Obligatory Summertime Reading–How to Use the EU's New Clinical Trials Regulation

The official position of the European Medicines Agency and the European Commission is that the clinical trial regulation–that is scheduled finally to come into effect in January 2022–will streamline the entire CT process in Europe. As from then, sponsors will be able to apply for clinical trial authorization in up to 30 European countries with a single application. The predictions may be accurate–but as with any streamlining exercise, there is going to be a quite a bit of preliminary work by all concerned to create an air-smooth body. So forget about the latest spy novel or passionate love story for your beach time reading, and pick up a "sponsors' handbook".

Right at the end of July the final obstacle to the new rules was lifted – with a formal announcement by the EU that the portal and database on which the new regulation relies are now ready to go live, bringing "substantial changes to the authorization and supervision of human research on medicinal products." Between now and the start of the new system, sponsors are going to have to familiarize themselves with the way the new system will operate. Most of the complexities are attached to the clinical trial information system (CTIS), which has proved challenging to build–a task that has accounted for much of the eight-year delay between the legislation's passage and its coming into effect.

No-one is taking this 'streamlining' for granted. EMA has just issued a lengthy sponsor handbook to give advance notice to everyone generating CTs of what they will have to do under the new rules. There is also a training catalogue with "several modules covering the full lifecycle of clinical trial submission, authorization and supervision." Reassuringly, this acknowledges that sponsors "have multiple and complex structures and partnerships for managing clinical trials." But less reassuringly, it then goes on to point out that "there is a need for sponsors to fully understand the CTIS user management functionalities to facilitate completion of processes and organizational designs so that management of user permissions in the CTIS serves the creation, review and submission of CTAs, modifications and notifications through the CTIS. Sponsors also need to understand user/roles so that they can ensure that they have the correct confidentiality agreements in place."

And that's just the start. The 30-page handbook consists largely of references to websites that contain the detail of how those roles will be discharged. CTIS allows sponsors to manage system users and their roles within their organizations, compile clinical trial dossiers including document upload for new and updated trials, cross-refer in the application to other trials, where for example the same product was used, receive alerts and notices for Enhanced Patient Safety Support to Innovation & Research ongoing trials, respond promptly to requests for information, view deadlines, search and access clinical trials and record a summary of clinical study results.

It lists the data fields to be completed and to be uploaded for each form present in the notifications section implemented in the system. They include the start of trial, start of recruitment, end of recruitment, end of trial, global end of trial, temporary halt, restart of trial, restart of recruitment, update anticipated date of summary results, unexpected event, serious breach, urgent safety measure and third-country inspectorate inspection. And in recognition of the scale of the tasks that sponsors will have to take on,

But for all the data that will have to be input by sponsors, "CTIS is, however, not a clinical trial management system." It provides a digital secured archive of documents, decisions and information on a clinical trial, but "it should therefore not be relied upon by sponsors to store information on a clinical trial." Sponsors should ensure they utilize their own information management system to store information needed for compliance purposes, it says.

The regulation, with its nominal aims "to stimulate clinical trials in the EU, to protect trial participants, and to increase transparency of clinical trial information," will be implemented on 31 January 2022–some eight years after it was adopted. Its use will be voluntary for the first year, and mandatory for new clinical trials as from 31 January 2023. And by 31 January 2025 all ongoing trials approved under the current clinical trial directive will need to transition to the new regulation.

Time to start reading–and making notes.