get.oc.comb.kb {Keyboard}

Operating Characteristics for Drug-combination Trials

Description

This function generates the operating characteristics of the Keyboard design for drug-combination trials.

Usage

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, then we stop the trial and select the MTD based on the observed data.
The default value is 100.

marginL

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

marginR

The difference between the target and the upper 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 value to eliminate an overly toxic dose and all higher doses for safety.
The default value is 0.95.

extrasafe

Set extrasafe=TRUE to impose a stricter 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 is 0.05.

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:

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

2. the 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

Author(s)

Xiaomeng Yuan, Chen Li, Hongying Sun, Li Tang and Haitao Pan

References

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

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

### 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=p.true, ncohort=20, cohortsize=3,
                          n.earlystop=12, startdose=c(1, 1), ntrial=100)