FDA Issues Guidelines to Support Applications for Accelerated Approvals

The FDA has issued draft guidance to improve applications for accelerated approvals, according to a recently issued news release.



The FDA has issued draft guidance to improve applications for accelerated approvals, according to recently issued news release. The agency seeks 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.1

The draft guidance addresses the design, conduct, and analysis of data through 2 randomized clinical trial approaches: conducting 2 separate randomized controlled clinical trials or using one trial for both accelerated approval and to verify clinical benefit. The agency provides considerations for sponsors to determine the adequacy of single-arm studies to support an application.

The agency often turns to the accelerated approval pathway for oncology drugs because of the serious and life-threatening nature of cancer, and because intermediate clinical end points such as progression-free survival or overall response rate are likely predictors of clinical benefit. Oncology drugs have accounted for 85% of all accelerated approvals issued over the past decade, translating to more than 172 indications as of May 2021.2

“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that can be practice changing,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence.1 “Today’s draft guidance provides recommendations to sponsors for designing clinical trials to support accelerated approval.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 agency has required post-marketing confirmatory trials to verify and describe the anticipated clinical benefit for drugs granted accelerated approval. The draft guidance suggests that one advantage of randomized clinical trials over single-arm trials is that the use of the one-trial approach, in appropriate cases, may not require separate clinical trials. In those instances, longer term follow-up in the same trial could fulfill a post-marketing requirement to verify clinical benefit.

The FDA also noted that confirmatory trials that are in progress at the time of accelerated approval are more likely to result in a timely verification of clinical benefit, therefore minimizing the period of uncertainty for patients. The median time to verification of clinical benefit and granting of traditional approval is 3.1 years (range, 0.5-17.6), according to Oncology Center of Excellence staff. In the majority of the 38% of cases for which confirmatory trials are ongoing, the accelerated approval was granted within the past 3 years.3

Delayed withdrawals that occur when investigators have not initiated a confirmatory trial at the time of the accelerated approval are the most dangerous and cause the most uncertainty for patients. 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.3

The Center of Excellence has launched Project Confirm to promote transparency of outcomes related to accelerated approval for oncology indications. The project also aims to foster discussion and research on the accelerated approval program.

Confirm has developed a searchable database with information on the status of all oncology accelerated approvals. The FDA’s Center for Drug Evaluation and Research model adopted that same model for all accelerated approvals.


  1. FDA issues draft guidance aimed at improving oncology clinical trials for accelerated approval. News release. FDA. March 24, 2023. Accessed March 24, 2023. www.fda.gov
  2. Beaver JA, Pazdur R. “Dangling” accelerated approvals in oncology. N Engl J Med. 2021;384(18):e68. doi:10.1056/NEJMp2104846
  3. Fashoyin-Aje LA, Mehta GU, Beaver JA, Pazdur R. The on- and off-ramps of oncology accelerated approval. N Engl J Med. 2022;387(16):1439-1442. doi:10.1056/NEJMp2208954

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