Impact of lack-of-benefit stopping rules on treatment effect estimates of two-arm multi-stage (TAMS) trials with time to event outcome

Table 7 Bootstrap results for the trials that reach the final stage based on ICON3 and RE04

		I and D outcomes are OS^a				I outcome is PFS^b, D outcome is OS^a
		Estimated H R _Dfor trials reached final stage				Estimated H R _Dfor trials reached final stage
α ₁ ^c	δ ₁ ^d	e ₁ ^e	%Pass^f	Mean (centiles)	%Bias	e ₁ ^e	%Pass^f	Mean (centiles)	%Bias
b) RE04 –		H R _D(95% bootstrap CI): 1.05(0.90–1.21)
0.50	1.00	118	62	0.96(0.86,1.07)	− 1	116	45	0.96(0.85,1.07)	− 1
0.40	0.97	153	45	0.97(0.85,1.06)	0	152	48	0.95(0.85,1.07)	− 2
0.30	0.94	195	48	0.95(0.85,1.06)	− 2	194	67	0.96(0.86,1.07)	− 1
0.20	0.91	252	58	0.95(0.85,1.06)	− 2	250	88	0.97(0.86,1.08)	0
0.10	0.89	342	56	0.95(0.85,1.05)	− 2	339	71	0.96(0.86,1.06)	− 1
b) RE04 –		H R _D(95% bootstrap CI): 1.05(0.90–1.21)
0.50	1.00	118	66	1.02(0.89,1.16)	- 3	116	67	1.03(0.89,1.19)	− 2
0.40	0.97	155	64	1.02(0.89,1.16)	- 3	152	33	1.01(0.88,1.16)	−4
0.30	0.95	199	29	0.98(0.87,1.10)	−7	196	21	0.99(0.87,1.13)	−6
0.20	0.93	259	16	0.95(0.85,1.04)	−10	255	27	0.99(0.87,1.13)	−6
0.10	0.91	355	21	0.97(0.86,1.08)	−8	351	3	0.94(0.80,1.07)	−10

^aOverall survival events;
^bprogression-free survival;
^cone-sided significance level at stage 1;
^dpredefined threshold at stage 1;
^ecumulative number of control arm events required at end of stage 1;
^fpercentages of trials that pass the interim stage and continue accrual to the final stage.

ISSN: 1745-6215