Table 1.
Dose-escalation and de-escalation rule for TITE-BOIN with a target DLT rate of 0.2 and a cohort size of 3.
| Number Treated | Number of DLTs | Number with data pending | STFT |
||
|---|---|---|---|---|---|
| Escalate | Stay | De-escalate | |||
| 3 | 0 | ≤1 | Y | ||
| 3 | 0 | ≥2 | Suspend Accrual | ||
| 3 | 1 | ≤2 | Y | ||
| 3 | ≥2 | ≤1 | Y&Elim | ||
| 6 | 0 | ≤3 | Y | ||
| 6 | 0 | ≥4 | Suspend Accrual | ||
| 6 | 1 | ≤3 | Y | ||
| 6 | 1 | ≥4 | Suspend Accrual | ||
| 6 | 2 | ≤4 | Y | ||
| 6 | ≥3 | ≤3 | Y&Elim | ||
| 9 | 0 | ≤4 | Y | ||
| 9 | 0 | ≥5 | Suspend Accrual | ||
| 9 | 1 | ≤2 | Y | ||
| 9 | 1 | 3 | ≥0.77 | <0.77 | |
| 9 | 1 | 4 | ≥2.15 | <2.15 | |
| 9 | 1 | ≥5 | Suspend Accrual | ||
| 9 | 2 | 0 | Y | ||
| 9 | 2 | 1 | >0.52 | ≤0.52 | |
| 9 | 2 | 2 | >1.59 | ≤1.59 | |
| 9 | 2 | 3 | >2.66 | ≤2.66 | |
| 9 | 2 | 4 | >3.73 | ≤3.73 | |
| 9 | 2 | ≥5 | Suspend Accrual | ||
| 9 | 3 | ≤6 | Y | ||
| 9 | ≥4 | ≤5 | Y&Elim | ||
NOTE: “Number treated” is the total number of patients treated at the current dose level, “Number of DLTs” is the number of patients who experienced DLT at the current dose level, “Number with data pending” denotes that number of patients whose DLT data are pending at the current dose level, “STFT” is the standardized total follow-up time for the patients with data pending, defined as the total follow-up time (TFT) for the patients with data pending divided by the length of the DLT assessment window (example to calculate STFT is shown in the Appendix). “Y" represents “Yes,” and “Y&Elim” represents “Yes and Eliminate.” When a dose is eliminated, all higher doses should also be eliminated [22]. “Suspend accrual” means the following: patient accrual is suspended to await the availability of more data when more than 50% of the patients' DLT outcomes are pending at the current dose [22].