Table 2. Comparison of Rolling 6 and Phase 1 Queue Rolling 6 Design Decisionsa.
| Row | No. on current level | Dose level for next patient | |||
|---|---|---|---|---|---|
| Totalb | Evaluaablec | Dose-limiting toxicitiesd | IQ rolling 6e | Rolling 6e | |
| 1 | 0-5 | 0 | 0 | Same dose level | Same dose level |
| 2 | 6 | 0 | 0 | Hold accrual | Hold accrual |
| 3 | 1-5 | 1 | 0 | Same dose level | Same dose level |
| 4 | 6 | 1 | 0 | Same dose level | Hold accrual |
| 5 | 7 | 1 | 0 | Hold accrual | Not allowed |
| 6 | 2-5 | 2 | 0 | Same dose level | Same dose level |
| 7 | 6-7 | 2 | 0 | Same dose level | Hold accrual (patient 7 not allowed) |
| 8 | 8 | 2 | 0 | Hold accrual | Not allowed |
| 9 | 3 | 3 | 0 | Escalatef | Escalate |
| 10 | 4-5 | 3 | 0 | Escalatef | Same dose level |
| 11 | 6 | 3 | 0 | Escalatef | Hold accrual |
| 12 | 7-8 | 3 | 0 | Escalatef | Not allowed |
| 13 | 4 | 4 | 0 | Escalatef | Escalate |
| 14 | 5 | 4 | 0 | Escalatef | Same dose level |
| 15 | 6-8 | 4 | 0 | Escalatef | Hold accrual (patients 7 and 8 not allowed) |
| 16 | 5 | 5 | 0 | Escalate (or MTD)f | Escalate (or MTD)f |
| 17 | 6 | 5 | 0 | Escalate (or MTD)f | Escalate (or MTD)f |
| 18 | 7-8 | 5 | 0 | Escalate (or MTD)f | Not allowed |
| 19 | 1-5 | 1-5 | 1 | Same dose level | Same dose level |
| 20 | 6 | 1-3 | 1 | Hold accrual | Hold accrual |
| 21 | 6 | 4 | 1 | Same dose level | Hold accrual |
| 22 | 6 | 5 | 1 | Same dose level | Hold accrual |
| 23 | 7 | 4 | 1 | Hold accrual | Not allowed |
| 24 | 7 | 5 | 1 | Same dose level | Not allowed |
| 25 | 6-8 | 6-8 | 1 | Escalatef | Escalate (patients 7 and 8 not allowed)f |
| 26 | 2-8 | 2-6 | 2 | Deescalateg | Deescalate (patients 7 and 8 not allowed)g |
| 27 | 7 | 7 | 2 | MTD | Not allowed |
| 28 | 8 | 7 | 2 | Hold accrual | Not allowed |
| 29 | 8 | 8 | 2 | MTD | Not allowed |
| 30 | Any | any | 3 | Deescalateg | Deescalateg |
Abbreviations: IQ, phase 1 queue; MTD, maximum tolerated dose.
The IQ design and the corresponding parent design are side by side. Rare scenarios are not listed, but the full decision grid is available in the software input module available.7,8
The number of patients who consented to that dose level, excluding individuals who did not meet screening criteria or patients considered inevaluable with respect to dose-limiting toxicity.
The number of patients who provided an answer to the dose-limiting question (yes or no).
The number of patients who experienced a dose-limiting toxicity. The number pending is the difference between the total number and the number evaluable.
The action to be taken for the next patient for the IQ design and the parent design, respectively. If a patient pending evaluation on a lower dose experiences a dose-limiting toxicity, the principal investigator in consultation with the sponsor may choose to reduce the dose level of any patients currently on a higher dose level, pending review of the adverse event data.
If the next higher dose level is not available (there is no higher dose level or the higher dose level was already tested and found to be too toxic), a maximum of 8 patients can be treated at the current dose level and the principal investigator should declare the MTD with 0 or 1 dose-limiting toxicity of 6 (or 0 of 5) patients. For IQ 3 + 3, no more than 4 patients at risk are allowed, with no more than 6 patients at risk for the IQ rolling 6 design. Two dose-limiting toxicities in 7 or 8 patients means that the principal investigator can also declare the MTD (and it is suggested to continued using monitoring rules for the expanded cohort).
Current level exceeds the MTD. The MTD is the highest level at which less than 33% of patients had dose-limiting toxicities, with at least 6 patients evaluable.