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20th National Pharmacology Congress of the Turkish Pharmacological Society

Antalya, November 4th 2009

European Clinical ResearchInfrastructures Network

Jacques Demotes-Mainardjacques.demotes@inserm.fr

www.ecrin.org

ECRIN

Pan-European, distributedinfrastructure providingintegrated services to multinational clinical researchin the EU:

- access to patients throughout the EU

- despite the fragmentation of health and legislative systems

- support to investigators and sponsors in multinational studies

European Clinical ResearchInfrastructures Network

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BMS-ESFRI Roadmap

2006

2008

INFRAFONTIERINSTRUCTELIXIRECRINBBMRIEATRIS

BSL-4BBMRCOpenScreenEuroBioImaging

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ECRIN, a distributed infrastructure for clinical trials in the EU

• ECRIN-1 (RKP, 2004-2005) : Identifying bottlenecks

• ECRIN-2 (TWG, 2006-2008) :Design of the infrastructure

• ECRIN-3 (PPI, 2008 - 2011) : ESFRI roadmap infrastructuresupporting multinational clinical trials in the EU

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ECEC

EC

EC

ECEC

EC

EC

Coordination

ECRIN Management Office

GMPCRC

CRC

CRC

DM

CRCCRC = Clinical research centreDM = Data centre EC = European CorrespondentGMP = GMP facility for biotherapy NNC = National Network Coordination

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Referenzpathologie

Germany

13 „Coordinating Centers“ for Clinical Trials3 associated centres (Regensburg, LMU Munich,Hannover)

Central Office in Cologne

6 sites with an integrated pediatric module(PAED-Net):Freiburg, Heidelberg, Cologne, Leipzig, Mainz, Münster

Permanent cooperation partner:Surgical network (CHIR Net) represented by: Study centre of the German Surgical Societynationwide network

+ Regensburg

+ München

+ Hannover

Bichat

Henri Mondor(94 Créteil)

Pitié-Salpêtrière

Necker Enfants Malades/HEGP

Robert Debré

Saint-Louis

Saint-Antoine

HEGP

Les 15-20

CochinPasteur

IGR/Curie (Villejuif/Paris

)

Saint-Pierre

Ile de la Réunion

CIC-P (25)

CIC-CE (9)

CIC-BT (11)

Lille

Rennes

Nantes Tours

Nancy

Strasbourg

Lyon

MontpellierMarseille

Bordeaux

Toulouse

Grenoble

Rouen

Saint-Etienne

Dijon

Brest

Clermont-Ferrand

Besançon

CIC-TI (8)

Garches

Poitiers

Limoges

Cayenne

Pointe-à-Pitre

Fort-de-France

54 54 ClinicalClinical Investigation Centres Investigation Centres withwith 8 main 8 main specialisationsspecialisations((CardiologyCardiology, , DiabetologyDiabetology, , GastroGastro--hepatologyhepatology, Neurosciences, , Neurosciences, PaediatryPaediatry, , ThrombosisThrombosis, Vaccines, and , Vaccines, and OncohaematologyOncohaematology))

France

5

UK

Management

Legal status

ECRIN Management Office(Coordination and European

Correspondents)

Structure Developmentof services

QA Unit +Working parties

Design & Construction

Pilot Projects

Network Committee

Governance

FinancialPlan

Education

CapacityBuilding

Extension

Communication

Ethics

Regulation

Vigilance

Monitoring

Data centres

GMP Facilities

MinistriesFunding AgenciesNetwork committee

Scientific Board(independent experts and

ECRIN representatives)

StakeholdersRegulatorsUsers/ PartnersScientific agenciesScientific networksPatient’s associations

Project Development

Board

AdvisoryBoard

Joint StrategicBoard

ESFRI-BMS ccordinators

ECRIN-3

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ECRIN-PPI Work Packages

• WP2: selection of a legal status and of the governance structure • WP3: agreement on a financial plan leading to a long-term sustainability

during the construction step and the operation phase • WP4: survey on needs in terms of GMP facilities for biopharmaceuticals

and biotherapy, and their design • WP5: education programme for multinational clinical studies • WP6: extension to other EU member states • WP7: capacity building to help national networks fulfil the sponsor’s tasks• WP8: update and upgrade of the quality assurance system • WP9: internal and external communication • WP10: accreditation of data centres• WP11: support to pilot projects after evaluation by the scientific board

