09/27/2023
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On September 18, 2023, the U.S. Food and Drug Administration (FDA) released a draft guidance titled Demonstrating Substantial Evidence of Effectiveness Based on One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence to provide further detail on the accepted types of confirmatory evidence used to support the results of one adequate and well-controlled clinical investigation. The confirmatory evidence guidance expands on the draft guidance Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products (2019) and the final guidance Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products (1998).
The new guidance details how to use data from various sources (clinical trials, laboratory studies, and animal research) to demonstrate the effectiveness of an investigational product based on one pivotal trial. It also gives examples of the types of data that can be used as confirmatory evidence. The guidance stresses the importance of early communication with the FDA for sponsors planning to use this approach.
Types of confirmatory evidence discussed are:
Clinical Evidence from a Related Indication
Mechanistic or Pharmacodynamic Evidence
Evidence from a Relevant Animal Model
Evidence from Other Members of the Same Pharmacological Class
Natural History Evidence
Real-World Data/Evidence
Evidence from Expanded Access Use of an Investigational Drug
While the FDA's criteria for proving the effectiveness of an investigational product have remained unchanged since 1998, advances in drug development and scientific understanding have led to shifts in the types of product development programs submitted to the FDA. The 2023 draft guidance, in addition to the 2019 draft guidance, offers additional insights on the flexibility in the amount and types of evidence required to establish a product's effectiveness. This corresponds to ICH E8(R1) General Considerations for Clinical Studies which encourages flexibility in study design depending on the specifics of the investigational product, target population, and critical endpoint data.
Sponsors should consider the intended use of their proposed therapy when deciding whether to pursue this approach. Different diseases or conditions may require a different approach. While this guidance does not address safety issues, it reminds companies that proving an investigational product is effective is only part of the FDA approval process. An approval decision also hinges on confirming that the investigational product is safe for its intended use.
The FDA is accepting electronic or written comments until December 18, 2023 to be considered prior to writing the final version of the guidance. Click here for more information on submissions.
-The Clinical Pathways Team
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