Download Lysbilde 1 - the Nordic Database for Rare Diseases (version2)

Raredis.eu
Nordic database for rare diseases
www.raredis.eu
Dr. Ketil Heimdal, Medical genetics, Oslo Norway,
Dr. Hanne Hove, Centre for Rare Diseases, Copenhagen,
Denmark (curator of RAREDIS)
Acknowledging: The Nordic working group
RAREDIS
• Raredis is a Nordic database
for rare diseases supported
by the Nordic Council of
Ministers & The Norwegian
Directorate of Health
• Today represented by Oslo
• Other participating centres:
Aarhus, Helsinki, Uppsala,
Gothenburg, and Reyjavik
Nordic database?
Population 24 million – suitable for
registries for rare diseases
Large European countries often
divided into regions of ~5 million
The Nordic countries have a similiar
social structure and health service
1: What are suitable aims for a Norwegian, a Nordic
and a European RD database?
2: What should be the flow of data between these
databases?
Raredis financing (1 euro=8 NOK)
• 2007/2008:
• 2009:
• 2011:
• 2012+:
DKK 500.000
DKK 300.000
NOK 500.000
Research project financing
The Nordic countries:
a paradise for
national medical
registers
• For three reasons:
• 1)The structure of the health
systems – National health
insurance covers all citizens
• 2)The existence of nationwide
registers
• 3)Systematic use of national
registration numbers
•National registration numbers
• unique to each citizen
• widespread use in society
Birth
Hospital
Discharge
Psychiatric
discharges
Primary
Health service
Drugs
National Reg
number
Abortion
Socio
economic
Conscription
Malformations
Death
certificates
National health registries (Norway)
• 15 central health registries maintained by the central
health authorities
• Cancer registry, Birth registry, Registry of cause of death...
• Ongoing project to coordinate registries (legal and political
discussions)
• Mandatory reporting by health service
• No Rare Disease (RD) central registry
National health registries (Norway)
• 200 Medical quality registries
• 45 registries national coverage
• National central service of competency for all rare diseases
established 2014 – planning project on coordinating existing rare
disease registries and establishing registry for all rare diseases
• Established RD registries include
• NAPOS – national registry for porphyrias, planned and financed to
establish European registry for porphyrias
• Aims: Describe diagnosis, natural course and existing treatment in
Europe
• Investigate effect of treatments
• National neuromuscular disease registry
• Nordic collaboration RAREDIS
• 7 other Nordic registries (none i RD-area)
Raredis - the stepwise approach
• 2003: Local access database implementation – Copenhagen,
Denmark– craniofacial diseases -> all rare diseases
• 2005-: Norway (Oslo University Hospital) joined the database
• 2007: Web based standard registration of patients (without
patient identification)
• – SiteLab (commercial partner, technical solution)
• 2009: Research project protocol (for scaphocephaly) contained in
standard registration system
• 2013: Implementation of login-procedures that overcome the
legal differences in Nordic countries
Denmark
Nordic
Currently we have a database (the Nordic database) within a
database (the Danish database for rare diseases with many more
patients and diagnoses)
Raredis Principles
• We study selected rare diseases
-
Describe epidemiology, diagnosis, natural course and existing treatment, Investigate effect of
treatments
Act as a resource to identify RD patients suitable for projects
• Diseases that are so rare one nationwide register is not sufficient and
too common to necessitate a (pan-)European project
• Diseases that will benefit from long-time follow-up
• Future: Genetic disease for which treatments will become available
• One database for all rare diseases
• Core data = ID, age, sex, ICD10
• Petals
• Specific to the diagnosis
• Specific to a project
CORE data
PETALS
Diagnosis specific data
PETALS
Project specific data
General principles for Raredis
• We have created the framework for a Nordic
registry (legal, technical)
• Every institution own their data and may publish
separately
• Raredis does not own the database
• The Nordic countries (governments) do not own the
database
• Collaborators can apply to a board (representatives of
all contributing countries for the use of Raredis data
(on a project basis)
Raredis Principles (cont)
• Establish stable, fully functional networks of
collaborating researchers
• This is essential to secure the full support for the
Raredis effort from all the relevant scientific groups in
the Nordic countries
• Raredis language = English
• Avoiding problems of translation
Raredis Principles (cont)
• Study selected rare diseases
• Define projects
• Intervention projects – prospective, long term
• Scaphocephaly (premature fusion of sagittal suture in the skull ) project
• 130 patients / 18 months
• Prospective evaluation of treatment effects – different centres use
different operation techniques
• Complex craniosynostoses
• ~200 patients in Denmark and Norway (centralized treatment) Several genetic subgroups
• Study natural course and effect of surgery (retrospective)
• Evaluation of new treatment (operation techniques)
General principles (cont)
• Data collection is in the health service
• Web based manual entry
• Automatic data transfer from local hospital database
to Nordic database (Oslo only)
• Data flow should be
• (from the health service to)
• the local database to
• the central database
The successful implementation is
challenging – lessons learned
• Things take time - Probably at least a 5 year perspective
is needed
• General registration need dedicated resources at each
center (secretarial support)
• Research initiatives must be managed by dedicated
staff (phd-students or similar)
• The initiatives must be based on existing initiatives and
existing databases instead of starting new
• One real challenge is defining good projects
Future developments
• Adding more diagnoses – project based
• Legal and political aspects:
• Nordic council 2010: Expert committee to report on
how Nordic collaboration on highly specialized
treatment may lead to improved quality in each
country
• And how this may benefit the rare diseases
• 2012: Report prioritized 5 items including nordic
registries for highly specialized treatment
Future developments (cont)
• Subcommittee report on registries – databases
• Lists existing Nordic registries (n=8)
• Recommending two Nordic databases as pilots
• Injuries to the spinal cord
• Prothesis for ankle and wrist
• Model (to be determined): Either expansion of existing
local-national registries or the Nordic datase for rare
diseases
• Both models build on existing research environments
and infrastructure – databases are regarded as an
essential part of a scientific collaboration within the
health service (bottom up)
My thoughts on future
developments - Raredis
• ”Data flow should be from local database to the
central database”
• ? What about data flow from the Nordic database to
European databases for rare diseases (diagnosis
and/or project specific databases)
• Preparing for back transfer of data from the database
to the patient
• Aim: Identify patients suitable for theraputic trials
• Therapies may become independent of diagnosis, may become
mutation class specific (e.g. Therapy for nonsense mutations)
• In Raredis – contact via the submitting centre
My thoughts on future
developments - Raredis
• ”Data flow should be from local database to the
central database”
• Petal: Standardized Phenotype data
• ICD10, Orpha#, MIM, other?
• Human phenotype ontology?
• Petal: Standardized Genotype data
• HGDV format or similar
Status 2104: Databases of standardized
Genotype data do exist for significant groups
of RD patients
Data originally collected for health service
reasons (diagnostic activity)
•
•
•
Genomic variation databases expanding into gene single gene variation
detection by next generation sequencing
• Decipher, Ecaruca, ISCA
Large projects aiming at collecting both genotype and phenotype
• UK: the DDD-project
• DDD=deciphering developmental disorders
Computer tools for automatic funneling of data from local to central
databases is in development
• Microarray – Cartagenia
used by 120 labs – module to share data and
export to central databases
How do we connect existing data sources
(genotype-phenotype)?
Building on existing scientific
environments and infrastructure
•
National
databases
starting with
(clinical)
phenotype – now
expanding with
genotype data
?
•
Databases with
results of
(diagnostic) next
generation
sequencing
www.raredis.eu
[email protected]