IntiQuan AZ Workshop

Dear Participant,
thank you for your interest in the workshop!
There are no requirements for the participation at the workshop. You can just sit, listen, and relax while we present you state-of-the-art modeling and simulation approaches using R. If you, however, would like to obtain some hands-on experience, you are invited to bring a computer and make some prior preparations, listed below. The "Required preparations" take about 5-10 minutes. The others not much longer.
Note that during the workshop we will not have time to perform the setup of individual computers. But we are available via email (info@intiquan.com) to support you in the 2 weeks prior to the Workshop. You can also contact Giovanni to help you with it.
We are looking forward to a good and interactive Workshop!

Henning in behalf of The IntiQuan Team

Workshop Outline

The workshop material has been prepared and the outline is shown below. Nevertheless, the goal is to have an interactive workshop that allows us to also deviate from the prepared material to target specific questions and interests from the audience.

Morning session
- PK, PBPK, PKPD, and QSP modeling in Shiny - getting familiar with the model description syntax
- Behind the “Shiny scene”: IQR Tools
  - How to define and simulate models
  - Script based NLME parameter estimation in NONMEM, MONOLIX & NLMIXR
  - Generation of report-ready model diagnostics, parameter estimates tables, and model development tables
Afternoon session
- Robust parameter estimation in QSP based on sensitivity equations and multi-start optimization
- Hands-on examples
- Analyzing QSP models, informing modeling decisions, using profile likelihood
- Reporting to Microsoft Word

Required preparations

Windows users: need to install Rtools. Version 3.4 or 3.5 is a good choice at the moment - but check against your R version. The correct installation of Rtools can be tested by typing the following in R:
```
     install.packages("devtools")
     devtools::has_devel()
```
The last command should return "TRUE". Note that if "TRUE" is not returned, the installation of the IQRtools below will not work. If unsure how to install it, this is how we typically install it on our Windows machines: Installation_Guide_Rtools.pdf.
Installation of the newest IQRtools R package
- Open RStudio
- Execute:
```
     source("https://iqrtools.intiquan.com/install.R")
     installVersion.IQRtools(forceDependencies=TRUE,attemptNLMIXRinstall=TRUE)
```
  If your operating system is Redhat 6 or Centos 6, specify the additional argument centosRedhat6=TRUE as shown below:
```
     installVersion.IQRtools(forceDependencies=TRUE,attemptNLMIXRinstall=TRUE,centosRedhat6=TRUE)
```
  These installation commands will attempt to also install the supported version of NLMIXR. If this should fail and you are interested in running the NLMIXR examples during the workshop, ensure version 1.0.0.7 of NLMIXR is installed.
- After finishing of installation, execute in R:
```
     library(IQRtools)
     test_IQRtools()
```
  If an output resembling a data.frame is shown then IQRtools is correctly installed.
If you experience any issues, contact us and we will help you.

Recommended preparations

Interfacing NONMEM with IQR Tools
- Windows users:
  - It is assumed that NONMEM 7.3 or 7.4 is installed using the NONMEM provided installer using default settings. If this is the case then nothing needs to be done.
  - If you have a custom installation of NONMEM on Windows (or want to check that the default settings are correct), execute in R:
```
     library(IQRtools)
     setup_IQRtools()
```
    and update lines 54 and 55 as follows: Comment out the line that does not match your NONMEM version. If you have both versions of NONMEM installed, keep both. If you have a newer or older version of NONMEM as well, you can add additional lines in a similar style. Ensure that the paths to the *.bat files do exist or change them to match the NONMEM installation on your system.
  - For the purpose of the workshop, assign empty strings ("") to the list items in lines 65 and 66.
  - Save and close the setup file again.
  - If you cannot complete this step check with your system administrator or contact us.
- Linux/Mac users:
  - It is assumed that a command is available on your system that allows to execute NONMEM in the following syntax: "COMMAND CONTROL OUTPUT".
  - Execute in R:
```
     library(IQRtools)
     setup_IQRtools()
```
    and update lines 32 and 33 as follows: Comment out the line that does not match your NONMEM version. If you have both versions of NONMEM installed, keep both. If you have a newer or older version of NONMEM as well, you can add additional lines in a similar style. Ensure that the character strings define the correct commands for calling NONMEM on your system.
  - For the purpose of the workshop, assign empty strings ("") to the list items in lines 44 and 45.
  - Save and close the setup file again.
  - If you cannot complete this step, check with your system administrator.
Interfacing MONOLIX with IQRtools
- Windows users:
  - It is assumed that MONOLIX 2016R1, 2018R1 or 2018R2 is installed.
  - Execute in R:
```
     library(IQRtools)
     setup_IQRtools()
```
    and update lines 105-107 as follows: Comment out the line that does not match your MONOLIX version. If you have all versions of MONOLIX installed, keep all. Ensure that the paths to the monolix.bat file on your system is entered for 2016R1 and/or the path to the 2018R1/R2 installation folder for 2018R1/R2.
  - Save and close the setup file again.
  - If you cannot complete this step check with your system administrator or contact us.
- Linux/Mac users:
  - It is assumed that MONOLIX 2016R1, 2018R1 or 2018R2 is installed.
  - Execute in R:
```
     library(IQRtools)
     setup_IQRtools()
```
    and update lines 97-99 as follows: Comment out the line that does not match your MONOLIX version. If you have all versions of MONOLIX installed, keep all. Ensure that the paths to the monolix.bat file on your system is entered for 2016R1 and/or the path to the 2018R1/R2 installation folder for 2018R1/R2.
  - Save and close the setup file again.
  - If you cannot complete this step check with your system administrator.

Optional preparations

Installation of IQReport to allow generation of Word reports
This is only available for Windows (64 bit) and Linux. Mac is not supported at this point in time.
- Follow instructions on https://iqreport.intiquan.com
- Execute in R:
```
     library(IQRtools)
     setup_IQRtools()
```
  Windows: on line 125 provide the full path to the IQReport.exe file.
  Linux: on line 123 provide the full path to the IQReport.sh file
Installation of IQRsbml to allow import of SBML models to R
This is only available for Windows (64 bit). Mac and Linux are not supported.
- Follow instructions on https://iqrsbml.intiquan.com
- Execute in R:
```
     library(IQRtools)
     setup_IQRtools()
```
  On line 133 provide the full path to the IQRsbml.exe file.