FDA issues draft Guidance on Confirmatory Evidence of Clinical Trials

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Evidence guidance supplements and expands the recommendations in the 2019 Substantial Evidence of Effectiveness draft guidance by providing further detail on the use of data drawn from one or more sources (e.g., clinical data, mechanistic data, real-world data). It also provides examples of data types that could be considered confirmatory evidence and additional information on the flexibility in the amount and type of evidence needed to establish effectiveness.

Types of Confirmatory Evidence

Following is a list of examples that can be used to substantiate one adequate and well-controlled clinical investigation to demonstrate substantial evidence of effectiveness:

  • Clinical evidence from a related indication (e.g., submission of a new drug or biologics license application for a new indication for an already approved therapy) 
  • Mechanistic or pharmacodynamic evidence (e.g., obtained from in vitro testing)
  • Evidence from relevant animal data
  • Evidence from other members of the same pharmacological class
  • Natural history evidence
  • Real-World Data/Evidence (RWD / RWE)
  • Evidence from expanded access use of an IMP

Early engagement with the agency to discuss any plans to use RWE as confirmatory evidence is recommended. Sponsors should continue to meet with the agency throughout product development, particularly if changes to the clinical investigation or confirmatory evidence are contemplated.

More information is available in FDA's draft guidance Demonstrating Substantial Evidence of Effectiveness Based on One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence.

Go back

GMP Conferences by Topics