EMA Discusses European Clinical Trial Decline at DTRA

At the 2024 Decentralized Trials & Research Alliance (DTRA) Annual Meeting, Dr. Amir Kalali of the DTRA and Dr. Steffen Thirstrup from the European Medicines Agency (EMA) delved into the evolving landscape of clinical trials in Europe. The discussion centered on the challenges and innovations shaping the future of clinical trials, focusing on decentralized trials and the regulatory environment. As Europe grapples with declining clinical trials, the EMA is implementing strategic measures to revitalize the sector, ensuring it remains competitive and accessible to patients.

Understanding the EMA’s Role

Dr. Steffen Thirstrup provided a comprehensive overview of the EMA’s role, highlighting its distinct focus compared to the FDA. While the FDA’s broad mandate includes food, drugs, devices, cosmetics, and tobacco, the EMA concentrates primarily on pharmaceuticals. This narrower focus allows the EMA to specialize in drug regulation, although it does engage with drug-device combinations and companion diagnostics. Other areas, such as tobacco and cosmetics, fall outside its jurisdiction, with separate European agencies handling these sectors. For instance, food safety is managed by a distinct agency, though the EMA collaborates on issues like food additives. The EMA’s operations are further complicated by the European Union’s unique political structure, a union of 27 member states rather than a single nation. This necessitates a collaborative approach, with the EMA relying on a network of experts from these states. This network is crucial for coordinating clinical trials, which are increasingly global or multinational. The EMA’s role involves aligning diverse regulatory environments, requiring significant cooperation among member states.

Addressing the Decline in Clinical Trials

The decline in clinical trials within Europe was a primary concern addressed by Dr. Thirstrup, who noted that this trend is not aligned with the European Commission’s goals of maintaining competitiveness and ensuring patient access to new therapies. Clinical trials are vital for regulatory decision-making and advancing scientific knowledge through non-commercial academic trials. To counter this decline, the EMA has implemented a new clinical trial regulation, effective January 2022, to streamline the approval process. Previously managed nationally, the regulation seeks to create a more coordinated approach, facilitating multinational trials within Europe. Dr. Thirstrup referenced a recent report from the European Federation of Pharmaceutical Industries and Associations (EFPIA), highlighting that only a few member states have recovered from the COVID-19-related dip in clinical trials. This highlights the urgency of the EMA’s efforts to implement the new regulation effectively. The regulation is designed to enhance the representativeness of patient populations in trials, ensuring that regulatory decisions are based on comprehensive and diverse data sets.

Innovations in Clinical Trial Processes

The EMA is actively pursuing innovations to improve the clinical trial process, focusing on the Clinical Trial Information System (CTIS). This system is intended to serve as a one-stop portal for sponsors, allowing them to enter trial data and facilitate assessments by member states. Dr. Thirstrup acknowledged that the system faced initial technical challenges, describing them as “inborn errors.” However, he assured that many of these issues have been resolved, and the system functions more effectively. The CTIS is a key component of the EMA’s strategy to enhance trial coordination across Europe. It enables parallel assessments by regulatory authorities and ethics committees, streamlining the approval process for clinical trials. This system is particularly beneficial for sponsors conducting trials in multiple member states, as it reduces the administrative burden and facilitates a more efficient review process. In addition to the CTIS, the EMA has launched the ActEU initiative, which stands for Accelerating Clinical Trials in Europe. From 2022 to 2026, this multi-annual work plan includes ten priority actions to revitalize the clinical trial landscape in Europe. Among these actions are the development of methodologies for decentralized and complex trials, as well as the creation of a multi-stakeholder platform to engage with industry, academia, and patient organizations. These efforts reflect the EMA’s commitment to fostering innovation and collaboration in the clinical trial sector.

Embracing Digital and Real-World Data

Integrating digital endpoints and real-world data into clinical trials was another focal point of the discussion. Dr. Thirstrup emphasized that decentralized trials and digital endpoints are closely linked, as the latter are essential for collecting data in a decentralized manner. He noted that the EMA is open to discussions on digital endpoints and has developed a Q&A document to address the rapid evolution of digital health technologies. This approach allows the EMA to update its guidance quickly, keeping pace with technological advancements. Digital endpoints, such as those collected through wearable devices, can enhance the quality and scope of data collected in clinical trials. They enable the collection of real-life data, which can supplement traditional data sets obtained through on-site visits. This integration of digital endpoints can lead to more comprehensive and representative data, ultimately improving the quality of regulatory decision-making. Dr. Thirstrup explained that real-world data can be used not only for post-authorization safety monitoring but also for efficacy and effectiveness studies. This approach does not aim to replace randomized clinical trials but to supplement them, providing additional insights for regulatory and health technology assessment decisions.

Global Collaboration and Future Directions

Global collaboration is a cornerstone of the EMA’s strategy, particularly in the context of clinical trials, which are increasingly global in nature. Dr. Thirstrup highlighted the close relationship between the EMA and the FDA, noting that the two agencies have a longstanding confidentiality agreement and engage in regular meetings. This collaboration is powerful in major therapeutic areas such as oncology, where the EMA and FDA work together to harmonize regulatory practices. The EMA collaborates with other international regulatory bodies, including Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) and Health Canada. These collaborations are facilitated through initiatives like the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and the International Coalition of Medicines Regulatory Authorities (ICMRA). These efforts aim to align regulatory standards and facilitate the conduct of multinational clinical trials. Looking to the future, Dr. Thirstrup expressed optimism about the potential for hybrid clinical trials, which combine elements of traditional and decentralized approaches. He believes such trials can create more naturalistic data sets, improving the applicability of trial results to real-world settings. By reducing the number of traditional site visits and incorporating real-life data collection, hybrid trials can broaden recruitment and enhance the representativeness of patient populations.

The Impact of Brexit

The EMA’s move to Amsterdam, necessitated by Brexit, has had significant implications for the agency and the broader European regulatory network. Dr. Thirstrup described the physical transition as smooth, with the Dutch government providing a new building for the EMA. However, the loss of the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) as a key player in the European Medicines Network has posed challenges. Brexit has resulted in the redistribution of responsibilities for product assessments among the remaining member states, placing additional burdens on their regulatory agencies. Moreover, the loss of the MHRA’s expertise has made it more challenging for the EMA to maintain a high level of scientific and regulatory expertise within its network. Dr. Thirstrup noted that the network’s sustainability is a recurring topic of discussion among the heads of the member states’ regulatory agencies. Despite these challenges, the EMA continues to engage with the MHRA, although the relationship has changed significantly post-Brexit. The lack of a confidentiality agreement with the UK complicates collaboration, and the MHRA’s decision to stand independently has further distanced it from the European regulatory framework. Nonetheless, the EMA remains committed to fostering collaboration and maintaining high standards of regulatory oversight in the post-Brexit landscape.

Summary

In conclusion, the conference emphasized the EMA’s proactive measures to address European clinical trials’ challenges. The EMA aims to foster a robust and competitive clinical trial environment that benefits patients and the scientific community through regulatory innovations, digital integration, and global collaboration. The agency’s efforts to streamline processes, embrace new technologies, and enhance international cooperation are crucial to revitalizing the European clinical trial landscape and ensuring its continued relevance globally.