Statistical analysis
REGRESSION, SECONDARY
Based on the results of the U.S. fluoxetine study (Emslie et al., The sample size was set at 72 patients (36 patients/group) to provide 85% power to detect superiority of the ESC group over the placebo group. The hazard ratio (HR) for relapse for the ESC group versus placebo was 2.47 under these assumptions. The number of patients in the open-label period required to ensure 72 patients continued to the double-blind period was set at 134 patients, assuming a continuation rate of 54%.The primary analysis population used to analyze efficacy was the full analysis set in the double-blind period (FAS double-blind period). The FAS (double-blind period) included randomized patients who received at least one dose of the investigational drug in the double-blind period and who had at least one efficacy assessment after the start of the double-blind period. The primary endpoint was analyzed using the log-rank test and cox regression with treatment group as the main effect. The significance level was set at 5% (two-sided).The FAS (open-label period) included patients who received at least one dose of the investigational drug during the open-label period and who had at least one efficacy assessment after the start of the open-label period. For secondary endpoints in the open-label period, discrete variables were analyzed by change from baseline, and binary variables were analyzed by proportions. Where secondary endpoint values were missing, they were imputed using the Last Observation Carried Forward (LOCF) method.For secondary endpoints in the double-blind period, relapse was analyzed by Fisher's exact test and logistic regression by calculating the relapse rate. Analysis of CGI-I and change in CDRS-R total and CGI-S from start of double-blind period was carried out using analysis of covariance (ANCOVA). CGI-S worsening and CGI-I improvement were calculated as percentages (worsening rate for CGI-S and improvement rate for CGI-I) and analyzed by Fisher's exact test. If secondary endpoints were missing, they were imputed using the LOCF method. For CGI-S worsening, only the Worst Observation Carried Forward (WOCF) method was used.