NIHRDataInsights/HRCSData huggingface dataset:
Title: Bayesian multivariate evidence synthesis methods to incorporate surrogate endpoints in health care evaluation
Funder: Medical Research Council

Abstract: In health technology assessment (HTA) reimbursement decisions are made based on economic evaluation of new health technologies by taking into account clinical effectiveness and health related quality of life (HR QoL) estimates. Clinical effectiveness is estimated by meta-analysing clinical outcomes obtained from randomised controlled trials (RCTs). To measure these outcomes, however, often requires extended follow up time of the RCTs. Therefore surrogate outcomes, especially those that can be measured early, are increasingly investigated as endpoints in RCTs and HTA where they are used to predict longer term clinical endpoints of the primary interest or HR QoL. Multivariate meta-analysis (MVMA) methods are most suitable to evaluate surrogate endpoints as they take into account the correlation between the outcomes and all associated uncertainty. Bayesian methods have the advantage of allowing analysts to make direct probability statements about predictions. Also in this framework external information (based on external data or expert opinions) can be incorporated in a model in the form of prior distributions facilitating synthesis of all available evidence and potentially leading to the more accurate probability statements and hence more efficient decision making process. Novel Bayesian MVMA methods will be developed for evaluating surrogate endpoints, taking into account appropriate uncertainty and inter-relationships between all model parameters. The work will be extended to multiple surrogate outcomes (to include all relevant studies) and multivariate indirect comparisons and network meta-analysis (NMA) methods. Extending evidence base to a wider range of interventions in NMA may lead to a wider range of reported outcomes, therefore the development of multivariate IC and NMA methods will be required. Methods for mapping surrogate outcomes onto utility measures, such as EQ-5D commonly used in economic evaluation, will also be developed.


Research activity codes: 1.4 METHODOLOGIES AND MEASUREMENTS;8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: Understanding the relative valuations of research impact: Applying best-worst scaling experiments to survey the public & biomedical/health researchers
Funder: Medical Research Council

Abstract: The aim of the proposed research is to develop a comprehensive ranking of scaled research-impact levels across different groups or type of research-impact for two stakeholder groups: the general population and biomedical and health researchers. A conceptual framework with different categories of biomedical and health related impact and different intensities of each impact category will be developed initially through desk research. The framework will be tested and refined through focus groups and key informant interviews. This will result in a survey instrument that will elicit rankings for the different impact statements that will be obtained using Best-Worst Scaling Choice Experiments, a robust technique based on Random Utility Theory. We will develop sets of scaled research-impact levels for each group of research-impacts in which respondents will be asked to select the levels they feel reflect the most and least important impact in each group. These profiles will be generated using experimental design such as fractional factorial orthogonal designs. Following a pilot of 100 participants from the general population and 100 biomedical and health researchers, the main survey will seek responses from 1000 members of the general population and 500 researchers. Participants in the general population sample will be recruited via an Internet Panel and will be representative of the UK's demographic profile in terms of a range of dimensions including age, gender, region, level of education and household income. Biomedical and health researchers will be recruited from a pool of MRC grantholders, and we would work with the MRC to ensure that this approach complies with data protection requirements. We will use discrete choice analysis to analyse the data and obtain full ranking of research impact levels for the two groups of respondents, allowing a comparison of their relative valuations of different types of impact.


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: Supporting Evidence-based Public Health Interventions using Text Mining
Funder: Medical Research Council

Abstract: This project will address current limitations in Evidence-based public health (EBPH) interventions by exploring new research methods, beyond the PICO framework, which combine text mining and machine learning to produce novel search while screening tools for public health. The PICO framework is conventionally used to structure pre-defined research questions matching clinical needs, helping to identify the Population, the Intervention, the Comparator and the Outcome. However, it is not well suited to the needs of EBPH reviews such as those conducted by the National Institute for Health and Care Excellence (NICE). PH questions are always complex involving behaviour, culture and organizations and often need to be described using abstract, fuzzy terminology in ways that make defining all the parameters in PICO a priori extremely problematic We will investigate novel approaches to EBPH reviewing based on text mining-based unsupervised methods for the discovery of direct and indirect associations to support a dynamic and multi-dimensional relevance required for public health reviews. In particular, it will build on distributional semantics methods to improve term and document similarity measures by including contextual information in a novel way. Novel descriptive clustering algorithms will be developed that will use these measures to group documents, to analyse their topics to yield meaningful cluster labels and to simultaneously yield high quality document and label clusters. The project will also produce new ranking algorithms to order and visualise meaningful associations in an interactive manner, suitable for EBPH reviewing. A pilot Web-based system providing a quick, interactive way of screening while searching, and visualisation, based on terms, their associations, descriptive clusters, labels and their ranking will form the basis for quantitative and qualitative evaluation for public health reviews related with alcohol misuse and consumption.


