Real-World Evidence (RWE) refers to clinical evidence derived from real-world data (RWD) collected outside of traditional clinical trial settings. The significance of RWE in regulatory decision making has been growing worldwide due to its potential to provide valuable insights into the safety, efficacy, and effectiveness of therapeutic products. While traditional clinical trials remain the gold standard for establishing safety and efficacy, RWE complements these trials and fills critical gaps in understanding the real-world performance of drugs and medical devices. Several regulatory agencies have adopted a proactive approach in incorporating RWE & RWD into regulatory decision making, including Swissmedic through its position paper on RWE.
Recognizing the Importance of RWE in Regulatory Decision Making
This paper signifies Switzerland’s intent to initiate a dialogue on the use of RWE as supportive evidence for data from clinical trials. It highlights the need for guidance in this evolving area.
Swissmedic recognizes the evolving landscape of RWE in regulatory decision-making. However, it noted that there is a lack of legal basis for incorporating RWE into the authorization process for therapeutic products in Switzerland. While the Swiss law requires the results of GCP-compliant clinical trials as the basis for authorization, it also acknowledges that international guidelines recognize the relevance of RWE in specific cases, underscoring the need for flexible and adaptive approaches to accommodate its use.
To address the challenges and opportunities presented by RWE, Swissmedic published a position paper in July 2022. This paper serves as a pivotal step towards initiating a dialogue on the use of RWE in regulatory decision-making. Swissmedic accepts RWE as supportive evidence to complement traditional clinical trial data in marketing authorizations and variation applications. However, it is important to note that RWE is not accepted as the sole basis for new marketing authorizations.
The paper highlights the importance of data quality, outlining requirements for addressing research questions, study design, data sources, coding systems, study populations, statistical analysis plans, milestones, limitations, and compliance with legal and regulatory standards. Data anonymization and de-identification techniques are essential to protect patient privacy. Swissmedic is actively monitoring global developments related to the regulation and use of RWD and RWE. It is engaging in discussions with partners and regulatory authorities globally, such as the FDA Sentinel System and DARWIN EU, to evaluate the value that RWD/RWE adds for decisions related to products. The results of these ongoing discussions will shape the need for new international standards to harmonize RWE’s use in medicinal product reviews.
Regulatory Considerations
Submissions must align with the latest scientific and technological standards. Due to uncertainties associated with RWE and the evolving regulatory landscape, it’s advisable to discuss the appropriate use of RWE with Swissmedic before submitting an application.
If an application includes RWE, the rationale for using it must be outlined in the cover letter and detailed in the application dossier. RWE should be critically evaluated within the context of all available evidence. The sources of RWD used in RWE studies or analyses should be described in detail and appropriately referenced in the application.
New Marketing Authorizations and Variations
For new marketing authorizations and variation applications that expand the therapeutic scope of a medicinal product, Swissmedic accepts RWE as a complement to clinical trial data. However, Swissmedic currently does not accept new marketing authorizations based solely on RWE, as the legal, scientific, and regulatory frameworks for such applications are still evolving. Adequate clinical trial data remains a minimum requirement, but exceptions can be discussed with Swissmedic.
Post-Marketing Surveillance
In the post-marketing surveillance setting, Swissmedic allows the use of RWE for implementing or modifying risk minimization measures. For changes to the Information for healthcare professionals or other post-marketing modifications affecting the therapeutic use of a medicinal product, the marketing authorization application can be based solely on RWE.
Sources of RWE:
Electronic health data records and registry data can be used for signal detection and evaluating risk minimization measures. Social media and patient health application data may also be utilized in pharmacovigilance, but their use presents challenges, and careful statistical methods are required to ensure data accuracy. Factors like comorbidity and insurance may influence these data, and additional studies or information may be necessary to implement safety recommendations.
Global Overview on RWE in Regulatory Decision Making
In the United States, the 21st Century Cures Act, passed in 2016, mandated the FDA to develop a framework for evaluating the use of RWE in regulatory decision-making. In response, the FDA published this framework in 2018, marking a significant step toward the incorporation of RWE in regulatory processes. The FDA has also issued draft guidance documents for the industry, providing clarity on the use of registry data, electronic health records, medical claims data, data standards for RWE, and non-interventional studies using real-world data.
In Europe, the European Medicines Agency (EMA) outlined its commitment to enable the use of RWE in regulatory decision-making by 2025 in its “Regulatory Science to 2025” document. The EMA has also issued guidelines on registry-based studies and is actively working on integrating RWE into its decision-making processes. The UK Medicines and Healthcare products Regulatory Agency (MHRA) published guidelines in 2021 related to the use of RWE in randomized controlled trials using real-world data.
In the Asia-Pacific region, several regulatory agencies have made progress in incorporating RWE into their decision-making processes. The National Medical Products Administration (NMPA) in China has developed guidelines on the use and evaluation of RWE for drug development and regulatory decisions, emphasizing data quality and security. Australia’s Therapeutic Goods Administration (TGA) reviewed the use of RWE and patient-reported outcomes in regulatory evaluations in 2021. In Japan, the Pharmaceuticals and Medical Devices Agency (PMDA) established a working group in 2021 to discuss regulatory issues related to real-world data (RWD) and RWE, with a focus on data reliability and methodology. South Korea’s Ministry of Food and Drug Safety (MFDS) is developing a framework to leverage RWD in regulatory decision making.
Conclusion
The adoption of real-world evidence (RWE) in regulatory decision-making is a global trend with varying levels of acceptance and progress across countries and regions. Switzerland, through Swissmedic, is actively engaging with this evolving landscape and has issued a position paper to provide guidance on the use of RWE in therapeutic product authorization. As the regulatory landscape continues to evolve, RWE will play an increasingly vital role in supporting evidence-based decisions, optimizing therapeutic strategies, and ensuring the safety and effectiveness of healthcare products. It remains to be seen how international standards and regulations will adapt to fully incorporate the potential of RWE in the regulatory process.
DDReg has provided regulatory and pharmacovigilance support to its customers for several countries in Europe, including Switzerland. Reach out to the team at info@ddregpharma.com for more information. Read our previous blog on the Modernization of Cosmetic Regulation Act.