dfpk (version 3.5.1)

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

Description

nextDose is used to perform parameter estimation at each step during a dose-finding trial. Determines the next or recommended dose level in a phase I clinical trial.

Usage

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

Arguments

model

A character string to specify the selected dose-finding model. See for details dtox, pkcov, pkcrm, pktox, pkpop, pklogit.

y

A binary vector of the toxicity outcomes from previous patients; 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 threshold.

options

A list with the Stan model's options.

prob

The threshold of the posterior probability of toxicity for the stopping rule in 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 in the pkcrm model; defaults to theta in the PKCRM model and NULL for the models dtox, pkcov, pktox, pkpop and pklogit.

p0

The skeleton of CRM for pkcrm; defaults to NULL.

L

The AUC threshold to be set before starting the trial for pkcrm; defaults to NULL.

deltaAUC

A vector of 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.

CI

A logical constant indicating the estimated 95% credible interval; defaults to TRUE.

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 toxicity outcomes from previous patients; 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

The tocixity threshold.

options

List with the Stan model's options.

newDose

The next recommended dose (RD) level; equals to 0 if the trial has stopped, according to the stopping rules.

pstim

The mean values of the estimated probabilities of toxicity.

pstimQ1

The 1st quartile of the estimated probabilities of toxicity if CI = TRUE, otherwise is NULL.

pstimQ3

The 3rd quartile of the estimated probabilities of toxicity if CI = TRUE, otherwise is NULL.

parameters

The estimated model's parameters.

model

A character string to specify the selected dose-finding model. See for details dtox, pkcov, pkcrm, pktox, pkpop, pklogit.

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>.

See Also

nsim

Examples

# NOT RUN {
  
# }
# NOT RUN {
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)
# }
# NOT RUN {
# }