Under European Union Clinical Trial Regulation 536/2014 (EU-CTR), replacing the EU Clinical Trial Directive (Directive 2001/20/EC), drug developers must now anonymize or redact clinical trial documents at the same time they are preparing them for regulatory submission (read more about the redaction process in this blog). This makes complying with transparency and disclosure requirements necessary now, not later during the product approval stage.
This regulation came into effect on January 31st, 2022, through the online Clinical Trials Information System (CTIS) platform, allowing for a 3-year transition period for sponsors to become compliant. Beginning from January 31st, 2023, sponsors will need to use the CTIS for all new clinical trial submissions in the European Union (EU). All active trials would need to be transferred to CTIS by January 31st, 2025.
What are the goals of the EU-CTR?
The aim of the EU-CTR is to harmonize clinical trials throughout the EU and improve the way clinical trials are conducted and regulated. Previously, pharmaceutical companies had to submit clinical trial applications for each European country to gain regulatory approval. Now, a single clinical trial application on CTIS is sufficient for a trial anywhere in the EU. The Regulation makes the entire multinational clinical trial application process more efficient and permits faster authorization of trials. CTIS enables synchronized assessment across EU countries, improves patient recruitment, and provides greater transparency for data sharing within the biomedical research community.
Challenges And Lessons Learnt
Nearly 6 months after CTIS has gone live, first impressions have been more varied and suggestive of active collaboration among clinical operations, transparency and disclosure, and regulatory operations, to name a few, for timely submission. The publication of clinical trial documents on the CTIS requires proactive transparency and disclosure activities, unlike before. While the establishment of EU-CTR has reduced the administrative overhead of multiple application submissions to a single approval, it has challenges of its own. The relatively early transparency activities under a strict timeframe often means that clinical trial documents are anonymized on a rolling basis, since they may not be available all at once. Since the Regulation is still relatively new, sponsors may need to adjust organizational standard operating protocols (SOPs) for regulatory strategy and clinical operations accordingly, which could prove to be time consuming.
The availability of only a draft guidance document and a lack of established direction from the EMA to Sponsors (unlike EMA Policy 0070) hinders the overall transparency process. Per this guidance, CTIS users are responsible for the quality, accuracy, and adequacy of anonymization/redactions applied to structured data or documents uploaded and submitted to CTIS for publication. Although the draft guidance refers to Policies 0070 and 0043, there may be discrepancies. For instance, while the Investigator curriculum vitae are out-of-scope for Policy 0070, they are required for publication on CTIS. Similarly, unlike Policy 0070, non-English content is in-scope of publication on CTIS. Recognizing the scope of required documents and including them for the submission, is one way to eliminate added transparency efforts required in such cases.
The occurrence of protected personal data (PPD) may be fewer/less frequent due to the inherent nature of the documents involved, like the protocol and the Investigator’s Brochure. However, clinical trial applications for newer drugs may contain significant Commercial Confidential Information (CCI). CCI refers to any information contained in the clinical reports submitted to EMA by the applicant which is not in the public domain or publicly available and where disclosure may undermine the legitimate economic interest of the applicant. The identification of CCI requires collaboration between multiple stakeholders (for instance, transparency and disclosure team, clinical operations, regulatory affairs, and the legal team) to ensure documents are accurately anonymized while maintaining data utility. Transparency subject matter experts recommend that medical writing teams write clinical trial documents (such as protocols, investigational brochures, and investigational medicinal product dossiers; IMPDs) to minimize the amount of CCI to facilitate the T&D process.
Furthermore, EMA has provided templates for documents such as the curriculum vitae. Documents prepared in accordance with the templates require minimal redaction, thus streamlining the process. This change in templates may require organizational SOP changes.
While the pharmaceutical industry has now been engaged in EU-CTR submissions via CTIS for over six months, there isn’t evidence that the EMA reviews the documents submitted for publication on CTIS. This leaves the sponsor liable for leaked PPD information or sensitive CCI information.
As sponsors prepare to submit clinical trial applications via CTIS and navigate through new waters, preparedness is crucial. The key to success is internal organizational readiness and development of working groups to ensure timely decisions to establish internal workflows are taken.
The strict approval timeline has compelled sponsors to acquire the help of transparency subject matter experts, such as those at Certara to assist in the process. Our in-house expertise and AI enabled technical services provide the ultra-fast turn arounds that are required for timely CTIS submissions. Our transparency team at Certara caters to the unique requirements of each company and provides an optimized solution for transparency, with ‘on-call’ support for guidance and resolution of transparency emergencies.
Certara can be your next partner for all your EU-CTR needs as a leading technology and services provider in the transparency and disclosure space. Our years of experience in successfully supporting programs across regions, as well as our exclusive team of experts, are primed to help you meet and exceed your compliance requirements. Click below to learn more and to contact us.