Model template

Select the Model template link in the left list.

Darwin_ModelTemp

Note that clicking the “Enable ADVANS” or “Enable Covariates” header collapses and expands the lists.

Darwin_ModelTempCollapse

Choose the type of parametrization: Micro or Clearance.

When Clearance is selected, ADVAN10 is removed from the ADVAN list.

Enable ADVANS

Check the boxes for any ADVANs to include in the search.

List of ADVANs:

ADVAN1 is a 1-compartment linear model

ADVAN2 is a 1-compartment linear model with first-order absorption

ADVAN3 is a 2-compartment linear model

ADVAN4 is a 2-compartment linear model with first-order absorption

ADVAN10 is 1-compartment model with Michaelis-Menten model elimination

ADVAN11 is a 3-compartment linear model

ADVAN12 is a 3-compartment linear model with first-order absorption

Each ADVAN with a checked box has a tab for specifying settings. Unchecking a box removes that ADVAN tab.

Darwin_ModelTempADVAN

For each parameter on an ADVAN tab, set the parameter and its corresponding Omega Presence:

None — Absent in all candidates

Present – Present in all candidates

Searched – May or may not be present

Parameters that are required for the selected ADVAN are set automatically to Present.

Enter the value for the Lower Bound, Initial Estimate, and Upper Bound of Theta and the Initial estimate of Omega in the first row to apply the entered value to all parameters.

Or

Enter different values for individual parameters in the corresponding row.

Check the Freeze all box in the first row to apply fix values for all parameters.

Or

Fix the values for a particular parameter by checking the Frozen box in the parameter’s row.

Enable Covariates

In the Enable Covariates section at the top right section of the window, check the box to enable a covariate.

To define a dependency between a covariate and a parameter in an ADVAN:

Go to the tab for the ADVAN.

Check the Show covariate box in the parameter row.

Darwin_ADVAN_Covariates

In the Covariates section, for each covariate that was enabled, set the Presence:

None — Absent in all candidates

Present – Present in all candidates

Searched – May or may not be present

Note:    Once the Covariates section is also visible, you can collapse the Thetas/Omegas section to clear up the display. Click the up arrow next to the Theta title or Omega title. (Expand the section again by clicking the down arrow next to either name.)

Select the Relationship of the covariate to the parameter. For the continuous covariate, choose from Exponential, Linear, or Power. For the categorical covariate, choose from Exponential or Linear.

Enter the value for the Lower Bound, Initial Estimate, and Upper Bound in the first row to apply the entered value to all covariates.

Or

Enter different values for individual covariates in the corresponding row.

Check the Freeze all box in the first row to freeze the values for all covariates.

Or

Fix the values for a particular covariate by checking the Frozen box in the covariate’s row.

The covariate Theta Name column is a concatenation of the parameter name, covariate name, and (for categorical covariates) the category value. Since NONMEM only supports letters, digits, or underscores (“_”) in theta covariate names, any non-valid symbols, such as a minus sign (“-”) or a period (“.”), found during the concatenation will be replaced with an underscore (“_”).


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