EU CTR: Transparency

In the end of January 2022, the EU CTR (EU/536/2014) came into effect within the European Union (EU), replacing the EU Clinical Trials Directive (2001/20/ EC). Under the EU CTR, a new EU database – the Clinical Trials Information System (CTIS) was created to provide a single-entry point for submitting, assessing, authorizing, supervising, and reporting a clinical trial in all member states in the EU and European Economic Area (EEA).

Transparency

As an overall policy of the European Medicines Agency (EMA) to increase transparency standards globally, the EU CTR requires that all information in the CTIS is publicly available once the trial is approved. As a core provision, the EU CTR states that any data submitted as part of a clinical trial application (CTA) in any EU member state will be made public unless there is a superior justification not to do so. According to Article 81(4) of the regulation there are some exceptions to the rule, such as: (i) protecting personal data in accordance with applicable regulations, and (ii) protecting commercially confidential information (CCI) considering the status of the marketing authorization (MA) for the medicinal product.

Protecting Personal Data

Under the EU General Data Protection Regulation (GDPR) it is crucial to protect personal data when deciding to disclose information. As such, as a general principle, only personal data that are strictly necessary for the assessment of the trial should be provided. Article 81(7) of the EU CTR sets out that no personal data of trial participants may be made publicly accessible; as such, the sponsor has an obligation to protect the rights of trial participants. Additionally, it is the responsibility of the sponsor to ensure that only redacted personal data of clinical investigators, sponsor employees, or other personnel working on the trial are included in documentation submitted with a CTA, or in the clinical trial report.

The CTIS enables the submission of “for publication” (redacted, unreadable personal data) and “not for publication” (unredacted) versions of documents. With this in mind, the default version of the trial documentation is marked “for publication” and should always be provided and uploaded first, which is then immediately followed by the version that is “not for publication”, if one is needed. Special attention should be given to the content of the structured data fields in CTIS, because no redaction is possible for those data fields.

Protection of CCI

Information included in the CTA, or shared throughout the trial lifecycle that could harm the legitimate economic interests or competitive position of the sponsor of the trial – or later the applicant/holder of the marketing authorization, can be redacted or deferred for a certain period of time. As such, it is up to the sponsor to determine what qualifies as CCI, depending on the phase of the trial or the development status of the investigational medicinal product (IMP) being used, safeguarding patentable information at the current development stage but also with regards to the future.

In case of deferral, it is assumed that by the time the deferral period ends, the majority of the information will no longer qualify as CCI, and redaction of deferred documents is therefore not needed or expected. However, the guidance indicates that in certain exceptional circumstances, some pieces of information (e.g., the quality data in the protocol) could still be considered CCI after the deferral period has ended and can still be redacted from the documents that will be published on public domain, although member states can override these decisions. As such, involving a patent attorney early in the process of deferral discussions is useful, along with educating stakeholders on deferral options and justifications.

EMA’s policy regarding the mechanisms to avoid publication of CCI has shifted from allowing both redaction and deferral, to now emphasizing only on one approach or the other. In this regards, the policy might evolve further as an outcome of the ongoing EMA consultation of transparency requirements with stakeholders.

For trials with an integrated Phase 1/Phase 2 design, the transparency guidance identifies the details of IMP maximum daily dose (MDD) allowed and maximum total dose (MTD) allowed as potential CCI. The sponsor will need to provide justified grounds why this may be patentable information that should not go into the public domain.

Member state assessment report and CCI

Another transparency reality is that CCI that is included in CTA documentation may also carry through into the member state assessment report, and the sponsor has no possibility to review the assessment report content prior to the publication by the member state. The EU transparency guidance recognizes this issue, and to minimize the potential for unintended inclusion of CCI when preparing the assessment report, it is recommended that the sponsor flags in the CTA document version “not for publication” which data should be redacted in the matching “for publication” version. This will allow the member states to exactly align their redactions in the assessment report to the sponsor’s request.

Conclusion

If not managed effectively, the increased transparency obligations in the EU pose a considerable operational burden for sponsors. Such obligations need to be factored into the resource and timeline considerations when planning new study applications under the EU CTR. Notwithstanding, the aim for all the involved is to enhance public trust and promote informed decision making, while maintaining data integrity in clinical development.

Image: Stock Photo