England Rare Diseases Action Plan 2025: annexes

Question 1

Annex A: detailed progress update on actions, metrics and milestones

Accepted Answer

Over the last year the progress of ongoing actions from our 3 previous action plans have continued to be monitored through our England Rare Diseases Framework Delivery Group. The group brings together publicly-funded delivery partners and representatives of the rare disease patient and clinician communities, and meets regularly to review delivery of existing commitments and agree on future activities. In addition to our regular meetings, in September 2024 we held an in-person all day meeting of this group where progress was presented and future collaboration discussed. Progress has also been reported and discussed at the UK Rare Diseases Framework Board and at the UK Rare Diseases Forum, with feedback returned to the delivery group.

This next section of the action plan reports on progress made against open actions from previous action plans. Previously completed and closed actions are not included in this section, but a full summary of actions is contained in this annex.

Priority 1: helping patients get a final diagnosis faster

The UK Rare Diseases Framework highlighted the importance of getting a rapid and accurate diagnosis. This can ensure timely access to treatment and care, provide a possible prognosis and offer options for family planning. The diagnostic odyssey - the often lengthy delay between symptoms first presenting and receiving a diagnosis - can represent years of anxiety, financial difficulties, impacted career and educational opportunities, and deterioration of physical and mental health. Providing a timely diagnosis, in the right way, will provide patients and families of those living with rare conditions with more certainty, make the best use of NHS resources and create treatment and research opportunities.

Around 80% of rare conditions have a genetic basis and the NHS Genomic Medicine Service (GMS) provides genomically-informed care and treatment in England. As a result of increased growth in testing in NHS GMS, compliance with turnaround times has been impacted. Minimising backlogs and the time taken to deliver a genomic test is a key priority for NHS England and the NHS genomic laboratory hubs (GLHs). NHS England continues to monitor the backlogs as part of the NHS GLH assurance framework, and those NHS GLHs with a backlog have submitted a backlog recovery plan to NHS England which is reviewed and monitored closely in contract monitoring meetings. A number of NHS GLHs do not have a backlog.

To maximise the benefit to population health of a diagnostic genetic test result, clinical genetics services add value to patient care at multiple stages:

diagnostic
treatment pathway
identification of risk
managing risk

Recognising increased demand and the need to use finite resources as effectively as possible, in June 2024 the Clinical Genetics Society and Genomics Clinical Reference Group published consensus referral guidelines in their report Maximising the Patient Benefit of Genomics - the evolving role of the Clinical Genetics Services.

Action 1: improving how decisions are made on newborn screening for rare diseases

In our first action plan published in 2022, action one set out our commitment to improve the evidence base to support how decisions are made on newborn screening for rare disease. Part of this was establishing the UK National Screening Committee (UK NSC) Blood Spot Task Group (BSTG). BSTG continues work to identify approaches to help researchers develop evidence that can support the UK NSC make good recommendations. The UK NSC’s horizon scanning process helps to prioritise, assess and follow up evidence. The research and methodology group keeps abreast of research related to screening and identifies research requirements, and the UK NSC routinely considers international evidence.

Recruitment to the in-service evaluation (ISE) of newborn screening in NHS services for severe combined immune deficiency has been completed with the National Congenital Anomaly and Rare Diseases Registration Service (NCARDRS) supporting the data linkage work required. A consultation on the results of the ISE will be undertaken in 2025. Detailed planning continues for the ISE of newborn screening for spinal muscular atrophy (SMA), in parallel with a new modelling study. The model’s preliminary findings were discussed with stakeholders at a workshop in November 2024. Initial analysis suggested screening might be cost-effective or cost-saving compared to a no-screening (plus treatment) arm, though uncertainties and limitations were noted. The next steps will be for the modelling team to address the feedback received at the workshop, and to complete the model and the remaining analyses before moving through the UK NSC evidence review process. Evidence from the modelling study and the ISE will inform an updated UK NSC recommendation on screening for SMA. A new evidence review into newborn screening for metachromatic leukodystrophy will take place during 2025 to 2026.

Work continues to synthesise the findings of a literature review workshop focusing on developing practical recommendations regarding test accuracy study designs suitable for newborn screening. The 2024 action plan detailed a project focusing on how disease registries, data linkages and improved data coding could help provide evidence on rare disease outcomes. The BSTG decided to undertake a 2-phase project for this workstream. For phase 1, the National Institute for Health and Care Research (NIHR) West Midlands evidence synthesis group has been commissioned to develop a scoping review on methods and mechanisms to measure and monitor outcomes of newborn blood spot screening which will identify the breadth of available evidence. The protocol for this work has been published. The scoping review will inform the second phase of the project when relevant methods and mechanisms identified in the scoping review will be evaluated.

The BSTG projects, modelling work and in-service evaluations will all benefit the rare disease community by improving the evidence base for screening for rare diseases which, in turn, will help the UK NSC to make robust recommendations.

Metrics and milestones as published in the 2024 action plan:

UK NSC to continue work to improve the evidence available to them in evidence reviews
draft report on methodological principles for screening test accuracy study designs in rare disease settings, in summer or autumn 2024
publish a paper on technical and procedural considerations for modelling exercises around newborn screening in summer or autumn 2024 (timelines dependent on scientific journal publishing specifications)
publish a paper on use of registries in the newborn screening evaluation process

Metrics and milestones for 2025:

consultation on the results of the ISE in 2025
modelling team to address the feedback received at the November workshop and to complete the model and the remaining analyses before moving through the UK NSC evidence review process
use the phase 1 scoping review to inform the second phase of the project when relevant methods and mechanisms identified in the scoping review will be evaluated

Action 2: whole genome sequencing (WGS) to screen for genetic conditions in healthy newborns

In the first action plan published in 2022, we recognised the importance of early detection in facilitating faster access to available interventions for rare conditions and the impact this can have on reducing or avoiding harm and improving long term outcomes. Action 2 was introduced which aimed to harness WGS to screen for genetic conditions which are not currently covered by the NHS newborn blood spot programme in healthy newborns. Now known as the Generation Study, this work is underway as an NHS embedded research study that aims to undertake WGS on up to 100,000 babies and screen for over 200 rare conditions. Currently, the study is open and recruiting at 27 hospitals across 18 NHS trusts - any results have started to be returned to participants.

Engagement has taken place with paediatric specialists and patient organisations about any further conditions that are felt to meet the study’s principles, and 3 community of practice meetings have been held so far. The community of practice will continue to meet regularly in the year ahead to share experiences and learnings across recruiting NHS trusts and NHS Genomic Medicine Service Alliances involved in the study.

As part of the evaluation and monitoring of this action, the evaluation provider has been established and has initiated evaluation activities, including publication of their evaluation protocol.

Metrics and milestones as published in the 2024 action plan:

research study rolled out to the number of trusts agreed with NHS England, following full adherence to an agreed readiness checklist
data gathered (a combination of qualitative and quantitative metrics including user research) and changes made to study materials and process from the experiences of initial sites that are planned to start early 2024
following publication of the initial list of genes and conditions to be included in the study, and based on live experience analysing results, a consultation process will be planned to inform a future iteration of genes, conditions and variants to be tested in the study in collaboration with NHS England
establish community of practice to share experiences and learnings across recruiting NHS trusts and NHS Genomic Medicine Service Alliances involved in the study
external evaluation provider established and initiated mixed-methods approach to address study research questions, including: experiences and attitudes of participants, healthcare professionals, patient groups and the public
impacts of the study on families and the health services, health economic analysis, interim report of initial findings of the evaluation to be published by late 2024

Metrics and milestones for 2025:

the community of practice will continue to meet on a monthly basis in the year ahead
updates on progress of Generation Study to be provided to England Rare Diseases Framework Delivery Group

Action 5: pilot new approaches for patients with undiagnosed rare conditions

Building on the learnings from pilots in Wales for new approaches for patients with undiagnosed rare conditions, action 5 focused on setting up 2 clinics for syndromes without a name (SWAN) pilot clinics within the NHS in England. The service description has now been finalised including the definition of referral criteria. The provider selection plan was agreed in December 2023 and further work has been undertaken to ensure that commissioning this service can proceed. However, further progress is dependent on new funding and we anticipate we will need to pause before commissioning the 2 pilot sites in the 2026 to 2027 financial year. We remain committed to taking these pilots forward to demonstrate how care for patients with undiagnosed conditions can be improved.

SWAN clinics have the potential to demonstrate how care for patients with undiagnosed conditions can be improved and, in some cases, apply new and novel technological approaches which may yield diagnosis. This would improve diagnosis times for patients, unlocking social and educational care and preventing ineffective interventions given before diagnosis.

Metrics and milestones as published in the 2024 action plan:

select the 2 pilot sites for the clinics and implement in 2024

Metrics and milestones for 2025:

NHS England to update England Rare Diseases Framework Delivery Group on funding and progression for next financial year

Action 17: commission research on how best to measure the diagnostic odyssey

In the 2023 action plan we committed to commissioning research through NIHR to measure the diagnostic odyssey - the length of time it takes between people first reporting symptoms of a rare condition and diagnosis. This was important to help us gain a greater understanding of what factors contribute to delays in diagnosis. This research is now funded under a 2 year contract running from May 2024 with Consilium Scientific and Realise Advocacy. Milestones for this research were published on the UK Rare Disease Forum’s online platform in August and are set out in this annex. Significant progress has been made towards the key milestones. A research advisory group (RAG) and patient and public involvement and engagement (PPIE) group were successfully established by July 2024, creating a solid foundation for further stakeholder engagement and ensuring diverse input into project decisions.

The process to identify data sources was completed in September 2024, providing valuable insights for the next phases of the project. The evidence review was completed in January 2025. While the stakeholder engagement workshops planned for autumn 2024 have been delayed to allow for the addition of more comprehensive content, they have now been consolidated into a single workshop scheduled to take place in spring 2025, ensuring an enriched and thorough consultation process. Preparatory work for the workshop will commence in February 2025. The research team has revisited its approach to defining indicator conditions, starting with a comprehensive list of over 150 conditions. Indicator conditions will be selected from this long list using criteria to be agreed by the team, RAG and PPIE groups. This process is already underway and will continue into spring 2025.

We know the diagnostic odyssey is a well-documented challenge of the patient journey for patients with rare conditions and their families. We hope that being able to have a data-informed estimate for the diagnostic odyssey will contribute to the evidence base for raising awareness of rare diseases and their challenges. Understanding better the factors that contribute to the delay in receiving a diagnosis will allow for gaps to be identified in the healthcare system and better support advocacy and allow for better informed decisions regarding where resources and training would be best allocated to benefit patients. We strive to keep the patient voice at the core of our action plan and our stakeholder groups have made clear the importance of not only receiving a diagnosis but doing so in a timely manner.

Metrics and milestones as published in 2024 action plan:

research team and milestones for the year ahead publicly announced by April 2024 (through the UK Rare Diseases Forum and online platform)
progress will be reported in the 2025 action plan

Metrics and milestones for 2025:

stakeholder engagement workshops to take place by spring 2025
indicator conditions to be identified by summer 2025
findings from evidence review to be reported by spring 2025

National disease registries capture a patient’s complete journey from referral, diagnosis, treatment, outcomes, experience and survival through the collection, curation and linkage of many differing data sources into a unified information resource. The National Disease Registration Service (NDRS) is part of NHS England and manages 2 disease registration services: the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS) and the National Cancer Registration and Analysis Service (NCRAS). NDRS aims to collect, curate, quality-assure and analyse data from every patient in England diagnosed and/or treated with these conditions.

Many patients with rare diseases receive a diagnosis through genomic testing. Action 18 aimed to increase data sharing between Genomics England and NHS England (including NCARDRS and the NHS GMS). The goal was to bring patient benefit by increasing the number of rare disease patients whose data was registered within NCARDRS as part of a well characterised cohort. It also aimed to enable population-level analysis to improve the understanding of the equity of access to genomic testing. Progress has been made in working through information governance processes to allow data sharing between Genomics England and NCARDRS. Approval has also recently been granted to allow Patient Level Contract Monitoring (PLCM) data commissioned by the NHS GMS to be shared with NCARDRS.

The process is being tested through 2 use cases initially: congenital malformation and dysmorphism syndromes and paediatric and/or syndromic cardiomyopathy. Discussions are also underway to progress data sharing for other relevant rare conditions.

