NIHRDataInsights/HRCSData huggingface dataset:
Title: The Centre of Excellence for Public Health (NI) - Phase II (CoEfPHNI/II)
Funder: Medical Research Council

Abstract: Our mission is to build capacity for public health research, strengthen the evidence base for public health policy and practice and to improve the health of the population. Our aims are to ensure that our research is excellent while extending its reach and impact. Therefore our strategy and objectives for this renewal phase of the Centre are: (1) to expand and develop our staff and equip them with the skills for trans-disciplinary public health research; (2) to build on a platform of excellence in key programmatic areas {exploiting existing data; social determinants of health and disease; and health behaviours}, extending our research infrastructure and strengthening themes of priority to our partners and funders; (3) to consolidate our partnerships to ensure stakeholder engagement and active participation; (4) to work more closely with the other UKCRC Centres of Excellence to ensure that the initiative delivers its objectives for national and international leadership in the field; (5) to incrementally increase our grant income to ensure longer term sustainability. Our priority will be to use the unique opportunities that exist in Northern Ireland, with its distinctive approach to integrated health and social services and well connected civic and public sector structures, to research the social and biological causes of chronic disease and the main causes of inequalities in health experienced in the UK. In so doing we will demonstrate the added value of stronger multi-disciplinary public health research networks and provide a bridge between the academic and non-academic communities to ensure better knowledge integration and translation.


Research activity codes: 3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION);8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE
Title: Fuse, the Centre for Translational Reseach in Public Health (renewal)
Funder: Medical Research Council

Abstract: Fuse's mission is to transform health and wellbeing, and reduce health inequalities through the conduct of world class public health research and its translation into value for money policy and practice. Fuse's research will be conducted across six programmes: early life & adolescence, healthy ageing, behaviour change, health inequalities, complex systems, and translational research. These will focus on understanding public health problems and developing, evaluating and translating interventions to tackle them. Our work will involve food and nutrition, alcohol, smoking, physical activity, immunisation, risk taking, social determinants of health, diagnostic and treatment pathways, health policy, and translation of research into practice. As many public health problems are multifactorial and cannot be tackled in isolation, there will be significant overlap and interaction between the research conducted within each programme. Fuse brings together the diverse strengths of researchers based in the five North East universities, working collaboratively with local public health practitioners and policy makers to make a significant impact on major public health problems. We will make use of a wide range of research methodologies across our multi-disciplinary team, including: systematic reviews, secondary data analysis, natural experiments, randomised controlled trials, N-of-1 experiments, realist evaluation, and a range of qualitative approaches. Whilst we will follow a sequential approach to develop, evaluate and translate complex interventions, these steps are understood to be part of iterative, overlapping cycles. Central to Fuse's mission is developing understanding of how research findings can impact on mainstream public health practice and what governs this process. Fuse encourages meaningful involvement of policy and practice partners in all of its research activity and promotes thinking about wider implementation of findings from the start.


Research activity codes: 3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION);8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE
Title: MRC North West Hub for Trials Methodology Research
Funder: Medical Research Council

Abstract: The Medical Research Council funded North West Hub for Trials Methodology Research (NWHTMR) is a collaborative centre which brings together experts in biostatistics, clinical trials methodology, pharmacoeconomics, sociology and clinical psychology from the Universities of Liverpool, Lancaster, Bangor and Manchester. Our mission is to create a world-class centre where methodological issues facing the clinical trials community can be investigated, the overall aim being to improve patient care by improving the validity and relevance of the healthcare evidence base. The Hub has four major methodological themes as follows. (1) Early phase trial design and analysis Early phase trials lend themselves to adaptive procedures which allow research to proceed in stages. Bayesian methods may be utilised, in which prior information is incorporated and updated by data as they accumulate. The objective of the research group is to develop, promote, and implement adaptive methods for early phase trials. (2) Later phase trial design and analysis Later phase, or effectiveness trials, involve particular methodological issues. The objective of this theme is to address priority topics, for example the choice of outcomes important to patients and other decision-makers, and the identification of interventions to improve recruitment and retention of participants. (3) Patients' perspectives This theme is focussed on three workstreams: (i) optimising patient and public involvement in trials; (ii) ensuring patient centred and effective recruitment; (iii) incorporating patient priorities in outcome measurement. (4) Efficacy and mechanism evaluation of targeted therapies The idea that a given medical treatment will have more benefit for some patients than for others is the underlying foundation of what is termed personalised or stratified medicine. This group will develop trial designs for stratified medicine within which evaluation of mechanism is a key feature.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: The MRC ConDuCT-II Hub. COllaboration and iNnovation in DiffiUlt and Complex randomised controlled Trials In Invasive procedures
Funder: Medical Research Council

