transforming the nhs through genomic and personalised medicine, pop up uni, 12.00, 2 september 2015
TRANSCRIPT
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Changing Clinical Care
Transforming the NHS through genomic
& personalised medicine
Professor Sue Hill OBE
NHS Chief Scientific Officer for England
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Care in the era of non-communicable disease • Traditional ‘One size fits all’ model of care failing to account for much of
the chronic inflammatory and degenerative disease facing society,
These non-communicable diseases are increasing as survival improves
• Life style influences are creating a time bomb in non communicable
diseases for example in cancer, obesity, diabetes, hypertension
• Drug treatment based on a drug discovery approach of ‘one size fits all’
business model is ineffective in between 30 and 60% of patients
• Five Year Forward View recognises that NHS sustainability requires
revolutionary change in service provision – informed by research
and innovation, with a new focus on prevention and earlier detection of
disease and delivery by new ways of working.
Condition Efficacy Rate (%)
Alzheimer’s 30 Asthma 60 Diabetes 57 Hep C 47 Cancer 25 Osteoporosis 48 Rheumatoid arthritis 50 Schizophrenia 60
Limits of pharmaceutical effectiveness
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Profound scientific and technological innovation influencing NHS transformation
and effectiveness ; a major step change in the pathway to personalised care
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The 100,000 Genomes project -a major catalyst for change in an integrated health system
• Project will sequence 100,000 whole genomes (WGS) from patients with cancer and rare disease representing a 300 fold increase in the genetic information available for diagnostic purposes
• Other samples from across the functional genomic pathway will be collected to enable complex cellular processes and the expression of genetic variants in these diseases to be understood
• Detailed clinical and diagnostic data will be collected both at the start and longitudinally and stored together with the WGS in the Genomics England secure Data centre to enable analysis of the individual genotype and phenotype and comparison within others
Major legacies for patients,
the NHS and the UK
economy by 2017
Increased discovery of pathogenic variants leading to new treatments, devices and diagnostics
Stimulate and advance UK life sciences industry and commercial activity in genomics
Accelerate uptake with advanced genomic medicine practice integrated into the NHS
Increase public understanding and support for genomic medicine
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Involvement of multiple clinical
specialities in new MDTs
Step change in analysis of
information , validation &
reporting
Partnerships & networks
working across
geographies
Capture of data from multiple systems against defined datasets and
standards
Key roles of NHS GMCs
Upskilling the NHS
Workforce
Sample collection, processing & logistics to defined protocols &
quality standards
Return of results to participants & clinical
care according to guidelines
Transforming the NHS – improving
outcomes & reducing variation
Patient & Public
Involvement
Transforming the NHS for the future – Genomic Medicine Centres
Network of 11 Wave One GMCs overseeing genomic services for population of 3-5 million
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Informing the personalised medicine approach • Technological advances and the breadth of information captured about patients - exemplified in
the 100,000 Genomes Project - are moving the NHS to a new model of diagnosis and treatment based on identifying and understanding the underlying causes of disease rather than deduction from symptoms and individual tests
• Effective capture and analysis of all diagnostic (including genomic)and other clinical data will identify novel disease pathways – and the patient subgroupings that will inform effective management.
• 4 Ps of Change: Medicine will move from a reactive to a proactive discipline over the next decade; one that is predictive, personalised, preventive and participatory
• Integral to delivering this step-change in provision will be further developments in informatics and other underpinning diagnostic services driven by scientific and technological advances
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Personalised medicine - definition
• Personalised medicine: ..the tailoring of medical treatment to the individual characteristics of each patient... using diagnostic tests to select the most appropriate treatment for individual patients – the right drug at the right time, earlier screening and treatment, smarter monitoring and adjustment of treatments.
• Interventions can then be concentrated on those who will benefit and preventing side effects in those who will not
• First generation of personalised pharmaceuticals
already here (100+ licensed by 2014) – eg Herceptin®, Zelboraf ®
BRAF inhibitor treatment for malignant melanoma
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Why this is important in improving outcomes
Targeted disease prevention Identification of predisposition markers or
underlying processes can predict future disease
Early disease detection 2-8 yrs before onset & symptoms become
obvious with low cost stratification
Accelerated diagnosis based on underlying cause and incidental findings – rather than
just grouped symptoms
Targeted therapy Identification of effective personalised treatments
Improves outcomes
• Greater efficiency from streamlined care pathways • Earlier and more precise diagnosis and treatment • Fewer and less complicated surgical interventions • Fewer patients getting cancer and other diseases
£
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Combining the elements for delivery Informing and transforming common treatments such as Anticoagulant therapy
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The need for cultural change • Personalised medicine demands a new approach – to treat the patient’s
disease and not the disease in general, to understand variation from patient to patient and within a patient across the life course
• Treatment decisions will increasingly be driven by individual patient data – requiring a much greater focus on new management and analysis of the data that professionals capture
• Effective integration of multiple different types of data and its intelligent interrogation will identify novel disease pathways
• Need to maintain the momentum and the NHS transformation that participation initiated through the 100,000 Genomes Project has initiated
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Where is the wisdom
we have lost in knowledge ?
