applied_titecrm {dtpcrm}R Documentation

Execute the TITE-CRM

Description

applied_titecrm is used to execute the time-to-event continual reassessment method with specified design options to determine the dose for the next subject.

Usage

applied_titecrm(prior, target, tox, level, followup, obswin,
    no_skip_esc = TRUE, no_skip_deesc = TRUE, global_coherent_esc = TRUE,
    stop_func = NULL, ...)

Arguments

prior

A vector of prior estimates of toxicity probabilties for the dose levels.

target

The target DLT rate.

tox

A vector of subject outcomes; 1 indicates toxicity, 0 otherwise.

level

A vector of dose levels assigned to subjects. The length of level must be equal to that of tox.

followup

A vector of follow up times of subjects. The length must be equal to that of tox.

obswin

The observation period with respect to which DLT is assessed.

no_skip_esc

If FALSE, the method will not enforce no skipping of doses in escalation. Default is TRUE.

no_skip_deesc

If FALSE, the method will not enforce no skipping of doses in de-escalation. Default is TRUE.

global_coherent_esc

If FALSE, the method will not enforce global coherent escalation, that is, escalation if the overall rate of toxicity seen at the current dose level is above the target rate. Default is TRUE.

stop_func

An optional argument to provide a function which will utilised alongside the TITE-CRM to determine if the trial should be stopped.

...

Any other arguments detailed in dfcrm::titecrm.

Details

The adaptive weighting scheme is given in Cheung and Chappell (2000) given in the reference list.

Value

An object of class "mtd" is returned as per package "dfcrm", additional information is provided if a stopping function is used.

prior

Initial guesses of toxicity rates.

target

The target probability of toxicity at the MTD.

ptox

Updated estimates of toxicity rates.

ptoxL

Lower confidence/probability limits of toxicity rates.

ptoxU

Upper confidence/probability limits of toxicity rates.

mtd

The updated estimate of the MTD.

prior.var

The variance of the normal prior.

post.var

The posterior variance of the model parameter.

estimate

Estimate of the model parameter.

method

The method of estimation.

model

The working model.

dosescaled

The scaled doses obtained via backward substitution.

tox

subjects' toxicity indications.

level

Dose levels assigned to subjects.

followup

Follow-up times of subjects.

obswin

Observation window with respect to which DLT is assessed.

weights

Weights assigned to subjects.

entry

Entry times of subjects.

exit

Exit times of subjects.

scheme

Weighting scheme.

stop

A logical variable detailing if the trial should be stopped; TRUE to stop, FALSE otherwise

stop_reason

A detailed reason for why the trial should be stopped. Only provided if stop is TRUE

References

O'Quigley, J. O., Pepe, M., and Fisher, L. (1990). Continual reassessment method: A practical design for phase I clinical trials in cancer. Biometrics 46:33-48.

Cheung, Y. K. (2011). Dose Finding by the Continual Reassessment Method. New York: Chapman & Hall/CRC Press.

Cheung, Y. K. and Chappell, R. (2000). Sequential designs for phase I clinical trials with late-onset toxicities. Biometrics 56:1177-1182.

Examples

prior    <- c(0.1, 0.3, 0.5)
target   <- 0.2
tox      <- c(0, 0, 1, 0, 1, 1)
level    <- c(1, 1, 1, 2, 2, 2)
followup <- c(96, 82, 77, 60, 51, 44)
obswin   <- 80

applied_titecrm(prior = prior, target = target, tox = tox,level = level,
                followup = followup, obswin = obswin)


[Package dtpcrm version 0.1.1 Index]