‘Dysfunctional’ trial registry threatens drug research across Europe
Serious flaws in the new European clinical trial registry CTIS could lead to a “catastrophe” if the system’s planned rollout is not put on hold, German trialists have warned.
In an unusually strongly worded joint press release, a coalition of major German industry and academic medical research associations has called for the switch to the new system to be suspended indefinitely until major flaws in CTIS have been fixed.
UPDATE 13 December: European phama lobby group EFPIA takes a different stance, see below.
According to European regulations, all new investigative drug trials in the European Union must be registered on the CTIS registry from February 2023 onwards, ending a one-year transition period during which sponsors had the choice between using the old EudraCT or the new CTIS registry.
According to the statement by German trialists:
“[T]he CTIS portal suffers from serious deficiencies even after ten months of practice and is largely unmanageable for all parties involved. These deficiencies have not been eliminated in the past months, but have increased.”
“As a result, the submission of applications for clinical trials as well as their processing by the ethics committees is massively impaired and unmanageable.”
“This will foreseeably lead to a considerable weakening of the competitiveness of Europe as a research region and to disadvantages and risks for patients… the careful review of research applications by ethics committees is severely hampered by the dysfunctionality of the portal.”
Georg Schmidt, the chair of the Association of Medical Ethics Committees, told the newspaper Sueddeutsche Zeitung that currently only round ten percent of relevant German ethics applications are processed through the new system.
If all applications were to be channelled through the new system from February 2023 onwards as planned, there will be a “catastrophe,” he warned.
Trials put on hold
According to the newspaper:
Even today the portal regularly crashes, Schmidt says. On occasion documents cannot be uploaded at all. The up to 500 documents that have to be included with an application can only be organized within two folders within the system, making it virtually impossible to gain an overview.
“Some commissions from other EU countries have blanket refused applications as a kind of ‘emergency brake,’” Schmidt says, “because they were not able to demand amendments to protect trial participants.”
“Rather than just letting through an application that cannot be adequately reviewed due to flaws in the platform, you just have to refuse it.”
EFPIA supports planned launch date
Update 13 December: section below added
European phama lobby group EFPIA provided the following statement to TranspariMED:
"It has taken eight years to develop CTIS, an enabler for CTR [the EU Clinical Trial Regulation] to come into its full application to ensure we can start reaping the benefits of a streamlined application and authorisation process and increased transparency for clinical trials in Europe.
EFPIA member companies do have ongoing concerns about the functionality of CTIS and the impact that the technical failures are having on our ability to start and run clinical trials under the CT Regulation. We are working hard and in collaboration with EMA and Member States to tackle the existing bugs in the system and to have a robust platform for every involved stakeholder to use.
EFPIA does not currently believe that a further deferral of the full implementation of the CT Regulation will serve a useful purpose for making the EU an attractive place to conduct clinical research.
Currently, EFPIA does believe there may be value in requesting an extension of the transition period for ongoing studies (beyond 31 Jan 2025) to ensure the capacity of the system is not overloaded and enable all the technical issues encountered with new studies to be fixed."
In a nutshell, this means that EFPIA supports the mandatory registration of all new drug trials on CTIS from February 2023 onwards, as is currently planned. However, the industry group appears open to the idea of postponing the planned migration of data on older (but still ongoing) trials to CTIS.
The buck stops with EMA
The president of German’s medicines regulator BfArM told the newspaper that the new system offers opportunities to reduce bureaucracy and improve transparency, but declined to comment on current dysfunctionalities, noting that the European Medicines Agency was responsible for running CTIS.
The European Medicines Agency conceded that “some users have problems with the system,” and noted that it had invested additional resources to ensure that the transition to the new registry would be able to proceed within the planned time frame.
The launch of the CTIS trial registry has been repeatedly delayed.
While sponsors will be legally required to upload the results of investigative drug trials onto the platform within 12 months of trial completion, the registry’s results reporting function has not yet been developed.
On the positive side, the European Medicines Agency has put substantial effort into providing trainings for future CTIS users.
Legal gaps in Germany and Europe
CTIMPs. Under European law, all Clinical Trials of Investigative Medicinal Products (CTIMPs) will have to be registered on CTIS from February 2023 onwards. CTIMPs only account for a small minority of all clinical trials; many drug trials are not CTIMPs. Non-CTIMPs cannot be registered on CTIS.
Medical device trials. In the European Union, some trials of medical devices are required to be listed on the recently launched EUDAMED medical device database, which has also been plagued by substantial delays and technical problems.
Other clinical trials. A recent report by TranspariMED and allied groups found that other types of clinical trials occupy a regulatory vacuum both on the European and national levels. There are no legal requirements to register or publish the results of non-CTIMP drug trials, of medical device trails not covered by EUDAMED, or of trials involving physiotherapy, surgical techniques, or behavioural interventions in Germany or in other major European countries.
According to WHO standards, all interventional clinical trials should make their results public on a trial registry within one year of trial completion. Current laws and regulations in Europe fall short of these standards.
Note: Translations from German into English above by TranspariMED. The article in Sueddeutsche Zeitung can be accessed here. The joint press release by German stakeholders is available here. A recent TranspariMED guest blog examines CTIS critically from a user perspective.