from the psychic and somatic anxiety factors scores of the HAM-A, Sheehan Disability Scale, HADS, CGI-I and the Patient Global Impression Improvement (PGI-I) scales. Patients completed a 3- to 30-day screening phase and then were randomly assigned to duloxetine 20 mg once daily, duloxetine 60 to 120 mg once daily, venlafaxine 75 to 225 mg once daily or placebo. For the higher duloxetine dose group and for venlafaxine the dose was titrated according to response throughout the 10-week treatment period. Statistical analyses were conducted on the intent to treat population. The primary efﬁcacy analysis was the change from baseline in the HAM-A total score, which was compared between treatment groups using an analysis of covariance (ANCOVA) model with treatment and investigator as ﬁxed effects and baseline score as a covariate. A mixed model repeated measures analysis was also performed. Based on the LOCF and mixed models analyses all three active treatment groups demon- strated a statistically signiﬁcant difference from placebo in reducing the HAM-A total score (duloxetine 20 mg versus placebo p 0.01; duloxetine 60–120 mg and venlafaxine versus placebo p 0.001). Similar results were also obtained for psychic and somatic anxiety factors. For effect size calcu- lations Cohen’s d was used. For the comparison of duloxetine 20 mg and placebo d was 0.34 (95% CI 0.08–0.61) and for duloxetine 60 to 120 mg and placebo d was 0.42 (95% CI 0.20–0.62). Both effect sizes were similar to that which could be calculated for the comparison of venlafaxine and placebo (d = 0.44; 95% CI 0.22–0.66). There were no differences between venlafaxine and duloxetine 20 mg/day (d = 0.09; 95% CI –0.18 to 0.36) or duloxetine 60 to 120 mg/day (d = 0.02; 95% CI –0.20 to 0.25) based on the calculation of Cohen’s d. Similarly duloxetine 20 mg and duloxetine 60 to 120 mg were not different (d = 0.07; 95% CI –0.20 to 0.34). Again the study provides evidence for the efﬁcacy of duloxetine in the treatment of GAD at least as effective as venlafaxine. Duloxetine for GAD Duloxetine was compared to venlafaxine in adult patients with GAD using non-inferiority criteria (Allgulander et al 2008). In this report data from two previous trials (see Hartford et al 2007; Nicolini et al 2008) were combined and six non- inferiority criteria were established by an independent (of the pharmaceutical manufacturer) panel of experts. The consen- sus panel’s recommendations for non-inferiority are noted in Table 2. The ﬁrst four criteria needed to be satisﬁed before the last two were considered. The statistical analysis used the HAM-A score as the primary outcome measure while the non-inferiority analyses used a lower bound of a one-sided 97.5% conﬁdence interval for the difference between the test intervention and reference intervention as recommended by the International Committee on Harmonization (ICH 1998). The primary analysis was conducted on the per-protocol patients who were treated with duloxetine (n = 239) or ven- lafaxine XR (n = 262). The per-protocol sample was deﬁned as patients who had completed at least 4 weeks of treatment, had baseline and post-baseline HAM-A ratings after at least 4 weeks of treatment, and did not have any protocol viola- tions that were judged to potentially have an impact on the analysis or conclusions. Duloxetine 60 to 120 mg/day met all statistical and clinical criteria for non-inferiority with a mean difference in HAM-A total score improvements between duloxetine and placebo of −3.8, compared to the differ- ence between venlafaxine XR and placebo of −3.6 points. Subtracting the two drug-placebo mean differences yielded a point estimate of 0.20 HAM-A total score points in favor of duloxetine. The lower bound of the conﬁdence interval for this point estimate was −1.28 in the per-protocol sample which was within the pre-speciﬁed −1.5 margin. Thus the criterion for non-inferiority was met. Response rates for duloxetine, venlafaxine XR, and placebo were 56%, 58% and 40%, respectively. A further pooled analysis of data from the four clinical trials was performed to examine the efﬁcacy and tolerability Table 2 Non-inferiority criteria used for comparative analysis of duloxetine and venlafaxine in generalized anxiety disordera 1. At least one three-arm double-blind comparison trial for test intervention with an active comparator. 2. Both the test intervention and the active comparator should be superior to placebo by a clinically meaningful difference in the HAM-A total score (set at 2 points by the panel). 3. Treatment response rates (deﬁned as 50% reduction in HAM-A total score from baseline to study end point) for the test and active comparator groups should be at least 10 percentage points greater than the response for placebo. 4. Both the active and test intervention have to be statistically signiﬁcantly better than placebo on the primary outcome measure. 5. The non-inferiority margin between the test intervention and the active comparator is 50% of the difference between active comparator and placebo, and this difference is not clinically meaningful. 6. The response rate of the test intervention is not more than 5 percentage points lower than the response rate in the active comparator group. aFrom the pooled non-inferiority comparison reported by Allgulander et al 2008. Neuropsychiatric Disease and Treatment 2008:4(6) 1175