Abstract: The ConDuCT-II Hub is based within the School of Social and Community Medicine, at the University of Bristol and led by Blazeby, Professor of Surgery. It will build on the achievements of the ConDuCT Hub to develop the Hub into a world class centre of excellence for high-quality, cutting-edge methodological research of relevance to pragmatic randomised controlled trials (RCTs) in general, but with a particular focus on the needs of RCTs in surgery. Within the Hub there will be four interlinked research themes. The themes include: (1) trial prioritisation and design, (2) trial recruitment, (3) feasibility study design and trial conduct, and, (4) outcome assessment, reporting and integration into decision-making. Each theme is underpinned by expertise in statistics and qualitative methods and there are close links to practising clinicians and the two registered clinical trials units (CTUs) in Bristol. The Hub has regional and national collaborations with other registered CTU and MRC Hubs and it will develop new relationships with the Royal College of Surgeons of England Surgical Trials Centres and international collaborations with surgical trials centres in continental Europe and North America by providing innovative methods to optimise the conduct of trials in surgery and by provision of specialist training. The Hub will deliver a training programme for clinicians and methodologists in specialists areas to optimise the design and delivery of complex healthcare interventions and trials in surgery. The Hub will integrate new and improved methods into new trials in collaboration with regional and national CTUs working closely with clinicians (especially surgeons). The combination of new methods, training courses, workshops and apprenticeship opportunities offered by the Hub will lead to more and better trials to be developed to answer critical questions of relevance to patients and the NHS.


Research activity codes: 5.4 SURGERY;6.4 SURGERY;8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: Million Women Study
Funder: Medical Research Council

Abstract: In 1996-2001 we recruited a cohort of 1.3 million women, a quarter of the female UK population then aged 50-64 years. About 99% have been followed for more than 10 years for hospital admissions and deaths. Mean age is now 70 years and conditions associated with ageing, such as dementia and osteoporosis, are becoming increasingly common. We plan to focus on these emerging health problems, following the cohort for a further 5 years by electronic linkage to NHS records. The increasing availability of electronic routinely collected NHS records has revolutionized questions that can be addressed in cohort studies. Only recently was it possible to obtain linked NHS records for cause-specific hospital admissions in England. Linkage to NHS primary care prescription and diagnostic data has just become available. For women with a primary care or hospital record of dementia, we will confirm diagnoses and classify them by phenotype, where possible. We will then examine associations with postulated risk factors, taking care to avoid 'reverse causation bias' by focusing on the 15,000 women first diagnosed with dementia 10+ years after reporting risk factors. Bisphosphonates are increasingly used for osteoporosis, but surprisingly little robust information exists about their safety. Recent reports of serious pathological lesions of the bone and other possible long-term side effects are stimulating debate about the balance between beneficial and adverse effects in users. Randomized trials have been too small, with too little follow-up, to evaluate such effects. About 10% of study participants have used bisphosphonates, permitting reliable assessment of their net effect, overall and by duration of use. The uniqueness and timeliness of the research planned derives mainly from the size and maturity of the cohort, the wealth of prospectively collected personal data, and the virtually complete follow-up via electronic NHS records.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: GENERIC HEALTH RELEVANCE
Title: MICA: Children's Oxygen Administration Strategies Trial
Funder: Medical Research Council

