Title: NIHR Global Health Research Group on Atrial Fibrillation management at the University of Birmingham
Funder: Department of Health and Social Care

Abstract: University of Birmingham (UoB) has global ambitions around its reach and research impact, based on effective engagement, collaboration and partnerships to inform, utilise and contextualise its research. UoB has world-leading experts in AF management, and strengths in the improvement of ambulatory and local health care. Various global research studies into AF epidemiology and management are ongoing (Lip, Lane, Kirchhof). This, in partnership with LMIC counterparts’ regional expertise, can be co-developed to synergistically achieve a global impact on the management of AF and its direct health benefits to patients with this condition. Alongside this broad strategy UoB also supports focused engagement in several key strategic regions including China and Brazil (2 of our bid partners, although our focus will be on impoverished populations in these settings), to develop research to improve care and reduce inequalities. Moreover, UoB is investing in a new Institute for Global Innovation and Development (IGID), which brings together multidisciplinary research to address the most pressing global challenges. The Institute of Applied Health Research (IAHR) has a growing international reputation in a number of health themes and methodologies including epidemiology, biostatistics, health economics, systematic reviews, qualitative research and clinical trials. These existing investments are complementary to this proposal. In collaboration with clinicians and scientists IAHR delivers translational applied health changes to improve care, for example in COPD, obesity (behaviour change) and CVD management (Jolly, Lasserson, Manseki-Holland, Thomas). Cheng established one of the first academic GP departments in China. We have worked with International NGOs, WHO and UNICEF on designing and delivering country based programmes, health systems reform, adaptation and the development of complex health care and health promotion interventions, including delivery of quality health services from village to provincial hospital level in 3 provinces in Afghanistan and 2 in Tajikistan (Manseki- Holland). The present proposal builds on these multidisciplinary strengths and initial links with our partner countries, and would improve research capacity in the latter, with access to our multidisciplinary AF expertise. The Institute of Cardiovascular Sciences(ICVS) has a global reputation in AF research ranging from AF epidemiology and pathophysiology (Lip, Lane); novel mechanisms (Kirchhof); improvements of AF patient care pathways, incl. stroke/bleeding risk assessments, optimizing thromboprophylaxis, etc (Lip, Lane); and clinical trials (BCTU, Lip, Kirchhof). ICVS are involved in ongoing and published guideline-shaping AF trials and lead several international projects (MRC, Leducq Foundation, NIHR, BHF, EU H2020) aiming at improving AF management in HICs. Research from our group has informed national (NICE) and international AF management guidelines (ESC, ACCP, APHRS) and has helped to inform patients and the public about AF, its consequences, and therapy. Together the Institutes have delivered a programme of clinical trials within the UK in AF including: • The only randomized trial of community AF screening (SAFE(1); Lip, Jowett) • BAFTA, the Birmingham AF Treatment of the Aged trial(2) (Lip, Jowett) • Cardiovascular rehabilitation post-MI (BRUM trial(3)) and heart failure (BRUM-CHF(4)) which included integrated care that involved lifestyle modification and exercise (Jolly, Lip, Lane) IAHR and ICVS research capacity (300 staff) allows expertise to be drawn on when required, and high research income aids with the retention of expertise. IAHR also hosts the NIHR Global Health Research Group COPD and NIHR Global Health Unit for surgical clinical trials. These networks provide invaluable opportunities for shared learning and growth in research capacity for global health research. Post award support and delivery expertise from these existing awards will be drawn on from central university services to ensure streamlined processes. Our campus-based International Office, China Office (Guangzhou) & Brazil Office (São Paulo) will facilitate collaborative working with international partners (e.g. links to healthcare providers/government departments, assisting organisation of stakeholder meetings). UoB will support this research by subsidising input from senior academics (especially development/delivery of training), provision of office/facilities & general research support. UoB would cover senior academic costs for the first 6 mths (value ~£160k). In recognition of their importance, UoB will also provide honorary contracts to international partner co-applicants, allowing access to resources e.g. e-journals. To support sustainability post-grant, UoB will deliver a workshop for co-applicants after completion of the project and support further grant application development for future work in this important area. LMIC Partners: We have links with investigators in Brazil, China and Sri Lanka, and as part of this proposal we plan to engage health systems caring for very deprived communities within these 3 countries, 1: Brazil (upper-middle income; per capita GDP US$8,649, 207M population): Butantã favela (slum), São Paolo; 2: China (upper-middle income (per capita GDP US$8,123, 1,379M population): Shanxi province, the 4th poorest province; and, 3; Sri Lanka (lower-middle income (per capita GDP US$3,835), 21.2M population): Northern province. Data from these settings are very limited, and suggest that there is a major need to educate patients and improve the care pathways for AF management. Current status of AF in partner countries is detailed in the Additional Information section. This proposal will help us address these needs, not only to assess the health burden of AF, but will also to help assess the knowledge of the patient on their health condition and the care available for these patients at the community level. As documented in the WP1-3 below, all co-applicants will identify gaps and review approaches for provision of care for AF patients through systematic reviews as well as document existing management pathways in each setting. We will identify perceptions/perspectives from key stakeholders (patients, families, HCPs, service commissioners) of knowledge (AF and its consequences, available/possible treatment modalities and their benefits/implications) and current management pathways. This will inform the teams in each country, who in conjunction with the UoB team, will enable their prioritisation of the key research areas to be further developed. These priorities need to be appropriate for their current setting in terms of acceptability to key stakeholders aligning with financial constraints, stakeholder knowledge/perceptions and the existing management pathway. For prioritisation, each partner will consult with local policy-makers, healthcare professionals and AF patients to consider different dimensions (fit with local policy goals, perceived importance among local AF patients & clinicians, logistic complexity of delivery, technical feasibility, available resources). Findings will be presented and a final decision made in consultation with all co-applicants and input from international advisory groups. Most projects will involve mixed-methods (quantitative & qualitative) and include a health economic modelling (eg measurement of resource use/health benefits, WP4), with patient and public involvement/advice (eg patient groups including AF Association, Stopafib.org). These aspects bring ‘added value’ to LMICs with training and research opportunities. The applicants would also be advised by an International Advisory Board, consisting of multidisciplinary, multinational experts and patient representation.

