Introduction
The US Food and Drug Administration (FDA) may approve drugs under the accelerated approval pathway based on surrogate endpoints likely to predict clinical benefit. However, this pathway has faced criticism due to manufacturers' delays in completing required confirmatory studies. A recent cross-sectional study examines the time taken from accelerated approval to the initiation of these confirmatory studies for both cancer and noncancer drugs.
Methods
The study utilized the FDA report "CDER Drug and Biologic Accelerated Approvals Based on a Surrogate Endpoint" to identify drugs granted accelerated approval from 2009 to 2019. It reviewed accelerated approval letters in the Drugs@FDA database to identify postmarketing requirements and abstracted final report submission dates. The study also screened ClinicalTrials.gov for corresponding confirmatory studies to determine whether studies were underway at the time of accelerated approval and to calculate the time from approval to study initiation.
Results
For 103 cancer–indication pairs and noncancer products, 20.31% of confirmatory studies were not underway at the time of accelerated approval, with a median time from approval to study initiation of 1.41 years. Noncancer products had a larger proportion of confirmatory studies initiated after accelerated approval (37.04% vs 15.84%) and a longer median time from approval to study initiation (2.11 years vs 1.20 years) compared with cancer product–indication pairs.
Discussion
The findings suggest that initiation lags may increase delays in confirmatory study completion, building on prior evidence that suggests such lags increase the overall time to conversion to full approval or market withdrawal. The study highlights the need for the FDA to use its expanded statutory authority to require confirmatory studies to be underway at the time of accelerated approval, potentially supporting the simplification and completion of these studies.
Limitations
The analysis faced limitations, including the inability to identify some confirmatory studies due to limitations in publicly available data and to determine the reasons why confirmatory studies were or were not underway at the time of accelerated approval.
Conclusion
While the FDA has endorsed the timely initiation of confirmatory studies, additional reforms may be necessary for the timely completion of these studies and verification of products’ clinical benefit. The study underscores the importance of addressing delays in the accelerated approval pathway to ensure patient access to effective treatments.
