Genome UK – State of the nation by Professor Dame Sue Hill, Chief Scientific Officer for England and NHS Genomics Programme Senior Responsible Officer.

1. GENOMICS STRATEGY
AND IMPLEMENTATION IN
THE NHS IN ENGLAND
Professor Dame Sue Hill
@CSOsue │ sue.l.hill@nhs.net
Chief Scientific Officer for England and
Senior Responsible Officer for Genomics in the NHS
Central and South GMS Alliance conference
November 22nd 2023

2. 2
Genome UK
In 2020 the government published Genome UK, a 10-year strategy to create the most advanced genomic healthcare system
in the world.
The strategy sets the direction for the UK genomics ecosystem, including the four devolved healthcare systems and other
system partners, including Genomics England, National Congenital Anomaly and Rare Disease Registration Service, UK
biobank, NIHR BioResource, Our Future Health and others.
Diagnosis and
personalised medicine
Incorporating the latest genomic
advances into routine healthcare to
improve the diagnosis, stratification
and treatment of illness
Prevention
Enabling predictive and preventative
care to improve public health and
wellness
Research
Supporting fundamental and
translational research and ensuring a
seamless interface between
research and healthcare delivery
Enabled by:
• Engagement and dialogue with the public, patients and our healthcare workforce
• Workforce development
• Supporting industrial growth in the UK
• Maintaining trust
• Delivering nationally coordinated approaches to data and analytics

3. 3
NHS Genomics Strategy – published in 2022
UK Life Sciences Vision sets 10-
year strategy for sector to solve
some of the biggest healthcare
problems of our generation including
in cancer.
Genome UK; the future of
healthcare sets out a 10 year vision
how we will achieve progress in
genomic medicine across Diagnosis
& Personalised medicine, Prevention
and Research
NHS Long Term Plan
genomics commitments
aligned to other policies for
example cancer,
cardiovascular, diabetes.
Key themes include:
1. Embedding genomics across the NHS, through a world leading innovative service
model from primary and community care through to specialist and tertiary care
2. Delivering equitable genomic testing for improved outcomes in cancer, rare,
inherited and common diseases and enabling precision medicine and reducing
adverse drug reactions
3. Enabling genomics to be at the forefront of the data and digital revolution,
ensuring genomic data can be interpreted and informed by other diagnostic and clinical
data; and
4. Evolving the service driven by cutting-edge science, research and innovation to
ensure that patients can benefit from rapid implementation of advances
Building on Genome UK and other government strategies, in 2022 NHS England published the NHS Genomics Strategy which outlines our
vision for the power of genomics in predicting, preventing and diagnosing disease, and targeting treatment to be accessible to all as part
of routine care in the NHS. The strategy sets out a 5 year action plan

4. 4
“Having a national health service allows for the uptake of genomics rapidly and at scale. The UK’s
progress in implementing genomics also stems from the efforts of individuals who have championed
genomics, whether at the grass roots level, in political or governmental and healthcare system
leadership, or leaders of the medical community”
This report identified the main challenges for embedding genomics:
• the costs, availability, accessibility, and coverage of genomic testing;
• the genomic literacy of specialists, primary care providers, and the public;
• the need for clinical decision support tools;
• availability of genetic counsellors as well as medical and laboratory geneticists;
• clinical usefulness and actionability of findings;
• the quality, diversity, and broad applicability of reference data sets;
• computing infrastructure capabilities needed to analyse, store, share, and
reanalyse vast amounts of genome sequencing data from within and across health
care systems;
• lack of professional guidelines
The NHS is world-leading in implementing genomics

5. 5
The benefits of embedding genomics

6. 6
The NHS Genomic Medicine Service launched in 2018 offers access to comprehensive genomic testing for all patients
and the public in the NHS in England. This is made possible by our novel approaches to genomic medicine.
NHS Genomic Medicine
Service (GMS)
with national oversight,
contracting, resourcing,
standard setting,
management data &
performance
regimen
7 Genomics
Laboratory
Hubs
(GLHs)
7 Genomic
Medicine
Service
Alliances
(GMSAs)
17 Clinical
Genomics
Services
NHS
Genomics
Education
Programme
and other
clinical
services
Our service model approach
A multi-regional approach
Embedding and equity is dependent upon the sharing of
expertise across the country, and some services are being
provided nationally. We also realise the benefits of both UK and
international collaborations.
A multi-professional approach
Embedding requires involvement from all staff groups across the
NHS. We are working with numerous professional groups, and
have pursued cross-professional involvement in MDTs.
A multi-specialty approach
GMSAs have been – and will continue to be - key to embedding,
maintaining a broad range of specialties and supported at all
levels by clinical genomics.
Serving all patients and the public
A patient and public approach
Involvement throughout the GMS governance structures to
ensure services are co-created and co-designed and ongoing
delivery is viewed through their lens
Delivering a comprehensive offer
Cellular
Pathology
Genomic
Centres
(CPGCs)
Genomics
England
(WGS
service and
NGRL)

