REGULATORY CORNER

Let’s start by going into the way back time machine. It was in 1962 that Congress amended the Food, Drug and Cosmetic Act (FD&C Act) to require that drugs be effective as well as safe prior to approval for marketing. The law required that effectiveness of a drug was to be established by substantial evidence, defined as “adequate and well controlled investigations.” The standard FDA interpretation has been that “investigations” means more than one study. Thus, the requirement for two adequate and well-controlled studies. In 1997, Congress amended the FD&C Act to make it clear that FDA may consider data from one adequate and well-controlled study and confirmatory evidence sufficient to establish efficacy.

Those of us working in drug development for several years have likely, at one time or another, focused on the requirements for the development of a combination product. They are listed in 21CFR300.50 Fixed-combination prescription drugs for human use; a regulation dated March 27, 1975 and amended on January 5, 1999. FDA also issued a guideline in 2013, Codevelopment of Two or More New Investigational Drugs for Use in Combination (the 2013 Codevelopment Guidance) that further expands on the information in the regulation.

In August 2025, FDA issued the draft guidance, Approaches to Assessment of Overall Survival in Oncology Clinical Trials. This guidance is based in part on discussions held at a joint FDA, American Association for Cancer Research (AACR), and American Statistical Association (ASA) public workshop held in July 2023. It also puts into writing feedback that I have received from the Agency on oncology clinical trials and guidance that I have related to our oncology clients.