NIHRDataInsights/HRCSData huggingface dataset:
Title: Novel methods for optimising health systems payment for performance interventions to improve maternal and child health in low-resource settings
Funder: Medical Research Council

Abstract: This project will apply novel methods rooted in complexity science to understand and optimise health systems payment for performance (P4P) interventions to maximise impact on maternal, newborn and child health (MNCH) in low-resource settings. P4P is a mechanism to improve the availability, quality and utilisation of essential health services through financial incentives to providers and healthcare managers. It has been applied widely in high-income settings and low and middle income countries (LMIC) have also started its implementation to improve MNCH. This research focuses on Tanzania and Zambia - a low- and a lower-middle income country, respectively, which have been implementing P4P schemes to improve MNCH outcomes since 2011. This study will build a system dynamic model (SDM) and an agent-based model (ABM) of the Tanzanian health system and its response to P4P. System dynamics represents a top-down approach to model the complex macro behaviour of the health system. ABM, on the other hand, is a bottom-up approach which can model emergent behaviour resulting from interactions between health workers, health care managers and patients. These models will be developed based on in-depth interviews, available data and literature reviews, and calibrated using 85%-90% data from the impact and process evaluations of P4P in each country. We will validate the SDM and ABM in the Tanzanian and compare ABM and SDM in characterising the P4P scheme in Tanzania. We will examine the generalisability of the model to Zambia. We will use these novel models to examine the intended and unintended effects of the P4P scheme that were not previously measured or observed, and to predict the effects of feasible changes to the design of the P4P scheme and examine what changes to the programme design would be needed to reach the desired output/outcome level. We will also build capacity among decision makers and researchers on SDM and ABM to study health systems using models in LMIC.


Research activity codes: 8.2 HEALTH AND WELFARE ECONOMICS
Health categories: GENERIC HEALTH RELEVANCE
Title: HNA: Development and evaluation of methods to assess the quality of audit data used to calculate risk-adjusted performance indicators
Funder: Medical Research Council

Abstract: Many national clinical audits (NCA) can be viewed as multi-centre prospective cohort studies into the quality of care. Their primary aim is to produce comparative information about organisational performance using a number of outcome indicators, and NCAs will generally develop regression models which capture the relationship between the outcome and patient factors in order to remove the effect of patient casemix (ie, regression models are used to produce risk-adjusted outcome statistics). Audit data are prone to numerous types of measurement error. These can arise in a random or systematic way, and can affect the outcome variable or explanatory / patient variables. There can also be structural patterns (eg, organisational level) in the distribution of errors, and the records of some patients might contain more errors than others, reflecting relationships between variables. These data errors can affect the estimation of organisational performance in two ways: 1. By influencing the accuracy of the coefficients in the risk-adjustment model 2. By influencing the adjustment process when an incorrect value is multiplied by the risk model coefficients. There are a range of statistical techniques available to detect potential data errors, including various post-estimation diagnostic statistics that are available after fitting a regression (risk-adjustment) model. Epidemiologists have also described techniques to assess the degree to which a specified bias mechanism might affect the estimated relationship between some exposure and outcome. However, these techniques are focused on the first problem of incorrect regression coefficients due to data errors. For NCAs, the second problem of incorrect values is of equal (or greater) concern than incorrect regression coefficients. Consequently, there is a need to develop a coherent set of practical tools for detecting measurement errors. We address this issue in the proposed research project.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES);8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: HSM:Development of methodology and computationally efficient software for analysis of PGx exome sequencing studies of complex "time-to-event" outcomes
Funder: Medical Research Council

