Regulatory
a digital portal for application submission and oversight of clinical trials for all EU member states. The CTIS took eight years to develop. When the CTIS was finalised in 2022, the market was given a one-year grace period before all trials conducted in Europe had to abide by the new CTR rules. Almost a year later, there are some who feel that the reality of the new regime has not lived up to expectations.
Indeed, a joint statement released in August 2023 headed ‘Dysfunction of the Clinical Trials Information System harms Europe’ from The Association of Medical Ethics Committees (AKEK) – an association of public ethics committees that review biomedical research projects in Germany – pulls no punches. The statement, signed by AKEK chair Dr Georg Schmidt, along with many others, points to the “massive functional deficiencies of the CTIS platform” and calls for an independent audit at EU level to “avert damage to patients and Europe as a research location”. These are strong views that are not universally shared, but they do highlight the need to rethink some aspects of the new regulatory landscape.
Expectation versus reality A key goal for the change is to encourage more participation in clinical trials, as recruitment and retention of participants have been increasingly challenging, and trial enrolment has been in decline due to a lack of engagement and understanding of the clinical trial process. CTR requires a Plain Language Summary (PLS) for every trial conducted in Europe to explain the trial and its results without scientific jargon. Furthermore, under CTR it is mandatory for drug developers to anonymise or redact clinical trial documents in preparation for regulatory submission. Anonymisation involves the removal of variables that allow direct or indirect identification of a trial participant or staff member. There are two elements – Part I contains scientific and medicinal product documentation, while Part II contains the national and patient-level documentation. So far, so good. There is little to no resistance to these changes in the market, and the motives behind the change are widely respected.
“The main benefit is that all EU member states are following the same regulation on clinical trials and a harmonised submission process through a single EU portal,” says Edyta MacioĊek, Regulatory Affairs Manager at JJP Biologics and EU CTR (CTIS) Specialist at CTR Consulting. “I support the intentions behind the legislation. Clinical trials sponsors should prepare and transition ongoing projects, if needed, as soon as possible.”
The same perspective is held outside of commercial (bio)pharma companies too. Alexander Roussanov, life science and privacy partner at Arnold and Porter Kaye
Clinical Trials Insight /
www.worldpharmaceuticals.net
Scholer LLP was previously a senior legal adviser in the Legal Department of the European Medicines Agency – the regulatory body tasked with creating the CTIS database and transparency rules. “It could be a success and it is an improvement,” he says. ”It is a step in the right direction and companies will get used to it, but they need to adapt their processes and understand what new regulation means in terms of submissions and transparency.”
The CTIS could – and perhaps already has – revolutionised clinical trial initiation, amendment, and completion processes, which previously involved the submission of forms to several scientific and ethical review committees. The CTIS centralises and documents all submission milestones within its database. Furthermore, it facilitates the submission of annual safety reports, the addition of new member states to ongoing trials, the receipt of agency feedback and assessment information, direct responses to agency requests for information, and the uploading of redacted and anonymised trial details for public viewing. Though driven by the loftiest of motives, the implementation of CTR has nevertheless stumbled over practical problems with the CTIS, which was billed by regulators as being “at the cutting edge of the art and user-friendly so that there is no unnecessary work”, but that has not been borne out by responses from users, as the AKEK statement clearly shows.
“One big positive is that this is one of few cases where industry, the EMA and all stakeholders are on the same page.”
Alexander Roussanov
AKEK members claim that the platform is unstructured, lacking in user-friendliness and prone to errors. As a result, the evaluation of study applications is “made more difficult with a considerable additional effort for unnecessary formalities”, as the organisation’s statement reads.
“Companies are now publishing less information but much faster, so my clients can’t kick the can down the road,” notes Roussanov. “They must provide information that is properly redacted, but they are nervous about the transparency issues. The need to provide heavily redacted documents that are reviewed by member states, though I’m not sure how carefully states check them.”
A lack of harmonisation
In comparing the new system with the Clinical Trials Directive, there are clear differences. Firstly, directives are not regulations, so rules were previously made on a state-by-state basis under the
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