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: Better measurement of the complementarity between UK public, charity and private medical research
Funder: Medical Research Council

Abstract: We intend to create time series for the last 20+ years. Using the splits of public, charity and private research spending into 8-10 major therapeutic areas we will estimate models of the form: (1) Change in Private R&D = f (public research, charitable research, control variables) + time lags of changes (2) Change in Public or/and charitable research = g (private R&D, control variables) + time lags of changes Three main challenges face the econometric work: the possibly long time-lags between shocks/interventions and their effects; the possible presence of stochastic time trends; and the possibly bi-directional causality between public/charity and private expenditures. Since the implications of the implied lagged response are important, the model itself should be subjected to stringent testing. Information contained in long-run trends is lost when only time-differenced data are analysed, and this second methodological opportunity and the directionality issue could both be addressed by studying the panel cointegration properties of the various expenditure and control variables, adapting the modelling strategy accordingly. In this approach, private R&D and public/charitable research are regarded as co-determined in the long run, while it is possible to allow for differences in their short-run dynamics. We intend to break R&D expenditure down into therapeutic areas by developing techniques in bibliometric and patent analysis. We will use publications and patents as proxies for intensity of activity in those areas, controlling for the assumption that some fields are prone to more publication or patent activity than others.


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: A holistic statistical modelling approach to quantitative discovery proteomics and metabolomics for underpinning integrative systems medicine
Funder: Medical Research Council

Abstract: The huge body of evidence from life sciences research provides ample justification for the widespread potential of mass spectrometry-based discovery proteomics and metabolomics in systems medicine. Current bioinformatics methodology is reliant on the characteristics of controlled systems biology studies, but there is a step-change in complexity, heterogeneity and confounding within typical disease models and clinical samples. The pervasive approach to label-free liquid chromatography-mass spectrometry analysis is an ad-hoc series of data-reduction steps. Once the rich raw data is gone, multiple confounding effects are coalesced into single measurements with complex error distributions, non-linearity and large amounts of outliers and missing data. Data integration into rigorous statistical models for pre-clinical and clinical trial design, prediction models and latent endotype models is reliant on appropriate statistical handling, which is currently problematic. There is an opportunity to supersede the current ad-hoc quantitation pipeline with holistic Bayesian modelling able to cope with the demands of translational and clinical data: (1) We will develop variational Bayes latent variable selection methodology for unmixing, extraction and quantification under uncertainty, with strength borrowed via consensus signal morphology across runs. This will deliver statistically valid measurements with approximate posteriors. (2) We will develop a holistic modelling platform for systems medicine with Bayesian mixed-effects, integrating Bayesian protein and metabolite inference on the extracted posteriors, Bayesian transcriptomics methodology and experimental metadata. (3) We will acquire and disseminate first-in-class translational and clinical proteomics/metabolomics model experiments faithfully reflecting the challenges, plus apply the methodology to production experiments. This will answer how to appropriately validate for systems medicine applications.


Research activity codes: 1.4 METHODOLOGIES AND MEASUREMENTS;2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE
Title: Developing methodology for designing and evaluating theory-based complex interventions: an ontology for linking behaviour change techniques to theory
Funder: Medical Research Council

Abstract: Despite the recommendations that complex interventions to change behaviour should be informed by theory, there is a lack of guidance as to how to do this. We need a reliable, transparent method to link behaviour change techniques (BCTs) to theoretical mechanisms (operationalised as 'constructs' or 'domains'). This linkage ('ontology') will enable researchers to apply a systematic, shared method for (i) Intervention design: selecting BCTs on the basis of their judged mechanism/s of action, (ii) Evidence synthesis: aggregating interventions by BCT and/or hypothesised mechanism and (iii) Understanding mechanisms of action in order to both optimise interventions and develop theory. Such a behaviour change (BC) ontology requires the development of a method to produce it. This project aims to: 1. develop a systematic and replicable method for generating a BC ontology of reliably identified links between BCTs and theory (operationalised as theoretical domains and component constructs) (Studies 1-4). 2. produce a web resource and manual including guidance on how to use the ontology in intervention design and evaluation, and evidence synthesis, illustrated with examples from effective interventions (Activity 1). 3. maximise the engagement of the international scientific community in the use and future development of the BC ontology (Activity 2).


