[9/18/2023] Today, CDER, along with FDA’s Center for Biologics Evaluation and Research and the Oncology Center of Excellence, issued the draft guidance Demonstrating Substantial Evidence of Effectiveness Based on One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence.

This guidance (the Confirmatory Evidence guidance) complements the draft guidance for industry Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products (December 2019) and the guidance for industry Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products (May 1998).

The Confirmatory Evidence guidance supplements and expands the recommendations in the 2019 Substantial Evidence of Effectiveness draft guidance by providing further detail on the use of data drawn from one or more sources (e.g., clinical data, mechanistic data, animal data) to support the results of one adequate and well-controlled clinical investigation. It also provides examples of types of data that could be considered confirmatory evidence. Importantly, this guidance emphasizes the need for early engagement with the agency for sponsors that intend to establish substantial evidence of effectiveness with one adequate and well-controlled clinical investigation and confirmatory evidence.

Although FDA’s standard for demonstrating effectiveness has not changed since the publication of the 1998 guidance, drug and biologic development and science has evolved, leading to changes in the types of product development programs submitted to the agency. This guidance issued today, along with the 2019 draft guidance, provide additional information on the flexibility in the amount and type of evidence needed to establish their effectiveness.

Sponsors should consider the clinical context for the proposed therapy when evaluating whether to approach establishing substantial evidence of effectiveness with one adequate and well-controlled clinical investigation and confirmatory evidence. Disease- or condition-specific considerations may be relevant to whether such an approach is appropriate.

Although safety considerations are beyond the scope of this guidance, decision-making about a drug development program should also consider the data necessary to demonstrate that a drug is safe. The finding of substantial evidence of effectiveness is necessary but not sufficient for FDA approval. An approval decision also requires a determination that a drug is safe for its intended use.

Comments regarding this draft guidance should be submitted following the information in the notice of availability that will be posted in the Federal Register shortly.