sim.data: Generate and store PK and toxicity data.

Description

This function can be used to generate and store PK and toxicity data in order to be used for simulation according to the dose-finding model.

Usage

sim.data(PKparameters, omegaIIV, omegaAlpha, sigma, doses, limitTox, 
         timeSampling, N, TR, seed=190591)

Arguments

PKparameters

Subject's pharmacokinetic's (PK) parameters from the population distributions defined by the population mean.

omegaIIV

The inter-individual variability for the clearance and the volume of distribution; possible values may be 70% or 30% in different simulated data.

omegaAlpha

The patient's sensitivity parameter.

sigma

The additive or proportional error.

doses

A vector with the doses panel.

limitTox

The toxicity threshold.

timeSampling

The sampling time points.

The total sample size per trial.

The total number of simulated datasets.

seed

The seed of the random number generator that is used at the beginning of each trial; defaults to 190591.

Value

An object of class "scen" is returned, consisting of simulated PK and toxicity data. Objects generated by sim.data contain at least the following components:

PKparameters

Subject's pharmacokinetic's (PK) parameters from the population distributions defined by the population mean.

nPK

The length of the time points.

time

The sampling time points.

idtr

The id number of the corresponding simulated dataset.

The total sample size per trial.

doses

A vector with the doses panel.

preal

The prior toxicity probabilities.

limitTox

The tocixity threshold.

omegaIIV

The inter-individual variability for the clearance and the volume of distribution.

omegaAlpha

The patient's sensitivity parameter.

conc

The concentration computed at the PK population values.

concPred

The concentration values with proportional errors for each patient at each dose.

tox

The toxicity outcome.

parameters

The simulated PK parameters of each patient.

alphaAUC

A vector with the computed AUC values of each patient.

tab

A summary matrix containing the sampling time points at the first row followed by concPred, parameters and alphaAUC. It used by the simulation function nsim.

References

Ursino, M., et al, (2017) Dose-finding methods for Phase I clinical trials using pharmacokinetics in small populations, Biometrical Journal, <doi:10.1002/bimj.201600084>.

Toumazi, A., et al, (2018) dfpk: An R-package for Bayesian dose-finding designs using pharmacokinetics (PK) for phase I clinical trials, Computer Methods and Programs in Biomedicine, <doi:10.1016/j.cmpb.2018.01.023>.

Examples

Run this code

# NOT RUN {
TR = 10
N = 30
limitTox <- 10.96                                                
PKparameters <- c(2,10,100)       # PK parameters ka,CL,V
omegaIIV <- 0.7                   # Inter-individual
omegaAlpha <- 0                    
doses <- c(12.59972,34.65492,44.69007,60.80685,83.68946,100.37111)
timeSampling <- seq(0,24,length.out=48)    
sigma <- rep(0.2,length(timeSampling))  # sigma: Additive or proportional error

gen.scen <- sim.data(PKparameters,omegaIIV,omegaAlpha,sigma,doses,
                     limitTox,timeSampling, N, TR, seed=190591) 
gen.scen[[1]]     # returns the first simulated dataset. 


#### Graphical representation of the first simulated data
# plot(gen.scen[[1]])

# }