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FAQ

We list here the questions regarding the use of Monolix when everything runs fine. If you have an issue with download, installation, run and display, please check Frequent installation issues.

If you think there is a bug in one of the MonolixSuite apps, please check if it is already in our List of known bugs, and otherwise write us at support@lixoft.com.

Regulatory

  • What is needed for a regulatory submission using Monolix? Monolix is used for regulatory submissions (including the FDA and the EMA) of population PK and PK/PD analyses. The summary of elements needed for submission can be found here.

  • How to cite Monolix, Simulx or PKanalix? Please reference each application as here (adjusting to the version you used):

CODE 
Monolix 2024R1, Simulations Plus
Simulx 2024R1, Simulations Plus
PKanalix 2024R1, Simulations Plus

Running Monolix

  • On what operating systems does Monolix run? MonolixSuite runs on Windows, Linux and MacOS platform. The requirements for each platform can be found on our download page.

  • Is it possible to run Monolix using a simple command line? Yes, see here. In addition, there is a complete R API providing the full flexibility on running and modifying a Monolix project.

  • When trying to re-open a project, I get an error “Parse error in (file location), line XX: Expected STRING, but the actual syntax is a TREE_LIST.”. This happens when trying to open with version 2023 a Monolix project saved with version 2024. The mlxtran file saved in version 2024 contains syntax elements that are new and not known by the 2023 version.

Initialization

  • How to initialize my parameters? There are several ways to initialize your parameters and visualize the impact. See here the different possibilities.

Results

  • Can I define myself the result folder? By default, the result folder corresponds to the project name. However, you can define it by yourself. See here to see how to define it on the user interface.

  • What result files are generated by Monolix? Monolix proposes a lot of different output files depending on the tasks done by the user. Here is a complete listing of the files along with the condition for creation. See here for more information.

  • Can I replot the plots using another plotting software? Yes, if you go to the menu Export and click on “Export charts data”, all the data needed to reproduce the plots are stored in text files. See here for the description of all the files generated along with the plots.

  • When I open a project, my results are not loaded (message “Results have not been loaded due to an old inconsistent project”). Why? When loading a project, Monolix checks that the project (i.e all the information saved in the .mlxtran file) being loaded and the project that has been used to generate the results are the same. If not, the error message is shown. For instance if one runs a project, then do “use last estimates”, save and try to reload the project, the saved project has the “last estimates” as initial values which are different from the initial values used to run and generate the results. In that case the results will not be loaded because they are inconsistent with the loaded project. This is also explained with some examples in this video.

    It is possible to check what is preventing the load of the results by comparing the content of the .mlxtran file to load and the .mlxtran file located in the hidden .Internals folder in the result folder. To see the .Internals folder, the “show the hidden files/folders” must be activated on the machine.

  • Are the results of Monolix reproducible if I rerun the same analysis? Yes, see here for more information.

  • The Observed data plot or VPC plot is emtpy or with non-appropriate axis limits
    The problem appears after having clicked “Export > Export charts settings as default” on a previous project where the y-axis limits were different and this is now applied as default. It is possible to delete the default setting corresponding to the axis limits in the following way:

    • Open the file C:/Users/<username>/lixoft/monolix/monolix2023R1/config/settings.default in a text editor

    • Delete the following lines:

      CODE 
      VPCContinuous\yInterval= ...
outputPlot\yInterval= ...

    • Save the file

    • Reopen your project

  • Where can I find the epsilon-shrinkage? The epsilon shrinkage (for the residual error) is not calculated by Monolix. However, it is possible to calculate it using the result file predictions.txt with the following R code:

    pred <- read.csv("predictions.txt")

    epsilon_shrinkage = 1 - sd(pred$indWRes_mode)

Tasks

  • How are the censored data handled? The handling of censored data is described here.

  • How are the parameters without variability handled? The different methods for parameters without variability are explained here.

  • What is the convergence indicator, displayed during SAEM? Its meaning and function is explained here.

  • When estimating the log-likelihood via importance sampling, the log-likelihood does not seem to stabilize. What can I do? The log-likelihood estimator obtained by importance sampling is biased by construction (see here for details). To reduce the bias, the conditional distribution pϕi|yi

  •  should be known as well as possible. For this, run the “conditional distribution” task before estimating the log-likelihood.

Model definition

  • Is it possible to use time-varying covariates? Yes, however the covariates relationship must be defined in the model instead of the GUI. See here how to do that.

  • Is it possible to define complex covariate-parameter relationships such as Michaelis-Menten for instance? Yes, this can be done directly in the model file. See here how to do it.

  • Is it possible to define a categorical covariate effect on the standard deviation of a parameter? Yes, this can be done directly in the model file. See here how to do it.

  • Is it possible to define mixture of structural models? Yes, it may be necessary in some situations to introduce diversity into the structural models themselves using between-subject model mixtures (BSMM) or within-subject model mixtures (WSMM). The handling of mixture of structural models is defined here. Notice that in the case of a BSMM, the proportion p between groups is a population parameter of the model to estimate. There is no inter-patient variability on p: all the subjects have the same probability and a logit-normal distribution for p  must be used to constrain it to be between 0 and 1 without any variability.

  • Is it possible to define mixture of distributions? Yes, the handling of mixture of structural models is defined here.

  • Can I set bounds on the population parameters for example between a and b? It is not possible to set bounds for the estimated population parameters. However it is possible to define bounded parameter distributions, which as a consequence also bound the estimated fixed effect parameter. See here how to do it.

  • Can I put any distribution on the population parameters? Not directly through the interface. Using the interface, you can only put normal, lognormal, logitnormal and probitnormal. However, you can set any transformation of your parameter in the EQUATION: part of the structural model and apply any transformation on it. See here how to do it.

  • Can I set a custom error model? No, this is not possible. It may however be possible to transform the data such that the error model can be picked from the list. For an example with a model-based meta-analysis project, see here.

  • What are the units of estimated parameters? Can I define a scale factor? The units of the estimated parameters depend on the units of the data set and are implicit. Check here to learn how to include a scale factor.

Tricks

  • How to compute AUC, time interval AUC, … using Mlxtran in a Monolix project?  See here.

Export

  • How to export to Datxplore, Mlxpore and Simulx?

  • I exported the chart settings as default, how can I come back to the default Monolix settings for all plots? Delete the file <home>/lixoft/monolix/monolix2020R1/config/settings.default . In windows, the path to the <home> folder is C:\Users\<username>.

Reporting

  • How can I include plots and table from different Monolix projects into the same Word document? It is currently not possible to include plots and tables coming from different Monolix runs into the same Word document in one step. You can add placeholders to an already generated report and use it as a template for another project, however we are aware that this is not a very convenient solution. If generating a single report for several projects is important for you, please let us know so that we take it into account for future versions.

  • The report I generated via command line or via R do not contain plots. This is a known limitation of the current implementation of the reporting feature.

Legacy Documentation

  • Can I still access the documentation for versions prior to 2016?

Please check Legacy Documentation.

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