Lessons from ICMRA on real-world evidence and global regulatory cooperation

A new article in Clinical Pharmacology & Therapeutics reflects on the ICMRA COVID-19 RWE and Observational Studies Working Group’s experience, summarizing key lessons and recommendations to strengthen global preparedness and evidence-based responses to future public health challenges.

The International Coalition of Medicines Regulatory Authorities (ICMRA), a collaboration between 38 global medicines regulatory authorities aims to foster collaboration to address shared challenges and enhance collaboration, including leveraging RWE. During the COVID-19 pandemic, the coalition played a key role through the ICMRA COVID-19 RWE and Observational Studies Working Group, co-chaired by the European Medicines Agency (EMA) and Health Canada. Established in April 2020, the group brought together 28 regulatory authorities to address challenges in RWE and observational studies, focusing on disease characterization, treatment safety, and vaccine effectiveness.

Examining the Working Group’s experiences and challenges

A major takeaway was the importance of large-scale collaboration in addressing evidence gaps. Individual studies often lacked sufficient power, but

“pooling resources, expertise, and data on an international scale is a strategic approach to enhance evidence robustness.”

The CONSIGN project demonstrated this by leveraging multinational data to study pregnancy and COVID-19 vaccine safety.

The need for a governance structure was also emphasized, with the group being established within two months of the pandemic’s onset, using existing networks to facilitate rapid decision-making. Members stressed the value of maintaining “collaborations and networks that are ‘ever warm’ collaborations to avoid time loss during the initial setup phase of emergencies.”

Project management improvements were critical for operational success. The use of joint master protocols, standardized data models, and structured timelines ensured efficient collaboration across diverse regulatory authorities. Projects such as coagulopathy in COVID-19 and steroid utilization studies highlighted how common protocols enhance study efficiency.

Timely information sharing was another essential factor, as members highlighted the

“critical role of effective and timely information sharing, expertise, and data in addressing COVID-19 challenges.”

The 2022 ICMRA RWE Workshop, co-chaired by EMA, the US Food and Drug Administration (FDA), and Health Canada, resulted in an ICMRA statement on international RWE coordination, reinforcing the need for transparency and knowledge exchange.

Challenges in international collaboration included time zone differences, funding limitations, and inconsistent data standards. Members acknowledged that “managing time differences proved difficult, hindering active contribution and sustained involvement.” Standardization of terminologies and coding systems remains an area for improvement.

ICMRA recommendations for strengthening RWE in regulation

The ICMRA COVID-19 RWE and Observational Studies Working Group developed seven recommendations to improve global collaboration, transparency, and research efficiency in public health emergencies. These recommendations support regulatory agencies and are also relevant for health technology assessment (HTA) bodies, public health entities, clinicians, and researchers. They align with the ICMRA statement on international collaboration on RWE, emphasizing harmonization, readiness, and transparency.

1. Develop an international governance structure for oversight and coordination of international observational studies

A dedicated international governance structure is essential to ensure the oversight and coordination of global observational studies. This framework should identify regulatory agencies capable of providing oversight, enabling efficient collaboration while working within existing mandates.

Key initiatives: DARWIN EU (Data Analytics and Real-World Interrogation Network) and the Big Data Steering Group, which aim to strengthen RWE capabilities in medicine regulation.

2. Form a “coalition of the willing” of regulatory agencies ready for swift collaboration

A Coalition of the Willing would comprise regulatory agencies prepared to rapidly engage in collaborative observational studies. By using common protocols and data models, this coalition would streamline decision-making and enhance research efficiency, particularly in response to emerging public health issues.

Key initiative: ENCePP (European Network of Centres for Pharmacoepidemiology and Pharmacovigilance) – provides methodological standards and guidance for RWE studies.

3. Advancing regulatory science and methodology for RWE

To improve research efficiency and decision-making, sub-groups should be created with clear mandates to focus on specific areas, such as pregnancy and vaccine safety. These teams would ensure that infrastructures and networks remain sustainable beyond public health emergencies, facilitating long-term regulatory improvements.

Key initiative: OPTIMAL framework – defines operational, technical, and methodological aspects to enhance RWE usability.

4. Organize periodic workshops for sustained collaboration and information exchange

Regular workshops provide a platform for agencies to share progress, exchange research updates, and promote best practices. The 2022 ICMRA RWE Workshop, co-chaired by EMA, the FDA, and Health Canada, demonstrated the value of such initiatives, leading to the ICMRA statement on international RWE coordination. Future workshops would enhance global regulatory preparedness and collaboration.

Key initiative: DARWIN EU – launched in 2022 to support safety monitoring, disease epidemiology, and post-market studies conducted by regulators and other stakeholders.

5. Develop common protocols, timelines, and data model templates for enhanced operational efficiency

Collaboration with patients, healthcare professionals, industry, HTA bodies, payers, academia, and public health agencies is essential for ensuring that RWE is developed and utilized effectively. To optimize collaboration, data sharing, and project alignment, standardized protocols, timelines, and data model templates should be developed. This would streamline regulatory processes and improve efficiency across studies.

Key initiative: Big Data Steering Group – implements the Big Data Task Force recommendations, facilitating cooperation across regulatory agencies and stakeholders.

6. Leverage existing infrastructure for enhanced international collaboration

To support the increasing use of RWE, regulators should maximize the use of established resources, such as DARWIN EU, European Health Data Space (EHDS), and national regulatory networks. By integrating existing data platforms and analytical tools, agencies can efficiently evaluate medicine benefits and risks, ensuring a coordinated approach to RWE use.

Key initiative: DARWIN EU, EHDS, and national regulatory networks and knowledge-sharing initiatives across EU agencies to enhance RWE assessment capabilities.

7. Strengthen outreach for transparency and engagement

To enhance transparency and stakeholder engagement, regulatory agencies should actively disseminate materials through agency websites, social media, and targeted mailings. This includes press releases, research summaries, and workshop reports, ensuring broader access to key regulatory findings. By increasing visibility, this initiative supports evidence-based decision-making and public trust in RWE use.

By implementing these recommendations, global regulatory agencies can enhance preparedness, improve methodological consistency, and optimize the use of RWE in medicine regulation, ultimately supporting public health and evidence-based policy-making.