Transcript Document

The View from Europe
Professor Helen Dolk
EUROCAT Project Leader
EUROCAT Central Registry, University of Ulster
Annual BINOCAR Meeting, Swansea
Cotober 2014
NORWAY
Map of EUROCAT Full and
Associate Member Registries
UNITED KINGDOM
Wessex
Thames Valley
E Mid & S York
Northern England
South West England
Wales
DENMARK
Odense
GERMANY
Saxony-Anhalt
Mainz
POLAND
Wielkopolska
IRELAND
Dublin
South East Ireland
Cork & Kerry
UKRAINE
BELGIUM
Antwerp
Hainaut-Namur
Associate Member
CZECH
REPUBLIC
FRANCE
Paris
Strasbourg
Rhone-Alps
Ile de la Reunion
French West Indies
HUNGARY
AUSTRIA
Styria
Size of Circle
< 10,000 births per year
10,000 - 40,000 births per year
>40,000 births per year
FINLAND
NETHERLANDS
Northern Netherlands
Central Registry
Belfast
Full Member
SWEDEN
CROATIA
Zagreb
PORTUGAL
South Portugal
SWITZERLAND
Vaud
SPAIN
Basque Country
Valencia Region
Spain Hospital
Network
ITALY
Emilia Romagna
Tuscany
MALTA
Why European Collaboration?
•
Pooling of data
•
Comparison of data between registries/countries
•
Sharing of expertise
•
Joint approach to European public health questions
•
Sharing of resources (e.g. website, software)
History of EUROCAT
•
Conceived in 1974, at a
Workshop convened by the
European Economic Community's
Committee on Medicinal and
Public Health Research to
improve "the methodology of
population studies throughout the
Community". Congenital
anomalies chosen as first topic for
concerted action.
•
EUROCAT established in 1979 as
a prototype for European health
surveillance aiming to assess the
feasibility of pooling data across
national boundaries, in terms of
standardization of definitions,
diagnosis and terminology and
confidentiality. Central Registry in
Department of Epidemiology,
Catholic University of Louvain,
Brussels.
• Michel Lechat 1927-2014
Co-founder of EUROCAT with
Josephine Weatherall
Timeline 1979-2014 and beyond
Continued:
•Population-based registries
•Central Database and standard dataset
Creation
•
1991 transfers from “Research” to
“Health Information”. Central Registry
at Scientific Institute for Public Health,
Brussels. Central Registry moved
briefly to LSHTM, UK in 1999.
•
2000-2014 - Funded by EU DSanco as
Rare Diseases activity, Central
Registry at University of Ulster
•
2015 Central Registry will move to
Joint Research Centre at ISPRA, Italy,
under the EU Rare Diseases Platform.
•Expansion in Europe and Associate Members
•Paper to electronic data
Expansion
•EDMP software & electronic transmission
•Website dissemination
•Data Quality Indicators
•Statistical Monitoring
Systems
development •Use of data for Research
Institutional
sustainability
•Separation of central functions and research?
•Integration with other European institutions,
systems and databases?
•Member State support?
What is a disease registry and is
there an ideal size?
The bringing together of sources of expertise (people) and sources of
data to shed light on a disease in relation to its prevalence,
causes/prevention and care/services in a specified population
-
expertise: different clinical areas, epidemiology, statistics, public health,
specific exposure assessment fields ……….. and the expertise of those
personally affected
-
data sources
- Electronic data sources present increasing opportunities, but also
challenges, across Europe
- Registry = validated data
Regional (up to 40,000 births), national networking, European
networking
Types of surveillance based on CA
registries
• Statistical Monitoring (without prior hypothesis)
– Recent Clusters in time
– Trends in time, geographical differences
• Response to exposure incidents/health threats/disasters
– Chernobyl
– Swine Flu/H1NI
• Surveillance oriented to identifying environmental causes (with
different levels of prior hypothesis)
– Pharmacovigilance
– Envirovigilance
• Surveillance oriented to evaluating primary prevention
– NTD prevalence and prevention by periconceptional folic acid
• Surveillance oriented to health service needs and evaluation
– Prenatal screening and diagnosis, TOPFA, mortality rates
– Children needing services
Antiepileptic studies
Literature review for
signals
.
