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

Trevor.cole@bwhct.nhs.uk

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 SyndromeClinical Molecular

For Against For AgainstIts 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 MTC

PhaeochromocytomaHyperparathyroidism

• 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 surgeryNon neoplastic CCH 1Borderline CCH 1CCH 3MTC 5Await histology 1

• MTC identified in 5 /11 (~45.5%) at prophylactic surgeryC618S 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???)