Genomics and personalised medicine
Dr Tom Fowler, Deputy Chief Scientist & Director of Public Health WHO Symposium on the Future of Digital Health Systems in the European Region
February 2019
About me
• Tom – Deputy Chief Scientist & Director of Public Health, 100,000 Genomes Project
• 100,000 Genomes Project
• Sequencing 100,000 genomes from around 85,000 people. Participants are NHS patients with a rare disease, plus their families, and patients with cancer.
• NHS Genomic Medicine Service
• Supporting the implementation of a national Genomic Medicine Service in England.
2 08 March 2019
1. To bring benefit to NHS patients
2. To create an ethical and transparent
programme based on consent
3. To enable new scientific discovery
and medical insights
4. To kickstart the development of a UK
genomics industry
Reaching 100,000
3 08 March 2019
• On 5 December 2018, the Health and Social Care Secretary announced that Genomics England reached the major milestone of 100,000 whole genomes sequenced
• From here, we are still working hard to turn around returning results to the Genomic Medicine Centres
• We are also working in partnership with NHS England to deliver 1 million genomes, as part of the Health and Social Care Secretary’s ambition to sequence 5 million genomes
• As of February 2019, we have sequenced over 104,000 whole genomes from patients and their families
From 100,000 to 5 million
4 08 March 2019
• 500,000 whole genomes through the Genomic Medicine Service • Plus other genomic tests
• 500,000 whole genomes through upgrade of UK Biobank sequencing
• Whole genome sequencing of strategic cohorts (unmet needs and long term value to the healthcare system)
• Research cohort sequencing (whole genome and other genomic tests) funded by current and future funding
• Exploratory programme for self-paying volunteers who wish to be early adopters of genomic analysis
5 08 March 2019
How the 100,000 Genomes Project works • 13 NHS Genomic Medicine Centres covering England, over 90 hospitals • Responsible for identifying and recruiting participants and for clinical care following
results • Northern Ireland, Scotland and Wales have now joined
Discovery Forum Industry Users
Definition of public health
6 08 March 2019
The Acheson Report, London, 1988
“The science and art of promoting and protecting health and well-being, preventing ill-health and prolonging life through the organised efforts of society.”
The four ‘P’s of personalised medicine
1. Prediction and prevention of disease
2. More precise diagnosis
3. Targeted and personalised interventions
4. A more participatory role for patients
7 08 March 2019
8
Improving outcomes through personalisation
£
Improves outcomes
Targeted therapy Identification of effective personalised treatments
Accelerated diagnosis
based on underlying cause and incidental findings – rather than just
grouped symptoms
Early disease detection
2-8 yrs before onset & symptoms become obvious
with low cost stratification
Targeted disease prevention
Identification of predisposition markers or underlying processes
can predict future disease
Delivering the 4 Ps of Personalised Medicine • Prediction (& prevention)
of disease, • More Precise diagnoses,
Personalised and targeted interventions
• More Participatory role for patients
Technology, Innovation & Knowledge Base
DNA
Genomics
Metabolomics
Personalised Therapeutics
Clinical Change Model
Infrastructure Policy & System Alignment
Transcriptomics
Proteomics
Informatics and digital health
Phenotypic characterisation & diagnostics
Patient Self-reporting
Shaping healthcare through a wealth of new information
9 08 March 2019
Phenotypes & Pedigree
Tiered variants
Gene Panel
Variant filtering
Gene Panels
GeCIP(s)
Validation
Outcomes
Reporting tool
Scalable rare disease diagnostics
Report QC
Patient/ family
DNA
Genome sequence
Annotated VCFs
Annotation Companies
Review
Clinical assessment
11
The vision: A move from illness to health
ILLNESS HEALTH
Using science and technology to improve outcomes and health through • Prognosis • Earlier disease stages offering more
treatment options • Influencing lifestyle factors • Stratified medicine
This will deliver the 4 Ps of Prediction (& prevention) of disease
• Delayed diagnosis • Late stage disease • Multiple conditions • Restricted treatment &
management options • Poorer outcomes &
patient experience
12
The ethical frontline of scientific advance
• Many new technologies are bringing with them ethical challenges - such as the use & handling of data, or if they have predictive ability – but issues can occur if science is felt to move too fast…. or too slowly
How far should the science go? Are the public ready?
