Prsentation PowerPoint

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KKSN Symposium, 10 November 2007 European
Clinical Research Infrastructures
Network Jacques Demotes, INSERM,
Paris 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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Challenges to clinical research in Europe

• Main bottlenecks
• Access to patients
• fragmentation of health systems
• Cost
• fragmentation of public funding
• Quality of infrastructures

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ECRIN proposals

• 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
• 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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EC/EMEA Conference on the Clinical Trials
DirectiveWhat should a new legal framework look
like?

• A single and comprehensive legislation covering
  all clinical research
• protecting the participants according to the risk
  associated to the category of study, not to its
  commercial or non-commercial objective
• with a single assessment by one competent
  authority
• with accredited ethics committees
• with a clear guidance on their respective roles
  and harmonised interactions
• promoting trust, transparency and optimal use of
  data through open registration, reporting, and
  data repositories

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ICREL project (FP7) Impact on Clinical Research
of European Legislation

• Measures the impact of the current EU
  legislation, analysing its direct and indirect
  consequences on all the categories of clinical
  research through information compilation and
  surveys
• WP2 Clinical trials in large pharmaceutical
  industry and SMEs
• WP3 Non-commercial trials
• WP4 Clinical research other than clinical trials
  on medicinal products
• WP5 Impact on competent authorities,
  pharmacovigilance, monitoring, infrastructure and
  funding for clinical trials
• WP6 Impact on ethics committees and protection
  of participants.

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The current monitoring strategies

• Alternative monitoring
• procedures in
• Investigator-initiated trials
• meeting report
• 3rd April 2006, Frankfurt/Germany
• C. Ohmann, J. Demotes, F. Sweeney, P.H.Bertoye,
  B. Davis, B. ONeill, G. Danielsson, G. Schwarz,
  D. Lacombe, O. Chassany, S. Meredith, G. Chene,
  V. Journot, B. Pfistner, M. Wenzel, O. Brosteanu

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Survey on data management, tools and procedures
within ECRIN
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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, FUNDING
  MECHANISMS
• 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, Pl, Gr, Pt, Ser, Tur, 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 local SOP
  requirements, audits ?
• 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 scientific board

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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
INSTRUCT Structural Biology
BBMRI Biobanks Biomolecular Resources
EATRIS Translational
INFRAFRONTIER Animal models
ECRIN Clinical Res.
ELIXIR 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