ICH reflection paper marks milestone in harmonization of real-world evidence use in medicines regulation

The International Council on Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) finalizes its reflection paper to harmonize the regulatory use of real-world data (RWD) and evidence (RWE) globally.

Following public consultation in 2023, the ICH has recently released its, “ICH reflection paper on pursuing opportunities for harmonisation in using real-world data to generate real-world evidence, with a focus on the effectiveness of medicines.” Co-developed by the European Medicines Agency (EMA), the US Food and Drug Administration (FDA), and Health Canada, and adopted by the ICH Assembly in June 2024, this reflection paper represents a significant step toward global convergence in the regulatory use of RWD and RWE.

Despite their potential, the use of RWD and RWE in regulatory contexts faces several challenges, including the lack of standardization in terminology, the heterogeneity of RWD sources, and the variability in data quality and study designs. The ICH reflection paper addresses these issues by proposing a strategic, incremental approach towards harmonization. Building upon a 2022 statement from the International Coalition of Medicines Regulatory Authorities (ICMRA), this approach aims to provide a robust framework for future ICH guidelines on the assessment and utilization of RWD and RWE, paving the way for more effective regulatory practices.

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Key areas for harmonization

The ICH reflection paper identifies two key areas for harmonization:

	Topic	Objective	Deliverables	Tentative timeframe
1	RWD/RWE terminology, metadata, and assessment principles	Promote a common understanding of the types and scope of RWD/RWE Guide the discoverability, identification, and description of RWD Inform the assessment of RWD/RWE for regulatory purposes	Common operational definitions of RWD and RWE, with clear scope, breadth of potential RWD sources, and level of granularity (e.g., pertaining to RCTs and non- interventional studies Core list and use of metadata General principles for assessment of RWD/RWE RWD/RWE protocol & report format, and study transparency	Submit new ICH topic proposal in Dec 2024
2	RWD/RWE protocol & report format, and study transparency	Agree on common principles regarding formats for RWD/RWE protocols and reports of study results submitted to regulators Promote transparency by encouraging registration of study protocols and study reports in publicly available registries	Principles for structure and content of protocols and reports (for medicines developers) Recommended ‘best practices’ for registration of study protocols/results Initiate work after the first guideline reaches Step 4 of the ICH Procedure	Initiate work after the first guideline reaches Step 4 of the ICH Procedure
From ICH reflection paper on pursuing opportunities for harmonisation in using real-world data to generate real-world evidence.

 

ICH anticipates synergies with other ICH guidelines, including the recently-announced ICH M14 draft guideline on pharmacoepidemiological studies using RWD.

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Consultation and feedback

The ICH reflection paper underwent revision following a public consultation process in 2023. This initiative received 151 comments from 16 parties, including learned societies, clinical research organizations, academia, industry associations, and international regulators. The feedback overwhelmingly supported the initiative, highlighting the importance of standardization and international harmonization. One commenter noted,

“We welcome the initiative of international harmonization of real-world evidence terminology and convergence of general principles regarding planning and reporting of studies using real-world data, with a focus on effectiveness of medicines.”

The ICH has provided high-level overview of the comments received, outlining where and how the range of comments were considered and how they might influence the next steps in the process.

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Future guidelines and next steps

The ICH plans to develop two guidelines based on the reflection paper to facilitate the integration of RWE into regulatory submissions and decision-making. These guidelines will cover principles for data collection, data quality management, and the conduct of RWD-based studies, including considerations on study design and data analysis. By standardizing terminology, formats, and promoting transparency, the ICH aims to support the safe and effective use of medicines, address unmet medical needs, and facilitate the development of innovative treatments.