Metrics and milestones as published in 2024 action plan:

hold workshop with patient organisations
explore how data sharing can be maintained and incorporated into business as usual
relevant analytical outputs to be produced during 2024 to 2025, including demand modelling and equity of access to certain testing indications where data is available
evaluate the feasibility of a mapping exercise to understand the overlap between the conditions list that has been published for the Generation Study and the rare conditions prevalence data collected by NDRS, by February 2025

Metrics and milestones for 2025:

continue discussions to ensure data sharing for all relevant rare conditions can be incorporated into ‘business as usual’ work
PLCM data commissioned by the NHS GMS to be shared with NCARDRS and tested in congenital malformation and dysmorphism syndromes and paediatric and/or syndromic cardiomyopathy

NCARDRS 10 year anniversary

This year marks a decade since the launch of the National Congenital Anomaly and Rare Disease Registration Service. Established in 2015, NCARDRS has become a cornerstone of the UK’s commitment to improving the lives of individuals and families affected by congenital anomalies and rare diseases.

Over the past 10 years, NCARDRS has worked to collect and curate high-quality data, providing critical insights that shape policy, drive research and enhance care pathways. By fostering collaboration with clinicians, researchers and patient communities, NCARDRS has contributed to groundbreaking advancements in understanding rare diseases. This has led to improving early diagnosis and ensuring better access to tailored treatments and has delivered significant milestones that have transformed the landscape of congenital anomaly and rare disease registration, including:

achieving national coverage for congenital anomaly registration in England, ensuring comprehensive and high-quality data, and becoming the largest active congenital anomaly register in the world
securing recognition of the NCARDRS Annual Congenital Anomaly Statistics Report as an official statistic, highlighting its credibility and impact
publishing the first national rare disease prevalence report, providing vital insights for patients, clinicians and policymakers
supporting the evaluation and monitoring of national screening programmes, including the rollout of non-invasive prenatal testing as part of antenatal care
building partnerships with academic, clinical and patient communities, leading to high-profile studies such as the MELODY study and EXPRESS study
contributing to international collaborations, including EUROCAT and the International Clearinghouse on Birth Defects Surveillance and Research, to advance global understanding and care

These achievements reflect NCARDRS’s commitment to improving outcomes for individuals and families affected by congenital anomalies and rare diseases.

NCARDRS support to research and service design

NCARDRS collaborated with Great Ormond Street Hospital for Children, Birmingham Women’s and Children’s Hospital and the University of Oxford, as part of the EXPRESS study. This study evaluated the impact of rapid prenatal whole exome sequencing (pWES) - R21 in the national genomic test directory for rare and inherited disease - as part of antenatal care, looking at variability in testing and diagnostic pick up rates and any associated factors. This new test is offered during pregnancy when anomalies identified during ultrasound suggest a possible genetic disorder.

With the potential to increase genetic diagnoses in a timeframe that informs prenatal decision-making, pWES could change the landscape of prenatal diagnostic services within the NHS.

An underlying genetic cause was confirmed in one-third of pregnancies receiving this testing, improving our understanding of the prenatal presentation of certain rare genetic conditions and crucially providing timely information to support decision making during pregnancy. In 2024, 2 papers were published reporting positive experiences of both parents and healthcare professionals involved in this study. The study included identification of any factors associated with inequalities. Variation was observed in the uptake and outcomes of R21 testing in the fetal setting, providing actionable evidence that can be used to improve availability and/or uptake of this rapid diagnostic test in pregnancy.

To understand the overlap between the conditions list that has been published for the Generation Study and the rare conditions prevalence data collected by NCARDRS, a mapping exercise has been completed. The results have been shared between both organisations and a gap analysis is underway with the aim to establish a plan to ensure routine data collection for all conditions in this study, where possible.

Priority 2: increasing awareness of rare diseases among healthcare professionals

People with rare diseases often interact with many different healthcare professionals over their health journey. This includes primary care staff such as GPs who people will interact with routinely, emergency care staff and specialists. With over 7,000 rare diseases, no healthcare professional can receive training on every rare disease. By raising awareness of rare diseases more broadly, healthcare professionals can be alert to considering them, for example at first presentation or in emergency settings, and confident about where to go to for additional support and resources.

Celebrating Rare Disease Day in the NHS

Rare Disease Day 2024 was the first time celebrations were co-ordinated across the NHS. Each trust was empowered to deliver their own activities and communication on the day through a toolkit shared from the central communications team. A joint rare disease day blog by the Chief Scientific Officer for NHS England and the head of highly specialised commissioning in NHS England was published, which raised awareness around rare conditions and spoke about treatment and diagnosis for people living with rare conditions delivered through the NHS.

NCARDRS published its first national rare disease prevalence report on Rare Disease Day 2024, providing vital insights for patients, clinicians and policymakers. The story of a mental health nurse working in the NHS living with the rare condition osteogenesis imperfecta was shared across social media channels. As well as centrally-led efforts from NHS England, organisations such as Medics4Rare Disease and Genetic Alliance UK played a significant role in raising awareness of healthcare professionals on Rare Diseases Day 2024.

Within the NHS there was a drive to raise awareness and educate health professionals on rare diseases. This included publishing 5 new articles about rare disease on the GeNotes Knowledge Hub, providing healthcare professionals with an introduction to rare disease and familiarising them with some key concepts to be aware of when working with people living with rare conditions.

The NHS England Genomics Education Programme (GEP) developed a series of short films, ‘My genomics journey: three perspectives’, to shine a light on patients with different conditions and the ways in which their lives have been affected, both before and after diagnosis. The programme also ran its 2-week online course, ‘A clinician’s guide to genomic testing for rare disease’, offering NHS professionals a practical guide to the testing process. Those who enrolled on Monday 4 March were joined by a team of expert mentors who provided support during the course.

We are committed to building on the success of efforts in 2024 and broadening our reach so that our co-ordinated communications around rare diseases day reach more healthcare professionals across the NHS. This year, for the second time, we are working with colleagues in NHS England to celebrate Rare Diseases Day 2025 across the NHS. This has included working closely with Medics4RareDisease and Genetic Alliance UK to develop messaging.

Action 6: develop an innovative digital educational resource (‘GeNotes’) - providing healthcare professionals with relevant and concise information to support patient management, linking to the NHS Genomic Test Directories, and signposting to extended learning opportunities

GeNotes is an online resource for clinicians, providing educational information at the point of need in the clinic, as well as opportunities for extended learning through the Knowledge Hub. This action first appeared in the 2022 action plan and we have continued to extend and build on it. NHS England’s flagship GeNotes resource continues to grow, with more than 500 resources featured across 9 specialties. This resource is currently available for:

oncology (including cancer predisposition syndromes)
fetal and women’s health
paediatrics
primary care
cardiology
endocrinology
pharmacogenomics
nephrology
neurology

Gastro-hepatology will be launched in February 2025. Articles cover a wide range of clinical scenarios, genomic testing guidance and further learning, and many have been updated in line with the latest Genomic Test Directory updates. GeNotes attracts visitors from both within the UK and beyond and has been accessed by 370,000 individuals worldwide to date. Of these, this year over 117,000 visitors accessed the page from the UK, with nearly 270,000 total page views.

NHS England is also exploring other routes for users to access GeNotes. This includes contributing GeNotes content to a pilot of an AI-based mobile app to support clinical decision-making. They are also currently piloting GeNotes being available as an integrated part of clinical decision-support templates that will be accessible across 87% of primary care systems. Work to scope further collaboration and integration with the National Genomic Test Directory is also underway.

Throughout its development GeNotes has been tested with users to make sure that it provides the information healthcare professionals need in the form they need it. Ongoing evaluation ensures its content is fit for purpose and reaching the appropriate audiences. By working together NHS England and Medics4RareDiseases (M4RD) have been improving the awareness of GeNotes and wider resources with healthcare professionals. This includes through podcasts, social media and in-person training with GPs, effectively demonstrating the value of these resources to their target audience.

Giving clinicians easy access to timely and accurate information on rare conditions helps them make the right genomics decisions at each stage of a clinical pathway, supporting quality healthcare provision to people living with rare diseases.

Metrics and milestones as published in 2024 action plan:

continue to develop speciality specific content for existing specialties - throughout 2024 to 2025
introduce more speciality working groups - to be decided and established throughout 2024 to 2025
during quarter 1 of 2024 to 2025 GeNotes working groups will be reviewed to ensure both multi-professional workforce representation and patient and public involvement in content development
development of the GeNotes app, consisting of 3 phases:
- user testing in quarter 1, 2024 to 2025
- app discovery (ensuring the app can be found by users) in quarter 2, 2024 to 2025
- testing to assess capability and functionality in quarter 2, 2024 to 2025
pilot project to syndicate GeNotes contents into GP systems in quarter 4, 2024 to 2025

Metrics and milestones for 2025:

release of a ‘minimal viable product’ for a digitised test directory at the end of quarter 1 2025 to 2026
from quarter 2 2025 to 2026 onwards, plan integrations between the digitised test directory and GeNotes
quarter 3 2025 to 2026, the GEP will prioritise an identified backlog of development work
the first phase GEP aim to deliver by quarter 1, 2026 to 2027
progress pilot of an AI-based mobile app to support clinical decision-making - the app will go to user testing by the end of quarter 4, 2024 to 2025
update England Rare Diseases Framework Delivery Group on piloting GeNotes being available as an integrated part of clinical decision-support templates
during quarter 4, 2025 to 2026 and beyond, scope further templates that GeNotes could support and update England Rare Diseases Framework Delivery Group

Action 7: determine how best to include rare diseases in UK health professional education and training frameworks

As well as GeNotes, which provides information to healthcare professionals at the point of need, the national GEP is also developing a range of training and educational resources on rare diseases. Action 7 looked to determine how best to include rare diseases in UK health professional education and training frameworks. As part of this, NHS England is working closely with the Academy of Medical Royal Colleges (AoMRC) Genomics Professional Partnership Group. This group brings together genomic leaders and experts across the whole NHS to support, advise on and integrate the safe implementation of genomic medicine and education across the UK. It includes representation from 30 royal colleges or professional organisations and 17 specialties. NHS England is currently collaborating on the evaluation of medical curricula and development of training frameworks to ensure information on rare disease is appropriately integrated.

NHS England is working with M4RD on a review of current activity within the GEP around rare diseases and will be making recommendations around integration and collaboration with the rare diseases community.

In addition, NHS England continues to update and launch clinical pathway initiatives with the inclusion of, for example, cancer predisposition syndromes and resources to assist those developing clinical pathways. This is a method to support the integration of competencies into NHS workforce education and training in a nationally co-ordinated and consistent way.

NHS England has an established patient advisory group for genomics education (PAGE). The group meets 3 times a year to ensure lived experience and patient voices are an integral part of the GEP resources and to determine the direction of travel for the programme aligned to their priorities.

Quote from PAGE member:

I have lived experience as a rare disease patient and parent, and my family has benefited from genomic testing.

I joined the PAGE group as I felt it was important to share personal experiences to help facilitate, where possible, improvements in the diagnosis and understanding of conditions that have a genetic origin. In essence, I wanted to be able to give something positive back to the healthcare system that had helped myself and my family.

Through the PAGE group, I have been able to participate in the production of a short film that shares my experience of my diagnostic odyssey and how genomic testing was key to the identification of my rare disease. It has been shown at genomics conferences, used by my regional GMSA, and uploaded to YouTube. I hope my story is able to help improve understanding of the impact and importance of genomic testing for clinicians, researchers and other health professionals who are the touch points for future patients who may have a genetic condition. And I hope that the diagnostic odysseys for these patients are reduced because of it.

Embedding rare diseases in medical curricula will empower the next generation of clinicians to consider the needs of people living with rare conditions in a variety of settings and help ensure people get the best possible care.

