select.mtd: Select the maximum tolerated dose (MTD) for single agent...

Description Usage Arguments Details Value Note Author(s) References See Also Examples

View source: R/select.mtd.R

Description

Select the maximum tolerated dose (MTD) when the single-agent trial is completed

Usage

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

Arguments

target

the target DLT rate

npts

a vector containing the number of patients treated at each dose level

ntox

a vector containing the number of patients who experienced dose-limiting toxicity at each dose level

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.

verbose

set verbose=TRUE to return more details of the results

Details

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

Value

select.mtd() returns (1) target toxicity probability ($target), (2) selected MTD ($MTD), (3) isotonic estimate of the DLT probablity at each dose and associated 95\% credible interval ($p_est), and (4) the probability of overdosing defined as Pr(toxicity>\code{target}|data) ($p_overdose)

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 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.

Yuan Y., Hess K.R., Hilsenbeck S.G. and Gilbert M.R. (2016). Bayesian Optimal Interval Design: A Simple and Well-performing Design for Phase I Oncology Trials, Clinical Cancer Research, 22, 4291-4301.

See Also

Tutorial: http://odin.mdacc.tmc.edu/~yyuan/Software/BOIN/BOIN2.6_tutorial.pdf

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

Examples

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### select the MTD for BOIN single agent trial
n <- c(3, 3, 15, 9, 0)
y <- c(0, 0, 4, 4, 0)
selmtd <- select.mtd(target=0.3, npts=n, ntox=y)
summary.boin(selmtd)
plot.boin(selmtd)

BOIN documentation built on April 10, 2018, 5:05 p.m.

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