Lay abstract: Atrial fibrillation(AF), the most common heart rhythm disorder globally, is associated with a high risk of death, disability, ill health and poor life quality. Over 25%of strokes are due to AF and adults have a 1 in 4 lifetime risk of developing AF. The main causes of AF (eg high blood pressure, diabetes) are common in low- & middle-income countries (LMICs). AF under-treatment is common, leading to missed opportunities in preventing fatal and disabling strokes. A third of people with AF, more in LMIC settings, do not know they have the condition and are not receiving life-saving treatment. Anticoagulation to stop blood clotting can be highly effective in reducing stroke. Warfarin, the most common anticoagulant, needs careful monitoring, but services are patchy. Newer direct oral anticoagulants are too expensive and care is rarely joined-up (‘integrated care’) (incl. detection, anticoagulation and management of other conditions). Our established group has successfully led changes in AF management locally, in the UK, and in European countries with different healthcare systems by promoting stroke risk assessment and enabling clinicians to initiate oral anticoagulation in an integrated manner. Given the importance of this need, we plan to support our LMIC partners to develop tailored research to improve AF management to reduce AF-associated stroke which is common yet under-diagnosed or under-treated in these settings. Our teams working with disadvantaged populations in China, Brazil and Sri Lanka will document current management delivery and identify their research needs. The countries have different populations, risk profiles with distinct healthcare systems and needs. AF research is limited, and current AF management is suboptimal. By developing/adapting known effective methods to increase awareness of AF and its complications and implement evidence-based treatments, we can contribute to improving lives and outcomes. This will be an opportunity for us to learn how to adapt our approaches to other global healthcare settings. As deliverables, we will collaboratively determine country-specific working methods, agree on shared relevant research topics focussing on improvement of AF care quality and identify training needs. We will prioritise and plan 1-2 pilot research project(s) per country by consulting with local patients, families, healthcare providers (HCPs) and policy-makers and findings from our systematic reviews. Training will be designed and delivered, patients recruited and projects completed. As pilot data emerges we will focus on developing new funding proposals to sustain the collaboration in the longterm. Engagement with major stakeholders (e.g. Government/NGOs, HCPs) will allow us to initiate sustainable improvements in AF patient care, aiming to develop models of best care tailored for our target regions but will be suitable for sustained wider use. We will raise the profile of AF in partner countries with their national policy-makers and healthcare professionals with strategic high-profile meetings (through existing links between partners & national decision-making bodies, and patient groups) and involve them directly in the research. In summary, we will develop partnerships with specific LMICs to stimulate development of community based research and co-develop the capability, networks & platform to deliver effective research with a view to expanding collaborations to other LMICs to improve the lives of AF patients worldwide.

Research activity codes: 7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT);8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: CARDIOVASCULAR