Background
Methods
Results
Guidance for the number of patients enrolled by dose-levels | |||
---|---|---|---|
Algorithm-based methods (such as 3 + 3) n (%) | Model-based methods (such as CRM) n (%) | ||
Guidance for the dose-escalation
| Modified-Fibonacci sequence | 92 (46.4) | 0 (0) |
Fixed increment: <+33% | 28 (14.1) | 0 (0) | |
Fixed increment: >100% | 62 (1.3) | 1 (0) | |
PK-guided | 3 (1.5) | 1 (0) | |
Other | 7 (3.5) | 4 (2) |
Planned dose in | Actual doses | |||||
---|---|---|---|---|---|---|
Dose-level (nof studies reaching the dose-level) | Genuine Fibonacci sequence | Modified Fibonacci sequence | Median of actual dose | Min. of actual dose | Max. of actual dose | Mean (± SD) of actual dose |
1(81)
| 1 | 1.0 | 1 | - | - | - |
2(81)
| 2 | 2.0 | 2.00 | 0.80 | 10 | 1.82 (0.65) |
3 (77)
| 3 | 3.3 | 3.00 | 0.80 | 3.33 | 4.08 (1.65) |
4 (67)
| 5 | 5.1 | 4.00 | 0.97 | 10.00 | 9.23 (3.12) |
5 (58)
| 8 | 6.60 | 5.32 | 1.20 | 33.33 | 17.61 (4.71) |
6 (43)
| 13 | 8.80 | 7.80 | 0.90 | 56.25 | 34.49 (6.89) |
7 (32)
| 21 | 11.8 | 11.93 | 1.86 | 80.00 | 67.96 (9.77) |
8 (19)
| 34 | 15.6 | 15.78 | 6.67 | 128.00 | 35.64 (5.43) |
9 (13)
| 55 | 20.8 | 19.50 | 13.33 | 256.00 | 78.11 (8.69) |
10 (7)
| 89 | 27.8 | 23.00 | 18.00 | 512.00 | 133.38 (12.69) |
11 (5)
| 144 | 36.8 | 28.89 | 23.50 | 1024.00 | 227.16 (17.85) |
12 (3)
| 233 | 49.0 | 38.44 | 35.83 | 2048.00 | 707.43 (29.89) |
13 (0)
| 377 | 65.2 | - | - | - | - |
Dose-levels | Incremental ratio in genuine Fibonacci sequence | Incremental ratio in Modified Fibonacci sequence | Incremental ratio of median dose in 81 phase I |
---|---|---|---|
1
| - | - | - |
2
| 2.000 | 2.000 | 2.000 |
3
| 1.500 | 1.670 | 1.500 |
4
| 1.667 | 1.500 | 1.333 |
5
| 1.600 | 1.333 | 1.333 |
6
| 1.615 | 1.333 | 1.333 |
7
| 1.619 | 1.333 | 1.333 |
8
| 1.617 | 1.333 | 1.300 |
9
| 1.618 | 1.333 | 1.350 |
10
| 1.618 | 1.333 | 1.320 |
11
| 1.618 | 1.333 | 1.240 |
12
| 1.618 | 1.333 | 1.250 |
13
| 1.618 | 1.333 | - |