Test signals in Casemalformed control design
for specificity
3.9 million births, 19952005
19 registries: pooling
Including TOPFA
Exposure data collected
mainly prospectively in
pregnancy
Epilepsy: 3 per 1,000
women, now AEDs used
for other indications
To develop a European reproductive pharmacovigilance system
•
•
•
To develop and test an efficient and cost-effective system for safety evaluation of drugs
during pregnancy, based on EUROCAT registries combined with existing healthcare
databases
– Signal detection and signal evaluation
– Registry Linkage to prescription databases, exposed cohorts, population databases
– Designs: case-malformed control, cohort
To quantify the risk of congenital anomalies related to four drug classes:
– new antiepileptics,
– insulin analogues,
– anti-asthmatics,
– Antidepressants (SSRIs)
To develop a framework for evaluation of the efficacy of pregnancy-related drug safety
measures including
– drug utilisation studies
– monitoring the effectiveness of pregnancy prevention programmes (e.g. isotretinoin)
– a scoping study of the role of internet access to
drugs and related safety information by pregnant women
Antidepressant (SSRI) exposure in early
pregnancy
•
Aims: To examine the specificity of association between specific SSRIs and specific congenital
anomalies
•
Case-malformed control study
•
Population: 12 EUROCAT registries , 1995-2009, 3.3 million births
•
SSRI exposure among registrations 0.8%
•
Cases: CHD, CHD subtypes, and other CA “signals” from the literature
•
Controls: other CA (excl genetic syndromes)
•
EUROCAT study Results:
• Severe CHD OR 1.56 (1.03-2.38)
• OR>2 for anorectal atresia&stenosis, gastroschisis, renal dysplasia, clubfoot
• Risks similar for all types of SSRI
•
Interpretation: non-specific SSRI teratogenic effect? depression? Susceptibility to
depression? Lifestyle confounders? Or more than one of these.
•
EUROmediCAT: updating data to 2012, prescription data linkage where available,
population cohort in 3 countries, drug utilisation study
Types of surveillance based on CA
registries
• Statistical Monitoring (without prior hypothesis)
– Recent Clusters in time/ clusters in space
– Trends in time, geographical differences
• Response to exposure incidents/health threats/disasters
– Chernobyl
– Swine Flu/H1NI
• Surveillance oriented to identifying environmental causes (with
different levels of hypothesis)
– Pharmacovigilance
– Envirovigilance
• Surveillance oriented to evaluating primary prevention
– NTD prevalence and prevention by periconceptional folic acid
• Surveillance oriented to health service needs and evaluation
– Prenatal screening and diagnosis, TOPFA, mortality rates
– Children needing services
Has periconceptional folic acid supplementation in
Europe prevented neural tube defects?
Prevalence per 10,000 births of Neural Tube Defects, for All Full
Member Registries, from 1991 – 2010
*Still births and Fetal Deaths from 20 weeks gestation
*
Primary Prevention of Congenital
Anomalies
•
•
•
EUROCAT in collaboration with EUROPLAN have developed recommendations
on policies to be considered for the primary prevention of congenital anomalies in
National Plans (and Strategies) on Rare Diseases
– EUCERD approval
– J Public Health Genomics 2014, Taruscio et al.
In the field of:
– Medicinal drugs
– Food/nutrition and lifestyle (e.g. folic acid, obesity, smoking, alcohol)
– Health Services (e.g. vaccination, women with chronic diseases, genetic
counselling)
– Environmental pollution incl. the workplace
Mechanisms:
– Preconceptional care – high vs low risk parents
– Health promotion to future parents and awareness raising: major health
determinants + pregnancy specific issues
– Public health approaches: vaccination, food fortification
– Regulatory policies (pharmaceutical, food, environmental, tobacco, alcohol)
– Research and surveillance (CA and exposure), and expert review
Key Public Health
Indicators for CA
2008-2012:
where is the UK?
EUROCAT
UK
Ukraine
Switzerland
Spain
Portugal
Poland
Norway
Netherlands
Malta
Italy
Ireland
Hungary
Germany
France
Denmark
Croatia
Belgium
Austria
Rate per 1,000 births
Perinatal Mortality due to CA
By Country 2008-2012
4
3.5
3
2.5
2
1st week deaths
1.5
Fetal deaths
1
0.5
0
Prevalence of Prenatally Diagnosed CA
By Country 2008-2012
40
35
Rate per 1,000 births
30
25
20
Diag n/k
Not PD
15
PD non-chromo
PD chromo
10
5
0
Termination of Pregnancy for Fetal Anomaly
By Country 2008-2012
9
8
Rate per 1,000 births
7
6
5
4
Non-chromo
Chromosomal
3
2
1
0
EUROCAT
UK
Ukraine
Switzerland
Spain
Portugal
Poland
Norway
Netherlands
Malta
Italy
Ireland
Hungary
Germany
France
Denmark
Croatia
Belgium
Austria
Rate per 1,000 births
Down Syndrome By Country 2008-2012
(9% of all CA)
4
3.5
3
2.5
2
TOPFA
Fetal death
1.5
Live birth
1
0.5
0
Proportion of all births to mothers 35
years and older, 1990-99,2000-9.