Where is the knowledge
we have lost in information?
TS Elliot
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Manchester Centre for Genomic Medicine
William G Newman MD PhD
Professor of Translational Genomic Medicine, University of Manchester
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Manchester Genomic Medicine Centre
Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust – rare diseases
Christie Hospital NHS Foundation Trust – Cancer care
Mission : to deliver the benefits of Genomic Medicine to all
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Manchester Genomic Medicine Centre
Rare Diseases - MCGM
• Largest Centre in Europe • Translation from research to
service serving a diverse local population of 6m.
• 12,000 patients /year • >50,000 genetic tests
• unified laboratory - biochemical genetics, cytogenetics, molecular genetics including cancer pharmacogenomics
Cancer- Christie
• Largest Centre in Europe
• Close links between research (especially clinical trials) and treatment
• >44,000 patients /year
• Expertise in personalised medicine – lung cancer, melanoma
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Innovation Pathway
INVENTION EVALUATION
Understanding the molecular basis of Genetic Disease
Studies: Understanding
Molecular Basis of Genetic
Disorders
Neurological & Immune
function
Renal Tract Abnormalities
Developmental disorders
Learning disability
RASMAP-K pathway
Schwannomatosis
Neurofibromatosis 2
Breast Cancer
Cardiac disorders
Retinal dystrophies
Congenital cataracts
Evaluation of Novel Therapies
Novel therapies for
•Marfans syndrome
•Neurofibromatosis 1 & 2
•Huntington’s disease
•Fragile X
•Niemann-Pick B
•Mucopolysaccharidoses
•Lysosomal Acid Lipase deficiency
(infant and adult)
Gene therapy
•Choroideraemia
Screening
•women at risk of breast cancer
•Mammography-Predicting the Risk
at Screening
Studies: Improving Services
• Accessibility for patients with
sensory impairment
•Improving services for those with
inherited retinal disease
•Improving Communication in the
Genetic Eye Clinic
•Patient Empowerment in clinical
genetics services
•Delivering therapies for rare
diseases – ERT for MPS I, II, VI
•Management: Nationally
commissioned specialist services
(Complex NF1, NF2, LSDs)
ADOPTION
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Use of WGS in Discovery
cleft lip/palate,
hearing loss,
choanal atresia (blocked nose)
= Burn-McKeown Syndrome
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Advantages of Whole Genome Sequencing in Discovery
Wieczorek et al Am J Hum Genet 2014 December
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Basal Cell Carcinoma
Affects ~1 million people/ year in the USA
Familial Basal cell carcinoma – Gorlin syndrome
•Multiple basal cell carcinomas (>5 in lifetime)
•Jaw cysts
•Brain calcification
•First degree relative with Gorlin's syndrome
Some cases
•Skeletal problems - Vertebral/rib anomalies
•5% medulloblastoma (childhood brain tumour)
•Most have mutations in a gene – PTCH1
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Discovery • Genome Sequencing of 4 PTCH1 -ve familial cases
• Causative mutations in SUFU
Family 1
A A G A A T T C A G C A C A T G C T G C T G A C A G A G G A C C C A C A G A T G C A G C C C G T G C A G A C A C C C T T T G G G G T A
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Fragment
10E
c.550C>T (p.Gln184*)
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Fragment
10D
c.544G>T (p.Asp182Tyr)
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• Negative regulator of hedgehog signalling pathway
Implications for treatment:
• SUFU cases not responsive to
hedgehog inhibitors
(vismodegib) - £6k /month
Hedgehog inhibitor
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Medulloblastoma risk
• Present in 3 of 10 SUFU mutation +ve cases
• Contrasts with 2 of 115 PTCH1 mutation +ve cases (p=0.003)
• Implications for screening:
? MRI brain surveillance in SUFU mutation +ve, -6 monthly till 2 years, then
annually, but not justified in PTCH1 +ve cases
Smith et al Journal of Clinical Oncology December 2014
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Providing the evidence to alter clinical practice Diagnostic yield in retinal disease – inherited blindness
NGS panel WGS
Increased pick up of 27%
Pathogenic variants identified
No pathogenic variants identified Heterozygous pathogenic variant identified in a gene expected to cause recessively inherited disease
Unpublished – Prof Graeme Black
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Cancer diagnostics
• Transition from single gene tests e.g. EGFR in lung cancer to panels of all relevant genes
• Increase identification of patients eligible for trials of new therapeutics
• Identify genetic changes (translocations) challenging to detect by other
types of genetic test
• Discovery of markers for resistance – swap treatment
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100,000 Genome Project
EVALUATION ADOPTION INVENTION
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100,000 Genome Project
Participant Experience
Seana Donaghy
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Diagnosis • 8 months pregnant
• Usual pregnancy symptoms
• Echocardiogram
• Left ventricular dilated cardiomyopathy
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Reasons for participating • Family
• Early detection
• Peace of mind
• Improvements in treatments
• Acceptance
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Taking part • No pressure invitation
• Sit down meeting
• Blood test
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THANK YOU