title: Clinical Evidence Supporting US Food and Drug Administration Approval of Otolaryngologic Prescription Drug Indications, 2005-2014.
abstract: 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.
authors.affiliation: 1 Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.|2 Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Rathi
authors.affiliation: 3 Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: 4 Center for Outcomes Research and Evaluation (CORE), Yale-New Haven Hospital, New Haven, Connecticut, USA.|5 Section of Health Policy and Administration, Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut, USA.|6 Section of General Internal Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Ross
authors.affiliation: 7 Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Downing
authors.affiliation: 8 Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Kesselheim
authors.affiliation: 1 Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.|2 Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Stacey T
authors.initials: ST
authors.lastname: Gray
mesh_terms: D015415:Biomarkers; D002986:Clinical Trials as Topic; D003430:Cross-Sectional Studies; D017277:Drug Approval / Q000706:statistics & numerical data; D006801:Humans; D010036:Otolaryngology; D055553:Prescription Drugs; D012107:Research Design; D012189:Retrospective Studies; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D015415:Biomarkers; D055553:Prescription Drugs
keywords: FDA; orphan drug; otolaryngology; pharmaceutical; pivotal study