genomics and personalised medicine · •tom – deputy chief scientist & director of public...

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.

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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

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• 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

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• 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

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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

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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

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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

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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

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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

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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

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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)

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• 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

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Research Environment

Genomic dataset

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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).

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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)

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Image courtesy of Health Education England

Building the future NHS Genomic Medicine Service

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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

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Credits

• Chief Scientific Office for NHS England, Prof Sue Hill

• PHG Foundation

• Academy of Medical Sciences

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