PK Automation

AutoPilot Toolkit supports automation of PK analyses through the use of the NCA model object’s out­put. The PK Automation settings in the user interface can be saved as a Phoenix project or template file for re-use. The PK analyses supported by AutoPilot Toolkit can also be retrieved as scenarios from the PKS.

Use one of the following to add a PK Automation object to a Workflow:

Right-click menu for a Workflow object: New > AutoPilot > AP Automation.
Or Main menu: Insert > AutoPilot > AP Automation.
Or right-click menu for a worksheet: Send To > AutoPilot > AP Automation.

An AP Automation object must have a source of input data assigned to it as a first step. When the input source is selected, AutoPilot Toolkit then creates the AP Automation user interface based on the input data.

Usually the Final Parameters table from an NCA model is mapped to the AP Automation object. In a trough automation project, on the other hand, the Observations dataset is used. Datasets from differ­ent operational objects can also be mapped to a trough automation project. For example, a worksheet that is created by the Column Transformation or Bioequivalence objects can be mapped to an AP Automation object as long as the worksheet contains valid data for trough automation.

When connected to an NCA object, the AP Automation object detects any changes to the NCA model and generates an alert. The AP Automation object does not correct the problem. It only alerts users that changes were detected in Sort Keys, Model Types, Dose Types, or Sparse settings. Users must revert their NCA changes or make the necessary changes to the AP Automation object. The Automa­tion object will be marked as “out of date” if changes to the NCA model are detected or if the NCA model input data is changed. In the latter case, the NCA model will also be marked as “out of date.”

Note:The reference treatment must exist in both the study worksheet and in the NCA model output in order for the PK Ratios and PK Statistics tables to be created. If the reference treatment does not exist in the NCA model output (due to less than two time points or invalid concentration values), then the two tables cannot be created and an error is displayed.

To change a source of input data

Once a source of input data is mapped to an Automation object, it can be changed by simply remap­ping the input to the new source. AutoPilot Toolkit will check the compatibility of the new source with the object.

This section contains the following topics:

List of output typesInput panel

Input panel

Table panels

Graph panels

General tab

Stratification/Normalization tab

Display tabs

Ordering tab

Automation results

See also:

 

“PK Automation tables” lists tables available for each combination of study design, dosing, regimen, and matrix.

“PK Automation graphs” lists graphs available for each combination of study design, dosing, and matrix.

“PK Automation appendix output” lists appendices available for each study design.

List of output types

The Setup tab consists of two areas, a hierarchical listing consisting primarily of output types avail­able for the AP Automation object selected in the Object Browser, and a panel area for displaying options specific to an item selected in the hierarchical list.

Setup_tab.png 

Note:Be sure to uncheck the Continuous Demographic graph if the study does not contain continuous demographic variables.

Selecting Tables in the hierarchical list is only possible when stratifications or exclusions are set, or when the input data is stacked by analyte.

Input panel

When an AP Automation object is inserted into a project, the input source must be assigned before the object can be used or modifications to object settings can be made. The input source can be mapped to an NCA Final Parameters worksheet or observations dataset.

Note:The units specified in a data set and in the NCA Model Options > Units tab must match in order for the output to make sense.

Or

In the Diagram tab, right-click an AP Automation object and select View Setup.

Input_panel_no_source.png 

In the previous figure, no input source has been defined, so the options available are restricted to selecting the source and specifying an alternative source for configuration settings (refer to “General tab” for more information on configuration settings).

Table panels

Users can set the variables, statistics, or precision for each table type. The options available depend on the type of table selected.

The following sections describe the table options available:

Main Tables panel

Variables and Statistics tabs

Standard/Normalize tab

Precision tab

Statistical Analysis option

Main Tables panel

The main Tables panel is only available if the input source is stacked by analyte, or when stratifica­tions or exclusions are set, and at least one individual table’s checkbox must be checked. The panel shows options that can be applied when generating the tables. The options vary depending on whether the source is stacked or if stratifications and/or exclusions are defined.

AP_Auto_stacked_data_main_Tables_panel.png 

Grouping is not available for the Demographics table.