35.0
% mothers 35+ years
30.0
25.0
20.0
15.0
1990-99
10.0
2000-09
5.0
0.0
See Loane et al European Journal of Human Genetics 2013: Twenty-year trends in the prevalence of Down
syndrome and other trisomies in Europe: impact of maternal age and prenatal screening.
EUROCAT
UK
Ukraine
Switzerland
Spain
Portugal
Poland
Norway
Netherlands
Malta
Italy
Ireland
Hungary
Germany
France
Denmark
Croatia
Belgium
Austria
Rate per 1,000 births
Neural Tube Defects By Country 2008-2012
(3.6% of all CA)
4
3.5
3
2.5
2
TOPFA
1.5
Fetal death
Livebirth
1
0.5
0
Conclusions - 1
• Why European?
– To pool, compare, and share people & resources
• Why CA Surveillance?
– For prevention and care
• Why registers?
– To bring the people (expertise of many kinds)
together with the data
– TOPFA coverage essential
Conclusions - 2
– Why are not having more success preventing CA?
• TOPFA are preventable too
• Expectations
• Preconceptional and interconceptional interventions
– Emerging issues:
• Obesity and diabetes
• Asthmatics/asthma and antidepressants/depression
• Internet availability of teratogenic drugs
EUROCAT Registry Leaders
Prof. Martin Haeusler (Styria, Austria)
Dr. Vera Nelen (Antwerp, Belgium)
Prof. Christine Verellin-Dumoulin (Hainut, Belgium)
Prof. Ingeborg Barisic (Zagreb, Croatia)
Dr. Antonin Sipek (Czech Republic)
Dr. Ester Garne (Odense, Denmark)
Dr. Annukka Ritvanen (Finland)
Dr. Babak Khoshood (Paris, France)
Dr Bruno Schaub (French West Indies, France)
Dr Hanitra Randrianaivo (Reunion, France)
Dr. Annette Queisser-Luft (Mainz, Germany)
Dr. Anke Rissmann (Saxony Anhalt, Germany)
Dr. Judit Beres (Hungary)
Dr. Robert McDonnell (Dublin, Ireland)
Dr. Carmel Mullaney (SE Ireland)
Dr. Mary O’Mahoney (Cork and Kerry, Ireland)
Dr. Gioacchino Scarano (Campania, Italy)
Prof. Elisa Calzolari (Emilia Romagna, Italy)
Dr. Fabrizio Bianchi (Tuscany, Italy)
Dr. Miriam Gatt (Malta)
Dr. Ieve Grinfelde and Dr. Ivea Cirule (Latvia)
Dr. Marian Bakker (N Netherlands)
Prof. Marta Ebbing (Norway)
Prof. Anna Latos-Bielenska (Wielkopolska, Poland)
Dr. Carlos Matias Dias (S Portugal)
Dr Gorazd Rudolf (Slovenia)
Dr. Larraitz Arriola (Basque Country, Spain)
Prof. Maria-Luisa Martinez Frias (Spain Hospital Network)
Dr. Oscar Zurriaga (Valencia, Spain)
Dr Karin Kallen (Sweden)
Dr. Marie-Claude Addor (Switzerland)
Prof. Liz Draper (EMYSCAR, UK)
Prof. Judith Rankin (N England, UK)
Dr. Rosie Thompson (SW England, UK)
Dr. Catherine Rounding (Thames Valley, UK)
Mr David Tucker (Wales)
Dr. Diana Wellesley (Wessex, UK)
Prof Joan Morris (UK)
Dr Wladimir Wertelecki (Ukraine)
EUROCAT Central Registry (University of Ulster, UK)
Prof. Helen Dolk
Ms Maria Loane
Mrs Ruth Greenlees
Mrs Barbara Norton
Dr. Nichola McCullough
Dr. Breidge Boyle
Mrs Barbra Webber
Dr. Rhonda Curran
Percentage of births in population
covered by EUROCAT registries 2011
(should it be 100%? – quality vs quantity)
Austria (1F)
Belgium (2F)
Croatia (1F)
Czech Republic (1A)
Denmark (1F)
Germany (2F)
Ireland (3F)
Spain (2F, 1A)
Finland (1A)
France (3F, 1A)
Hungary (1F)
Italy (2F)
Malta (1F)
Netherlands (1F)
Norway (1F)
Poland (1F, 1A)
13%
27%
20%
100%
8%
3%
62%
34%
100%
14%
100%
14%
100%
10%
100%
100%
Portugal (1F)
Sweden (1A)
Switzerland (1F)
