Table 2.
Simulation results with sample size of 36 and cohort size of 3
| Methods | Dose level | MSE | Duration | Stop | Poor | Overdose | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | (in months) | (%) | (%) | (%) | |||
| Scenario 1 | Pr(tox) | 0.13 | 0.28 | 0.41 | 0.50 | 0.60 | 0.70 | |||||
| R6 | Sel% | 43.2 | 30.5 | 7.8 | 0.8 | 0.0 | 0.0 | 1.3 | 35.9 | 17.7 | 83.5 | 10.0 |
| Pts% | 45.6 | 29.0 | 9.0 | 1.5 | 0.1 | 0.0 | ||||||
| TITE-CRM | Sel% | 8.4 | 58.7 | 29.2 | 2.7 | 0.1 | 0.0 | 0.5 | 24.6 | 0.9 | 15.6 | 27.1 |
| Pts% | 25.2 | 42.6 | 25.1 | 5.7 | 0.7 | 0.0 | ||||||
| TITE-mTPI | Sel% | 14.7 | 58.8 | 22.8 | 3.2 | 0.2 | 0.0 | 0.5 | 24.8 | 0.3 | 20.8 | 21.8 |
| Pts% | 29.4 | 46.0 | 20.0 | 3.9 | 0.4 | 0.0 | ||||||
| TITE-keyboard | Sel% | 13.9 | 58.2 | 23.2 | 4.0 | 0.4 | 0.0 | 0.6 | 25.2 | 0.3 | 8.4 | 15.7 |
| Pts% | 33.3 | 41.9 | 19.3 | 4.5 | 0.7 | 0.1 | ||||||
TITE-keyboard
|
Sel% | 14.4 | 58.1 | 23.1 | 3.6 | 0.3 | 0.0 | 0.6 | 25.2 | 0.4 | 8.3 | 14.6 |
| Pts% | 34.2 | 42.0 | 18.7 | 4.1 | 0.6 | 0.1 | ||||||
| CRM | Sel% | 7.9 | 58.9 | 29.8 | 2.6 | 0.1 | 0.0 | 0.5 | 49.4 | 0.7 | 17.4 | 30.0 |
| Pts% | 22.9 | 42.1 | 27.2 | 6.4 | 0.8 | 0.1 | ||||||
| Scenario 2 | Pr(tox) | 0.08 | 0.15 | 0.29 | 0.43 | 0.50 | 0.57 | |||||
| R6 | Sel% | 20.3 | 40.2 | 25.9 | 5.4 | 0.6 | 0.0 | 2.0 | 38.0 | 7.5 | 94.2 | 0.0 |
| Pts% | 30.3 | 35.6 | 20.6 | 6.1 | 1.0 | 0.1 | ||||||
| TITE-CRM | Sel% | 0.2 | 14.1 | 61.7 | 21.9 | 1.9 | 0.1 | 0.5 | 26.6 | 0.2 | 17.1 | 18.2 |
| Pts% | 14.0 | 23.1 | 39.5 | 19.3 | 3.6 | 0.3 | ||||||
| TITE-mTPI | Sel% | 1.0 | 21.8 | 56.4 | 17.7 | 2.7 | 0.3 | 0.6 | 26.9 | 0.0 | 26.5 | 12.7 |
| Pts% | 16.4 | 29.6 | 37.0 | 14.3 | 2.3 | 0.3 | ||||||
| TITE-keyboard | Sel% | 1.1 | 20.8 | 55.5 | 19.9 | 3.3 | 0.4 | 0.6 | 27.2 | 0.0 | 15.4 | 7.5 |
| Pts% | 17.8 | 31.5 | 33.3 | 13.8 | 3.0 | 0.4 | ||||||
TITE-keyboard
|
Sel% | 1.0 | 21.1 | 55.9 | 18.5 | 3.1 | 0.4 | 0.6 | 27.2 | 0.0 | 15.8 | 6.7 |
| Pts% | 18.1 | 32.1 | 33.2 | 13.5 | 2.7 | 0.4 | ||||||
| CRM | Sel% | 0.1 | 13.1 | 62.8 | 22.4 | 2.1 | 0.1 | 0.5 | 49.8 | 0.0 | 16.2 | 19.4 |
| Pts% | 12.3 | 20.8 | 42.5 | 20.6 | 3.8 | 0.5 | ||||||
| Scenario 3 | Pr(tox) | 0.28 | 0.42 | 0.49 | 0.61 | 0.76 | 0.87 | |||||
| R6 | Sel% | 36.2 | 8.8 | 1.1 | 0.0 | 0.0 | 0.0 | 0.8 | 23.3 | 53.9 | 70.8 | 9.9 |
