Transcript Slide 1

The NHS in the genomics era
Mark Bale
Department of Health
100,000 Genomes Project
“It is crucial that we continue to push
the boundaries and this new plan will
mean we are the first country in the
world to use DNA codes in the
mainstream of the health service”
The Rt Hon David Cameron MP
The Prime Minister
10 December 2012
Genetics White Paper
The rate of change
• Sequencing costs are dropping rapidly
and new sequence data consequently
rising
• Research is advancing at a rapid rate,
but understanding of the role of genes
in health and disease is still in its
infancy
•Applications in some areas (such as
cancer) are already here and the NHS
must start to adapt for the advent of
genomic medicine
•Benefits in reduced diagnostic time,
better precision and possible savings
from other (futile) treatment options
•Capacity challenges and bottlenecks in
data storage and interpretation
•Concerns that investment unlikely
piecemeal under current assumptions –
industry and other private investment
The UK Strategy for Rare Disease
• Launched November 2013
• 51 commitments across all 4
devolved administrations
5 themes:
1.
2.
3.
4.
5.
Empowerment
Diagnosis
Prevention & early intervention
Better coordination of care
Research and development
Rare inherited diseases
Deciphering Developmental Disorders (DDD)
https://decipher.sanger.ac.uk
7
NIHR Rare Diseases Translational Research
Collaboration (RD-TRC)
• >7,000 rare diseases (fewer than 5 in 10,000) have been identified
• The UK is at the cutting edge of research in rare diseases internationally
• ‘Deep’ phenotyping information combined with data on genomic
abnormalities will increase research opportunities, enable faster diagnosis
and support improved management and treatment of rare diseases
• RD-TRC will provide world-class NHS research infrastructure as a key element
to harness the unique strength of the NHS to support fundamental discoveries
and translational research on rare diseases
• Co-chaired by John Bradley (Cambridge BRC) and Patrick Chinnery (Newcastle
BRC)
NIHR BioResource - Rare Diseases
Sequencing Projects
NIHR BioResource Rare Diseases: Approved BRIDGE~ sequencing projects per 30 November 2013
Rare
Disease/Condition
Lead
Investigator
Biomedical
Research
Centre/Unit
Bleeding and Platelet
Disorders
Prof Willem H
Ouwehand
Cambridge
Steroid Resistant Nephrotic
Syndrome
Dr Ana Koziell
Pulmonary Arterial
Hypertension
No. of WES
in pipeline/
completed
No. of WGS
in pipeline/
completed
800
658/524*
0/0
Guy’s and St 500
Thomas’
8
0/0
0/0
Prof Nick
Morrell
Cambridge
1000
360
47/0
96/0
Primary Immune Disorders
Prof Ken Smith
Cambridge
1000
283
47/0
48^/0
Intrahepatic Cholestasis of
Pregnancy
Prof Catherine
Williamson
Guy’s and St 270
Thomas’
0
-
-
Specialist Pathology:
Evaluating Exomes in
Diagnostics
Dr Lucy
Raymond
Cambridge
1000
550
94/0
192/0
Primary
Membranoproliferative
Glomerulonephritis
Dr Daniel Gale
UCL
93
70
0/0
48^/0
Ehler-Danlos (ED) and EDlike Syndromes
Prof Tim
Aitman
Imperial
400
10
0/0
0/0
Cambridge
700
0
-
-
Multiple Primary Malignant Prof Eamon
Tumours
Maher
Capacity
allocated
1000
Participants
recruited
Cancer
• Disease of disordered
genomes – over 200
drivers known
• Stratified medicine and
targeted therapy
• Drug metabolism
• Immunological targets
• International Cancer
Genomes Consortium- the
Cancer Genome Atlas
• Optimise Molecular
Pathology
Signal transduction pathways
affected by mutations in human
cancer
Vogelstein et al. Science 339,
1546 (2013)
Incidence v survival at 5 years
Lung cancer before and after Gefitinib
BRAF inhibitors for Melanoma
Antimicrobial resistance
A vision for NHS genomics
Human Genomics Strategy Group (2012)
• By 2020, the NHS will be a world leader in the
development and use of genomic technology in
the areas of healthcare and public health. It will
be seen as a first-choice partner for industry,
academia and research, contributing substantially
to the global genomics knowledge base by
supporting and facilitating innovation and novel
research.
