Table 2.

Approvals with evidence of superiority or non-inferiority against active comparator

Evaluation	Study: design (primary outcome/arms)	Comparator	Study durationa	Number of subjects
Positive superiority initiation trials v. active comparator
Aripiprazole (O): bipolar disorders	CN138008: response/aripiprazole flexible dose 15–30 mg/day and comparator	Haloperidol, flexible dose, 10–15 mg/day	12 weeks	347 (randomised)
Olanzapine (O): schizophrenia	FID-EW-E003: not specified/olanzapine fixed doses 1–17.5 mg/day and comparator	Haloperidol, fixed doses, 10–20 mg/day	6 weeks	431 (initial)
Olanzapine (O): schizophrenia	FID-MC-HGAJ: not specified/olanzapine 5–20 mg/day and comparator	Haloperidol, 5–20 mg/day	6 weeks	1996 (included)
Olanzapine (IM): agitation in manic episode	HGHW: PANSS excited component/olanzapine fixed dose 10 mg, placebo and comparator	Lorazepam IM, fixed dose, 2 mg	2 h	228 (screened)
Varenicline (O): smoking cessation	A3051028: 4 weeks continuous quit rate/varenicline, fixed dose, 2 mg/day, placebo and comparator	Bupropion, fixed dose, 300 mg/day	12 weeks	1025 (randomised)
Varenicline (O): smoking cessation	A3051036: 4 weeks continuous quit rate/varenicline, fixed dose, 2 mg/day, placebo and comparator	Bupropion, fixed dose, 300 mg/day	12 weeks	1027 (randomised)
Positive non-inferiority continuation trials v. active comparator
Olanzapine (O): bipolar disorder	HGHT: relapse/olanzapine and comparator. NIB: 7.3%	Lithium	12 months	431 (randomised)
Positive non-inferiority initiation trials v. active comparator
Aripiprazole (IM): schizophrenia	31-07-247: relapse/aripiprazole IM depot flexible dose 300–400 mg/month, aripiprazole IM depot flexible dose 25–50 mg/month and comparator. NIB : 11.5%	Oral aripiprazole flexible dose 10–30 mg/day	26 weeks	662 (randomised)
Duloxetine (O): depressive disorder (pooled results)	Pooled F1J-MC-HMAT(a,b): HAMD17/duloxetine fixed doses 40 and 80/day, placebo and comparator. NIB: 2.2	Paroxetine fixed dose 20 mg	8 weeks	707 (randomised)
Duloxetine (O): depressive disorder (pooled results)	Pooled F1J-MC-HMAY(a,b): HAMD17/duloxetine fixed doses 80 and 120 mg/day, placebo and comparator. NIB: 2.2	Paroxetine fixed dose 20 mg	8 weeks	759 (randomised)
Duloxetine (O): anxiety disorders (pooled results)	Pooled HMDU, HMDW: HAMA/duloxetine flexible dose 60–120 mg/day, placebo and comparator. NIB: −1.5	Venlafaxine flexible dose 75–225 mg/day	10 weeks	1068 (randomised)
Olanzapine (IM): schizophrenia	F1D-MC-HGKA: relapse/olanzapine IM depot fixed dose 150 and 300 mg/2 weeks and comparator. NIB: 5%	Oral olanzapine fixed dose 10–20 mg/day	24 weeks	1065 (randomised)
Olanzapine (O): bipolar disorder	HGHQ: Y-MRS/olanzapine 5–20 mg/day and comparator	Valproate 500–2500 mg/day	3 weeks	251 (randomised)
Olanzapine (IM): agitation (in schizophrenia)	F1D-MC-HGHB: PANSS excitement component/olanzapine fixed dose, placebo and comparator	Haloperidol IM	2 h	311 (type of population not given)
Paliperidone (IM): schizophrenia (3-month injection)	PSY-3011: relapse/paliperidone IM depot fixed doses 175–525/12 weeks and comparator. NIB: 15%	Paliperidone fixed dose 50–150 mg/month	48 weeks	1016 (randomised)
Paliperidone (IM): schizophrenia	PSY-3006: PANSS/paliperidone IM depot flexible dose 50–150 mg/month and comparator. NIB: 5	Risperidone IM flexible dose 25–50 mg/2 weeks	13 weeks	1220 (randomised)
Vortioxetine (O): depressive disorders	14178A: MADRS/vortioxetine flexible dose 10–0 mg/day and comparator. NIB: 2	Agomelatine flexible dose 25–50 mg/day	12 weeks	501 (randomised)

NIB, non-inferiority boundary.

Missing data (for doses, route, NIB) in the table are due to missing data in the EPARs.

^aDuration between randomisation and endpoint.