AseBio

January 30: A key date for clinical research in europe: the transition to CTIS will mark a turning point

We interviewed Lidya Domínguez, Director of Clinical Research at Sermes CRO, experts in European clinical trial regulation and CTIS, who have been involved in its development since 2017 as members of the working group organized by the EMA for sponsors and CROs.

Lidya Domínguez, directora de Investigación Clínica de Sermes CRO
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On January 30, a crucial milestone will be reached for clinical trial sponsors across Europe: the deadline for transitioning clinical trials to the Clinical Trial Information System (CTIS). This marks the final step in the full implementation of the Clinical Trials Regulation (CTR), which aims to modernize and harmonize clinical trial procedures across Europe. Trials continuing beyond this date must comply with the Clinical Trials Regulation (CTR), which replaces the previous Clinical Trials Directive (CTD). This transition is not immediate and may take up to three months, making planning over recent months essential to ensure that ongoing trials extending beyond January 2025 comply with the new regulation.

As the deadline approaches, AseBio interviewed Lidya Domínguez, Director of Clinical Research at Sermes CRO. Sermes CRO is an expert in European clinical trial regulations and CTIS and has been involved in the development of this new portal since 2017 as members of the EMA working group for sponsors and CROs.

AseBio: What are the key differences between the CTD (Clinical Trials Directive) and the CTIS under the Clinical Trials Regulation (CTR)?

Lidya Domínguez: This change in clinical trial regulation represents a true paradigm shift for conducting and managing clinical trials in Europe. On paper, the transition from CTD to CTR harmonizes how clinical trials are evaluated across EU countries, standardizes response times, and aligns requirements among nations. These aspects, which previously varied greatly between countries before the CTR and CTIS, are now unified. Moreover, the new system promotes transparency in research outcomes for the benefit of patients.

The CTR facilitates multinational clinical trials by allowing a single authorization request to all participating countries through a single portal, CTIS. Part I documents (central study documents such as the protocol, information about the investigational medicinal products, etc.) are jointly evaluated by all participating countries. This is an advantage compared to the previous legislation, where authorization had to be requested individually for each country. This often resulted in variations in the study documentation based on the requests of individual Member States, meaning the documentation was not uniform across countries.

Furthermore, CTIS not only centralizes the submission of clinical trials but also manages the entire lifecycle of the study across all countries, including amendments, notifications, and result reports.

As we mentioned earlier, another significant change introduced by the CTR is increased transparency. Certain information from trial documents (such as the protocol) is now accessible to the general public.

AseBio: Why is January 30, 2025, such a crucial date for the clinical trial industry in Europe?

Lidya Domínguez: In January 2022, CTIS became operational, marking the start of a three-year transition period from CTD to CTR. This transition period ends on January 30, 2025, after which all clinical trials must be conducted under the CTR using CTIS. For studies previously approved under the CTD, the transition to the CTR must be completed before this deadline.

The implications for clinical trial sponsors are significant, as they have had to adapt all their internal procedures and processes to this new way of managing clinical trial documentation. This transition has deeply impacted not only the regulatory departments of sponsors but also the coordination between various departments involved in the submission and monitoring of clinical trials.

This has been a major challenge for all stakeholders, including sponsors, regulatory agencies, ethics committees, participating centers, researchers, and patients. We would particularly like to highlight the challenges faced by academic research organizations, which have more limited resources than multinational sponsors, making this transition even more demanding for them.

AseBio: What are the most notable advantages of CTIS compared to the previous system in terms of transparency and efficiency?

Lidya Domínguez: A public portal has been enabled, allowing anyone to access information on all clinical trials being conducted, which represents a significant advancement from the perspective of patient rights. Certain trial information and documents are made public on this portal, enabling the general population, researchers, and patients to gain visibility into ongoing research and the characteristics of these studies. While the CTD did publish some trial information, it did not include documents. The CTR offers an advantage by making key study information, such as the patient information sheet, accessible to patients, helping them decide whether to participate in a trial.

Regarding efficiency, CTIS not only offers the benefit of joint evaluations for multinational studies but also includes defined maximum evaluation timelines, aiding in study planning. Additionally, the platform’s accessibility for sponsors can enhance research design efficiency, expand future patient options, foster innovation, and eliminate redundancies.

Although the tool still requires a transitional period to overcome certain challenges, CTIS is expected to significantly improve efficiency, enabling Europe to compete effectively with regions like the United States and Asia. Under the CTD, time, processes, and resources were often multiplied, but these are now optimized. CTIS is part of the "Accelerating Clinical Trials in the European Union (ACT EU)" initiative, which aims to transform the EU into a region that supports clinical trial development, fostering collaboration and innovation throughout the clinical research lifecycle. This vision includes seamless coordination among stakeholders, regulatory bodies, and ethics committees, leading to enhanced cross-border collaboration.

