Table 1.
Operating Characteristics of a Trial Based on 1,000 Simulated Hypothetical Trials
| Trial Design | Dose Levels |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
| Trial design 1 | ||||||||||
| Initial curve A | 0.01 | 0.015 | 0.02 | 0.025 | 0.03 | 0.04 | 0.05 | 0.10 | 0.17 | 0.30 |
| Dose toxicity curve 1 | 0.01 | 0.03 | 0.05 | 0.1 | 0.12 | 0.15 | 0.3 | 0.5 | 0.6 | 1 |
| Accuracy (percentage of trials) | 0 | 0 | 0 | 0.7 | 2.5 | 17 | 56 | 23 | 1 | 0 |
| Allocation (No. of patients) | 1.1 | 1.1 | 1.2 | 1.4 | 2.1 | 4.3 | 12.2 | 9.1 | 2.7 | 0.7 |
| Percentage of patients | 3 | 3 | 3 | 4 | 6 | 12 | 34 | 25 | 8 | 2 |
| Safety (No. of patients with DLTs) | 0.01 | 0.03 | 0.06 | 0.13 | 0.27 | 0.66 | 3.6 | 4.5 | 1.7 | 0.5 |
| Trial design 2 | ||||||||||
| Initial curve A | 0.01 | 0.015 | 0.02 | 0.025 | 0.03 | 0.04 | 0.05 | 0.10 | 0.17 | 0.30 |
| Dose toxicity curve 2 | 0.0001 | 0.01 | 0.05 | 0.1 | 0.12 | 0.3 | 1 | 1 | 1 | 1 |
| Accuracy (percentage of trials) | 0 | 0 | 2 | 5 | 27 | 58 | 9 | 0 | 0 | 0 |
| Allocation (No. of patients) | 1.1 | 1.4 | 2.4 | 4 | 8.9 | 12.6 | 5.1 | 0.5 | 0 | 0 |
| Percentage of patients | 3 | 4 | 7 | 11 | 25 | 35 | 14 | 1 | 0 | 0 |
| Safety (No. of patients with DLTs) | 0 | 0.02 | 0.13 | 0.42 | 1.1 | 3.8 | 5.1 | 0.5 | 0 | 0 |
| Trial design 3 | ||||||||||
| Initial curve A | 0.01 | 0.015 | 0.02 | 0.025 | 0.03 | 0.04 | 0.05 | 0.10 | 0.17 | 0.30 |
| Dose toxicity curve 3 | 0.05 | 0.1 | 0.12 | 0.3 | 0.5 | 0.6 | 0.7 | 0.8 | 0.9 | 0.99 |
| Accuracy (percentage of trials) | 1 | 5 | 25 | 40 | 23 | 5 | 0 | 0 | 0 | 0 |
| Allocation (No. of patients) | 2.6 | 4.2 | 7.5 | 8.7 | 7.1 | 3.5 | 1.7 | 0.5 | 0.1 | 0.009 |
| Percentage of patients | 7 | 12 | 21 | 24 | 20 | 10 | 5 | 1 | 0 | 0 |
| Safety (No. of patients with DLTs) | 0.1 | 0.5 | 0.9 | 2.6 | 3.5 | 2.1 | 1.2 | 0.4 | 0.1 | 0.009 |
| Trial design 4 | ||||||||||
| Initial curve B | 0.06 | 0.125 | 0.19 | 0.25 | 0.31 | 0.37 | 0.44 | 0.50 | 0.56 | 0.63 |
| Dose toxicity curve 2 | 0.0001 | 0.01 | 0.05 | 0.1 | 0.12 | 0.3 | 1 | 1 | 1 | 1 |
| Accuracy (percentage of trials) | 0 | 0 | 0 | 1 | 25 | 69 | 5 | 0 | 0 | 0 |
| Allocation (No. of patients) | 1.0 | 1.1 | 1.4 | 2.7 | 9.3 | 17.2 | 3.3 | 0 | 0 | 0 |
| Percentage of patients | 3 | 3 | 4 | 8 | 26 | 48 | 9 | 0 | 0 | 0 |
| Safety (No. of patients with DLTs) | 0 | 0.02 | 0.07 | 0.3 | 1.1 | 5.2 | 3.3 | 0 | 0 | 0 |
NOTE. No. of patients, 36; acceptable toxicity rate, 30%; assuming the model presented in O'Quigley et al1 and presumed/initial curves used in Neuenschwander et al.20 Bold font indicates the true MTD. Accuracy: percentage of trials of 1,000 simulated trials that selected each dose as the final MTD (eg, 56% of trials selected level 7 as the MTD in example 1).
Abbreviations: DLT, dose-limiting toxicity; MTD, maximum-tolerated dose.