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

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.