Paliperidone Example
paliperidone_example.Rmd
Usage
The Certara.SimcypVBE
package contains an example
SimcypTM V23 workspace file PP1M_150mg.wksz
for
Paliperidone Palmitate and an observations data file
PP.xml
. After installing the Certara.SimcypVBE
package, the files will be available inside your R library folder, in
the subfolder Certara.SimcypVBE/examples
.
To identify your R library folder, run the .libPaths()
command from R. The first path will likely be your R user library, and
the second path your R site library.
Pro-tip, you can open any folder location in R using the
browseURL()
command.
In the next step, we will copy these files into a separate folder (e.g., your working directory in Pirana).
Run Simcyp VBE from Pirana
In Pirana, navigate to the folder where the example files have been
copied. This is considered your “Pirana root directory”, and while not
required, it is best practice to have any files used in your analysis
saved inside this folder (e.g., the wksz
and
xml
files).
Next, ensure that you are in the vbe
context menu and
have All folders
selected.
Then, select Models > New Model (or use the shortcut Ctrl + n) to launch a Pirana dialog to select the example files for the VBE analysis.
Select the location of the wksz
and xml
files. Finally, select the “Create” button to launch the Shiny
application.
Generate reference group results
The initial simulation with the supplied wksz
file is
often assumed to be the “reference group”. To simulate with given inputs
supplied in the original wksz
, navigate to the Simulate top
level menu, and select the “Simulate” button in the left sidebar.
Note: The observation data points from the xml
file
will be visible in the plot, even if no simulation has yet been
performed.
Next, ensure the “Virtual Population” radio button is selected (optionally edit the number of subjects from the default value of 10). Finally, ensure the “Reference” radio button is selected, then select the “Run” button to run the simulation.
Navigate to the Results > Virtual Population tab to visualize results.
Perform sensitivity analysis
For the Paliperidone example PP1M_ 150mg.wksz
, the key
inputs in the Shiny application to vary for sensitivity analysis include
the Polydispersed Particle Size Distribution (PSD), which is in the
Formulation Index subsection of Substrate > Absorption.
Navigate to this section in the Shiny application and enter a comma
separated list of values or a sequence statement e.g.,
seq(0.1,0.9, 0.1)
as illustrated in the inputs below.
Next, navigate back to the simulate tab - you will see an expanded grid of all parameter combinations given the input values you have entered.
Select the “Simulate” button in the left side bar and select the “Sensitivity Analysis” radio button. This perform simulation for a representative subject in the population, for each iteration of the unique parameter combinations.
Navigate to the “Results” tab in the left side bar and preview sensitivity analysis results from the “Sensitivity Analysis” tab.
You can select a row in the table below for a given iteration to observe the best fit through the data.
Generate test group results
Next, we will perform a virtual population simulation for our test group using Iteration 9 of our parameter combinations. We can select the “Simulate” button in the table for the given row, or, select the Simulate button in the left sidebar as we did previously.
Ensure that the “Test” radio button is selected, and that you have selected the correct iteration in the table that you want to use for the simulation. Finally, select “Run”.
Navigate back to the “Results” tab in the left sidebar and select the “Virtual Population” tab to view new simulation results for the test group. Select “Save & Exit” to close the Shiny application and return to Pirana.
Click the “refresh” icon in Pirana and you will see that the vbe
output folder has been attached to the vbe model object in the Pirana
table. Additionally you will see that the
{vbe_name}_reference_group.csv
and
{vbe_name}_test_group.csv
files have been copied to the
Pirana root directory and renamed.
Note: These files are additionally available inside the
simcyp_vbe_output_{n}
subfolder with a timestamp, allowing
you to create multiple test/reference combinations inside the Shiny app
for exploration, however, only the last generated files are copied to
the Pirana root directory and renamed accordingly e.g.,
{vbe_name}_reference_group.csv
and
{vbe_name}_test_group.csv
.
Navigate to the Pirana scripts tab, with the {vbe_name}
selected in the Pirana table (also ensuring that the corresponding
{vbe_name}_reference_group.csv
and
{vbe_name}_test_group.csv
files are indeed available in the
Pirana root directory as visible in above screenshot), you can double
click a script name or right-click > run script to generate the
corresponding plot output.