NIHRDataInsights/HRCSData huggingface dataset:
Title: Widening patient engagement for orphan drugs trials
Funder: Medical Research Council

Abstract: Aim: To improve clinical trials and medicine use, to benefit both people with orphan conditions and the pharmaceutical industry. Objectives: 1) To generate theoretically informed and empirically grounded knowledge to inform wider patient engagement in orphan drug development. 2) To embed the use of qualitative research methods in pharmaceutical developments and practice, to enable a wider group of patients to participate and inform orphan drug research. 3) To synthesise understanding from objectives 1 and 2 to enable the redefinition, expansion and reconceptualising of orphan drug engagement to widen their reach and benefit. Research questions: 1) How do patients and other members of the public experience engaging with the process of orphan drug development, and how can engagement be optimised? 2) What is the promise of orphan drugs for patients and where are the gaps in understanding patients' experience and perspectives in drug development? 3) What would a broader definition of patient engagement entail and how can it best be embedded in the practice of orphan drug development to maximise productivity? Methods: I will: 1) Convene a patient advisory group to provide insights throughout the project. 2) Conduct semi-structured interviews with 30 patients with IPF; ten health professionals who support them; and ten members of organisations that recruit patients to trials. 3) Conduct nonparticipant observation of host organisations' staff practice (n=15) and semi-structured interviews with key staff (n=10). Support host organisation to trial and evaluate the use of qualitative methods to embed patient engagement into industry organisational practices. Outputs: 1) Draft guidance for embedding patient engagement for knowledge exchange in industry activities. 2) Ethnography of host's transformation planning for widening patient engagement. 3) Co-designed resources to recruit patients to orphan drug trials, seminar series and publications.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;7.3 MANAGEMENT AND DECISION MAKING;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE
Title: Alleviate: Hub for Pain
Funder: Medical Research Council

Abstract: The Alleviate will adopt a hybrid architecture: each group donating a pain dataset will choose whether to use the centralised hub or act as a federated node based upon data governance, size and complexity of the data and technical feasibility. The Research Data Management Platform (RDMP) open-source software tool will be utilised to curate, clean and transform data and automatically upload metadata and data dictionaries into the HDR Gateway. Within each federated node, a pseudonymised version of the data will be made available within a secure VM so that it can be queried by federation software integrated into the HDR Gateway. This will enable researchers and innovators to discover what data is available for pain research across the UK and run high level meta-analysis across the datasets to find relevant cohorts. Such capability will support the research community to find relevant datasets which can be efficiently re-used and support recruitment to clinical trials. Alleviate will automate the process to extract research project specific data from across the federated network into a single TRE, streamlining access to data once data governance approvals have been granted. Alleviate will upload pain specific phenotypes into the HDR phenotype portal. The Alleviate hybrid secure cloud Trusted Research Environment (TRE) will be delivered in partnership with Amazon Web Services, building on an existing successful collaboration over the past year. The environment will provide Next Generation capabilities including: - A suite of regularly updated, out-the-box software tools supporting machine learning (ML) and artificial intelligence (AI) development, statistical analysis and data management - Improved support for multi-modal data cohorts including imaging & genomics integration - Rapid scalability / elasticity / flexibility - as project demands require - Reduced capital investment in new physical infrastructure - High-availability - On-Demand Self-Service


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION);8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: Developing guidance for design and conduct of cluster randomised trials
Funder: Medical Research Council

Abstract: Cluster randomised trials are a firmly established alternative to individually randomised trials. It is well known that the CRT increases sample size, but it is less appreciated that the design is at greater risk of biases compared to the individually randomised design. There is a growing body of methodological work on how to mitigate these risks. We argue that there is no specific and comprehensive guidance available to help design and conduct CRTs so they are free or low risk of bias; and no guidance on when the risk of bias in a CRT would be so great that an individually randomised trial would be preferable. The overarching aim of this proposal is to develop guidance on when CRTs are appropriately justified and to improve the conduct of CRTs to reduce their risk of bias. The broad aims of these linked guidelines are thus to enable researchers to determine: When is a CRT an appropriate design choice and when is an individually randomised trial preferable? What is the appropriate choice of cluster to maximise efficiency and minimise contamination? How should a CRT be conducted to mitigate biases, especially due to identification and recruitment biases? How should randomisation and analysis be performed in a CRT to ensure inferences are free from bias? This guidance will be developed by conducting a review of the methodological literature (capitalising on novel methods) to inform the development of a consensus guidance document, developed iteratively using a Delphi process. The PI and three CIs are arguably world leaders in the methodology of cluster randomised trials, as well as having considerable applied experience. All have extensive international collaborations and through these collaborations the members of the steering committee are expected to consist of many of the world's leading cluster trialists. The consensus guidelines will be accessible to applied researchers and will include key guidance as well as exploration and elaboration.


