The 21st Century Cures Act, signed into law in 2016, mandated the FDA to establish a framework for the evaluation of RWE in regulatory decision-making. This draft FDA guidance document forms part of the FDAs RWE program and addresses several key regulatory considerations for the use of RWE in regulatory decision-making. Let’s explore each of these considerations in more detail:

FDA Draft Guidance – Considerations for the Use of Real-World Data and Real-World Evidence to Support Regulatory Decision-Making for Drug and Biological Products (Dec 2021): https://www.fda.gov/media/154714/download

[1] Applicability of 21 CFR Part 312: Interventional studies involving drugs generally meet the definition of a clinical investigation (clinical trial) and are subject to FDA regulations under 21 CFR Part 312. On the other hand, non-interventional studies analyse data reflecting the use of a marketed drug in routine medical practice, as such non-interventional studies are not clinical investigations as defined under 21 CFR 312.3 and do not require an investigational new drug application (IND).

[2] Early Engagement with the FDA: Transparency is essential in non-interventional studies to ensure the reliability of the data collected. Sponsors should engage with the FDA in the early stages of study design, provide draft versions of protocols and statistical analysis plans for review, and finalise these documents before conducting the study analyses.

[3] RWD Data Access: Sponsors should discuss with the FDA their expectations regarding access to RWD for their development program. They should ensure that patient-level data from RWD can be submitted to the FDA when required and have agreements in place with third-party data owners to provide relevant data for inspection.

[4] Study Monitoring: Study monitoring in non-interventional studies focuses on maintaining the reliability of RWD and data integrity. Sponsors should ensure that applicable human subject protection requirements are met (IRB approval and informed consent – 21 CFR 50 and 21 CFR 56) and consider a risk-based approach to study oversight.

[5] Safety Reporting: Adverse events identified during non-interventional studies must be reported to the FDA in accordance with postmarketing safety reporting regulations (21 CFR 314.80).

[6] Other Sponsor Responsibilities: Sponsors are responsible for various activities related to the design, conduct, and oversight of non-interventional studies. These activities include selecting qualified researchers, ensuring compliance with protocols and regulations (e.g., 21 CFR 11), maintaining study records, registering the study on clinicaltrials.gov, and providing access to relevant records upon request.

In summary, this FDA guidance document provides valuable insights into the considerations for leveraging RWE to support regulatory decisions. By adhering to the guidance and engaging with the FDA early in the study design process, industry stakeholders can effectively utilise RWE to enhance the safety and effectiveness evaluation of drugs and biological products.