dfpk (version 2.0.0)

pktox: Dose finding method PKTOX.

Description

The PKTOX model introduced to test the behaviour of one possible way to estimating probabilities of toxicity. This way consists of estimating probabilities of toxicity of doses passing through the AUC or another PK measure of exposure. This model is essentially the PKLOGIT model with the difference that uses $\Phi$ function instead of logit in the posterior probability of toxicity.

Usage

pktox(y, auc, doses, lev, theta, p_0, L, betapriors, D_AUC, options)

Arguments

y

A vector of patient's toxicity outcomes; TRUE indicates a toxicity, FALSE otherwise.

auc

The AUC values of each patient.

doses

The dose levels of the drug.

lev

A vector of dose levels assigned to the patients.

theta

The toxicity (probability) target.

p_0

The skeleton of CRM; defaults to NULL. (must be defined only in the PKCRM model)

L

A threshold set before starting the trial; defaults to NULL. (must be defined only in the PKCRM model)

betapriors

A vector of the regression parameters in the model.

D_AUC

A vector specifying the difference between the AUCs and AUC_pop; defaults to NULL.

options

A list of three integers specifying the stan model's number of chains, how many iterations for each chain and the number of warmup iterations. defaults to options <- list(nchains = 4, niter = 4000, nadapt = 0.8)

References

Ursino, M., et al, (2016) Dose-finding methods using pharmacokinetics in small populations (under review).

Whitehead, J., Zhou, Y., Hampson, L., Ledent, E., and Pereira, A. (2007) A bayesian approach for dose-escalation in a phase i clincial trial incorporating pharmacodynamic endpoints. Journal of Biopharmaceutical Statistics, 17 (6), 1117-1129.

See Also

pklogit, scenarios, nsim, nextDose

Examples

p_0 = NULL
L = NULL
d <- c(12.59972,34.65492,44.69007,60.80685,83.68946,100.37111)
theta <- 0.2
options <- list(nchains = 2,
        niter = 4000,
        nadapt = 0.8)
AUCs <-  c(0.43, 1.4, 5.98, 7.98, 11.90, 3.45)
x <- c(1,2,3,4,5,6)
y <- c(FALSE,FALSE,FALSE,FALSE,TRUE,FALSE)
D_AUC <- c(0, 1.3, -0.34, -2.7,0.39, -2.45)

### Betapriors ###
betapriors = NULL

pktox(y, AUCs, d, x, theta, p_0, L, betapriors, D_AUC,options)