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

2. 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

3. 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

4. Legal origin

5. 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

6. Current Status – Version 6

7. 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

8. Total number of EudraCT numbers issued

9. 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

10. 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.

11. June Version 7

12. 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

13. 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

14. Transparency – legal framework finalised

15. 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

16. 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

17. 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

18. Protocol information – Version 8

19. 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

20. 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

21. Results information – Version 9

22. 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

23. 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.”

24. 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

25. 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

26. 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

27. Workshop in June 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

28. Thank you