NIHR Global Health Research Group on warfarin anticoagulation in patients with cardiovascular disease in Sub-Saharan Africa, University of Liverpool

Personalised Health is a University-wide research theme at Liverpool. Using our knowledge of clinical pharmacology, genomics and our understanding of diseases, our aim is for every patient to receive the right drugs at optimal doses, maximising efficacy and tolerability, and pre-empting adverse drug reactions. We have shown that personalising medicines to individual patients, based on their genetics, clinical and environmental factors, can reduce both risk and time it takes for the medicine to become effective. Our work has largely focused on developed countries; it is important that the drive towards personalised health does not ignore LMICs, which would exacerbate health inequalities. The WHO has stated that “genomic health divide must be kept in check and ultimately bridged through equitable economic investment, clinical research, and provision and use of genomic services and technologies globally”. Personalisation does not only depend on genomic testing, but can also be based on clinical algorithms. Our aim is to use our expertise in a clinically important NCD area (anticoagulation), which also represents an unmet clinical need in Sub-Saharan Africa, to identify needs and develop solutions that can be implemented cost-effectively. We have extensive experience of research with warfarin in the UK, EU and US, with 39 papers published since 2003 (2 in the NEJM). This project forms the pathway for increasing our LMIC work with the aim of improving the benefit-risk ratio of medicines. Liverpool is at the forefront of personalised health research, as evidenced by the award of the NHS Chair of Pharmacogenetics (2007), the development of the Wolfson Centre for Personalised Medicine (in 2009) and the award of the MRC Centre for Drug Safety Science (CDSS; in 2008, renewed in 2014). Our expertise is evidenced by publications (>400 over the last 10 years), funding record (>£60M in 10 years) and evidence of clinical translation including work with Industry. UoL has a long track record of work in LMICs, mainly in infectious diseases. CDSS, part of the University-wide personalised health research theme, has many collaborations nationally and internationally, and with regulators (MHRA) and industry (pharma, diagnostics and informatics). While we have undertaken drug safety investigations in LMIC countries (e.g. in anti-TB drug induced liver injury), drug safety has been under-studied in LMICs by the global research community. This therefore represents an unmet clinical and scientific need which will become increasingly important as access to treatments improves in LMICs. The development of a global health research group therefore represents a golden opportunity to begin tackling drug safety issues, by focusing on warfarin, a widely used but poorly understood drug in LMIC countries. Our aim is for this project to develop into a sustainable and world-leading program of research into drug safety in LMICs, whilst increasing capability and capacity in the LMICs. The mission of Infectious Diseases Institute, Kampala, Uganda, is to support health systems in Africa, with emphasis on infectious diseases, through research and capacity development. The proposed study will build on and enhance existing infrastructure. Warfarin is the standard oral anticoagulant used in public healthcare facilities in South Africa, with limited access to more costly new oral anticoagulants. Despite dedicated warfarin therapy clinics and close patient follow up, therapeutic control is suboptimal (PMID 27247158). Pharmacogenetic variants determining warfarin dose requirements have not been well studied in sub-Saharan African patients. Collaboration on this study will increase local capacity to perform pharmacogenomic research. Programme of Activities. Thrombosis is a major contributor to disease burden globally (PMID: 25312343). Oral anticoagulation is needed for venous thromboembolism, valvular heart disease and stroke prevention in AF patients. Mixe