Abstract
Many candidate drugs for dry eye disease (DED) have been assessed over the years in pursuit of demonstrating efficacy in both signs and symptoms. However, patients with DED have very limited treatment options for management of both signs and symptoms of DED. There are several potential reasons behind this including the placebo or vehicle response, which is a frequent issue observed in DED trials. A high magnitude of vehicle response interferes with the estimation of a drug's treatment effect and may lead to failure of a clinical trial. To address these concerns, Tear Film and Ocular Surface Society International Dry Eye Workshop II taskforce has recommended a few study design strategies to minimize vehicle response observed in DED trials. This review briefly describes the factors that lead to placebo/vehicle response in DED trials and focuses on the aspects of clinical trial design that can be improved to mitigate vehicle response. In addition, it presents the observations from a recent ECF843 phase 2b study, wherein the study design approach consisted of a vehicle run-in phase, withdrawal phase, and masked treatment transition, and led to consistent data for DED signs and symptoms and reduced vehicle response post randomization.