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dfped

The dfped R package provides an unified method for designing and analysing dose-finding trials in paediatrics, while bridging information from adults.

Description

dfped package includes three extrapolation methods in order to calculate the dose range: linear, allometry and maturation adjustment, using pharmacokinetic (PK) data. To do this, it is assumed that target exposures are the same in both populations. The working model and prior distribution parameters of the dose-toxicity and dose-efficacy relationships can be obtained using early phase adult toxicity and efficacy data at several dose levels through dfped package. Priors are used into the dose finding process through a Bayesian model selection or adaptive priors, to facilitate adjusting the amount of prior information to differences between adults and children. This calibrates the model to adjust for misspecification if the adult and paediatric data are very different. User can use his/her own Bayesian model written in Stan code through the dfped package. A template of this model is proposed in the examples of the corresponding R functions in the package. Finally, in this package you can find a simulation function for one trial or for more than one trial.

Installation

Establish Version

A latest version of the package dfped is available on CRAN and can be loaded via

install.packages("dfped")
library(dfped)

Development Version

To install the dfped package from GitHub, first make sure that you can install the rstan package and C++ toolchain by following these instructions. The program Rtools (available on https://cran.r-project.org/bin/windows/Rtools/) comes with a C++ compiler for Windows. On OS-X, you should install Xcode. Once rstan is successfully installed, you can install dfped from GitHub using the devtools package by executing the following in R:

if (!require(devtools)){
  install.packages("devtools")
  library(devtools)
}

install_github("artemis-toumazi/dfped")

If installation fails, please let us know by filing an issue.

Details on formula syntax, families and link functions, as well as prior distributions can be found on the help page of the dfped function:

help(dfped)

FAQ

Can I avoid compiling Stan models?

Unfortunately, fitting your Stan model with dfped, there is currently no way to avoid the compilation.

What is the best way to ask a question or propose a new feature?

You can either open an issue on github or write me an email to (artemis.toumazi@gmail.com).

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Version

Install

install.packages('dfped')

Monthly Downloads

229

Version

1.1

License

GPL (>= 3)

Issues

Pull Requests

Stars

Forks

Maintainer

Artemis Toumazi

Last Published

March 27th, 2018

Functions in dfped (1.1)

Cladu

Clearance of the unbound fraction of a specific molecule for the adult population.
Clch.Mat

Paediatric clearance according to the maturation adjustment (MA) for a specific age.
Clch.Allo

Paediatric clearance according to the allometry adjustment (AA) for a specific age.
Clch.Linear

Paediatric clearance according to the linear adjustment (LA) for a specific age.
KCYP1A2

Fraction of adult CYP1A2 abundance according to age.
KCYP2C8

Fraction of adult CYP2C8 abundance according to age.
KCYP2C18_19

Fraction of adult CYP2C18/CYP2C19 abundance according to age.
KCYP2B6

Fraction of adult CYP2B6 abundance according to age.
concCh

Concentration of a specific molecule in plasma for the paediatric population.
Clchu

Clearance of the unbound fraction of a specific molecule for the paediatric population.
dfped-package

Extrapolation and Bridging of Adult Information in Early Phase Dose-Finding Paediatrics Studies
alpha1AGage

Concentration of alpha1-acid glycoprotein according to age.
Fch

Paediatric bioavailability according to age.
concAd

Concentration of a specific molecule in plasma for the adult population.
albAge

Concentration of albumin according to age.
metaPhase

Meta-analysis function of dose-finding studies proposed by Zohar et al, (2011).
sigmaLI

Compute the least informative prior variance for the adaptive prior.
KCYP2E1

Fraction of adult CYP2E1 abundance according to age.
sigmaEss

The variance of the effective sample size (ESS).
doseChoice

Choice of the next given dose level.
KCYP3A

Fraction of adult CYP3A abundance according to age.
fuCh

Unbound fraction of the molecule in the plasma for children.
weightCYPsum

Proportion of the molecule metabolised by the CYPs for a child according to age.
KCYP3A4_5

Fraction of adult CYP3A4/CYP3A5 abundance according to age.
doseRange

Dose-range for the paediatric population according to adult clearance, adult doses and paediatric clearance.
kickoffControl

Control for presence of at least toxicities and efficacies for the good run of bCRM model.
KCYP2C9

Fraction of adult CYP2C9 abundance according to age.
simu

A simulation of a single dose-finding trials in paediatrics.
KCYP2D6

Fraction of adult CYP2D6 abundance according to age.
simulation

Simulate one or "n" dose-finding trials in paediatrics.
priorChoice

Decision function for the choice of variance (sigmaHI or sigmaLI) in the adaptive prior variance calibration.
sigmaHI

Compute the informative prior variance for the adaptive prior.
skeleton

Build a working model.
waic

Function for the Watanabe-Akaike information criteria (WAIC)