innovation
The EU legislation on clinical trials has gone through some significant modifications during the last decade. These changes started in 2004 with the implementation of the Clinical Trials Directive and continued in 2005 with the publication of the Good Clinical Practice Directive (Directive 2005/28/EC). 425 More recently the legislative landscpape for clinical trials was updated by the Clinical Trials Regulation that is scheduled to become effective by October 2018 at the latest. The main objective of the Clinical Trials Directive is to ensure that: the rules for conducting clinical trials are consistent throughout the EU; and information is made publicly available on the authorisation, conduct, and results of each clinical trial carried out in the EU.426 The Clinical Trials Regulation also strives for increasing transparency of clinical trials in the EU, from the point of authorisation of the trials to the publication of the results. Hence it seeks to improve the availability of information to patients, caregivers and healthcare professionals on ongoing clinical trials.427 Transparency is also expected to foster
422 Mikolášik, M. Report on the on the proposal for a regulation of the European Parliament and of the Council on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004 (COM(2005)0567 – C6-0401/2005 – 2005/0227(COD))Committee on the Environment, Public Health and Food Safety, see amendment 3. Available at:
http://www.europarl.europa.eu/sides/getDoc.do?pubRef=-//EP//TEXT+REPORT+A6-2007-0031+0+DOC+XML+V0//EN. Accessed 19 August 2016.
423 See e.g. Judge, supra note 421, 53–71.
424 Pirnay, et al., supra note 22, 539. Pirnay, et al. criticise the fact that ethical considerations were left outside the scope of the ATMP Regulation.
425 European Commission. “Consultation document: Risk proportionate approaches in clinical trials”
“Available at: http://ec.europa.eu/health/files/clinicaltrials/2016_06_pc_guidelines/gl_4_consult.pdf Accessed 21 June 2016.
426 European Medicines Agency. Clinical Trial Regulation. Available at:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000629.jsp&mi d=WC0b01ac05808768df. Accessed 21 June 2016.
427 European Medicines Agency. Public consultation on implementation of transparency requirements of
the European Clinical Trial Regulation,p.1. Available at:
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innovation and stimulate research. It is also predicted to help avoidance of unnecessary duplication of clinical trials, and repetition of trials that have been terminated due to major safety or efficacy concerns.428 The Clinical Trials Regulation will apply to interventional clinical trials on medicines once the Clinical Trial Regulation is in operation, and to all trials authorised under the previous Clinical Trials Directive and still ongoing three years after the Clinical Trials Regulation has entered into force. After the Clinical Trials Regulation has become effective, the Clinical Trials Regulation requires the EMA to develop and maintain a clinical trial portal and database to be used for the submission, authorisation and supervision of trials in the EU. Yet, authorisation and oversight of clinical trials remains the competence of EU Member States. The portal and database is purported to serve as source of public information on the clinical trial applications assessed, and all clinical trials conducted in the EU.429
Article 82(1) of the Clinical Trials Regulation requires the EMA to draw up the functional specifications together with the time frame for their implementation, in collaboration with the Member States and European Commission. The EMA consulted on its proposals with EU Member States, the European Commission and stakeholders representing non-commercial and commercial clinical-trial sponsors, healthcare professionals and patient groups. To finalise the functional specifications, the EMA released a draft proposal for public consultation from 10 October to 31 October 2014. A total of 47 individuals and organisations submitted more than 500 comments.430 To get further perspectives on its proposals for implementing the transparency requirements, EMA released a draft documents for public consultation from 21 January to 18 February 2015.431 Over 80 different individuals and organisations submitted more than 1100 comments.432 Beyond comments of technical nature, concerns were raised
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2015/01/WC500180632.pdf. Accessed:
21 June 2016.
428 Ibid.
429European Medicines Agency. Clinical Trial Regulation. Available at:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000629.jsp&mi d=WC0b01ac05808768df. Accessed 21 June 2016.
430European Medicines Agency. Overview of comments received on “Draft functional specifications for the EU portal and EU database to be audited”. Available at:
http://www.ema.europa.eu/docs/en_GB/document_library/Overview_of_comments/2015/11/WC5001973 24.pdf. Accessed 21 June 2016.