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: The BLAST Network: Building Links in Ageing Science and Translation
Funder: Medical Research Council

Abstract: The demographic shift towards an ageing population poses significant health and societal challenges across the globe, with chronic ageing-related diseases, frailty and susceptibility to infection leading to poor quality of life and high healthcare costs. Despite significant advances in understanding drivers of biological ageing and discovery of interventions that have reached early-stage human clinical trials for age-related chronic and infectious diseases, there is a lack of 'joined-up' thinking across disparate ageing research disciplines, and the new science of ageing has not penetrated into clinical practice or social policy. These barriers block progress in both new discovery science and in implementing research findings into practice through the translational pipeline. To overcome these barriers, we will establish a new multidisciplinary network capable of 'Building Links in Ageing Science and Translation' (BLAST). The BLAST network will focus on increasing scientific understanding of the mechanistic drivers and biomarkers of biological ageing, by breaking down silos between researchers in the life, physical, environmental and social sciences. Through holding inclusive multidisciplinary workshops, summer schools and journal clubs, supporting new research through pump-priming funding, as well as establishing a significant online and social media community, we will facilitate interaction between network members to increase knowledge of ageing biology mechanisms and biomarkers. We will develop online training resources for health care practitioners and increase dissemination of ageing research findings to academics, business, policy makers and the general public. We will further partner with biotechnologists, chemists, engineers, health care professionals, social scientists, economists and policy makers to identify effective interventions in ageing processes and develop routes for translation of such interventions to improve health in later life.


Research activity codes: 7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT);8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: Football for Health: Increasing physical activity levels and improving mental health and wellbeing of girls and women in Somalia
Funder: Medical Research Council

Abstract: The aim of this study is to develop an effective intervention to increase physical activity levels and improve mental health and wellbeing of girls and women in Somalia by examining and refining a real-world grassroots football initiative. In Somalia, girls and women are less active than boys and men, especially in urban areas. The number of women who have depression is higher compared to men. Gobanimo Women's Football Club in Hargeisa was established in 2016 by local girls and women who wanted a safe space for physical activity and socialising. It has proven to be popular; growing from 6 to 50 girls and women between the ages of 13 and 45 years playing weekly. However, it is not clear who it reaches and whether it produces desired change. We would also like to know more about its potential impacts, how it works, what is needed for it to work best, and what stops it working. We will (1) Define the football intervention by conducting individual interviews with club founders and members to find out what activities take place and how they are delivered. (2) Understand the individual, contextual, and system-level factors that impact the intervention. (2a) We will conduct a workshop with girls and women to explore perceived barriers and facilitators to sport participation and impact of playing sport (or not) (2b) We will interview stakeholders to explore perceptions on norms and beliefs related to sport participation, and existing resources, facilities and opportunities for girls and women. (3) Develop or adapt the intervention and further refine a Theory of Change to make explicit the causal pathways leading to intended impacts. We will also identify instruments for assessing factors underlying the mechanisms of change. (4) Refine the proposed intervention through workshops with stakeholders to elicit feedback and develop a manual for delivering the intervention in new settings and pilot the intervention. This study will inform the design of a future feasibility study.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: GENERIC HEALTH RELEVANCE
Title: Improving the credibility and utility of in vitro research
Funder: Medical Research Council

Abstract: In vitro studies are integral to our basic understanding of human health, disease related pathophysiology and the drug development pipeline. We use them both to complement the understanding of mechanistic phenomena observed in in vivo and clinical studies and to inform the decision to advance to testing interventions in vivo. It is critically important that in vitro research be robust and reliable and that scientists are equipped to systematically identify, appraise and synthesise such evidence. In vitro research has not yet been subjected to the same levels of systematic scrutiny as in vivo and clinical research, and pilot data suggest that it is at high risks of bias. Unlike in vivo and clinical research, the tools and infrastructure to identify, synthesise and appraise in vitro research do not yet exist. Our aim, with key stakeholder engagement, is to develop these tools and infrastructure. We will identify and reach consensus of the critical facets that strengthen the experimental validity of in vitro studies using a systematic review of existing guidance, followed by a Delphi exercise. We will develop search strategies and compare the most effective methods to identify systematically primary in vitro studies for systematic review. We will develop the appropriate methodological framework and a protocol template for conducting systematic reviews of in vitro studies, using existing systematic review guidance and summaries of in vitro systematic reviews, followed by a Delphi exercise. Finally, we propose to test the feasibility of our tools and infrastructure and present the reporting and impact of key study design variables on outcome by conducting an exemplar in vitro systematic review. High quality systematic reviews are an important and critical tool to generate empirical evidence to guide improvements in the design, conduct and reporting of research. The proposal meets an unmet need to improve the quality of in vitro systematic reviews.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);5.1 PHARMACEUTICALS;8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: Virtual Clinical Trial Emulation with Generative AI Models
Funder: Medical Research Council

Abstract: This research will apply newly emerging generative AI technology to transform biomedical and health research by enabling virtual clinical trial emulations with synthetic data. AI research has made great advances in creating new data. With new generative AI models, we can generate synthetic patient populations that faithfully preserve the statistical attributes of real populations. Experiments with synthetic data will allow clinical researchers to perform "virtual-trials" to gain quantitative insight into causal relations between a target effect and its causes. This will enable prediction and comparison of hypothetical interventions to seek answers to important research questions that currently cannot be answered in real trials, including clinical questions associated with underrepresented populations of children, older adults, and patients with multi-morbidities and polypharmacy - these people are commonly excluded in trials. The project aims to validate the concept by seeking answers to the primary research questions including: 1) Can we use generative AI models to generate synthetic data that preserve the same value for research as real-world health data? 2)Can we perform virtual clinical trial emulations by discovering correct causal relations from the synthetic data? Within the scope of this feasibility study, we will focus on a specific Type 2 diabetes mellites (T2DM) use case, which is a confirmatory study to test the ability of the AI-driven virtual trial emulations by emulating established clinical trials to replicate their results. We will target the effect of an exemplar drug (i.e. Liraglutide, a GLP-1 receptor agonist). Over the years, several RCTs have been conducted in the LEAD (Liraglutide Effect and Action in Diabetes) program to collect detailed evidence about the effect of this drug on HbA1c and weight, cardiovascular risk, the lipid profile, and blood pressure. The trial emulations will attempt to rediscover their findings.


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: Establishment of a cell culture facility at Biogelx for the in-house validation and testing of Biogelx hydrogels
Funder: Medical Research Council

Abstract: Biogelx develops and produces 3D cell culture scaffolds, in the form of synthetic peptide hydrogels, which act as extracellular-matrix environments to support cell growth. Biogelx currently collaborate with researchers in industry and academia to provide bespoke hydrogels tailored to the client's specifications and driven by the user's specific research questions. A key future strategic goal for Biogelx is to establish an in-house tissue culture facility with the aim of generating proof-of-concept 3D models. This will greatly expand the applications of the Biogelx technology and increase the commercial impact of the company. Biogelx require the expertise of a biologist with a strong background in in vitro tissue culture to lead the establishment of the Biogelx tissue culture facility and train staff in standard tissue culture techniques. The proposed secondee, Dr Fiona Murphy, is a postdoctoral research scientist with more than 10 years' experience in the use of tissue culture models for the hazard assessment of pathogenic and novel particles and the elucidation of the mechanisms underlying particle-related pulmonary disease. Dr Murphy's research goals have a strong focus on the development and adoption of alternative in vitro methods to reduce the burden of animal models used in biomedical research and applied toxicology testing. The alignment of the strategic goal of Biogelx to develop in-house cell culture facilities with secondee's research aims to develop physiologically-relevant models of lung disease and in vitro alternatives for toxicology testing underpins the objectives of the secondment. Successful completion of the secondment will directly provide Biogelx with prototype validation of the tissue culture facilities and provide pilot data to support further funding applications by the secondee to establish biologically-relevant in vitro models to replicate pulmonary disease.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE
Title: Understanding Society
Funder: Department of Health and Social Care

Abstract: 2.2 The ESRC is a non-departmental public body, funded by the Department Business, Innovation and Skills (BIS). It is the leading agency in the UK for funding social science research and training in academic institutions and independent research institutes. ESRC interest in Understanding Society is to support the establishment of a major new resource for the academic and policy and practitioner communities. 2.3 The department’s purpose is to help people to live better for longer. Its priorities for 2012 to 2013 are: • making sure patients and the public are at the heart of the health and care system • improving the nation’s health through better health services • making the health and care system more accountable • improving public health • reforming long-term and social care DH leads across health and care by creating national policies and legislation, providing the long-term vision and ambition to meet current and future challenges, putting health and care at the heart of government, and being a global leader in health and care policy. The department provides funding for the health and social care system, assuring the delivery and continuity of services, and accounting to Parliament in a way that represents the best interests of the patient, public and taxpayer. 2.4 Specific policy topics of interest to DH in relation to Understanding Society are: • Health status • Health behaviours • Determinants of health • Wellbeing • Nutrition • Alcohol consumption • Equality and protected characteristics • Health and work • Biomeasures • Young people and families

Lay abstract: This Memorandum of Understanding between the Economic and Social Research Council (ESRC) and the Department of Health (DH) sets out the arrangements in respect of Government co-funding of Understanding Society. DH is engaging with the ESRC to commission research on its behalf according to Research Council research funding rules . The ESRC is acting as the lead commissioning authority for the Study for DH and other Government Departments and Devolved Administrations.

Research activity codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE
Title: Multimorbidity in the context of socioeconomic deprivation: A mixed methods exploration of how individual and community factors interact to influence patient capacity to manage multimorbidity (MOSAIC)
Funder: Chief Scientist Office, Scotland

Abstract: Managing illnesses can be hard work: we know that some people find it easier than others and that the community you live in can make a difference. Having support from friends and family, transport or knowing how to cope with illness are all important but we don’t know whether they are more important for some people than others. People living in areas where socio-economic deprivation is common are more likely to struggle to manage their illnesses. We want to identify what support or resources they use, or could use, to help manage illness. We will do this by firstly looking at how current “interventions” for people with multiple conditions support people to manage them. We will then concentrate on one community, speaking to individuals living with and managing illness, exploring community resources and community understanding of managing multiple conditions. We will see how the community factors interact with the individual ones. Finally, we will examine results from another study in the west of Scotland to find out whether what we found matches others’ experiences. By understanding what supports people to manage their multiple conditions well, we will be able to create services and treatments that are manageable, and flexible.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: GENERIC HEALTH RELEVANCE
Title: Should Scotland provide whole genomic sequencing for diagnosis of rare disorders: A health economic analysis?
Funder: Chief Scientist Office, Scotland

Abstract: Around 6-8% of the Scottish population have a rare disease, 80% of which have a genetic origin. Most rare diseases are severe, life-threatening and have a profound impact upon the individual and their family. The journey to diagnosis, often referred to as a ‘diagnostic odyssey’, can take many years, involves numerous hospital visits, costly and invasive tests, multiple misdiagnoses, and is often unsuccessful leaving shattered hopes and expectations. Recent developments in genomic medicine bring promise of improved diagnostic rates, potentially enabling earlier and more accurate diagnosis. Such information is useful for future family planning and even treatments. Whilst the new genomic tests are more expensive than standard care, fewer hospital visits and tests and opportunities for targeted treatments, could offset NHS costs of current testing, and be highly valued by patients and their families. NHS Scotland must decide soon which patients should receive which genomic tests. As science pushes forward, it is important not to lose sight of users at the centre of care. We propose to compare the costs and benefits of genomic testing for rare disorders, from the perspectives of service-users and the NHS, with NHS current practice.


Research activity codes: 8.2 HEALTH AND WELFARE ECONOMICS
Health categories: GENERIC HEALTH RELEVANCE