Release Notes MonolixSuite 2023R1

February 2023

This document outlines the release notes for MonolixSuite2023R1, detailing the new features, updates, and bug fixes introduced in the 2023R1 version.

NEW FEATURES

Licensing

• With cloud licenses, possibility to use https in addition to the already existing http communication

Global interoperability

Extended interoperability enabling exporting a PKanalix, Monolix, or Simulx run to any other application within the MonolixSuite. New export/import functionalities include:

• Exporting a PKanalix CA run to Simulx to predict individual responses to alternative dosing regimens.

• Exporting a Simulx run, Monolix individual fits, or VPC simulations to PKanalix for NCA on simulated data.

Global display

A new reporting module for generating reports automatically based on a custom Word template file:

• Placeholders can be inserted into any Word template and replaced with plots and tables from a PKanalix or Monolix run.

• Placeholders can be generated in the GUI for each plot and table and copied into the Word template.

• Placeholders for plots and tables can be customized to appear as desired in the report.

• Custom axis limits can be set for observed data and VPC plots.

• Trendlines (mean and standard error) can be merged for different groups on the same plot after splitting by a covariate in the plot Observed Data.

• Direct feedback on the software can now be sent from the interface of any MonolixSuite application.

Data set

A data formatting module in the interface for more flexible input formats:

• Merge several observation types from an input dataset.

• Add censoring information based on BLQ tags.

• Add treatment information from an external file or specify it manually with various options (multidose regimen, repeat cycles, infusions, combined therapies, amount depending on a category, use dose intervals as occasions, etc.).

• Add covariate and regressor columns from another file.

PKanalix

• Additional normalized units for the amount column, per body weight or body surface area.

• Use any model in CA, self-written in mlxtran syntax or from MonolixSuite libraries.

• Improved algorithm in CA to escape local minima and improve the fit.

• New cost function based on Generalized Least Squares for comparing models with AIC and BIC.

• New weighting option: 1/|Ypred*Yobs|.

• Individual cost reported in the individual parameters table, and a new Cost tab showing global cost, -2LL, AIC, and BIC.

• New Observations vs predictions plot for CA to diagnose the fit.

• Additional summary metrics: geometric CV and harmonic mean.

• Custom aliases for NCA parameter names and summary metrics names.

Monolix

• Coefficients of variation reported in addition to standard deviation of random effects in the table of population parameters.

• Easier sequential approach by adding PK parameters from another run as regressors to the dataset directly in the interface.

Simulx

• Mapping of simulated IDs to original identifiers in tables and plots.

• Merge simulated output distributions for different groups on the same plot.

• New elements created after importing a Monolix run to simulate the effect of covariates or parameter uncertainty on a typical individual.

• More post-processing possibilities for calculating outcomes such as duration below/above/between specific values, value of the output at a custom time, normalization relative to min/max values, and defining an outcome reporting time as continuous or event type.

• Conversion of an individual element to a population element in one click, and vice versa.

• Visual cues automatically switch to OFF after setting a visual cue.

Lixoft Connectors / Command Line

• New Monolix connector to run convergence assessment from R.

• New Simulx connectors to define and compute outcomes and endpoints as in the interface.

• New connectors covering new features available in the interface (formatData, generateReport, getCACost).

• New function reportGenerator to generate reports directly from the command line.

• New connector to select a library model using the same filters as in the GUI.

• Improved error and warning messages for non-recognized arguments.

• Extensive documentation of Simulx connectors with detailed descriptions and working examples for every function.

• setConsoleMode (displaying the progress of computations as in the GUI) now available for Simulx and PKanalix.

UPDATES

• The ODE solver CVODE upgraded to version 5.5.

BUGS FIXED

Global interoperability

• Slow file export when exporting to a shared drive has been fixed.

Global display

• Dosing times set as always visible disappeared when removing dots and lines.

• Axis limits based on dots even if dots were not displayed on the plot.

• "Random colors" option not working for all plots.

• Legend not properly updated when going from one page to another in a paginated plot.

• Parameters displayed when selecting a model from the library were not always the input parameters of the model.

Data set

• In some cases, '1' in the CENS column was considered as right censoring instead of left.

• Stratification covariates did not appear in the covariate statistics tab.

PKanalix

• Acceptance criteria used to filter individuals even for parameters that do not use lambda_z.

• It was not possible to remove partial parameters from the list of computed parameters if partial AUC was selected.

• IDs and occasions displayed as double instead of integers in the table of individual estimates.

• PKanalix crashed when reloading a project where Cc was used as a header in the dataset.

• Significant digits did not apply to all values in result tables.

Monolix

• Observation models other than normal distribution were not handled correctly by the auto-initialization algorithm.

• Names of error parameters based on default observation names and not modified if observation names were changed manually.

• Vertical scroll bar disappeared when a formula was displayed.

• Selecting and then unselecting "time after last dose" did not bring back to the same state in terms of bins.

Sycomore

• NaNs for RSEs were not displayed, and cells appeared empty in the comparison tab.

• Folder and "scan" button did not appear when selecting a folder containing only one mlxtran file.

Simulx

• Inter-occasion variability was not taken into account when there was only one occasion period.

• Endpoints summary tab appeared in the results even if there were only one replicate.

• Renaming outcome duplicated the result in group comparison summary.

Lixoft Connectors / Command Line

• getChartsData computed charts data for all plots even if a specific plot was requested.

• Option to scale treatment by a covariate was available in the GUI but not in the connector.

• Crash instead of an error when trying to set a population parameter element with several lines.

• Error when setting several elements to the same simulation group.

• Option --no-gui was not taken into account if option -t monolix was used.

• newProject did not work with modelFile="lib:...".

• deleteOccasionElement deleted mlx_Cov if no occasions were present in the project.

• setData (and functions of Rsmlx that use it: bootmlx, confintmlx) did not properly set the data on some machines in certain cases, giving the error "Inconsistent observation names between observation types and data file inputs".

• Occasion-wise definition of common elements did not properly take into account the occasion column.

• getTreatmentElements() returned a truncated number of lines.