Metrics and milestones as published in 2024 action plan:

national GEP will continue to work with AoMRCs and our fellows throughout 2024 to 2025 to continue to ensure genomics using rare disease examples are embedded into curricula, academic frameworks and learning plans
NGE programme is contracted with M4RD in 2023 to 2024 to develop further education and training resources to meet the needs of the multi-professional workforce and raise awareness across profession and specialities - we are committed to continuing this partnership in the 2024 to 2025 financial year
during 2024 to 2025 there will be further development of clinical pathway initiatives with additional rare disease pathways to be decided and added

Metrics and milestones for 2025:

PAGE to continue to meet 3 times a year
NHS England to update England Rare Diseases Framework Delivery Group on review of current activity within the GEP around rare diseases
NHS England to update England Rare Diseases Framework Delivery Group on new clinical pathway initiatives

Action 8: extend the remit of the GEP to include non-genetic rare diseases

While around 80% of rare diseases have an identified genetic component, ‘non-genetic’ conditions affect a significant proportion of people living with rare conditions. These can include conditions like autoimmune diseases. Extending the remit of the NHS England GEP to include these conditions will improve clinical decision-making for more of the rare disease community.

Since this action first appeared in the 2022 action plan significant progress has been made. Work continues, in partnership with M4RD to expand the programme’s remit into non-genetic rare disease. In early 2023, M4RD undertook a review of the Rare Disease Education Hub and other educational resources in rare disease, providing a report and recommendations for improvement and further development.

Further work has been undertaken to develop a clear strategy on what the GEP wants to achieve overall in this space with focused actions to achieve outputs. This will mainly be delivered by facilitating the faster turnaround of rare disease content for GeNotes through nurturing links with patient advocacy groups and responding quickly to workforce and patient needs.

In developing material NHS England will work collaboratively with groups producing high quality resources within rare disease to reduce duplication and increase rate of resource creation, and will work with and support Medics4RareDiseases on its #ShowYourStripes campaign for Rare Disease Day.

Metrics and milestones as published in 2024 action plan:

NGE will continue to work with M4RD throughout 2024 to 2025 including to extend the remit of the programme to include non-genetic rare disease
enhance patients, family members and carers involvement in the NGE through the patient group PAGE
as part of the development of the communication skills resource, continue to work with families, patients and carers on the impact their health outcomes and how best to optimise communication in different scenarios
include patient and public involvement on the NGE expert reference group which meets bi-monthly in meetings throughout 2024 to 2025
deal with the pre-diagnostic uncertainty for families and anxiety with patients with SWAN through ongoing partnership with M4RD throughout 2024 to 2025

Metrics and milestones for 2025:

NHS England to update England Rare Diseases Framework Delivery Group on future of programme beyond March 2025

Action 19: publishing and implementing specific strategies for increasing awareness of rare diseases in the nursing and midwifery, pharmacy and primary care workforce

It’s important to consider all healthcare professionals in raising awareness of rare diseases, as people living with these conditions interact with all parts of the health system. In the 2023 action plan, we introduced a focus on increasing awareness of rare diseases in the nursing and midwifery, pharmacy and primary care workforce which have been further developed through the GEP in 2024.

Nursing and midwifery:

NHS England has developed a survey of higher education institutes’ undergraduate and postgraduate genomics content in curricula. This aims to develop core principles with a higher education institute in London and, following the survey, expand and review these to ensure national consistency.

In March 2024, NHS England undertook a survey with 56 lead midwives for education to assess the status of genomics within midwifery curricula. In May 2024, an interactive genetics and genomics in midwifery module was developed and embedded into Royal College of Medicine iLearn.

In September 2024 a genomics learning passport for midwives was developed to assess personal development and as a guide for lead midwives for education to select genomic level and/or topic for lectures.

Pharmacy:

The Pharmacy Genomics Workforce, Education and Training Strategic Framework was published in January 2024. This was followed in July 2024 by publication of an indicative curriculum. Its adoption into practice is being considered by the NHS England Pharmacy Genomics Workforce Group.

An online tutorial has been developed to support pharmacists, pharmacy technicians and trainees working in primary and/or secondary care who currently have limited experience working with pharmacogenomic education (over 5,000 visits since the start of March 2024). This will help support better decisions around which medicines people should be prescribed, depending on their genetic makeup.

In the year ahead the GEP will also support further engagement and communication with the pharmacy workforce including through supporting educational webinars.

Primary care:

Progress has also been made on primary care with the GEP working with the NHS England primary care lead to champion genomics in general practice and to develop resources including GeNotes.

The GP with Extended Role (GPwER) Clinical Genetics/Genomics Framework is available on the Royal College of General Practitioners (RCGP) website. It’s recommended that those working in clinical roles now use this as a title rather than GPwSI. The GEP alongside RCGP will be communicating and raising awareness across the system.

A PGCert in Genomics in Counselling skills course has also been commissioned, which will include rare diseases learning outcomes.

While many patients with rare conditions will need to access highly specialised services we know that they also access wider generalist services, such as GPs and pharmacies, and come into contact with many healthcare professionals outside of highly specialised services such as nurses, midwives and pharmacists. Therefore, it is important that patients feel listened to and understood not just when they access specialist secondary or tertiary level care but also when they access primary care and community services. Through the above action, we have strived to raise awareness in these sectors of the NHS and ensure that patients feel able to discuss their needs with a range of healthcare professionals and that these professionals in turn feel supported to be able to do so and confident they have the knowledge to support patients with rare conditions.

Metrics and milestones as published in 2024 action plan:

develop framework to effectively gather evidence to evaluate the impact and uptake of resources to be published in the 2025 action plan
continuation of evaluation of the impact and uptake of resources in midwifery, pharmacy and primary care
take forward the activity identified in the Genomics Pharmacy Workforce strategy to develop this workforce further
incorporate resources developed by the nursing transformation team into NGE education and training
incorporate rare diseases into the learning outcomes into the PGCert in Genomics in Counselling skills course

Metrics and milestones for 2025:

Genomics Education England to continue working with the NHS England primary care leads to develop more resources including GeNotes and its use to guide primary care practice, and update the England Rare Diseases Framework Delivery Group by the start of 2026
continue consideration by the NHS England Pharmacy Genomics Workforce Group of the indicative curriculum’s adoption into practice and update England Rare Diseases Framework Delivery Group by the start of 2026
GEP will support further engagement and communication with the pharmacy workforce including through supporting educational webinars
GEP alongside RCGP to communicate and raise awareness across the system of the published Clinical Genetics/Genomics Framework

Action 30: developing a genomics communication skills resource

Following the 2024 action plan, NHS England has started working on developing a communication skills resource to aid healthcare professionals in having sensitive conversations that ensure the patient feels supported in their diagnosis of a rare condition. This includes a 3-tiered educational approach to communications skills for both the specialist and wider workforce. The core skills tier is in development and the first content is expected to be published in spring 2025. The learning outcomes are currently being reviewed and storyboarding is taking place for e-learning modules, with M4RD supporting the links into the rare disease community to ensure lived experience is represented in the content.

For the mid-tier applications in practice element, NHS England has been trialling a virtual reality solution which completed in September 2024. This will enable healthcare professionals to more easily practice having sensitive conversations. The effectiveness of this will be evaluated through a survey and NGE hope to develop this further into an immersive training solution.

NHS England has also commissioned Manchester University to work with them to develop content, approach and deliver advanced tier face-to-face genomics communication skills workshops.

As part of Genomics Training Academy (GTAC) delivery communication skills education will be developed for the specialist genomic workforce.

This action will ensure that healthcare professionals are appropriately skilled to have sensitive conversations and patients are better supported.

Metrics and milestones as published in 2024 action plan:

learner feedback and usage to be monitored on a quarterly basis, progress will be reported through the workforce steering group, GTAC steering group and the England Rare Diseases Action Plan Delivery Group
usage numbers monitored and reported in 2025 action plan
in-depth follow-up of use in practice beginning at the launch of the bronze tier in quarter 2 of 2024 to 2025.

Metrics and milestones for 2025:

first content of the core skills tier of communications skills to be published in spring 2025
blended learning approach for the advanced skills tier to be delivered starting spring 2025
effectiveness of a virtual reality solution will be evaluated and NGE to review results with a view to integrating an immersive training solution in future training. NGE to update the England Rare Diseases Framework Delivery Group by the start of 2026

Action 31: developing the specialist genomics workforce through GTAC

In last year’s plan we reported the development of the specialist genomics workforce through GTAC. GTAC is a national initiative led by NHS England’s GEP and Genomics Unit. The academy provides training and education to the specialist genomics laboratory and clinical workforce within the UK, including bioinformaticians, clinical geneticists, clinical scientists, biomedical scientists, genetic counsellors and genetic technologists. Building a specialist workforce will expand capacity for genetic testing, diagnostics and support in a clinical setting.

Progress on the GTAC over the last year includes the development of governance and reporting structures, content development methodologies and processes to ensure quality assurance of resources, guidance documentation for specialists developing content, the provision of a learning management system (Moodle) and the creation of an evaluation framework to assess both resources and the academy model itself. In September 2024 a number of virtual reality learning packages were launched showing laboratory orientation and processes in an immersive environment. This will be available across GLHs for trainees and the headsets and the hardware required to use this technology have been distributed.

Metrics and milestones as published in 2024 action plan:

evaluation of the GTAC model to demonstrate value for money and return on investment starting to report by quarter 4, 2024 to 2025
number of specialist workforce available per patient population measured to be completed quarter 4, 2024 to 2025
measure the impact of the resource on the genomics workforce training, resources and the service with a report being published in quarter 4, 2024 to 2025

Metrics and milestones for 2025:

delivery of the additional assets to GLHs aiming for March 2026
preliminary evaluation data expected by August 2025. NHS England to update England Rare Diseases Framework Delivery Group by 2026

Priority 3: better co-ordination of care

Rare diseases are often life-long conditions, affect different parts of a person’s body and have impacts on different aspects of their health and lives. People living with rare conditions need support from many different parts of the health and social care system, as well as from wider services, throughout their life. Ensuring that different aspects of care are co-ordinated is important for improving health outcomes, reducing financial burdens on families and reducing health inequalities.

Action 20: commission research to provide the evidence needed to operationalise better co-ordination of care in the NHS

In the 2023 action plan we committed to commissioning research through NIHR to build on the earlier CONCORD study and provide the evidence needed to operationalise better co-ordination of care in the NHS. This study investigates how services for people with rare conditions are co-ordinated in the UK and how those affected by rare conditions and their healthcare providers would like these services to be co-ordinated. This was important so that we could understand how to best make improvements to care co-ordination in a way which aligned to the needs of patients with rare conditions and which was as cost effective as possible for the NHS.

This research is funded through NIHR - a 2-year contract running from May 2024 with RAND Europe and University of Cambridge. Milestones for this research were published to the UK Rare Disease Forum’s online platform in August and are set out in this annex. Significant progress has been made towards the key milestones.

Metrics and milestones of this study will be reported on and an evaluation process is in place. Additionally, the Lived Experience Expert Group has been set up, with membership confirmed and meetings underway. The review (now a full systematic review rather than a scoping review) is also currently underway, and study sites are being recruited for the mixed-methods evaluation.

Metrics and milestones as published in 2024 action plan:

research team and milestones for the year ahead publicly announced by April 2024 (through the UK Rare Diseases Forum and online platform)
progress will be reported in the 2025 action plan

Metrics and milestones for 2025:

results of the full systematic review to be reported by spring 2025
progress to be reported in 2026 final paper

Action 21: include the definition of co-ordination of care in all new and revised services specifications for patients with rare diseases, and ensure the priorities of the UK Rare Diseases Framework are embedded across NHS England highly specialised services

In order to continue improving co-ordination of care within the NHS for patients with rare conditions, action 21 set out to include the definition of co-ordination of care (as defined in the original CONCORD study in all new and revised services specifications for patients with rare diseases. Service specifications are produced or renewed over time. Following this change, service specifications for 2 conditions are being published which include the definition of co-ordination of care: cystinosis and haemophilia.

The service specification for the rare disease cystinosis - Cystinosis diagnosis and co-ordination of management (all ages) - has been specifically constructed with care co-ordination in mind. Data from the cystinosis centres is sent to the Renal Registry and there are ongoing discussions about the onward transmission of that data to NCARDRS.

The specification for haemophilia services (all ages) will be published later this year and will include reference to care co-ordination and data from the haemophilia centres is sent to the National Haemophilia Database.

These changes will mean that measures to ensure care is well co-ordinated for patients with cystinosis and haemophilia are embedded as services for these conditions are designed and procured. New service specifications for other rare conditions will be produced, similarly centred around providing well co-ordinated care for all patients. Over time this will help underpin improved co-ordination of care.

