The new draft guidance “Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products” (here) provides the industry with a foundation for providing one adequate and well-controlled study with appropriate confirmatory supporting data to satisfy the Agency’s requirement for demonstrating safety and efficacy. While this may, on its face, appear to be a boon for companies in that it will lower the cost of clinical trials to support a market application, there very well may be hidden landmines in thinking this is a panacea.
The FDA notes that “this guidance clarifies how sponsors can rely on one scientifically rigorous adequate and well-controlled clinical investigation with confirmatory evidence to satisfy the statutory substantial evidence of effectiveness standard as defined in section 505(d) of the Federal Food, Drug, and Cosmetic Act (FD&C Act).” The wildcard here is exactly what constitutes confirmatory evidence!
The Agency strongly suggests that sponsors meet with the FDA prior to embarking on the one adequate and well-controlled study option to ensure that they have a good understanding of what might be required by the FDA and to gain agreement on the extent of the necessary confirmatory evidence to support this one clinical study. Jumping the gun on a path forward without significant consultation with the FDA could easily lead to a disastrous outcome. The guidance gives general observations as to what might qualify as confirmatory data, but warns that “[w]hether sponsors have demonstrated substantial evidence will depend on the strength of the evidence provided.” Also, don’t forget that the FDA expects a demonstration of the safety of the proposed drug product as well.
The draft guidance addresses the following topics:
Legal Standard of Effectiveness for Drug and Biologic Products
- Factors impacting the strength of the evidence of effectiveness
- Trial design
- Trial conduct
- Trial analysis plan
- Evaluation of trial results
- Aspects of the overall development program
Approaches to Meeting the Substantial Evidence Standard
- Evidence from an adequate and well-controlled trial plus a source of strong confirmatory evidence
- Evidence from a highly persuasive, adequate, and well-controlled trial plus early-phase confirmatory evidence
The draft guidance goes on to discuss certain regulatory flexibilities but, again, the devil is in the details. Perhaps the FDA, as suggested by some commenters, might want to place more specifics around what constitutes confirmatory evidence. Perhaps, before this guidance goes final, the FDA will come out with more explicit information to take some of the guesswork out of the industry’s decision-making process. Be cautious in jumping in with both feet until there is more clarity or you have reached an agreement with the FDA on a path forward.