Abstract: Personalised medicine promises to transform healthcare by maximising benefit whilst minimising harm from drugs. Pharmacogenetics (PGx) is of key importance to personalised medicine. Whole exome-sequencing offers compelling advantages over genome-wide association studies due to enrichment with functional variants and ability to investigate rarer SNPs likely to explain a larger proportion of heritability of complex traits. By using annotation, rare coding variants can be aggregated into groups exerting broadly similar molecular effects, and subjected to "gene-based" analyses, offering considerable power advantages over single-variant methodologies. However, available methodologies for gene-based analyses are aimed at binary and quantitative traits, making them unsuitable for PGx studies, which often have time to event outcomes e.g. time to remission or drug failure. An analytical bottleneck therefore exists for identifying genetic factors associated with treatment response. The proposed research aims to address this bottleneck. We aim to identify suitable models for single-variant analyses, including models to deal with more complex time to event outcomes e.g. involving competing reasons for drug withdrawal or those requiring a multi-component mixture modelling approach to fully reflect different remission status (i.e. immediate remission, delayed remission, no remission). The models will be extended to allow gene-based analyses, borrowing from gene-burden and gene-dispersion tests available for binary and quantitative traits. Of key importance, we will develop user-friendly, computationally efficient software for implementing the methodology. Whilst our methods and software will initially be applied to investigate genetic predictors of anti-epileptic drug response and age of onset of cardiovascular disease and type II diabetes, they will have valuable application across a range of complex disease and PGx traits which are currently not able to be explored optimally.


Research activity codes: 6.1 PHARMACEUTICALS;1.4 METHODOLOGIES AND MEASUREMENTS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: GENERIC HEALTH RELEVANCE
Title: War and Peace: The Health and Health System Consequences of Conflict in Colombia
Funder: Medical Research Council

Abstract: We will investigate the consequences of long-term internal conflict for health and the health system, and for post-conflict health policymaking, through an in-depth study of the Colombian experience of conflict and peace agreement. A peace accord between rebels and the Colombian government was agreed in December 2016, which creates a unique window of opportunity to conduct research of immediate policy relevance for Colombia and other conflict-afflicted countries. Key knowledge gaps exist about the dynamics of health and health systems during and after conflict. Our project will fill gaps in several areas and respond to the information needs expressed by Colombian policymakers, using a broader array of data than available for previous studies in Colombia and elsewhere. Our research will be undertaken through two linked work packages, guided by a suitable theoretical system framework. The quantitative package will rely mainly on two secondary datasets complemented by primary data we will collect with a new household survey, analysed using innovative econometric modelling. This work will uncover the consequences of conflict on child and adult health outcomes; variation of impacts across population groups; and the main mechanisms for impacts related both to individual demand for and system supply of health services. The qualitative and historic package will employ focus groups with conflict-affected communities, interviews with key stakeholders, and examination of policy documents and historic data sources. This package will further scrutinise channels behind the quantitative findings; examine how health policymakers have responded to the conflict consequences; identify key post-accord challenges for the Colombian health system; and identify possible strategies for responding to these. The results from these two work packages will be linked to specific, practical policy options within the Colombian context, informed by constant dialogue with national stakeholders.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE
Title: Routinely embedding recruitment and retention interventions within randomised controlled trials
Funder: Medical Research Council

Abstract: Many aspects of randomised controlled trials (RCTs) have, ironically, not been subjected to rigorous evaluation. In particular interventions to enhance recruitment and retention tend often to be based on 'custom and practice' rather than using approaches that have been tested using the most rigorous methodological approaches: particularly randomisation. However, there is an increasing interest in embedding methodological studies within randomised controlled trials. The MRC funded the START study, which aimed to test out two interventions for recruitment and retention across a number of clinical trials by performing 'Studies within a Trial' or SWATs and found it is feasible to undertake SWATs across a range of different trials and to undertake a pre-planned meta-analysis of their results. Furthermore, a SWATs Repository has been established with the aim of encouraging dissemination of SWAT ideas and their standardisation to facilitate future meta-analysis and synthesis. The aim of this programme of research is to build on the START initiative and make embedding 'Studies within a Trial' or SWATs as standard practice across multiple clinical trials units. We intend to pump prime and facilitate the start of at least 20 SWATs across multiple trials units within 30 months. We have established a network of trials units who have committed to starting at least two SWATs in the areas of recruitment and retention within 30 months of starting this study. The ultimate aim is to make the inclusion of SWATs routine when conducting a clinical trial.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: GENERIC HEALTH RELEVANCE
Title: DRIVERS OF HUMAN EXPOSURE TO ANTIBACTERIAL RESISTANCE IN THE SRI LANKAN ENVIRONMENT
Funder: Medical Research Council

