Table B1.

Simulation results comparing drug development with different phase II components. The simulations vary accrual, hazard ratios, and control medians. The PFS and OS are correlated and generated according to two exponentials Y₁ with median 3 months and a treatment effect hazard ratio of 1.5 and Y₂ with median 6 months and a treatment hazard ratio of 1.3. Progression is the min(Y₁,Y₂) and survival is Y₂. All designs have 81% power to conclude there is a positive effect on OS under the global alternative while having probability of less than .05 (when using a 2-sided test) of concluding a positive effect on OS under the global null. E[N] is the expected sample size and E[T] is the expected study time. All time is in months.

Accrual per month	Hazard Ratios		Medians		Designs		Global Null		Global Alternative
	Y1	OS	Y1	OS		α1	E[N]	E[T]	E[N]	E[T]
30	1.5	1.3	3	6	Futility based on OS	.2	513	17.1	719	24.0
						.5	504	16.8	699	23.3
					Sequence of studies	.1	325	14.44	935	39.6
					Integrated II/III (f1=0)	.1	350	11.7	713	23.8
						.2	336	11.2	704	23.5
15	1.5	1.3	3	12	Futility based on OS	.2	524	34.9	725	48.3
						.5	500	33.3	670	46.6
					Sequence of studies	.1	297	24.0	906	74.2
					Integrated II/III (f1=0)	.1	292	19.4	708	47.2
						.2	302	20.2	705	47.0
15	1.3	1.2	3	6	Futility based on OS	.2	765	51.0	1253	83.6
						.5	819	54.6	1210	80.7
					Sequence of studies	.1	629	45.4	1702	121.9
					Integrated II/III (f1=0)	.1	586	39.1	1249	83.3
						.2	547	36.5	1227	81.8