## [1] "DesignGrouped"A logistic log normal model will describe the relationship between dose and toxicity: \[ p(Tox | d) = f(X = 1 | \theta, d) = \frac{e^{(\alpha + I_c \times \delta_0) + (\beta + I_c \times \delta_1) \cdot log(d/d^*)}}{1 + e^{(\alpha + I_c \times \delta_0) + (\beta + I_c \times \delta_1) \cdot log(d/d^*)}} \]where d* denotes a reference dose and Ic is a binary indicator which is 1 for the combo arm and 0 for the mono arm.
The prior for θ is given by\[ \boldsymbol\theta = \begin{bmatrix}\alpha \\ \beta \\ log(\delta_0) \\ log(\delta_1)\end{bmatrix}\sim N \left(\begin{bmatrix} 0.00 \\ 0.00 \\ 0.00 \\ 0.00\end{bmatrix} , \begin{bmatrix} 1.00 & 0.00 & 0.00 & 0.00 \\ 0.00 & 1.00 & 0.00 & 0.00 \\ 0.00 & 0.00 & 1.00 & 0.00 \\ 0.00 & 0.00 & 0.00 & 1.00\end{bmatrix} \right) \]
The reference dose will be 1.00.
If 20 or more participants have been treated.
| Min | Max | Increment |
|---|---|---|
| 0 | 2 | 2 |
| 2 | Inf | 1 |
Placebo will not be administered in the trial.
The dose recommended for the next cohort will be chosen in the following way. First, doses that are ineligible according to the increments rule will be discarded. Next, any dose for which the mean posterior probability of toxicity being in the overdose range - (0.35, 1] - is 0.25 or more will also be discarded. Finally, the dose amongst those remaining which has the highest chance that the mean posterior probability of toxicity is in the target toxicity range of 0.2 to 0.35 (inclusive) will be selected.
A constant size of 3 participants.
No participants are yet evaluable.
The dose grid is 1, 2 and 3.
The starting dose is 1.
If 20 or more participants have been treated.
| Min | Max | Increment |
|---|---|---|
| 0 | 2 | 2 |
| 2 | Inf | 1 |
Placebo will not be administered in the trial.
The dose recommended for the next cohort will be chosen in the following way. First, doses that are ineligible according to the increments rule will be discarded. Next, any dose for which the mean posterior probability of toxicity being in the overdose range - (0.35, 1] - is 0.25 or more will also be discarded. Finally, the dose amongst those remaining which has the highest chance that the mean posterior probability of toxicity is in the target toxicity range of 0.2 to 0.35 (inclusive) will be selected.
A constant size of 3 participants.
No participants are yet evaluable.
The dose grid is 1, 2 and 3.
The starting dose is 1.
No combination dosing may occur until the results of at least one monotherapy cohort are available.
When monotherapy and combination therapy are used in the same cohort for the first time, the use of a different dose in each regimen is permitted.
Whenever monotherapy and combination therapy are used in the same cohort, the same dose must be used for both regimens.