United States Regulatory Approval of Topical Treatments for Dry Eye

Abstract

PurposeTo report the heterogeneity in methodology of clinical trials submitted to the U.S. Food and Drug Administration (FDA) for approval of topical dry eye treatments. DesignComparative analysis of clinical trials’ methods. MethodsWe reviewed the online, publicly available FDA database, application review files, ClinicalTrials.gov registry records, and journal articles for each FDA-approved topical dry eye treatment. For each trial, we extracted information about the study, patient demographics, treatment names and doses, sample size in each arm, and the measurement instrument in a systematic fashion. ResultsFourteen trials were included that assessed five topical treatments for dry eye (cyclosporine 0.05%, cyclosporine 0.09%, lifitegrast 5%, and loteprednol 0.25% eye drops and varenicline 0.03 mg nasal spray). Median treatment duration was 12 weeks (range, 2 to 24 weeks). In all trials, treatments, including varying concentrations of the same treatment, were compared with vehicle. Twelve trials (85.7%) evaluated a primary clinician-measured clinical sign, and 10 trials (71.4%) evaluated a primary patient-reported symptom. Corneal staining was the most frequently evaluated clinical sign primary outcome, reported in half (6/12) of the trials, and was graded using four different scoring systems. Conjunctival staining, conjunctival hyperemia, and tear production were each measured using two different scoring systems. Ocular discomfort, the only patient-reported symptom primary outcome, was measured using five different instruments. ConclusionA variety of outcome measures were used in these clinical trials. Clinically meaningful dry eye outcome measures and standardized measurements can optimize the assessment of and comparison of therapeutic benefits.