•
•
•
•
Genomic information and clinical genetic testing will be
used equitably across the NHS, improving diagnosis and
treatment decisions by identifying the right therapies to
maximise efficacy and reducing adverse effects.
Healthcare providers within the NHS will confidently use
genomic information within their roles
Effective public engagement will increase awareness of
the role of genomic information in healthcare; how it can
inform health choices; and the need for consent to access,
study and use genomic data for the greater good.
There will be a vibrant SME sector and large life sciences
company investment in and around our best universities
and genomics hubs.
CMO priorities for genomics in the NHS – 2012
1.
2.
3.
4.
5.
6.
7.
8.
Reconfigure NHS laboratories around genomic technologies for single gene and
gene panel diagnostic testing
Ensure fast, high quality testing services for high penetrance genetic
variants of common diseases such as cardiac, eye and metabolic
disorders
Develop a “discovery diagnostic” network of excellence for rapid
translation into the clinic
Commission appropriate genome diagnostics on all children from
specialist units where a diagnosis is unclear
Improve pathways for genetic testing or sequencing of cancers to build
on current stratified medicines initiatives
Align standards and architecture to collect genomic data and
phenotypes
Facilitate a network of clinical bioinformatics, with powerful computing
and data analysis
Review the role of sequencing in antenatal and adult screening, for
example new developments in fetal DNA testing and cervical screening
Genetic Services in the NHS:
What is likely to change
Genetic services in the NHS at present are primarily focused on testing for rare
monogenic disorders, via specialist genetic service fundamental shift in approach
FACTOR
CURRENT SITUATION
EMERGING TREND
Nature of
tests
Relatively limited number of tests provided,
primarily for relatively rare single gene disorders*
Many more tests - including for monogenic forms
of common diseases, pharmacogenetic tests and
genome-wide tests for risks of common diseases
Nature of
information
Few data points, clinical implications usually clear
(single genes with large effects)
Large volume of complex, risk-based information;
clinical significance often less clear cut
How the
information is
used
Primarily to diagnose those identified as at risk
(due to family history) of inherited genetic disorders
Increasingly to select most appropriate treatment
strategy. In the longer term, potential shift to
prevention based on risk-based information
Workforce
requirements
Genetic testing provided via specialist clinical
geneticists and genetic counsellors
Genetics will increasingly enter into mainstream
care – with requirement for professionals across
NHS to be trained in genetics and its implications
Consumer
expectations
Relatively low level of awareness of genetics
amongst general population – beyond those
affected by genetic disorders
Increasing access to information sources on-line
and to direct-to-consumer testing is likely to see
increased awareness and demand
*According to UKGTN second report (Nov 2010), between Apr 2008 and Mar 2010 the NHS
Directory of Genetic Testing contained 503 diseases and 688 associated tests
Discovery Diagnostics
Diagnosis from research studies using
genomic technologies in a clinical
translation research setting:
DDD (UK)
Analysed first 1,133 families, with a
diagnostic rate of aprox 30%, discovered 12
new genes
Gilissen etal (2014) – Nijmegen
42% diagnosis rate of 50 children with
severe intellectual disability using WGS
Beaulieu etal (2014) – FORGE Canada
Consortium
45-95% diagnosis rate of 264 patients using
whole exome sequencing
WGS500 Results
• 7 Novel genes for
disease
• 6 Novel phenotypes for
known genes
• 2 pathogenic regulatory
variants in or
downstream of known
candidate genes
• 6 genes missed by prior
Sanger Sequencing
MENDELIAN
Of 95 families, to date
• 23 families have new diagnosis
• pre-screened for known genes
• result will increase with follow-up
• 74 families in follow up studies
• Over 50% of these have strong lead
candidate
Genomic medicine
• Specialist genetics, pathology and specialist clinical workforce in Genomic
Medicine
• Increase in specialised scientific training fellows funded over 3/5 years:
• Molecular Pathology including Infections and Pathogens
• Genetics / genomics
• Bioinformatics
• Commission bioinformatics workshops in conjunction with partners
• Develop specialist on line on-line learning and an MSc in Genomic Medicine
• Develop an MSc in Genomic Medicine
• CPD access to MSc modules for specialist practitioners
Conclusion
• Genomic Medicine is here
• Time for translation is now
• Prime therapies or repurpose treatments
• It needs further optimisation
• Together we can transform Genomic Medicine in the NHS