SimRMD {phase1RMD}

Simulate trial characters of the phase I dose-finding design.

Description

SimRMD uses the design parameters to simulate the trial characters of phase I dose-finding design.

Usage

SimRMD(seed=2014, strDose=1, chSize=3, trlSize=36,
   numTrials=1000, sdose=1:6, MaxCycle=6, tox.target=0.28,
   control, iter=10000, burnin=4000, thin=1, chains=1,    
   pathout='./', tox.matrix, wm = matrix(c(0, 0.5, 0.75, 1  , 1.5, 
                                        0, 0.5, 0.75, 1  , 1.5, 
                                        0, 0  , 0   , 0.5, 1  ), 
                                        byrow = T, ncol = 5), toxmax = 2.5)

Arguments

seed

Random seed of the simulation (default = 2014).

strDose

Start dose (default = 1).

chSize

Size of each patient cohort (default = 3).

trlSize

Total number of patients in the trial (default = 36).

numTrials

Number of simulated trials (default = 1000).

sdose

Dose range (default = 1:6).

MaxCycle

Maximum treatment cycle (default = 6).

tox.target

Target toxicity score (default = 0.28).

control

Prior distributions as specified by parm function.

iter

Total number of MCMC simulations (default = 4000).

burnin

Number of burn-ins in the MCMC simulation (default = 1000).

thin

Thinning parameter (default = 1).

chains

Number of chains in the MCMC simulation (default = 1).

pathout

The output directory of simulation results (default = './').

tox.matrix

Four-dimension array contains Dose, Cycle, Toxicity Type, Toxicity Grade.

wm

Clinical weight matrix, where toxicity types define the rows while the toxicity grades define the columns. Usually solicited from physicians.

toxmax

The normalization constant used in computing nTTP score. For details, see Ezzalfani et al(2013).

Details

The SimRMD function uses the patient data structure patdata to fit the linear mixed model as specified by formula based on the prior distributions as specified by control. The parameters of the MCMC simulation are specified by iter: the number of iterations, burnin: burn-ins, thin: thinning parameter and chains: number of chains in the MCMC simulation. The target nTTP score is defined by tox.target, default = 0.28.

Value

A list containing the following elements:

DOSE-RECOMMENDED

Recommended dose for the next patient cohort.

Estimate

Mean, SD, and median estimates of the toxicity score at each dose level.

Quantiles

2.5%, 25%, 50%, 75%, 97.5% quantile estimates of the toxicity score at each dose level.

Examples

# Setup the prior distributions for the phase I dose-finding model:
control <- list(
 beta.dose = parm("normal", mean = 0, var = 1000),
 beta.other = parm("normal", mean = 0, var = 1000 ),
 gamma = parm("normal", mean = 0, var = 100 ),
 s2.gamma = parm("invgamma", shape = 0.001, scale = 0.001),
 s2.epsilon = parm("invgamma", shape = 0.001, scale = 0.001)
 )


# Generate the toxicity matrix
# tox.matrix <- GenToxProb(
#    toxtype = c("Renal", "Neuro", "Heme"), 
#	intercept.alpha = c(2, 3, 4.2, 5.7), 
#	coef.beta = c(-0.2, -0.4, -0.7), 
#	cycle.gamma = 0)

# Simulate the dose-recommendation based on the toxicity matrix
# simu <- SimRMD(seed=2014, strDose=1, chSize=3, trlSize=12,
#    numTrials=1, sdose=1:6, MaxCycle=5, tox.target=0.28,
#    control=control, iter=10, burnin=2, thin=1, chains=1,    
#    pathout='./', tox.matrix=tox.matrix)