Note:At least one stratified table must be selected if stratifications are specified or the object will not pass verification.

AP_Auto_unstacked_stratified_with_exclusions_main_Tables_panel.png 

See also:

Stratification/Normalization tab

Output Options tab for defining exclusions.

Variables and Statistics tabs

The Variables and Statistics tabs are formatted the same for most tables. See “PK Parameters” for a full list and descriptions of supported PK parameter study variables. See “Summary Statistics” for a full list and descriptions of supported statistics.

Note:The Variables tab may/may not be available, depending on the table type.

Variables and statistics that are in the Selected column will be included in the output and will be reported in the order that they appear in the column.

Variables_tab.png 

The following instructions apply to both the Variables tab and the Statistics tab.

Note:Selecting a large number of PK Parameters for statistics can generate a table that will not fit on a single page and the table-splitting option does not currently work for the PK Stats table. Choose only 7 or 8 parameters for this table. If you require more parameters to be listed, perform additional Automation runs for the additional desired parameters and generate only the PK Stats table

When PK Statistics are specified, the AutoPilot Toolkit object should be executed directly and not as part of the Phoenix workflow or the PK Stats table creation may fail.

Intext Table Statistics tab

The Statistics tab for Intext PK Parameter tables contains different options than Statistics tabs for other tables.

Intext_Table_Statistics_tab.png 

Note:Changes made to the non-time dependent and time dependent statistics options in one Intext table are copied to the other Intext table. For example, if Comparison Intext PK Parameter II Ana­lyte is selected in the Tables tab and the settings for A and B in the Non-Time Dependent Stats area are changed, the changes are automatically applied to the Comparison Intext PK Parameter I Analyte table.

Standard/Normalize tab

This tab becomes available for PK Parameter tables when normalization schemes are defined (see “Stratification/Normalization tab”).

Precision tab

For each variable and statistic, the precision can be set by the number of significant digits or decimal places. Selection of the type and value of numerical precision is also done through this tab.

Precision_1.png 

Precision_2.png 

Statistical Analysis option

An option is available for PK Ratios and PK Statistics tables to include inferential statistics calcula­tions and PK parameter ratios in order to produce additional output tables titled PK_Ratios and PK_Statistics. See “PK Automation tables” for descriptions of the tables.

The Reference can be selected in the PK Ratios and PK Statistics panels. The specified reference treatment will be used as the denominator in the ratio and inferential statistics calculations.

Reference_Treatment_menu.png 

Graph panels

AutoPilot Toolkit allows the user to apply different attributes to each graph. These attributes include Y-axis scaling, summary value display, error bar display, and regression line options. Selection of PK parameters to include in the graphs is also available.

The following sections describe the graph options available for each graph type:

Main Graphs panel

Time Concentration panel

Categorical Standard panel

Categorical Box and Whisker panel

Continuous Dose Standard panel

Continuous Dose Box and Whisker panel

Continuous Demographic panel

Main Graphs panel

Parameters that are in the Selected column will be included in the output.

PK_parameter_Graphs_menu.png 

Time Concentration panel

time_and_conc_graph_options_1.png 

time_and_conc_graph_options_2.png 

There are three types of Table Concentration graphs available:

Individual by Subject: A separate graph is generated for each subject involved in the study. Each line on the graph represents a separate treatment.

By Treatment: A separate graph is generated for each treatment performed during the study. Each line in the graph represents a separate subject. An additional Summary Value line may also be present.

Summary by Treatment: A single graph is generated. Each line represents a separate treat­ment.

The panel displays a table of options for the Time Concentration graphs, grouped into categories and sub-categories:

Output 

Time_Concen_Graph_Strat_Options.png 

Display 

Check/Uncheck the Graph box to use/not use the Y-axis scaling method. Checking boxes for both Linear and Log will generate two graphs, one using each method.

Available for By Treatment and Summary by Treatment types, select the statistic to use as the Summary Value when plotting the summary line: Mean, Median, Geometric Mean, Har­monic Mean, None.