United Kingdom (6F)
19%
100%
10%
32%
Affilliates and applicants
Bulgaria
Cyprus
Greenland
Latvia
Moldova
Slovenia
EU countries not covered
Estonia, Greece, Lithuania,
Luxembourg, Romania, Slovakia
Styria, Austria
EUROCAT
Wessex, UK
Wales, UK
Thames Valley, UK
S W England, UK
N England, UK
E Mids & S Yorks, UK
Ukraine
Vaud, Switzerland
Valencia Region, Spain
Basque Country, Spain
S Portugal
Wielkopolska, Poland
Norway
N Netherlands
Malta
Tuscany, Italy
Emilia Romagna, Italy
S E Ireland
Dublin, Ireland
Cork and Kerry, Ireland
Hungary
Saxony Anhalt, Germany
Mainz, Germany
Paris, France
Isle de la Reunion, France
French W Indies, France
Odense, Denmark
Zagreb, Croatia
Hainaut, Belgium
Antwerp, Belgium
Rate per 1,000 births
Perinatal Mortality By Registry 2008-2012
4
3.5
3
2.5
2
1.5
1st week deaths
1
Fetal deaths
0.5
0
Styria, Austria
Antwerp, Belgium
Hainaut, Belgium
Zagreb, Croatia
Odense, Denmark
French W Indies, France
Isle de la Reunion, France
Paris, France
Mainz, Germany
Saxony Anhalt, Germany
Hungary
Cork and Kerry, Ireland
Dublin, Ireland
S E Ireland
Emilia Romagna, Italy
Tuscany, Italy
Malta
N Netherlands
Norway
Wielkopolska, Poland
S Portugal
Basque Country, Spain
Valencia Region, Spain
Vaud, Switzerland
Ukraine
E Mids & S Yorks, UK
N England, UK
S W England, UK
Thames Valley, UK
Wales, UK
Wessex, UK
EUROCAT
Rate per 1,000 births
Termination of Pregnancy for Fetal Anomaly
By Registry 2008-2012
12
10
8
6
4
Non-chromo
Chromosomal
2
0
Styria, Austria
EUROCAT
Wessex, UK
Wales, UK
Thames Valley, UK
S W England, UK
N England, UK
E Mids & S Yorks, UK
Ukraine
Vaud, Switzerland
Valencia Region, Spain
Basque Country, Spain
S Portugal
Wielkopolska, Poland
Norway
N Netherlands
Malta
Tuscany, Italy
Emilia Romagna, Italy
S E Ireland
Dublin, Ireland
Cork and Kerry, Ireland
Hungary
Saxony Anhalt, Germany
Mainz, Germany
Paris, France
Isle de la Reunion, France
French W Indies, France
Odense, Denmark
Zagreb, Croatia
Hainaut, Belgium
Antwerp, Belgium
Rate per 1,000 births
Prenatal Diagnosis By Registry 2008-2012
50
45
40
35
30
25
20
Diag n/k
15
Not PD
PD non-chromo
10
PD chromo
5
0
EUROCAT
Wessex, UK
Wales, UK
Thames Valley, UK
S W England, UK
N England, UK
E Mids & S Yorks, UK
Ukraine
Vaud, Switzerland
Valencia Region, Spain
Basque Country, Spain
S Portugal
Wielkopolska, Poland
Norway
N Netherlands
Malta
Tuscany, Italy
Emilia Romagna, Italy
S E Ireland
Dublin, Ireland
Cork and Kerry, Ireland
Hungary
Saxony Anhalt, Germany
Mainz, Germany
Paris, France
Isle de la Reunion, France
French W Indies, France
Odense, Denmark
Zagreb, Croatia
Hainaut, Belgium
Antwerp, Belgium
Styria, Austria
Rate per 1,000 births
Down Syndrome By Registry 2008-2012
5
4.5
4
3.5
3
2.5
2
TOPFA
1.5
Fetal death
1
Live birth
0.5
0
EUROCAT
Wessex, UK
Wales, UK
Thames Valley, UK
S W England, UK
N England, UK
E Mids & S Yorks, UK
Ukraine
Vaud, Switzerland
Valencia Region, Spain
Basque Country, Spain
S Portugal
Wielkopolska, Poland
Norway
N Netherlands
Malta
Tuscany, Italy
Emilia Romagna, Italy
S E Ireland
Dublin, Ireland
Cork and Kerry, Ireland
Hungary
Saxony Anhalt, Germany
Mainz, Germany
Paris, France
Isle de la Reunion, France
French W Indies, France
Odense, Denmark
Zagreb, Croatia
Hainaut, Belgium
