FDA Issues Draft Guidance Aimed at Improving Oncology Clinical Trials for Accelerated Approval

SILVER SPRING, Md., March 24, 2023. Today, the U.S. Food and Drug Administration issued draft guidance, Clinical Trial Considerations to Support Accelerated Approval of Oncology Therapeutics, regarding clinical trial design considerations to support accelerated approval applications. The accelerated approval pathway is commonly used for the approval of oncology drugs in part due to the serious and life-threatening nature of cancer and because of available intermediate clinical endpoints likely to predict clinical benefit.

“The FDA’s accelerated approval program has provided patients with cancer earlier access to novel treatments that can be practice-changing,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence. “Today’s draft guidance provides recommendations to sponsors for designing clinical trials to support accelerated approval. Building quality and efficiency into the design of oncology clinical trials is a crucial component in providing maximum benefit to those living with cancer.”

The draft guidance discusses the design of clinical trials and ways to improve the data available at the time of accelerated approval and reduce clinical uncertainty for patients by initiating postmarketing confirmatory studies in a timely manner. Specifically, the draft guidance addresses the design, conduct, and analysis of data through two randomized clinical trial approaches – conducting two separate randomized controlled clinical trials or using one trial for both accelerated approval and to verify clinical benefit. The draft guidance also provides considerations for sponsors to determine the adequacy of single-arm studies to support an application.

For drugs granted accelerated approval, postmarketing confirmatory trials have been required to verify and describe the anticipated clinical benefit. The draft guidance discusses a potential advantage of randomized clinical trials–compared to single-arm trials–by highlighting that the use of the one-trial approach, in appropriate cases, may not require separate clinical trials because longer-term follow-up in the same trial could fulfill a postmarketing requirement to verify clinical benefit. Moreover, confirmatory trials that are in progress at the time of accelerated approval are more likely to result in timely verification of clinical benefit, therefore minimizing the period of uncertainty for patients.

In a commentary in the New England Journal of Medicine in 2022, Oncology Center of Excellence staff outlined the concepts included and expanded upon in the draft guidance. The Oncology Center of Excellence has also launched Project Confirm. This initiative promotes the transparency of outcomes related to accelerated approval for oncology indications and fosters discussion and research on the accelerated approval program. The project developed a searchable database with information on the status of all oncology accelerated approvals, a model that FDA’s Center then adopted for Drug Evaluation and Research for all accelerated approvals.

The FDA, an agency within the U.S. Department of Health and Human Services, protects public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines, and other biological products for human use and medical devices. The agency is also responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and regulating tobacco products.

SOURCE U.S. Food and Drug Administration

Posted: March 2023