ssimCrm {UBCRM}

Simulation of n dose-escalation study with the Continual Reassessment Method

Description

The ssimCrm function simulates n dose-escalation study with the CRM and provides summarized results.

Usage

ssimCrm(prior, n, firstdose = NA, truerate = prior, cohortsize = 3, target = 1/3,
nptmax = 24, nmaxmtd = nptmax, nmaxdose = nptmax, sd = 1.34, approach = "bayes",
method = "fpost", model = "power", nextlevel = "ntarget", upskipping = F,
downskipping = F, r = 2, seed = NULL)

Arguments

prior

Numeric vector of prior DLT probabilities.

n

Number of studies to simulate.

firstdose

Integer representing the dose at which the first cohort will be treated.

truerate

A nlevel-length vector of true rates for the DLTs.

cohortsize

Size of the cohort. Default value = 3.

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".

method

Estimation method for the posterior probabilities. "fpost" (default) estimates the mean of the posterior distribution of the paramater 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 appropriate 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.

r

Integer, number of digits for percentages in output.

seed

If not empty, the seed to use for random generation.

Value

data

Summarized result in a "np1" view.

norecommendation

Percentage of studies with no recommendation for the MTD (in case of the first level is considered as toxic).

mean.npt

Mean number of enrolled patients.

mean.ndlt

Mean number of observed DLTs.

mean.lastdose

Mean last experimented dose level.

mean.prob

Mean of posterior DLT 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. <https://doi.org/10.2307/2531628>

O'Quigley J., Shen LZ. (1996). Continual Reassessment Method: a likelihood approach. Biometrics 52, 673-684. <https://doi.org/10.2307/2532905>

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. <https://doi.org/10.1002/sim.3682>

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. <https://doi.org/10.1191/1740774506cn134oa>

See Also

Crm, simCrm

Examples

ssimCrm(c(0.1,0.2,0.3,0.35,0.45),firstdose=1,target=0.33,n=100)