Abstract: In this project, we will develop, parameterise and validate a modelling framework to identify: the levels of exposure of the human population in Sri Lanka to antibacterial compounds and antibacterial resistance genes in the environment; and the health, socio-economic and environmental drivers resulting in the greatest levels of exposure. The work will be delivered using a combination of model development and parameterisation work; country-wide surveillance studies of antibacterial compounds (ACs) and antibacterial resistance genes (ARG); and ethnographical and anthropological studies. Initially, a spatially explicit model will be developed to estimate concentrations of ACs and levels of associated ARGs in different environmental media across Sri Lanka over time. Anthropological and ethnographic methods will characterise the way in which humans in the country will be exposed to ACs and ARGs in the environment. The information will be combined to develop a spatially explicit framework for estimating the level of exposure of different human sub-populations across Sri Lanka to the environmental resistome. Information on antibiotic use, land use, demographics and environmental characteristics will be used alongside data from surveillance studies for ACs and ARGs in order to parameterise and evaluate the framework. The exposure framework will then be applied to model exposure of the human population of Sri Lanka to ACs and ARGs in the environment to allow us to identify hotspots of exposure across the country and to establish which drivers are contributing the most to these exposures. This knowledge will be used to evaluate the scale of the problem and in a co-design approach, with key decision makers in Sri Lanka, to inform the design and selection of social, policy and technological interventions for minimising exposure of the citizens of the country to ARGs in the environment.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION;2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE
Title: "Iraqibacter": Exploring the Links Between War and Antimicrobial Resistance
Funder: Medical Research Council

Abstract: Our working hypothesis is that heavy metal exposure is driving antimicrobial resistance in the setting of contemporary Middle East conflicts. This would represent a previously unknown epidemiological pathway for AMR of enormous public health significance in the Middle East and a game changer for understanding and addressing AMR globally. The drivers of AMRs in war settings are outlined by several factors that would impact the selection, survival and spread of AMR, such as poor hygiene, improper infrastructure, lack of proper antibiotic stewardship, in addition to cross border transmission of resistance through travelling organisms and populations. However, little attention has been paid to the role of heavy metals, because it is not widely known that these metal toxicants can co-select for antibiotic resistance-as demonstrated in emerging literature in industrial and agricultural settings. In the current conflicts, high levels of heavy metals have been demonstrated in conflict zones in the Middle East, and have been linked to a number of health-related outcomes among war-afflicted populations. Destruction of the built environment, a new feature of contemporary conflicts, also releases heavy metals contained in building and civic infrastructures, and can lead to leakage of antibiotics otherwise contained by waste treatment systems. These observations and reports raise many questions about the links between environmental contamination with heavy metals and the proliferation of AMR among the war wounded. Our goal in this project is to develop an interdisciplinary research program focused on the emerging problem of multi-drug resistant infections in war setting, with a focus on MDRAB. The overall research question investigates the development of MDRAB and the impact of war practices and use of heavy metal weapons on its emergence. Developing this program will help in understanding the drivers of AMR and develop regional strategies to limit it.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE
Title: Novel inter-disciplinary approaches for identifying and tackling the spread of AntiMicrobial Resistance through Environmental pathways in PAKistan
Funder: Medical Research Council

