This is the third and final part of a series of articles where GCP Central goes in-depth into the challenges, learnings, and critical findings of implementing the new European Clinical Trials Regulation (EU CTR). In this instalment, we look at issues encountered in this first year of working with CTIS and essential information about how to cope with these.
Since the introduction of the EU CTR and the adoption of CTIS, change has been implemented in the way clinical trials are required to be submitted for approval. As we explained in our last blog, since the launch of CTIS, sponsors can apply for clinical trial approval either through the Clinical Trial Regulation (CTR) via CTIS or via the Clinical Trials Directive (CTD).
A Period of Change
This year, 2022, has been a year of learning, both by sponsors and Member States, on how to comply with the EU CTR and detect issues in CTIS to be fixed before the end of January 2023. This was highlighted in the recent CTIS newsletter issued by the EMA here.
2023 will be an essential year, as the possibility to submit initial CTAs under the CTD stops. All initial CTAs and current trials submitted via CTIS will be managed via CTIS, which puts a heavy burden on the system that is still in development.
The EMA is planning ahead to maintain the heavy workload they will face and has set up a structure to ensure all users are supported using CTIS and identified issues are resolved. (Source)
A CTIS forum has been created to allow direct exchanges of information and discussion of the user experience of CTIS. It brings users and experts together from Member States, EU sponsors in academia and industry, contract research organizations (CROs), and patients and healthcare professionals (HCPs).
The forum held its first meeting on October 12th, 2022. It will meet every quarter to review CTIS functionalities, system use, development, user support, and knowledge acquisition.
In this last quarter of 2022, CTIS will be updated to fix some issues that Sponsors and Member States encountered. Which issues were these?
Overview of Known Issues
There are 38 known issues listed that sponsor users may encounter when creating a new clinical trial application, a substantial or non-substantial modification, 7 issues related to the review of CTAs and Substantial Modifications by Member States, issues in the Communication between Sponsors and Member States via the Change Application process, issues with the data lock mechanism when users work simultaneously on a document and problems with the publication functionality.
Here are some examples of known issues and their solutions:
- (Access issue) Assigning a User Role in CTIS to an unintended user is not prevented.
Solution: The CTIS process now includes a step for verification of the added user’s email address.
- (Publication issue) The supportive documentation submitted by the sponsor within the overall section of the RFI may not be published as per the system specifications.
Solution: In this case, no solution has been created, and no workaround exists at this point. A fix will be provided in a future system release.
- Connecting a Substantial Modification to multiple trials gives an error.
Solution: Enter the trials for which the Substantial Modification applies one by one.
- The “CT Admin” and/or the “Application Submitter” for a specific trial cannot create substantial or non-substantial modification applications on the trial over which they have been granted the role.
Solution: In this case, no solution has been created, and no workaround exists at this point. A fix will be provided in a future system release.
- It is not possible to upload certain documents to CTIS. Sometimes the problem is that the file size for uploading PDFs is restricted to 10MB.
Solution: Split your PDFs into more than one file to allow easier uploads. There are workarounds in other cases, like content labeling of IMPs and Proof of Payment.
- The sponsor cannot create organizations via CTIS when creating a new CTA when adding a clinical trial site, or adding a legal entity.
Solution: Add any new organizations via OMS before creating a new CTA.
You can find a list of all the known issues via the document in this link. The list of fixed problems in CTIS and the development plans for implementing the remaining fixes is available via this link.
Maintenance Timeline
It is unclear which issue will be fixed when, though the EMA has 2-weekly and monthly maintenance windows where bug fixes are made. Interestingly, the focus seems to be on bug fixing, where the industry is also looking forward to other significant improvements to improve the efficient use of CTIS, such as the development of an API connecting CTIS directly with Sponsors and CRO systems.
Useful Links for Support and Information for CTR and CTIS
GCP Central offers a comprehensive overview of the requirements for how to be EU CTR compliant in our Expert EU CTR training course. Available via our myGCP learning portal, this convenient, on-the-go training can be completed in your own time, at your own pace.
The EMA has also released a Q&A document about the EU CTR (updated September 2022) with the latest guidelines about using CTIS here.
You can also stay up to date with the best practices shared during the EMA walk-in clinics and webinars. Simply click this link, and scroll to Training and Information Events.
The Future Under CTIS
As we head towards January 2023 and the end of the CTD, CTIS will continuously be refined and updated to ensure not only that all the issues are sorted but also that best practices are shared and implemented.
The future of transparent clinical trials in Europe starts with the full implementation of the EU CTR and the adoption of CTIS for trial submission and management. Are you #EUCTRReady? Let GCP Central help you with our range of EU CTR Training solutions. Need a quote for your company? Get in touch.
Find part 1 of this series here and part 2 here.
Find our EU CTR Expert training here and our EU CTR Expert and VGO in the Netherlands training here.