7. 7
NHS GMS geographies
Requires systems and partners working together to deliver a national Genomic Medicine Service for all patients and the
public in the NHS in England.

8. 8
National Genomic Test Directory – a national offer
We drive equitable access through a single mandated National Genomic Test Directory focused on: (1) Rare and inherited disease; (2)
Cancer ; (3) Pharmacogenomics These support a standardised offer of funded testing across England and a new pricing model
Covers a full repertoire of testing through a multi-modal approach
(single gene, panel tests, WES, WGS)
Fast track application process which can respond to new
developments, for example to reflect licensing decisions including for
Olaparib and NTRK inhibitors.
Cements WGS as central to service delivery
Approximately 3,200 rare diseases and over 200 cancer clinical
indications
Updated annually through the Test Evaluation Working Groups.
Through the Test Evaluation process to date, recent publication
included tests such as whole genome sequencing for Sudden
Unexplained Death in Childhood.

9. 9
NHS Genomic Medicine Service: NGS from sample to result
NHS Test Directory
1
Variants
CNVs
SVs
3
2 4
7 NHS Genomic
Laboratory Hubs
Variant calling
Genomic Tumour
Advisory Board

10. 10
1. Co-creating services, infrastructure and an operating model with patients and the public.
2. Developing a sustainable infrastructure across testing, clinical services and research and innovation.
3. Building greater clinical and professional leadership and developing the capacity and capability of the
workforce.
4. Developing national and international collaborations and partnerships.
Priorities
Embedding
genomics in the
NHS, through a
world leading,
innovative
service model
1
NHS Genomics Strategy
National and global collaboration –
France, Japan, Thailand, Singapore,
Taiwan, India and Sweden
Integrated governance and
networks
Key areas of progress
Genomic training
academies, NHS
workforce strategy
published, STP funding
increased, international
workforce summit
Establishing Cellular
Pathology Genomic
Centres

11. 11
Education and training: supporting clinicians
Creating national networks and a systematic
approach to workforce development of the role of
pharmacists in genomics and driving personalised
medicine.
Pharmacy programme
Medical Programme
Working with the Academy of Medical Royal
Colleges to support the systematic roll out
of genomic medicine within clinical
pathways and to ensure clinicians have
access to the right education and
information at the right point
Nurse & Midwifery led Genomics
Collaborative
Working with Chief Nurses across
England to systematically and
sustainably embed genomics into
nursing and midwifery roles and
responsibilities

12. 12
• Workforce agnostic, competency based
• Bite sized integration of genomic medicine
• Sharing of best practice: ‘do once and
share’
• Avoids duplication;
• Underpinned by robust evaluation.
Integrating genomics into patient pathways: The Clinical Pathway Initiative
(CPI)

13. 13
Delivering
equitable
genomic testing
for improved
prevention,
diagnosis, and
precision
medicine
1. Systematically introducing new clinical indications for genomic testing and embedding comprehensive
genomic testing within end to end clinical pathways.
2. Driving the use of precision treatments and optimising the use of medicines through genomics.
3. Enabling the rapid evaluation and adoption of affordable, efficient, and innovative genomic technologies
Priorities
2
Evolving the genomic
testing strategy
Aligning clinical trial
targets with standard
of care and working
to nationally agreed
cancer turnaround
times
Key areas
Working with NICE
to establish a
genomic med tech
pathway

