nyone involved in obtaining approval to conduct clinical trials in the EU who has had to navigate the disparate and complicated systems in place since the Clinical Trials Directive was implemented in 2001 has long dreamt about change. Having a harmonized clinical trial approval system that would relieve the administrative burden and misalignment between countries in the EU so that the region would become the place to conduct clinical research in the future was and remains the goal.

The Clinical Trials Regulation (CTR) was EU regulators’ response to that dream. In many ways, the needs of sponsors and other stakeholders, such as an EU-level Clinical Trial Application (CTA) assessment process managed by EMA akin to the centralized procedure, were taken on board in the Regulation which came into force on 31 January 2022. That new Regulation is now the mandatory framework for approval and oversight of new clinical trials in the EU.

The EU does now have a portal into which a single CTA is submitted, regardless of whether the trial is being conducted in 1 or in all 27 Member States. The structure of the scientific and technical part of the submission (Part I) is harmonized, and the decision on the acceptability of the trial is reached by consensus of all the Member States involved in the trial. As a result, the days of national differences in the way a trial is conducted in different EU States should be numbered.

In addition, EU citizens and patients will increasingly see which trials have been approved in which countries. Should they find a relevant clinical trial, they will also see which centers are recruiting patients, empowering them to seek to join those trials if they want. In time, after trials have been completed and results uploaded into the portal per the Regulation, patients will be able to read summaries of the results of their trials in patient-friendly language, validating the time and effort they expend to participate in and advance clinical research.

For sponsors, however, the reality of the implementation of the Regulation and of the portal or IT system which supports it (Clinical Trials Information System, or CTIS) does not yet live up to the dream and is a potential missed opportunity. Whilst the new Regulation brings in alignment of submission, approval, and oversight processes, and harmonizes decision making on the scientific and technical aspects of the application, it falls short in several respects:

• The Regulation did not harmonize requirements or processes for evaluation of the country-specific part of the application (Part II), nor did it supersede national requirements to meet the EU deliberate and contained release laws for genetically modified organisms. Consequently, national differences in the assessment of trials will persist.
• The Regulation considers clinical research as a linear process in which one step is completed before the next is initiated; in practice, clinical research is much more complex. Not having parallel processes so that multiple changes can be assessed in the same timeframe makes some studies, particularly complex trials, difficult to manage and lengthens their timelines.
• 21st century IT systems are expected to be smart, streamlined, and interoperable with other systems (in particular, a sponsor’s document management system). The IT tool developed by EMA to implement the Regulation (CTIS) is time-consuming, repetitive, and requires workarounds to be effective.
• Transparency and disclosure of clinical trial information is one of the Regulation’s key deliverables. However, the confidentiality of trade secrets also needs to be maintained. This is accomplished in the CTIS via a mixture of redaction (blacking out confidential text) and deferral (delaying publication) of some documents, which necessitates preparation of duplicate documents and their associated workload. Even so, because confidential material can still be disclosed during the review process, the risk to confidentiality remains. When coupled with long approval times, this has prompted some Sponsors to consider moving their early research to countries and regions where confidentiality is guaranteed, and processes are more streamlined.

That said, CTR and CTIS are a big step forward in the right direction. CTIS is in the early stages of implementation and will improve with use. Once all stakeholders involved in the CTA submission and approval process and management of clinical trials have climbed the mountain ahead of them including realigning internal processes; have learned the ins and outs of a new system and its workarounds; have transitioned their long-running trials to the new system; and CTIS and CTR become the norm, perhaps they will look back and wonder what all the fuss was about, just as we did when the Clinical Trial Directive was first introduced in 2001.

The author has recently retired from Bayer UK and the European Federation of Pharmaceutical Industries and Associations.