Objective The US Food and Drug Administration (FDA) approves indications for prescription drugs based on premarket pivotal clinical studies designed to demonstrate safety and efficacy. We characterized the pivotal studies supporting FDA approval of otolaryngologic prescription drug indications. Study Design Retrospective cross-sectional analysis. Setting Publicly available FDA documents. Subjects Recently approved (2005-2014) prescription drug indications for conditions treated by otolaryngologists or their multidisciplinary teams. Drugs could be authorized for treatment of otolaryngologic disease upon initial approval (original indications) or thereafter via supplemental applications (supplemental indications). Methods Pivotal studies were categorized by enrollment, randomization, blinding, comparator type, and primary endpoint. Results Between 2005 and 2014, the FDA approved 48 otolaryngologic prescription drug indications based on 64 pivotal studies, including 21 original indications (19 drugs, 31 studies) and 27 supplemental indications (18 drugs, 33 studies). Median enrollment was 299 patients (interquartile range, 198-613) for original indications and 197 patients (interquartile range, 64-442) for supplemental indications. Most indications were supported by ≥1 randomized study (original: 20/21 [95%], supplemental: 21/27 [78%]) and ≥1 double-blinded study (original: 14/21 [67%], supplemental: 17/27 [63%]). About half of original indications (9/21 [43%]) and one-quarter of supplemental indications (7/27 [26%]) were supported by ≥1 active-controlled study. Nearly half (original: 8/21 [38%], supplemental: 14/27 [52%]) of all indications were approved based exclusively on studies using surrogate markers as primary endpoints. Conclusion The quality of clinical evidence supporting FDA approval of otolaryngologic prescription drug indications varied widely. Otolaryngologists should consider limitations in premarket evidence when helping patients make informed treatment decisions about newly approved drugs.
Keywords: FDA; orphan drug; otolaryngology; pharmaceutical; pivotal study.