BOIN (version 2.0)

select.mtd.comb: Select the maximum tolerated dose (MTD) for drug combination trials

Description

select.mtd.comb is used to select the maximum tolerated dose (MTD) when the drug combination trial is completed.

Usage

select.mtd.comb(target, npts, ntox, cutoff.eli=0.95, extrasafe=FALSE, 
offset=0.05, print=TRUE)

Arguments

target

target toxicity rate

npts

a matrix containing the number of patients treated at each dose combination

ntox

a matrix containing the number of patients experienced dose-limiting toxicity at each dose combination

cutoff.eli

the cutoff to eliminate overly toxic doses for safety. We recommend the default value of (cutoff.eli=0.95) for general use.

extrasafe

set extrasafe=TRUE to impose a more strict stopping rule for extra safety

offset

a small positive number (between 0 and 0.5) to control how strict the stopping rule is when extrasafe=TRUE. A larger value leads to a more strict stopping rule. The default value offset=0.05 generally works well.

print

prints out the dose selection result.

Value

• select.mtd.comb() returns the MTD based on the trial data.

Details

select.mtd.comb() selects the MTD based on isotonic estimates of toxicity probabilities. select.mtd.comb() selects as the MTD dose j*, for which the isotonic estimate of the toxicity rate is closest to the target. If there are ties, we select from the ties the highest dose level when the estimate of the toxicity rate is smaller than the target, or the lowest dose level when the estimate of the toxicity rate is greater than the target. The (matrix) isotonic estimates are obtained by the pooled-adjacent-violators algorithm (PAVA) (Barlow, 1972).

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. (2015). Bayesian Optimal Interval Designs for Dose Finding in Drug-combination Trials, Statistical Methods in Medical Research, to appear.

See Also

Tutorial: http://odin.mdacc.tmc.edu/~yyuan/Software/BOIN/BOIN2.0_tutorial.pdf

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

Examples

## 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)