14. 14
Alignment with treatment intervention
• Variation to drug response affected by multiple factors, including
genetic and epigenetic variation1,2 - responses to drugs 25-80%
• NHS - £17.1 billion in drug spend per annum3
• An additional £2.2 billion estimated due to Adverse Drug
Reactions (ADRs)4 - contribute to 8.5 - 5.6% of hospital
admissions
• Genomic and precision medicine, and pharmacogenomics
have the potential to individually characterise causes and optimise
treatment for patients5
• Pre-emptive pharmacogenomic testing and subsequent
evidence-based pharmacogenomic interventions recently shown
to reduce incidence of ADRs.6
• Personalised medicines accounted for more than 25% of FDA
approvals for each of the last eight years, mostly for cancer or
rare disease
1.Grant M, NHS England 2016, 2. Spear, Trends Mol Med 2001, 3.NHSBSA,2021 4.Osanlou BMJ Open, 2022, 5. Pirmohamed, Nat Rev Genetics 2023, 6. Swen JJ, Lancet, 2023

15. 15
NHS Genomics Medicine Service
Transition driven by:
▪ Cost (for depth)
▪ Performance
▪ Turnaround times
▪ Value/benefit of test
▪ Number of tests vs tissue
volume
Future direction: single WGS to
capture clinical and research
requirements
Current Practice
SNVs
CNVs
Fusions
TMB
HRD
MSI
FISH
Cyto-
genetics
IHC for
Diagnosis
Pharmaco-
genomics
DPYD
Deficiency
Inherited
cancers
(germline)
National Test
Directory
https://www.england.nhs.uk/publication/nati
onal-genomic-test-directories/
NGS creates a ‘One Stop Shop’ for diagnosis

16. 16 |
Non-small cell lung cancer as an example of end to end pathways that
are needed to be established
There are 8 genomic targets in NSCLC for which there are licensed targeted drugs. All 8 have a NICE-
approved treatment option.
• Currently 2100 patients/year treated: 1700 as initial treatment, 400 as subsequent therapy.
• EGFR exon 19 and 21 mutations: osimertinib 1000 patients/year for initial therapy of advanced
disease, 200/year as adjuvant therapy after resection
• ALK alterations: 250/year initial therapy, split between alectinib and brigatinib
• ROS1 alterations: entrectinib 50/year initial therapy
• MET exon 14: tepotinib 70/year initial therapy and 50/year subsequent treatment
• KRAS G12C: sotorasib 300/year subsequent treatment
• BRAF: dabrafenib plus trametinib 70/year initial therapy
• EGFR exon 12: mobocertinib 70/year
• RET fusion: 25/year for subsequent treatment but now initial therapy access this month.

17. 17
Impact of clinical practice gaps on the delivery of precision
oncology for advanced NSCLC
64% of potentially eligible patients with advanced NSCLC are not benefiting from precision oncology therapies.
Addressing practice gaps and building sustainable care infrastructure are critical to deliver on the promise of precision medicine.
Source: Sadik et al. JCO 2022

18. 18
Driving the use of personalised treatments - optimising the use of
medicines through genomics
Use cutting-edge technology to deliver tailor-made genetic material into
a patient’s cells to treat disease and inclusive of newer rare disease
treatments eg ASOs
Gene therapies &
ATMPs
Based on an increased understanding of the genomic basis for disease
and diagnosis​ particularly in cancer and increasingly in rare disease
New targeted
treatments
Guide treatment decisions and dosing using genomic data to predict
adverse drug reactions
Pharmacogenomics
New indications for existing medicines
Repurposing
Drug resistance and pathogen resistance
Predicting
From novel
therapeutics
To optimising
existing
medicines

19. 19
Thousands of cancer patients are benefitting from the introduction of DPYD testing which
can prevent adverse drug reactions and NTRK gene fusion testing to support new
histology independent cancer treatments
The rollout of Non-Invasive Pre-natal Diagnosis for Retinoblastoma is one of more than
number of new tests and amendments to the National Genomic Test Directory
The GRAIL partnership is looking at early detection of cancer and is being piloted in
165,000 people from the general population will report in 2025. A ctDNA pilot in NSCLC
with Guardant (and Roche) is showing average overall detection rate for actionable
mutations with targeted therapies was 21.5% and leading to technology transfers
Oliver was born with a 6cm lump on his leg and initial investigations suggested infantile
fibrosarcoma. He was referred for WGS and it was found that the mass was in fact a
myofibroma, a benign tumour so no treatment was needed. In Paediatric cancers
In cystic renal disease WGS led to clinical action in 48% of those tested and 71% of
those with a diagnostic variant inclusive of use of Tolvaptan or decision to transplant or
informing surveillance frequency
Cancer: Blood test for 50
types to be trialled by
NHS
NHS to pilot blood test
that could detect over
50 different cancer
types
Gene test spares
baby unnecessary
chemotherapy
Transformative genomic medicine in practice

