Better evidence to translate innovation into medicines

Evidence on safety, quality and efficacy is the basis on which regulators assess medicines. In 2024, EMA strengthened processes and procedures to ensure that the European regulatory network can harness health data and benefit from rapid technological advancements, especially the use of AI for the benefit of patients. When used safely and responsibly, data and new digital tools can help regulators assess scientific innovations and translate them into safe and effective treatments.

Clinical trials remain the bedrock of clinical evidence on medicines. The Accelerating Clinical Trials in the EU initiative (ACT EU) is ongoing and the Clinical Trials Regulation is fully implemented as of 30 January 2025. The year 2024 was important in preparing the EU's regulatory system to fully embrace the potential of data to complement the results of clinical trials. EMA increased efforts to generate real-world evidence (RWE) from everyday healthcare data. Expanding data sources allowed access to more diverse data across Europe, resulting in a higher number of studies to support EMA committees and EU regulators. In response to the fast development of new technologies, the network continued delivering a multiannual AI work plan to coordinate efforts in maximising the benefits of AI while mitigating the risks.

Strengthening the ecosystem for clinical trials in the EU

EMA, the HMA, and the European Commission have an ambitious vision: transforming the clinical trials environment in the EU. The umbrella for this transformation is the ACT EU initiative, which aims to bring all stakeholders together to enhance the clinical trials landscape.

ACT EU is a collaborative effort, crucial for promoting the development of high-quality, safe and effective medicines, and better integrating clinical research into the European health system. The initiative has established a multi-stakeholder platform (MSP) to ensure engagement across stakeholders on clinical trials. In March 2024, the MSP advisory group held its first meeting, marking a significant milestone. The launch of the MSP promotes open dialogue around the challenges and opportunities represented by advances in clinical trials regulation, methodologies and technology for the benefit of EU citizens.

A central focus of the efforts in 2024 was supporting stakeholders in the final year of transition to the Clinical Trials Regulation (CTR) . All ongoing clinical trials in the EU approved under the previous legal framework, the Clinical Trials Directive, needed to be transitioned to the CTR by 30 January 2025 through submission to the Clinical Trials Information System (CTIS) . CTIS serves as the single-entry point for sponsors and regulators for the submission and assessment of applications for clinical trials in the EU. The system includes a public searchable database for healthcare professionals, patients and the public, delivering the high level of transparency mandated by the regulation.

Throughout 2024, sponsors were reminded of the approaching end of the CTR transition period. To ensure a smooth migration and enhance the quality of clinical trial applications, guidance and support were offered to stakeholders through various resources, including guidance documents, best practice guides and dedicated training activities.

In June, a new version of CTIS was launched, allowing earlier and more efficient access to clinical trial information. Revised transparency rules eliminated the previously available deferral mechanism, which allowed clinical trial sponsors to delay publishing certain data and documents for up to seven years after a trial's completion to protect commercially confidential information. Under the new rules, more than 8,600 clinical trials with issued decisions are now publicly accessible through the CTIS search.

Beyond the support to the CTR transition, ACT EU launched two new advice pilots in 2024 to improve the quality of clinical trial applications. The first pilot offers joint scientific advice on clinical trials and marketing authorisation applications. The second provides technical and regulatory support on the dossier of a clinical trial application before submission through CTIS. By strengthening the coordination of the European medicines regulatory network, these advice pilots offer applicants additional support to enhance the quality of their applications for marketing and/or clinical trial authorisation.

ACT EU also intensified efforts to provide dedicated support to non-commercial sponsors. This included the creation of a helpdesk for technical and regulatory advice on clinical trials and an interactive map of existing national support initiatives.

Enhanced useof real-world evidence

High-quality clinical evidence is at the heart of well-informed decisions on medicines. While clinical trials remain central, experts can use real-world data (RWD) from routine healthcare settings to generate real-world evidence (RWE). The use of RWE helps regulators address knowledge gaps and complement the evidence picture by enhancing their understanding of the use, safety and benefits of medicines.

In 2024, EMA continued to generate evidence based on knowledge and expertise, embracing diverse data and methods, and exploring, enabling and validating new approaches. Together with the HMA, the Agency worked towards a joint vision of establishing the use and enabling the value of RWE in regulatory decision-making.

EMA took steps to help regulators, researchers and companies navigate, identify and utilise health data. Two public RWD catalogues for data sources and for studies were launched, promoting transparency, good practices and trust in RWD research. EMA also developed guidance on RWD, engaged with stakeholders through public consultations and events, and collaborated internationally to initiate common guidelines for RWD studies. A big data newsletter was launched to share the latest updates.

