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Orientation pursuits hit high gear as formal rule compliance inches closer.
Regular readers of Applied Clinical Trials who feel perfectly relaxed about the new European clinical trials rules are permitted, without feeling at all smug, are free to ignore this reminder that there are fewer than six months left before the system goes through yet another huge change. As of Jan. 31 2023, no new clinical trial applications in the EU can be submitted via national systems, and all initial applications must go via the Clinical Trials Information System (CTIS). And that’s not all. There are plenty more changes on the way too, including on disclosure of trial information.
The European Medicines Agency (EMA), which is pretty much at the center of the new system, is not confident that everyone knows enough about CTIS or about the new rules in general, and how a lot of other things are going to work from early next year.1 In conjunction with national regulators in Europe, it is still working assiduously at the task it faces in encouraging clinical trials stakeholders to fully get to grips with the “inclusive patient-oriented medicines development and delivery” that the new system is intended to bring in.
Driving clinical trial applications through CTIS is meant to lead not only to greater efficiencies, but also to a new degree of transparency. However, how much information is going to made public—and when—on the database at the heart of the new system, or on the associated public website, is still up for grabs. The rules says that the database “shall be publicly accessible” unless “confidentiality is justified” in order to protect personal data, commercially confidential information, or confidential communication between national authorities. But there are nuances, such as where there is “overriding public interest in disclosure.” The fine print of those rules is still under discussion—including on achieving a common understanding of what may or may not be considered commercially confidential.
There’s plenty more novelty on the way, too. What’s in store for complex clinical trials, for instance? Later in 2022, new recommendations will be published—and, simultaneously, a workshop will provide the opportunity to discuss and comment on this new version with a view to keeping it updated. This could be of particular interest to anyone contemplating a platform trial, since the system at present does not provide for them.
What about decentralized clinical trials? Did you know that a recommendation on the use of decentralized elements in clinical trials is also planned for publication before the end of the year? If you didn’t, an EMA workshop on Oct. 4 may be of interest, as regulators, ethicists, and good clinical practice inspectors will be listening to input from sponsors, patients, and investigators prior to the finalization of the recommendation.2
And in the background, European regulators are reflecting on how to implement the revised international guideline on good clinical practice, ICH E6 (R3), which describes the responsibilities in relation to monitoring, reporting, and archiving of trials. New guidelines are in the pipeline here, too, and in a bid to ensure they are responsive to current clinical trial practices with all the diversity of trial designs, data sources, and different contexts, yet another workshop will be held later this year prior to the opening of a public consultation on the revised guidance.
Meanwhile, sponsors are increasingly making use of the new system, even while it remains, until next January, optional (applications are still being made at national level under the soon-to-be-superseded—and much maligned—2001 clinical trials directive). The latest official figures, published in late July, show that 195 clinical trial applications were submitted through CTIS during the six months since the launch of the system at the end of January 2022. Most (188) were new applications, four were substantial modifications of existing applications, and three were to add a further member state to a trial. Decisions in total had been issued on 43 applications, split almost evenly between academic and commercial applications, with 10 already in Phase IV, six in Phase III, and 16 in Phase II.
The fastest decision took just five days from submission to decision, but the other 42 received a decision between 16 and 117 days of application. Of these, four trials were classified at the end of July as “ongoing”—which means that they had been authorized in at least one member state and recruitment of patients had started at the clinical investigator sites. For comparison, there had been just 14 applications when this column last visited the question in May.3
One of the major benefits of using the new system, according to Inge Christoffer Olsen of Oslo University Hospital, is that its single-entry point of applications for all countries makes it easy to know exactly what has been approved at any point during the process. He is involved in an application for a multi-country adaptive platform trial evaluating treatments in hospitalized patients with COVID-19. He also welcomes what he calls "a tremendous step forward on transparency," which he sees as conducive to "scientific rigor and value of European clinical trials." And he is particularly appreciative of "firm timeframes" in the system, under which tacit approval is granted wherever a member state does not meet decision deadlines.
Still smug? EU regulators certainly hope so. Nothing would please them more than knowing the international clinical trials community is fully up to speed with the new regulation.