Crm: Dose-escalation with the Continual Reassessment Method

In UBCRM: Functions to Simulate and Conduct Dose-Escalation Phase I Studies

Dose-escalation with the Continual Reassessment Method

Description

The function gives the next level to include patients following a model-based design. Needs an updated input dataframe with the CreData() structure.

Usage

Crm(Dk, prior, target = 1/3, nptmax = 24, nmaxmtd = 6, nmaxdose = nptmax, sd = 1.34,
approach = "bayes", model = "power", method = "fpost", nextlevel = "ntarget",
upskipping = F, downskipping = F, lastdose = NA)

Arguments

Dk	Study dataframe with CreData() structure.
prior	Numeric vector of prior DLTs probabilities.
target	Target used for the MTD determination.
nptmax	Maximum number of patients to include in the study.
nmaxmtd	Maximum number of patients to be treated at the designated MTD. Assign a high value (=nptmax) to avoid such a stopping rule.
nmaxdose	Maximum number of patients to be treated at the same dose. Assign a high value (=nptmax) to avoid such a stopping rule.
sd	Standard deviation used in case of a normal distribution assumption for the parameter.
approach	Character indicating the estimation method: "bayes" (default value) for CRM or "mle" for CRML.
model	Character indicating the dose-DLT relationship model: "power", "tangent" or "logistic". More informations in the details section.
method	Estimation method for the posterior probabilities. "fpost" (default) estimates the mean of the posterior distribution of the parameter alpha (hat_alpha=E[alpha]) and uses it in psy(hat_alpha,...). "ppostp" and "pposts" directly estimate the mean of the posterior DLT probability. "ppostp" uses prior as singletons whereas "pposts" calculates appropriates singletons (see ail, ait or aip functions).
nextlevel	Character option used for determining the next dose level. "ntarget" (default) if the next level is chosen as the closest level to the desired target (may be higher than target). "utarget" if the next level is the closest level with the restriction to be lower than the target value.
upskipping	Boolean option used for determining the next dose level. If TRUE no level skip in escalation will be allowed. If FALSE (default) the level skips will be permitted.
downskipping	Boolean option used for determining the next dose level. If TRUE no level skip in desescalation will be allowed. If FALSE (default) the level skips will be permitted.
lastdose	Integer representing the last experimented dose level.

Details

Details of the 3 dose-DLT relationship proposed models: "power" for the power model psy(s,a)=s^exp(a), "tangent" for the hyperbolic tangent model psy(s,a)= ((tanh(s)+1)/2)**a, "logistic" for the logistic model psy(s,a) = exp(3+a*s)/(1+exp(3+a*s)). Note: power and tangent models are equivalent after an appropriate transformation on the parameter.

Value

nextdose	An integer representing the next recommended dose to experiment.
mtd	If reached, an integer representing the MTD.
prob	Posterior DLTs probabilities.

Author(s)

Benjamin Esterni, Baboukar Mane. Unite de Biostatistique et de Methodologie, Institut Paoli-Calmettes, Marseille, France.

References

O'Quigley J., Pepe M., Fisher L. (1990). Continual Reassessment Method: a practical design for Phase I clinical trials in cancer. Biometrics 46, 33-48.

O'Quigley J., Shen LZ. (1996). Continual Reassessment Method: a likelihood approach. Biometrics 52, 673-684.

Paoletti X., Kramar A. (2009). A comparison of model choices for the Continual Reassessment Method in phase I cancer trials. Statistics in Medecine 28, 3012-3028.

Chamorey Emmanuel. (2009). Methodologie des essais de phase precoce en cancerologie: evolution des schemas et apport de la pharmacologie. These.

Garret-Mayer Elizabeth. (2006). The Continual Reassessment Method for dose-finding studies: a tutorial. Clinical Trials: 57-71.

See Also

simCrm, ssimCrm

Examples

data<- CreData(5)
data<- updata(data,1,3,0)
data<- updata(data,2,3,1)
data<- updata(data,2,3,1)
data
Crm(data,prior=c(0.1,0.15,0.25,0.35,0.45),target=0.3,nextlevel="ntarget",nptmax=24,nmaxmtd=6)
data<- updata(data,3,3,2)
data
Crm(data,prior=c(0.1,0.15,0.25,0.35,0.45),target=0.3,nextlevel="ntarget",nptmax=24,nmaxmtd=6)

UBCRM documentation built on May 17, 2022, 1:07 a.m.