Metrics and milestones as published in 2024 action plan:

monitoring of the numbers and examples of service specifications that include the agreed definition of care co-ordination and references to submitting data to NCARDRS

Metrics and milestones for 2025:

ongoing discussions about the onward transmission of data from the Renal Registry to NCARDRS. NCARDRS to update England Rare Diseases Framework Delivery Group by 2026
new service specifications for other rare conditions will be produced, similarly centred around providing well co-ordinated care for all patients - NCARDRS to update England Rare Diseases Framework Delivery Group by 2026

Action 32: implement networked models of care for patients with rare diseases ensuring that specialist expertise is always available while allowing patients to be treated and cared for as close to home as possible

Action 32, introduced last year, worked on implementing networked models of care which will ensure patients can access specialist care as close to home as possible. The first 2 networked models of care are planned to be for amyloidosis and inherited metabolic disorders.

During this year NHS England has made good progress towards putting in place the framework needed to commission amyloidosis and inherited metabolic disorders networked models of care. A provider selection exercise is being run to secure amyloidosis network partners in the north-west, south-west, Midlands and north-east and Yorkshire. These are expected to be mobilised by May 2025. A specification has been drafted for a networked model of care for metabolic services and engagement on the draft is taking place with stakeholders. This is dependent on funding and it is currently expected this will move forward for commissioning in 2026.

The networked models of care will enable patients with amyloidosis and inherited metabolic disorders to access care closer to home, avoiding the need to travel. This will reduce the financial burden and minimise the time needed to attend appointments and the disruption to everyday life. If this model can be shown to be successful for the first 2 conditions it can be rolled out to more rare conditions over time so that more people can benefit.

Metrics and milestones as published in 2024 action plan:

proposals for networked models of care for inherited metabolic disorders and amyloidosis developed by February 2025 and reported on the 2025 action plan
networked models of care for inherited metabolic disorders and amyloidosis implemented in 2024 to 2025
progress regularly reported to the Highly Specialised Services Oversight Group

Metrics and milestones for 2025:

amyloidosis network partners in the north-west, south-west, Midlands and north-east Yorkshire expected to be mobilised by May 2025. NHS England to update England Rare Diseases Framework Delivery Group
networked model of care for metabolic services is dependent on funding and it is currently expected it this will move forward for commissioning in 2026

Priority 4: improved access to specialist care, treatment and drugs

There are over 7,000 identified rare diseases, which can be both life-limiting and life-threatening and disproportionately affect children. Seventy-five percent of rare diseases affect children and more than 30% of children with a rare disease die before their fifth birthday. However, only 5% of rare conditions have an effective and approved treatment. Improving access to specialist care, treatment and drugs is vital to save and improve lives. The UK’s strong life sciences sector and single payer healthcare system makes it well placed to be a world leader in advancing treatments for rare conditions. However, we know that new treatments in rare diseases face specific challenges around the numbers of people eligible for clinical trials, manufacturing and scale up capacity, and the regulatory environment.

Action 13: implementing NICE’s new methods and processes to support access to new treatments for rare disease patients

In February 2022, the National Institute for Health and Care Excellence (NICE) implemented its updated methods and processes following extensive stakeholder engagement, giving particular consideration to the suitability of its methods and processes for treatments of rare diseases. In the 2022 action plan we introduced action 13 to capitalise on these changes and to implement NICE’s new methods and processes to support access to new treatments for rare disease patients.

Of note, in 2022 the severity modifier was introduced by NICE in order to place greater value on health benefits provided for people with more severe diseases. A review of how the current NICE methods are working with respect to the severity modifier was presented to the NICE board meeting in September 2024. The board agreed that the report demonstrated that the severity modifier is doing what it is designed to do, with higher approval rates for both cancer and non-cancer treatments and allowing treatments for a broader range of diseases to be recommended for patients, such as cystic fibrosis. NICE will do further work to try to understand the impact this has had on rare diseases.

As part of the manual underpinning the way NICE prioritises topics, it has set out 3 key strategic principles upon which it consulted earlier this year relating to rare diseases. These principles inform decision making by NICE’s prioritisation board which makes decisions on priorities for NICE guidance and routes medicines to the appropriate programme.

The criteria review for determining whether a medicine should be routed to NICE’s highly specialised technology programme for the evaluation of very rare diseases is being undertaken and a public consultation on this closed on 30 January 2025. The refined highly specialised treatment (HST) criteria are expected to be implemented from April 2025. The review is intended to make the criteria more explicit and objective without changing the essence or intent of how the criteria are interpreted. Additional guidance and clarity will be provided on application of the criteria to improve transparency of the selection decisions.

Metrics and milestones as published in 2024 action plan:

NICE will be in a position to publish the impact of 2022 manual changes in a report by the end of 2024

Metrics and milestones for 2025:

NICE will complete work to understand the impact the review has had on rare diseases by the end of 2025
meeting between NICE and members of the Genomic Medicines Service to support horizon scanning to be arranged for quarter 2, 2025
refined HST criteria to be implemented from April 2025

Action 14: monitor overall uptake of drugs for patients with rare diseases and map geographical access to those drugs

In last year’s action plan we reported on the progress NHS England had made to analyse the uptake and geographical equity of drugs which had found that in the majority of cases, overall uptake exceeded or was in line with anticipated uptake. During the coming year, NCARDRS will explore the development of a reproducible analytical pipeline that can evaluate uptake of drugs at an individual patient level and be applied and/or scaled to other conditions or drugs.

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis, a group of rare autoimmune diseases, will be the first condition which will be explored as part of wider pathway data work currently underway within NCARDRS. Dependant on this initial analysis, the remaining 3 metrics and milestones proposed last year under action 14 - to inform NHS England’s Highly Specialised Commissioning Team for drugs used in highly specialised service or the relevant clinical reference group in other specialised services of the findings of analysis, submission of a publication for peer-review describing the process and outcome, and scoping of other condition the pipeline can be applied to - will be progressed in the year ahead.

Metrics and milestones as published in 2024 action plan:

initial analyses on hemophagocytic lymphohistiocytosis as an exemplar, but with a view to producing a reproducible analytical pipeline that can be scaled to other conditions or drugs
NHS England’s Highly Specialised Commissioning Team will be informed of findings of the above analysis - if applicable, agree output and route of dissemination to measure impact of interventions
if possible, the submission of a publication for peer-review describing the process and outcome
scoping of other conditions the analytical pipeline can be applied to, in consultation and agreement between NHS England Highly Specialised Commissioning and NDRS

Metrics and milestones for 2025:

NCARDRS will explore the development of a reproducible analytical pipeline that can evaluate uptake of drugs at an individual patient level and be applied and/or scaled to other conditions or drugs. NCARDRS will update the England Rare Diseases Framework Delivery Group by 2026
dependant on analysis, the other remaining 3 metrics and milestones proposed last year under action 14 will be progressed 2025

Action 22: improved ‘findability’ of people living with rare diseases using NCARDRS

A pivotal action to improve our understanding of rare diseases - including access to treatment and care - is improving the ‘findability’ of people living with rare diseases using NCARDRS. NCARDRS collects data from a variety of sources to support rare disease registration and is continuing to engage with specialised and highly specialised services, and rare disease collaborative networks, to establish data flows and increase the number of conditions registered in NCARDRS to support service planning and commissioning.

To improve standardisation of data collection and reduce burden on data providers, NCARDRS has produced a formal rare disease data set, with input from clinical experts and aligned closely with the EU-RD Platform’s common data elements for rare disease registration. See NCARDRS’ rare disease data set, including a data submission template for providers.

NCARDRS published its first Rare Disease Prevalence report on Rare Disease Day 2024. This initial proof of concept publication included several rare diseases, rare congenital conditions and rare cancers. Feedback on the prevalence report will be gathered through a questionnaire and engagement with Genetic Alliance UK and other patient organisations. The prevalence report will be updated annually and new conditions will continue to be added in an iterative manner.

The NCARDRS team is working towards getting this output badged as an official statistic in development. NCARDRS is committed to providing a solution that allows rare disease patients to self-report for registration purposes. The interim solution of an email-based self-reporting system has been paused due to capacity constraints and limited utility of the data collected in this way. However, NCARDRS continue to explore options within the NHS England Transformation Directorate that would support rare disease patients to self-register which remains an important objective for the service. Once a solution has been found NCARDRS will engage with stakeholders across the rare community to ensure that the call to self-report is effectively disseminated.

Metrics and milestones as published in 2024 action plan:

increased number of specialised services sharing data with NCARDRS; all outstanding services to be contacted regarding data sharing throughout 2024 to 2025
publication of rare disease prevalence tool prototype and gathering of stakeholder feedback in early 2024
digital solution for self-reporting established by end of 2024 to 2025
continued publication of peer-reviewed work throughout 2024 to 2025

Metrics and milestones for 2025:

NCARDRS to continue to explore options within the NHS England Transformation Directorate that would support rare disease patients to self-register and update the England Rare Diseases Framework Delivery Group by 2026
Rare Disease Prevalence report will be updated for February 2026

Action 25: review the effectiveness of EAMS, ILAP and the IMF in supporting access to treatments for people living with rare diseases

The Early Access to Medicines Scheme (EAMS), the Innovative Licensing and Access Pathway (ILAP) and the Innovative Medicines Fund (IMF), are access pathways across the regulatory and access system designed to support innovative treatments being available to patients who need them earlier.

In recent years, the health system has established a number of initiatives to ensure the timely adoptions of innovative treatments that meet a high level of clinical need, including:

ILAP: an integrated pre-market pathway where developers can work collaboratively with the UK’s national health system, the regulator and health technology assessment bodies from the early stages of clinical development.

EAMS: which allows important drugs to be used in clinical practice during the later stages of the regulatory process, typically when they do have not received a marketing authorisation but where there is a clear unmet medical need.

IMF: a managed access fund that provides a route to faster patient access while further data can be collected, ensuring that treatment using the latest health technologies can begin without delay and that NHS clinicians can help build the evidence-base for a new treatment.

We are grateful to the Association of the British Pharmaceutical Industry (ABPI) and the BioIndustry Association (BIA) who in 2023 conducted a survey of their members to understand experience of engaging with EAMS, ILAP and IMF. The survey received responses from 20 companies creating a rich picture of the experiences the life science sector of these access pathways specifically for rare disease treatments.

The survey results describe challenges around UK launch decisions, with some instances of companies choosing not to launch in the rare disease area, citing factors around the HST criteria and low prospects of reimbursement through the single technology appraisal (STA) process. In 2024, NHS England, NICE and MHRA attended a meeting with BIA, ABPI and wider representative from industry, to discuss the findings of the survey and rare disease specific challenges faced in developing and accessing new therapies. We are grateful to the patient and clinical representatives who attended the meeting, bringing valuable insights on access to treatments.

As committed to in the 2024 action plan, MHRA, NICE and NHS England produced a joint written response to the survey which is included in annex C. Acknowledging some of the challenges highlighted in the survey around EAMS, ILAP and IMF, the MHRA, NHS England and NICE response highlighted the following.

For EAMS:
Updated information on EAMS applicants was provided with enhanced guidance on real world data collection and implementation. MHRA reported that it is undertaking a review of licensing pathways as well as being open to working with industry to produce further guidance on EAMs or other licensing routes. NICE and NHS England note the risk that temporary reimbursement prior to guidance does carry substantial risk in undermining their processes, especially if this incentivises companies to delay NICE guidance. MHRA, NHS England and NICE made a request that industry further articulate the challenge that temporary reimbursement solves and provide tangible examples of where this would have supported market access.

For ILAP:
At the time the response was written, the review of ILAP was under way. The response commits to making further improvements, taking into account the survey responses to ensure ongoing support for rare disease therapies and views of patient organisations. The challenges of the current version of ILAP were recognised and a commitment was made to provide further details on the proposed improvements.

For IMF:
It was acknowledged that there had been limited use of this form of reimbursement for rare diseases. However, 3 indications have now been funded through IMF for managed access, 10 more have received earlier access through interim funding in IMF and many more topics considered as potentially suitable for IMF have gone on to secure a routine commissioning recommendation. NHS England and NICE continue to work in collaboration to monitor potential managed access indications, though it should be noted that IMF entry requires the support of the drug’s manufacturer. NICE and NHS England also point to their earlier response to engagement on proposals for IMF.

