If your life has been touched by rare disease, you know that a rapid and accurate diagnosis is vital. Unfortunately, the average rare disease patient waits four years to receive a final diagnosis after consulting with five doctors and receiving three misdiagnoses. When an accurate diagnosis is made, the diagnostic odyssey and its multiple referrals, inconclusive tests and confusion end. The journey, however, is not without personal and societal cost.
A report from 2018 showed that over a 10-year period, the diagnostic odyssey for rare diseases cost NHS England over £3.4 billion. For every individual that didn’t receive a final diagnosis, his or her health was deteriorating and the opportunity for certain treatments, such as gene therapies, was closing.
A timely and accurate diagnosis is vital because it can:
• Facilitate access to treatment and care
• Shed light on what the future may hold
• Assist with family planning
• Open the door to connect with patient organisations
• Introduce the possibility of partaking in a clinical trial or other research initiatives
England’s Action Plan acknowledges that advances in genomics offer substantial potential in yielding faster, accurate diagnoses. The plan has also considered that 20% of rare conditions aren’t genetic in nature and that many continue to go undiagnosed. It is why Action 5 of this priority is focused on supporting patients who are living with undiagnosed conditions.
Join us as we summarise the five actions that’ll be taken to help patients get a final diagnosis faster!
Action 1: Improving how decisions are made on newborn screening for rare diseases
As many of you know, 75% of all rare conditions affect children. What may come as a surprise is that this accounts for approximately a third of infant mortality in the UK.
Currently, only nine rare conditions are screened for in newborns through the NHS newborn blood spot screening programme. The Department of Health and Social Care wants to improve how decisions are made across the UK on newborn screening for rare diseases by:
• Creating a new UK National Screening Committee (UK NSC) with a broader remit, revised terms of reference and a greater collaboration with researchers and stakeholders, including those with an interest in rare disease
• The establishment of a UK NSC Bloodspot Task Group to identify practical and innovative approaches to facilitate research and evidence, which will inform evaluations of blood spot screening
The new UK NSC will engage in international activities to learn from and contribute to international best practices on screening. Keep an eye out for an upcoming paper that compares the UK NSC bloodspot screening policy processes and programme delivery to proposed EURORDIS newborn screening criteria to identify areas of good practice and improvement!
Action 2: Whole Genome Sequencing (WGS) to screen for genetic conditions in healthy newborns
It is believed that Whole Genome Sequencing (WGS) could significantly increase the diagnoses of genetic conditions that are not currently covered by the NHS newborn blood spot screening programme. Early detection of rare diseases improves an individual’s long-term outcome, support options and condition management.
Genomics England and NHS England and NHS Improvement are co-designing and running an ethically approved research pilot using WGS to screen for rare genetic conditions in healthy newborns.
The pilot received funding in October 2021, and will:
• Sequence the genomes of up to 100,000 newborns and follow their progress to better understand the clinical benefits and potential risks of newborn genomic screening
• Be designed through careful consultation with the rare disease community, healthcare professionals, the UK National Screening Committee and other key stakeholders
• Include careful testing of how the whole pathway – from diagnosis through to genetic counselling and care – can be rolled out within the NHS, if there is proven benefit
• Ensure robust processes are in place for consent, return of results, data use and access
• Develop a framework to identify genes for targeted analysis, based on clinical and genomic evidence and wide consultation
• Improve understanding of the patient experience of genomic newborn screening
• Provide evidence to support the UK NSC to make recommendations for future NHS screening programmes
Action 3: Continuously develop the National Genomic Test Directory
The NHS Genomic Medicine Service (GMS) is supporting England’s Action Plan through a:
• National network of seven NHS Genomic Laboratory Hubs and seven NHS GMS Alliances
• National Genomic Test Directory
• NHS GMS Research Collaborative
• Integrated clinical genomics service
The National Genomic Test Directory currently includes 375 rare and inherited clinical indications that are reviewed annually. The GMS wants to move toward targeted, personalised care so they can complete single gene tests, exome sequencing, whole genome sequencing and diagnose conditions based on broader phenotypes.
Action 4: Further develop the Genomics England clinical research interface
Action 4 aims to help researchers and clinicians collaborate when working with complex genome data by passing their findings and information back to the NHS.
The goal of furthering the clinical interface is to:
• Return at least 100 diagnoses a year
• Foster collaboration between researchers and clinicians
• Accelerate new discoveries
Action 5: Pilot new approaches for patients with undiagnosed rare conditions
Patients living with undiagnosed rare conditions would benefit from a recommended care package and better signposting to existing support services. NHS England and NHS Improvement will be piloting new approaches for those living with undiagnosed conditions, such as outpatient appointments, inpatient stays and assessment by multiple clinicians, to aid in condition management, support and care.
Research is the underpinning theme of the five actions mentioned above. Research improves our understanding of rare diseases and can help patients reach an accurate, final diagnosis faster. Due to rare diseases having small patient numbers, an international, collaborative approach must be used to accelerate research and the speed of diagnosis.
It’s important to remember that some patients and their families may never receive a diagnosis even after genomic or non-genomic diagnostic tests were done. A person’s condition could be so rare and complex that he or she is the only one in the world who has that mutation.
When this happens, the patient, family and healthcare professionals involved in his or her care must be supported and equipped to manage the condition. They should be signposted to those who are best aligned to support them on their journey, such as SWAN UK.
Reaching a rapid, accurate diagnosis is only half the battle. In December 2021, Genetic Alliance UK set out to better understand the experience of diagnosis by speaking with those who are living with a rare condition. Their report ‘Good Diagnosis: improving the experiences of diagnosis for people with rare conditions’ discusses three key stages – the search for a diagnosis, receiving a diagnosis and life post-diagnosis – and the experiences that occur throughout each.
The Good Diagnosis report concludes with four recommendations on how to improve the diagnosis experience based on conversations with those living with a rare condition during Genetic Alliance UK’s ‘Good Diagnosis’ workshops. If you haven’t had the chance to read the full report yet, we’ve condensed its 29 pages into one blog to bring you its findings quickly and concisely. Read it now and share!