phoenix winnonlin 8.0 release notes - certara · 2021. 2. 10. · phoenix® 8.1 release notes...

Phoenix® 8.1

Release Notes

June 2018

Contents

Installation Notes .................................................................................................................2

Phoenix Product Interoperability .........................................................................................2

Certara® Contact Information ..............................................................................................2

What’s New .........................................................................................................................3

AutoPilot Toolkit ............................................................................................................ 3

Data Tools and Plots ....................................................................................................... 4

Framework ...................................................................................................................... 7

NLME ............................................................................................................................. 7

Validation Suite .............................................................................................................. 8

WinNonlin ...................................................................................................................... 9

Issues Corrected .................................................................................................................10

CDISC Navigator .......................................................................................................... 10

Data Tools and Plots ..................................................................................................... 11

Framework .................................................................................................................... 13

IVIVC ........................................................................................................................... 16

JMS ............................................................................................................................... 16

NLME ........................................................................................................................... 16

Validation Suite ............................................................................................................ 18

WinNonlin .................................................................................................................... 18

Known Issues .....................................................................................................................20

AutoPilot Toolkit .......................................................................................................... 21

Data Tools and Plots ..................................................................................................... 33

Framework .................................................................................................................... 38

IVIVC ........................................................................................................................... 44

JMS ............................................................................................................................... 50

Phoenix Licensing Wizard ............................................................................................ 50

NLME ........................................................................................................................... 50

Validation Suite ............................................................................................................ 55

September 2020: Added known issue QC 18053.

Revised September 2020

WinNonlin .................................................................................................................... 55

Phoenix® 8.1 Release Notes Installation Notes - AutoPilot Toolkit

Revision 1 of 58 September 2020

Installation Notes

To activate named user local machine licenses, use the Preferences dialog in

Phoenix.

To activate named user server licenses, use the Phoenix Licensing Wizard,

which can be downloaded using a link from the purchase order email. To view

and manage licenses on the server, use the WlmAdmin.exe tool that is located

in the license server installation directory, by default in C:\Program Files

(x86)\Pharsight\Licensing\Server.

The Phoenix installer only checks for an installation of the previous version to

notify the user that they need to uninstall it. There is no check on whether the

user has versions installed that are older than the previous version. So for

Phoenix 8.0, users with Phoenix 1.4 or prior need to manually uninstall using

Start > Certara > Uninstall Phoenix or the Control Panel, before installing

Phoenix 8.0 (QC 17320).

Use the Remove or Install options to uninstall the previous version. The

Modify feature within the Phoenix installer cannot uninstall Phoenix.

When installing on a Windows 8.1 machine that had Phoenix previously

installed, the MPI service registration must be done manually. To do this, opena command prompt with administrator privileges (Run as Administrator) and

navigate to the C:\Program Files (x86)\Certara\MPICH2\bin

directory. Type the command: smpd –install

Phoenix Product Interoperability Phoenix 8.1 is compatible with the PKS 4.0.3.

Phoenix can co-exist on the same workstation and can run independently with Trial

Simulator 2.2.2.

Certara® Contact Information

Technical support

Consult the software documentation to address questions. If further assistance is

needed, contact Certara Support through e-mail or our website. E-mail: [email protected]

Web: support.certara.com/support

For the most efficient service, e-mail a complete description of the problem, including

copies of the input data.

User forum.

Get tips and discuss Certara software with other users at:

https://support.certara.com/forums

mailto:[email protected]?subject=Phoenix%20support

https://support.certara.com/support

https://support.certara.com/forums/

Phoenix® 8.1 Release Notes What’s New - AutoPilot Toolkit

Revision 1 of 58

What’s New

AutoPilot Toolkit .................................................................................................................3

Statistics .......................................................................................................................... 3

Tables .............................................................................................................................. 3

Data Tools and Plots ............................................................................................................4

Descriptive Statistics ....................................................................................................... 4

Documentation ................................................................................................................ 4

Plots/Charting ................................................................................................................. 5

Tables .............................................................................................................................. 6

Framework ...........................................................................................................................7

Documentation ................................................................................................................ 7

NLME ..................................................................................................................................7

User Interface .................................................................................................................. 8

Validation Suite ...................................................................................................................8

WinNonlin............................................................................................................................9

AutoPilot Toolkit

Statistics

2.5 and 97.5 have been added to the standard percentiles (QC 9747 Phoenix).

