models of care for the implementation of genomic medicine ukgtn commissioning workshop 22 nd...
TRANSCRIPT
Models of care for the implementation of Genomic Medicine
UKGTN Commissioning Workshop
22nd November 2012
Dr Trevor ColeConsultant and Honorary Reader in
Clinical and Cancer GeneticsWest Midlands Regional Genetics
ServiceBirmingham Womens Hospital
Sub-committees to
identify educational
needs
Equitable delivery of high quality
integrated pathways
NHS ill-
prepared
www.geneticseducation.nhs.uk
Patient management
Family management
Molecular test
Management could mean :-
• Diagnosis
• Patient Treatment (personalised medicine)
• Pre-symptomatic testing
• SurveillanceMaximise to obtain most clinical benefit and
utility
Patient management
Family management
Molecular test
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
Patient access
• Equal access
Diagnostic process
• How• Who• Consent
Personalised medicine
• Education of NHS
• Engagement with pharma and biotech
Extended family engagement where appropriate
Access: success and failure
Retinoblastoma
Highly successful
Informed expert driven
Breast and Colon cancer
Quite successful
Patient driven and medical reactive
Common Disorders: Hypercholesterolaemia, Diabetes, Chronic Renal
failure
Much less successful
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
In comfort zone
Still some benefit even if wrong aortopathy
I just saved £500!
Not made a definite diagnosis
Not recognised correct aortopathy
Life long follow up at risk
Precise diagnosis
Identify at risk relatives, or exclude.
Personalised medicine
Additional up-front expense
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
Patient access
• Equal access
Diagnostic process
• How• Who• Consent
Personalised medicine
• Education of NHS
• Data collection
• Engagement with pharma and biotech
Extended family engagement where appropriate
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 multisystemBut 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 cardiacdisease
Led by clinical genetics
Cancer genetics Led by clinical genetics with pathways integrated into primary and secondary care
Neurogenetics Provided from within neurology
Endocrine geneticsService
Led by endocrinology with integrated clinical genetics
Familialhypercholesterolaemia
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
Patient access
• Equal access
Diagnostic process
• How• Who• Consent
Personalised medicine
• Education of NHS
• Engagement with pharma and biotech
Extended family engagement where appropriate
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
Unexplained cardiac collapse
Cardio-myopathy
Myocardial infarct
Aortopathy
Conduction disorder
SmokingObesity
CholesterolDiabetes
Hypertension
Obesity (Leptin)Cholesterol (FH)
Diabetes (MODY)
Hypertension (GRBP)
DrugsMetabolic
AlcoholDrugsViral
AgeHypertensio
nSmoking
MarfansEhlers Danlos
Non Syndromic familial
aortopathies
HOCM, Fabry Disease
DMDHaemochromato
sis
LQT / Channelopathies
MetabolicMyotonic Dystrophy
Non Geneitc
Genetic
Geleophysic – Acromicric DysplasiaNeed 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 MTCPhaeochromocytomaHyperparathyroidism
• MEN 2B MTCPhaeochromocytomaMarfanoid habitusMucosal neuromaGanglioneuromatosis 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 43y maleV804M homozygous 54y femaleC618S heterozygous 30y female
Subsequent cascade testing in at risk family 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 V804M families53y female 65y female40y female36y female29y 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 testingor
(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???)
