Download Genetics - EMGO Institute for Health and Care Research

VU University Medical Center
Preliminary Training
18-20 June 2015, Rome
The PRECeDI project has received funding from the European Union’s Horizon 2020
research and innovation programme under grant agreement No 645740.
VU-VUMC Section Community Genetics
• Department of Clinical genetics
• University Medical Center
– 2 UMCs in Amsterdam, one head of Clinical Genetics
– EMGO research institute for Health and Care Research
• Research on societal aspects of large scale genetic/genomics
applications (e.g. population screening, cascade testing)
• Projects: Non invasive prenatal testing, carrier testing for
autosomal recessive diseases, pharmacogenomics (Dutch
grants);
Computer modelling for genomic medicine (ERC grant);
Genetic education primary care (EU Erasmus+ grant)
• Public & Professional Policy Committee Eur Soc Hum Genet
Role in the Project – WP 5
• WP leader – Martina Cornel
5.1 Task leader – Martina Cornel
5.2 Task leader – Martina Cornel (together with Bartha Knoppers,
Mc Gill )
Tasks:
• 5.1. to make a sociotechnical analysis of the balancing of pros and
cons of informing healthy individuals on their genome
• 5.2. zoom in:
to study and improve the current role of pathologists in (1) testing
relevant tumors for microsatellite instability or panels of mutations,
and (2) organizing that the message reaches the family.
Candidate
•
Hosting Researchers:
– 1 Early Stage Researcher from Spain (LinkCare) will be hosted at VUMC for 6 months (Month
12-17).
– able to conduct interviews with stakeholders, study literature on guidelines on genetic testing
and perform socio technical analysis of dynamics between stakeholders
– Health scientist/ sociologist / MD from oncogenetic field or cardiogenetic field
•
Sending Researchers:
1 ER 1 month at LinkCare, Spain [Isa Houwink]
3 ER 4-6 months in total at Better Value Healthcare ltd, UK
[Hanne Meijers, Carla van El, Olga Damman]
1 Experienced Researcher 2 months at Myriad Genetics Srl [Martina Cornel]
2 ER 6 months in total McGill, Canada [Danielle Timmermans, Nikki Damen]
1 ESR 3 months Mc Gill, Canada [Dalisa van den IJssel]
Integrating Genomics in Health care
Service development in oncology
and cardiology
Martina Cornel,
Professor of community genetics & public health genomics
PRECeDI Rome 18-20 June 2015
The PRECeDI project has received funding from the European Union’s Horizon 2020
research and innovation programme under grant agreement No 645740.
Public Health Genomics: definition
• The responsible and effective translation of
genome-based knowledge and technologies
into public policy and health services for the
benefit of population health
• genome-based knowledge and
technologies=GBIT
• PACITA report p. 88 (and elsewhere)
Learning goals
• The student can describe the fast scientific
developments in genome-based knowledge
and technologies
• The student can discuss what is needed for
translation of genomics knowledge into health
care
2000: genome sequence published
• Bill Clinton: We are here to celebrate the
completion of the first survey of the entire human
genome …
• With this profound new knowledge, humankind is
on the verge of gaining immense, new power to
heal. Genome science will have a real impact on
all our lives -- and even more, on the lives of our
children. It will revolutionize
the diagnosis, prevention
and
treatment of most,
if not all,
human diseases.
Collins FS (Right at photo). Nature 2010 &
© AP PHOTO/RON EDMONDS
http://www.genome.gov/images/content/cost_per_megabase2.jpg
Result of large scale genomic research
Shifting focus:
• From single gene (Mendelian) conditions
– cystic fibrosis, Duchenne muscular dystrophy, Huntington’s
disease
• To common, complex conditions
– diabetes, cardiovascular disease, schizophrenia
Gene or environment?
Heart
disease
PKU
Schizophrenia
Cancer
Cystic
fibrosis
Duchenne
muscular
dystrophy
Totally
Genetic
Fragile X
Multiple
Diabetes sclerosis
Asthma
Motor
vehicle
accident
Alzheimers
TB
Struck
by
Meningococcus
lightning
Autism
Obesity
Rheumatoid
arthritis
Totally
Environmental
Understanding the cause of disease
• Genome wide association studies (GWAS)
– Common disorders
– SNPs that contribute little to the risk
• Array and sequencing techniques
– Rare disorders (rare variants of common
disorders)
– Panels to analyse several genes at once
• Information technologies (high throughput)
– Faster and cheaper analysis
Extending scope of testing?
Will shifting research lead to shifting health care?
– From reproductive tests to predictive testing
• Clinical genetics for infants with MR/MCA, but increasingly
oncogenetics & cardiogenetics?
– From reproductive decision making to personal risk
reduction
– From rare monogenic to common complex diseases
• Monogenic subtypes
– From families to large (sections of) healthy populations
• Screening
Learning goals
• The student can describe the fast scientific
developments in genome-based knowledge and
technologies
• The student can discuss what is needed for
translation of genomics knowledge into health
care
–
–
–
–
From bench to bedside
Phases of translation (Khoury)
Stakeholders (Rigter)
Guidelines (PPPC)
Genetics: “bench” or “bedside”?
Science and/or health care?
On the left: Watson and Crick
describe the structure of DNA
http://education-portal.com/academy/lesson/james-watsoncontributions-double-helix-quiz.html#lesson
http://www.umcutrecht.nl/subsite/erfelijkheid/erfelijkheidsv
oorlichting/Wanneer_erfelijkheidsonderzoek.htm
Above: clinical geneticist
explains the consequences to
patients
Translation needed
www.st-hughs.ox.ac.uk/library
Libraries cannot be built fast enough to keep up
with modern scientific output.
But moving this knowledge off the shelves and
into practice.. requires translation.
