On 22 and 23 June 2023, EPHA attended the kick-off workshop of the multistakeholder platform for the Accelerating Clinical Trials in the EU (ACT EU) initiative organized by the European Medicines Agency. EPHA also contributed to a session aimed at discussing “how to ensure that key clinical trial information is publicly available while achieving a balanced protection of sponsors’ legitimate economic interest?”
The remarks that follow built upon the work of some of our members and partners in the European Alliance for Responsible R&D and Affordable Medicines that have made recommendations to improve the transparency of clinical trials.
Transparency of clinical trials in the EU Clinical Trials Regulation
Transparency of clinical trials is a key pillar of the European Clinical Trials Regulation (CTR). Article 81 (4), which regulates the EU database on clinical trials (CTIS) states that:
“The EU database shall be publicly accessible unless, for all or part of the data and information contained therein, confidentiality is justified on any of the following grounds:
- protecting personal data in accordance with Regulation (EC) No 45/2001;
- 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 disclosure;
- protecting confidential communication between Member States in relation to the preparation of the assessment report;
- ensuring effective supervision of the conduct of a clinical trial by Member States.”
Such exceptions need to be interpreted narrowly and according to the spirit of the Regulation. Indeed, recital 67 emphasises 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”.
What are the current issues with clinical trials transparency in the implementation of the CTR?
In the short remarks shared during the session on transparency of clinical trials, EPHA recognised the efforts and progress made by the European Commission, the European Medicines Agency, and the national authorities and welcomed the open debate within the multistakeholder platform kick-off workshop. A few areas requiring further attention include the use of deferrals and redactions to key documents published in the Clinical Trial Information System (CTIS), which is the central EU database on clinical trials.
Deferrals and redactions
Allowing companies to defer publication of the underlying trial protocols is problematic, and indeed, the guidance document recognizes that: “extensive deferrals could significantly reduce the utility of clinical data in CTIS”.
Delaying the publication of clinical trial protocols after trial completion is not included in the CTR (it was included in an annex), and defeats its purpose advance the transparency of clinical trials in order to benefit scientific research, patients and society at large.
This was explained by a joint letter developed by several patients, healthcare professionals and other health NGOs and sent to the EMA Management Board last year, which asked the Board “to direct the agency to disclose unredacted clinical trial protocols for Phase II and Phase III trials on CTIS at the time that the summary results of the related trials are made public.”
And while redactions might be preferable to deferrals as a mechanism to balance the potential need to protect the economic interest of sponsors, they should also be used with caution as explained by a guidance document:
“Application of redaction should be done with scrupulous judgment. It should be considered that extensive redaction in the document versions ‘for publication’ would go against the spirit of transparency of CTR. It needs to be emphasized that the redacted documents have to remain meaningful to the public, including potential trial participants and health care professionals”.
Monitoring progress of transparency is crucial to achieve the goals of the Clinical Trials Regulation
In 2021, Health Action International (HAI) and Transparimed published a paper looking at progress made and identifying key areas to further improvement the CTIS. One of the key recommendations of this report is to integrate public performance dashboards within the CTIS database. This would enable sponsors to monitor their own compliance and will also allow the general public (including patients and healthcare groups) to monitor progress and identify remaining gaps.
Indeed, while clinical trial sponsors have been obliged to publish the results of some drug trials on EudraCT since 2014, as revealed by the EU Trials Tracker launched in 2018, huge compliance gaps remain. To avoid this, the CTIS (and also Eudamed) should incorporate performance dashboards that make compliance (or lack thereof) visible to the same sponsors, and to interested stakeholders and the public at large.
