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ECRIN-PPI www.ecrin.org
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Finland FinnCRIN
Sweden SweCRIN
Denmark DCRIN
Ireland ICRIN
UK UKCRN
EORTC
Germany KKS
EFGCP
Austria ATCRIN
France Inserm
Hungary HECRIN
Switzerland SCRN
Spain SCReN
Italy IRFMN CIRM
National networks of Clinical Research Centres /
Clinical Trial Units
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ECRIN objectives

• Integration of EU clinical research capacity
• support to investigators
• support to sponsors in multinational studies
• -gt unlocking latent potential scientific,
  patients
• Integration of public funding
• -gt avoiding duplication of studies wasting of
  money
• Harmonisation of tools, training and practice
• Improved quality, credibility, transparency
• ----gt harmonisation of legislative systems ?

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Which clinical research projects ?

• Any type of clinical research
• Clinical trials on health products, biotherapy
• Surgery, radiotherapy, multimodal trials
• Diagnostic, imaging, biomarker, genetic studies
• Physiology, physiopathology, epidemiology
• Any medical field
• Special focus on rare diseases / orphan drugs
• Any sponsor public institution, public-private
  partnership, biotechnology medical device SMEs,
  pharmaceutical industry
• -gt support to investigators
• -gt support to sponsors in multinational studies

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ECRIN, an integrated infrastructure for clinical
trials in the EU

• ECRIN-1 (2004-2005)
• Identifying bottlenecks
• ECRIN-2 (2006-2008)
• Design of the infrastructure
• ECRIN-3 (2008 -gt ) ESFRI roadmap
• Preparation, construction and operation
• of the infrastructure supporting
• multinational clinical trials in the EU
• In line with expectations of FP7
• Innovative Medicines Initiative

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ECRIN-1 (2004-2005) identifying bottlenecks
ECRIN-RKP (FP6-funded) -gt survey and
comparative analysis on 1 - Structures and
objectives of centres and networks 2 -
Financing, sponsoring 3 - Ethics 4 -
Legislation, regulatory affairs, insurance 5 -
Adverse event reporting, drug dispensing 6 -
Methodology, data management, data monitoring 7 -
Quality management, SOPs, audits 8 -
Communication, partnerships 9 - Study registers
10 - Education and careers -gt reports on
www.ecrin.org
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ECRIN-2 (2006-2008) designing the infrastructure

• ECRIN TWG (FP6-funded)
• TRANSNATIONAL WORKING GROUPS
• -gt Guidelines and procedures
• 1 - ethics
• 2 - regulation
• 3 - adverse event reporting
• 4 - data management
• 5 - monitoring
• 6 - quality assurance SOPs
• 7 - education

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Which category of research ?

• Survey on categories of research
• 1 CT on medicinal products
• 2 CT on medical devices
• 3 Other therapeutic trials
• 4 Diagnostic studies
• 5 Nutrition studies
• 6 Other clinical research
• 7 Epidemiology

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Comparison of national requirements
EC CA sponsor insurance AER
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The definitions allow to determine which is the
relevant category of research (WP6, English) The
checklists summarise the requirements for
multinational support to sponsors and
investigators, stratified by category of research
(WP6, English) The procedures, stratified by
task, provide detailed description of the
specific requirements for each category of
research. They are based on a core element valid
throughout the EU, with adaptation to the
particularities of each country (each WP, English)
National laws and regulations
All documents are based on the national laws and
regulations (national language), and updated.
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ECRIN-3 (2008-) Integrated services to
multinational studies

• Flexible, integrated services (one-stop shop) in
  the conduct of the study
• 1 - interaction with ethics commitees
• 2 - interaction with competent authorities,
  regulatory affairs
• 3 - drug dispensing
• 4 - adverse event reporting
• 5 - data management data centres
• 6 - study monitoring
• 7 - circulation and storage of blood and tissue
  samples
• 8 - GMP manufacturing of biotherapy products
• 9 - patients recruitment and investigation

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ECRIN-3 (2008-) Integrated services to
multinational studies (2)

• Information and consulting during the preparation
  of the study
• 1 - Methodology, protocol review and adaptation
  of study protocol to transnational constraints
• 2 - Ethical review
• 3 - Meta-analysis
• 4 - Centre selection, stimulation of patients
  enrolment
• 5 - Cost evaluation
• 6 - Funding opportunities
• 7 - Biostatistics
• 8 - Data safety and monitoring committees
• 9 - Insurance

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CRC Clinical research centre DC Data centre
EC European Correspondent GMP GMP
facility for biotherapy NNC National
Network Coordination

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ECRIN - PPI preparation phaseWorkpackages

• 1 - Management
• 2 - Legal status and governance
• EU legal status (Art 171 ?) allowing staff
  recruitment, circulation of money, contracts with
  sponsors, application to calls
• framework contracts, management of IP
• Governance
• Coordination, network committee, advisory board,
  working parties, EU correspondents PLUS
• Project development board financial plan
• Scientific board and rules of access
• Joint strategic board (with biobanks EATRIS)

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ECRIN - PPI preparation phaseWorkpackages

• 3 - Financial plan -gt business plan, mechanism
  for long-term financial sustainability
• Survey on costs of services (to investigators, to
  sponsors)
• Survey on national funding to the infrastructure
• Survey on public and PPP funding to projects
• -gt ERA NET ?
• Cost of construction
• Capacity building
• GMP facilities
• Datacenters
• Cost of operation
• National and EU components, including management
  and QA

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ECRIN - PPI preparation phaseWorkpackages

• 4 - GMP facilities for biotherapy /
  biopharmaceuticals
• Survey on existing resources and needs
• Cost evaluation, implementation plan
• 5 - Education and training
• training for staff, e-tool
• 6 Extension
• New MS (NL, Be, Ice, Tur, Pt, Ser, Pl, etc)
• New infrastructures (pediatrics ?)
• 7 - Capacity building - relay to sponsors tasks
• Allow national coordinations to relay sponsors
  tasks

