FDA Issues Draft Guidance Recognizing the Role of Real-World Evidence in Learning More about Populations Underrepresented in Clinical Trials for Drugs and Biological Products

By: Ulka Campbell, Head of Scientific Strategy, Aetion

Of the many potential use cases for real-world data (RWD) and real-world evidence (RWE), one of the most important is improving the information available about how medical products work in populations that have been historically underrepresented in clinical trials. Striving for health equity and increasing the visibility of underrepresented populations is a critical topic for the U.S. healthcare system. The safety and effectiveness of treatments cannot be accurately assessed without understanding their effects in all relevant populations. To support this understanding, the U.S. Food and Drug Administration (FDA) released draft guidance on diversity plans in April 2023, Project Equity, and the Diversity in Clinical Trials Initiative.

FDA’s most recent guidance in this space, “Postmarketing Approaches to Obtain Data on Populations Underrepresented in Clinical Trials for Drugs and Biological Products” (released on August 10, 2023), is the latest step in FDA’s systematic effort to improve representation in the health data it reviews.  In this guidance, FDA confirmed the important role of RWD and RWE in achieving this goal.

The Draft Guidance discusses mechanisms through which sponsors can collect information on historically underrepresented populations to provide a more comprehensive picture of a medicine’s benefits and risks. FDA explicitly recognized that RWD studies can be directly used to generate evidence of clinical benefit and safety in underrepresented populations. To help assure robust use of RWD, the Agency also provided recommendations for ensuring the suitability of RWD and RWE used for this purpose, including that sponsors should carefully evaluate whether RWD sources and RWE study design are adequate to assess the research questions at hand and that sponsors should approach FDA to discuss the underlying complexities.

Looking more broadly, there are several other ways sponsors can use RWD to support evidence generation in underrepresented populations.  RWD-derived benchmarks of data representativeness can inform diversity plans and recruitment strategies, and inform simple post-hoc trial sensitivity analyses that explore treatment effects in more representative populations. Combined with real-world evidence, synthetic evidence generation, which is based on analysis of data simulated using artificial intelligence and machine learning methods, may be used to extrapolate a pivotal trial result to the real-world population and understand the potential impact of underrepresented subgroups in the trial.  A complementary approach of robust RWE and synthetic evidence generation is critical to inclusive trial design, supplementing trial data with real-world safety and effectiveness data from subgroups, and estimating treatment effects in broader populations when trial data are limited despite best efforts and before sufficient post-approval accumulation of RWD.

The generation of robust RWE to advance public health goals, such as representativeness, is at the heart of what Aetion does. Our company’s North Star, the principle that guides all of our work, is to help build a world in which we know what health treatments work, for whom, and what we should pay for them. By recognizing the role that RWE can play, FDA’s Draft Guidance helps move us closer to realizing that vision.  If you are interested in learning more about how RWD, RWE, and synthetic data generation can help improve your understanding of the holistic picture of a medicine, please connect with us.