By Robert Honigberg, MBA, MD, MS&T Consulting, LLC
Neil Belson, JD, Law Office of Neil A Belson, LLC
EXECUTIVE SUMMARY
The 21st Century Cures Act, enacted in 2016, requires the U.S. Food and Drug Administration (FDA) to assess the use of Real-World Evidence (RWE) for applications that include new drug indications and satisfying post-approval drug study requirements. RWE can contribute to showing that a drug or medical device is safe and effective, within the context of the FDA’s “totality of evidence approach” for evaluating regulatory submissions. The FDA has approved both drugs and medical devices based on regulatory submissions which have included RWE.
KEY WORDS: Real-World Data (RWD), Real-World Evidence (RWE), totality of evidence, FDA
INTRODUCTION
The 21st Century Cures Act (2016) requires the U.S. Food and Drug Administration (FDA) to assess the use of Real-World Evidence (RWE) for applications that include new drug indications and satisfying post-approval1,2. The FDA issued a final guidance document for medical devices in 2017, in which the Agency stated that the applicant could use Real-World Data (RWD) to support regulatory determinations under the right conditions3. While the FDA has not yet followed up with a guidance for pharmaceutical products, their 2018 Framework for FDA’s Real-World Evidence Program outlined the potential applications of RWE for regulatory decision-making regarding the effectiveness of marketed products4. In the instance of an original approval for a product, the FDA recommended that an evidence package could contain three types of studies: clinical pharmacology, non-clinical toxicology, and clinical studies. However, for post-marketing labeling changes (i.e., use in a new population or a new indication), the evidence package could include prior submitted evidence and new evidence, traditionally represented by randomized clinical studies but also RWE studies. What is important for Medical Affairs and Regulatory teams to understand is that regardless of study type, setting, or design, the FDA does not have to evaluate one study type (i.e., Randomized Clinical Trial (RCT)) only when making regulatory decisions. Instead, the FDA uses a totality of evidence approach, examining all available evidence in the regulatory materials submitted including the quality of the studies and context of the manufacturer’s request4.