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ECRIN / ESFRI preparation phaseWorkpackages

• 8 - Update and upgrade of the QA system
• Update of multinational SOPs and guidelines
• (change in national and EU regulation, new
  members)
• WP1 Ethics
• WP2 Regulation
• WP3 Vigilance
• WP5 Monitoring
• Upgrade of national QA system
• Coordination with EATRIS, Biobanks
• 9 Communication
• With users, with patients, with citizens
• 10 Datacentres
• Specification for accreditation of datacentres,
  cost evaluation
• Accreditation of a prototype
• 11 - Pilot projects

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National networks, national project coordinators,
European correspondents
EATRIS BBMRI
Joint strategic board
Ministries agencies
Network Committee
Scientific board
Advisory board
Project development board
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ECRIN / ESFRI after the preparation phase

• 1 Operation phase
• Progressive development of services to
  investigators and sponsors
• -gt Sustainability self-financing / operation
  revenues (public, industry, PPP), open I3 calls,
  national support
• 2 Construction phase
• Capacity building public institutions acting as
  sponsors
• GMP facilities for biotherapy
• Datacentres
• -gt National funding, loan to EIB (RSFF),
  structural funds, limited funding from the
  Capacity programme

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Synergies with other ESFRI Infrastructures
biobanking model validation
samples data biomarkers
samples data targets biomarkers
targets
Biobanks Biomolecular Resources
Clinical Trials Biotherapy
Structural Biology
EATRIS
INFRAFRONTIER
Bioinformatics
Phase III
Target Id
Target Val
Hit
Lead
Lead Optim
Preclin
Phase I
Phase II
Research
Discovery Development
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Synergy ECRIN EATRIS
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Synergy / ECRIN EATRIS - Biobanks

• ECRIN will support EATRIS projects reaching the
  clinical step EATRIS / phase 1, ECRIN / phase 2
  and full development
• GMP manufacturing facilities for clinical batches
  
• ECRIN -gt generic centres and centres for
  biotherapy / cell therapy
• EATRIS -gt disease-oriented biopahramaceuticals
  (recombinant proteins, monoclonals,
  oligonucleotides, vaccines)
• Joint working groups EATRIS Biobanks - ECRIN
• databases - knowledge management
• regulation - legislation
• SOPs
• Public-private partnership through IMI

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Bottlenecks identified in the Innovative
Medicines Initiative (IMI) Strategic Research
Agenda




Knowledge Management
Education Training
Predictive toxicology
Identification of biomarkers
Validation of biomarkers
Patient recruitment
Efficacy
Safety
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Synergy / ECRIN IMI

• IMI as an user implementation of efficacy and
  safety PPP precompetitive IMI projects requires
  an infrastructure for clinical trials in the EU,
  particularly to address
• the definition and validation of biomarkers
• patients recruitment
• post-marketing safety studies
• IMI as a partner (with other ESFRI-BMS
  infrastructures)
• IMI knowledge management integrated,
  interoperable and multidisciplinary databases
• IMI education and training multidisciplinary /
  multinational profiles, mobility academia
  industry.

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FP7 IMI Europe-wide infrastructures and
disease-oriented networks
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ECRIN PPI advisory board
- European stakeholders and regulators 1 - EU
Commission, also representing Innovative
Medicines Initiative (IMI) 2 - European
Medicines Agency (EMEA) 3 - Clinical Trials
Facilitation Team (competent authorities from the
27 EU MS). - Users and partners Industry 4
EFPIA, also representing IMI 5 EuropaBio
(representing the biotechnology SME
sector) Public sponsors and scientific
agencies 6 - European Science Foundation (ESF) 7
- Europe Developing Countries Clinical Trials
Programme (EDCTP) Scientific associations and
networks (users) 8 disease-oriented learned
society (on a rotational basis) 9
disease-oriented learned society (on a rotational
basis) Patients associations 10 - European
AIDS Treatment Group (EATG) 11 - European
Association for Rare Diseases (EURORDIS) Partner
in communication 12 - Orphanet
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ECRIN PPI scientific board

• Projects will be evaluated, selected and followed
  by the Scientific Board, composed of
• representatives of the national infrastructures,
  
• of scientific experts in the field,
• of methodologists and biostatisticians,
• of members of the working parties on ethics,
  regulation, vigilance, and monitoring,
• and of representatives of patients associations.
  
• Distinct from Network Committee, but at least one
  common member
• -gt nomination of
• members of the ECRIN Scientific Board,
• and of its Chair

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ECRIN PPI contract negotiation

• Management structure
• Annex I
• A forms
• Budget
• Consortium agreement
• Communication plan

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ECRIN PPI contract negotiation

• Evaluation reduction in WP11 on Pilot projects
• Funding 6.428 -gt 5.8M (-10)
• Cut in WP11 budget
• - Reduction in manpower
• 184 -gt 78 person-month
• - Operating budget almost unaltered (scientific
  board)
• 50.000 -gt 36.983

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ECRIN PPI Related EU projects

• Structuring projects
• ICREL EU Directive
• Videoconferencing system
• Connecting disease-oriented network (bipolar
  disorder)
• Other ?
• Possible pilot projects
• Transvac
• Polypill
• BENEDIC
• Other ?
• Possible funding mechanisms
• EU funding (Health priority, IMI, Infrastructure
  I3)
• coordination of national funding (ERA-net)

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ECRIN PPI Impact on EU legislation

• Written suggestions for the EC-EMEA conference on
  the revision of the clinical trials Directive
• Lobbying
• National
• Commission
• EU Parliament