Antwerp, Belgium
Styria, Austria
Rate per 1,000 births
Anomalies Typically Requiring Surgery By
Registry 2008-2012 (Excluding
Chromosomal Cases)
8
7
6
5
4
3
TOPFA
Fetal death
2
Livebirth
1
0
Styria, Austria
EUROCAT
Wessex, UK
Wales, UK
Thames Valley, UK
S W England, UK
N England, UK
E Mids & S Yorks, UK
Ukraine
Vaud, Switzerland
Valencia Region, Spain
Basque Country, Spain
S Portugal
Wielkopolska, Poland
Norway
N Netherlands
Malta
Tuscany, Italy
Emilia Romagna, Italy
S E Ireland
Dublin, Ireland
Cork and Kerry, Ireland
Hungary
Saxony Anhalt, Germany
Mainz, Germany
Paris, France
Isle de la Reunion, France
French W Indies, France
Odense, Denmark
Zagreb, Croatia
Hainaut, Belgium
Antwerp, Belgium
Rate per 1,000 births
Neural Tube Defects By Registry 2008-2012
2.5
2
1.5
1
TOPFA
Fetal death
Livebirth
0.5
0
Types of surveillance based on CA
registries
• Statistical Monitoring (without prior hypothesis)
– Recent Clusters in time
– Trends in time, geographical differences
Cluster output: Scan method
Cluster detection for the period 2007-2013 by year: no. EUROCAT
registries included in monitoring and their population coverage,
number of tests conducted and clusters detected, and results of
cluster investigations.
2007
2008
2009
2010
2011
2012
2013
Total 2007-2013
10
11
10
16
16
17
18
-
234,31
7
11,891
226,01
1
10,687
272,97
5
12,048
390,51
0
16,654
401,28
2
18,275
473,67
5
22,152
505,250
-
23,619
-
Congenital anomaly subgroups (n)
75
75
75
76
76
73
72
-
Tests performed (n)
482
500
487
766
805
882
901
4823
Cluster detection rate (%)
2.90%
3.40%
4.72%
3.92%
2.48%
3.06%
3.77%
3.42%
Total clusters detected (n)
14
17
23
30
20
27
34
165
New* clusters (n)
12
15
18
21†
16
24
20
126
Old* clusters (n)
2
2
4
4
3
3
7
25
Continuing* Cluster (n)
0
0
1
5
1
0
7
14
Investigation results (new clusters
only)
Cluster confirmed, no explanation
2
9
6
7
2
11
7
44 (34.9%)
Cluster due to data quality issues
3
3
5
6
2
6
10
34 (27.8%)
Cluster due to increasing prenatal
diagnosis
Heterogeneous anomalies in cluster
0
0
2
1
7
0
0
10 (7.9%)
4
3
2
3
5
6
3
26 (20.6%)
No investigation
3
0
3
4
0
1
0
11 (8.7%)
Registries (n)
Annual population covered (no.
births)
Cases of Congenital Anomaly (n)
Anomalies Typically Requiring Surgery By
Country 2008-2012 (Excl Chrom)
20% of all CA, half of all cases needing surgery
9
8
6
5
TOPFA
4
Fetal death
Livebirth
3
2
1
EUROCAT
UK
Ukraine
Switzerland
Spain
Portugal
Poland
Norway
Netherlands
Malta
Italy
Ireland
Hungary
Germany
France
Denmark
Croatia
Belgium
0
Austria
Rate per 1,000 births
7
Overview:2008-2012
Types of surveillance based on CA
registries
• Statistical Monitoring (without prior hypothesis)
– Recent Clusters in time
– Trends in time, geographical differences
• Response to exposure incidents/health threats/disasters
– Chernobyl
– Swine Flu/H1NI
Pandemic influenza studies
•
Time series study
– January 2007 – March 2011 conceptions
– 26,976 non-chromosomal congenital anomaly registrations from 10 European
countries
•
Exposure based on country-specific influenza season data from WHOEuroFlu influenza season tables
LMP
Conception
EUROCAT CA case delivery
Corresponding
CA-specific
Critical Period
A fortnight
Is added
Gestational age
is subtracted
Timeline