Statistical analysis
ADVERSE EVENT, EVENT, EVENTS
At 80% power and 2.5% one-sided level of significance, an estimated sample size of 79 would be expected to detect a non-inferiority margin of 0.2 for the mean difference in the primary endpoint with standard deviation of 0.45. Considering a drop out rate of 20%, the final sample size for each arm was set at 100 eyes (50 patients). Datasets generated through compilation of data entered into an electronic data capture system (Clinion v3.0) by investigators and/or authorized site staff were analysed using standard statistical analysis software (SAS v9.4). Individual patient data was included or excluded from analysis based on criteria defined for the ‘intention-to-treat’ (ITT) dataset and the ‘per-protocol’ (PP) dataset. The ITT dataset included all randomized subjects who were available for at least one post-baseline assessment. In case of missing data at a scheduled assessment time point in the ITT dataset, the last available observation was carried forward. The PP population was defined as all subjects who were available for the specified assessment within the time window permitted by the study protocol without any protocol deviations that may affect the efficacy of the drug, subject safety, or subject’s rights, including, but not limited to, violation of selection criteria, violation of study or assessment procedures, use of prohibited medications, and inadequate (< 75%) study drug compliance as reported by the patient or assessed by the investigator. All patients who received at least one dose of study medication were included in the safety analysis.All scored efficacy endpoints were tested for significance by comparing the mean change in scores from baseline in the test groups with that in the control group, using the Student’s t test with α value of 0.05. For each patient, both eyes were individually included in the analysis. Wilcoxon’s rank sum test was used to test individual symptom scores and CGET grades.Adverse events (AEs) were coded by system organ class (SOC) and preferred term using the Medical Dictionary for Drug Regulatory Affairs (MedDRA) version 20.1, and tabulated by treatment group, to indicate the number of patients experiencing each event and number of events experienced. AEs were also evaluated and tabulated by relation to study drug, seriousness, severity (using US NCI-CTCAE v3.0 criteria), and outcome.