Martina C Cornel Professor of Community Genetics VU University Medical Center

1. MAG-CMSB introduction &Pros and cons of genetic screening in Dutch policy making in the last decades7th Novembre 2008 Martina C Cornel Professor of Community Genetics VU University Medical Center Clinical Genetics/EMGO Institute Amsterdam, The Netherlands

2. We in the USA, both health providers and members of the public, are not applying what we know. Lenfant 2003

3. Translation needed • 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

4. Expectations (from 2004 presentation) “Genomics research will dramatically accelerate the development of new strategies for the diagnosis, prevention and treatment of disease, not just for single-gene disorders but for the host of more common complex diseases, e.g. cardiovascular disease…” Collins FS, NEJM 1999;341:28-37.

5. September 2007(from 2004 presentation) • Genomics researchers identify a variant of the Z-gene, that appears to be an important risk factor for obesity, diabetes mellitus and cardiovascular anomalies. • Pathway (metabolomics) suggests an existing drug (Y) might be useful. • Nature Genetics, Science October 2007 • Frontpage NRC, Volkskrant, Telegraaf

6. Societal aspects(from 2004 presentation) • Epidemiology • How frequent in NL; how strong association; what is population attributable fraction • Ethical, legal, psychological, social issues • Do inhabitants NL understand that life expectancy can improve if they participate in genetic screening? Risk perception, risk communication • Implementation & care research • Implementation by public health service? Uptake? Compliance? Insurance?

7. Societal aspects- MAG-CMSB agenda - • Reshaping genetic screening criteria in the age of genomics – contemporary history & users perspective (Cornel & Pieters) • Three projects on genetic predisposition for overweight/diabetes/cardiovascular disease and risk perception/motivation for interventions

8. Societal aspects- MAG-CMSB agenda - • Parents perceptions towards overweight of their children. Perceived role of genetic susceptibility and health risks Detmar TNO-PG-Leiden • Do low-educated patients with familial hypertension, diabetes or overweight have fatalistic beliefs about the effectiveness of preventive behaviour? Janssens, Erasmus MC, Rotterdam • Using family history as a tool to increase risk awareness and to motivate preventive behaviour of individuals at risk for diabetes type 2. Henneman, VUmc, Amsterdam

10. 2008-2012: MAG → CSG

11. 2008-2012: MAG → CSG

12. 2008-2012: MAG → CSG

13. 2008-2012: magCMSB → CSG • Knowledge from bench to bedside • Translation to policy makers • Is it allowed? Legal restrictions • Translation to health care settings • Tailored intervention strategies • ELSI issues in multifactorial testing • DTC; clinical utility may be low • Information to public (www.watisgenomics.nl) • Training of primary health care workers

14. 2008-2012: MAG → CSG Translation is co-evolution Achterbergh et al. Health Policy 2007; 83: 277-286.

15. 2008-2012: MAG → CSG CSG agenda

16. Part 2: screening Pros and cons of genetic screening in Dutch policy making in the last decades • Dutch publications on history & current opinions of citizens • Input in debates Health Council, FBG.. • Screening: between hope and hype 2008 • Some results forthcoming

17. Reshaping screening criteria • Goal • Treatment and prevention • Reproductive choice (informed decision making) • Confusion of tongues • Population screening • Offer to all • Treatment available • Citizens want autonomous choice for some untreatable conditions • Obligation to protect

18. Screening in NL • Screening criteria • Time frame: 1970s: neonatal screening 1980s: prenatal screening 1990s: regulation 2000>: new directions - Recent developments

19. Wilson & Jungner criteria 1968 WHO Disease -Important health problem -Latent or early symptomatic stage -Natural course must be understood Test Treatment -Suitable test - Accepted treatment -Acceptable test - Facilities diagnosis and -Case finding continuing process treatment Cost -Cost balanced in relation to health care (Categories Crossroads ’99)

20. New issues in the age of genomics Wilson & Jungner criteria 1968: • For early detection of existing disease • Pre dating prenatal testing and ‘boom’ in genetics Aim screening: treatment and prevention Additional issues in the age of Genomics: • Prenatal screening and testing (abortion) • Carriers, familial aspects • Concern about social and psychological aspects: • Privacy, stigma, insurance, counseling, informed consent • Genetic risk or susceptibility in case of multifactorial diseases Aim screening: treatment and prevention, reproductive options risk reduction options (life style, medication)

21. 1970s: Neonatal screening 1974 newborn screening Phenylketonuria PKU, voluntary (1981 Congenital Hypothyroidism) (2002 Congenital Adrenal Hyperplasia) (2007 package 17 disorders )

22. 1970s: Developing standards clinical genetics • Health Council Genetic Counseling 1977 • Ethics of Genetic Counseling 1980 • Manifesto of emerging medical specialty • Crucial role ‘geneticist’ Hans Galjaard • First genetic screening criteria by Health Council • (Privacy, stigma, insurance, autonomy, • informed consent,emotions, carriers and • family members)

23. 1980s: Prenatal screening Intense attention media and public for genetics & policy a.o. -1987 Documentary Series ‘Better Than God’ Will we create a society without handicapped people ? -1987 Department of Health report ‘Prevention of Congenital Anomalies’ -1988 Health Council Report on Neural Tube Defects