Lenfant NEJM 2005;349:868
“Lost in translation” in Lenfant 2005
… the last and perhaps most important segment,
… taking the findings of clinical investigations
and translating them into the practice of
medicine at the community level.
1981 benefits of beta-blockers for patients who
were recovering from myocardial infarction
1996 beta-blockers were being prescribed for
only 62.5 percent of patients who had had a
myocardial infarction
“Lost in translation” in Lenfant 2005
Late 1980s … benefits of cholesterol lowering in
patients with coronary heart disease
1999: only half to three quarters of patients who
have had a myocardial infarction are even
being screened for elevated serum cholesterol
levels, much less being prescribed cholesterollowering regimens
Phases in translational research
• The continuum of translation research in
human genetics: types of research
Khoury M et al. Genet Med. 2007;9:665-74.
Framework for translational research
• T1 BRCA mutation is associated with breast
cancer
• T2 Determine the positive predictive value of
BRCA mutations, develop guidelines for testing
• T3 What proportion of women from BRCA
families are tested?
• T4 Does BRCA testing contribute to living longer
and healthier?
– These steps need to be planned, they do not come
automatically
How translational is human genomics research?
Premature translation??
Translation
• Doesn’t happen automatically
– Only small percentage of research budget devoted
to translation
• May come premature
– Valorisation=making money/value after
investment
• If you feel a change is needed: look for
opportunities and other stakeholders involved
People don’t like change
• We work in a certain structure, culture &
practice
• Dynamics within or outside this constellation
may cause instability
• Opportunity for change!
– 2005: cardiac arrest young footballplayer in
Sweden
• Sense of urgency, not only for clinical
geneticists but also for cardiologists etc.
Rigter, J Community Genet (2014) 5:337–347
Learning goals
• The student can describe the fast scientific
developments in genome-based knowledge and
technologies
• The student can discuss what is needed for
translation of genomics knowledge into health
care
–
–
–
–
From bench to bedside
Phases of translation (Khoury)
Stakeholders (Rigter)
Guidelines (PPPC)
What is needed for responsible translation?
Source: PhD thesis Tessel Rigter Ch 8 http://dare.ubvu.vu.nl/handle/1871/51733
We need other stakeholders!
• A new technique in the laboratory
• A clinical geneticist can explain the test results
• Who will inform the patient that the test is
available?
• Who will refer?
• For many fields (cancer, cardiovascular disease,
diabetes) too many patients to counsel in genetic
centres
• Collaboration needed, new division of tasks
What is needed for responsible translation?
Sources: PhD thesis Tessel Rigter Ch 1 http://dare.ubvu.vu.nl/handle/1871/51733
And Achterbergh et al. Health Policy 2007;83:277-286.
Scaling up
• Changes start at a small scale and need
deepening, broadening, and scaling up before
a full transition is accomplished and a new
constellation (with adapted culture, structure,
and/or practice)
– Maturity Onset Diabetes of the Young (MODY)
testing UK
– initiative of a consultant diabetologist, a molecular
geneticist, and a diabetes specialist nurse
– Network of diabetic nurses
Rogers technology adoption life cycle
Source: wikipedia
Hereditary cancer program in Catalonia, Spain
• Initiated within the Catalan Institute of Oncology
by a group of clinicians and geneticists at the
Department of Prevention and Cancer Control in
1998
• Most referrals come from medical specialists
• More than 1,000 carriers of highly penetrant
cancer predisposing genes have been identified
and are under surveillance
• More than 900 healthy relatives have been
withdrawn from intensive surveillance because
they had not inherited the pathogenic mutation
What determines success?
• Clinical need
• Evidence for clinical validity, clinical utility
• Perceived need
– Stakeholder’s priority and awareness (patients,
payers, doctors, etc.)
– Public priority and awareness
• Health economic evaluation
– Are the benefits outweighing the costs?
New constellation?
• The service is paid for by the Catalan health system
• Nowadays, similar services are available in other
regions in Spain (scaling up) without clear national
guidance.
• Little comparable services are offered for other
conditions than cancer because it seems hard to
convince other disciplines of the importance of
cascade screening.
• In addition, private companies are increasingly
offering testing, which could keep patients and/or
family members from utilizing the services offered in
regular health care.
Learning goals
• The student can describe the fast scientific
developments in genome-based knowledge and
technologies
• The student can discuss what is needed for
translation of genomics knowledge into health
care
–
–
–
–
From bench to bedside
Phases of translation (Khoury)
Stakeholders (Rigter)
Guidelines (PPPC)
Developing guidelines: example
• Stakeholder meeting
• Circulate draft consensus statement to
participants
• Invite comments from other experts / www
• Finalize
• Evaluate results
• Plan, do, check, act in due time.
PPPC guidelines
•
•
•
•
•
Genetic testing in common disorders
Direct-to-consumer genetic testing
Genetic testing in minors
Whole genome sequencing in health care
Whole genome sequencing for newborn
screening
PPPC guidelines
• Not a ‘law’
• But influential (Council of Europe, IVD
regulation)
• Pinpoint relevant issues for policy making in
country
• Provide & clarify argumentation why
something is important
• May help you to contribute to translation!
Conclusion
• Integrating genomics techniques in health
care needs you!
• Phases in translation
– Protocol, training, evaluation
• Other stakeholders involved
• Scaling up from small initiatives
• Use a structured approach
Where are your stakeholders?
• Prepare for tomorrow a presentation on YOUR
translational challenge (Poster, PPT)
• Assignment available on paper
– Make a list of relevant stakeholders in your PRECeDI research project
or field of interest
– Where does the dynamics come from in this field?
– Where do you see barriers for implementation?
– In what stage would you describe your field of interest to be?