1. EMGO Institute for Health and Care Research Quality of Care Martina Cornel, MD, PhD Professor of community genetics & public health genomics On behalf of the Tender NBS team Governance of the European newborn screening systems. What framework for future EU newborn screening policies in the EU Community Genetics, Dept Clinical Genetics EURORDIS Amsterdam 14th May 2011

2. Introduction Survey –Who decides –Transparency

3. Neonatal screening (heelprick)

4. Neonatal screening NL 2006-2007 Biotinidase deficiency Cystic fibrosis (conditional; pilot 2008; start 2011) Galactosemia Glutaric aciduria type I HMG-CoA-lyase deficiency Holocarboxylase synthase deficiency Homocystinuria Isovaleric acidemia Long-chain hydroxyacyl CoA dehydrogenase deficiency Maple syrup urine disease MCAD deficiency 3-methylcrotonyl-CoA carboxylase deficiency Sickle cell disease Tyrosinemia type I Very-long-chain acylCoA dehydrogenase deficiency 2006 PKU (1974) Congenital hypothyroidism (1981) Congenital Adrenal Hyperplasia (2001) Medication or diet to avoid mental retardation or sudden death

5. Why more diseases? More treatment available –Early detection: less health damage More tests available (high throughput) –MS/MS Many more promises in the age of genomics: how to proceed?

6. Sir Muir Gray (Nat Scr Comm UK) All screening programmes do harm. Some do good as well and, of these, some do more good than harm at reasonable cost.

7. To screen or not to screen? How to balance pros and cons?

8. Screening criteria: W&J still apply! When to screen? –Wilson en Jungner WHO 1968. –A variety of sets of criteria derived from W&J Important public health problem (prevalence & severity) Is treatment available? Does early treatment help? Course of disease known; frequency known Good test (high sensitivitity; high specificity, high positive predictive value) Uniform treatment protocol; knowing whom to treat Etc

9. Screening criteria (Grosse, Public Health Genomics 2010) Evidence –Early treatment leads to less mortality, morbidity, loss of weight, days in hospital, pain, suffering, better QoL Economics –Limited health care resources; cost per QALY under limit Ethics –More pros (longer and healthier life) than cons (false positives; mild cases; incidental findings)

10. Introduction Survey –Who decides –Transparency

11. EU Tender “Evaluation of population newborn screening practices for rare disorders in Member States of the European Union” Deliver: –Report on the practices of NBS for rare disorders implemented in all Member States –Expert opinion document, including decision-making matrix, on the development of European policies in the field of newborn screening for rare diseases –EU Network of Experts on NBS (EUNENBS) –European Experts Consensus Workshop on NBS (June 2011)

12. European Commission decisions + actions Nov 11, 2008: adoption of Commission Communication nr 679 June 9, 2009: Council recommendation on a European Action in the field of Rare Diseases July 18, 2009: EAHC call for tender 2009/Health/09 concerning evaluation of population newborn screening practices for rare disorders in EU Member States

13. EU Tender, project group Luciano Vittozzi, Domenica Taruschio (ISS, Rome, Italy) –Project leader, logistics Martina Cornel, Tessel Rigter, Stephanie Weinreich (VUmc, Amsterdam, Netherlands) –Governance Gerard Loeber (RIVM, Bilthoven, Netherlands) –Screening (blood sampling, assays, reports, storage) Georg Hoffmann, Peter Burgard, Kathryn Rupp (Univ Heidelberg, Heidelberg, Germany) –Confirmatory diagnostics, treatment

14. EU Tender, action plan (2010) Set up surveys stratified to parts of the neonatal screening programme (2010) Compile lists of experts (DoH, laboratories, paediatricians) (2010-2011) Receive and evaluate results of survey Workshops (March 2010, Dec 2010) (2011) Draft documents sent out for comments (2011) Finalisation of documents (May-June) (2011) Consensus workshop (June)

16. Introduction Survey –Who decides –Transparency

17. Governance –Attunement between parties Achterbergh et al. Health Policy 2007; 83: 277-286. Andermann et al. Journal of Health Services Research & Policy 2010; 15: 90-97.