New Sum statistic added (QC 10719 Phoenix): This new statistic computes the sum

of the values in the column mapped to Summary. If a weight variable is used, then

Sum is computed as the sum of the values in the column mapped to Summary

multiplied by the values in the column mapped to Weight, i.e., SUM(wi * xi).

New Geometric SD statistic added (QC 11125 Phoenix): This new statistic is

computed as exp(SD Log).

A stacked Units column is now added when more than one Summary variable is

mapped and the unit is not the same (QC 12166 Phoenix /CRM 151540): When

more than one Summary variable is mapped, at least two of those variables have units

in the input dataset, and the units differ, a stacked Units column is now included in the

output.

Tables

Applying sample size rule using raw values is now configurable in the

Administration user interface (QC 3885).

September 2020

Phoenix® 8.1 Release Notes What’s New - Data Tools and Plots

Revision 1 of 58

Data Tools and Plots

New Ratios and Differences Operational Object available (QC 17477): The

Ratios and Differences object in Phoenix is a data manipulation tool that is used to

compare data from either one or two worksheets by computer ratios or differences. It

is part of the Data group of objects. In Pharmacokinetics, ratios are often computed

for observation data collected under two different scenarios and for resulting final

parameters from two NCA or Modeling executions.

Descriptive Statistics

User-specified percentiles now allowed (QC 8881): A User Percentiles option has

been added to the Options tab. Check the checkbox and enter the percentile(s) to be

computed.

2.5 and 97.5 have been added to the list of standard percentiles calculated (QC

9747).

New Sum statistic added (QC 10719): This new statistic computes the sum of the

values in the column mapped to Summary. If a weight variable is used, then Sum is

computed as the sum of the values in the column mapped to Summary multiplied by

the values in the column mapped to Weight, i.e., SUM(wi * xi).

New Geometric SD statistic added (QC 11125): This new statistic is computed as

exp(SD Log).

A stacked Units column is now added when more than one Summary variable is

mapped and the unit is not the same (QC 12116/CRM 151540): When more than

one Summary variable is mapped, at least two of those variables have units in the

input dataset, and the units differ, a stacked Units column is now included in the

output that repeats the units of the Summary variables.

Descriptive Stats Options tab now has a hierarchical listing of the available

statistics with checkboxes to allow users to select the ones to include in the output

(QC 16242).

The statistic “CV% Geometric Mean” is now called “Geometric CV% (QC

16852): This change is to better match conventions in the literature and to clarify that

this statistic is not the CV of the Geometric Mean.

Documentation

Several sections in the User’s Guides have moved to improve usability (QC

17408):

September 2020


Revision 1 of 58

Documented examples for the Table object have been moved from the Phoenix

WinNonlin User’s Guide to the Data Tools and Plots Guide, in which the

Table object is described.

The Reporter chapter that was located in the Third Party Tools User's Guide

has been added to Data Tools and Plots Guide.

Plots/Charting

New Quick Styles option allows lines and markers to be colored by Group (QC

30): Checking the Each Group by Color checkbox in the Quick Styles tab causes the

same color to be used for the lines and markers associated with the specified Group

(selected from the menu), when two or more Group variables are mapped to the Group

context.

Titles for reference lines can now be moved (QC 5839): The new Title Position

option is available for each reference line that has a title specified. Depending on the

Axis selection, the positions available are:

X Axis: Left Top, Left Center, Left Bottom, Right Top, Right Center, Right

Bottom. (Left/Right controls which side of the line the title appears on,

Top/Center/Bottom controls the position along the line.)

Y or Y2 Axis: Below Right, Below Center, Below Left, Above Right, Above

Center, Above Left. (Below/Above controls which side of the line the title

appears on, Left/Center/Right controls the position along the line.)

Error bars can now be added to Column plots (QC 8667): Column plots that do

not have a Group mapping now have the same user interface and options for error bars

as XY Plot and XY Plot (X-Categorical). The mappings panel has also been updated

to allow mapping of the Lower error bar, the Upper error bar, or both.

Font style and font size of reference line titles can now be changed (QC 9275):

The Reference Lines sub-tab now has a Font column for setting the font, font size, and

font style for each reference line.

