Appendix on transparency rules to the Functional ...

1 30 Churchill Place Canary Wharf London E14 5EU United Kingdom An agency of the European Union Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website European Medicines Agency, 2015. Reproduction is authorised provided the source is acknowledged. 2 October 2015 EMA/228383/2015 Endorsed Appendix , on disclosure rules , to the Functional specifications for the EU portal and EU database to be audited - EMA/42176/2014 Draft reviewed with the clinical trials information system expert group 8 December 2014 Consultation with the MS for release for public consultation 9 December 2014 - 13 January 2015 Consultation with the European Commission for release for public consultation 9 December 2014 13 January 2015 Public consultation 21 January 18 February 2015 Consultation of the final document by the European Commission 7 September 2015 Consultation of the final document by the Member States 7 September 2015 Endorsement by European Medicines Agency Management Board 2 October 2015 Sign off by the Deputy Executive Director 5 October 2015 Appendix .

2 On disclosure rules , to the Functional specifications for the EU portal and EU database to be audited - EMA/42176/2014 EMA/228383/2015 Page 2/29 Appendix , on disclosure rules , to the Functional specifications for the EU portal and EU database to be audited - EMA/42176/2014 Table of contents 1. Executive summary .. 3 2. Background and introduction .. 4 3. Legal basis .. 5 The disclosure requirements of the Clinical Trial Regulation .. 5 The disclosure requirements of the Paediatric Regulation (EC) No 1901/2006 .. 7 Application of Regulation (EC) No 1049/2001 .. 8 Status of clinical trials made public under the current clinical trial legislation in the EU Clinical Trial Register .. 8 4. Application of the disclosure requirements - Data and documents to be made public and timing of publication.

3 8 Background .. 8 Protecting personal data in accordance with Regulation (EC) No 45/2001 .. 8 Protecting commercially confidential information, in particular through taking into account the status of the marketing authorisation for the medicinal product, unless there is an overriding public interest in 11 Protecting confidential communication between Member States in relation to the pr eparation of the assessment report .. 22 Ensuring effective supervision of the conduct of a clinical trial by Member States .. 22 Reporting of unexpected events in accordance with Article 53 and urgent safety measures in accordance with Article 54, and temporary halts and early terminations of clinical trials.. 24 Clinical study reports submitted by the marketing-authorisation applicant.

4 25 Arrangements for payment of investigators and sites .. 25 ANNEX I: details of documents supporting clinical trial applications and the rationale for the times at which they are made public.. 26 Appendix , on disclosure rules , to the Functional specifications for the EU portal and EU database to be audited - EMA/42176/2014 EMA/228383/2015 Page 3/29 1. Executive summary The clinical trial Regulation (EU) No 536/2014 aims to foster innovation through simplification of the clinical trial application process, and to increase transparency and availability of information on clinical trials and their results. The key instrument to ensure transparency of clinical trials is the EU cli nical trial portal and database that will be used for submission and maintenance of clinical trial applications and authorisations within the European Union.

5 The database serves as the source of public information on clinical trial applications assessed, and clinical trials conducted in the EU, from the time of decision to authorise a trial up to the finalisation of those trials and inclusion of their results in the database. The Regulation gives EMA responsibility for the development and maintenance of the portal and database. The Regulation states that the EU database shall be publicly available unless one or more exceptions apply . These exceptions are: to protect personal data; to protect commercially confidential information, in particular taking into account the marketing authorisation status of the medicinal product, unless there is an overriding public interest in disclosure; to protect confidential communication between Member States in preparing their assessment; to protect the supervision of clinical trials by Member States.

6 This Appendix sets out rules and criteria for the application of these exceptions in relation to the disclosure provisions of the European Clinical Trial Regulation. This Appendix complements the Functional specifications for the EU portal and database to be audited, which were drawn up by the Agency and endorsed by its Management Board in December 2014 and its addendum on Functional requirements to support transparency endorsed by the Agency Management Board in March 2015 . A balanced approach is needed to protect public health and also foster the innovation capacity of European medical research, thus supporting the EU as a location for innovative, cutting edge research that results in the development of novel products and research into new and better uses of existing products.

7 The information that will be made public for all clinical trials registered in the system includes: the main characteristics of the trial comprising design, scientific and, where applicable, therapeutic intent, title, identification of the investigational medicinal products (IMPs), treatment arms, treatment population and number of subjects, inclusion and exclusion criteria and main objectives and endpoints; conclusion of the assessment and decision on the trial; information updated during the trial to indicate the start and end dates of recruitment; substantial modifications to the trial; the end date of the trial, with reasons for which trials are ended prematurely where applicable, and, 12 months later, the summary of results and a summary in lay language; clinical study reports for clinical trials on medicines for which a marketing authorisation has been granted, the procedure completed or the marketing authorisation application withdrawn.

8 Appendix , on disclosure rules , to the Functional specifications for the EU portal and EU database to be audited - EMA/42176/2014 EMA/228383/2015 Page 4/29 The list of abbreviations of the Functional specifications of the EU portal and EU database to be audited will be updated to include the abbreviations contained in this document. 2. Background and introduction 1. Clinical trials are performed in many different contexts. They are conducted to generate data to support applications for marketing authorisation and to expand scientific knowledge on medicines through publications in medical journals. Therefore, clinical trials are an indispensable part of clinical research which, in turn, is essential to develop medicinal products and improve medical treatment.

9 Without clinical trials, there would be no new medicines, no further development of existing medicines, and no evidence-based improvement of treatments with medicines. 2. The EU Clinical Trial Regulation (EU) No 536/2014 has a number of objectives and aims amongst others: To protect the rights, safety, dignity and well-being of subjects and the reliability and robustness of the data generated. The interests of the subjects should always take priority over all other interests. To this end clinical trials are subject to prior authorisation. Foster innovation and simplify the clinical trial application process, in particular for multistate trials. To provide publicly available information from the EU database, increasing transparency of clinical trials and their results - this should contribute to protecting public health and fostering the innovation capacity of European medical research, while recognising the legitimate economic interests of sponsors.

10 3. The Regulation foresees transparency on the conduct of trials in the European Union1 from the point of their authorisation to the publication of the results of those clinical trials. Information published at the time of decision on the trial should be updated, if it is changed ( by substantial modification or other notification) during the course of the trial. The application of the disclosure rules and criteria should ensure that all of the following requirements are met. Public access to clinical trial information is provided to: Ensure that a public record exists of all clinical trials conducted in the EU and their outcome, thus, providing the EU contribution to the global objective of ensuring that all clinical trials in human subjects are publicly registered.