Harmonizing Global Frameworks for Real-World Evidence - Regulatory Alignment for the Benefit of Patients
The demand for real-world data (RWD) to generate real-world evidence (RWE) by regulators is growing around the world. At the recent RAPS Convergence, a timeline illustrating the growth of RWE legislation across jurisdictions in the U.S., Europe, Japan, South Korea, and China demonstrated the prioritization of RWE by regulators to demonstrate safety and effectiveness of medical products, particularly medical devices, globally. But, as with so many global initiatives, there is also growing recognition of the need to harmonize expectations for the collection, synthesis, and submission of RWE on a global scale. The alternative, namely a patchwork of differing regulations, would impose burden and cost on industry, and ultimately patients. Now is the time to ensure that RWE regulatory requirements are aligned across regulatory bodies.
Harmonization of RWE requirements is not a new concept. In 2016, the International Medical Device Regulators Forum (IMDRF) issued a Final Document, Principles of International System of Registries Linked to Other Data Sources and Tools, in which the agency advocated for harmonization across global medical device registries to “harness the global strength of international experience with devices.” The IMDRF used examples from orthopedics and cardiovascular registries to make the case that harmonized device registries across global jurisdictions would allow regulators to leverage the global experience with medical devices across therapeutic areas. Currently, country-specific registries use idiosyncratic methods for classifying types of devices, categorizing failure modes, and analyzing and summarizing registry data. Even the more robust national registry data are not always comparable across countries due to these differences (i.e., Australia National Joint Replacement Registry and United Kingdom National Joint Registry). Imagine RWE frameworks beyond specific registries that differ depending on the prerogative of stakeholders contributing to the policies and the preferences of country-specific regulators.
More recently, in September 2023, the International Council on Harmonization (ICH) generated a draft ICH Reflection Paper, International Harmonisation 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. This document more broadly emphasizes the need for consistency across terminology, data quality, data formats, and study designs that utilize RWD to support regulatory decision-making. While the ICH is focused on medicines regulation, these concerns are applicable to both medicine and medical device RWE studies. I would argue that the challenges of using RWE for medical device regulatory submissions is even more difficult given the inconsistent use of Unique Device Identifiers (UDI) in clinical records, particularly in the United States. The National Evaluation System for Health Technology Coordinating Center (NESTcc) published a position paper about the need for consistent UDI use in medical records in 2022.
The U.S. FDA has led the way for establishing regulatory framework and guidance for RWD/RWE in the evaluation of medical device regulatory submissions. However, many challenges remain with the use of these data for medicines and device evaluation. Data quality, common data models, alignment on statistical methodologies, data linkage technology, data access and privacy, stakeholder agreements for data sharing, patient input and consent, and ethical concerns persist. These challenges should be addressed by a broad coalition of regulatory authorities to ensure global consistency for RWE expectations. We exist in an era of unprecedented technological capabilities for data linking, tokenization to protect privacy, and big data analytics. It is the responsibility of regulators to collaborate such that industry can leverage these capabilities in a least burdensome way and ensure RWE is used to effectively and efficiently get innovative medicines and technologies to patients around the world.