Models of care for the implementation of
Genomic Medicine
UKGTN Commissioning Workshop
22nd November 2012
Dr Trevor Cole
Consultant and Honorary Reader in Clinical
and Cancer Genetics
West Midlands Regional Genetics Service
Birmingham Womens Hospital
Trevor.cole@bwhct.nhs.uk
NHS
ill- prepared
Sub-committees to
identify
educational needs
www.geneticseducation.nhs.uk
Equitable delivery of
high quality
integrated pathways
Molecular test
Patient management
Family management
Management could mean :• Diagnosis
• Patient Treatment (personalised medicine)
• Pre-symptomatic testing
• Surveillance
Maximise to obtain most clinical benefit and utility
Molecular test
Patient management
Family management
What are we trying to achieve?
Patient
Access
Diagnostic
Process
Personalised
Medicine
What are we trying to achieve?
Optimisation of each of the Steps
Patient access
• Equal access
Diagnostic
process
• Who
• How
• Consent
Personalised
medicine
• Education of
NHS
• Engagement
with pharma
and biotech
What are we trying to achieve?
Optimisation of each of the Steps and
Extended family engagement where appropriate
Patient access
• Equal access
Diagnostic
process
• How
• Who
• Consent
Personalised
medicine
• Education of
NHS
• Engagement
with pharma
and biotech
Access: success and failure
Retinoblastoma
Breast and Colon cancer
Common Disorders:
Hypercholesterolaemia, Diabetes,
Chronic Renal failure
Highly successful
Quite successful
Much less successful
Informed expert
driven
Patient driven and
medical reactive
Why?
Less aware public and
professions
Access success – simple!! (If only)
• Educated and engaged public
• More aware profession and easier access
to pathways (know when to refer)
• Commissioning process that encourages
early intervention for the “well” – primary
and secondary care
Illustration of Diagnostic Process
Deliberations and Consequences :- Is it?
• Marfan syndrome
• Rare aortopathy
• Homocysteinuria
Making the Diagnosis of Marfan Syndrome
Clinical
Molecular
For
Against
For
Against
Its cheap
Not made a
definite diagnosis
Precise diagnosis
Additional upfront expense
In comfort zone
Still some benefit
even if wrong
aortopathy
I just saved £500!
Not recognised
correct
aortopathy
Life long follow
up at risk
Identify at risk
relatives, or
exclude.
Personalised
medicine
If wrong gene
money down the
drain!
No relatives in my
area
Worried about
consent and
sharing
confidential
information
How to encourage most appropriate diagnostic process :–
make it part of a required pathway
• Homocysteinuria – urine adequate only if no
other management issues
• Marfans – is a clinical diagnosis adequate to
answer “all the other medical issues” to the
benefit of “the whole NHS”
• Rare aortopathy – do I need to be aware of
these alternative diagnoses and management
issues
Use SCN and NHSCB through CRG to :• Promote commissioning of MDT working
• Optimise pathway
• Support most appropriate clinical involvement
(eg Marfans – expert cardiology, cardiothoracic
surgeons, ophthalmology, clinical geneticists,
nurse specialist/ genetic counsellors,
orthopaedics, physiotherapy etc)
What are we trying to achieve?
Optimisation of each of the Steps and
Extended family engagement where appropriate
Patient access
• Equal access
Diagnostic
process
• How
• Who
• Consent
Personalised
medicine
• Education of
NHS
• Data
collection
• Engagement
with pharma
and biotech
For “each patient” MDT discussion or agreed
protocols to consider appropriate :-
• Diagnosis (What do I need to achieve 2 &3)
• Management
• Genetic Cascade
• “premium for care” in “quality assured
pathways” to cover initial expenses but to
ensure downstream benefits (central to
UKGTN gene dossiers – link from NLMC)
Engagement of Public and Professionals
(Requirement of the quality assured pathway)
• HGSG – importance of engagement and
•
•
•
•
•
education
GMC – medical school requirement
Royal Colleges and NMC – JCMG report
HEE – ensure part of the “CPD curriculum” for
LETB’s – remove the “unknown unknowns”
Member of NCB with remit to genomics and
promotion of education across the NHS
Commissioners only support “QAP”
Encourage engagement of Pharma and
Biotechnology
• Smaller number of collaborators for more
patients enrolled
• More consistent cohorts
• More consistent evaluations
• More cost effective research
More consistency of consent
• More consistency of consent process
• Increased awareness of equivocal results and
•
•
interpretation
Greater support for interpretation of equivocal
results
Greater emphasis on sharing information for
knowledge and family management as norm
rather than exception or retrospective
Should not be “a charter for ivory towers” practice :
Criteria should be QAP delivery
• Rare is common – 3 million people in England
have a rare disorder.