Abstract: The spread of antibacterial resistance (ABR) in human pathogens is a looming public health disaster. The combination of high burden of infectious disease, intensification of agriculture, poor sanitation, political instability, and unregulated antibiotic usage makes Pakistan a particularly high risk country for ABR. It is the sixth most populous nation in the world with over 200 million people but ABR in Pakistan receives far less attention than in India. We will redress this imbalance through an inter-disciplinary research programme. We will conduct a survey of ABR across multiple areas within Pakistan chosen to determine the importance of our hypothesised ABR risk factors: urbanisation, globalisation, intensive agriculture, pollution, and antibiotic usage. They will include the city of Karachi, which combines a high density of human population with both intensive agriculture and pharmaceutical manufacture, but also low-density rural areas. Within these areas we will take samples from a range of environments including health facilities, rivers, sewage, and slurry from intensive animal rearing. These will be subjected to microbiological tests for ABR including metagenomics sequencing, high throughput qPCR, and isolate cultivation. This will enable us to determine the importance of alternative ABR drivers and the rate of transmission into human pathogens. Concurrent, with the biological sampling will be an in-depth health systems study utilising geographical information systems (GIS), to characterise, and map the potential sources of ABR. This will be used to develop intervention strategies based around changes in antibiotic usage or sanitation. These two sources of data will be integrated into predictive epidemiological models of ABR spread allowing the efficacy of the alternate policies to be tested in silico. Finally, the most effective but politically feasible options - as determined by the health policy research component - will be recommended to stakeholders.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: GENERIC HEALTH RELEVANCE
Title: Supporting the National Action Plan on AMR in Tanzania (SNAP-AMR)
Funder: Medical Research Council

Abstract: We aim to provide novel insights into the biological, social and cultural drivers of antimicrobial resistance (AMR) that will help policy makers tasked with implementation of the Tanzanian National Action Plan against AMR to prioritise the use of limited human and financial resources via targeted, evidence-based interventions. We will use qualitative and economic methods to examine antibiotic prescribing and usage in the community and health system, examining practices and attitudes among hospital doctors, community pharmacists, drug shop workers, district veterinary officers, livestock officers and farmers. Key-informant interviews, surveys and focus-group discussions will provide a rich baseline understanding that will inform the design of stated preference choice experiments to identify trade-offs when making choices about antibiotic use and allow prediction of behavioural change given interventions such as a social norm 'nudge' or improved knowledge. We will examine genomic data from hospital and community-isolated Escherichia coli using phylogenetic analysis, plasmid reconstruction and identification of niche-indicators, to explore the link between hospital and community resistance (especially ESBL), and the link between AMR in human and livestock E. coli. Our findings will provide evidence to prioritise change in antibiotic usage in the community or health care settings, or in the human or livestock context. We will use social-science and design based approaches to visualise the pathways taken by antibiotic drugs; to capture the exchange of information between stakeholders at different organisational levels in the delivery of government policy; to design, deliver and evaluate a mass media campaign on AMR that recognises the need for change at the individual, community, cultural and societal levels; and provide social-science based media and communications training to build capacity in Tanzania amongst those in public health policy and communication.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE
Title: How do human and bacterial behaviour interact in urban and rural African environments to facilitate the stable acquisition of antimicrobial resistance
Funder: Medical Research Council

Abstract: The development of antibacterials has saved millions of lives; however, the massive global usage of these agents has created huge selective pressure for the emergence of antibacterial resistant (ABR) bacteria and drug resistant infection (DRI). This, combined with the flow of new antimicrobial agents slowing profoundly, has made ABR a public health threat of global importance and new approaches are necessary to reduce morbidity and mortality from DRI. In Low and Middle Income countries (LMIC), there is a huge burden of severe bacterial infection, a critical lack of accessible health system infrastructure to diagnose and appropriately treat bacterial infections and widespread availability of antimicrobials without prescription. This situation is responsible for a huge burden of disease, and is increasing selective pressure for ABR emergence. LMIC settings will be the last to benefit from new classes of antimicrobials and it is therefore of urgent importance to undertake research addressing ABR in LMICs that aims to identify drivers and interrupt transmission pathways of ABR pathogens. Only a truly interdisciplinary approach, from laboratory to policy implementation can impact on this problem. We will therefore describe the spatial and molecular epidemiology of ABR pathogens in the human, animal and environmental context in which antimicrobials are used, to: 1. Determine treatment strategies that leverage the fitness cost to pathogens of acquiring ABR thus minimising the emergence and persistence of resistance 2. Develop antimicrobial management and usage strategies across all sectors that both improve equity of access and restrict reserve agents in a manner acceptable to governments, communities and end users to minimise the local emergence and persistence of resistance; 3. Identify and addresses barriers to sustainable delivery of collaborative actions to address ABR at national and district level, both within and between human and animal health systems.


Research activity codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE