Factors That Influence FDA Decisions for Postmarketing Requirements and Commitments During Review of Oncology...

With the recent use of expedited drug development and approval programs for several oncology products in the United States, the importance of postmarketing plans to confirm clinical benefits and safety is increasing. To discuss postmarketing requirements (PMRs) and postmarketing commitments (PMCs) required for oncology products approved in the United States, we investigated the factors that influenced the US Food and Drug Administration (FDA) decisions for PMR/PMCs during FDA review.

Characteristics of new drug approvals and PMR/PMCs for oncology products (new molecular entities and new therapeutic biologic products) in the United States between 2008 and 2015 were analyzed.

Of the 58 oncology products analyzed, PMR/PMCs were required for 54 products. The proportion of approvals that required confirmatory PMR/PMCs was 100% for accelerated approval (AA) and was 39% for regular approval (RA). Median development times for AA and RA were 7.41 and 7.50 years, respectively. Randomization, number of patients, and end point in pivotal studies were identified as key potential factors that influenced the decision to require PMR/PMCs for both confirmatory and clinical safety studies.

Robustness of the pivotal study design was identified as one of the key factors for the decision by the FDA to require PMR/PMCs-in particular, significant PMR/PMCs, such as those for confirmatory studies. That is, the FDA approved products with surrogate markers and smaller studies but required PMR/PMCs to fully prove the risk-benefit profile in the postmarketing period.