XY Plot (X-Categorical): new option to display lines that connect the profiles

(QC 9850/CRM 154028): Options have been added to the Appearance tab that

control the display of lines, line style, color, and width. These options can be used to

change the appearance of lines in all groups by selecting the X-categorical plot in the

tree. If an individual group is selected, then the changes will only be applied to the

data for that individual group.

Capability of ordering legends is now available (QC 9942): Using the new Legend

> Order tab, the order in which Group values are displayed in the legend can be

specified as order in the source data, ascending order, descending order, or a custom

order. The Order tab is only available for plot types that allow Group mappings (i.e.,

September 2020


Revision 1 of 58

XY Plot, XY Plot (X-Categorical), Bar, Column, and Box) and at least one Group is

mapped.

Setting global default fonts and layout sizes for plots is now available in the new

Plotting Defaults page of the Edit | Preferences dialog (QC 11868): The default

settings for font and font sizes can be set for each type of text field: title, lattice title,

axes labels, tick labels, legend, and reference lines. The default settings will be used

when creating new plots; they do not override settings in existing projects or

templates. An option is included to reset the default settings to the Phoenix system

defaults.

When error bars go beyond 0, negative values are no longer shown on the X axis

(QC 12462): In order to prevent overlapping and overflowing of error bars, Phoenix

would adjust the range to each side of the X boundaries by 10%. This sometimes

resulted in negative values along the X axis. Phoenix 8.1 no longer adjusts the range

for error bars, i.e., the min and max of the X-axis are only determined by the (x,y)

data, the error bars are not considered.

Ordering of categorical axes values can now be specified (QC 12556): A new

Options sub-tab is now available for XY Plot, XY Plot (X-Categorical), and Column

plots. In the Order sub-tab, specify whether to use the order in the source data,

ascending order, descending order, or customize the order.

Offsetting is now available for all overlaid graphs and the offset can be to the left

or right (QC 15945, QC 16272): Previously, only the second overlaid graph could

be offset and only shifted to the right. With Phoenix 8.1, every graph that is overlaid

(every graph except the first graph) can be offset either to the right or left. Offsetting

to the left is accomplished by entering a negative number of time units.

The following plot types now use the AutoScale Best option for the x-axis by

default: XY plots (X-Categorical), Box plots, Bar plots, and Column plots (QC

16382): This default option will be used when creating new plots; it will not change

existing projects or templates.

Regression lines can now be displayed in front of data points (QC 16814): A new

Bring to Front checkbox allows the user to display the regression line in front of the

data points. This is useful when the data points are very dense and the regression line

may be obscured by the points.

New Layout menu allows selection of how items in the legend are to be listed (QC

16822): In the Legend > Appearance tab, there is now a Layout menu. Users can

choose from display legend items in a single column, a single row, or in a table.

Tables

New Sum column included as part of the table statistics (QC 10719): This new

statistic computes the sum of the values in the column mapped to Summary. If a

September 2020

Phoenix® 8.1 Release Notes What’s New - Framework

Revision 1 of 58

weight variable is used, then Sum is computed as the sum of the values in the column

mapped to Summary multiplied by the values in the column mapped to Weight, i.e.,

SUM(wi * xi).

New Geometric SD column included as part of the table statistics (QC 11125): This new statistic is computed as exp(SD Log).

The statistic “CV% Geometric Mean” is now called “Geometric CV% (QC

16852).

Framework

The version of Microsoft .NET on which the Phoenix 8.1 platform is built has

been updated to 4.7 (QC 17517).

Documentation


17552): The contents of the Third Party Tools Guide have been moved into other

Guides.

PKS, NONMEM Comparer, ODBC, and the Third Party Tools (NONMEM,

PsN, R, SAS, SigmaPlot) chapters have been added to the Phoenix Framework

User’s Guide.

The Reporter chapter has been added to Data Tools and Plots Guide.

NLME

Special Note for Grids: If you are upgrading from Phoenix 8.0 and already have a

grid set up with Phoenix 8.0, you must update the R library package Certara.NLME8

on your remote host with the package distributed with Phoenix 8.1, per installation

instructions in Appendix A of the Phoenix NLME User’s Guide.

VPC on ordinal data is now supported with Phoenix 8.1 (QC 16383, QC 16836).

NLME can now perform a predictive check on time-to-event data and build

Kaplan-Meier plots (QC 17369).