Specify the Value (SD, SE, Variance, Min and Max, None, 68% Range) and Direction (Both, Down, Up) of error bars to display on Summary by Treatment graphs.

Time_Concen_Graph_Exclusion_and_Group_Options.png 

Individual: Specify the symbol to use when plotting individual subject data points on a By Treatment graph. Fixed Individual uses the same symbol for all the individual subject data, Variable Individual uses a different symbol for each individual subject’s data, None shows only the resulting line.

Summary: Specify the symbol to use when plotting the summarized data on a By Treatment graph. Fixed Summary displays the summary points on the graph using a symbol. None shows only the resulting line.

None: Do not display a legend.

Individual and Summary: Include the symbol for individual subject data points and the sym­bol for summary points.

Summary Only: Include only the symbol for summary points.

Categorical Standard panel

Categorical_Standard_Graph_Options.png 

The PK Parameters available in the study are listed as rows in the table.

The panel displays a table of options for the Categorical Standard graphs, grouped into categories and sub-categories:

Output 

If normalization schemes are also defined (see “Stratification/Normalization tab”), check/uncheck the Normalize subcategory boxes to normalize/not normalize the graphs.

Categorical_and_Continuous_Std_output_panel.png

 

If normalization schemes are also defined, check/uncheck the Normalize subcategory boxes to normalize/not normalize the stratified graphs.

Display 

The graphs are generated with a Linear scaled Y-axis.

Time_Concen_Graph_Exclusion_and_Group_Options_1.png 

Categorical Box and Whisker panel

Note:There must be at least three subjects in the study to create Box and Whisker graphs.

Categorical_Box_Graph_Options.png 

The PK Parameters available in the study are listed as rows in the table.

Output 

If normalization schemes are also defined (see “Stratification/Normalization tab”), check/uncheck the Normalize subcategory boxes to normalize/not normalize the graphs.

Categorical_and_Continuous_Std_output_panel_1.png

 

If normalization schemes are also defined, check/uncheck the Normalize subcategory boxes to normalize/not normalize the graphs.

Display 

Time_Concen_Graph_Exclusion_and_Group_Options_2.png 

Continuous Dose Standard panel

Continuous_Dose_Standard_Graph_Options.png 

The PK Parameters available in the study are listed as rows in the table.

The panel displays a table of options for the Continuous Dose Standard graphs, grouped into several categories and sub-categories:

Output 

If normalization schemes are also defined (see “Stratification/Normalization tab”), check/uncheck the Normalize subcategory boxes to normalize/not normalize the graphs.

Categorical_and_Continuous_Std_output_panel_2.png

 

If normalization schemes are also defined, check/uncheck the Normalize subcategory boxes to normalize/not normalize the graphs.

Display 

Select the statistic to use as the Summary Value when plotting the summary line: Mean, Median, Geometric Mean, Harmonic Mean, None.

Specify the Value (Min and Max, Pseudo SD, SD, SE, Variance, 68% Range) of the Error bars. The only option available for Direction is Both.

Continuous_Dose_Std_Exclusions_and_Group_Options.png 

Continuous Dose Box and Whisker panel

Note:There must be at least three subjects in the study to create Box and Whisker graphs.

Continuous_Dose_Box_Graph_Options.png 

The PK Parameters available in the study are listed as rows in the table.

Output 

If normalization schemes are also defined (see “Stratification/Normalization tab”), check/uncheck the Normalize subcategory boxes to normalize/not normalize the graphs.

Categorical_and_Continuous_Std_output_panel_3.png

 

If normalization schemes are also defined, check/uncheck the Normalize subcategory boxes to normalize/not normalize the graphs.

Display 

Continuous_Dose_Box_Exclusion_Options.png 

Continuous Demographic panel

Continuous_Demographic_Graph_Options.png 

The panel displays a section for selecting up to two demographic(s) to use for the X-axis (Demo­graphic 1 and Demographic 2).

When a second demographic type is selected, a second tab is created in the Continuous Demo­graphic panel.

Continuous_Demographic_Graph_2tabs.png 

The PK Parameters available in the study are listed as rows in the table. For each parameter, there are two sub-rows:

The lower part of the panel contains a table of options for the Continuous Demographic graphs, grouped into several categories and sub-categories:

Output 

 

If normalization schemes are also defined (see “Stratification/Normalization tab”), check/uncheck the Normalize subcategory boxes to normalize/not normalize the graphs.

Categorical_and_Continuous_Std_output_panel_4.png

 

If normalization schemes are also defined, check/uncheck the Normalize subcategory boxes to normalize/not normalize the graphs.

Display 

Continuous_Demographic_Exclusion_and_Group.png 

General tab

The General tab allows users to select the study design type, configuration settings, and whether or not to try to complete an automation run if an error occurs.

General_tab.png 

The study design options in the General tab depend on the configuration settings. If the settings are changed, then the options could be different from the options listed below.

Note:The configuration settings must be specified before a dataset is mapped to the AP Automation object.

Study Design 

Configuration Settings 

Stratification/Normalization tab

The Stratification and Normalization options allow users to create additional table and/or graph out­put.

Stratification-Normalization_tab.png 

Stratification 

Results can be stratified (i.e., layered) using discrete demographic variables. Each stratification level can use one or two discrete demographic variables. If two variables are specified, they are associated using the logical operator AND.

Note:At least one stratified output type must be selected if stratification is enabled or the Automation project will not pass verification.

If stratifications are selected, the automation run creates one table per stratum for the time and con­centration, PK parameter, and intext PK parameter tables, using the stratification scheme as an addi­tional group variable.

If graphs include stratification, the stratification schemes are used either as X-axis variables (sorted by treatment) or new sort variables (sorted by demographics), depending on the AutoPilot Toolkit Admin settings.

Normalization 

Use the Normalization section to define normalization schemes to apply to the results. Each normal­ization scheme must use a different continuous demographic variable.

AutoPilot Toolkit calculates the normalized PK parameters and includes them in the results. Users can select the PK Parameter, Intext PK Parameter, PK Ratios, and PK Statistics tables in the hier­archical list and choose which normalized parameters to display in each table. This allows PK Param­eter automation tables to include both normalized and non-normalized values.

For more on using the table panels, see “Table panels”.

Column headers for the normalized variables include a normalization variable and its units. For exam­ple, oral clearance normalized by weight: CL/F/Weight (L/hr/kg). If graph output is selected that includes normalization, each normalized PK parameter is displayed in a separate graph. The Y-axis labels display the normalization in the same manner as tables.

PK parameters that are excluded from normalization are listed in “PK automation parameters”.

Display tabs

The Display tab contains four tabs that allow users to set output and display options, table and graph orientation, and the X- and Y-axes scaling for graphs.

Output Options tab

Display Options tab

Orientation tab

Time Scale Algorithm tab

Output Options tab

The Output Options tab allows users to define exclusions, the LOQ value, and the AUC percent extrapolation threshold value.

Display_tab.png 

The options for LOQ vary depending on the type of data used and the system configuration set­tings.

To set the LOQ value using the input data, click Use setting from data.

To enter a value, click Use value and type a value in the corresponding field.

Click No limit of quantification to not set an LOQ limit.

If the input dataset contains stacked data, a different LOQ can be set for each analyte.

Display_-_Output_Options_tab_for_Stacked_data.png 

Turn on the Use LOQ values found in study data checkbox to set the values for LOQ using the input data.

Enter an LOQ value for each analyte in the Value column. (The concentration units are taken from the input dataset.)

To not use LOQ values, turn off the Use LOQ values found in study data checkbox and leave the Value column entries blank.

Note:If the LOQ is set to a value that exceeds all concentration values, no Concentration graphs will be created.

Setting the LOQ value for all analyts can significantly extend the execution time.

For more information, see “LOQ replacement”.

The following option is applicable to both stacked or unstacked input data:

See “PK parameter percent-extrapolated threshold” for details.