The European Commission is heavily invested in this program through various projects. Regarding CTIS specifically, there is a continuous monitoring group working with the EMA to improve the platform continuously.

We should see the results of these efforts throughout 2025, enabling comparisons between the number of trials attracted to the EU versus other regions and previous years.

AseBio: What have been the main challenges for organizations preparing for this transition?

Lidya Domínguez: Adapting to the CTR has been a significant challenge for sponsors, requiring a thorough review of internal processes to align companies with the new system’s requirements. The functionality of CTIS has also been a complex point.

For instance, CTIS integrates with multiple databases (e.g., WHO, XEVMPD), necessitating a prior review of all records for participating organizations and products to be used before submitting a clinical trial authorization request. Implementing new transparency rules has also posed difficulties, as sponsors now face a paradigm shift in making certain study documents public. Determining which information is confidential and which is not—and redacting sensitive data to avoid impacting planned drug development—has been a particular challenge.

AseBio: What support does the European Commission or local regulatory agencies provide to facilitate this change?

Lidya Domínguez: A significant effort has been made by all parties involved to facilitate this regulatory transition. The EMA has created a dedicated webpage with CTIS training resources for sponsors, regulatory agencies, and ethics committees. It also hosts regular open-access online meetings to address questions related to the CTR and CTIS. Additionally, a CTR Q&A document has been published to address practical aspects of implementing the regulation.

National agencies have also produced guidelines to help apply the CTR at the local level. For unresolved questions, sponsors can reach out to the EMA or national agencies, which have shown great collaboration in addressing these inquiries.

AseBio: What regulatory consequences could clinical trials face if they fail to comply with the CTR before the deadline?

Lidya Domínguez: According to the EMA, failure to transition to the CTR before the deadline could result in sanctions under the regulation. For trials that have yet to transition, the Spanish Agency for Medicines and Health Products (AEMPS) is proactively issuing communications to sponsors, reminding them of the need to comply with the regulation before the specified date.

AseBio: What will happen to the data from ongoing clinical trials that are not transferred to CTIS by the set deadline?

Lidya Domínguez: Clinical trials that do not transition to the European regulation cannot continue within the EU, meaning they cannot recruit or treat patients. Sponsors will need to close these trials and evaluate whether the collected data can be used for future research under existing legislative tools.

AseBio: What impact could this transition have on patients’ perceptions of clinical trials?

Lidya Domínguez: Under the CTR, more information and study documents are made public compared to the CTD, which should positively impact patients by providing them with more information. For example, patients can now access key details to decide whether to participate in a trial.

For trial participants, the patient information sheet must inform them that study information and results will be available on the public portal. A final step would be to educate the general population about the portal's existence and the availability of clinical trial information and other therapeutic alternatives currently under study.

AseBio: What improvements are expected in the clinical research ecosystem due to the adoption of the CTR and CTIS?

Lidya Domínguez: The implementation of the CTR establishes a unified legislative framework for the requirements to conduct clinical trials. This harmonization of criteria has yielded positive results in Part I documents of clinical trials, as these are common to all countries participating in a study, facilitating the execution of multinational clinical trials in Europe. However, work remains to be done to harmonize criteria for Part II documents (local clinical trial documents, such as the patient information sheet) to establish common requirements across countries and further enhance the execution of international trials.

Additionally, the availability of clinical trial documents under the CTR transparency rules, such as the study protocol, could lead to improvements in the design of new clinical trials, refining study execution to achieve optimal results.

AseBio: How is this transition expected to influence Europe’s competitiveness in the global clinical trial landscape?

Lidya Domínguez: The data clearly showed a decline in the competitiveness of Europe’s clinical trial sector compared to other regions, such as the United States (where the FDA serves as the sole regulatory agency for a population of approximately 350 million people) and Asia, with powerful players like China.

In the European Union, with a population of roughly 450 million across 27 member states, it was evident that moving toward a harmonized model was essential to avoid further loss of competitiveness.

While there are critics of the CTIS model’s implementation, in my view, and acknowledging that improvements are still needed, it was both essential and urgent to harmonize our clinical trial management system on the “old continent.”

AseBio: Looking ahead, what other regulations might need adjustments to maintain sector harmonization?

Lidya Domínguez: While the CTR has harmonized clinical trial legislation at the European level, there are still related regulations that could benefit from harmonization or the adoption of common tools like CTIS for trial submission and monitoring. For example, in the case of clinical trials involving medicinal products that contain or consist of genetically modified organisms (GMOs), even if the trial is approved for all European countries via CTIS, national applications are still required for the voluntary release of GMOs. This process could benefit from a centralized submission system, similar to what CTIS has achieved.

Another relevant issue is the need to harmonize the submission process for trials involving both a medicinal product and a medical device. Currently, two separate submissions are required: one via CTIS and another through the AEMPS General Register directed to the Medical Devices Department.