The Diagnostic Odyssey in rare diseases; a Task and Finish Group report for the Department of Health and Social Care

The Diagnostic Odyssey in rare diseases; a Task and Finish Group report for the Department of Health and Social Care Authors: Eleanor Hay, Frances Elmslie, Peter Lanyon and Trevor Cole April 2021 Keywords: rare diseases, diagnostic odyssey, outpatient diagnostic coding, Tuberous Sclerosis Complex, Bardet Biedl Syndrome, ANCA-associated Vasculitis, NCARDRS INTRODUCTION Background Rare diseases can be defined as life-threatening or chronically debilitating conditions that have a frequency of less than 1 in 2000 in the population at risk. While individually rare, with greater recognition it is apparent that as many as 1 in 17 people will develop a rare disease over their lifetime, equating to approximately 3.5 million people in the UK alone. Over 75% of rare diseases affect children and currently 30% of patients die before reaching their 5th birthday 7. Whilst it is estimated that 80% of rare diseases are genetic in origin, only a quarter of these have had their molecular basis defined. This has led to difficulty in recognising and effectively diagnosing these conditions 7. The journey from initial presentation to the NHS through to receiving an accurate diagnosis is termed the diagnostic odyssey (DO). Whilst many individuals with rare diseases in the UK report excellent and timely patient journeys, a large European study, including a cohort of UK patients, looking at eight rare disease subsets, identified that 25% of patients had to wait between five and thirty years for a final diagnosis 8. In these prolonged diagnostic odysseys, patients may have multiple NHS encounters with a variety of specialists and endure serial and often invasive investigations 4. In a Rare Disease UK survey in 2016, it was found that on average from the time of first symptoms relating to the condition, to a formal diagnosis, individuals consulted five doctors and had three misdiagnoses 20. This is frustrating and stressful for the patient and family and an ineffective and expensive use of resources. A delayed or misdiagnosis may also have serious implications for patient health and lead to missed opportunities for effective intervention. The recently published 2021 Rare Diseases Framework has built on, and superseded, the 2013 UK strategy for Rare Diseases Report. The work and writing underlying this document was completed prior to the publication of the 2021 framework. In both the 2013 and 2021 documents however, a key recommendation is to reduce diagnostic delay and, in doing so, improve timely access to appropriate intervention4. The 2013 report set out several approaches to achieving this aim, including improved prenatal care and newborn screening programmes and carrier and cascade testing for relatives of individuals with known genetic conditions. Education of health care providers in recognising rare disease and understanding genomic testing was also noted, through massive open online courses (MOOC) and Health Education England funded programmes, ranging from stand-alone modules to full MSc courses in Genomic Medicine. Large sequencing projects, such as the Deciphering Developmental Disorders (DDD) and 100,000 Genomes project, have delivered many new diagnoses to families who have endured long odysseys and has set in motion the development of an NHS clinical whole genome sequencing service, with live clinical testing for selected rare disease phenotypes available from November 2020. Reconfiguration of NHS England laboratories into seven Genomic Laboratory Hubs has additionally met the aim to ensure equal access to high quality genomic testing 4. The 2021 Framework notes that, despite making significant progress, there remain areas for further development 5. The framework outlines a future vision, shared by all four UK nations, to address health inequalities, improve the quality and availability of care, and improve the lives of people living with rare diseases. The four key priorities highlighted include helping patients to get a final diagnosis faster, increasing awareness of rare diseases among healthcare professionals, better coordination of care and improving access to specialist care, treatments and drugs. In the related document, ‘Genome UK: the future of healthcare’, incorporating genomics into routine healthcare for the provision of diagnosis and personalised medicine for rare disease, is also highlighted as one of the three pillars supporting the strategy to create the most advanced genomic healthcare system in the world 6. The framework however, also raises greater awareness that a significant proportion of rare diseases, at least 20%, do not have a genomic aetiology but face many of the same issues. This focus on strategy implementation related to genomic advances reflects the fact that up to 80% of rare diseases are genetic in origin. However, implementation also needs to be inclusive of the needs of the remaining 20% of people living with rare non-genetic diseases, as further emphasized in the 2021 UK Rare Diseases Framework 5. An exemplar for this non-genetic group are the rare autoimmune rheumatic diseases, conditions which predominantly have onset in later life and share multisystem clinical features which occur when the body’s own immune system attacks healthy tissues, akin to “friendly fire”. The unmet needs of people living with these conditions, in particular related to diagnostic delay, coordination of care and lack of knowledge, are highlighted in a 2018 report by the Rare Autoimmune Rheumatic Disease Alliance (RAIRDA) 1. 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