Comparisons with active comparator drugs

Direct comparison of a new compound with an active drug used in the same indication can provide the following information  

A finding of no significant difference in outcome between two treatments is ambiguous unless a non-inferiority design is used. Two-arm non-inferiority designs require much larger sample sizes to test adequately the statistical hypothesis of no true difference in efficacy between a test and reference drug. 

Small differences in efficacy are very hard to detect using a two-arm study design because of the inherently large variance of psychopharmacological studies. 

The results of a non-inferiority design trial can lead to one of the following conclusions  

An adequately powered trial initially designed to demonstrate the noninferiority of a new compound compared with a standard treatment can also demonstrate the superiority of the new compound provided that a statistically significant difference in favor of the new1 treatment was detected. However, trials intended to show the superiority of one of the treatments cannot be interpreted, in the case of a statistically non-significant difference, as showing non-inferiority of the new1 chemical entity compared with the standard treatment. 

---

ECT is superior in efficacy when compared with placebo, sham ECT, and active drug therapy. Upon the introduction of effective pharmacotherapy for severe depression, the relative efficacy of drug versus ECT was frequently studied. Our review of the relevant literature led to an extrapolation of the data from selected studies (primarily class I or II designs) for a quantitative analysis of the efficacy of ECT versus other treatments for an acute depressive episode ( 53). The comparisons with ECT included simulated (or sham) ECT, placebo, the standard tricyclic antidepressants, and the monoamine oxidase inhibitors [ Table 8-1 (54, 55, 56, 57, 58 and 59), Table 8 2 (0g 6i 62 and 63), Table 8-3 (56, 61, 62, 63, 64, 65 and 66), and Table 8-4 (55, 60, 61, 62 and 63)]. We also compared the relative efficacy of the bilateral versus the UNID forms of administration [Table 8-5 (42, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77 and 78)]. A meta-analysis was... 

On the other hand, replacement of the morpholino moiety (ring C) by a 3-methyl-l,2,4-oxadiazol-5-yl g oup produces active compounds (2013EJMC533). Compounds 78a—d (F yne 27) show lower activity compared to linezolid against standard S. aureus, but a direct comparison could not be performed because the test were performed on racemic mixtures. Nevertheless, as a racemate, thioamide derivatives 78c,d showed major activity against MRSA strains, with MIC values twofold lower than those of reference drug. Moreover, a safety profile similar to HnezoHd was evidenced by means of cytotoxicity data on PK15, HaCat, and HepG2 cell lines. 

---