New example projects involving discrete and distributed delays available

(QC17397): Two projects have been added to the NLME folder in the Examples

directory:

LogisticGrowthModelWithGammaDistributedDelay.phxproj

ModelAbsorptionDelay_delayInfCpt.phxproj

In addition, a new section (called “Discrete and distributed delays”) describing these

two examples has been added to the “Language Structure and Syntax” chapter of the

Phoenix Modeling Language Reference Guide.

September 2020

Phoenix® 8.1 Release Notes What’s New - Validation Suite

Revision 1 of 58

For VPC, a separate sub-tabs are now available for setting the properties of each

specified observation (QC 17447).

Censored observations (below LLOQ) are no longer included in the plots (QC

17560).

User Interface

Simulation and Predictive Check are now separate run modes (QC 17367): The

Sim./Pred. Check run mode for population models has been replaced with two

separate run modes: Simulation and Predictive Check.

Validation Suite

The Phoenix Desc Statistics Weighting and No Weighting test cases have been

updated to test the new Phoenix 8.1 features for user-defined percentiles and for

new statistics (QC 17383, 17437).

The Validation Suite Report is now saved only as a PDF document (QC 17400):

In previous releases, a Word version of the Validation Suite Report was generated. In

Phoenix 8.1, a PDF version is saved instead. The Word document was initially

generated so users could add company information and logos, etc., to the report.

However, users should not be modifying the Validation Report document. They

should instead attach the PDF of the Validation Suite Report to their own

documentation.

Validation Suite now provides evidence of numerical comparisons (evidence of

the execution) (QC 17401): After execution of the Validation Suite, for each file

comparison that is done in a test case, the user now has access to three files, the

reference result, the user's result from the VS run, and a CSV file of the differences,

for example:

WNL MM 301 Final Parameters REF.csv

WNL MM 301 Final Parameters RUN.csv

WNL MM 301 Final Parameters DIFF.csv

The files are accessed through embedded links in the Validation Report.

Phoenix Model Object (NLME) individual modeling test cases now have status of

Not Applicable when WNL Validation Suite is executed (QC 17452): In the

previous release, these test cases had a status of ‘Failed’ when the Validation Suite

was executed on 32-bit systems because NLME can only be executed on 64-bit

systems. Although this was the expected behavior, the status of ‘Failed” was

confusing to users, so a new status of ‘Not Applicable’ has been added.

Validation Suite Semicompartmental Modeling test cases now pass when the user

has only the IVIVC Toolkit license (QC 17533): In the prior release, these test

cases were expectedly failing because the licensing changes for Phoenix 8.0 did not

September 2020

Phoenix® 8.1 Release Notes What’s New - WinNonlin

Revision 1 of 58

include Semicompartmental Modeling in the IVIVC license. It was decided to include

Semicompartmental Modeling in the IVIVC license for Phoenix 8.1.

Contents of the Validation Report have been modified (QC 17566): Several

changes have been made in the Phoenix 8.1 Validation Report document.

New line for the name of the company or institution.

Header row of tables repeats on each page.

Test Objective added for each test case.

A Ratios and Differences test case was added to the Validation Suite to validate

this new Phoenix 8.1 feature (QC 17670).

WinNonlin


17408):

Documented examples for the Table object have been moved from the Phoenix

WinNonlin User’s Guide to the Data Tools and Plots Guide, in which the

Table object is described.

The Examples chapter in Phoenix WinNonlin User's Guide has been moved to

Appendix G at the end of the User’s Guide.

September 2020

Phoenix® 8.1 Release Notes Issues Corrected - CDISC Navigator

Revision 1 of 58

Issues Corrected

CDISC Navigator ...............................................................................................................10

Data Tools and Plots ..........................................................................................................11

BQL .............................................................................................................................. 11

Data ............................................................................................................................... 11

Data Wizard .................................................................................................................. 11

Join ................................................................................................................................ 11

Plots/Charting ............................................................................................................... 11

Tables ............................................................................................................................ 13

Word Export ................................................................................................................. 13

Framework .........................................................................................................................13

DataLink ....................................................................................................................... 13

Diagram ........................................................................................................................ 14

History .......................................................................................................................... 14

Installation .................................................................................................................... 14

Object Browser ............................................................................................................. 14

