Transcript International Rare Disease Research Consortium (IRDiRC)

and Curators meeting, Leiden,
1 | TGDOC
November 2014
TREAT-NMD Alliance
A global network of national registries for
neuromuscular diseases
THE SHOT HEARD AROUND
THE WORLD
and Curators meeting, Leiden,
2 | TGDOC
November 2014
BioBank
Standard
Operating
Procedures
Joint
Research
Patient
Registries
Three year
work plan
Website &
Communications
Care & Trial
Site Registry
Outcome
Measures
TACT
Standards of
Diagnosis &
Care
www.treat-nmd.eu
Outcome
Patient
Care
Joint
EuroBioBank
Standards
Action
&
2007-2011
Website
Registries
measures
Trial
research
SOPs
TACT
Plan
Site
of
&
EU
fundedRegistry
Network
Diagnosis
Communication
& Care
Standardized
genetic
&
Unique
network
of
18
Tests
to decide
whether
TREAT-NMD
Unified
Regular
experimental
meetings
3 year
Advisory
plan
to
clinical2012
core
data
for trial
members
treatment
being
tested
in
onwards
Committee
consolidate
protocols
for
Therapeutics,
improve
efforts
and
thea
International
consensus
Information
Extensive
about
website
each
recruitment
trial
is Alliance
having
any
effect
funded
Milestone-driven
comparability
jointly
tackle
of
approach
common
studies
publication
recommended
registered
trial
site
kept
in
Stores
&
distributes
440,000
Expert
multidisciplinary
problems
through
multiple
250,000
standards
annual
page
ofbody
care
hits
Interface
can
vary
between
one
location
for
ease
of
quality
Vital
DNA,
to
use
cell
the
and
correct
tissue
Drawn
Maintains
up
by
a
group
network
of
streams
global
countries
whilstwith
still able
to
comparison
outcome
measure
to
samples
prove
if
70,000
visitors
annually
momentum
Independent
Topics
independent
based
&share
establish
and
on
researchers
necessity,
objective
new
DMD-SMA-CMD-LGMD
core
data
partners
&
membership
aon
treatment
works
guidance
(listed
hosting
in
advancing
each
to
be
protocol)
rotated
goals
new
Addresses
organisational
Monthly
newsletter
sent
to
Ethical &
governance
best
therapies
for
between
neuromuscular
partners
Family
guides
difficulties
of
identifying
Governance
Working to
harmonise
the
3,500
recipients
practice
Approx
40
sops
diseases
updated
in
25
different
languages
appropriate
sites when
Chair
– Annemieke
Aartsma-Rus
use
of most appropriate
regularly
translations
verified
Vice
Chair
– Ericup
Hoffman
setting
a trial
Proven
communication
>10,000
outcome
DMD
patients
measures
across
for
platform
different
30
countries
diseases
Chair
Executive
–
Dominic
Committee
Wells
Printed booklets
or
Leads
Eric
Hoffman
Annemieke
Supported
by academic
advisory
Leads
- Marina
Mora
download
from
website
Leads
Verschuuren
Lead- -Jan
Eugenio
Mercuri
Aartsma-Rus
board
force”)
of NMD
Funding
- (“task
US (Dept
Lucia
of Dawkins
Defense)
Monaco
Secretariat
Hugh
Kate
Bushby
Filippo
Buccella
leaders
Marco
Crimi
Leads
Thomas
Volker
Sejersen
Straub
Coordinated
by University
Funding
- Telethon
&
Parent
Funding
Kathy
- AFM
North
& EC
Medical
Center
Freiburg
Organizations
Funding
COST
Funding
Fondazione
Telethon
Funding – EC (operating grant)
and Curators meeting, Leiden,
3 | TGDOC
November 2014
Impact: research projects multiply
TREAT-NMD
CARE-NMD
NeurOmics
RD-Connect
10M EUR “network of
excellence” for rare inherited
neuromuscular diseases
Implementing care standards
for DMD across Europe, in
particular Eastern Europe
12M EUR research project on
nextgen omics approaches to
neuromuscular and
neurodegenerative disease
12M EUR RD infrastructure:
central global hub connecting
registries, biobanks and
clinical bioinformatics
NMD-Chip
MYO-SEQ
RARE Bestpractices
High throughput sequencing
(gene chips) for NMD
diagnostics
Exome sequencing of 1000
patients with limb girdle
phenotype
Infrastructure for best practice
sharing across rare diseases
EUCERD Joint Action
for Rare Disease
BIO-NMD
SKIP-NMD
OPTIMISTIC
SCOPE-DMD
Identifying and validating preclinical biomarkers for
diagnostics and therapeutics
Clinical trial for morpholino
antisense oligonucleotide
exon skipping (53) in DMD
Natural history and exercise
therapy clinical study in
myotonic dystrophy
Clinical trial for 2O-ME
antisense oligonucleotide
exon skipping (45) in DMD
3Gb‐TEST
BIOIMAGE-NMD
MYO-MRI
FUTURE …
Introducing diagnostic
applications of ‘3Gb‐Testing’
in human genetics
Development of imaging
technologies for therapeutic
interventions in rare diseases
Applications of MR imaging
and spectroscopy techniques
in neuromuscular disease
Horizon 2020
Implementing RD policy and
national plans across Europe
INNORARE
06 July
A N I N TE G R ATE D PL ATFO R M
CO N N E C TI N G DATA BAS E S ,
R E G I STR I E S , B I O BA N KS A N D
C L I N I C A L B I O I N FO R M ATICS FO R
R A R E D I S EAS E R E S EA RC H
International Lead: Hanns Lochmuller
Overview and Key Objectives
5
Overarching objectives:

Develop integrated, quality-assured and comprehensive platforms in which complete clinical profiles are
combined with -omics data & sample availability for rare disease research.
Specific objectives:

Harmonisation and development of common standards for databases and patient registries for RD by
collaborating internationally to implement common registry infrastructure and data elements across a
federated system.

and a common catalogue for RD biobanks that collect and provide standardised, quality-controlled biomaterials for
translational research.

Develop a suite of clinical bioinformatics tools, including data mining and knowledge discovery tools for
analysis and integration of molecular and clinical data to discover new disease genes, pathways and
therapeutic targets.

Develop an integrated platform to host the processed data from Neuromics, EuRenOmics and IRDiRC projects.

Develop best ethical practices for balancing patient-related interests associated with RD research using
databases/registries, biobanks and omics databases, engaging with relevant stakeholders, e.g. patient
organisations, clinical and research networks, legislators and policymakers, pharma industry

Develop a regulatory framework for linking of medical & personal data related to RD

Ensure access to project results & broad global impact in diagnostic and translation sciences including
industrial collaborations.
06 July 2015
RD-Connect partners
6
6
27 full partners, 17 associated partners, 17 countries
RD-Connect Clinical Exemplars
7
7

European Consortium for High-Throughput Research in Rare Kidney Diseases (Franz
Schaefer, Universitätsklinikum Heidelberg, Germany)

No formal Australian partner named in application, but interest in involving Australian
kidney disease researchers – Hugh Dawkins coordinating

Integrated European Project on Omics Research of Rare Neuromuscular and
Neurodegenerative Diseases (Olaf Riess, Institute of Human Genetics, University of
Tübingen)

Formal Australian partner: Nigel Laing, Neuromuscular Diseases Laboratory, University of
Western Australia

Additional NMD/NDD researchers may potentially contribute well characterised patients for
omics analysis
RARE-Bestpractices
A platform for sharing best practices for the
management of rare diseases
Background
 The project focuses to the specific action
HEALTH.2012.2.4.4-3: Best practice and
knowledge sharing in the clinical management of
rare diseases.
 4 year project (January 2013-December 2016)
1
Project Outline
GOAL:
 To create a platform to improve the management of rare disease
patients.
AIMS:
 To promote communication on the management of rare diseases
by disseminating trustworthy guidelines globally;
 To identify and prioritize rare diseases research needs;
 To facilitate timely, effective and efficient translation of research
results into patient oriented strategy on the clinical as well as the
public health level; and
 To support IRDiRC activities.
1
Specific Project Objectives





Build a comprehensive public database of trustworthy guidelines,
ranging from diagnostic tests and treatments to the organization of
care, to help professionals, patients, policy makers with the best and
most up to date information
Produce mechanisms to identify and prioritize rare diseases clinical
research needs to optimize as well as redefine the clinical research
agenda taking into consideration both patients’ and clinicians’ needs
and interests
Identify available notations for graphic representation of processes
within guidelines to improve user understandability and implementation
Define to what extent conclusions from cost-effectiveness analyses for
pharmaceuticals are accounted for and implemented in best practice
guidelines across a range of countries
Set up training activities targeted at key stakeholders to spread
expertise and knowledge in the field of guidelines.
1
International Rare Disease
Research Consortium (IRDiRC)
Co-operation at international level to
stimulate, better co-ordinate &
maximise output of rare disease
research efforts around the world
GOALS