Patient involvement - the National Participant Panel
13 08 March 2019
Role of the Panel is to ensure the interests of participants are always at the centre of the 100,000 Genomes Project. They do this by: • Making sure experiences of participants are at the heart of the
project • Responding to feedback • Overseeing who should have access to participant data
Discovery Forum
Ethics Advisory
Committee
GeCIP Board
Access Review
Committee
Participants
Genomics England Clinical Interpretation Partnership (GeCIP)
14 08 March 2019
• A research consortium with over 3,200 researchers from academia and the NHS, trainees, plus international collaborators (over 2,100 currently eligible for data access)
• Currently 37 out of 42 domains have been approved
• We have now received suggestions of diagnoses for 41 families from the Research Environment
• Includes GeCIP and Discovery Forum users • Includes both:
• new, clear-cut diagnoses • new discoveries/research collaborations
The Discovery Forum
15 08 March 2019
Research Environment
Genomic dataset
Gen
om
ics
Engl
and
St
akeh
old
ers A
cadem
ic Stakeh
old
ers
Health service Stakeholders
Industry Stakeholders
Business value
Discovery Forum
• Exploring the business value of genomic medicine data.
• Connecting industry stakeholders to the Genomics England community.
• Providing a gateway to our Research Environment and dataset.
• Leading to discovery and development of precision methods, diagnostics, and therapeutics.
• Over 100 Discovery Forum members (9 full members).
16 08 March 2019
Data in our Research Environment
80,883 genomes
• 19,305 Cancer
• 61,578 Rare Disease
Genomes Primary
clinical data
Secondary data*
• Hospital Episode Statistics (HES)
• Diagnostic Imaging Dataset (DID)
• Patient Reported Outcome Measures (PROMs)
• Mental Health Services Data Set (MHSDS)
• Office for National Statistics (ONS) – mortality data
and cancer flagging
Clinically interpreted data & QC
• 16,659 families with Tier 1, 2 and 3 variants from interpretation pipeline
• 2,469 families with GMC exit questionnaires
• 31,686 tiered and quality checked rare disease genomes; 12,537 quality checked cancer genomes
Quick view
tables
• Key information from different tables, merged and filterable
• Merged with QC data
• Allow cohort-building and project feasibility assessment
* Secondary data is available up to January 2018, and will be updated as soon as possible
85,070 participants
• 17,062 Cancer
• 68,008 Rare Disease
What are we telling participants? • Information about a patient’s main condition
• Information about additional ‘serious and actionable’ conditions (optional)
• Carrier status for non affected parents of children with rare disease (optional)
17 08 March 2019
Image courtesy of Health Education England
Building the future NHS Genomic Medicine Service
18 08 March 2019
As of 2019 the NHS now:
• Has a national Genomic Medicine Service providing consistent & equitable care for 55 million population
• Is operating to common national standards, specifications & protocols
• Has standardised genomic consent for NHS care and Research
• Is delivering an approved national testing directory covering use of single gene to WGS
• Is building a single UK Genomic Knowledgebase
• Has a national NHS database with all tests that will enable care, effectiveness, and outcomes
• Has de-identified data for academic & industry research
19 08 March 2019
Credits
• Chief Scientific Office for NHS England, Prof Sue Hill
• PHG Foundation
• Academy of Medical Sciences
20 08 March 2019
Stay in touch
Follow ‘Genomics England’
www.genomicsengland.co.uk
@genomicsengland #genomes100k
Subscribe to our newsletter:
www.genomicsengland.co.uk/sign-up
Like the ‘Genomics England’ page