18. Attunement between parties Health regions –Society, medicine, industry, government Countries –Society, medicine, industry, government EU? –Some aspects of attunement are not country specific-> room for collaboration –Learn from others?

19. Governance 17 of 35 jurisdictions surveyed reported to have laws or regulations on newborn screening 18 have a body which oversees newborn screening (“steering committee”) 22 have changed NBS program in last 5 years –health authorities almost always involved physicians specialized in paediatrics and clinical chemistry in one case (Sweden) –health technology assessors sometimes –patient organisations sometimes

21. 22 jurisdictions (21 countries) expanded their neonatal screening programs in the last 5 years. In 8 of these 22 cases patient groups were involved in the decision to expand neonatal screening. Involvement of patient organisations in changes in NBS programs 2005-2010

22. Advocacy groups for screened disorders: 2010 22 jurisdictions 17have advocacy groups specific to screened disorders –started after NBS –existing before NBS 2 do not 3 unknown

23. NBS policy changes 2005 to 2010 Advocacy groups involved Advocacy groups not involved No policy changes in last 5 years or no indications Advocacy groups existing 2010 Belgium (Flanders) Bulgaria France Ireland Poland Romania Norway Belgium (French Community) Czech Republic Germany Netherlands Portugal Slovakia Spain Sweden UK Iceland Austria Estonia Finland Italy Latvia Lithuania Malta Slovenia Croatia Serbia Switzerland Advocacy groups not existing 2010 -Greece FYROM Cyprus Albania Advocacy groups existence unknown 2010 Hungary (item missing) Denmark Luxembourg -

24. Questions for further research When were the advocacy groups founded? Which countries chose not to involve already existing groups in the expansion of NBS? Are all screened conditions now covered by advocacy groups in all countries?

25. Evaluation -> decision?

26. Introduction Survey –Who decides –Transparency

27. Transparency: extend further? Reports of committees (HTA) –Review of literature –Expert hearings Pilot studies Lists of evaluation criteria –International recommendations; professional societies Decision of ministry in official statement

28. Transparency: information to parents Website in 19 out of 35 countries where anyone can get information about the newborn screening program 7 out of 35 of the responding jurisdictions do not actively inform prospective parents No country specifically informs prospective parents in the first or second trimester of the pregnancy 13 countries inform prospective parents only after birth at the time of blood sampling 12 out of 35 countries parents are informed at two or even three time points

29. Transparency: information to parents Material to support the first communication of the meaning of consequences of a positive NBS result is available in 41% of the countries. Predominantly the material is authored by local heads or directors (68%), but apparently applied on a national level (83%). Printed or digital material on treatment is available in 69% of the countries. Across all disorders printed or digital material is available in 69% of the countries. Authors predominantly are local heads or directors (61%).

30. Informed consent 20 of the 37 responding jurisdictions report to ask for informed consent (or dissent). 17 of them also have the possibility to opt-out. 17 of the 37 report that they do not ask informed consent (or dissent) from parents before the blood sampling –6 out of 17 report that they do have the possibility to opt-out from screening –7 said not to have informed consent (or dissent) nor to allow opting out

31. Fireworks disaster Enschede 13 mei 2000 Children amongst 23 victims Identification? Heelprick cards? -> discussion in media undermining trust

32. Research? In 15 out of 33 countries parents are informed about the fact that bloodspots are retained

33. Information on blood spot retention More than half of countries do not inform parents of blood spot retention This is an easy topic; information should be available in all countries Large variation in length of storage (1 y till >20 y) Striking number of countries with no defined length Variation within countries e.g. Spain and Italy Discussion is needed on storage

34. Conclusion Challenging field, fast changes in most EU countries Huge variety Not all patients with rare diseases profit from optimal NBS programs Collaboration needed –Training –Exchange of experiences, materials, etc Role for patients(organisations)!

35. Framework for future policies? Attunement in jurisdictions –Supported by HTA at EU level? Important health problem, treatment available, early treatment helps to prevent irreparable damage (assessment W&J criteria) –Horizon scanning at EU level to support decision making in member states? Learn from other EU memberstates –Training, translation of protocols, exchange?

36. Thanks !!!