The survey and the meeting have helped to support understanding of the experiences of industry of engaging with EAMS, ILAP and IMF. This has been fed into the review of ILAP. The ILAP partnership has now relaunched its offer in response to the evolving needs of our fast-paced life sciences ecosystem. It has been substantially reworked since the pathway’s launch back in 2021. Full details of the pathway were published in January 2025 and the new ILAP will open to applications in March 2025. NHS England, NICE and MHRA will meet annually to continue to discuss progress and the role of EAMS, ILAP and IMF in supporting access to treatments for people living with rare diseases. These meetings will include representatives from patient advocacy groups, industry and clinical researchers. The first of these meetings will happen in summer 2025.

Improving the understanding of specific challenges affecting rare disease therapies aims to increase the relevance of access pathways, in the long-term increasing the number of effective and approved treatments available for patients.

Metrics and milestones as published in 2024 action plan:

by May 2024, NHS England, NICE and MHRA will have met with ABPI and BIA to further understand the results of the 2023 survey on EAMS, ILAP and IMF
by summer 2024, NHS England, NICE and MHRA will have provided a written response to the 2023 survey conducted by ABPI and BIA on EAMS, ILAP and IMF
further progress on this action will be reported in the 2025 action plan

Metrics and milestones for 2025:

NHS England, NICE and MHRA will meet annually to continue to discuss progress and the role of EAMS, ILAP and IMF in supporting access to treatments for people living with rare diseases. These meetings will include representatives from patient advocacy groups, industry and clinical researchers. The first of these meetings will happen in summer 2025

Action 26: registration of national data for exemplar rare genetic conditions which cause an inherited predisposition to cancer

In the 2023 action plan, this action was introduced to improve the registration of national data for exemplar rare genetic conditions which cause an inherited predisposition to cancer, creating a National Inherited Cancer Predisposition Registry. A core data set has been agreed with input from the UK Cancer Genetics Group and all cancer susceptibility genes tested as part of the National Genomic Test Directory for Rare and Inherited Diseases are in scope of the National Inherited Cancer Predisposition Registry. A National Inherited Cancer Predisposition Registry Steering Group has been established, including representation from NHS England (NDRS, cancer, genomics and screening programmes), UK Cancer Genetics Group, and NHS clinical genetics, counsellors and clinical scientists.

To support this activity, in October 2024 we committed £750,000 through the NHS England National Cancer Programme to all regional clinical genetics services to enable a one-off retrospective data collection exercise which will be completed by April 2025. NCARDRS are modifying their API portal to facilitate prospective data reporting from all regional clinical genetics services; this will also be completed by April 2025. This action builds on the infrastructure and success of the national Lynch syndrome registry in 2023.

Metrics and milestones as published in 2024 action plan:

target initial genes prioritised by UK Cancer Genetics Group

Metrics and milestones for 2025:

one-off retrospective data collection exercise will be completed by April 2025
NCARDRS are modifying their API portal to facilitate prospective data reporting from all regional clinical genetics services and this will be completed by April 2025

Action 27: improving the NIHR Be Part of Research platform for people living with rare diseases

NIHR Be Part of Research is an online service that helps members of the public understand what research is, what taking part might involve, as well as helping people find research studies and volunteer to take part. Last year we worked with the rare diseases community to look at how well NIHR Be Part of Research works for people living with rare conditions and to identify what improvements could be made. This work included conducting a survey and in the 2024 action plan we committed to making changes to the service based on the survey outcomes and to testing of the NIHR Be Part of Research platform. NIHR have added ‘sarcoma’ and ‘paediatric conditions’ to the A to Z list of conditions as recommended by the survey and are now undertaking a wider review of conditions listed. This work is ongoing and will includes people living with rare conditions in the testing of proposed changes as well as to other changes to the service over the last year.

The benefits of the work for people living with rare conditions from the changes which are being made to NIHR Be Part of Research are that it will make it easier for people to find information about rare disease research trials and to register to be involved in research if they wish to do so. It will also raise awareness about research being part of a conversation between clinicians and patients at appropriate points on the healthcare pathway.

Metrics and milestones as published in 2024 action plan:

Be Part of Research will implement the recommendations from the survey from October 2023, with all milestones to be implemented by autumn 2024. These are:
- improve categorisation of health conditions on the A-to-Z conditions list by using survey feedback and insights from usability testing with the rare disease community - this will ensure people with rare conditions can find an appropriate category for their condition on the Be Part of Research site
- optimise the navigation on the A to Z conditions list to make it easier for people with rare conditions to find research related to their condition
- include at least one member of the rare condition community in each round of user testing for future developments to the service

Metrics and milestones for 2025:

undertake a wider review of conditions listed on Be Part of Research and update the England Rare Diseases Framework Delivery Group for 2026

Action 33: develop funding mechanism that sufficiently incentivises centres to undertake whole body scans on individuals with rare conditions resulting in a genetic predisposition to developing cancer prematurely

Identifying cancer early on significantly improves survival and outcomes for patients. The NHS Long Term Plan sets out the ambition that 75% of cancers be diagnosed at early stage by 2028. Some rare conditions such as neurofibromatosis type 1 and multiple endocrine neoplasia type 2 result in people being more likely to develop cancer. It is important that they are monitored closely to ensure cancers are caught as early as possible. One monitoring technique is carrying out full body scans in this population. In last year’s action plan we committed to developing a funding mechanism that sufficiently incentivises centres to undertake whole body scans for individuals with rare genetic conditions that predispose them to developing cancer prematurely. During this year NHS England has made good progress towards delivering this action.

A ‘gateway 3’ (procurement) implementation paper setting out the proposed processes for separately identifying adult (expressions of interest) and paediatric (market engagement in the first instance) providers was agreed in August 2024. Awarding of contracts will be subject to funding agreements for 2025. Once this service is in place, the benefit will be that people living with rare conditions resulting in a genetic predisposition to developing cancer prematurely will receive improved access to whole body scans. This will result in earlier diagnosis of cancer, earlier intervention and improved outcomes.

Metrics and milestones as published in 2024 action plan:

identify the number of eligible individuals patients receiving scans tracked progress regularly reported to the Highly Specialised Services Oversight Group

Metrics and milestones for 2025:

awarding of contracts will be subject to funding agreements for 2025. If funding is available then contracts will be awarded during 2025 to 2026
progress regularly reported to the Highly Specialised Services Oversight Group and England Rare Diseases Framework Delivery Group updated by 2026

Action 34: building on the work in action 25, review the effectiveness of IDAP pilot in supporting access to medical devices, including diagnostics, for people living with rare disease

In the 2024 action plan we introduced a review of the effectiveness of the Innovative Devices Access Pathway (IDAP) pilot in supporting access to medical devices, including diagnostics, for people living with rare disease and how IDAP can support rare disease activity going forwards.

The IDAP pilot was launched to support the development of innovative technologies that address unmet clinical needs in the UK. To qualify for the programme, products needed to target conditions that are life-threatening or seriously debilitating while also fulfilling a significant unmet clinical need. Despite this criterion being a key part of the selection process, the pilot did not receive applications focused on rare diseases.

The pilot was open to applications from commercial and non-commercial developers from the UK, and international markets who have developed new medical devices; there are currently 8 successful applicants who are receiving support from IDAP partners at key stages of their product development journey. While none of the selected technologies are directly relevant to rare diseases, the evaluation of the pilot will consider what action can be taken to implement these learnings into any future programme to support the route to market for early stage innovations which could include diagnostics and treatments specifically for people living with rare diseases.

The pilot is set to conclude in March 2025 and will be evaluated to inform its effectiveness and identify areas for improvement. Based on these findings, a decision will be taken whether to establish IDAP as an ongoing pathway. This will need to be informed by engagement with stakeholders to ensure the pathway can evolve to be inclusive and supportive of products for the diagnosis, treatments or management of diseases, including rare diseases.

Metrics and milestones as published in 2024 action plan:

proportion of applications in the pilot which are rare disease medicines reported in 2025 action plan
conclusions from the IDAP pilot review reported in the 2025 action plan

Metrics and milestones for 2025:

not applicable - action concluded in 2025

Action 12: develop a strategic approach for gene therapies and other advanced therapeutic medicinal products (ATMPs) - based on horizon scanning by NHS England

NHS England has developed a strategic approach to commissioning ATMPs. This involves ‘horizon scanning’ across a 3-year horizon so that it can be understood when therapies are likely to be available following a NICE recommendation and services can be effectively planned. This includes working closely with industry, patient charities and clinical specialists so that service delivery requirements can be understood. During 2024 NHS England has continued engagement on the strategic approach including at national and international events.

The benefit for patients is that the NHS is ready to commission services as soon as a NICE recommendation is received and patients are able to access newly approved therapies as rapidly as possible, such as Casgevy (exagamglogene autotemcel), a gene therapy, which was approved for sickle cell anaemia and thalassemia in 2024.

Metrics and milestones as published in 2024 action plan:

NHS England will continue to communicate with stakeholders on its strategic approach in this rapidly evolving area, including at events and through its membership of ATMP engage

Metrics and milestones for 2025:

not applicable - action concluded in 2025

Metrics and milestones for remaining actions

Action 15: map the rare disease research landscape to identify gaps and priorities for future funding

With so many individual rare diseases identified, understanding ongoing and existing research is important to understand unmet need, engage with the rare disease community and support prioritisation in addressing gaps. While some conditions or groups of conditions attract significant research interest, others are less studied and understood, widening health inequities across rare diseases.

In 2023, the UK Rare Diseases Research Landscape report was published, mapping research into rare diseases across the UK for the first time. The report found a significant breadth and depth of rare disease research at sites across the UK, across a range of specialisms, and that government, industry and charities all play a significant role in funding and supporting rare disease research. The NIHR programmes and Medical Research Council (MRC) rare disease research portfolio comprised 698 awards within a 5-year snapshot (2016 to 2021). The total awarded value of these awards was almost £627 million, equating to approximately £125 million annually. Of all MRC and NIHR awards within the timeframe, the rare disease research portfolio accounted for around 7% of the total number of awards and 7% of the total value of award funding. Over the timeframe of the project, 107 Association of Medical Research Charities (AMRC) charity members invested £580 million into over 2,300 rare disease research studies. There were 254 industry supported rare disease research projects identified in the UK.

The importance of collaborative funding between government, industry and charity was also evident. This included co-funding of specific awards, government funded infrastructure supporting industry or charity funded projects and collaboration with charity funded registries and biobanks. However, the report also found gaps - while there were some rare diseases with multiple associated research awards, there were many which had no research awards associated over the timescale of the report.

In 2024, the steering group that supported the publication of the landscape report re-convened to discuss the findings, and identify strengths, opportunities, and areas of unmet need. In autumn 2024, DHSC hosted a series of workshops to communicate outcomes of the report and understand views of the rare diseases community on research gaps and priorities. This was supported by the James Lind Alliance, although not following the methodology for a full priority setting exercise. These workshops included discussions of 12 research themes, based on opportunities or gaps found through the research report and the steering group. A summary of findings of the workshops are published in annex D. This year, we will follow up by holding a similar workshop with industry and charitable funders of research. These findings will be disseminated to inform the work and strategies of research funders across the rare diseases space, including to ensure the patient voice is embedded into future work.

Metrics and milestones as published in 2024 action plan:

research funders steering group reconvened and a meeting held to provide steer on outputs of the landscape report and next steps by April 2024
series of workshops held by DHSC to communicate outcomes of the report and understand views of the rare diseases community on research gaps and priorities by autumn 2024
findings from report communicated by DHSC to research funders steering group by February 2025

Metrics and milestones for 2025:

not applicable - action concluded in 2025

Action 28: develop a plan to include rare diseases in NHS England’s Core20PLUS5 Framework

During this year we have made significant progress in understanding inequities in accessing health and care services for people living with rare conditions. The NIHR funded Exeter Policy Research Programme Evidence Review Facility has carried out a scoping review which systematically gathered together published research and grey literature describing the nature and extent of health inequalities experienced between the rare disease community and the general population, and within the rare disease community, with respect to receipt of a diagnosis and access to services. As part of this work an advisory group was established, with representation from people with lived experience.

The review identified 136 studies which report data relating to inequity experienced by the rare disease community. These include 96 primary studies conducted in the UK and 40 systematic reviews which report data from international settings. The most frequently reported rare diseases in the studies were motor neurone disease, sickle cell disease and cystic fibrosis. Overall, several hundred types of rare diseases are represented in the findings.

Inequities were categorised in the review as experienced either across the rare disease community, or by specific groups within the rare disease community.

Eleven types of inequity were identified across the rare disease community, including:

delayed diagnosis
lack of knowledge among healthcare professionals
lack of information provision
limited service provision across several primary, secondary, specialist and social care services
lack of services for people with undiagnosed conditions
lack of care co-ordination between services

These inequities were found to be exacerbated for specific groups with the rare disease community according to 6 characteristics which stratify health opportunities and outcomes:

place of residence
race or ethnicity
gender
socioeconomic status
age
disability

A summary of the review is published at annex E and has also been submitted for publication in an academic journal.

We continue work to understand how these findings can be used to support integrated care boards to address health inequalities under the NHS England Core20PLUS5 framework.

The Exeter Policy Review Programme Evidence Review Facility is working on a follow up output which will map the identified inequities in the scoping review onto an explanatory framework. This extends the current work by taking the descriptive findings of the scoping review and mapping them onto a framework which draws out where inequities are experienced across the health and social care pathway for people with rare diseases. These findings will be shared by summer 2025.

Metrics and milestones as published in 2024 action plan:

search protocol will be finalised by March 2024
scoping review will be completed by the end of 2024
if there is sufficient evidence, an evidence synthesis will be undertaken with the aim of reporting early 2025
findings will be reported in the 2025 rare diseases action plan and communicated with the NHS England Core20PLUS5 team

Metrics and milestones for 2025:

scoping review to be published in 2025
follow up output which will map the identified inequities in the scoping review onto an explanatory framework will be completed by summer 2025

Action 35: publish and disseminate a health inequalities toolkit for highly specialised services

We are working hard to reduce inequalities for patients within NHS England highly specialised services and last year introduced 2 new actions to help achieve this.

Action 35 aimed to publish and disseminate a health inequalities toolkit for highly specialised services, using feedback received from these services. The toolkit will be published in 2025.

Metrics and milestones as published in 2024 action plan:

final version of toolkit to be published in 2024 to 2025
monitoring of changes and actions taken within highly specialised services to reduce health inequalities

Metrics and milestones for 2025:

toolkit to be published in 2025

Action 36: map and measure the geographic spread of patients accessing highly specialised services

Within the specialised commissioning portfolio, there are over 80 highly specialised services (HSS). These HSS are delivered in a small number of centres, which are commissioned by NHS England for their experience and expertise in the management of rare diseases. The services typically have small caseloads of patients, usually no more than 500. Due to the limited number of centres, it’s possible that some patients may have difficulty accessing the services. Therefore, every 3 to 4 years, the HSS team reviews the geographical spread of patients using NHS England commissioned highly specialised services to ensure that all patients have access and are not disadvantaged. As part of action 36, NHS England mapped and measured the geographic spread of patients accessing highly specialised services by calculating the systematic component of variation (SCV) to assess whether there is systematic variation greater than expected by chance.

The previous analysis in 2020 was undertaken for all eligible HSS (59 out of 70). Some services were not eligible for analysis at that time as their patient cohort was too small or the service was newly commissioned, and a data set was not available. Due to resource constraints, the 2024 exercise focused on services where there was evidence of geographic spread of patients higher or lower than expected in the 2020 exercise and any services that had become eligible for inclusion since then. Findings were presented to the Highly Specialised Services Oversight Group in November 2024 and the NHS England Rare Diseases Advisory Group in January 2025. The analysis is not able to diagnose or exclude geographical inequity in access (unfairness in the system) but instead identifies variations in spread of patients accessing the service that may warrant further investigation.

Of 26 services analysed, 10 had unexpected regional variation in the number of patients using the service. Of the 19 services analysed previously, all except one had reduced their SCV. Of the 7 services being analysed for the first time, 6 had the expected geographic spread of patients accessing the service. Where the analysis found unexpected variation, providers have been asked to develop action plans to address these inequities. Providers who have been successful in reducing variation have also been asked to share this good practice. Discussion of the geographic spread of patients has been added to the agenda of all annual clinical meetings with relevant services from February 2025 and a repeat of the analysis for all HSS should take place in 2027 to 2028.

Metrics and milestones as published in 2024 action plan:

publication of report in 2025 action plan
repeat exercise in 3 to 4 years to ensure any inequity of access is addressed

Metrics and milestones for 2025:

all annual clinical meetings with relevant services to discuss geographic spread of patients from February 2025
repeat exercise in 3 to 4 years to ensure any inequity of access is addressed

Action 29: commission portfolio level evaluation of action plans with input from the rare disease community on design of metrics

We have commissioned a portfolio-level evaluation of the rare diseases action plans with input from the rare disease community on design of metrics. This work is funded through the NIHR - a 2 year contract running from May 2024 with Consilium Scientific and Realise Advocacy alongside the research to understand the diagnostic odyssey (see action 17 above). Milestones for this research were published to the UK Rare Disease Forum’s online platform in August and are set out in annex D.

This evaluation has made notable progress, with the Research Advisory Group and the Patient and Public Involvement and Engagement group successfully established in July 2024, providing a strong base for collaborative decisionmaking. The evidence review was completed as scheduled in September 2024, ensuring a solid foundation for the next phases of the research.

Further work was necessary to strengthen pre-existing logic models which resulted in the Delphi exercise running behind the originally scheduled timepoints. However, recruitment of Delphi participants has now been completed and the launch of the eDelphi exercise is scheduled for March 2025.

Evaluating the influence of the framework will tell us whether the interventions over this 5-year period have been effective in making a difference to what matters most to the rare diseases community and will help shape future rare diseases policy.

Metrics and milestones as published in 2024 action plan:

research team and milestones for the year ahead publicly announced by April 2024 (through the UK Rare Diseases Forum and online platform)
progress will be reported in the 2025 action plan

Metrics and milestones for 2025:

launch of eDelphi exercise in March 2025
progress will be reported by 2026

Action 37: clinics for multi-system disorders

Metrics and milestones as published in 2024 action plan:

not applicable - new action for 2025

Metrics and milestones for 2025:

engagement with the existing clinics, for example, DNA repair disorders clinic, to learn from their experience
report on progress in 2026

Action 38: reform of the clinical trials regulations

Metrics and milestones as published in 2024 action plan:

not applicable - new action for 2025

Metrics and milestones for 2025:

the new clinical trial legislation, laid in Parliament on 12 December 2024, will be subject to debate before being made into law
once enacted, it will come into force following a 12-month implementation period
progress will be reported in 2026

Action 39: develop an operational framework for individualised therapies in the NHS

Metrics and milestones as published in 2024 action plan:

not applicable - new action for 2025

Metrics and milestones for 2025:

the scope of the operational framework for service delivery of individualised or n-of-1 therapies to patients within the NHS, detailing what needs to be in place when commissioning a service will be agreed by February 2026 and reported in the action plan

Question 2

Annex B: Individualised Therapies System Information Day

Accepted Answer

Summary

The aim of the day was to understand the specific challenges of truly individualised therapies, including their regulation, reimbursement and administration, while exploring emerging technologies and identifying pathways for UK advancement. Fostering collaboration among stakeholders such as MHRA, NICE and NHS England as a key to developing actionable solutions, considering both ‘platform’ approaches and individual agents and fostering innovative perspectives on these critical issues.

The day brought together stakeholders to understand and start to think about solutions for the challenges in the development and implementation of therapies tailored to rare diseases.

Professor Matt Brown highlighted the limitations in research funding, regulatory inefficiencies and disparities and challenges in patient recruitment for clinical trials. He emphasised the need for collaborative approaches to accelerate diagnosis and therapy development, with initiatives like WGS through Genomics England and the Rare Therapies Launch Pad working to provide vital pathways.

Kath Bainbridge discussed the UK Rare Disease Framework, emphasising faster diagnosis, improved access to care and the need for pioneering research. She outlined the governance structure supporting these goals, involving NHS England, MHRA and other delivery partners, and highlighted the draft 2025 action plan as a possible route to making a commitment to integrating individualised therapies into the NHS.

Fiona Marley shared NHS England’s perspective on integrating individualised therapies into the health system and outlined the action NHS England had put forward for the 2025 action plan. She emphasised the importance of creating a robust operational framework for delivering these therapies, including considerations for patient pathways, genomic testing and evidence generation. Lessons from international models demonstrated the value of centralising expertise in condition-specific centres (that is, expertise with the condition rather than drug administration in the centre. The ability to administer these therapies is more widespread).

Mel Dixon provided a patient’s perspective, sharing the journey of addressing ultra-rare conditions, in her case with DHDDS variants. She underscored the challenges of isolation, funding and the need for collaboration, while highlighting the importance of building international research networks and initiating drug repurposing projects. The need for accessible therapies locally, without reliance on international travel, was a recurring theme. For more information see Cure DHDDS.

Professor Stephan Sanders elaborated on the potential of ASOs (antisense oligonucleotides) and CRISPR (clustered regularly interspaced short palindromic repeats) technologies in treating neurodevelopmental and genetic disorders. He presented examples of successful therapies and outlined the hurdles in safety, regulatory approval and cost-efficiency. He emphasised the transformative impact of individualised therapies and the opportunities these technologies present in advancing precision medicine, but noted the need for systemic changes in research and regulation to realise their full potential.

Professor Fyodor Urnov outlined a path for CRISPR cures, emphasising its potential to revolutionise treatment for rare genetic conditions. He highlighted the current regulatory hurdles that treat each CRISPR guide RNA (gRNA) adaptation as a new product, driving up costs and delays. This was showcased with his Jammie Dodger analogy - changing the filling of a Jammie Dodger from raspberry to strawberry does not require re-evaluating the entire regulatory process for every ingredient in the biscuit - only the new filling undergoes review. Similarly, a focused regulatory approach could be applied to CRISPR technologies, where modifications are assessed individually without revisiting established components. He proposed platform-based approaches to pool patients by syndrome and streamline manufacturing and regulatory processes. He underscored the UK’s unique position, with its single-payer integrated healthcare and genomic infrastructure, to be able to lead globally in precision medicine by adopting accelerated approvals and collaborative pipelines for severe paediatric diseases.

The panel discussion and subsequent workshop explored actionable strategies for changing healthcare systems to meet these needs. Stakeholders identified the importance of streamlined regulation, collaboration across sectors and robust data collection frameworks to support therapy efficacy and safety. The day concluded with commitments to further refine strategies in the upcoming action plan.

See further details on the Individualised Therapies System Information Day (PDF, 1.06MB) on the Genomics England website.

Question 3

Annex C: response to ABPI and BIA survey by NHS England, MHRA and NICE

Accepted Answer

Summary

NICE, MHRA and NHS England have come together to provide a joint response to the ABPI and BIA survey which was finalised in November 2023 and formally discussed at the Rare Diseases Action 25 Meeting on 31 July 2024.

Overall, we welcome the joint ABPI and BIA survey and the comprehensive insights the survey provides. We note the report reflects the views of individual companies and does not necessarily reflect the views and policy positions of ABPI or BIA.

The Rare Diseases Action 25 Meeting on 31 July provided a valuable multi-stakeholder platform to discuss not only the survey results, but also the 2024 action plan. All parties remain committed to supporting people living with rare conditions and delivering commitments as set out in the action plan.

The survey contained 5 main sections and other industry observations. We have responded to the key points in each section as it was not proportional to respond to each individual question. It should be noted that while this is a joint response (defined as ‘we’), certain sections are more relevant to individual organisations and this is reflected in the drafting. It’s also worth noting that some of the key points and issues raised in the survey are not exclusive to rare diseases.

A full version of the response is available on the UK Rare Diseases Forum online platform. You can request access by emailing gset@dhsc.gov.uk.

