Transcript Document

Extending neonatal screening
programmes building on
screening criteria
ESPKU conference
Liverpool, 20th Octobre 2012
Martina C Cornel
Professor of Community Genetics & Public Health Genomics
Amsterdam, The Netherlands
Screening:
Definition US Commission on Chronic Illness 1951:
The presumptive identification of unrecognized disease or
defect by the application of tests, examinations or other
procedures which can be applied rapidly. Screening tests
sort out apparently well persons who probably have a
disease from those who probably do not. A screening test
is not intended to be diagnostic. Persons with positive or
suspicious findings must be referred to their physicians
for diagnosis and necessary treatment.
Neonatal screening (heelprick)
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
mental retardation or
•
3-methylcrotonyl-CoA carboxylase deficiency
sudden death
•
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
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?
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
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.
Pros and cons need to be evaluated
• Live longer & healthier
• False positives
• Uncertainty
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
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)
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
The challenges of a screening programme
Tender NBS 2011
Neonatal screening in EU practice?
•
Which diseases?
•
Quality control?
•
Who decides?
Expert Opinion Document
•
Interest of the child should be central
Austria
Belgium (Flemish)
Belgium (French)
Bulgaria
Cyprus
Czech Republic
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Ireland
Italy
Latvia
Lithuania
Luxembourg
Malta
Netherlands
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Croatia
FYROM
Iceland
Turkey
Albania
Bosnia-Herzegovina
Kosovo
Montenegro
Serbia
Norway
Switzerland*
Number of disorders
in national screening programs
Diversity in EU
(Tender NBS)
40
30
20
10
0
ch
hpa
cah
msud
mcadd
cf
gaI
galt
iva
vlcadd
bio
hci
tyrI
lchadd
mmacbl
pa
cptI
cptII
asa
3mcc
gaII
hcsd
cud
citI
3hmg
s-s
arg
tyrII_III
btha
sc
hptI_III
bkt
scaddd
udp
citII
schadd
mma
Number of screening Countries
Number of screening countries per disorder
30
Frequency EU (28)
Frequency CC (4)
Frequency PCC (5)
20
10
0
Disorders
Tender NBS 2011
Neonatal screening in EU practice?
•
Which diseases?
•
Quality control?
•
Who decides?
Expert Opinion Document
•
Interest of the child should be central
Quality control in seven steps after result
Burgard 2012 JIMD
Tender NBS 2011
Neonatal screening in EU practice?
•
Which diseases?
•
Quality control?
•
Who decides?
Expert Opinion Document
•
Interest of the child should be central
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.
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
Involvement of patient organisations
in changes in NBS programs 2005-2010
• 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.
NBS policy changes 2005 to 2010
Advocacy
groups involved
Advocacy groups not
involved
No policy changes
in last 5 years or
no indications
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
-
Advocacy groups
existing 2010
Evaluation -> decision?
Tender NBS 2011
Neonatal screening in EU practice?
•
Which diseases?
•
Quality control?
•
Who decides?
Expert Opinion Document
•
Interest of the child should be central
Newborn screening in Europe: Expert Opinion document
• 70 opinions, including:
14. The decision whether a screening program
should be performed can be based on a
framework of screening criteria updated from the
traditional Wilson and Jungner criteria, relating to
disease, treatment, test and cost.
15. The interest of the child should be central in the
assessment of pros and cons.
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)!
Thanks !!!
Further reading
• Grosse SD, Rogowski WH, Ross LF, Cornel MC, Dondorp WJ, Khoury
MJ. Population Screening for Genetic Disorders in the 21st Century:
Evidence, Economics, and Ethics. Public Health Genomics
2010;13:106–115.
• Loeber JG, Burgard B, Cornel MC, Rigter T, Weinreich SS, Hoffmann
GF, Vittozzi L. Newborn screening programmes in Europe;
arguments and efforts regarding harmonization. Part 1 - From
Blood Spot to Screening Result. Journal of Inherited Metabolic
Disease 2012;35:603-11.
• Burgard P, Rupp K, Martin Lindner M, Haege G, Rigter T, Weinreich
SS, Loeber JG, Taruscio D, Vittozzi L, Cornel MC, Hoffmann GF.
Newborn screening programmes in Europe; arguments and efforts
regarding harmonization. Part 2 - From screening laboratory results
to treatment, and follow-up, and quality assurance. Journal of
Inherited Metabolic Disease 2012;35:613-25.
• EU Tender newborn screening practices:
http://www.iss.it/cnmr/prog/cont.php?id=1621&lang=1&tipo=64
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
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
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%).
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
Fireworks disaster Enschede 13 mei 2000
• Children amongst 23 victims
• Identification?
• Heelprick cards?
-> discussion in media undermining trust
Research?
• In 15 out of 33 countries parents are informed
about the fact that bloodspots are retained
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
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?
PKU phenylketonuria
Autosomal recessive
Without treatment severe mental retardation
Treatment: diet with limitation of phenylalanine
intake
20 per year in NL
Starting 1974 in NL