200 new therapies for rare
diseases by 2020

Means to diagnose most
rare diseases by 2020
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IRDiRC Members
October 2104
Australia
Belgium
Canada
Canada
China
China
China
Europe
EU
Finland
France
France
France
France
Germany
Georgia
Ireland
Italy
Italy
Italy
Saudi Arabia
Netherlands
Netherlands
Western Australian Department of Health
European Organisation for Treatment & Research on
Cancer (EORTC)
Canadian Institutes for Health Research
Genome Canada
BGI
Chinese Rare Disease Research Consortium
WuXi AppTec Co., Ltd.
E-RARE 2 Consortium
European Commission
Academy of Finland
Agence National de la Recherche, ANR
French Foundation for Rare Diseases
French Muscular Dystrophy Association, AFM
Lysogene
Federal Ministry of Education and Research (BMBF)
Children's New Hospitals Management Group
Shire
Chiesi Farmaceutici S.p.A.
Istituto Superiore de Sanita
Telethon Foundation
Saudi Human Genome Project
Prosensa
Netherlands Organisation for Health Research &
Development
South Korea
Spain
UK
USA
USA
USA
USA
USA
USA
USA
(NIH)
USA
USA
USA
USA
USA
USA
USA
Europe
USA
USA
Korea National Institute of Health
National Institute of Health Carlos III
National Institute for Health Research
Food and Drug Administration, Office of Orphan
Products Development (FDA)
Genzyme
Isis Pharmaceuticals
National Cancer Institute (NIH)
National Eye Institute (NIH)
National Human Genome Research Institute (NIH)
National Center for Advancing Translational Sciences
National Institute of Arthritis and Musculoskeletal
and Skin Diseases (NIH)
National Institute of Child Health and Human
Development (NIH)
National Institute of Neurological Disorders and
Stroke (NIH)
Office of Rare Diseases Research (NIH)
Sanford Research
NKT Therapeutics
PTC Therapeutics
European Organisation for Rare Diseases,
EURORDIS
Genetic Alliance
National Organization for Rare Disorders, NORD
Framework Program 7
15
€12 million
€12 million
€12 million
SUPPORT
€6 million
Partner Funded Programs
40 PARTNERS
>> €1billion
06 July 2015
ERA-Net for Research Programmes on Rare
Diseases
Joint Calls
Funding transnational collaborative research through yearly joint
transnational calls is one of the major objectives of E-Rare. This is the
most important and effective joint activity to enhance the cooperation
between European scientists working on rare diseases and thus reducing
the fragmentation of research in this field.

Two “general” joint calls (2011 and 2013) with broad and open
topics are foreseen to allow researchers to choose their projects
based on state of the art and research demand for the specific
disease. This bottom-up approach is seen as the most suited to
cluster the most competitive national research groups in common
projects, and effectively opens the national programmes for more
international collaboration.

