Implementing the Clinical Trials Regulation’s various provisions and staying on top of relevant new information is a challenge for many companies conducting clinical trials in the EU.
Since the CTR became applicable on 31 January 2022 and EU Member State law was adapted accordingly, there has been a constant flow of new guidance documents, information material and events, as well as frequent updates to the published information. All of this is communicated through different channels by the European Commission (EC), European Medicines Agency (EMA), Heads of Medicines Agencies (HMA) and the individual member states (MS)i, ii, iii. This can make it very difficult to keep track of all relevant regulatory intelligence.
However, given the criticality of being in compliance with the CTR, it is highly advisable to have an internal or external expert or team of experts charged with following these developments. This ensures no relevant recommendations and requirements escape sponsors’ notice, and they can plan accordingly.
Update brings clarity
One recently announced important change is the update of the transparency rules iv. This is likely to be welcomed by many sponsors who found the previous rules unnecessarily complex.
Sponsors struggled with deciding whether to redact commercially confidential information (CCI) in documents that would be made publicly available or use the publication deferral option in Clinical Trials Information System (CTIS), because the implications of the different options weren’t clear. Even though this was discouraged by the EMA many opted to do both CCI redaction and deferral.
One reason for this uncertainty may be that some sponsors have been unaware of the EMA’s recommendations. In our view, another reason is likely that even though it is stated in the Commission’s CTR Q&A documentv that it would be possible to redact information still considered CCI after expiry of the deferral, no process has been implemented and no guidance published that clarified how and when this was supposed to be done.
Moreover, in addition to having to navigate the rules, the very act of performing the redactions created considerable workload for sponsors while the net benefit to the public of publishing all this information was somewhat questionable.
The update of the transparency rules addresses these difficulties and, at least with regard to implementation of CTR transparency requirements, will likely facilitate and streamline the dossier preparation process. The new rules aim to simplify the process and provision as well as to reduce the complexity of information to be published by focusing more on information and documentation that is of true interest to the public and corresponds better to the needs of patients and clinical researchers.
Key changes to the transparency rules:
- Fewer documents will be made publicly available and thus need to be redacted. (Only protocol, synopsis, patient facing documents, the summary of product characteristics (SmPC, if available), recruitment arrangements/procedures/material, and for category 2 and 3 trials (phase I/II, II, III, IV and low interventional trials) the summary of results and the summary of results in lay language)
- The deferral option will be removed from CTIS.
- Publication of information from category 2 and 3 trials can no longer be deferred.
- For category 1 trials, i.e. phase 0, phase I, bioequivalence/bioavailability, therapeutic equivalence and biosimilar trials (adult population), publication of the documents listed above as well as of some data fields (e.g. product details) is automatically deferred until 30 months after the end of the clinical trial. (For category 1 trials in pediatric populations, the documents are published at the time the results summary is submitted.)
- Publication of product details for Phase I/II trials is deferred. (Such trials formally fall under category 2, but the sensitivity of some data of such early phase trials is recognized and protected.)
The new guidance document, which was published on 5 October 2023, is connected to a technical update of CTIS and is expected to become mandatory in the second quarter of 2024, at the earliest. However, the new rules can already be applied for submissions, for example of transition applications, before the system update vi. In practice, this means that for documents not to be made publicly available according to the new rules, a placeholder (instead of a redacted document) can be uploaded in the “for publication” slot in CTIS. This placeholder needs to contain the wording provided in Annex I of EMA’s transparency Q&A document vii. In the “not for publication” section, the unredacted version of the document has to be provided (as before). For documents to be made publicly available, even after the new rules are applicable, both a redacted and an unredacted version still need to be uploaded.
It is important to note that until go-live of the system update, it will technically still be possible to apply for deferrals. Deferral mechanisms, however, will not be implemented, and EMA discourages sponsors from using this function.
In addition, for trials (including transitional trials) that have already been submitted according to the old transparency rules and that may have deferrals in place instead of redactions, nothing will get published until the new rules are applicable and sponsors have updated their dossiers for compliance with the new rules. What that means is those trials are not at risk of sensitive information being made publicly available as a result of an overlapping application between the old and new rules.
About the author:
Xandra Neuberger is Associate Director Regulatory Affairs and international service lead for clinical trial applications at PharmaLex, leveraging her extensive experience with clinical trial applications and life cycle management to support the industry. She also handles project and team coordination in her role. Xandra is a registered pharmacist in Germany and has also practiced pharmacy in the UK.
Notes
ii https://health.ec.europa.eu/medicinal-products/eudralex/eudralex-volume-10_en
iii https://www.hma.eu/about-hma/working-groups/clinical-trials-coordination-group.html
iv Revised CTIS Transparency Rules, EMA and HMA, Oct 2023. https://www.ema.europa.eu/en/documents/other/revised-ctis-transparency-rules_en.pdf
v https://health.ec.europa.eu/system/files/2023-12/regulation5362014_qa_en_0.pdf
