dfpk (version 3.3.0)

nextDose: Next dose determination of a phase I clinical trial.

Description

nextDose is used to determine the next or recommended dose level in a phase I clinical trial using Pharmacokinetics (PK).

Usage

nextDose(model, y, AUCs, doses, x, theta, options, prob = 0.9,
  betapriors = NULL, thetaL = NULL, p0 = NULL, L = NULL,
  deltaAUC = NULL)

Arguments

model

A character string to specify the working model used in the method.

y

A binary vector of patient's toxicity outcomes; 1 indicates a toxicity, 0 otherwise.

AUCs

A vector with the computed AUC values of each patient for pktox, pkcrm, pklogit and pkpop; defaults to NULL.

doses

A vector with the doses panel.

x

A vector with the dose level assigned to the patients.

theta

The toxicity target.

options

List with the Stan model's options.

prob

The probability of toxicity for the corresponding stopping rule of the selected model; defaults to 0.9. See for details dtox, pkcov, pkcrm, pktox, pkpop, pklogit.

betapriors

A vector with the value for the prior distribution of the regression parameters in the model; defaults to NULL.

thetaL

A second threshold of AUC; must be defined only in the PKCRM model.

p0

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

L

The AUC threshold to be set before starting the trial for pklogit, pkcrm and pktox; defaults to NULL. (must be defined only in the PKCRM model).

deltaAUC

The difference between computed individual AUC and the AUC of the population at the same dose level (defined as an average); argument for pkcov; defaults to NULL.

Value

An object of class "dose" is returned, consisting of determination of the next recommended dose and estimations. Objects generated by nextDose contain at least the following components:

N

The total number of enrolled patients.

y

A binary vector of patient's toxicity outcomes; 1 indicates a toxicity, 0 otherwise.

AUCs

A vector with the computed AUC values of each patient.

doses

A vector with the doses panel.

x

A vector with the dose level assigned to the patients.

theta

Tocixity target.

options

List with the Stan model's options.

newDose

The next recommended dose level; equals to "NA" if the trial has stopped, according to the stopping rules.

pstim

The mean values of estimated probabilities of toxicity.

pstimQ1

The 1st quartile of estimated probabilities of toxicity.

pstimQ3

The 3rd quartile of estimated probabilities of toxicity.

parameters

The estimated model's parameters.

model

A character string of the selected working dose-finding model.

References

Ursino, M., et al, (2017) Dose-finding methods for Phase I clinical trials using pharmacokinetics in small populations, Biometrical Journal.

See Also

nsim

Examples

  
doses <- c(12.59972,34.65492,44.69007,60.80685,83.68946,100.37111)
theta <- 0.2 
options <- list(nchains = 4, niter = 4000, nadapt = 0.9)     
AUCs <- c(1.208339,  5.506040,  6.879835,  3.307928,  3.642430, 
          10.271291,  3.885522,  3.086622,  2.537158,  5.525917,  
          8.522176,  4.642741, 11.048531, 10.246976,  5.226807)
x <- c(1, 2, 3, 4, 5, 6, 4, 4, 4, 5, 5, 4, 4, 5, 5)
y <- c(0, 0, 0, 0, 0, 1, 0, 0, 0, 0, 1, 0, 0, 0, 0)
nextD <- nextDose(model = "pktox", y=y, AUCs=AUCs, doses=doses, 
                  x=x, theta=theta, options=options)