Food and Drug Administration approvals in phase 3 Cancer clinical trials

Abstract

Abstract Background Phase 3 oncologic randomized clinical trials (RCTs) can lead to Food and Drug Administration (FDA) approvals. In this study, we aim to identify trial-related factors associated with trials leading to subsequent FDA drug approvals. Methods We performed a database query through the ClinicalTrials.gov registry to search for oncologic phase 3 RCTs on February 2020. We screened all trials for therapeutic, cancer-specific, phase 3, randomized, multi-arm trials. We then identified whether a trial was used for subsequent FDA drug approval through screening of FDA approval announcements. Results In total, 790 trials were included in our study, with 225 trials (28.4%) generating data that were subsequently used for FDA approvals. Of the 225 FDA approvals identified, 65 (28.9%) were based on trials assessing overall survival (OS) as a primary endpoint (PEP), two (0.9%) were based on trials with a quality of life (QoL) PEP, and 158 approvals (70.2%) were based on trials with other PEP (P = 0.01). FDA approvals were more common among industry funded-trials (219, 97.3%; P < 0.001), and less common among trials sponsored by national cooperative groups (21, 9.3%; P < 0.001). Finally, increased pre-hoc power and meeting patients’ accrual target were associated with FDA approvals (P < 0.001). Conclusions The majority of FDA approvals are based on data generated from trials analyzing surrogate primary endpoints and trials receiving industry funding. Additional studies are required to understand the complexity of FDA approvals.

Keywords

• Oncology
• Clinical trials
• FDA
• Primary endpoint
• Surrogate endpoint
• Industry