The FDA's accelerated approval pathway, designed to expedite the availability of promising drugs based on surrogate endpoints, faces scrutiny due to delays in initiating confirmatory studies. A cross-sectional study analyzing data from 2009 to 2019 reveals significant lags between accelerated approval and the commencement of studies designed to confirm clinical benefit, particularly for noncancer drugs.
The study, which examined 103 cancer-indication pairs and noncancer products, found that 20.31% of confirmatory studies were not underway at the time of accelerated approval. The median time from approval to study initiation was 1.41 years. Notably, noncancer products exhibited a significantly larger proportion of confirmatory studies initiated after accelerated approval (37.04%) compared to cancer products (15.84%, P = .008). The median time from approval to study initiation was also longer for noncancer products (2.11 years) than for cancer products (1.20 years, P = .02).
Impact of Delays on Study Completion
The research highlights a correlation between delayed study initiation and the likelihood of missing FDA deadlines for confirmatory study completion. Studies underway at the time of accelerated approval were less likely to be submitted past FDA-designated deadlines (37.04%) compared to those initiated after approval (61.11%). This trend was particularly pronounced for noncancer products, where all confirmatory studies initiated after approval missed FDA deadlines, compared to 41.67% of cancer product studies (P = .04).
Implications for Regulatory Policy
The findings underscore the need for the FDA to enforce its statutory authority, as granted by the Consolidated Appropriations Act of 2023, to mandate that confirmatory studies be underway at the time of accelerated approval. Such a measure could streamline patient recruitment, enrollment, and overall study completion, ultimately expediting the verification of clinical benefit. The study authors suggest that additional reforms, such as linking payer reimbursement to FDA-designated confirmatory study deadlines, may be necessary to ensure the timely completion of confirmatory studies and the validation of product efficacy.
Study Limitations
The authors acknowledge limitations, including the inability to identify all confirmatory studies due to data limitations and the lack of insight into the reasons behind delays in study initiation. Despite these limitations, the study provides valuable evidence supporting the need for stricter enforcement of timely confirmatory study initiation within the FDA's accelerated approval pathway.
