next.comb.kb {Keyboard}

Find the Next Dose Combination

Description

This function determines the dose combination for the next cohort of patients in drug-combination trials.

Usage

next.comb.kb(
  target,
  npts,
  ntox,
  dose.curr,
  n.earlystop = 100,
  marginL = 0.05,
  marginR = 0.05,
  cutoff.eli = 0.95,
  extrasafe = FALSE,
  offset = 0.05
)

Arguments

target

The target dose-limiting toxicity (DLT) rate.

npts

A J*K matrix (J<=K) containing the number of patients treated at each dose combination.

ntox

A J*K matrix (J<=K) containing the number of patients who experienced a dose-limiting toxicity at each dose combination.

dose.curr

The current dose combination, i.e., the dose combination that was used to treat the most recently enrolled cohort of patients.

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 limit of the "target key" (proper dosing interval) to be defined.
The default is 0.05.

marginR

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

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.

Details

Given the observed data thus far, this function determines the dose combination for treating the next cohort of new patients. The observed data are as follows: the number of patients treated at each dose combination (npts), the number of patients who experienced dose-limiting toxicities (DLTs) at each dose combination (ntox) and the level of the current dose (dose.curr). The number of patients for doses that have not been used in the trial is zero.

Value

This function returns the recommended dose for treating the next cohort of patients ($next_dc).

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(), get.oc.comb.kb(), select.mtd.comb.kb()

Examples

### Drug-combination trial ###

n <- matrix(c(3, 0, 0, 0, 0,
              7, 6, 0, 0, 0,
              0, 0, 0, 0, 0), ncol=5, byrow=TRUE)
y <- matrix(c(0, 0, 0, 0, 0,
              1, 1, 0, 0, 0,
              0, 0, 0, 0, 0), ncol=5, byrow=TRUE)

nxt.comb <- next.comb.kb(target=0.3, npts=n, ntox=y, dose.curr=c(2, 2))
summary_kb(nxt.comb)