A gated group sequential design for seamless Phase II/III trial with subpopulation selection

Table 2 Parameters for three simulation settings

Setting	Sample Size	Subgroup Proportion	Enrollment Duration	Futility boundary	Dropout rate (yearly)	Median survival time	HR^b	Design	Full Group		Sub-Group
Setting	Sample Size	Subgroup Proportion	Enrollment Duration	Futility boundary	Dropout rate (yearly)	Median survival time	HR^b	Design	\({\alpha }_{1}\) (OS)	\({\alpha }_{2}\) (PFS)	\({\alpha }_{3}\) (OS)	\({\alpha }_{4}\)(PFS)
1	554	0.75	28 months	0.9 (SG^a)	10% (PFS)	4 (PFS SG) 3 (PFS NSG^a)	0.7	GSD & AD	0.22%	0.165%	1.28%	0.835%
1	554	0.75	28 months	0.85 (FG^a)	1% (OS)	10.5 (OS SG) 5.7 (OS NSG)	0.7	gGSD	1.429%	1.071%	1.513%	0.987%
2 & 3	924	0.5	33 months	0.85 (SG^a)	10% (PFS)	4 (PFS SG) 3 (PFS NSG)	0.7^c	GSD & AD	0.025%	0.017%	1.458%	1.00%
2 & 3	924	0.5	33 months	0.83 (FG^a)	1% (OS)	10.5 (OS SG) 5.7 (OS NSG)	0.7^c	gGSD	1.488%	1.012%	1.48%	1.02%

^aSG Subgroup, FG Full group, NSG Complementary ofsub-group
^bHazard ratio (HR) is set to be the same for PFS, OS and sub-group, complementary of sub-group
^cHR = 1 for full group in setting 3. Complementary of sub-group is defined as the full group excluding the sub-group

ISSN: 1471-2288