titesim1 {titecrm}R Documentation

TITE-CRM Simulator

Description

Returns an object of class ``sim'' that generates and summarizes the dose assignments of a simulated trial by the TITE-CRM.

Usage

titesim1(PI, prior, target, n, obswin=1, rate=1, accrual="fixed", 
surv="uniform", scheme="linear", method="bayes", scale=sqrt(1.34),
seed=1099)

Arguments

PI A vector of the true toxicity probabilites associated with the doses.
prior A vector of initial estimates of toxicity probabilities associated with the doses. Must be of same length as PI.
target The target DLT rate.
n Sample size of the trial.
obswin The observation window with respect to which the MTD is defined.
rate Patient arrival rate: Expected number of arrivals per obswin. Example: obswin=6 and rate=3 means expecting 3 patients arrive in 6 time units.
accrual Patient arrival scheme. Default is ``fixed'' whereby inter-patient arrival is fixed. Alternatively, use ``poisson'' to simulate patient arrivals by the Poisson process.
surv Distribution for time-to-toxicity. Default is ``uniform'' where toxicity, if occurs, occurs uniformly on the interval [0,obswin]. Other survival distributions including exponential and Weibull are to be made available.
scheme A character string to specify the method for assigning weights. Default is ``linear''. Adaptive weight using Kaplan-Meier ``KM'' is to be made available.
method A character string to specify the method for parameter estimation. The default method ``bayes'' estimates the model parameter by the posterior mean. Estimation using ``mle'' is to be made available.
scale Standard deviation of the normal prior of the model parameter. Default is sqrt(1.34).
seed Seed of the random number generator.

Details

Dose-toxicity relationship is assumed as an empiric power model $a_i^{exp(β)}$ where $a_i$ is the initial estimate of toxicity probability of dose level i and the model parameter $β$ has a normal prior with mean 0 and scale to be provided by users.

The simulation starts the first patient at the prior MTD.

Value

An object of class ``mtd'' is returned, consisting of the summary of dose assignments and the final dose recommendation in a simulated trial.

PI True toxicity probabilites.
prior Initial estimates of toxicity probabilities.
target The target probability of toxicity at the MTD.
recommend The recommended dose level for the next patient.
scale The standard deviation of the normal prior.
estimate Estimate of the model parameter.
level Dose levels assigned to patients.
tox Patients' toxicity indications.
arrival Patients' arrival times.
ttox.pt Patients' times-to-toxicity.
ttox.cal Patients' times-to-toxicity on study time.
obswin Observation window with respect to which the MTD is defined.
weights Weights assigned to patients.
scheme Weighting scheme.
accrual Patient's arrival pattern.
rate Rate of patient's arrival.
surv Distribution of time-to-toxicity.

References

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

Examples

PI <- c(0.10,0.20,0.40,0.50,0.60,0.65)
prior <- c(0.05,0.10,0.20,0.35,0.50,0.70)
target <- 0.2
# Generate a trial of size 24
foo <- titesim1(PI,prior,target,24,obswin=6,rate=4,accrual="poisson")
rec <- foo$recommend  # recommend a dose level for next patient
plot(foo)  # summarize trial graphically

[Package titecrm version 0.1-1 Index]