The Food and Drug Administration (FDA) has issued draft guidance designed to improve the quality and efficiency of applications seeking accelerated approval, particularly for oncology drugs. This initiative aims to enhance the data available at the time of accelerated approval and reduce clinical uncertainty for patients by ensuring timely initiation of postmarketing confirmatory studies.
The draft guidance outlines recommendations for the design, conduct, and analysis of clinical trials to support accelerated approval. It highlights two randomized clinical trial approaches: conducting two separate randomized controlled clinical trials or using one trial for both accelerated approval and verification of clinical benefit. The agency also provides considerations for sponsors to determine the adequacy of single-arm studies.
Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, stated, “The FDA’s accelerated approval program has provided patients with cancer earlier access to novel treatments that can be practice changing. Today’s draft guidance provides recommendations to sponsors for designing clinical trials to support accelerated approval.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 FDA emphasizes the importance of post-marketing confirmatory trials to verify and describe the anticipated clinical benefit for drugs granted accelerated approval. The guidance suggests that randomized clinical trials offer advantages over single-arm trials, as a single trial can potentially fulfill post-marketing requirements through longer-term follow-up, thereby negating the need for separate clinical trials.
According to the Oncology Center of Excellence staff, the median time to verification of clinical benefit and granting of traditional approval is 3.1 years (range, 0.5-17.6). The FDA also noted that confirmatory trials in progress at the time of accelerated approval are more likely to result in timely verification of clinical benefit, minimizing uncertainty for patients. Delayed withdrawals, which occur when investigators have not initiated a confirmatory trial at the time of accelerated approval, pose the greatest risk and uncertainty. The median time to withdrawal of an indication was 3.8 years (range, 1.3-12.5) compared with 7.3 years if such a trial had not been initiated.
To enhance transparency and foster discussion on the accelerated approval program, the Center of Excellence has launched Project Confirm. This project includes a searchable database with information on the status of all oncology accelerated approvals. The FDA’s Center for Drug Evaluation and Research has adopted a similar model for all accelerated approvals.
