Download and Installation | MonolixSuite Documentation

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Requirements

Quarto version 1.4 or above. Note that lower Quarto versions will generate documents with improperly rendered inline R code and table captions and cross-references.
MonolixSuite 2024R1 or above
lixoftConnectors 2024.1 or above
R packages: ggplot2, flextable, ggpubr, quarto

Functions overview

The R scripts provide a set of functions to perform a standard conc-QTc analysis from data preparation to report generation. The main functions are:

process_QTcData(): format an input dataset for analysis by averaging triplicates, extracting baseline values, calculating QTc, etc
generateAllQTcProjects(): generate Monolix projects to run a conc-QTC analysis using the standard linear model as well as alternative non-linear models
quarto_render(input = "../_mlxQTcTools/QTc_quarto_allModels.qmd"): generate a report (e.g as Word document) using a Quatro template. The report contains exploratory data analysis plots, assessment of key modeling hypotheses, and modeling results.

See the detailed documentation of each function.

Using the R scripts

The code is open and can be adjusted to the users needs. In order to use the code, download the .zip file, and unzip it to a convenient location. Note that MonolixSuite and the lixoftConnectors R package must be installed as well. Before calling the functions, the mlxQTcTools.R file should be sourced. See the examples for more details.

source('path_to_unzipped_location/_mlxQTcTools/mlxQTcTools.R')

Included files

The .zip is organized in the following way:

_mlxQTcTools: contains the scripts to run the analysis
- mlxQTcTools.R: contains the functions process_QTcData() and generateAllQTcProjects(), as well as auxiliary functions.
- mlxReportingTools.R: contains auxiliary functions to generate the Quarto report
- QTc_quarto_allModels.qmd: Quarto template for the report
- models: contains the structural models to create Monolix projects in case of ΔQTc and ΔΔQTc with no effect, linear, Emax, Hill, or Logarithmic effect, with or wihtout effect compartment to create a delay.
Example_XXX: one folder per example dataset

Change log

Version 1.3 (lastest version)

support of datasets without placebo
support of datasets with time-matched baseline (in addition to predose baseline which was already supported)
support of additional categorical variables in the linear model, for instance to handle data over multiple days and add a "day" factor
support of additional variable used for stratification of plots in the report
population QT correction with estimated coefficient
for models with delay, added a security on the tau0 parameter and changed to stiff ODE solver
added correlations between random effects for dQTc models, to implement an unstructured covariance matrix
replaced the inline r code syntax from `{r}` to `r` to support Quarto versions before 1.4
improved loadProject() check to handle different output types (NULL or logical) in different lixoftConnectors versions
fixed a typo in the formatted dataset name for the Dofetilide example
added examples for time-matched datasets and datasets over multiple days

Version 1.2

replaced .csl file referring to online website for bibliography style by self-contained .csl file which does not require internet access
improved the check leading to the error "There must be at least a Monolix run named ddQTc_Linear.mlxtran in the folder” on linux system due to different behavior of file.exists() in windows and linux
improved the error message "The Monolix run ddQTc_Linear.mlxtran could not be loaded." to explain possible reasons
improved the check leading to "The Monolix run ddQTc_Linear.mlxtran could not be loaded." to handle loadProject() returning either NULL or a logical depending on the MonolixSuite versions
added a check if connectors are not initialized with version 2024 in the .qmd file