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: Stakeholder Engagement in EQUIPT for Impact (SEE-IMPACT)
Funder: Medical Research Council

Abstract: There is a growing literature on the potential of stakeholder engagement as a mechanism for promoting research use and impact, but limited analysis of how it best works in practice. The main objective of our proposed study (SEE-IMPACT) is to use a prospective approach to facilitate a more nuanced, empirically grounded analysis of the ways in which stakeholder engagement might operate as a key pathway to maximising impact from health research. The study also provides the opportunity to investigate ways of enhancing the transferability, and hence impact, of research. The SEE-IMPACT study will focus on an EU funded study (EQUIPT), which aims to achieve immediate impact through working with stakeholders to generate and disseminate bespoke information about the economic and wider returns from investing in evidence-based tobacco control agendas. The starting point is a 'return on investment' (ROI) tool developed in the UK, which will provide a baseline case study. Partly drawing on previous Payback studies, the SEE-IMPACT study will use a multi-method approach to test a series of hypotheses drawn from the literature. To seek to overcome the limitations of self report and recall in retrospective impact studies, the approach will also go further than previous Payback studies, as it will be prospective in design and will make greater use of participant and non-participant observation. The project will produce a detailed account of the evidence supporting (or refuting) the set of hypotheses distilled from the literature. In addition, the project will produce a detailed data set that might not only help identify preliminary indicators of effective stakeholder engagement, but also be one that could be revisited in a subsequent retrospective analysis. Representatives from research funding organisations who make decisions about stakeholder engagement will be involved in the project's international virtual advisory group so as to enhance the potential use of the findings.


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: Regenerative medicine: instrumentation for flow cytometry and cell printing
Funder: Medical Research Council

Abstract: Cell analysis and sorting Fundamental to stem cell research is high-quality instrumentation for analysis and selection of cell populations for research and translation. Flow cytometry and FACS instruments (with sterile hood) are essential to the regenerative medicine hub research in all 3 UKRMP hubs to which UoM is contributing. The requested machines would replace current obsolete 7 and 9 year old machines. Most suitable options are: - BD FACSAria Fusion with sterile hood (4 laser, 16 colour) which has fluidics allowing aseptic sorting, exceptional optical detection and fluorescence sensitivity, high numerical aperture light collection, precise coordination of optics and fluidics. - BD LSR Fortessa X-20 Research Flow Cytometer System delivers high performance multicolor analysis with up to 5 lasers, enabling detection of up to 20 parameters simultaneously. Cell/gel printer: a high-capacity cell/gel printer will transform our ability to test multiple cell/gel niche combinations, enabling evaluation of the complexity of stem cell niches through 'printing' stem cells within injectable self-assembling hydrogel solutions (fully-defined, animal product-free and relatively cheap to manufacture to GMP). Short peptides will be tested that self-assemble into beta-sheet type structures to create hydrogels suitable for encapsulation of stem cells (Merry CLR et al, PCT Submission GB2013/050295). These can be modified to display functional motifs (e.g. for binding cells) and for mechanical properties, and can support stem cell transplantation.. The only suitable instrument is: - CJ100004-2 CellJet, 4-channel (Digilab) (c£100k) can take up cells suspended in a pre-gel from a multiwell plate and decant them onto slides (or plates) in 10-100 nanolitre drop/spot sizes, using non-contact printing to maintain cell viability. Up to 4 channels/nozzles offers the opportunity to print in less restricted 3D patterns to better replicate tissue-specific environments.


Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING)
Health categories: GENERIC HEALTH RELEVANCE
Title: The application of interrupted time series designs for the evaluation of public health interventions
Funder: Medical Research Council

Abstract: Background: Randomized controlled trials are often not possible in the evaluation of population level health interventions due to significant limitations including contamination of the control population, lack of realistic generalisability, no feasible control and other ethical, legal or practical issues. Alternative methods for evaluating such interventions exist, however, these are not well established and there is a lack of clear guidance on their appropriate usage. This is limiting the appropriate evaluation of many public health interventions. The interrupted time-series (ITS) design is one of the most powerful quasi-experimental methods for evaluating the effectiveness of an intervention. A clearer understanding is required of when ITS is most appropriate and how it is best applied in the context of public health intervention research. Purpose: To develop the ITS design for the evaluation of complex population level health interventions, apply the design to evaluate the effectiveness of at least two interventions, and generate methodological guidance on the use of ITS designs in public health research. Methods: 1) A systematic review will be conducted of public health interventions studies using an ITS design in order to identify specific facilitators, barriers and methodological issues. 2) At least two population level health interventions will be evaluated using ITS designs. 3) ITS methods will be adapted and expanded in order to address barriers to validity. 4) The knowledge gained will be used to develop guidelines on the appropriate use of interrupted time series designs for the evaluation of public health interventions Scientific opportunities: Appraisal of ITS for public health intervention research; guidelines on the use of ITS for the evaluation of public health interventions; methodological developments; application of ITS to evaluate public health interventions as example case-studies.


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: Increasing the uptake of health services in low-income countries: What can we expect from user fee removal and financial incentives?
Funder: Medical Research Council

Abstract: Motivation: Additional evidence on the direct role of income on health services utilisation and on the health policies that indirectly increase income to stimulate the uptake of health services in LMICs is needed to increase the allocative efficiency of health expenditure. Aim: To provide additional evidence on the direct and indirect role of income on the use of health services in LMICs Method: (1) The effect of income on health care use controlling for the characteristics of health facilities will be estimated by using instrumental variables approach to correct for the endogeneity of income and the availability and quality of care. The analysis will be conducted in 4 LMICs (Ethiopia, India, Peru and Vietnam). I will compare the findings and investigate why income is a stronger predictor of health care use in some contexts. (2) A double difference estimator will be used to quantify the impact of user fee removal in Zambia on health care use, out-of-pocket medical expenses and catastrophic expenditure. The econometric analysis will report the intention to treat the local average treatment effect. (3) In Nigeria, HIV negative partners in sero-discordant relationship will be randomly selected in ART clinics to participate in a study that will consist in analysing the effect of income, risk aversion and their interaction on adherence to PrEP. Information on income and on direct and indirect costs of PrEP will be collected and risk aversion level will be assessed through a experimental economic game. (4) The results obtained from the research experiment in Nigeria will be used to design a RCT that will highlight the best manner to allocate a financial incentive (lottery versus cash payment) and the amount of the financial incentive that is likely to be the most cost-effective. Outputs: I expect to publish those findings in top health economics or development economics journals. Findings will be widely disseminated to academics and policy makers.


Research activity codes: 8.2 HEALTH AND WELFARE ECONOMICS
Health categories: GENERIC HEALTH RELEVANCE
Title: Direct and indirect impact of food taxes and subsidies on food consumption and population health
Funder: Medical Research Council

Abstract: The fellowship project aims to enhance the existing evidence on the effectiveness of taxes and subsidies in influencing consumers towards healthier food consumption, and thus on health outcomes. Specific objectives are: Obj 1. To test if, in the context of food consumption, people change consumption patterns less when subsidies are involved compared to their reaction to taxes. Obj 2. To test whether consumers' response can be assumed to be linear with respect to large and small taxes and subsidies. Obj 3. To test whether the indirect (cross-price and income) effects undermine, reinforce or do not affect the direct impact (own-price effect) of taxes and subsidies on food consumption. Obj 4. To analyse whether taxes and subsidies have further indirect effects on non-food consumption patterns. Obj 5. To explore the importance of other determinants of demand, such as habits and preferences, in consumer decisions. Obj 6. To test whether the above effects vary across different socio-economic groups or other sub-populations defined by the quantities of foods consumed or the BMI measure. These objectives will be achieved through implementation of two empirical studies. The first will use a highly disaggregated household panel micro-data set from Kantar World Panel UK and apply econometric models based on the Quadratic Almost Ideal Demand System (QAIDS). The QAIDS model will be extended to enable exploration of differential response mechanisms with respect to price increases and decreases, for example by implementing a two-stage approach where the first stage discriminates between the two situations. The second study will employ discrete choice experiment methodology to test the consumers' response to food taxes and subsidies. The experimental setting allows relaxing neo-classical assumption of consumer rationality and test the (in)direct impact of various scenarios of taxes and subsidies and explore the role of other attributes that affect consumption choice.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: GENERIC HEALTH RELEVANCE