20. 20
1. Developing an interoperable informatic and data infrastructure that enables the NHS to use and share
genomic data appropriately to improve patient care.
2. Putting the NHS at the forefront of using genomic data alongside other health data to drive health
improvements for individuals and populations.
3. Enabling the NHS to use cutting-edge analytical tools and up to date variant databases to maximise
diagnosis, access to precision medicine and efficiency.
Priorities
Implementation Plan – Priorities
Identified
Genomic Data and Digital Steering Group
established
Genomic Data and Digital framework in
development
Interoperability (Phase 1) :
Master Data Set validation
complete Unified
Genomic
Record
Digitised Test
Directory
Better coordination
and interoperability
Enabling
genomics to be
at the forefront
of the data and
digital
revolution
3
Key areas of progress

21. 21
Data generation in the NHS Genomics Medicine Service
“With personal technology,
doctors can see a full,
continuously updated picture of
each patient and treat each
individually” Topol. 2014. Cell
1. Genomic data – generated from genomic
testing, including phenotyping and staging data
to enable interpretation. The value of this
genomic data can only be maximised if linked
with other diagnostic and clinical data sources
across the life course often at a national level
and in standardised formats.
2. Clinical data – where additional patient
data, for example clinical symptoms, and
longitudinal health data are used to inform
genomic analysis and ongoing research
insights.
3. Management data – for operational
improvement and evaluation – national collection
of the genomic testing activity, variation in access,
turnaround times and linked with outcomes and
treatment data.

22. 22

23. 23
1. Enabling patients to make informed choices on the use of their data for research and innovation.
2. Enriching existing and developing new NHS GMS relationships to support innovation and the generation of
evidence for adoption and improvements in health and care.
3. Ensuring ongoing alignment with clinical trials and national life sciences projects and supporting the
growth of life sciences in the UK
Priorities
Evolve the NHS GMS Research
Collaborative
Planning with Genomics
England to initiate the
Generation Study
Better
coordination and
understanding of
genomics
research to
ensure
developments fed
into the NHS for
patient benefit
Research to be
delivered at scale
and speed
Increasing
volume of high-
quality genomic
research in the
NHS with reliable
genomic insights
that are easy to
request and
interpret
Researchers through
data, infrastructure
and insights to
collaborate and
accelerate
fundamental and
translational research
Evolving the
service through
cutting-edge
science,
research and
innovation
4
NHS Genomic Networks of
Excellence agreed and to be
established in 2023/24
Key areas

24. 24
The NHS Cancer Vaccines Launch Pad
The NHS Cancer Vaccines Launch Pad (CVLP) is designed to act as a bridge to enable NHS cancer patients to get the
earliest possible access to personalised cancer vaccine trials and other immunotherapies, by providing a defined and
expanded standard of care pathway for tumour molecular analysis and sequencing incorporating elements of the NHS
Genomic Medicine Service.
Tissue Sampling Pathway Genomics Pathway
Data infrastructure

25. 25
Central and South GLH Phase One Sites
• CPGC
• Thames Valley/Oxford
• Wessex/ Southampton
• North West Midlands/ BCPS
• CVLP
• Oxford; sample route to Oxford
• Southampton: sample route to
Southampton
North West Midlands
CPGC lead site: BCPS
CVLP samples: site not
identified
Thames Valley
CPGC lead site: Oxford
CVLP samples: Oxford
Wessex
CPGC lead site: Southampton
CVLP samples: Southampton

26. 26
Linking with Genomics England and the NGRL for WGS
Diagnostic Discovery
Accelerating genomic
research
Evolving genomic
healthcare
DISCOVERY TRANSLATION ADOPTION DIFFUSION
Through the National
Genomic Research
Library (NGRL)
populated with 100,000
Genome Project and
consented deidentified
NHS GMS WGS data.
Establish putative
pathogenicity of VUS
Researchers granted access to the
deidentified NGRL database to review
genomic and clinical data
Ongoing variant
interpretation from
diagnostic discovery and
return of WGS results to
GLHs from the GMS
service informs genes
on panel app and the
semi automated pipeline
and evidence informs
the National Genomic
Test Directory and
clinical guidelines
Diagnostic
discovery
Deidentified data
Reporting of
results
Over 1,500 putative
diagnostic discoveries
have been returned to
the NHS
Results from diagnostic discovery are
reidentified by GEL reviewed and further
validated by GLHs and feedback to clinicians