Two "focused" joint calls (2012 and 2014) are also planned to
address themes of rare diseases research that need special
attention. The calls are designed to promote the multidisciplinarity
necessary for progressing towards a translational research
approach, thus serving the patients suffering from rare diseases.
The resulting synergies will ensure a higher cost-effectiveness of the
limited funding.
Orphanet
Ana Rath
Hugh Dawkins
A/Director, Orphanet
Country Coordinator Australia
[email protected]
Caron Molster
Ségolène Aymé
International Director
Information Scientist
[email protected]
[email protected]
www.orpha.net
www.orpha.net/national/AUEN/index/homepage
www.orpha.net
An International consortium:
Started in France in 1997
Orphanet is recognised by
the EC Public Health as “the
most important database in
the EU for rare diseases and
orphan drugs for the general
public. It contains
information about 6 000
diseases and is freely
accessible”
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www.orpha.net
Orphanet established in 1997
to address identified problems…..
Lack of information
Inventory and Encyclopaedia
Scarce expertise
Directory of experts/clinics
Too few collaborations
Directory of research projects
Difficult recruitment
Directory of clinical trials
Isolation of patients
Directory of patient organisations
www.orpha.net
A comprehensive, curated and open
access dataset related to rare diseases
and orphan drugs, downloadable in
reusable xml format
orphacode
Make rare diseases visible in your health
information system
www.orphadata.org
The ORPHA nomenclature is a stable, evidence
based, collaborative product of Orphanet
 Based on published expert classifications
 Peer reviewed
 Supported by the European Commission and
many national health institutions
 Download in PDF or XML format
 Updated monthly
Directory of
Expert Resources
Expert clinics
Medical Laboratories
Patient organisations
The Orphanet mobile application
All the
information
about rare
diseases at your
fingertips
Free for iPhone, iPad and Android
Research & trials
www.orpha.net
Different applications for different users
orpha.net
orphadata.org
Orphanet
database
Orphanet
Report Series
Ontology
Nanopublica
tions
www.orpha.net
Orphan Diseasome
An Orphan Diseasome permits investigators to
explore the orphan disease (OD) or rare disease
relationships based on shared genes and shared
enriched features (e.g., Gene Ontology Biological
Process, Cellular Component, Pathways, Mammalian
Phenotype).
The red nodes
represent the
orphan diseases
and the green ones
the related genes.
A disease is
connected to a
gene if and only
if a mutation which
is responsible of
the disease has
been identified on
this gene.
http://research.cchmc.org/od/01/index.h
AIMS
To tailor existing and novel tools provided by the research infrastructures on the ESFRI (European Strategy
Forum on Research Infrastructures) roadmap to the specific needs of the RD community.
The proof of principle of an accelerated Research Infrastructure-driven pathway for translational research in
rare diseases.
To improve the research environment and health initiatives , including industry engagement.
To provide better access to diagnosis, clinical trials and therapy development.
To ensure alignment with the International Rare Disease Research Consortium (IRDiRC)
Linked with the Global Alliance for Genomics and Health (GA4GH)
Supporting the translational pathway for RD and ensuring a sustainable platforms, and fully integrated data.
INTERNATIONAL LEAD: Katie Bushby
BIOINFORMATICS ECO SYSTEM
AND
KNOWLEDGE MANAGEMENT
PEOPLE LIVING WITH RARE DISEASES
• Equity of Access
• Lead the best life possible
• Quality of life choices and measures
• Improve health system experience
• Empowered with knowledge
• Influence health care
• Opportunity to influence policy
VOICE OF THOSE
AFFFECTED
• RD patients, families, carers
• Clinical & Academic
• Industry & Manufactures
• Government
• Hospital (private & public)
EXPERT HUMAN KNOWLEDGE
• Implicit and explicit knowledge
MACHINE SYSTEMS
• Information capture
• Systems Integration
• Analysis
• Interpretation
• Technology
• devices, instruments,
bioinformatics, systems
• Clinical expertise/experts
• Natural History
• Integrated Omics
• Interpretation & application
NEW
KNOWLEDGE
VOICE OF EXPERTS
VOICE OF DATA
(EVIDENCE)
CONTINUOUS KNOWLEDGE
MANAGEMENT CYCLE
WHAT TO USE (NOT TO USE) = PRECISION MEDICINE
WHERE & WHEN TO INTERVENE = PRECISION PUBLIC HEALTH
• Genotype:Phenotype
• Disease classification & codification
• Treatment monitoring
• Incidence, prevalence, Burden of Disease
• Therapeutic targets
• Best practice
• Biomarkers
• Knowledge transfer
POLICY
• Trial Optimisation
• Capacity building
IMPLEMENTATION
THE SOLUTION
EMPOWERING NATIONAL
PATIENT ORGANISATIONS
GLOBALLY
for health innovation and improving the well
being of all people living with a rare disease
GLOBAL PUBLIC HEALTH ACTIVITIES
NATION
Population size




1,338,612,968
1,156,897,766
475,304,355
302,047,000
CHINA
INDIA
RARE DISEASES COHORT
USA
http://www.blackswanfoundation.ch/en/
DATE: AUGUST 2013
International Patient Organisations
Emerging National Patient
Organisations
•
Indian Organization of Rare Diseases (I-ORD) [80 Million]
–
•
Organization for Rare Diseases India (ORD-I)
–
•
Established 18 October 2013 to defend and be the voice of more than 42 million people
with rare diseases in Latin America
Taiwan Rare Diseases Foundation [2 Million]
–
•
•
Catalyze rapid development/delivery of affordable diagnostics and treatments for rare
diseases in India through innovative collaborations / partnership among stakeholders
for the benefit of rare disease patient community. http://ordindia.org
Latin American Alliance for Rare Diseases (ALIBER) [45 Million]
–
•
Established 2010 to raise awareness of rare diseases in India where the large
percentage of poverty as well as the diverse cultures make it problematic to properly
identify and/or educate people about rare diseases http://www.i-ord.org
established in 1999, has been an active force in advocating for rare disease patients in
respect of medication, education, and employment, and will continue to give its best
effort to light up the lives of many rare disease patients.
Malaysia – in progress [2 Million]
China – in progress [90 Million]