get.oc.comb.kb: Operating Characteristics for Drug-combination Trials

Description Usage Arguments Value Uses References See Also Examples

View source: R/get.oc.comb.kb.R

Description

Generates the operating characteristics of the KEYBOARD design for drug-combination trials.

Usage

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get.oc.comb.kb(
  target,
  p.true,
  ncohort,
  cohortsize,
  n.earlystop = 100,
  marginL = 0.05,
  marginR = 0.05,
  startdose = c(1, 1),
  cutoff.eli = 0.95,
  extrasafe = FALSE,
  offset = 0.05,
  ntrial = 1000
)

Arguments

target

the target dose-limiting toxicity (DLT) rate.

p.true

a J*K matrix (J<=K) containing the true toxicity probabilities of combinations with J dose levels of agent A and K dose levels of agent B.

ncohort

a scalar specifying the total number of cohorts in the trial.

cohortsize

the number of patients in the cohort.

n.earlystop

the early stopping parameter. If the number of patients treated at the current dose reaches n.earlystop, stop the trial and select the MTD based on the observed data.
The default value, 100, essentially turns off this type of early stopping.

marginL

the difference between the target and the left bound of the "target key" (proper dosing interval) to be defined.
The default is 0.05.

marginR

the difference between the target and the right bound of the "target key" (proper dosing interval) to be defined.
The default is 0.05.

startdose

the starting dose combination level for the drug-combination trial.
The default is c(1, 1).

cutoff.eli

the cutoff to eliminate an overly toxic dose and all higher doses for safety.
The recommended value for general use and default is 0.95.

extrasafe

set extrasafe=TRUE to impose a more stringent stopping rule.
The default is FALSE.

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 stricter stopping rule.
The default value of 0.05 generally works well.

ntrial

the total number of trials to be simulated.
The default value is 1000.

Value

The function returns the operating characteristics of the KEYBOARD combination design as a list, among of which are:

  1. true toxicity probability at each dose level ($p.true),

  2. selection percentage at each dose level ($selpercent),

  3. the percentage of correct selection ($pcs),

  4. the number of patients treated at each dose level ($nptsdose),

  5. the number of toxicities observed at each dose level ($ntoxdose),

  6. the total number of toxicities observed in the trial ($totaltox),

  7. the total number of patients in the trial ($totaln),

  8. the total percentage of patients treated at the MTD ($npercent).

Uses

This function uses get.boundary.comb.kb and select.mtd.comb.

References

1. Yan F, Mandrekar SJ, Yuan Y. KEYBOARD: A Novel Bayesian Toxicity Probability Interval Design for Phase I Clinical Trials. Clinical Cancer Research. 2017; 23:3994-4003. http://clincancerres.aacrjournals.org/content/23/15/3994.full-text.pdf 2. Pan H, Lin R, Yuan Y. Keyboard design for phase I drug-combination trials Contemporary Clinical Trials. 2020 https://doi.org/10.1016/j.cct.2020.105972

See Also

Other drug-combination functions: get.boundary.comb.kb(), next.comb.kb(), select.mtd.comb.kb()

Examples

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### Drug-combination trial ###

p.true <- matrix(c(0.01, 0.03, 0.10, 0.20, 0.30,
                   0.03, 0.05, 0.15, 0.30, 0.60,
                   0.08, 0.10, 0.30, 0.60, 0.75), byrow=TRUE, ncol=5)

oc.comb <- get.oc.comb.kb(target=0.3, p.true, ncohort=20, cohortsize=3,
                          n.earlystop=12, startdose=c(1, 1), ntrial=100)

summary.kb(oc.comb)

plot.kb(oc.comb$ntoxdose) # can plot either $selpercent, $nptsdose,
                          # or $ntoxdose.

hongyingsun1101/KEYBOARD documentation built on March 25, 2020, 2:42 a.m.