The response covers findings from the ABPI and BIA survey, as well as responses from delivery partner organisations. These covered:

understanding UK launch decisions and the course of NICE technology appraisals
EAMS
ILAP
IMF
HST programme
other industry considerations of potential barriers to access to rare disease medicines in the UK, outside of EAMS, ILAP, IMF and HST - these included challenges within the NICE STA process, as well as the wider commercial environment for medicines in the UK

In addition, it was highlighted by the lay members and/or expert witnesses who are involved in NICE technology appraisals at the Rare Diseases Action 25 Meeting on 31 July, that they often felt the weight of the disease community expectations during appraisals. While they felt fully supported by the People and Communities Team at NICE, the responsibilities were real.

While NICE cannot remove this responsibility for lay members and/or expert witnesses, communications and support can be framed to ensure that participants are clear about processes and supported more in their communication with voluntary and community sector groups.

The People and Communities Team at NICE has a new 3-year strategy for involvement and engagement. Working alongside people and communities, the strategy will co-produce our involvement processes in partnership with voluntary and community sector groups, our expert panels and our NICE involvement and engagement leaders network.

Question 4

Annex D: summary of rare disease research landscape workshops and outcomes

Accepted Answer

Independent facilitators:

Suzannah Kinsella
Caroline Magee - James Lind Alliance

Summary

In November 2024, 42 people living with rare disease, carers, health professionals and patient group representatives came together in 2 workshops to help shape a set of gaps and opportunities to enhance and expand rare disease research in the UK.

Twelve draft gaps and opportunities were identified through the DHSC UK Rare Disease Landscape Report (published in 2023) and the subsequent work by experts on the Landscape Steering Group. These are:

incentivising collaborative research partnerships across sectors, including government, industry and charity-based funding
maximising impact of rare disease research by identifying multiple impact routes, for example considering if findings are applicable to rare diseases with overlapping needs
improving access to clinical trials, for example through recruitment by healthcare professionals to widen access to research and treatment opportunities
investing strategically in research infrastructure to maximise benefits to the rare disease community
addressing health inequalities in rare diseases and intersections with other areas of inequity
resourcing and accessing a national genomic research library and secure data environment
maximising the impact of rare disease registries as data sources for research
building on UK strength in mature patient advocacy groups
integrating best practice into care pathways through research, including identifying commonalities between rare conditions
increasing access to molecular diagnoses for diseases with a known or unidentified genetic component
supporting research on ultra rare conditions
mapping of rare disease prevalence to available research funding

Key findings

We start by sharing 5 important things that participants believe need to happen to enable better rare disease research. This is followed by a summary of what participants thought of the 12 gaps and/or opportunities to improve future rare disease research.

Data and registries - fix the fragmentation and fill the gaps

Participants emphasised the need for comprehensive and inclusive rare disease registries to improve data aggregation and access for research. Addressing fragmentation, standardising data collection and integrating registries were highlighted as critical steps.

Patient-centred research

The workshops underscored the importance of early and sustained patient involvement throughout the research lifecycle, supported by training, resources and meaningful compensation for patient advocacy groups.

Addressing inequalities

Rare disease research must address systemic inequities related to ethnicity, geography, socioeconomic status and underrepresentation in studies. Tailored outreach, inclusive research design and better data collection on health disparities are proposed solutions.

Governance: centralising, streamlining, enabling networks and partnerships

Effective partnerships between government, industry, academia and patient groups are deemed essential for impactful research. Barriers such as governance complexities and competing agendas were identified, alongside enablers like sharing best practice frameworks, for example, a LinkedIn page for rare disease research.

Finding commonality with other rare and non-rare conditions

Commonality with prevalent conditions was seen as a real opportunity to reframe the rare disease dialogue. If some of the challenges in rare disease can be solved, then this can disseminate and diffuse learning into more prevalent conditions.

Views on the 12 gaps and opportunities were as follows.

Incentivising collaborative research partnerships

Collaboration is critical for impactful research, yet barriers such as competing agendas, governance complexities and unequal access to funding persist. Enablers include frameworks for best practices, enhanced patient involvement, networking opportunities and flexible funding models.

One example of good collaboration is the HERCULES project for Duchenne muscular dystrophy, which highlights the benefits of shared tools and data.

Maximising impact through multiple routes

Identifying overlaps among rare diseases can expedite treatment development and enhance resource efficiency. Participants emphasised shared mechanisms and basket trials but warned against overshadowing ultra-rare diseases or limiting research to conditions with common components.

Improving access to clinical trials

Accessibility to clinical trials is hindered by geographic disparities, low patient numbers and logistical challenges. Participants suggest regional hubs, virtual consent methods and better co-ordination among research teams to enhance inclusivity.

Investing strategically in research infrastructure

Participants want to see infrastructure investments aligned with rare disease needs, such as reducing bureaucratic burdens, creating rare disease boards and streamlining funding processes. Many see infrastructure as a foundation for other priorities.

Addressing health inequalities

Rare disease research must tackle inequities related to ethnicity, socio-economic status and geography. Suggestions included improved data collection on disparities, tailored outreach and inclusive research design.

National Genomic Research Library and secure data environment

Concerns about the under-resourcing of genomic sequencing services, consent management and the inclusion of rare diseases in genomic data repositories were raised. Participants call for robust data management practices and broad consent frameworks.

Maximising the impact of rare disease registries

Current registries are fragmented and underutilised. Recommendations include centralising registries, standardising data collection and ensuring diverse representation. Patient advocacy groups should help shape priorities for registry data.

Building on UK strength in patient advocacy groups

UK patient advocacy groups are a valuable asset. Early, sustained involvement in research, reduced duplication of efforts and financial support for small, fragile groups are necessary to strengthen their role in driving research priorities.

Integrating best practices into care pathways

Participants want to see more translation of research into clinical care pathways. This should focus on shared best practices, commonalities between rare diseases and addressing barriers like entrenched practices and funding constraints for implementation.

Increasing access to molecular diagnoses

While molecular diagnoses are widely available for children, gaps exist for adults, ethnic minorities and individuals with intellectual disabilities. Participants highlighted the need for equitable access and better representation in genetic databases.

Supporting research on ultra-rare conditions

Research into ultra-rare conditions faces challenges like small patient numbers and the need for international collaboration. Participants suggest leveraging existing data and ensuring findings from broader research benefit ultra-rare conditions.

Mapping rare disease prevalence to research funding

Aligning research funding with disease prevalence is essential to address underfunded conditions. Participants emphasise the use of data-driven approaches to prioritise resource allocation effectively.

Question 5

Annex E: summary of health inequity scoping review

Accepted Answer

Full title: ‘Evidence on health inequities experienced by the rare disease community with regards to receipt of a diagnosis and access to health and social care services: a scoping review’.

Authors: Briscoe, S; Martin Pintado, C; Sutcliffe, K; Garside, G; Melendez-Torres, G.J; Lawal, HM; Orr, N; Shaw, L; Thompson Coon, J. Exeter PRP Evidence Review Facility (University of Exeter); London-York PRP Evidence Reviews Facility (University College London, University of York, London School of Hygiene and Tropical Medicine).

Executive summary

Rare diseases are diseases which affect fewer than one in 2,000 people. Although rare diseases are individually rare, they are collectively common, affecting around 1 in 17 people in the UK. The Orphanet website lists around 7,000 documented rare diseases, ranging from relatively common rare diseases such as motor neurone disease (MND), sickle cell disease and cystic fibrosis, to ultra-rare diseases such as POEMS syndrome, which affects around one in 300,000 people. Seventy-five percent of rare diseases affect children and around 30% of children with a rare disease die before reaching 5 years of age - see UK Rare Diseases Framework.

Evidence gathered from surveys and workshops conducted in the UK has found that people living with a rare disease face many challenges with accessing health and social care services^{[footnote 1]}. This can arise due to factors such as a lack of knowledge among clinicians to support timely diagnosis and appropriate treatment, and limited access to specialist centres where appropriate care is provided. Evidence also shows that the diagnosis of rare diseases can take a long time, during which the symptoms may get progressively worse. Furthermore, these experiences are exacerbated for some people within the rare disease community, including ethnic minorities, women and according to socioeconomic status and where you live^{[footnote 1]}.

These experiences indicate that people with a rare disease may have worse health outcomes than people in the general population due to the limited services and support available to them. The experiences also point to unequal support within the rare disease community itself.

Differences in health opportunities (such as service access) and outcomes (such as morbidity) which are systematic, avoidable and unfair are defined as health inequities, which are important to address to ensure that services are equitable for all people in the UK^{[footnote 2]}.

What we wanted to know

The UK Rare Diseases Framework and England’s rare disease action plans (first report published in 2022, second report published in 2023 and third report published in 2024) are committed to addressing health inequities associated with rare diseases. The Exeter PRP Evidence Review Facility were asked to carry out a review which systematically gathers together published research and grey literature which describes the nature and extent of health inequities experienced between the rare disease community and the general population, and within the rare disease community, with respect to receipt of a diagnosis and access to services. This could help to inform how to address health inequities associated with rare diseases.

Aims and objectives

Aims

Our review aimed to identify and summarise evidence on health inequities experienced within the rare disease community or between the rare disease community and general population with regards to receipt of a diagnosis and access to health and social care services.

Objectives

The objectives were:

To carry out a scoping review which will systematically identify and describe the available evidence on health inequities experienced within the rare disease community, or between the rare disease community and general population, with regards to receipt of a diagnosis and access to health and social care services.
To draw out findings relevant to the UK context.

What we found

Key characteristics of included studies

We identified 136 studies which report data relating to the experience of inequity in the rare disease community with respect to receipt of a diagnosis or access to services. These comprise of 96 primary studies conducted in the UK and 40 systematic reviews which include studies conducted both in the UK and around the world.

The most frequently reported rare diseases in the identified UK primary studies and systematic reviews were MND and sickle cell disease. Some studies included multiple rare diseases, including more than 100 rare diseases in several studies. It was not possible to ascertain the number of rare diseases represented in the review, as the names of diseases were not always reported in the identified studies.

Most of the UK primary studies included both male and female participants (66%), with a small proportion of studies focusing on one gender (10% on female participants only; 1% on male participants only). The remainder did not report gender. Adults (18 years and over) were the most frequently occurring age group in the UK primary studies (41%), with an additional 32% of studies reporting data on both adults and children and 18% reporting data solely on children. Ethnicity was reported in 24% of UK primary studies. The characteristics of participants in systematic reviews were similar to the UK primary studies.

Around half of the UK primary studies were qualitative studies (52%), with a smaller proportion of quantitative studies (22%) and mixed methods studies (26%). Most of the systematic reviews included multiple study designs (75%). Twenty percent included solely qualitative studies and 5% included solely quantitative studies.

Types of inequity

We identified 17 types of inequity across the 136 UK primary studies and systematic reviews. These included 11 types of inequity which were identified across the rare disease community and 6 types of inequity which were identified in subgroups within the rare disease community. The latter were identified using the PROGRESS-Plus framework, which sets out characteristics which stratify health opportunities and outcomes.

The types of identified inequity which are shared across the rare disease community included:

delayed diagnosis: experiencing delays to receiving a diagnosis
lack of knowledge about rare diseases among health and social care professionals which hinders diagnosis and access to services, which can also include dismissive attitudes towards symptoms of rare diseases
lack of information: a lack of signposting by health and social care professionals to relevant and sufficient information about rare diseases
limited service provision in several areas including:
- mental health
- emergency services
- dentistry
- specialist
- social care
there was also a category for services in general where no specific service was mentioned in the data (data relating to affordability of services was captured under socioeconomic inequities)
limited services for undiagnosed conditions - specific challenges around accessing services for people with symptoms of a rare disease but without a diagnosis
lack of care co-ordination between primary, secondary, specialist and social care services, which can adversely affect the receipt of a diagnosis and accessing services

In addition, we identified 6 characteristics of sub-groups in the rare disease community which lead to inequity:

place of residence
race or ethnicity
gender
socioeconomic status
age
disability

All of these types of inequity could be experienced both between the general population and the rare disease community, and within the rare disease community itself. This is illustrated in table 1. The main report is structured around these headers to make it clear where the inequity is being experienced.

Table 1: how the categories of identified inequities overlap, with examples.