Flexible, integrated services in the conduct of the study

- Decentralised1 - interaction with ethics committees2 - interaction with competent authorities3 - participant recruitment and investigation4 - drug dispensing5 - circulation and storage of blood and tissue samples6 - study monitoring

- Centralised7 - adverse event reporting8 - data management – data centres9 - GMP manufacturing of biotherapy products

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Information and consulting duringthe preparation of the study

- Practical information1 - Ethical requirements 2 - Regulatory requirements3 - Insurance4 - Centre selection5 - Cost evaluation6 - Funding opportunities

- Methodology7 - Systematic review, meta-analyses, and trial sequential analyses8 - Methodology, protocol design9 - Biostatistics10 - Data safety and monitoring board

Consulting

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Support/services

Management

Legal status

ECRIN Management Office(Coordination and European

Correspondents)

Structure Developmentof services

QA Unit +Working parties

Design & Construction

Pilot Projects

Network Committee

Governance

FinancialPlan

Education

CapacityBuilding

Extension

Communication

Ethics

Regulation

Vigilance

Monitoring

Data centres

GMP Facilities

MinistriesFunding AgenciesNetwork committee

Scientific Board(independent experts and

ECRIN representatives)

StakeholdersRegulatorsUsers/ PartnersScientific agenciesScientific networksPatient’s associations

Project Development

Board

AdvisoryBoard

Joint StrategicBoard

ESFRI-BMS ccordinators

ECRIN-3

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Legal status : ERICmembers = national ministries

• transnational team involved on a full-time basis in multinational studies (EU coordination, EU correspondent, national hubs)

• national networks, whose activity remains mostly national, with varying status, and who are involved on a part-time basis in multinational activities

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ECEC

EC

EC

ECEC

EC

ECCoordination

ECRIN Management Office

GMPCRC

CRC

New contacts

SpainSCReN

FranceInserm

GermanyKKS

UKUKCRN

IrelandICRIN

EORTC

ItalyCIRM & IRFMN

SwitzerlandUBern-SCRN

AustriaATCRIN

HungaryHECRIN

SwedenSweCRIN

FinlandFinCRIN

DenmarkDCRIN

Belgium

The Netherlands

Poland

Turkey

Portugal

Luxembourg

Croatia

Regional hubs ?

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Procedure and criteria for connection of new hubs: WP6

• Connection will be open to a national co-ordination of clinical research infrastructures (clinical research centres / clinical trials units), or to a national co-ordination of clinical research networks, reaching the critical mass and representing the standard in their own country, able to provide support to clinical research projects in any medical field, for any category of clinical research. In addition, they should also receive a support from national ministries or funding agencies for their participation in the FP7 ECRIN-PPI project.

• Pending on these criteria, the network committee will decide on the connection of additional national networks.

• These new networks will also benefit from the capacity buildingprogramme (WP7) both before and after their connection to ECRIN,facilitating the setup of competencies to effectively support investigators and sponsors in multinational studies.

Procedure and criteria for connection of new hubs: WP7

• A capacity building programme will help strengthening the capacity of national co-ordination to perform sponsor’s tasks in EU-wide studies and to make the co-ordination of new national networks able to provide the full range of services proposed to investigators andsponsors.

• capacity to provide services for the conduct of the study : interaction with ethics committees, interaction with regulatory authorities,vigilance, drug dispensing, circulation of blood and tissue samples, study monitoring, data management, patients enrolment and investigation

• capacity to provide consulting, during the preparation of the study

• quality assurance system within the national centres and network reaching the requirements defined in WP8.

