New FDA Guidance on Clinical Trial Design—and an Admonition from Commissioner Gottlieb

March 18, 2019 — With mere days left before his departure as FDA Commissioner, Dr. Scott Gottlieb is trying to focus attention on one of the lesser-known of his major initiatives – improving the design of clinical trials in drug development. In a statement released along with the publication of a new guidance, Gottlieb highlighted the FDA’s recent efforts to change how clinical trials are conducted and regulated. He also criticized pharmaceutical sponsors and contract research organizations for what he terms “a continued reluctance to adopt innovative approaches,” saying that their business models often work against collaboration and data sharing.

“Dr. Gottlieb’s initiatives on clinical trials tie in with two major themes of his tenure as Commissioner: To bring the FDA and its processes up to date with the best current science and use of newer data sources, and to make the drug development process more efficient as a means to bring more products to market,” noted Jon Bigelow, executive director of the Coalition for Healthcare Communication.

The new guidance announced March 15 in the Federal Register covers several clinical trial “enrichment strategies.” For example, it discusses “adaptive enrichment” to address the problem that it is not always clear before a trial begins what sample size will be adequate to detect a therapeutic effect (positive or negative), which presents a risk that a study will not achieve its objectives. Prospectively-planned adaptations to sample size or entry criteria, for example, can allow trial investigators to take advantage of information gained on a marker’s performance during the course of the trial.

The opportunity Gottlieb sees in this and a long list of similar potential changes is to reduce the time and resources needed to generate data on the efficacy and safety of an investigational agent. “The initial design of a clinical trial can have a major impact on whether important signs of efficacy and safety are detected and, ultimately, on how quickly a product eventually gets to market,” said Bigelow.

The FDA last week also announced the availability of a clinical trial draft guidance covering risk-based monitoring, which Gottlieb describes as facilitating “efficient development of novel innovations, while also generating the robust evidence needed to better assess product safety and efficacy.” A third, final guidance, “Severely Debilitating or Life-threatening Hematologic Disorders: Nonclinical Development of Pharmaceuticals,” also was released.