Challenges of Multicenter Studies in Europe, EURECNET, Bratislava, 13 April 2012 Hartmut Krafft, PhD CTFG-Chair VHP-Coordinator Head, Section clinical trials Paul-Ehrlich-Institut Paul-Ehrlich-Str. 51-59 63225 Langen Germany Fax: 49 (0)6103 771277 Phone: 49 (0)6103 771811 E-Mail: CT@pei.de http://www.pei.de
Disclaimer The views presented in this presentation/these slides are those of the author and should not be understood or quoted as being made on behalf of the HMA and/or its Working Parties and/or Member States of the EU EURECNET, Challenges of Multicenter Studies in Europe; 13.4.2012 H. Krafft Page 2
Situation of clinical trials in Europe before CTD EURECNET, Challenges of Multicenter Studies in Europe; 13.4.2012 H. Krafft Page 3
Situation of clinical trials after the implementation of the Clinical Trials Directive in 2004 15/27 Member States working with the same english versions of documents like - Investigational Medicinal Product Dossier (IMPD) - Protocol - Investigators Brochure - SmPCs but EURECNET, Challenges of Multicenter Studies in Europe; 13.4.2012 H. Krafft Page 4
Situation of clinical trials after the implementation of the Clinical Trials Directive in 2004 not harmonised are - Assessments - Treatment options and standards - Some documents related to the clinical trial applications due to different interpretations of guidance documents - Application times at the national Competent Authorities EURECNET, Challenges of Multicenter Studies in Europe; 13.4.2012 H. Krafft Page 5
Distribution of Clinical Trials in Europe in one Member State vs multinational in percent 100 Percent of clinical trials 80 60 40 20 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Member States per clinical trial Status 19.5.2010 EURECNET, Challenges of Multicenter Studies in Europe; 13.4.2012 H. Krafft Page 6
The Voluntary Harmonisation Procedure offers a solution to address these points within the existing European legal framework Akademie für Fortbildung Heidelberg; 16.2.2012; Voluntary Harmonisation Procedure; H. Krafft Page 7
Present EU Voluntary situation Harmonisation for the approval Procedure of a (VHP) for multinational a multinational Clinical Clinical Trial Trials Time 0 Competent Authorities Ethics Committees 30 60 90 120 nat.approval - Result of Clinical Trial Application - EURECNET, Challenges of Multicenter Studies in Europe; 13.4.2012 H. Krafft Page 8
Coordinated Assessment Procedure (CAP) for a multinational Clinical Trials? Competent Authorities and Ethics Committees Time 0 Rapporteur Member States 1-3 Member State 4 30 60 90 120 - nat.approval Opt out; i.e. no participation of MS in this clinical trial No nat. approval possible? Voluntary Harmonisation Procedure;BMG; 2.5.2011 H. Krafft Page 9
Key features of the Voluntary Harmonisation Procedure Only electronic documents sent to one address (one stop shop) Only general documents required, which are part of any clinical trial application (Protocol, Investigators brochure, Investigational Med. Product Dossier) Reliable timelines for Sponsor and Member States Harmonised scientific discussion resulting in harmonised applications in the Member States - no Member States specific modifications necessary - consolidated lists of grounds for non-acceptance, if needed EURECNET, Challenges of Multicenter Studies in Europe; 13.4.2012 H. Krafft Page 10
Features of a New Regulation Single (electronic) portal - Harmonisation of requirements* Assessment Committee & Assessment Coordination - A Coordinated Assessment Procedure (CAP)* Risk Adaptation - adapt requirements (regulatory, monitoring, pharmacovigilance, insurances, etc.) for clinical trials to the related risks* Decisions * http://www.biopeople.dk/fileadmin/filer/jette/final_report_- _EFGCP_EORTC_Consensus_Workshop_4_July_2011.pdf EURECNET, Challenges of Multicenter Studies in Europe; 13.4.2012 H. Krafft Page 11
Submission of the clinical trial application Single portal for NCAs and ECs - really for 75% clinical trials in 1 Member State (3000 CT p.a.)? - Portal for Clinical Trial Applications and substantial amendments - Not only distributing or forwarding documents >>> 27 copies - Containing all documents also the country specific info. like informed consent information on trial centers - Access of all MS to all information (as in EudraCT) not only concerned Member States - Validation by VHP-C and Ref-NCA Repository for NCA and EC for shared documents - e.g. Assessment reports; Status (reports) for each procedure - anybody can not do ~1000 multinational CT p.a. by mails etc. EURECNET, Challenges of Multicenter Studies in Europe; 13.4.2012 H. Krafft Page 12
Evaluation Process The Assessment Committee: - Representation of each MSs NCA and EC - Meeting every month / dealing with 80 CTA? - Tremendous Costs - Legal basis for CTFG to serve as Assessm. Com. Assessment Coordination - No proposal of Rapp. by Sponsor (independence) - Coordination per procedure needs harmonisation again, better one coordinating body - Who answers questions/by mail/phone EURECNET, Challenges of Multicenter Studies in Europe; 13.4.2012 H. Krafft Page 13
Decisions Majority votes / opting out / serious health concerns are contradictions After a joint positive assessment by the Member States approval should be issued by each Member States in short timelimes In a second wave the Member States must have the same rights as in the first (GNA and timelines, etc) - Support by the Ref-NCA - Access to the repository EURECNET, Challenges of Multicenter Studies in Europe; 13.4.2012 H. Krafft Page 14
Learn from the 3 years experience of CTFG More than 170 VHPs EURECNET, Challenges of Multicenter Studies in Europe; 13.4.2012 H. Krafft Page 15
Lessons from 3 years VHP Saving resources by avoiding unnecessary assessment Effective IT is crucial No separation of administrative and scientific steps possible without losing quality and time Active scientific management is needed to meet timelines and find solutions case by case Flexibility in the decisions has to be possible (conditions, commitments, for new questions ask the concerned MS) Fees are justified for the procedure as a lot of resources at the sponsor is saved (consolidated list of GNA, one application, no paper, etc) EURECNET, Challenges of Multicenter Studies in Europe; 13.4.2012 H. Krafft Page 16
Don t forget: Saving time and simplification is not the most important issue TGN1412 Avoiding this and worse is the issue! EURECNET, Challenges of Multicenter Studies in Europe; 13.4.2012 H. Krafft Page 17