-chip models which industry desperately needs to accelerate the medicines revolution. This programme is therefore critical in providing a more efficient and sustainable preclinical testing pipeline to deliver safer and more effective therapies from bench to bedside.

While it has been recognised for some time that small particles from vehicle exhausts and other traffic related pollutants cause a range of health effects, policy within the UK and Europe has not directly targeted these. Emissions from vehicles and ambient air itself are regulated in terms of total particles, with no specific targeting of one component or another. While this is clearly prudent in that it potentially drives reductions in all types of particles, it is also inefficient as it is likely that some particles (or particle components) are more toxic than others. This project seeks to elucidate the more toxic components of the pollution mix in London, with particular emphasis on traffic generated particles. If successful this will inform a more focussed and more efficient policy process for regulating vehicle emissions and ambient air quality. As well as regulating vehicle emissions and ambient air, policy makers - particularly at local and regional government level-can influence air pollution impacts through traffic management and wider planning decisions. Here the project will provide better information on spatial and temporal exposures and their relation to adverse impacts of air quality. This dynamic exposure information will be a major step forward in assessing the scope for more focussed traffic and infrastructure planning and management in London, with possible applications elsewhere in the UK. Even though there is a substantial literature confirming the impact of traffic pollution on health there are still substantial gaps. There is very strong evidence that exposure to traffic pollution causes asthma exacerbations in children and reasonably strong evidence that it may cause other health effects including the onset of childhood asthma, non asthma respiratory symptoms, impaired lung function, total and cardiovascular mortality and cardiovascular morbidity. In this project we will undertake a number of new investigations to examine the relationship between chronic exposure to traffic pollution and health. These will include studies of mothers in pregnancy right through to senior citizens. These innovative studies will include health outcomes rarely if ever available for investigation of air pollution effects (e.g. primary care data, child cardiovascular risk factors). The use of exposure metrics on a fine spatial scale that are in routine use for policy in London will enable exposure response relationships to be used for quantifying policy options in terms of health impact. Further this will enable us to evaluate the health impact of trends in exposure to traffic related air pollution, most specifically the Low Emission Zone for London (LEZ).