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Structuring clinicalresearch in the EU

• Development of national networks and hubs• Development of multinational disease-oriented networks

– FP7 ENBREC• Funding to clinical research infrastructures (national / EU)• Funding to clinical research projects (national / EU)

• Communication with patients, citizens, stakeholders– International clinical trials’ day

• Pan-EU platform for Education and Training– IMI EMTrain

• Improvement of the legislative framework– ESF/EMRC Forward Looks– ICREL FP7 (Impact on Clinical Research of European Legislation)

Comparison of national requirementsEC CA Sponsor Insurance AER

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CTs performed before and after the CTD implementation

-2000

0

2000

4000

6000

8000

10000

Medicinalproducts

Medicinaldevices

Surgicalprocedures

Radiotherapy Otherinterventions

Observational

20032007Changes

Workload before and after CTD implementation

0

1

2

3

4

5

6

CTA to CA & EC Coordination andMonitoring

Pharmacovigilance Quality Assurance

FTE

Average/ organisation 2003Average/ organisation 2007Changes

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Forward Looks ‘Investigator-Driven

Clinical Trials’

European Science FoundationEuropean Medical Research Councils (EMRC)

Recommendations : ranking

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No. No. Recommendation Rank

21 4.1 Education and Training 124 5.1 Level of Funding 27 2.1 Risk-based approach 322 4.2 Careers 415 3.1 Clinical Trial Authorisations (CTA) Process 56 1.6 Large Scale IDCT 61 1.1 Categories of patient-oriented research 78 2.2 Management by risk-based approach 84 1.4 Commercial versus non-commercial trials 926 5.3 Models of Partnership 1016 3.2 Sponsor 1125 5.2 Prioritisation and mechanism of funding 129 2.3 Ethics Committee 1311 2.5 Insurance Requirements 135 1.5 Paradigm shift by biomedical breakthroughs 1514 2.8 Publication of Clinical Trials Results 1517 3.3 Investigational Medicinal Products (IMP) Requirements 17

18 3.4 Pharmacovigilance Reporting 1820 3.6 Project Management 1813 2.7 Data Storage Capacity 203 1.3 Phase I-II-III-IV categories 212 1.2 Interventional versus observational studies 2219 3.5 Pharmacovigilance Notification 2310 2.4 Adverse Event Reporting 2412 2.6 Intellectual Property Rights (IPR) 2523 4.3 Authorship 26

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Innovative Medicines Initiative

Discoveryresearch

Preclinicaldevelop.

Translationalmedicine

Clinicaldevelop.

Pharmaco-vigilance

Predictive pharmacology

Predictive toxicology

Efficacy Safety

Identification of biomarkers

Validation of biomarkers

Risk assessmentwith regulatory

authorities

Patient recruitment

Knowledge ManagementEducation & Training

ESFRI Biomedical Research Infrastructures

EATRISTranslational

ELIXIRBioinformatics

INFRAFRONTIER Animal models

ECRINClinical Res.

BBMRIBiobanks

BiomolecularResources

INSTRUCTStructuralBiology

TargetId

TargetVal Hit Lead

LeadOptim Preclin Phase I Phase II

Research Discovery Development

Phase III

biobankingmodel validation

samplesdata

biomarkers

samplesdata

targetsbiomarkers

targets

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National liaisonsProject Office(MUW and EFPIA)

WP 1: Management

WP 8: Learning and teaching concepts and methodology

WP 6: PhD programmes

WP 5: Master programmes

WP 4: AHEN *

WP 3: Mapping

WP 2: Strategy

WP 7: Continuing Professional Development

WP 9: Information, communication and dissemination

StrategicCoordination Board

Co-ordinators ESFRI-BMSRepresentatives T15-18

4 managing EFPIA membersChairs managing coordination board

Man

agin

gC

oord

inat

ion

Boa

rdW

P le

ader

san

d co

-lead

ers

External Advisory BoardNational ministries,

EU, NIH

Network CommitteePartner Universities

Patients AssociationsEUSJA, EMEA, ICH; Coordinators call 1-13

Teaching Experts

* Accreditation/Harmonisation/ Extension/National Implementation

IMI JU

Topics 15-18STEERING COMMITTEE

2 EFPIA members2 public consortium representatives

1

2

3

4

5

6

7

89

Thank you !