Abstract: COAST is a randomised controlled trial designed to provide the evidence for the most clinically-effective and cost-efficient targeted use of oxygen as a life-saving treatment with respect to the optimal oxygen saturation threshold for treatment and mode of delivery in 4200 African children, aged 2 months to 12 years, presenting to hospital with respiratory distress complicated by hypoxia (oxygen saturation (SaO2)< 92%). Children will be enrolled over 30 months on admission to hospital at 4 sites in 2 countries (Uganda and Niger) and followed for 28 days (a sub-sample to 90 days). The trial has a pragmatic design, to ensure this encompasses a spectrum of high-risk children, identified largely by clinical criteria, so that the results are applicable to health services in Africa, with limited-resources. The trial will have two randomisations: R1: For children with a baseline SaO2<92% but >or=80%, randomisation to liberal oxygenation versus a more conservative strategy allowing permissive hypoxia (routine care) R2: For children with a baseline SaO2<80% and for those randomised to liberal oxygenation for R1, high flow versus low flow delivery (routine care) R1 addresses the question of what threshold to give oxygen in children with hypoxia (above a threshold of SaO2>or=80%); R2 addresses how best to give oxygen all receiving to oxygen. For R1, a cut off of <92% assesses a range of saturations that would be consistent with international recommendations for use of oxygen in sick children to provide additional data about those at a higher threshold than currently recommended by WHO. Children randomised to permissive hypoxia will receive low flow oxygen if they ever develop severe hypoxia (SaO2<80%). All randomisations will be open. Primary outcome is mortality at 48 hours Secondary outcomes include survival to 28 days; time to hypoxia resolution; duration of respiratory support to 28 days; severe respiratory failure at 28 days; neurocognitive sequelae at 28 days.


Research activity codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE
Title: Renewal of the Network of Hubs for Trials Methodology Research.
Funder: Medical Research Council

Abstract: The Network has added value to the Hubs for Trials Methodology Research by coordinating activities, encouraging and facilitating high-priority research projects, and facilitating the implementation of good practice into clinical trials in the UK and internationally. The Network facilitates the conduct and implementation of research into the design, conduct, analysis, interpretation, and reporting of clinical trials through cross-Hub work, as well as work between the Hubs and external teams. The Hubs and the Working Groups serve as key elements in delivering the strategy. The Network's objectives for the next period will be: a) Promoting high quality collaborative methodological research, both across Hubs and with other groups, UK-wide and internationally b) Providing methodological advice to the clinical trials community c) Encouraging the implementation of the most effective and appropriate methodological practice, for example by providing a coordinated package of education and training d) Working with external stakeholders, in particular to agree on shared priorities for research and guidance e) Capacity building of training in the UK by supporting a cohort of clinical and non-clinical PhD students in methodology. The work encompasses research into various aspects of clinical trial methods, including adaptive designs, statistical analysis, selection of outcomes and reporting of data. The Network resources are managed by the MRC CTU in London, with the Hub Directors as key drivers of the science, along with the convenors of six Working Groups, supported by the Network Co-ordinator. There are close links to the UK-registered Clinical Trials Units, charities and research funders, and policy makers. The Network will strengthen its relationships with industry and build on existing relationships with clinicians through, for example, the Royal Colleges and with patients and the public through, for example, INVOLVE and the James Lind Alliance.


Research activity codes: 7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT)
Health categories: GENERIC HEALTH RELEVANCE
Title: Centre for Drug Safety Science (CDSS)
Funder: Medical Research Council

Abstract: Adverse drug reactions (ADRs) are a major public health problem. The Centre for Drug Safety Science (CDSS) has developed an integrated chemical, biochemical, molecular, cellular and genetic approach to analyse the fundamental and complex mechanisms of ADRs in both in vitro and in vivo models. We have a matrix approach for the: a) collection and biobanking of clinical material; b) construction of experimental methods with appropriate statistical and informatic modelling and c) application of state of the art qualitative and quantitative bioanalytical methodologies in order to be able to define the chemical, biological and genetic basis of clinically-relevant ADRs. This allows us to address each specific issue in a fundamental manner, but also to operate with efficiency and effectiveness in the CDSS across both established and newly emerging safety issues. The CDSS provides critical mass for bioanalysis in terms of equipment and specialised personnel for both the execution of research and for training the next generation of drug safety scientists (clinical and non-clinical). We have a truly inter-disciplinary environment within CDSS with pharmacologists, chemists, cell biologists, molecular biologists, geneticists, computational biologists, mathematicians, modellers, immunologists and clinicians working side-by-side with the aim of taking our findings from the bench to the bedside to application, and also in the reverse direction. Collaboration is critical for the maintenance of the technical capability of the CDSS. Thus we work closely with industry scientists and regulators, to develop and apply new scientific methods that become fit for purpose with respect to hazard identification and risk analysis for both established and new classes of therapeutic agents. The comprehensive approach adopted by the CDSS is designed to reduce the burden of ADRs for both patients and for Industry, thus achieving the dual aims of improving patient health and creating wealth.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: GENERIC HEALTH RELEVANCE
Title: The molecular and cellular mechanisms that trigger and sustain a regenerative response
Funder: Medical Research Council

