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

1 2 |

`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 |

`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).

the MTD(s) based on the trial data.

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.

Suyu Liu and Ying Yuan

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.

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

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

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)
``` |

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