Category	Inequities between the rare disease community and the general population	Inequities within the rare disease community
Inequities shared across the rare disease community (n=11)	Example: lack of knowledge among clinicians about rare diseases compared to more common diseases.	Example: lack of knowledge among clinicians about rare diseases which is comparatively worse for some rare diseases than others.
Inequities experienced by subgroups in the rare disease community [See note 1] (n=6)	Example: ethnic minorities experience specific challenges with accessing services for sickle cell disease compared to the general population.	Example: ethnic minorities experience specific challenges with accessing services for sickle cell disease which are not experienced by others in the rare disease community.

Note 1: groups identified with reference to PROGRESS-Plus, place of residence, race or ethnicity, gender, socioeconomic status, age, disability.

Summary of inequities experienced by the rare disease community

Overall, the majority of evidence of inequities related to the rare disease community as a whole compared with the general population. However, the data in UK primary studies and systematic reviews which indicated these types of inequity were not always comparative, which means that they were not comparing the experiences of the rare disease community with the general population. Instead, the studies mainly reported experiences which are specific to people living with a rare disease and their carers, and we have therefore suggested that the data was indicative of inequities. For example, the experience of lack of knowledge of rare diseases among clinicians is unlikely to be experienced by the general population with respect to more common diseases, which are likely to be better understood by clinicians. Similarly, the experiences of delayed diagnosis may be worse for the rare disease community due to lack of knowledge among clinicians.

Some of the experiences of the rare disease community may also be experienced by people in the general population. As such, for some of the identified experiences, we are less confident that these are experiences of inequity. For example, the identified lack of care co-ordination may be experienced by others in the general population with complex needs^{[footnote 3]}. The identified lack of access to mental health services may also be a problem among the general population^{[footnote 4]}. Thus, these findings should be interpreted with caution within the wider context of service access for the general population.

We also identified data on how these inequities are experienced differently within the rare disease community, albeit there were fewer examples of this. This included comparative data which showed greater satisfaction of clinician knowledge and information provision in specialist centres compared with non-specialist services when receiving a diagnosis of cystic fibrosis, MND and sickle cell disease^{[footnote 5]}, ^{[footnote 6]}. Comparative data also showed a minority of people with a rare disease have access to a specialist service^{[footnote 7]},^{[footnote 8]},^{[footnote 9]},^{[footnote 10]}.

Furthermore, the data showed that experiences of inequity for people with a rare disease are exacerbated for subgroups according to characteristics identified in the PROGRESS-Plus framework. For example, dismissive attitudes towards the symptoms of ethnic minorities and women were reported in qualitative studies, including the perception among women that the symptoms of rare diseases are dismissed by clinicians as part of normal menstrual health^{[footnote 11]}, and the perception among ethnic minorities that they are mistrusted by clinicians when experiencing pain related to sickle cell disease^{[footnote 12]}. There was also evidence that services for rare diseases are difficult to access due to geographical reasons and that this could be exacerbated by socioeconomic status^{[footnote 13]},^{[footnote 14]}.

Implications

This review has highlighted a need for more research on health inequities experienced by the rare disease community. Importantly, this needs to include research on the less common rare diseases, including ultra-rare diseases.

Interventions are required to address the inequities which we were able to identify. Future development of any such interventions can build on the ongoing work listed below:

education resources for clinicians in development by the national GEP, including the GeNotes tool and the Rare Disease Education Hub
the development of rare disease collaborative networks, which are embedded in NHS service specifications and underpinned by commissioned research on how best to operationalise better co-ordination of care in the NHS
the requirement for new and revised NHS service specifications to consider the psychosocial needs of patients, including for people with a rare disease - see Rare Diseases Action Plan 2024
Children and Young People’s Transformation Programme, which is developing a framework to improve experiences from child to adult care - see Rare Diseases Action Plan 2024
revised NICE quality standard on how transition from children’s to adults’ services can be made relevant to the needs of the rare diseases community^{[footnote 15]}
pilot testing of 2 SWAN clinics in England, one for children and one for adults, drawing on experience of SWAN clinics in Wales - see Rare Diseases Action Plan 2024
the Generation Study, which tests newborns for over 200 rare diseases with a view to improving the early identification of rare disease

There is also a need to address dismissive attitudes towards certain groups with rare diseases, including women, ethnic minorities and children. This may require interventions not limited to people with a rare disease, which tackle attitudes which undermine the experiences of these groups more broadly. Additionally, it is important to consider how differences in place of residence and socioeconomic status can affect the experience of diagnosis and access to services, and specific challenges faced by people with a disability.

How we got these findings

We carried out a scoping review to identify and summarise the extent of evidence on inequities experienced by the rare disease community, as set out in our research aim. This involved developing a protocol which set out the aims, objectives, inclusion criteria and methods, which was prospectively registered on the Open Research Exeter (ORE) repository^{[footnote 16]}. We searched for studies using a variety of systematic search methods and used a rigorous screening process to identify which studies met our inclusion criteria. We then extracted relevant data from the identified studies, including study characteristics and evidence of inequity. The data was then tabulated and narratively summarised in this report.

References

Muir E. The Rare Reality - an insight into the patient and family experience of rare disease. London: Rare Disease UK; 2016 ↩ ↩²
McCartney G, Popham F, McMaster R, Cumbers A. Defining health and health inequalities. Public Health. 2019;172:22-30 ↩
Melin Emilsson U, Strid A-L, Söderberg M. Lack of Coordination between Health Care and Social Care in Multi-Professional Teamwork - the Obstacle for Coherent Care of Older People Suffering from Multi-Morbidity. Journal of Population Ageing. 2022;15(2):319-35 ↩
Watson M. The wait for NHS mental health services – how long is it? HSJ. 2024 ↩
Chudleigh J, Buckingham S, Dignan J, and others. Parents’ Experiences of Receiving the Initial Positive Newborn Screening (NBS) Result for Cystic Fibrosis and Sickle Cell Disease. J Genet Couns. 2016;25(6):1215-26 ↩
O’Brien MR, McDermott C, Aoun S, and others. The diagnostic experience for people with MND and their caregivers in the U.K. J Neurol Sci. 2023;444:120483 ↩
Walton H, Ng PL, Simpson A, and others. Experiences of coordinated care for people in the UK affected by rare diseases: cross-sectional survey of patients, carers, and healthcare professionals. Orphanet J Rare Dis. 2023;18(1):364 ↩
Vallortigara J, Greenfield J, Hunt B, and others. Patient pathways for rare diseases in Europe: ataxia as an example. Orphanet J Rare Dis. 2023;18(1):328 ↩
Morris S, Hudson E, Bloom L, and others. Co-ordinated care for people affected by rare diseases: the CONCORD mixed-methods study. Health and Social Care Delivery Research. 2022;10(5):1-220 ↩
Morris S, Vallortigara J, Greenfield J, and others. Impact of specialist ataxia centres on health service resource utilisation and costs across Europe: cross-sectional survey. Orphanet J Rare Dis. 2023;18(1):382 ↩
Khair K, Pollard D, Steadman L, and others. The views of women with bleeding disorders: Results from the Cinderella study. Haemophilia. 2022;28(2):316-25 ↩
Berghs MJ, Horne F, Yates S, and others. Black sickle cell patients’ lives matter: healthcare, long-term shielding and psychological distress during a racialised pandemic in England - a mixed-methods study. BMJ Open. 2022;12(9):e057141 ↩
Clark R, Burren CP, John R. Challenges of delivery of dental care and dental pathologies in children and young people with osteogenesis imperfecta. Eur Arch Paediatr Dent. 2019;20(5):473-80 ↩
Rodger S, Woods KL, Bladen CL, and others. Adult care for Duchenne muscular dystrophy in the UK. J Neurol. 2015;262(3):629-41 ↩
National Institute for Health and Care Excellence. Transition from children’s to adults’ services National Institute for Health and Care Excellence; 2023 ↩
Briscoe S, Garside R, Lawal H, and others. Evidence on health inequities experienced by the rare disease community with regards to receipt of a diagnosis and access to health and social care services: protocol for a scoping review. Open Research Exeter; 2024 ↩

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Annex A: detailed progress update on actions, metrics and milestones

Priority 1: helping patients get a final diagnosis faster

Action 1: improving how decisions are made on newborn screening for rare diseases

Action 2: whole genome sequencing (WGS) to screen for genetic conditions in healthy newborns

Action 5: pilot new approaches for patients with undiagnosed rare conditions

Action 17: commission research on how best to measure the diagnostic odyssey

Action 18: increased data-sharing for patient benefit to improve our understanding of equity of access to genomic testing and support interpretation of genomic test results

NCARDRS 10 year anniversary

NCARDRS support to research and service design

Priority 2: increasing awareness of rare diseases among healthcare professionals

Celebrating Rare Disease Day in the NHS

Action 6: develop an innovative digital educational resource (‘GeNotes’) - providing healthcare professionals with relevant and concise information to support patient management, linking to the NHS Genomic Test Directories, and signposting to extended learning opportunities

Action 7: determine how best to include rare diseases in UK health professional education and training frameworks

Action 8: extend the remit of the GEP to include non-genetic rare diseases

Action 19: publishing and implementing specific strategies for increasing awareness of rare diseases in the nursing and midwifery, pharmacy and primary care workforce

Action 30: developing a genomics communication skills resource

Action 31: developing the specialist genomics workforce through GTAC

​Priority 3: better co-ordination of care

Action 20: commission research to provide the evidence needed to operationalise better co-ordination of care in the NHS

Action 21: include the definition of co-ordination of care in all new and revised services specifications for patients with rare diseases, and ensure the priorities of the UK Rare Diseases Framework are embedded across NHS England highly specialised services

Action 32: implement networked models of care for patients with rare diseases ensuring that specialist expertise is always available while allowing patients to be treated and cared for as close to home as possible

Priority 4: improved access to specialist care, treatment and drugs

Action 13: implementing NICE’s new methods and processes to support access to new treatments for rare disease patients

Action 14: monitor overall uptake of drugs for patients with rare diseases and map geographical access to those drugs

Action 22: improved ‘findability’ of people living with rare diseases using NCARDRS

Action 25: review the effectiveness of EAMS, ILAP and the IMF in supporting access to treatments for people living with rare diseases

Action 26: registration of national data for exemplar rare genetic conditions which cause an inherited predisposition to cancer

Action 27: improving the NIHR Be Part of Research platform for people living with rare diseases

Action 33: develop funding mechanism that sufficiently incentivises centres to undertake whole body scans on individuals with rare conditions resulting in a genetic predisposition to developing cancer prematurely

Action 34: building on the work in action 25, review the effectiveness of IDAP pilot in supporting access to medical devices, including diagnostics, for people living with rare disease

Action 12: develop a strategic approach for gene therapies and other advanced therapeutic medicinal products (ATMPs) - based on horizon scanning by NHS England

Metrics and milestones for remaining actions

Action 15: map the rare disease research landscape to identify gaps and priorities for future funding

Action 28: develop a plan to include rare diseases in NHS England’s Core20PLUS5 Framework

Action 35: publish and disseminate a health inequalities toolkit for highly specialised services

Action 36: map and measure the geographic spread of patients accessing highly specialised services

Action 29: commission portfolio level evaluation of action plans with input from the rare disease community on design of metrics

Action 37: clinics for multi-system disorders

Action 38: reform of the clinical trials regulations

Action 39: develop an operational framework for individualised therapies in the NHS

Annex B: Individualised Therapies System Information Day

Summary

Annex C: response to ABPI and BIA survey by NHS England, MHRA and NICE

Summary

Annex D: summary of rare disease research landscape workshops and outcomes

Summary

Key findings

Data and registries - fix the fragmentation and fill the gaps

Patient-centred research

Addressing inequalities

Governance: centralising, streamlining, enabling networks and partnerships

Finding commonality with other rare and non-rare conditions

Incentivising collaborative research partnerships

Maximising impact through multiple routes

Improving access to clinical trials

Investing strategically in research infrastructure

Addressing health inequalities

National Genomic Research Library and secure data environment

Maximising the impact of rare disease registries

Building on UK strength in patient advocacy groups

Integrating best practices into care pathways

Increasing access to molecular diagnoses

Supporting research on ultra-rare conditions

Mapping rare disease prevalence to research funding

Annex E: summary of health inequity scoping review

Executive summary

What we wanted to know

Aims and objectives

Aims

Objectives

What we found

Key characteristics of included studies

Types of inequity

Summary of inequities experienced by the rare disease community

Implications

How we got these findings

References

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Priority 3: better co-ordination of care