Transcript Document

Professional policy development in genetic
health care:
the challenge of discerning hopes from hypes
75th Anniversary of
Albert SzentGyörgyi’s Nobel Prize
Award
Szeged
Hungary
25.03.2012
Martina Cornel
Professor of Community Genetics and
Public Health Genomics
Quality of Care
Community Genetics, Dept Clinical Genetics
EMGO Institute for Health and Care Research
2000: genome sequence published
• Without a doubt, this is the most important, most
wondrous map ever produced by humankind.
• 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.
Human genome project 2000
Genetics: “bench” or “bedside”?
Science or health care?
Left: Watson and Crick
describe the structure of
DNA
Above: Breuning explains
the consequences
>10 years after …
• Results in health care modest
• Genetic variants (SNPs) explain only minority of
interindividual risk differences
• The human molecular system is more complex
than anticipated.
Finding the missing heritability..
Manolio, Nature 2009
Genomics has not revolutionized medicine
• Promises too optimistic
– GWAS, SNPs predict less than expected
• Complexity of human biological system
• Lack of translational studies
Prevention advice in 2020?
Premature translation??
Professional policy development in
genetic health care:
the challenge of discerning
hopes from hypes
Background Document & Recommendations
Collaboration: PPPC, EUroGenTest, IPTS
•
PPPC:
Members of PPPC: Nurten
Akarsu, Pascal Borry, Anne
Cambon-Thomsen, Martina
Cornel, Thoas Fioretos,
Francesca Forzano, Veronica van
Heyningen, Shirley Hodgson,
György Kosztolányi, Ulf
Kristoffersson, Jan Lubinski,
Meral Özgüz,Christine Patch, Aad
Tibben, Lisbeth Tranebjaerg,
Jorge Sequeiros.
Carla van El (researcher)
•
IPTS:
Dolores Ibarreta, Eleni Zika.
Stuart Hogarth (researcher)
•
EuroGentest:
Joerg Schmidtke,
Ulf Kristoffersson.
Frauke Becker (researcher)
•
Experts:
Workshop 'Clinical validity and utility
of genetic susceptibility testing in
common disorders' in Seville, October
8-10 2007 & input to the
Background Document and/or
Recommendations a.o:
Jacques Beckmann, Linda Bradley,
Angela Brand, Arnold Christianson,
Björn Dahlbäck, Wybo Dondorp, Karl
Freese, Alberto Gutierrez, Gunnar
Houge, Tony Holtzman, Michael
Hopkins, Alastair Kent, Mari-Lise
Migueres, Irmgard Nippert, KlausPeter Lesch, Jan Mous, Gert-Jan van
Ommen, Aurélien Perez, Dragica
Radojkovic, Beverly Searle, Barbara
Starfield, Birgit Verbeure, Dirk
Stemerding and the PHG Foundation
Process ….
• Meeting Seville 2007 PPPC, IPTS, EuroGentest
• Draft Background Document
• Expert working group on genetic
epidemiology Amsterdam 2008
• Draft Background Document and PPPC Recommendations
posted on the web 2009
• Incorporation of comments
• Approval by PPPC and Board ESHG
• Publication Background Document & Recommendations 2011
Statement
Process ….
• Building on earlier work of P. Borry et al for
EUROGENTEST
• January 2010. First draft P. Borry, C. Patch and M.
Cornel
• March 2010. Inclusion comments PPPC members
• April - May 2010. Consultation members ESHG
and external review
• 4 June 2010: revised version to ESHG Board
• 12 June 2010: Approved by ESHG Board
Genetic testing and common disorders
Common complex disorders
• Common diseases: frequently encountered in
health care
• Complex disease: diseases with variable etiology,
including multifactorial etiology as well as
monogenetic subsets
Spectrum from ‘strictly’ genetic to multifactorial diseases
Genetically determined
highly penetrant
Monogenic subtypes
Genetic load
Incompletely penetrant
Polygenic
Multifactorial
Environmental
Environmental effect
Modified from Bomprezzi et al, 2003
Genetic testing and common disorders
• Translation of research findings:
“There is hardly any effect on improving
diagnosis and prognosis, treatment and
prevention, such as lifestyle interventions or
effective therapies concerning common
complex disorders on the basis of these newly
established associations. Translation of
research findings on genes with low predictive
value into health-care practices (…) is
problematic.”
Does it improve health care?
Are effective interventions available?
Genetic testing and common disorders
Analytic validity:
• Assessment
ACCE model
Does the test accurately
measure the genotype (genetic
variant)
Clinical validity
Does the test accurately
measure the phenotype
(disorder)
Clinical utility
What are the health outcomes
associated with testing?
Ethical, legal and social aspects
Genetic testing and common disorders
• Priorities
“When considering implementation in health care,
priority should be given to genetic tests for
common complex diseases of proven clinical
utility and cost effectiveness.”
Long QT syndrome
Guidelines in cardiogenetics
www.youtube.com/watch?v=52RJWyjogY0&feature=related
www.youtube.com/watch?v=DU_i0ZzIV5U&feature=related
Family history and DNA in public health?
Extend programs aiming to diagnose monogenic
subtypes (cascadescreening FH)?
•HNPCC
•FAP
•BRCA
•HCM
•LQTS
•ARVD
•MODY
•hemochromatosis
Prediction
• Monogenic conditions
• Monogenic subtypes of complex disorders
• Multifactorial disorders
Janssens It J Publ Health 2006
How to recognize monogenic subtype?
• Different pattern
– No hypertension, obesity, smoking, age>60
– NB one-size-fits-all vs. personalized medicine
• Lower age
• Multiple locations cancer
• Multiple members of a family
• NB start asking! DNA test comes in later.
Genetic testing and common disorders
• Role for clinical geneticists in health care
• Counselling in relation to testing for common complex
disorders
• Genetic literacy of health-care professionals should be
considerably improved
• High quality information on genetic testing for common
disorders should be readibly available to the public at large
• Developing countries
DTC genetic testing for health-related purposes
• Pre-test information and genetic counseling
• Informed consent
• Genetic testing in minors
• Respect for private life
• Research
• Oversight of genetic testing
• Impact on the healthcare system
Conclusion: hope & hype
• Some genetic tests with clinical utility need
translation from bench to bedside
(implementation; monogenic subtypes)
• Not all tests that are available today have
proven clinical utility (hype)
• Education, discussion, debate,
recommendations to guide professional
policy