FDA has interpreted this substantial evidence requirement as generally requiring two adequate 44 and well-controlled clinical investigations, each convincing on its own, to establish effectiveness.

 Nevertheless, as noted in the 1998 Effectiveness guidance, FDA has also been flexible within the  limits imposed by the statute where data on a particular drug were convincing. In 1997, Congress amended section 505(d) to confirm FDA’s interpretation of the statutory requirements, making  clear that FDA may consider data from one adequate and well-controlled clinical investigation  and confirmatory evidence to constitute substantial evidence if FDA determines that such data are sufficient to establish effectiveness.

Specifically, Congress added to section 505(d) that FDA issued the 1998 Effectiveness guidance in response to this legislative change. The 1998  guidance provides examples of the types of evidence that could be considered confirmatory  evidence, with a specific focus on adequate and well-controlled trials of the test agent in related  populations or indications, as well as a number of illustrations of a single adequate and well controlled trial supported by convincing evidence of the drug’s mechanism of action in treating a  disease or condition.


Demonstrating Substantial Evidence of Effectiveness With One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence Guidance for Industry