Simulation is useful for situations where modelers have PK/PD parameter estimates from prior modeling and want to explore the potential impact of modifying certain conditions, such as dosing regimens, without having to collect more data. Simulations are based on the structural model and its parameter values.
Simulation can be performed with built-in, graphical, or textual models. For built-in and graphical models, PK/PD parameter values must be entered in the Parameters window. All engines bypass fitting in this mode (for Naive pooled, the variance inflation factor computation is done).
A Monte Carlo population PK/PD simulation is performed based on the values provided for Theta, Omega, and sigma. If a table is requested, two separate simulations are performed automatically, one simulation for the predictive check and another simulation for each table.
With Simulation selected from the Run Mode pulldown, select the OPTIONS tab.
Except for the following, descriptions for the other options can be found in the “Simple” run mode section.
For population models:
In the Seed Number field, enter an initial seed value for the random simulation instead of using a random seed.
Specify the number of simulated replicates to be generated in the Number of Replicates field. The maximum number of replicates allowed is 10,000.
Click Advanced Options to show/hide available advanced options.
The following options are available for Individual modeling:
Enter the amount of perturbation to apply to parameters to obtain partial derivatives in the Step Size to Calculate Partial Derivative field.
In the Number of Time Steps to Output Partial Derivative field, enter the number of time steps.
Plots of partial derivatives are spaced at this number of time values over the whole timeline. To get a coarse plot, specify a low number. To get a smoother plot, specify a larger number of steps.
The following options are available for both Population and Individual modeling:
In the ODE Rel. Tol. field, enter the relative tolerance value for the ODE solver.
In the ODE Abs. Tol. field, enter the absolute tolerance value for the ODE solver.
In the ODE Max Step field, enter the maximum number of steps for the ODE solver.
The TABLES tab provides tools for adding simulation tables to the run.
Click the Add Table + button.
For every simulation table added here, there is a results worksheet generated. The options available for a simulation table are described in the Simple run mode “Tables” section, except for the following options:
Click Structural below the table to add the parameters defined in the model stparm statement to the Variables field.
For Individual modeling, the following options are also available in the TABLES tab.
Enter the number of simulated data points to generate for the dependent variables in the Number of Simulation Points field.
The maximum number of simulation points allowed is 1,000. The value entered applies to all dependent variables.
Use the Maximum X Range field to specify the maximum independent variable value used in the simulation.
In the Y Variables field, specify the desired output variable(s) to capture from the model.
The captured variable(s) is displayed, in # points equal time/X increments, in the simulation worksheet. For example, entering 100 in the Number of Simulation Points field, 20 in the Maximum X Range field, and C, E in the Y variable(s) field simulates a PK/PD model that has 100 data points for C (concentration) and E (effect) between time zero and time 20.
Check the Simulation at Observations box to have the simulation occur at the times that observations happen as well as at the given time points.
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