Excluded profiles from summary statistics

Excluded_Profiles_From_Summary_Statistics_dialog.png 

Every profile in the study data is displayed in the Profile list on the left of the dialog. Users can exclude complete or partial profiles. The variables used to create each profile are displayed in the Sort Columns list. Each profile contains a subject ID and one or more treatments. By default, each profile is listed by subject ID, and the treatment or treatments are listed beneath each subject.

For example, if the treatment is moved to the top of the Sort Columns list, then the Profile list dis­plays the treatment first and lists the subject IDs underneath the treatment.

Excluded_Profiles_From_Summary_Statistics_dialog_with_treatment_first.png 

Sort Columns rearrange the order in which profiles are listed on the left

Select the item being excluded.

Enter the information in the Reason for Exclusion area below the profile list.

Turn on the Apply Reason To All Exclusions if the entered information is applicable to all items selected for exclusion in the profile list.

Display Options tab

The Display Options tab allows users to set table and graph output display options, select the time and concentration variables in the input dataset, and choose whether or not to include data source information.

Display_-_Display_Options_tab.png 

For trough projects with unstacked input data, this option changes to Concentration Output (Variable Used) for Analyte. Use the first pull-down to select the analyte whose concentrations are to be reported and then continue with specifying the concentration variables for the tables and graphs.

Trough_Display_Options_tab.png 

Orientation tab

Through the Orientation tab, the orientation of each output item is set. A few additional settings regarding the appearance of graphs in a Word document are available for appendices involving indi­vidual time-concentration graphs.

Display_-_Orientation_tab.png 

Note:Only certain tables and graphs can be changed to Landscape. If Landscape is not supported, the Orientation setting for that table or graph defaults to Portrait and the pull-down menu is disabled.

For the Individual Time Concentration appendix output type, the following specifications can also be made.

All linear then all log: Display the linear graphs (sorted by subject) before the log graphs (sorted by subject).

All log then all linear: Display the log graphs (sorted by subject) before the linear graphs (sorted by subject).

Per profile, linear then log: Graphs are grouped by subject and then by analyte, with the lin­ear graph presented before the log graph. In the output, the graphs are displayed in subject order.

Per profile, log then linear: Graphs are grouped by subject and then by analyte, with the log graph presented before the linear graph. In the output, the graphs are displayed in subject order.

Time Scale Algorithm tab

The Time Scale Algorithm tab is used to specify the scaling options for the axes, the lower and upper bounds for time scale ticks, the tick frequency, the tick units, and the maximum time scale on the X-axis. See “Time scale algorithm” for more information.

Display_-_Time_Scale_Algorithm.png 

The Major Ticks area contains a table where each row represents a separate time scale.

Use the Tick frequency and Tick units columns together to define the frequency with which tick marks are displayed along the X-axis.

A new row is added to the table below the row that was selected or modified last.

A minimum of two defined time scales is required.

Ordering tab

The Ordering tab is used to specify how the treatment descriptions and demographic study variables are ordered in the output.

Treatments sub-tab 

 

Discrete Variables sub-tab 

The Discrete Variables tab contains the tools to reorder the attributes of any variables used for strat­ification.

Discrete_Variables_tab.png 

Note: If the first treatment does not contain a stratification value then the order chosen in the Discrete Variables tab for the stratification is ignored in the graph output.

Analytes tab

This tab is present only if the input data is stacked and lists all of the analytes involved in the study.

Note:Concentration table output will not maintain the order specified in this tab.

Automation results

Caution:Do not perform any operations on the computer while the automation run is in progress. Doing so could cause unpredictable results; keyboard and mouse input during an automation run might affect automated AutoPilot Toolkit operations.

After the project successfully completes, all output is arranged in groups in the Results tab.

Not all output can be viewed in Phoenix. In such cases, the right side of the Results tab will display a message with suggestions on how to view the results. One suggestion is to open an external program and load the results by clicking View in External Viewer.

The automation output can be individually exported to disk or copied to Phoenix’s Data folder. All results can be exported using the File Explorer, which is located in the Reporting tab. For more using the File Explorer, see “AutoPilot File Explorer”.


Last modified date:6/26/19
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