EudraCT Public information on Clinical Trials - update Fergus Sweeney EMEA DIA GCP SIAC teleconference 23 April 2009

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 EMEA and/or its scientific committees

EudraCT - Developments Legal origin Current Status – Version 6 Version 7 - June 2009 Transparency – legal framework finalised Protocol information – Version 8 – Nov 2009 Results information – Version 9 - 2010

Legal origin

EudraCT established April 2004 Article 11 Dir 2001/20/EC - A European database accessible only to the competent authorities containing extracts from the request for authorisation any amendments made to the request any amendments made to the protocol opinion of the Ethics Committee; declaration of the end of the clinical trial; reference to inspections Article 57(2) of Regulation No (EC) 726/2004 and Article 41 of Regulation No (EC) 1901/2006 provide derogation from the confidentiality, so that some information will be made public data fields, to be identified by Commission guidelines including third country paediatric studies included in a PIP and results of the trials to be made public

Current Status – Version 6

Numbers of clinical trials registered in EudraCT (1 May 2004 to 28 February 2009) Distinct clinical trials – 19,219 composed of: Clinical trial applications: 37,938 Type of sponsor Commercial sponsor: 79.5% Non-commercial sponsor: 20% Sites Single site: 28% Multiple site: 65% Countries Multiple member state: 60% Including third country sites:50% 1200 GCP inspections

Total number of EudraCT numbers issued 2004 4613 2005 6214 2006 7124 2007 7987 2008 9334

EudraCT Version 6 One EudraCT number per clinical trial One associated record per involved member state CTA information NCA Authorisation/ethics committee opinion Amendment Interruption and end of trial

EudraCT Version 6 In production Alerts to all NCAs: NCA refusal/negative ethics committee opinion Interruption or premature end for reasons of: Safety, lack of efficacy, IMP quality issues Ability for NCAs to attach documents to CTA record – assessment reports, GNA letters etc.

June 2009 - Version 7

EudraCT Version 7 – key functionality Enhanced validation rules ISO standard tool with public XML of rules available for use by all CTA package – linked pdf, xml and validation report all identified by checksum, delivered in a ZIP file Compare XML – public and secure tool

EudraCT DataWarehouse Only accessible to Competent Authorities, EMEA and Commission Paralell development of EudraCT data warehouse Oracle BI data - warehouse Oracle answers query and reporting tool will be available 2/3 Q 2009

Transparency – legal framework finalised

New legal requirements Two Regulations Article 57(2) of Regulation (EC) No 726/2004 Relates to all clinical trials in EudraCT Article 41 of Regulation (EC) No 1901/2006 Relates to paediatric clinical trials Final guidance now published by Commission Two guidelines Article 57 related guideline published - Final July 2008 Paediatric guideline published–Final February 2009 Two lists of data fields to be made public Both published – Final February 2009

Requirements Article 41 of Regulation (EC) No 1901/2006 the “Paediatric Regulation” with respect to paediatric trials (less than 18 years old): Applies to all paediatric trials within EU, and third country trials if part of Paediatric Investigation Plan Protocol-related information at time of trial authorisation Submitted at the time of application Made public at the time of clinical trial authorisation/refusal Data entry by NCA for EU trials and by Marketing Authorisation Holder, Sponsor, or PIP addressee via EMEA for non-EU trials Results-related information Submission of results within 6 months of completion of trials and made public after submission Data entry by Marketing Authorisation Holder, Sponsor, or PIP addressee via EMEA

New legal requirements Article 57(2) of Regulation (EC) No 726/2004 and the guideline published by the European Commission): Applies to all clinical trials contained in EudraCT with the exception of Phase I trials, including trials of products without a marketing authorisation Protocol-related information Submitted by sponsor, at the time of the clinical trial application trial authorisation, entered by NCAs Made public at the time of the clinical trial authorisation Results-related information Submission of results within one year of the end of the trial, via EMEA Made public following submission

Protocol information – Version 8

What will be made available to the public? – Protocol EudraCT Clinical Trial application form includes information on objectives, population, indication under study, endpoint, medicinal products, contact point… NCA Authorisation and Opinion of Ethics Committee Status of trial – authorised or completed/ interrupted

Recent changes in the regulatory framework for pharmaceuticals and clinical trials will require changes to the CTA form Revised version to be published 2Q 2009 To be implemented and come into force for applications when Version 8 is launched in production - planned Nov 2009 Advanced therapies, first in human trials, facilitation of active substance coding

Results information – Version 9

What will be made available to the public? - Results EudraCT to include outcome: population included, endpoints, effect size, statistics, and status (completed, discontinued, etc.) Results as proposed by sponsor, Marketing Authorisation Holder, or PIP addressee, with a disclaimer that results have not been assessed Linked to the outcome of the assessment by Competent Authorities (e.g. European Public Assessment Report on EMEA website) if and when available Information made public as soon as submitted, following administrative validation

Issues Standardisation: “The EudraCT data fields are for the most part consistent with international initiatives relating to clinical trial registries, e.g. WHO International Clinical Trials Registry Platform (ICTRP) and the International Committee of Medical Journal Editors (ICMJE). Although EudraCT may have additional fields, the convergence of the information to be made public with the WHO ICTRP facilitates the work of sponsors and researchers submitting information to different registries for different purposes, and facilitates access to this information.”

Results limited standardisation of data elements Protocol related information already has significant degree of convergence, data can be mapped between systems to a good degree but can be improved de facto standards in use - EudraCT, WHO, ICMJE, clinicaltrials.gov Results limited standardisation of data elements Standards often only in development: ISO – med id , pharm id CDISC HL7 CTRR (Clinical Trial Registry and Results) ICH E3

Results information “At present, EudraCT does not contain results-related information on clinical trials. Publication of clinical trial results, both positive and negative, will take place as the information actually becomes available in EudraCT. Work to standardise reporting is ongoing and guidelines on the nature of the data collection process, structure of the collected data and structure of the public data will be included in this document and, if necessary, in additional technical documents.“ Development of data structure and standards for Results information: Requires data standard (semantic interoperability) and XML standard – single sponsor source to multiple registry destinations Nature of information, and customer: Granularity of structured data – objective, but less “communicative”, interpretation by user Extent of text information and discussion – less objective, interpretation by writer

Issues Search engines: Presentation: Disease/therapeutic area, IMPs, geography, sponsor… Presentation: Listing of trials Drill down for detail Default single view per trial – local variation Possible local language and English version of key free text Simple, user friendly, explanation and guidance on terminology, limitations of search and of data…. Results as submitted by sponsor – no review prior to publication – clear disclaimers re content and context Links to other product information, SmPCs, EPARs as they become available

Workshop in June 2008 - with commercial and non-commercial representation and patient/carers and healthcare professionals input Website “Reading Room” project – stakeholder surveys and proposal 2-3Q 2009 EudraCT TIG and JOG to work on implementation, results subgroup

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