Abstract: The overarching aim of this proposal is to investigate the molecular, cellular and biochemical events that trigger and sustain a regenerative response following injury. We will first elucidate the molecular mechanisms that trigger the production of ROS following injury and then we will elucidate the mechanisms that result in the sustained production of ROS throughout the regeneration process. We have already established several HyperYFP transgenic lines in Xenopus and zebrafish, which will permit easy assessment of ROS levels during regeneration. Using these transgenic lines we will perform gain and loss of function analyses of various candidate genes (using transgenesis and TALEN technologies), known to be involved in the production or removal of ROS during regeneration. From these studies, we will be able to identify which gene products are required for the sustained production of ROS during regeneration. We also wish to identify the downstream transcriptional targets of ROS during regeneration. For this, we will perform microarray and/or RNA seq experiments during regeneration under attenuated ROS levels. We will then assess the function of some of these ROS-dependent genes during tail regeneration. Furthermore, we wish to identify the direct targets of oxidation, which impacts on intracellular signalling and/or transcription. This will be done using a combination of gain and loss of function experiments, together with targeted thiol proteomic approaches. Finally we aim to uncover to what extent are the various roles of ROS during appendage regeneration conserved across different models of regeneration, including tail and limb regeneration in frog tadpoles and fin regeneration in zebrafish. To achieve this aim, we will use many of the same techniques to manipulate ROS levels during limb and fin regeneration in frog tadpoles and fish, respectively, and we will investigate the outcome of such manipulations on the efficiency of regeneration of these appendages.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: GENERIC HEALTH RELEVANCE
Title: Tissue Mechanics in Growth and Regeneration
Funder: Medical Research Council

Abstract: The genetic and biochemical control of tissue growth and regeneration has been extensively studied over the last century. However, it is still unclear how the mechanical properties of cells and tissues contribute to how they are formed and sculpted. What is clear is that in order to change the 3D architecture of any structure, there must be forces, acting on the system. Therefore, to fully understand how a tissue reaches its appropriate size, pattern and architecture, we must study its physical characteristics. To this end I aim to address two fundamental questions: 1) How important are the mechanical properties of cells and tissues in generating forces that control patterning, growth and regeneration? 2) Do these forces in turn influence gene expression and signalling pathways? I will use the Drosophila wing disc, a genetically tractable and easily accessible system, as a model tissue. My approach is to foster a constant interplay between in silico models and in vivo experiments such that hypotheses can be generated and tested more efficiently. I will measure the mechanical properties of developing and regenerating wing discs, and correlate this with the growth patterns of the wing. I will physically stretch or compress the wing disc using a novel tissue stretcher I have developed, and measure how exogenous forces affect the growth, patterning, and signalling pathways in the wing disc, as well as its regenerative capabilities. This will provide a more causative link between mechanical forces and growth and signalling. Finally, I will build in silico 2D and 3D models to study the sufficiency of mechanical contributions to tissue growth and architectural changes. Understanding how mechanics can affect tissue growth may eventually lead to novel physical treatment strategies for cancer and tissue regeneration. Implementing the proper mechanical cues in the diseased tissue could induce cellular behaviours that biochemical cues alone could not provide.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE
Title: Heterogeneity in treatment effects: Can modelling techniques provide personalized prediction of treatment response and uncover groups of respondents?
Funder: Medical Research Council

Abstract: The proposed research aims to develop and examine two alternative approaches, each from a different methodological area, for assessing differential effects of treatments in individually randomized and group-randomized studies. The first approach for testing differential effects is inspired by ideas in causal modelling and involves the use of missing data techniques to create a predicted individual treatment effect (PITE) for each respondent. Particular focus will be given to the parametrization of the prediction model and incorporating uncertainty into predicted values. The second approach, regression mixture models, identifies latent classes of individuals who respond differently to a predictor (e.g. treatment), and then add covariates to understand why differential effects occur. This proposal develops both methods for individually randomized studies and compares/contrasts the two approaches. Additionally, both approaches will be extended for use with group randomized trials (GRTs). Specific aims are to: 1. fully develop the PITE approach for individually randomized studies; 2. evaluate and contrast the efficacy of the different approaches for finding differential treatment effects in individually randomized studies; 3. extend and evaluate each of these approaches to allow for estimation of differential treatment effects in group-randomized trials; 4. develop open-source software and associated training tailored to applied statisticians working on randomized studies.


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE