NIHRDataInsights/HRCSData huggingface dataset:
Title: Stratified approaches to blood donation
Funder: Department of Health and Social Care

Abstract: This theme will address the NIHR BTRU mandate “to improve the sufficiency of supply and safety of donation by use of stratified/personalised approaches to donation” through a portfolio of quantitative and qualitative studies, as well as "proof of concept" trials 3.1: Using INTERVAL trial data and intensive resurvey data to be collected in subsets of donors while randomisation is still intact (Section 5.6), we will identify donors who are particularly resilient to, or at risk of, iron depletion as a result of repeated donation. Analyses will be initially undertaken separately in each sex-specific randomised group, combining the effects of different characteristics developed using multiple regression methods for longitudinal studies. Risk scores will be combined across the sex-specific randomised groups if they are sufficiently similar. 3.2: Informed by Theme 2, we will generate risk scores for health consequences of repeated donation. These risk scores will be developed and validated in a similar way to those for iron parameters in WP 3.1 above. Here time-varying risk scores may also include previous reporting of adverse side effects, and their severity. We will thus develop validated risk scores to separate donors into groups with different risks of adverse health consequences. 3.3: We will use the risk scores and stratifications developed above, so that donation intervals can be tailored to different groups according to their risk of adverse outcomes. These adverse effects, both on iron depletion and health, will be weighted in order to combine the information across outcomes. Assigning these weights will involve qualitative work with panels of blood donors, so that the weights adopted reflect their perceived importance to donors. The weights will also take into account the views of health professionals. As a hypothetical example, we could develop a risk score that predicts a composite (weighted) adverse outcome, which can be evaluated in male donors in the INTERVAL trial (Table 1). In this example, in order to maintain the 2-year adverse outcome rate at 10% or below, while maximising the blood donation rate, an 8-week interval is suitable for those in quintiles 1 and 2, 10-weeks for quintile 3, and 12-weeks for quintiles 4 and 5. Risk scores which are time-invariant will lead to stratified donation policies in which individuals maintain the same donation interval over time


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: GENERIC HEALTH RELEVANCE
Title: Determinants of donation-related biomarkers
Funder: Department of Health and Social Care

Abstract: This theme will address the NIHR BTRU mandate to identify and characterise “genetic, biochemical, lifestyle and other determinants of relevant blood cell traits…and measures of iron homeostasis, including determinants of the trajectories of these factors over time among donors”. 1.1: focus on the following panel of biomarkers: a) iron-related biomarkers, ie, soluble hepcidin, ferritin, and iron levels to be recorded through this award in all 50,000 INTERVAL donors at baseline and the 2-year resurvey, plus soluble transferrin receptor, total iron binding capacity, and zinc protoporphyrin recorded in the 2200 intensively monitored donors 1.2:focus on the ~820,000 variants measured in the Affymetrix “Biobank” array (Section 3.3), augmented by imputation of ~20M further variants using dense haplotype reference panels (eg, UK10K Project [chair: Dr Soranzo], 1000 Genomes Project). We will study these variants in relation to: a) baseline values of biomarkers mentioned in WP 1.1 b) changes observed in biomarker values between baseline and the 2-year survey and c) serial changes observed in biomarker values in subsets of donors between baseline and the 4-year survey, incorporating resurvey data to be obtained from 2200 intensively monitored donors 1.3: To identify and characterise non-genetic determinants of trajectories of donation-related biomarkers, we will study past donation history (obtained from NHSBT’s “PULSE” database), demographic and lifestyle factors (eg, diet, use of dietary supplements, smoking). To identify biochemical determinants of trajectories of donation-related biomarkers, we will use information on ~40 soluble clinical chemistry biomarkers and >220 metabolomic analytes (Section 3.3) in two ways. First, to help understand reasons for sex differences in recovery rates from donation, we will study soluble sex hormones (eg, testosterone, oestrogen) as predictors of trajectories of donation biomarkers. Second, we will widen the scope for discovery by conducting assumption-free exploratory analyses using all ~260 measured biochemical analytes.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE
Title: Improving donor selection or cellular composition of the haematopoietic stem cell graft for transplantation to improve patient outcome
Funder: Department of Health and Social Care

Abstract: First aim is to undertake epigenetic profiling of either the donor, the recipient, or of differences between them with respect to transplant outcomes such as Graft-versus-host disease (GvHD) or non-relapse-related mortality and define these signatures which can allow a better ‘epigenetically matched’ donor where a choice of donors exists, or of modulation of the transplantation strategy according to risk profile e.g. targeting T-cell depletion approaches to those at greatest risk. Work will include: Profile the methylome of matched donors/recipients, stratified for acute/chronic GvHD status and severity, malignancy, CMV status, HLA genotype, ethnicity and gender, using the 450K array [M1-12]. Identify methylation variable positions in donors that predict severity of acute/chronic GvHD in a well-characterised discovery cohort [M12-24]. Evaluate the identified epimarkers in a large, independent donor cohort using MethyLight, a cost-efficient methylation-specific qPCR assay [M24-36]. Identify stratification criteria for donors preceding transplant, concerning application of immunosuppressive therapy, e.g. T cell depletion/repletion and pharmacological treatment [M36-60]. Second aim is the development of a simple robust methodology for generating a T-cell product that will hasten global immune reconstitution without inducing GvHD. Steps include development of a trial protocol, gain regulatory approvals and open a multi-centre trial within 12 months of initiation of the BTRU following scale up runs [M1-12]. The initial proposal is for a randomised phase 2 trial, with biased randomisation 2:1 for active intervention, 16+8 patients (32 registrered to allow for drop-out); immunological primary endpoint, detailed seconday immune endpoints, plus clinically relevant infection-related secondary endpoints, delivered in 4 centres over 2 years [M12-36]


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;6.2 CELLULAR AND GENE THERAPIES
Health categories: GENERIC HEALTH RELEVANCE
Title: Developing and evaluating cellular therapies to prevent or treat post-transplant relapse and/or enhance graft-versus-leukaemia effect
Funder: Department of Health and Social Care

Abstract: Executing a phase I study (n=10) of a CD19CAR DLI with an additional step to genetically disrupt TCR expression. The recombinant lentiviral vector constructs integrating the CD19CAR and the RQR8 sort-suicide genes are already assembled and evaluated (Figure 7). We estimate the study will complete 2 years into the BTRU funding cycle, and we will use the outcome data to design the most appropriate follow-on phase II study. Work from WP4.1 should then facilitate involvement of NHSBT in the manufacturing process to support a multi-centre study, the execution of which is one of the long-term objectives of the proposal.


Research activity codes: 6.2 CELLULAR AND GENE THERAPIES
Health categories: GENERIC HEALTH RELEVANCE
Title: Maturation of cultured reticulocytes to erythrocytes
Funder: Department of Health and Social Care

Abstract: It is known that external factors can affect reticulocyte maturation, for example studies in mice have shown that a dyslipidemic lipoprotein environment causes abnormal cholesterol accumulation in erythrocyte precursors, which in turn inhibits reticulocyte maturation [6]. To explore the process and requirements for in vitro maturation, in vivo derived reticulocytes isolated from adult peripheral blood will be separated into Heilmeyer I-IV by FACS sorting, according to a recently described protocol. WP2.1 Evaluation and optimisation of a range of filters for increasing yield and maturity of cRBC [M1-24]. WP2.2 Characterisation of normal peripheral blood retics to benchmark with existing cRBC product [M1-30]. WP2.1 and WP2.2 Modify conditions to optimise process of cRBC production and repeat filtration experiments on matured cRBCs and explore storage and stability [M30-60].


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: GENERIC HEALTH RELEVANCE
Title: Immortalised cell lines for sustainable supply of rare blood group phenotypes
Funder: Department of Health and Social Care

Abstract: WP4.1 Identification of factors required for enhancing proliferation and enucleation of erythroid progenitor cell lines: By comparing data from transcriptomic and proteomic analyses of BEL-A1 with that of stage-matched homologous non-immortalised erythroblasts, we will seek factors essential for enucleation and proliferation that are missing/affected in BEL-A1. Relevant to this is development in our lab of methodology utilising a concatenated tandem array of TFREs [20] for targeted proteome-wide profiling of transcription factors in erythroid cells. Inducible knock in/out approaches will be used to manipulate aberrant expression of selected genes. Transcriptomic comparison of the iPSC-derived cell line HiDEP1 with adult erythroblasts has revealed differential expression of many genes, including reduced expression of CD44 and CDH1 (e-Cadherin). Analysis of the promoters of these genes shows differential methylation in HiDEP1 compared with adult erythroblasts (data not shown). We will conduct a similar analysis of BEL-A 1. Transcriptomic, multiplex proteomic approaches and cell imaging will also be used to characterise and compare gene expression profiles across a multiple cell lines (see below) and with that of normal adult cells to identify common defects WP4.2 Optimise procedures to achieve increased, proliferation and enucleation rates for immortalised adult erythroid lines: We will also immortalise erythroblasts at different stages of differentiation and alter culture conditions, to identify optimal conditions for cell line preparation, with the highest enucleation rates. Failure of BEL-A1 to achieve high enucleation rates may be a consequence of insufficient mechanical stress imposed on the cells. WP4.3 Generation of cell lines with rare blood group phenotypes: Primary goal is therefore to generate immortalised lines of U- phenotype, but also of Fya-, Ro, Jkb- phenotype. Cells will be immortalised using the optimal procedure (as developed in WP4.2) and eventually we envisage using a GMP compliant protocol. Research milestones: WP4.1: Omics comparative analysis of BELA1 with adult cells to identify aberrant gene expression/protein levels (M1-12), with gene manipulation of selected targets (M12-24). WP4.2: Generation of new lines under a variety of culture conditions (M1-24). Trial conditions to more closely mimic in vivo environment initially BELA1, subsequently new line(s); co-culture (M6-36), scaffolds (M36-48). Evaluate novel chemical compounds on enucleation or repeat chemical screens on new cell lines (M12-36). Multiplex omic and cell imaging comparison across all lines with normal adult (M36-48). WP4.3: Generate lines of erythroid cells with desired blood group phenotypes using optimised procedures (M36-60).


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: GENERIC HEALTH RELEVANCE
Title: Improvement Science and Quality Improvement
Funder: Department of Health and Social Care

Abstract: This theme is central to this application, providing a suite of Quality Improvement (QI) tools and methods that are designed to overcome the significant barriers to translation of research into practice that together constitute the second translational gap. This theme will provide support to Delivery themes in the planning, conduct and evaluation of their projects, and evaluate the impact and effectiveness of the overall systematic approach. This research will develop and refine an approach that can be replicated across the NHS and internationally.


Research activity codes: 8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: Implementing evidence and improvement
Funder: Department of Health and Social Care

Abstract: The IEI theme will conduct a programme of research that advances theory, methods and practice on the co-production and translation of evidence into healthcare practice. It addresses the learning needs of EM CLAHRC and EM AHSN to 1) appraise and establish an evidence base for its co-production and knowledge translation strategies; 2) determine the expectations, requirements and receptiveness of commissioners and service providers to co-produce and utilise research in collaboration with EM CLAHRC and EM AHSN. The short term (1-3 years) objective is to complete three linked appraisals of the EM CLAHRC co-production and translation strategy as applied to four types of service improvement (see Fig.1). These studies will deliver short term learning for EM CLAHRC and support future translation with regional stakeholders, including EM AHSN, LETB, CCGs, HWBs and service providers. The medium-term objective (year 3) is 1) to synthesise evidence from these initial projects to provide formative feedback to EM CLAHRC and EM AHSN; 2) to develop propositions on how research evidence does (or does not) contribute to service improvement. These propositions will be examined through subsequent Phase 3 research. The long term (years 3-5) objective is apply the learning and propositions from earlier research through subsequent Phase 3 studies on emergent co-production and translation strategies developed by EM CLAHRC, EM AHSN and other research partners, with particular reference to novel strategies for translation and commercial exploitation of IP within the regional and national health economy. This work will develop transferable lessons on the co-production, translation and application of research evidence to enable commissioners and providers to introduce improvements at practice, organisational and system levels. Theme members will apply for further funding from relevant sources, including the NIHR.


Research activity codes: 8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: Diagnostics and stratified medicine
Funder: Department of Health and Social Care

Abstract: Aim: To improve the health of people in the South West and beyond by: (1) producing generalisable research evidence about diagnostic strategies; (2) developing and spreading evidence-based diagnostic pathways in the South West Peninsula, and; (3) increasing the South West Peninsula’s capacity to deliver world-class research in diagnostics. These aims recognise that knowledge about individual tests is maximised only when it is translated into evidence about diagnostic strategies that are, in turn, integrated with evidence about patient management in diagnostic pathways. Linkage of evidence is thus important.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: GENERIC HEALTH RELEVANCE
Title: Prevention and detection of disease
Funder: Department of Health and Social Care

Abstract: In this theme we target prevention and early detection in early and midlife populations and in groups that have high risk but poor access to preventative and therapeutic services. We will work with three Local Authorities (Birmingham, Coventry and Warwick) to develop and evaluate interventions.


Research activity codes: 3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: GENERIC HEALTH RELEVANCE
Title: Methodological Innovation (‘Methods’)
Funder: Department of Health and Social Care

Abstract: Theme aim is to contribute methodological innovations that enable and enhance the conduct and implementation at scale of applied health research (AHR) for the benefit of patients, the public and the NHS. We will: • meet the methodological challenges of designing and delivering excellent research for direct patient and population benefit in the context of increasing structural and organisational complexity; • address current weaknesses in the production and implementation of research findings by improving the relevance, utility, efficiency and timeliness of AHR.


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: Evidence Based Transformation with the NHS (EBT)
Funder: Department of Health and Social Care

Abstract: Aim: To improve patient care and clinical outcomes across the region, disseminate actionable research findings that can be deployed nationally and internationally, contribute to the science of service improvement by: a) Supporting the AHSN Transformation theme in co-producing an evidence based approach to identify ‘positive’ (i.e. high quality) practice and understanding the behaviours and enablers that support such practice - sharing skills and knowledge across CLAHRC and the AHSN (short-medium term) b) Conducting rigorous research in collaboration with NHS partners to guide policy and practice on whether positive practice networks are a cost effective implementation method and leverage additional funding to support this work (medium term). c) Understanding the processes by which knowledge, skills and behaviours are spread and what factors act as levers and barriers through a social network analysis (medium-long term) d) Building regional capacity for improvement research and practice (by, for example, training courses, PhD studentships, clinical secondments and collaborations with other CLAHRC themes (medium -long term). e) Evaluating novel approaches to improvement with regional NHS partners e.g. patient involvement and feedback interventions, organisational peer to peer review, multi-professional training (medium-long term)


Research activity codes: 8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES);7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT)
Health categories: GENERIC HEALTH RELEVANCE
Title: Public Health and Inequalities
Funder: Department of Health and Social Care

Abstract: The overall aim is to undertake, and support implementation of, research which tackles the wider determinants of chronic conditions, and the associated inequalities in health, for those with chronic conditions, addressing key priorities for the Y&H region in collaboration with local authorities (LAs), public health practitioners and local communities.


Research activity codes: 7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT)
Health categories: GENERIC HEALTH RELEVANCE
Title: Avoiding Attendance and Admission in Long Term Conditions (AAA)
Funder: Department of Health and Social Care

Abstract: The overall aim of this theme is to implement and evaluate interventions to reduce avoidable attendances and unplanned admissions for patients with long term conditions. This will be achieved through establishing collaboration with key stakeholders including NHS providers, commissioners and patient groups in Yorkshire and Humber. The theme will develop new and existing research capacity of stakeholders and will aim to sustain research funding into interventions to reduce avoidable attendance and admissions in the long term, including developing national multi-centre studies.


Research activity codes: 7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT)
Health categories: GENERIC HEALTH RELEVANCE
Title: Telehealth and Care Technologies (TaCT)
Funder: Department of Health and Social Care

Abstract: The overarching aim of this theme is to produce a step change in knowledge and practice in the design and use of telehealth and care technologies in services that are effective, cost-effective and are usable by the broadest possible range of people.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE
Title: Health Economics and Outcomes Measurement (HEOM)
Funder: Department of Health and Social Care

Abstract: The overall aim of this theme is to work in partnership with the local NHS to meet the required improvements in efficiency and equity in the use of NHS funds over the next 5 years. It will seek to achieve this through the provision of a high quality relevant, flexible and accessible research capability in health economics and outcome measurement to the CLAHRC YH and its local NHS collaborators. It aims to undertake and implement international-class applied research to inform national and local NHS policy.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE
Title: Cross Programme Research
Funder: Department of Health and Social Care

Abstract: The theme supports ongoing learning and includes a range of activities: learning from evaluations to inform future work, project-specific evaluations, cross-programme and project comparisons and learning and sharing events.


Research activity codes: 8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES);7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT);3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION)
Health categories: GENERIC HEALTH RELEVANCE
Title: PPIE
Funder: Department of Health and Social Care

Abstract: The PPI Theme is cross-cutting and will interact with all the 8 CLAHRC Health Themes at three levels: (i) to collaborate with all health themes in order that PPI is embedded in their work; (ii) to evaluate the impact of PPI on research and implementation in the health themes and to develop robust and systematic methodologies for such evaluations; and (iii) to establish an SOG, with all PPI constituencies represented, to facilitate (i) and (ii).


Research activity codes: 8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES);7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT);3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION)
Health categories: GENERIC HEALTH RELEVANCE
Title: Dementia, Frailty annd End of Life Care
Funder: Department of Health and Social Care

Abstract: The overall aim of this theme is to develop the evidence base that will support the efficient delivery of safe, timely and coordinated patient-centred services to the older population transitioning to the fourth age of life and at the end of life.


Research activity codes: 7.2 END OF LIFE CARE
Health categories: GENERIC HEALTH RELEVANCE
Title: Health Economics
Funder: Department of Health and Social Care

Abstract: Overall strategic aim: To undertake work that ensures scarce NHS resources are allocated more efficiently. The health economics research theme of CLAHRC East will work with local health professionals and the Eastern Academic Health Sciences Network (EAHSN), providing advice regarding the potential implementation of health economic evidence arising from research of CLAHRC East or as a result of wider research.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE