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AdminDec 7, 20231 min read

Aetion’s comments to FDA on recent draft guidance on the substantial evidence standard

This week, Aetion submitted a letter to FDA commenting on the Agency’s recent draft guidance document Demonstrating Substantial Evidence of Effectiveness Based on One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence (the Draft Guidance).

The Draft Guidance provides helpful clarity to sponsors and real-world evidence (RWE) companies on the Agency’s articulation of the substantial evidence standard and how a single adequate and well-controlled clinical investigation can meet that standard when accompanied by appropriate confirmatory evidence. Aetion applauds FDA’s definitive statement that RWE can provide confirmatory evidence when generated in a principled, reproducible, and transparent manner.

The Draft Guidance’s approach to confirmatory evidence, and the ability of established natural history and other types of evidence based on real-world data to serve that function, is consistent with what Aetion has observed in FDA’s past practice. As discussed in our recent paper SURF: A Screening Tool (for Sponsors) to Evaluate Whether Using Real-World Data to Support an Effectiveness Claim in an FDA Application Has Regulatory Feasibility, FDA has already been exercising the flexibility to find substantial evidence of effectiveness based on a single adequate and well-controlled clinical investigation plus confirmatory evidence in the form of established natural history, which is particularly important when the single investigation is an externally controlled trial. We also appreciate FDA’s reinforcement of how natural history data can be used to increase confidence in conclusions from a single randomized trial.

In Aetion’s comment letter, we requested that FDA provide examples of some of the scenarios discussed in the Draft Guidance, including (1) the particular factors and characteristics of a pivotal study that are most likely to influence the quantity or nature of confirmatory evidence needed and (2) how evidence based on RWD, other than natural history, can serve as confirmatory evidence in product applications.

View our full comments here. To learn more about Aetion’s SURF framework, watch the on-demand webinarContact us today for more information on how we can partner with you to address your regulatory needs.