June 5, 2023
The Association for Clinical Oncology (ASCO) is supportive of the Food and Drug Administration’s (FDA) draft guidance to improve oncology clinical trials for accelerated approval, but is asking the agency to include plans for setting benchmarks and determining expected target dates for sponsors of confirmatory trials before finalizing the guidance.
In comments filed May 26, the Association thanked the FDA for its work to provide recommendations on designing, conducting, and analyzing data to provide “a more robust efficacy and safety assessment for designing trials” to support accelerated approval.
“This draft guidance is timely and important. Criticism of the accelerated approval pathway has increased as multiple drugs approved under this mechanism remain on the market without completion of confirmatory studies.” wrote Lori J. Pierce, MD, FASTRO, FASCO, then-Chair of the Board for the Association for Clinical Oncology.
Dr. Pierce also noted that the draft guidance makes clear that studies intended to verify clinical benefit be underway prior to approval. The Association’s comments indicate the guidance does not include FDA’s perspective on expediting withdrawals, when appropriate, and said “it will be beneficial for the public and sponsors to clearly understand the rigorous process and considerations for the withdrawal of an indication or therapy from the market.”
Additionally, the Association offered comments on the following recommendations:
- Regarding randomized controlled vs. single-arm clinical trial designs, ASCO agrees that there are limitations with the use of single-arm trials but noted there may be situations where other trial designs, including single-arm trials are appropriate and should be considered. For example, single arm trials may be of value in the context of rare disease populations or when patients have suboptimal standard treatment options.
- Regarding considerations for two randomized controlled clinical trials, the Association said there is a need for more education about the accelerated and conditional approval processes to help the public better understand that the withdrawal of a therapy or an indication should not be viewed as a failure of the program. ASCO said it agrees with FDA’s perspective that sponsors should have the confirmatory trials initiated when the accelerated approval marketing application is submitted to ensure more timely completion of the studies and avoid the challenges when there is broad use of the drug in clinical practice and patients do not enroll in trials.
- Regarding considerations for a single randomized controlled trial to support accelerated approval and confirm clinical benefit, ASCO agreed with the guidance that sponsors should have measures in place to prevent factors that may jeopardize the trial results, such as blinding of data for endpoints supporting verification of clinical benefit. The Association also agrees that sponsors should “strive to perform efficacy analyses to support accelerated approval when the trial is close to or fully enrolled to mitigate accrual challenges that could occur if the treatment receives accelerated approval.”
- Regarding considerations for a single-arm trial to support accelerated approval, ASCO reinforced its stance that there should be considerations for the use of single-arm trials when appropriate and said, “overall survival should be considered the gold standard endpoint for measuring clinical benefit.” The comments also noted that there are many ways to evaluate benefit to patients and their quality of life, and agreed that appropriate standardized criteria, such as Response Evaluation Criteria in Solid Tumors (RECIST) should be used for measuring objectives.
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