24. 1980s: Prenatal screening Intense attention media and public for genetics & policy a.o. -1987 Documentary Series ‘Better Than God’ Will we create a society without handicapped people ? -1987 Department of Health report ‘Prevention of Congenital Anomalies’ -1988 Health Council Report on Neural Tube Defects

25. 1987 Department of Health report ‘Prevention of Congenital Anomalies’ • Genetic counseling/advice under the heading of prevention, ‘will help minimize morbidity and mortality, just as rubella vaccination’ abortion mentioned as secondary prevention • Clinical genetic centers facilitate ‘responsible/justified parenthood’ in the transmission of hereditary disorders • Individual choice stressed, yet societal cost and burden are mentioned ‘in optimizing outcome reproductive behavior’

26. Criticism • Suspicion ‘eugenic population policy’ • Government no role in reproductive choices • ‘Optimizing reproductive behavior’ no task clinical geneticist • Prevention handicaps can be effect but is not goal of genetic counseling Goal is to inform and support • Rights and respect for handicapped people Impression: government stimulates genetic services to improve health and reduce costs health care through abortion Would parents be free not to test? Fear for pressure from government and society.

27. Explaining good intentions Dutch Parliament, The Hague May 1988 State Secretary of Health: ‘The birth of a handicapped child will never be regarded as a case of failed prevention.’ (photo site Chris Schram)

28. 1988 Screening Neural Tube Defects -1988 Health Council: pilot serum screening for neural tube defects (not unanimous) -1989 rejected, based on Wilson and Jungner criteria: -bad test characteristics (false positives, negatives) iatrogenic abortions through testing -no treatment available (abortion is no treatment) -medicalization natural childbirth, unacceptable for population Broad coalition against screening: a.o. christian democrats, ethical left-wing politicians No niche: obstetricians divided; prenatal care in hands of midwives (low tech) Opposition Galjaard: threat reputation clinical genetics

29. Consequences discussions 1980s 1: More precise and cautious terminology: - Prenatal screening and abortion: not under heading of prevention - attention rights and facilities handicapped people, choice not to test real option See: 1989 Report Health Council ‘Heredity: science and society’ 1994 Report Health Council ‘Genetic Screening’ Role of government: - Government careful/restrained regarding policy for reproductive issues

30. Consequences discussions 1980s 2: • Screening Population Act (WBO) <<1996 ‘traditional’ treatability stressed Screening for a disorder for which no treatment is available needs licensing. License given only in special circumstances. Treatability cornerstone of Dutch screening policy

31. Line of reasoning Population screening } Domain of Prevention: including genetic screening treatment available Reproductive options } Not in Domain of Prevention no treatment available No treatment? No screening! No population screening for reproductive options In the Netherlands no serum screening or NT until 2005

32. What about new issues age of genomics? Health Council 1994 Report ‘Genetic screening’ Revision screening criteria: ‘Treatment’ adapted to ‘options/ courses of action/interventions’ (reproductive choices, life style) Tension with legal framework (Population Screening Act)!

33. Note: dealing with tension Amniocentesis for women of 36+ years Initially not as a population screening programme, but medical indication (age). Reproductive options in domain of clinical genetics and individual doctor-patient relationships in obstetrics. Policy to redefine as screening programme: Licence special circumstance: it is already happening, serum screening also allowed for 36+

34. 2000> New developments -Change in public attitudes, reflected in Parliament, demand for testing -New and better technologies prenatal screening -New technologies problematise separation treatable-untreatable (MS/MS) (fetal anomaly scan) -International benchmarking? Globalization

35. Prenatal screening: Health Council versus Department of Health 2001: Health Council advises to abolish age limit screening (triple test 2nd trimester Down’s & NTDs) 2003: Department of Health age limit continued (screening only after 35+) DISCUSSION SOCIETY & PARLIAMENT 2004: Health Council avises again to offer screening to all pregnant women (blood test and NT 1st trim. for Down’s; NTDs ultrasound 2nd trim.) 2004: Department of Health age limit continued, but inform all pregnant women about prenatal screening (not: offer screening), no reimbursement 2006: Second trimester fetal anomaly scan for all pregnant women at 20 weeks

36. Conclusion Treatability criterion essential for Dutch policy Screening limited to treatable disorders Focus on protection Continued restraint in governmental policy for reproductive options Originating in the 1980s Technology and public attitudes call for new policy: Isolating screening in domain of prevention & treatment problematized by new technological developments (genomics, imaging techniques: anomaly scan/mid-pregnancy ultrasound scan, total body scan). Protection versus autonomy : ‘paternalistic’ policy versus informed public, ‘consumer genomics’

37. New directions Health Council Report 2008 ‘Screening between hope and hype’: • Autonomy acknowledged, yet protection more important than free choice, stress on treatability continued, esp. for programs funded collectively • Suggestion to form Dutch National Screening Committee to safeguard quality and inform public about quality

38. New directions Ministry of Health july 2008 “Kaderbrief screening” • Autonomy vs protection • Autonomy as guiding principle ⇨To be continued