431 European Medicines Agency. Draft proposal for an addendum, on transparency, to the “Functional specifications for the EU portal and EU database to be audited” and “Draft Appendices to Draft proposal for an addendum, on transparency, to the "Functional specifications for the EU portal and
EU database to be audited. Available at:
http://www.ema.europa.eu/ema/doc_index.jsp?curl=pages/includes/document/document_detail.jsp?webC ontentId=WC500180618&murl=menus/document_library/document_library.jsp&mid=0b01ac058009a3d c. http://www.ema.europa.eu/docs/en_GB/document_library/Other/2015/01/WC500180415.pdf.
Accessed 5 June 2015.
432 European Medicines Agency. Overview of comments on EMA/641479/2014 Draft proposal for an addendum, on transparency, to the “Functional specifications for the EU portal and EU database to be
audited - EMA/42176/2014. Available at:
http://www.ema.europa.eu/docs/en_GB/document_library/Overview_of_comments/2015/11/WC5001965 62.pdf. Accessed 21 June 2016. “Draft Appendices to Draft proposal for an addendum, on transparency,
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regarding unclear scope of the applicable exceptions to the publication requirements and protection of personal data in an automated system.
Under the Clinical Trials Regulation the information on all clinical trials must include the key features of the trial; details of treatment population and number of subjects; inclusion and exclusion criteria, main objectives and endpoints; the dates of the start and end of recruitment; substantial modifications made to protocol during the trial; the end date of the trial and, 12 months later, the summary of results and a lay summary.433 Furthermore, for clinical trials included in a marketing authorisation application in the EU, clinical study reports will also be published 30 days after the procedure for granting the marketing authorisation has been completed or the applicant for marketing authorisation has withdrawn the application. Despite the Regulation states that information on clinical trials shall be publicly available, confidential information do not need to be disclosed. 434 The Clinical Trial Regulation defines that confidentiality is justified for following reasons: protection of personal data; protection of commercially confidential information (considering the marketing authorisation status of the medicine, unless there is an overriding public interest); as well as protection confidential communication between Member States in the preparation of their assessment; and ensuring effective supervision of the conduct of clinical trials by Member States.435 Yet, no specific examples of information from registration or summary results that should be commercially confidential have been provided.Specific
to the "Functional specifications for the EU portal and EU database to be audited” EMA/641479/2014”
Available at:
http://www.ema.europa.eu/docs/en_GB/document_library/Other/2015/01/WC500180415.pdf. Accessed on 6 June 2016.
433 Clinical Trials Regulation, Recital 67 states that: “In order to ensure a sufficient level of transparency in the clinical trials, the EU database should contain all relevant information as regards the clinical trial submitted through the EU portal. The EU database should be publicly accessible and data should be presented in an easily searchable format, with related data and documents linked together by the EU trial number and with hyperlinks, for example linking together the summary, the layperson's summary, the protocol and the clinical study report of one clinical trial, as well as linking to data from other clinical trials which used the same investigational medicinal product. All clinical trials should be registered in the EU database prior to being started. As a rule, the start and end dates of the recruitment of subjects should also be published in the EU database. No personal data of data subjects participating in a clinical trial should be recorded in the EU database. The information in the EU database should be public, unless specific reasons require that a piece of information should not be published, in order to protect the right of the individual to private life and the right to the protection of personal data, recognised by Articles 7 and 8 of the Charter. Publicly available information contained in the EU database should contribute to protecting public health and fostering the innovation capacity of European medical research, while recognising the legitimate economic interests of sponsors.”
434 Clinical Trials Regulation, Recital 68 states that: “For the purposes of this Regulation, in general the data included in a clinical study report should not be considered commercially confidential once a marketing authorisation has been granted, the procedure for granting the marketing authorisation has been completed, the application for marketing authorisation has been withdrawn. In addition, the main characteristics of a clinical trial, the conclusion on Part I of the assessment report for the authorisation of a clinical trial, the decision on the authorisation of a clinical trial, the substantial modification of a clinical trial, and the clinical trial results including reasons for temporary halt and early termination, in general, should not be considered confidential.”
435 Article 81, para. 4.
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concerns were also raised that sponsors of clinical trials do not wish to disclose information on new indications and/or formulations for authorised products early, as this may affect patent protection. Furthermore, particular concerns were raised regarding endeavors to automate considerations of confidential commercial information and publication of anonymised of personal data. 436