| Pts% | 40.8 | 11.9 | 2.0 | 0.2 | 0.0 | 0.0 | ||||||
| TITE-CRM | Sel% | 54.0 | 25.2 | 2.6 | 0.1 | 0.0 | 0.0 | 0.6 | 20.5 | 18.1 | 10.4 | 28.3 |
| Pts% | 56.8 | 25.7 | 6.2 | 1.0 | 0.1 | 0.0 | ||||||
| TITE-mTPI | Sel% | 67.8 | 21.8 | 3.3 | 0.2 | 0.0 | 0.0 | 0.4 | 22.2 | 6.9 | 13.2 | 30.4 |
| Pts% | 65.0 | 25.7 | 5.1 | 0.5 | 0.0 | 0.0 | ||||||
| TITE-keyboard | Sel% | 61.1 | 23.9 | 3.6 | 0.3 | 0.0 | 0.0 | 0.5 | 22.9 | 11.1 | 5.3 | 25.0 |
| Pts% | 61.4 | 25.7 | 6.0 | 1.0 | 0.1 | 0.0 | ||||||
TITE-keyboard
|
Sel% | 62.4 | 22.7 | 3.3 | 0.3 | 0.0 | 0.0 | 0.5 | 22.8 | 11.4 | 4.6 | 22.9 |
| Pts% | 63.1 | 23.7 | 5.4 | 0.8 | 0.1 | 0.0 | ||||||
| CRM | Sel% | 52.5 | 25.8 | 3.0 | 0.1 | 0.0 | 0.0 | 0.6 | 43.6 | 18.6 | 11.0 | 29.6 |
| Pts% | 54.5 | 24.9 | 7.7 | 1.1 | 0.1 | 0.0 | ||||||
| Scenario 4 | Pr(tox) | 0.05 | 0.10 | 0.20 | 0.31 | 0.50 | 0.70 | |||||
| R6 | Sel% | 10.9 | 29.9 | 33.8 | 19.8 | 2.5 | 0.0 | 3.0 | 38.3 | 3.2 | 99.7 | 0.0 |
| Pts% | 24.0 | 31.2 | 25.6 | 12.6 | 3.6 | 0.4 | ||||||
| TITE-CRM | Sel% | 0.0 | 1.5 | 29.5 | 58.9 | 9.9 | 0.1 | 0.5 | 28.3 | 0.1 | 23.7 | 5.7 |
| Pts% | 11.3 | 14.1 | 29.1 | 33.3 | 11.2 | 0.9 | ||||||
| TITE-mTPI | Sel% | 0.2 | 5.2 | 35.3 | 49.5 | 9.7 | 0.3 | 0.7 | 28.5 | 0.0 | 38.9 | 3.4 |
| Pts% | 12.7 | 19.7 | 31.5 | 27.1 | 8.3 | 0.7 | ||||||
| TITE-keyboard | Sel% | 0.2 | 4.3 | 33.2 | 49.8 | 12.0 | 0.4 | 0.7 | 28.8 | 0.0 | 28.1 | 1.7 |
| Pts% | 13.5 | 21.2 | 30.4 | 25.0 | 8.9 | 1.1 | ||||||
TITE-keyboard
|
Sel% | 0.2 | 4.5 | 35.4 | 49.1 | 10.5 | 0.3 | 0.7 | 28.7 | 0.0 | 30.6 | 1.3 |
| Pts% | 13.7 | 22.1 | 31.1 | 24.3 | 7.9 | 0.9 | ||||||
| CRM | Sel% | 0.1 | 1.4 | 29.7 | 58.9 | 9.9 | 0.1 | 0.5 | 50.0 | 0.0 | 20.7 | 5.5 |
| Pts% | 10.3 | 11.8 | 28.7 | 36.9 | 11.3 | 1.0 | ||||||
| Scenario 5 | Pr(tox) | 0.06 | 0.08 | 0.12 | 0.18 | 0.30 | 0.41 | |||||
| R6 | Sel% | 7.6 | 13.6 | 21.9 | 30.7 | 17.1 | 4.8 | 5.0 | 36.4 | 4.4 | 100.0 | 0.0 |
| Pts% | 21.8 | 22.7 | 22.0 | 17.6 | 8.7 | 3.6 | ||||||
| TITE-CRM | Sel% | 0.0 | 0.4 | 5.7 | 32.2 | 47.4 | 14.2 | 0.8 | 30.0 | 0.1 | 42.1 | 6.5 |
| Pts% | 11.8 | 12.2 | 17.3 | 25.4 | 23.7 | 9.6 | ||||||
| TITE-mTPI | Sel% | 0.2 | 1.5 | 8.9 | 32.9 | 40.7 | 15.9 | 1.0 | 30.6 | 0.0 | 50.4 | 3.5 |
