1. On behalf of the Tender NBS team
Facing the challenge of extending newborn screening in Europe:
survey results
Graz
15 April 2011
Martina Cornel, MD, PhD
Professor of community genetics
& public health genomics
On behalf of the Tender NBS team
Community Genetics, Dept Clinical Genetics

2. Introduction
Survey
Diseases screened
Who decides
Transparency
How to contribute

3. Neonatal screening (heelprick)

4. Neonatal screening NL 2006-2007
PKU (1974)
Congenital hypothyroidism (1981)
Congenital Adrenal Hyperplasia (2001)
Medication or
diet to avoid
mental retardation or
sudden death
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

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
Decisions on screening build on the Wilson & Jungner framework, still the basis for the normative framework to assess population screening programmes, but they have been revised and made more specific.

9. Balancing pros and cons
Good test available?
False positives
Specificity (1-FP)
False negatives
Sensitivity (1-FN)
Positive predictive value
Disease→
Test
Result↓
Present
Absent
Positive A B
Negative C D
Some of the elements of “Wilson & Jungner” need to be made more explicit. Do we accept 5 false positives for 1 true positive? What is a “good test”?

10. 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)

11. Neonatal screening NL: disease categories
Considerable, irreparable damage can be prevented (category 1)
Add 14 diseases (biotinidase deficiency, galactosemia, glutaric aciduria type I, HMG-CoA lyase deficiency, holocarboxylase synthase deficiency, homocystinuria, isovaleric acidemia, longchain hydroxyacyl- CoA dehydrogenase deficiency, maple syrup urine disease, MCAD deficiency, 3-methylcrotonyl-CoA carboxylase deficiency, sickle cell disease, tyrosinemia type I and very-long-chain acyl-CoA dehydrogenase deficiency).
Less substantial or insufficient evidence of prevention of damage to health (category 2)
Consider adding cystic fibrosis if better test becomes available (improve specificity)
No prevention of damage to health (category 3)
An example of a transparent framework that came out of a Health Council committee on screening.

12. The role of the government (Health Council 2008)
Duty of care: ensure worthwhile screening
National population screening programme: provide facility itself
Available in basic healthcare package
Reproductive screening: special position: provide worthwhile options and guarantee both quality and informed decision making
Duty of protection against unsound screening
Guard citizens against health damage from risky or unsound forms of screening

13. Introduction
Survey
Diseases screened
Who decides
Transparency
How to contribute

14. 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)

15. 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

16. 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

17. EU Tender, action plan
(2010) Set up surveys stratified to parts of the neonatal screening programme
(2010) Compile lists of experts (DoH, laboratories, paediatricians)
( ) 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)

18. We covered modules A&B, which are on assesment and governance of NBS programs.
Scope of our workpackage:
- Data collection on current NBS policies
- Comparative analysis of current NBS strategies and policies
- Development of a decision tool

19. Austrian experts: Module A&B: Renate Fally-Kausek (Ministry of Health)
David Kasper (Medical University of Viena)
Bernhard Wieser (Inter-University Research Center (IFZ))
Module C&D:
Module E:
Barbara Plecko (Medical University Graz (Peadiatrics))
Klaus Kapelari (Endocrinological Center)

20. Introduction
Survey
Diseases screened
Who decides
Transparency
How to contribute

21. Phenylketonuria
Source: dr. G. Loeber, RIVM

22. Congenital Hypothyroidism
Source: dr. G. Loeber, RIVM

23. Congenital Adrenal Hyperplasia
Source: dr. G. Loeber, RIVM

24. Galactosemia
Source: dr. G. Loeber, RIVM

25. Cystic Fibrosis
Source: dr. G. Loeber, RIVM

26. Biotinidase deficiency
Source: dr. G. Loeber, RIVM

27. MS / MS (MCADD etc.)
Source: dr. G. Loeber, RIVM

28. Other conditions
Source:
dr. G. Loeber,
RIVM
DMD
SCD
G6PD
HCY

29. Screened conditions Large variation
Relatively few countries have started ms/ms analysis
Some countries test “all” ms/ms possibilities
Technology driven
Only report where health gain for infant

30. Introduction
Survey
Diseases screened
Who decides
Transparency
How to contribute

31. Governance Attunement between parties
Achterbergh et al. Health Policy 2007; 83:
Technology developed by Scientists; Organisation by physicians?; Demand from patients(organizations)?; Acceptability to be assessed by Regulatory, advisory and governmental agencies.
Many parties/ actors; potential for different views & priorities; how to attune?? Co-evolution, collective learing processes.
Andermann et al. Journal of Health Services Research & Policy 2010; 15:

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

33. 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”)
21 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

34. Laws

38. 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

39. 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

40. 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%).

41. 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

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

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

44. 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

45. 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

46. Comments to drafts (Dr. Wolfgang Sperl) potential member of EUNENBS
Introduction
Survey
Diseases screened
Who decides
Transparency
How to contribute
Comments to drafts (Dr. Wolfgang Sperl)
potential member of EUNENBS

47. Thanks !!!