FDA Releases Draft Guidance on Confirmatory Trials for Accelerated Approvals

• The FDA has issued a draft guidance that describes the criteria for confirmatory trials in accelerated approvals.
• The FDA considers trials underway if they have a clear target completion date, demonstrated progress, and initiated patient enrollment.
• Early engagement with the FDA, including draft protocol reviews and comprehensive trial plans, is encouraged to ensure timely and effective trial execution.

The FDA’s Oncology Center of Excellence has released a draft guidance document detailing its interpretation of when a confirmatory clinical trial is considered "underway" as part of the accelerated approval process.¹

This guidance aims to provide clarity for sponsors and ensure the timely completion of confirmatory trials, which are critical in verifying the benefits of oncology treatments approved under this expedited pathway.

The FDA stated that a confirmatory trial is considered underway prior to granting accelerated approval if: the trial has a target completion date that is consistent with diligent and timely progress; sponsors demonstrate sufficient planning and progress to assure timely trial completion; patient enrollment in the confirmatory trial has begun.

Recent amendments to the Federal Food, Drug, and Cosmetic Act (FD&C Act) via the 2023 Consolidated Appropriations Act grant the FDA additional authority to ensure confirmatory trials begin promptly. The agency may now require these trials to be underway prior to approval or within a specified timeframe post-approval.

Sponsors are encouraged to engage in early discussions with the FDA, ideally by the end-of-phase 2 meeting, to finalize the design of confirmatory trials and review draft protocols. Factors such as disease characteristics, alternative treatments, recruitment timelines, and projected timelines for efficacy analyses should be considered when setting trial completion dates.

“Appropriate target completion dates may differ across therapeutic areas. In oncology, for example, the median time from accelerated approval to verification of benefit is approximately 3 years (including FDA review) and has been decreasing over time. Specific target completion dates for a trial depend on more considerations than can be described here. In all cases, sponsors should provide FDA with a clear and sound justification of the proposed target completion date for the Agency’s consideration,” wrote the FDA’s Oncology Center of Excellence in the draft guidance.²

Background on Accelerated Approval

The FDA's accelerated approval pathway allows therapies for serious or life-threatening conditions to gain approval based on surrogate end points reasonably likely to predict clinical benefits.

However, confirmatory trials are required post-approval to verify the clinical benefit of an agent. While many of these trials are completed in a timely manner, some have faced delays, leading to concerns about their reliability and the implications for patient care.

In some cases, the FDA may not require a confirmatory trial to be underway before approval, especially if the trial depends on future contingencies.

The finalized guidance will provide additional details, offering greater clarity on implementation and helping stakeholders navigate the accelerated approval process more effectively.

“This draft guidance, when finalized, will represent the current thinking of the Food and Drug Administration on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.”

REFERENCES

1. Accelerated approval and considerations for determining whether a confirmatory trial is underway. FDA. January 6, 2025. Accessed January 8, 2025. https://tinyurl.com/tfb9duuv

2. Accelerated approval and considerations for determining whether a confirmatory trial is underway guidance for industry draft guidance. FDA. January 7, 2025. Accessed January 8, 2025. https://www.fda.gov/media/184831/download