Table 2.

Clinical trials conducted for ultra-orphan drugs and orphan drugs

	RCT (number of drugs)		Dose-response trial (number of drugs)						Extension trials (number of drugs)
	Japan	Outside of Japan	Japan			Outside of Japan
			Parallel-group trial and traditional 3 + 3 design	Forced titration trial	Optional titration trial	Parallel-group trial and traditional 3 + 3 design	Forced titration trial	Optional titration trial
All ultra-orphan drug	3/43 (7%)	21/43 (49%)	5/43 (12%)	4/43 (3%)	13/43 (30%)	16/43 (37%)	2/43 (5%)	8/43 (19%)	16/43 (37%)
Metabolic drug	1/16 (6%)	11/16 (69%)	1/16 (6%)	1/16 (6%)	6/16 (38%)	7/16 (44%)	1/16 (6%)	4/16 (25%)	10/16 (63%)
Anticancer drug	1/11 (9%)	4/11 (36%)	4/11 (36%)	0/11 (0%)	4/11 (36%)	6/11 (55%)	0/11 (0%)	2/11 (18%)	1/11 (9%)
Biological drug	1/8 (13%)	2/8 (25%)	0/8 (0%)	2/8 (25%)	2/8 (25%)	1/8 (13%)	1/8 (13%)	1/8 (13%)	2/8 (25%)
Others	0/8 (0%)	4/8 (50%)	0/8 (0%)	1/8 (13%)	1/8 (13%)	2/8 (25%)	0/8 (0%)	1/8 (13%)	3/8 (38%)
All orphan drugs other than ultra-orphan drugs	30/88 (34%)	41/88 (47%)	33/88 (38%)	1/88 (1%)	31/88 (35%)	30/88 (34%)	0/88 (0%)	13/88 (15%)	8/88 (9%)
Metabolic drug	8/12 (7%)	3/12 (25%)	5/12 (42%)	0/12 (0%)	7/12 (58%)	3/12 (25%)	0/12 (0%)	3/12 (25%)	2/12 (17%)
Anticancer drug	7/33 (21%)	9/33 (27%)	18/33 (55%)	1/33 (3%)	5/33 (15%)	11/33 (33%)	0/33 (0%)	5/33 (15%)	2/33 (6%)
Biological drug	3/7 (43%)	1/7 (14%)	2/7 (29%)	0/7 (0%)	3/7 (43%)	0/7 (0%)	0/7 (0%)	1/7 (14%)	0/7 (0%)
Others	12/36 (33%)	28/36 (85%)	18/36 (50%)	0/36 (0%)	16/36 (44%)	17/36 (47%)	0/36 (0%)	4/36 (11%)	4/36 (11%)

Classification of clinical trials of the ultra-orphan drugs and orphan drugs other than ultra-orphan drugs for each therapeutic category. Others: drugs other than metabolic drugs, anticancer drugs and biological drugs