• 80% genetic
• Many multisystem
But many
• Common enough to be managed in many
centres (1 versus >1 per “sector”)
• Need a lot of local support and input –
horizontal integrated care with IT systems to
share relevant data and protocol management
Inherited cardiac
disease
Led by clinical genetics
Cancer genetics
Led by clinical genetics with
pathways integrated into primary
and secondary care
Neurogenetics
Provided from within neurology
Endocrine genetics
Service
Led by endocrinology with
integrated clinical genetics
Familial
hypercholesterolaemia
Structured multidisciplinary
pathway led by lipid clinic
clinicians with family cascade
service hosted by regional
genetics service
Single gene diabetes
Led by diabetology with network
of specialist nurses
Extended family engagement where appropriate
Patient access
• Equal access
Diagnostic
process
• How
• Who
• Consent
Personalised
medicine
• Education of
NHS
• Engagement
with pharma
and biotech
Inherited cardiac disease
Led by clinical genetics
Cancer genetics
Led by clinical genetics with pathways integrated into primary and
secondary care
Neurogenetics
Provided from within neurology
Endocrine Genetics Service
Led by endocrinology with integrated clinical genetics
Familial Hypercholesterolaemia
Structured multidisciplinary pathway led by lipid clinic clinicians with
family cascade service hosted by regional genetics service
Single gene diabetes
Led by diabetology with network of specialist nurses
Non Geneitc
Genetic
Alcohol
Drugs
Viral
HOCM,
Fabry Disease
DMD
Haemochromatosis
Smoking
Obesity
Cholesterol
Diabetes
Hypertension
Cardiomyopathy
Drugs
Metabolic
Conduction
disorder
Unexplained
cardiac
collapse
LQT / Channelopathies
Metabolic
Myotonic Dystrophy
Myocardial
infarct
Obesity (Leptin)
Cholesterol (FH)
Diabetes (MODY)
Hypertension
(GRBP)
Aortopathy
Age
Hypertension
Smoking
Marfans
Ehlers Danlos
Non Syndromic familial
aortopathies
Geleophysic – Acromicric Dysplasia
Need to overcome - “Who pays for the test?”
• Geleophysic – AR due to mutations in
ADAMTLS2 gene
• Geleophysic/Acromicric – AD due to
mutations in the fibrillin gene
• Prognosis differs across spectrum
• Fibrillin mutation disorders show evidence
of response to anti TGF therapy
• Recurrence risk 1 in 2, 1 in 4 or very low
Multiple Endocrine Neoplasia type 2
(MEN 2)
• MEN 2A
MTC
Phaeochromocytoma
Hyperparathyroidism
• MEN 2B
MTC
Phaeochromocytoma
Marfanoid habitus
Mucosal neuroma
Ganglioneuromatosis gut
• Familial MTC
≥4 MTC
No phaeochromocytoma
No hyperparathyroidism
Joint MTC at QEH
19 apparently sporadic MTC presenting to QEH over 2 years
A mutation was identified in 3/19 (15.8%)
V804M heterozygous
V804M homozygous
C618S heterozygous
Subsequent cascade testing in at risk family
43y male
54y female
30y female
members
• → 18 predictive genetic tests → 13 positive
→ 11 prophylactic thyroidectomies
Joint MTC at QEH
Histology at prophylactic
surgery
Non neoplastic CCH
1
Borderline CCH
1
CCH
3
MTC
5
Await histology
1
• MTC identified in 5 /11 (~45.5%) at prophylactic surgery
C618S family
53y
40y
36y
29y
female
female
female
female
V804M families
65y female
Indications for using DNA testing :genetic management
•
•
•
•
•
Cascade screening
Prevention of unnecessary intervention
Appropriate surveillance for at risk individuals
Is presymptomatic diagnosis and intervention
going to change the outcome?
Does knowing the genetic basis change the
management – (Germline) Warfarin dosage,
PARP inhibitors, PTC124. (Somatic - oncology)
Herceptin, Gleevac and Iressa
Common Disease with a Major
Genetic Component
•
•
•
•
•
•
Renal Failure
Heart Disease
Hypertension
Osteoporosis
Diabetes Melitus
Most Types of Cancer
• All can be single gene or
•
•
•
•
•
multifactorial
All amenable to
intervention
Surveillance is often very
simple
Genetic testing maybe
difficult and expensive
Taking a family history is
very easy and cheap!
Some genetic testing is
very beneficial
Indications for genetic testing
or
(How to persuade your commissioners!)
• Diagnosis (avoidance of unnecessary investigations)
• Management
(most appropriate follow up and treatment)
• Genetic follow up (identification of gene carriers and
exclusion of population risk follow up)
• Ensure you get the maximum clinical
utility from you test (a no brainer???)