| Pts% | 13.2 | 15.5 | 20.1 | 23.9 | 19.2 | 8.2 | ||||||
| TITE-keyboard | Sel% | 0.1 | 0.8 | 7.5 | 30.3 | 43.3 | 18.0 | 0.9 | 31.0 | 0.0 | 37.4 | 0.9 |
| Pts% | 13.4 | 15.6 | 19.8 | 23.8 | 18.7 | 8.6 | ||||||
TITE-keyboard
|
Sel% | 0.1 | 1.3 | 7.9 | 32.5 | 42.0 | 16.2 | 0.9 | 30.8 | 0.0 | 41.3 | 0.9 |
| Pts% | 13.7 | 16.2 | 20.6 | 24.2 | 17.9 | 7.5 | ||||||
| CRM | Sel% | 0.0 | 0.4 | 4.6 | 30.7 | 49.4 | 15.0 | 0.7 | 50.4 | 0.0 | 37.0 | 7.3 |
| Pts% | 10.5 | 9.9 | 15.0 | 27.2 | 26.5 | 10.8 | ||||||
| Scenario 6 | Pr(tox) | 0.05 | 0.06 | 0.08 | 0.11 | 0.19 | 0.32 | |||||
| R6 | Sel% | 4.3 | 7.1 | 12.1 | 23.7 | 31.4 | 18.4 | 6.0 | 36.0 | 3.1 | 100.0 | 0.0 |
| Pts% | 19.6 | 19.7 | 19.5 | 18.2 | 12.3 | 8.2 | ||||||
| TITE-CRM | Sel% | 0.0 | 0.1 | 2.1 | 10.9 | 38.0 | 48.8 | 1.1 | 32.0 | 0.1 | 49.7 | 0.0 |
| Pts% | 11.2 | 11.0 | 13.7 | 17.8 | 23.5 | 22.9 | ||||||
| TITE-mTPI | Sel% | 0.1 | 0.5 | 2.6 | 11.2 | 38.0 | 47.7 | 1.2 | 32.6 | 0.0 | 48.9 | 0.0 |
| Pts% | 12.1 | 13.2 | 15.2 | 17.6 | 21.8 | 20.1 | ||||||
| TITE-keyboard | Sel% | 0.1 | 0.3 | 1.7 | 9.9 | 38.5 | 49.5 | 1.0 | 32.8 | 0.0 | 45.0 | 0.0 |
| Pts% | 12.2 | 13.1 | 15.2 | 18.8 | 21.7 | 18.9 | ||||||
TITE-keyboard
|
Sel% | 0.0 | 0.2 | 1.8 | 10.4 | 38.9 | 48.7 | 1.0 | 32.7 | 0.0 | 47.4 | 0.0 |
| Pts% | 12.2 | 13.2 | 15.5 | 19.1 | 21.7 | 18.3 | ||||||
| CRM | Sel% | 0.0 | 0.1 | 1.1 | 8.6 | 40.7 | 49.5 | 0.9 | 50.6 | 0.0 | 42.7 | 0.0 |
| Pts% | 10.0 | 9.2 | 11.4 | 17.6 | 25.8 | 26.0 |
The assessment window is 3 months and the accrual rate is two patients per month.
The MTD is in boldface. R6 is the rolling six design; TITE-CRM is the time-to-event
CRM; TITE-keyboard and TITE-mTPI are the proposed time-to-event versions of keyboard
and mTPI designs, respectively. TITE-keyboard
is the
design that utilizes the exact likelihood function (2.3). CRM is the continual reassessment method based on
the complete data. “MSE” is the mean squared error of the MTD estimation; “Stop%” is
the early stopping percentage; “Poor%” is the risk of poor allocation, which is the
percentage of simulated trials allocating fewer than six patients to the MTD;
“Overdose%” is the risk of overdosing, which is the percentage of simulated trials
that treat more than half of the patients at doses above the MTD.