# Select the maximum tolerated dose (MTD) or MTD contour for drug combination trials

### Description

Select the maximum tolerated dose (MTD) or MTD contour after the drug combination trial is completed using the BOIN design or waterfall design

### Usage

1 2 |

### Arguments

`target` |
the target toxicity rate |

`npts` |
a |

`ntox` |
a |

`cutoff.eli` |
the cutoff to eliminate an overly toxic dose for safety.
We recommend the default value of ( |

`extrasafe` |
set |

`offset` |
a small positive number (between 0 and 0.5) to control how
strict the stopping rule is when |

`print` |
to print out the dose selection results. |

`MTD.contour` |
set |

### Details

`select.mtd.comb()`

selects a MTD or the MTD contour based
on matrix isotonic estimates of toxicity probabilities, depending on
`MTD.contour`

is set as `TRUE`

or `FALSE`

. The (matrix)
isotonic estimates are obtained by the R package (Iso::biviso).

### Value

the MTD(s) based on the trial data.

### Note

The MTD selection and dose escalation/deescalation rule are two independent components of the trial design. When appropriate, another dose selection procedure (e.g., based on a fitted logistic model) can be used to select the MTD after the completion of the trial using the BOIN or waterfall design.

### Author(s)

Suyu Liu and Ying Yuan

### References

Liu S. and Yuan, Y. (2015). Bayesian Optimal Interval Designs for Phase I Clinical Trials, Journal of the Royal Statistical Society: Series C, 64, 507-523.

Lin R. and Yin, G. (2016). Bayesian Optimal Interval Designs for Dose Finding in Drug-combination Trials, Statistical Methods in Medical Research, to appear.

Zhang L. and Yuan, Y. (2016). A Simple Bayesian Design to Identify the Maximum Tolerated Dose Contour for Drug Combination Trials, under review.

### See Also

Tutorial: http://odin.mdacc.tmc.edu/~yyuan/Software/BOIN/BOIN2.4_tutorial.pdf

Paper: http://odin.mdacc.tmc.edu/~yyuan/Software/BOIN/paper.pdf

### Examples

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 | ```
## Select the MTD based on the data from a 3x5 combination trial
## matrix n contains the number of patients treated at each dose combination
## matrix y contains the number of patients experienced toxicity at each dose combination
n<-matrix(c(3, 5, 0, 0, 0, 7, 6, 15, 0, 0, 0, 0, 4, 0, 0), ncol=5, byrow=TRUE)
y<-matrix(c(0, 1, 0, 0, 0, 1, 1, 4, 0, 0, 0, 0, 2, 0, 0), ncol=5, byrow=TRUE)
select.mtd.comb(target=0.3, npts=n, ntox=y, MTD.contour=FALSE)
## Select the MTD contour based on the data from a 3x4 combination trial
## matrix n contains the number of patients treated at each dose combination
## matrix y contains the number of patients experienced toxicity at each dose combination
n<-matrix(c(6, 9, 24, 0, 6, 24, 9, 0, 12, 18, 0, 0), ncol=4, byrow=TRUE)
y<-matrix(c(0, 1, 5, 0, 1, 5, 4, 0, 1, 5, 0, 0), ncol=4, byrow=TRUE)
select.mtd.comb(target=0.3, npts=n, ntox=y, MTD.contour=TRUE)
``` |