Table 2 Operating Characteristics of the two-stage PO-TITE-CRM (with true DLT rates that imply 2b is more toxic than 2a) based on 10000 simulated trials. Definitions: DLT: Dose-limiting toxicity. P(select): Probability of selecting a dose as the TD25. Bold values indicate the correct decision

Scenario

Prior DLT

0.01

0.04

0.08

0.16

0.25

0.35

1: TD25 @-1

True DLT rate

0.25

0.4

0.45

0.5

0.55

0.6

P(select)

0.68

0.18

0.05

0.01

0

0

0.08

% of patients

39

32

20

6

3

0

Mean number of patients

10.17

8.46

5.33

1.67

0.69

0.07

2: TD25 @0

True DLT rate

0.12

0.25

0.4

0.45

0.5

0.55

P(select)

0.23

0.51

0.2

0.03

0.02

0

0.01

% of patients

17

35

29

11

6

1

Mean number of patients

5.24

10.48

8.75

3.4

1.83

0.26

3: TD25 @1

True DLT rate

0.09

0.12

0.25

0.4

0.45

0.5

P(select)

0.02

0.2

0.55

0.14

0.09

0.01

<0.01

% of patients

4

20

34

23

16

3

Mean number of patients

1.22

6.41

10.97

7.23

5.14

1.02

4: TD25 @2a

True DLT rate

0.06

0.09

0.12

0.25

0.4

0.45

P(select)

0

0.02

0.22

0.48

0.23

0.05

<0.01

% of patients

1

12

20

31

25

11

Mean number of patients

0.47

3.88

6.74

10.43

8.2

3.5

5: TD25 @2b

True DLT rate

0.03

0.06

0.09

0.12

0.25

0.4

P(select)

0

0

0.02

0.3

0.43

0.25

0

% of patients

1

10

12

24

28

25

Mean number of patients

0.25

3.36

4.15

8.17

9.33

8.33

6: TD25 @3

True DLT rate

0.01

0.03

0.06

0.09

0.12

0.25

P(select)

0

0

0

0.09

0.13

0.78

0

% of patients

0

10

11

18

18

42

Mean number of patients

0.1

3.13

3.49

5.46

5.6

13.14

7: Equal steps in DLT rate

True DLT rate

0.05

0.1

0.15

0.2

0.25

0.3

P(select)

0

0.03

0.12

0.31

0.28

0.26

<0.01

% of patients

2

13

18

26

23

19

Mean number of patients

0.55

4.03

5.72

8.32

7.15

5.96

8: All toxic

True DLT rate

0.5

0.6

0.65

0.7

0.75

0.8

P(select)

0.26

0

0

0

0

0

0.74

% of patients

56

26

15

2

0

0

Mean number of patients

9.05

4.27

2.4

0.37

0.04

0