Diagnostics for Nonlinear Mixed-Effect Models

A model building aid for nonlinear mixed-effects (population) model analysis using NONMEM, facilitating data set checkout, exploration and visualization, model diagnostics, candidate covariate identification and model comparison. The methods are described in Keizer et al. (2013) , and Jonsson et al. (1999) .

Xpose 4

by Andrew C. Hooker, Mats O. Karlsson and E. Niclas Jonsson

Introduction

Xpose 4 is a collection of functions to be used as a model building aid for nonlinear mixed-effects (population) analysis using NONMEM. It facilitates data set checkout, exploration and visualization, model diagnostics, candidate covariate identification and model comparison.

Installation

To install xpose you will need R (>= version 2.2.0).
To install Xpose in R use one of the following methods:

• latest stable release – From CRAN. Write at the R command line:

  install.packages("xpose4")
  

• Latest development version – from Github. Note that the command below installs the “master” (development) branch; if you want the release branch from Github add ref="release" to the install_github() call.

  # install.packages("devtools")
  devtools::install_github("UUPharmacometrics/xpose4")
  

Running Xpose 4

Start R and load xpose:

library(xpose4)
#> Loading required package: lattice

To use the classic menu system, type at the R command prompt:

xpose4()

Each function is independently available from the command line, once the Xpose library is loaded.

First we create a set of files from a NONMEM run

cur.files <- dir() # current files in temp directory

simprazExample() # write files from an example NONMEM run
new.files <- dir()[!(dir() %in% cur.files)]  # the new files created by simprazExample

Then we can import our files to Xpose

xpdb <- xpose.data(1) 

Display goodness-of-fit plots:

basic.gof(xpdb)

Clean up files that were created to show these examples:

unlink(new.files)

More help is available in the online documentation, which can be found by typing (for example) ?xpose4 at the R command line.

Don’t Panic

Andrew Hooker (andrew.hooker at farmaci.uu.se) should be able to get you an answer if you run into trouble. The website https://uupharmacometrics.github.io/xpose4/ should also be of help.

Release Schedule

Bugfix releases will be released regularly, fixing any problems that are found.

License

Xpose 4 is free software: you can redistribute it and/or modify it under the terms of the GNU Lesser General Public License as published by the Free Software Foundation, either version 3 of the License, or (at your option) any later version.

This program is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU Lesser General Public License for more details https://www.gnu.org/licenses/.

Known Bugs

None at present, but there will certainly be a few. Report them at https://github.com/UUPharmacometrics/xpose4/issues.