The Agency ramped up efforts to generate robust evidence for its committees and national regulators. The second report on regulator-led RWD studies summarises the progress made, covering 40 studies completed between February 2023 and February 2024. These included 13 studies on vaccine safety and effectiveness, and two on medicines at risk of shortages, such as antibiotics. One study examined the risk of suicide and self-harm in people using GLP-1 receptor agonists, helping EMA's safety committee to conclude there is no causal link.

Studies were conducted via three pathways: Data Analysis and Real World Interrogation Network (DARWIN EU), EMA's framework contract and by in-house experts. The number of studies continued to grow throughout the year, with 47 studies completed or ongoing by year-end via DARWIN EU.

In 2024, DARWIN EU became fully operational, emerging as the main pathway to generate RWE. The network provides the structure, data and tools to access relevant and reliable RWE on diseases, populations and medicine performance across Europe.

The inclusion of different real-world data sets increases the value of DARWIN EU for medicines evaluation. DARWIN EU onboarded ten new data partners, bringing the total to 30, including healthcare data from primary care, hospitals, registries and biobanks. This expanded the network's access to the health data of 160 million patients in 16 European countries.

Since its establishment in 2022, 58 studies are completed or ongoing via DARWIN EU. In 2024, these included research on the prevalence of rare blood cancers in Europe, the prescription of antibiotics and a study examining the characteristics of patients who have been prescribed GLP-1 receptor agonists, used for diabetes and weight management, and how these have changed over the past ten years.

The results from the studies are published in the HMA-EMA RWD catalogue and shared with the relevant EMA committees and stakeholders to support the evaluation of medicines.

All this work was coordinated by the Big Data Steering Group (BDSG), set up by EMA and the HMA to enhance the analysis and use of big data in medicines regulation. By the end of 2024, the BDSG wrapped up its five-year mandate, and the new Network Data Steering Group (NDSG), which merges the BDSG and Network Data Board, will lead the transformation towards more data-driven medicines regulation going forward.

From creating a European real-world data network of 160 million patients to building an expert workforce, the BDSG has demonstrated the value of large datasets in medicines regulation. It has ensured benefits to Europeans in multiple data-related areas, including data quality, discoverability and training. Within the past year, the BDSG has delivered an AI-driven knowledge mining tool, Scientific Explorer, and the HMA-EMA catalogues of real-world data sources and studies, which we as a competent authority consider to be of great importance, since they allow us to integrate big data in our regulatory procedures. Once again it proves that collaboration between the medicines agencies is highly valuable.

Nils Bjerregaard, Director General of the Danish Medicines Agency (DKMA). The DKMA has been the co-chair of the BDSG.

From vision to action: Enabling safe and responsible use of AI

In 2024, the use of AI and machine learning (ML) expanded remarkably, impacting even more facets of people's lives, including the regulation of medicines. As AI applications evolve, so do the ethical and policy considerations around their use. When used responsibly, digital tools help us to be more productive and efficient, as well as to understand diseases, treatments and medicine risks, with the potential to speed up medicines authorisation and ensure safe use. This leads to a more proactive and responsive regulatory system.

Companies increasingly apply AI tools in medicines development. Regulators must keep up with these developments to provide appropriate oversight, ensuring that AI is used safely and responsibly and benefits human and animal health.

To maximise the benefits while mitigating risks, the EU regulatory network began implementing its first work plan on AI that guides the use of AI in medicines regulation in Europe until 2028. This includes applying AI for personal productivity, process automation, and better insights into data and decision-making support. The approach embeds key ethical and patient-centric values and fosters stakeholder cooperation.

Within the AI work plan, EMA prepared for the implementation of the EU AI Act, which entered into force in August. The world's first comprehensive AI law provides a legal framework for Europe, aiming to be a global leader in safe AI.

Support is key in ensuring stakeholders can fully benefit from AI. EMA published the final reflection paper considering the use of AI throughout a medicine's lifecycle. Over 1,300 comments received from stakeholders via public consultation were valuable in consolidating the paper and informing the development of guidance. In response to the rapid developments of Large Language Models (LLMs), the Agency and the network developed guiding principles for EU regulators to support the safe and responsible use of these tools.

Keeping up with the pace of change, EMA leveraged the potential of AI to improve organisational and personal efficiency. The Agency accelerated experimentation with AI and explored opportunities to build pragmatic solutions for different business needs and automating routine processes. Scientific Explorer, an AI tool to help EU regulators find scientific information, was launched to simplify daily work and support the delivery of high-quality scientific advice to companies.

In a complex environment, collaboration and knowledge-sharing promote certainty and predictability. EMA launched a data science-training curriculum for the EU network and engaged with stakeholders through events and a well-attended public workshop on AI.