27. 27
Establishing NHS Genomic Networks of Excellence
During 2023/24 NHS England will, as part of the evolving NHS GMS Alliance infrastructure, establish ‘NHS Genomic Networks of Excellence’
NHS Genomic Networks of Excellence will be partnerships between the NHS, academia, the third sector and industry to generate evidence and
models of adoption for new technology and testing and, clinical and laboratory practice in defined topic areas of strategic importance.
DISCOVERY TRANSLATION ADOPTION DIFFUSION
NHS England has confirmed funding for:
► Prenatal Genomic Medicine Network of Excellence
► Circulating Tumour Biomarker testing for rapid diagnostics and monitoring for Cancer
of Unknown Primary, advanced metastatic Breast Cancer, Paediatric Cancer, circulating
miRNA test for Germ Cell Tumours and CSF testing for primary CNS lymphoma.
► Haemato-Oncology NHS Genomic Network of Excellence including rapid WGS
► NHS Rare and Inherited Disease Genomic Network of Excellence
► Severe Presentation of Infectious Disease Genomic Network of Excellence using
long read sequencing in a partnership with Oxford Nanopore
► Improving the identification and outcomes for individuals with inherited and acquired
cardiovascular disease NHS Genomic Network of Excellence
► Pharmacogenomics and Medicines Optimisation NHS Genomic Network of Excellence
focusing on primary care, mental health, as well as specific drug/gene pairs
► Genomics Artificial Intelligence (AI) NHS Genomic Network of Excellence

28. 28
Supporting life sciences projects in pathways to adoption
Diverse Data
Making data and analytics more powerful
to support our diverse population linking
for example with NHS sickle cell blood
group genotyping programme
Long-read Sequencing
To support rapid, precision NHS diagnostics
and treatment planning closer to the patient
using Oxford Nanopore technology as well
as a rare disease project comparing long
read with short read sequencing and
mulitomic profiling
Our Future Health
The UK’s largest ever health research
programme through the discovery and
testing of more effective approaches to
prevention, earlier detection and
treatment of diseases.
Aligning with research infrastructure
& investment
Working with the NIHR Biomedical Research
Centres and MRC Research Nodes to
advance genomics research
Supporting research studies
Supporting cutting edge research studies, for
example the Population Architecture using
Genomics and Epidemiology (PAGE) study
and the Deciphering Development Disorders
(DDD) Study, and many others
Newborns Genome Programme
Delivering the NHS-embedded Generation
Study, to explore the benefits, challenges,
and practicalities of sequencing and
analysing newborns' genomes

29. 29
The ecosystem of genomic medicine is constantly developing. We value - and credit our major successes – to the partnerships and
learning loops that we have established in the UK and internationally.
Sharing data, tools, experience, and knowledge to create a global “learning health system” is essential if we are to effectively accelerate
and sustain the integration of genomics into healthcare
Areas for engagement include:
• Exchanging information, sharing data and best practice including adoption and
embedding of genomic medicine at scale
• Establishing evidence synthesis against agreed policy domains
• Agreeing common standards and outcome metrics
• Enhancing interpretation of complex information and establishing global resources
• Communication and engagement
Maximum
benefit
Academia
International
NHS & other
health
systems
Charities &
professional
bodies
Patients
Industry
Establishing successful partnerships

30. 30
Making Genomics mainstream in medicine: 2020 and beyond
BIG QUESTION:
Can we deploy genomics broadly and equitably in medicine?
Green et al. (2020)

31. 31
Call to action
Identify areas of unmet need or inequalities that require concerted action
Work together to coordinate and embed genomics across NHS pathways and clinical specialties to
inform earlier decision making in conjunction with the NHS GMS infrastructure
Utilise the available and funded genomic testing for all defined conditions in all NHS Trusts and across
the care continuum
Support the tissue pathway developments and Cellular Pathology Genomic Centres to enable the
comprehensive genomic analysis of cancers by the NHS GLHs for all patients
Develop and support the multi-professional workforce to be leaders in genomics and to be upskilled to
use and interpret genomic information and to support patients and their families
Enable the monitoring of access to precision treatments and interventions based on genomic data
Support continued research and innovation projects and initiatives in the UK Life Sciences sector and
enable the ongoing population of a national genomic research library