. Author manuscript; available in PMC: 2018 Jan 30.

Published in final edited form as: Stat Med. 2016 Feb 29;36(2):215–224. doi: 10.1002/sim.6910

TABLE 3.

Two agents, Multiple endpoints (DLT, Response)

Defined by an acceptable toxicity profile (≤25% DLT rate) and the highest clinical response rate

Stop when an 11^th participant recommended to a dose combination that already has 10 participants

Maximum total accrual set at 28, 1000 simulations

Scenario		(true %DLT, true %Response) % combination recommended Avg # pts treated on combination			Avg Size, %-tiles	% stop	% DLT	% Rsp

	Agent A (mg per day)	Agent B (mg per day)
	Agent A (mg per day)	280	420	560

1 “Ideal”	400	(0.07, 0.55)	(0.15, 0.70)	(0.25,0.95)	19.1,
		0.12	0.12	0.67	25^th = 17	0.2	16.4	74.2
		1.72	2.30	7.46	50^th = 18

	200	(0.05, 0.40)	(0.07, 0.55)	(0.15,0.80)	75^th = 20
		0.07	0.08	0.14	90^th = 24
		2.30	2.30	3.06	95^th = 27

2 “Worst”	400	(0.25, 0.25)	(0.30, 0.40)	(0.40,0.50)	18.1,
		0.06	0.08	0.06	25^th = 16	7.0	25.6	38.3
		2.54	2.18	1.63	50^th = 18

	200	(0.20, 0.25)	(0.25, 0.40)	(0.30,0.50)	75^th = 21
		0.19	0.36	0.17	90^th = 25
		3.81	5.08	3.08	95^th = 27

3 Best Guess	400	(0.12, 0.55)	(0.18, 0.80)	(0.25,0.95)	19.8,
		0.02	0.10	0.58	25^th = 17	0.6	18.4	75.0
		1.97	2.77	6.72	50^th = 18

	200	(0.10, 0.40)	(0.15, 0.55)	(0.20,0.80)	75^th = 22
		0.07	0.08	0.16	90^th = 26
		2.57	2.77	3.16	95^th = 28

4 “Plateau”	400	(0.25, 0.35)	(0.30, 0.50)	(0.40,0.50)	18.2,
		0.06	0.08	0.03	25^th = 17	9.0	25.7	44.8
		2.55	2.19	1.46	50^th = 18

	200	(0.20, 0.35)	(0.25, 0.50)	(0.30,0.50)	75^th = 21
		0.20	0.38	0.15	90^th = 25
		3.83	5.47	2.92	95^th = 28

5 “Toxic”	400	(0.30, 0.40)	(0.40, 0.50)	(0.50,0.75)	18.4,
		0.09	0.09	0.03	25^th = 16	11.8	32.9	52.9
		2.94	2.20	1.10	50^th = 19

	200	(0.25, 0.40)	(0.30, 0.50)	(0.40,0.75)	75^th = 23
		0.26	0.25	0.17	90^th = 26
		4.41	4.59	3.12	95^th = 28

6 “Very Toxic”	400	(0.75, 0.40)	(0.85, 0.50)	(0.95,0.75)	4.3,
		0.00	0.00	0.00	25^th = 2	100.00	74.0	42.5
		0.95	0.09	0.00	50^th = 2

	200	(0.70, 0.40)	(0.75, 0.50)	(0.85,0.75)	75^th = 6
		0.00	0.00	0.00	90^th = 9
		1.98	1.07	0.17	95^th = 11

Notation:

Average (avg); percentiles (%-tiles); Response (Rsp); Average trial sample size (avg size); Percent of trials stopped early for safety (% stop); Percent of DLTs (% DLT); Percent of responses (% Rsp)