Title: Using Health Data Science and large-scale data to improve the lives of people with rare autoimmune rheumatic diseases and other rare diseases.
Funder: Department of Health and Social Care

Abstract: Background: A rare disease affects fewer than 1 in 2000 people. However, there are so many rare diseases that 1 in 17 people are affected by a rare disease in their lifetime. People with rare diseases often suffer unnecessarily and die prematurely due to not being able to access appropriate healthcare or no effective treatment yet being available. Research in rare diseases has been retarded due to inability to identify large cohorts of people with a disease. Public Health England's new National Congenital Anomaly and Rare Disease Registration Service (NCARDRS) has enabled a game-changing environment for rare diseases, by creating a national population-based register of everyone with rare diseases. Unfortunately, NCARDRS do not yet have methods to register people with rare diseases which are not congenital anomalies nor genetic in origin. Aim and objectives: The aim of this fellowship is to use a health data science approach to develop methods to achieve complete national registration of people with rare complex (non-genetic) diseases with NCARDRS, and use registration to improve healthcare delivery and support development of better treatments. I will achieve this by completing the following 3 work-streams using 3 rare autoimmune rheumatic diseases as exemplars: Takayasu's arteritis, ANCA-associated vasculitis and Giant Cell arteritis. Methods: Deliver national registration by assembling confirmed cases of each disease from data sharing with research studies, NHS networks and Blueteq, and suspected cases coded with relevant ICD-10 codes in Hospital Episode Statistics and death certificate data. I will validate the diagnosis of suspected cases by cross-reference with confirmed cases and in NHS medical notes. I will use traditional and machine learning methods to develop algorithms to identify people in electronic health records, and then validate these methods. This will deliver prospective national registration with NCARDRS using electronic health records. Improve healthcare delivery using the register, and linked Hospital Episode Statistics, death certificates and Bluteq data to discover information needed to plan better health services. I will: Describe incidence and prevalence of Takayasu's arteritis stratified by age, sex and ethnicity and share this with the national commissioner to inform service planning. I will describe important outcomes such as arterial aneurysms or stenosis, infections, cancer and death to inform patients and clinicians. Assess geographical equity of access to high-cost drug treatments in Takayasu's arteritis and ANCA-associated vasculitis, and share the results with patients and commissioners. Support development of better treatments and their recommendation in the NHS, through evidence from real-world studies. I will: Quantify steroid burden in Takayasu's arteritis and ANCA-associated vasculitis using linked NHS Prescription Service data, and investigate the association between cumulative steroid dose and complications/toxicity. Measure treatment costs and frequency of outcomes in Giant Cell arteritis under current treatment regimens to inform health economic modelling of new treatments. Anticipated impact and dissemination: This proposal aims to improve the lives of people with rare diseases by providing exemplars of how health data science can achieve national registration, and enable epidemiological studies needed to inform improvements to health service delivery and new treatments.

Lay abstract: Background:The government's rare disease plan (UK Strategy for Rare Diseases, 2013) aims to 'ensure that no one gets left behind just because they have a rare disease'. Although each rare disease affects fewer than 1 in 200 people, 1 in 17 of us will be affected by a rare disease in our lifetime. There is an urgent need to design better treatments and services for people with rare diseases to prevent unnecessary suffering and premature death. The new National Congenital Anomaly and rare Disease Registration Service (NCARDRS) gives us an opportunity to create major improvements for people living with a rare disease. Information on rare diseases has been scarce and scattered across different sources. NCARDRS are creating a national register (list) of people with a rare disease. This will improve the quantity, quality and availability of rare disease data, leading to better research and targeted healthcare service provision. In this proposal I aim to discover the best methods to find and register people with non-inherited rare diseases, of which the rare autoimmune rheumatic diseases are good examples. NCARDRS are already able to register people with rare diseases that are apparent at birth, start in early childhood, or have genetic causes, because they have existing methods to find them. This research is needed so that children and adults with later-onset, non- inherited diseases are not left behind. I will show the benefits of registration, through research addressing important issues for people with these diseases.Objectives: Build the national register: using multiple sources of existing information and develop methods for on-going automated registration. Improve healthcare delivery: find information needed to plan health services, discover outcomes, and assess whether current services are fair. Support development of better treatments: provide information necessary to plan clinical trials, and to approve new treatments in the NHS.Methods: Deliver national registration: I am assembling existing sources of information including research studies and electronic health records and linking them together to find everyone in England with rare autoimmune rheumatic diseases. I will use computer analysis of this data combined with a detailed understanding of healthcare (health data science) to develop and test methods to automatically add people to the national register (list) - unless they choose to opt out. This will also add value to existing research studies, by linking them to national datasets. Discover information for healthcare planners : I will use the complete national register to discover how many people in England have rare autoimmune rheumatic diseases, describe health outcomes for these diseases using linked electronic health records, and assess if people with rare autoimmune rheumatic diseases currently have equal access to high-cost treatments regardless of who they are and where they live. Healthcare planners can use this information to plan better services. Support innovation: I will describe steroid use in rare autoimmune rheumatic diseases, and test if there is a relationship between total (cumulative) steroid dose and complications such as broken bones, infections, diabetes, heart disease and dying sooner. I will provide evidence of current treatment pathways and outcomes for rare autoimmune rheumatic diseases which have new treatments in development. This information is needed for decision making when approving new treatments in the NHS.Stakeholder involvement: This project has been produced in collaboration with a patient partner, and a large team of doctors, researchers, and healthcare planners. Impact: I believe building a national register for Rare Diseases will position the UK as world leader in rare disease research. Research that can be conducted once rare diseases are registered will revolutionise healthcare services and treatments, and improve the lives of people with rare diseases.

Research activity codes: 7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT)
Health categories: GENERIC HEALTH RELEVANCE