PKS ............................................................................................................................... 14

Projects .......................................................................................................................... 15

Template ....................................................................................................................... 15

User Interface ................................................................................................................ 16

Watson-LIMS ............................................................................................................... 16

IVIVC ................................................................................................................................16

IVIVC Workflow .......................................................................................................... 16

JMS ....................................................................................................................................16

NLME ................................................................................................................................16

Engines .......................................................................................................................... 17

User Interface ................................................................................................................ 17

Validation Suite .................................................................................................................18

WinNonlin..........................................................................................................................18

Crossover ...................................................................................................................... 18

LinMix .......................................................................................................................... 18

NCA .............................................................................................................................. 18

Nonparametric Superposition ....................................................................................... 19

CDISC Navigator

CDISC SEND and SDTM now export text for the Label column (QC 17440):

When exporting PC domain with CDISC SEND or CDISC SDTM, the information in

the Label column was not being exported. This issue has been fixed.

September 2020

Phoenix® 8.1 Release Notes Issues Corrected - Data Tools and Plots

Revision 1 of 58


BQL

BQL rules are now being saved when multiple rule sets are created in BQL folder

(QC 17147/CRM 168232).

Data

A reported issue where custom filtering did not handle comparing two columns

of different types could not be reproduced and has been closed (QC 15174).

Data Wizard

Exclude/Include in Filter is now permitted for the values which are the same as

column names (QC 17362): Previously, the entered value to filter on was assumed to

refer to a column when a column existed that had the same name as the value entered.

With the redesigned user interface, the user can either select a column from a

dropdown list or type in a value to compare to when filtering. Type in NULL to filter

on cells that are blank.

Data Wizard custom function no longer fails when first value is blank (QC

17392): An issue was reported involving a custom function that would fail if the first

value in data was null, but would run without error as long as the first value was given.

This issue has been resolved with Phoenix 8.1.

Replacing a value in any column when the Replace All option is unchecked now

returns correct results (QC 17565): For a Filter operation, replacing a value with

the Column option set to Any and the Replace All option unchecked would replace

all matches. This issue has been fixed in Phoenix 8.1. Only the first match in each

column is replaced when the Replace All option is unchecked.

Join

Join function now correctly handles cases where multiple rows in the primary

worksheet correspond to a single row in the secondary worksheet (QC 17581): In

such cases, the algorithm was using a “by line” join. In Phoenix 8.1, a Cartesian join

is used, thereby producing the correct results for multiple to single row joins.

Plots/Charting

When using multiple monitors, the color palette for marker color is now

displayed in the same monitor as Phoenix (QC 6032/CRM 63733).

Options controlling the content of latticed plot titles now work correctly (QC

9354): Lattice titles can have two parts, the “Name = Value” part that comes from

September 2020

Phoenix® 8.1 Release Notes Issues Corrected - Data Tools and Plots

Revision 1 of 58

data that the lattice depends on, and the mapped lattice titles that come from a

worksheet. There are two settings that control the display of each these parts.

Setting the Lattice Titles Text option to None removes only the “Name =

Value” part of the title, the mapped titles remain.

Checking the Ignore Mapped Lattice Titles checkbox removes only the

mapped lattice titles, while leaving the “Name = Value” displayed.

Previously, setting the Text option to None would remove the entire title.

Error bars no longer disappear when switching from linear to logarithmic and

there are zero or negative Y-values (QC 11523/CRM 135552): In Phoenix 8.1, the

zero or negative Y-value is replaced with the minimum Y-axis value on the

logarithmic scale, thus keeping the error bars visible.

The font for a title or axis label that includes symbols can now be changed (QC

15851): If a new title was entered that included some symbols from the Insert Symbol

list, trying to enlarge the font of the new title would fail. This issue has been resolved.

Phoenix no longer re-uses colors and symbols when overlaying plots with

multiple mapped Y’s and a mapped Group (QC 15922): Previously, multiple lines

in a plot would be drawn starting with orange circles, then purple triangles, then red

squares. When the plots were overlaid, the overlay would use the same color and

symbol combinations, which made the plot unreadable for individual subjects. In

Phoenix 8.1, overlays use different default color and symbol combinations from those

used in plotting the individual lines.

XY Plot (X-Categorical) object now properly handles groups with no data (QC

16381): If a project had multiple groups defined, one of which had no data, and an

XY (X-Categorical) plot was generated, the plot would have a gap on the x-axis and

there was no indication that the gap corresponded to the group with no data. This

issue has been resolved.

September 2020

Phoenix® 8.1 Release Notes Issues Corrected - Framework

Revision 1 of 58

For Column Plots with y on a log-scale, the correct minimum value for the bars is

now determined (QC 16428/CRM 160282): In the Column Plot, when y was on a

log-scale, the bars would always extend from y=1, which caused some bars to go up

and some to go down (if some of the log-values were less than 1). This issue has been

resolved by determining the appropriate minimum value to use so that all bars go up.

Row and column latticing was collapsing sparse latticing, for all plot types (QC

16669): Lattice positions that would be empty with the specified latticing were being

filled with the next plots in the lattice (this is referred to as collapsing the sparse

latticing, i.e., removing empty plots). This issue has been fixed so that empty lattice

positions now remain empty by default, and the user can opt for collapsed sparse

latticing if that is preferred.

An issue where having Error Bars with logarithmic y-axis would cause a Phoenix

Overflow error has been fixed (QC 17413, QC 17444).

Tables

Summary Only option no longer overwrites ID variables with incorrect data (QC

16859/CRM 16242): If summary statistics were computed with a Tables object and

then the Summary Only option was checked and the object was re-executed, the

column statistics would overwrite the Row IDs. This issue has been fixed.

Word Export

Choosing to export everything in an NCA object no longer adds a column of

incorrect information (QC 17583): It was reported that Word Export would add a

column into the dosing information for the dose type and that the values in the column

were incorrect. This would only happen if the user selected everything for export.

This issue has been fixed in Phoenix 8.1.

Framework

In the Object Browser, the “Find Object in Browser” option has been added back

to the right-click menu for dependents (QC 17446): When showing dependents in

the Object Browser, the right-click menu for a dependent included a Find Object in

Browser option in Phoenix 7.0, but that option was inadvertently dropped in Phoenix

8.0. It has returned as a menu option in Phoenix 8.1.

DataLink

Exception no longer occurs when a column is being renamed to existing column

name (QC 17500): If the new name (e.g., “dosepoint”) contained the name of an

existing column (e.g., “dose”), an exception would occur when the user had typed

enough of the new name that it matched the existing name. This problem has been

resolved in Phoenix 8.1.

September 2020


Revision 1 of 58

Diagram

An issue where clicking a blank box in the Diagram caused an unhandled

exception has been fixed in Phoenix 8.1 (QC 17472).

History

Contents of the History sheet of worksheets in Data folder are maintained when a

project created using Phoenix 6.4 is opened in Phoenix 8.1 (QC 17326): The

History sheet was being cleared when the Phoenix 6.4 project was opened in Phoenix

7.0 or 8.0. This issue has been fixed for Phoenix 8.1.

Installation

An issue where Phoenix installation interferes with NONMEM7 installation has

been closed as obsolete (QC 12265): Changes made to the Phoenix installation have

resulted in this reported issue being obsolete.

Object Browser

NCA is no longer marked out-of-date by just selecting the Slope Selector or

Slopes under Setup (QC 17701).

PKS

Loading a Scenario no longer fails with unhandled exception if the scenario is

dependent on a Study View from another study and the user does not have access

to the other study (QC 15191).

When using Excel files as the Study Library, the File Import Wizard now displays

as expected (QC 17356): When Excel files were used as the Study Library, the File

Import Wizard would not appear, the step was by-passed, and the sheet would appear

in the data folder without the units in the column header. With Phoenix 8.1, the File

Import Wizard now displays, allowing for the specification of units in the column

headers.

When a scenario is reloaded after a new version of the library object is created,

the File Import Wizard no longer lists more than one file with the same name (QC

17357): In Phoenix 7.0, if a new version of the scenario’s library object was created

and then the scenario was reloaded, the File Import Wizard would incorrectly list files

with identical names (one file for each version of the object). This issue has been

fixed in Phoenix 8.1.

Audit reason is now properly recorded for Study and Global Library objects (QC

17358): When saving a Study or Global Library object, text entered in the Audit

Reason field was not being saved with the object and the Audit Reason field was

September 2020


Revision 1 of 58

missing from the Object Properties window in the PKS Browser and the PKS Web

Browser. These issues have been fixed in Phoenix 8.1.

The correct icon is now displayed when a new scenario is created (QC 17432): In

Phoenix 8.0, when a new scenario was created, a Phoenix project icon was displayed

in the PKS Browser for that new scenario. Once the new scenario was saved and

reloaded, the correct icon would appear. In Phoenix 8.1, the correct PKS Scenario

icon is displayed at the time of the scenario creation.

Projects

Double-clicking a Phoenix project file in Windows Explorer now opens the

project in Phoenix when Phoenix is already open (QC 14719): When Phoenix was

already open and you double-clicked a project file in a Windows Explorer window,

the project would not load into Phoenix. With Phoenix 8.1, double-clicking a Phoenix

project file in Windows Explorer will load the project into an existing Phoenix session

or start Phoenix and load the project if a Phoenix session is not running.

An issue where opening a project containing a worksheet view for which a sort

expression was defined caused an exception in Phoenix 8.0 has been fixed (QC

17402): When a user would change a column name, the Sort field was not getting

updated accordingly, even if the renamed columns are used in the sort expression.

Once the worksheet was saved (along with its view), attempting to load it resulted in

an exception, since the sort expression was now referring to a non-existent column.

With Phoenix 8.1, the Sort fields are now updated when column names are changed.

Template

Performance improvement with loading templates (QC 17261): Several customers

reported very slow loading times for large templates. Work has been done to reduce

the loading time as much as possible with the following results (based on loading the

same template and using the same machine):

Phoenix 7.0: 132 seconds



An exception no longer occurs when selecting partial areas for an NCA object

created from a template (QC 17330).

Exception no longer occurs on Save Template action (QC 17338): When applying

object settings to an operational object that had internal worksheets specified (e.g.,

Dosing in NCA), if the object settings did not have the same internal worksheets as the

current object, an error was generated when attempting to copy/paste the object, save a

September 2020

Phoenix® 8.1 Release Notes Issues Corrected - IVIVC

Revision 1 of 58

workflow template containing the object, or save object settings for the object. The

issue has been resolved and the exception error is no longer generated.

User Interface

An issue where the Project Exists dialog would pop up behind the model

Importing panel cannot be reproduced and has been closed (QC 8735).

Watson-LIMS

Reassayed samples are no longer automatically removed when importing Watson

LIMS data (QC 15584/CRM 147180, 160398, 161113): New options in the

Preferences dialog for Watson Import > Business Rules Configuration allow users to

decide whether or not reassayed samples should be included in the import. Reassayed

samples may also be filtered using fields for entering reasons and status.

IVIVC

IVIVC Workflow

A reported issue where running “Predict PK” on the Prediction tab would

occasionally cause the project to freeze has been fixed in Phoenix 8.1 (QC 17625).

JMS

JMS requires the NONMEM working folder to be present on the JMS server

(QC 12423): Specifying a NONMEM working folder with a drive letter that does not

exist on the JMS server will cause the job to fail. To work around the issue, either

specify a working folder with a drive letter that exists on the server or map the drive

letter to a folder on the server.

NLME

Parentheses are now retained when switching between Graphical and Textual

modes (QC 17092): An issue was reported where entering an expression in graphical

mode that involved parentheses (e.g., C<(-8)?2:3) and then switching to Textual mode

would result in the loss of the parentheses and cause an error. This issue has been

fixed in Phoenix 8.1.

VIFs are now calculated in Simulation mode for Indirect Response models (QC

17410): Prior to Phoenix 7.0, it was possible to calculate VIFs for IDR models when

running in simulation mode. In Phoenix 8.1, the problem that had prevented this

functionality from working has been fixed and it is once again available.

PK parameters mapped in the Setup tab as Sort keys are now correctly used for

each subject in individual mode (QC 17591/CRM 0016650): Fitting data

individually using an external fixed effects worksheet with sort keys has not been

working since Phoenix 1.4, but is fixed in Phoenix 8.1.

September 2020

Phoenix® 8.1 Release Notes Issues Corrected - NLME

Revision 1 of 58

Engines

MPI results are now the same as non-MPI results for most engines (QC 14206,

QC 14851): It has been noted in previous versions of Phoenix that MPI and non-MPI

results for the same engine often differed, mostly by a small amount but sometimes by

fairly large amounts. This issue has been resolved for all engines except IT2S-EM,

which could still produce different results depending on MPI threads.

An issue where a Bootstrap run caused an unhandled exception during CRT exit

procedure could not be reproduced in Phoenix 8.1 and has been closed (QC

17141/CRM 00163163).

mpiNLME7 no longer hangs when the number of threads exceeds the number of

subjects for Naïve Pooled run mode when Fisher Score method is selected (QC

17252).

Distributed delay results are now correct when running on Linux machines (QC

17354): In Phoenix 8.0, running a model on Linux (locally or remotely) that had a

statement or function related to Distributed Delay (AddInfCpt and delay with

additional shape parameter accordingly) could produce incorrect results. The issue

has been resolved in Phoenix 8.1.

VPC now includes all values of stratification variable (QC 17382/CRM

00165398): An issue was reported for Phoenix 8.0 where VPC plots were not

generated for all values of the specified stratification variable. (All plots were

generated when the same project was executed in Phoenix 7.0, however.) In Phoenix

8.1, all values are now included in the VPC and all plots are generated as expected.

User Interface

Issues regarding output for time-varying covariates are not reproducible and this

defect is now closed (QC 10692).

A reported issue that NLME would spend a long time creating empty plots when

the Stiff solver (or AutoDetect) failed could not be reproduced and has been

closed (QC 11710).

In a Visual Predictive Check run, error messages for such problems as mapping

errors, etc., are generated (QC 14027): It had been reported that a Visual Predictive

Check run was not reporting normal error messages, such as mapping errors, etc. This

issue has been fixed.

Message about fixed effects not being within the assigned bounds is now returned

from remote (grid) execution (QC 17602): When a project was run locally that had

fixed effects not within user-assigned bounds, an error was returned to that effect. If

the same project was ran remotely on the grid, the failure was reported but with no

September 2020

Phoenix® 8.1 Release Notes Issues Corrected - Validation Suite

Revision 1 of 58

details about the error. In Phoenix 8.1, the details are included with error if the project

fails when running remotely on the grid.

Validation Suite

Validation Suite User’s Guide for Phoenix 8.1 now includes details about

expected 10 test case failures on 32-bit machines (QC 17449/CRM 00165309,

00165313): The Phoenix WinNonlin Validation Suite includes test cases for the

Phoenix Model object with individual (non-population) modeling. The Phoenix

Model object (NLME engine) can only run on 64-bit systems, so any test cases for the

Phoenix Model object will expectedly not execute on 32-bit systems. This

information was not included in the Validation Suite User’s Guide for Phoenix 8.1,

but has been added in the Phoenix 8.1 version.

Validation Suite template documents should be updated for current guidelines

and for usability (QC 17499): The Template documents have been revised to align

with updated regulatory guidance for computer system validation such as ICH E6

Good Clinical Practice (GCP) R2. Additional sections have been added to the

Validation Plan, Requirements Specification, and Test Plan template documents to

address these updates including risk assessment, SOP requirements, security, and data

backup and recovery. Usability was improved by fixing the automatic numbering of

requirements in the Requirements and Traceability template documents and the

automatic section header numbering in all template documents. An additional column

was added to the Traceability template for providing justification of non-covered

requirements.

WinNonlin

Crossover

The Exact column has been removed from the Results worksheet (QC 7904/CRM

65507): In the Crossover Design tool, the Exact column in the results did not contain

the exact confidence levels as intended, plus the column was reportedly not being used

by customers. Therefore, it has been removed from the Crossover output.

LinMix

An issue where Linear Mixed Effects generated an unhandled error when using

very long string values cannot be reproduced using Phoenix 8.1 and is being

closed (QC 4880/CRM 138864).

NCA

Correct default units options are now displayed for Default and Preferred units

for volume and clearance parameters when observations and dosing have a

mixture of moles and grams (QC 4151/CRM 37868).

September 2020

Phoenix® 8.1 Release Notes Issues Corrected - WinNonlin

Revision 1 of 58

NCA object no longer executes twice when workflow is executed (QC 17332): There was an issue where an NCA object would go out of date during verification,

even when results were current. Due to this, the NCA object and its dependents could

execute more than once, depending on where it existed in the workflow. This issue

has been resolved.

When user-defined parameters are included with Final Parameters, carryalong

variables are no longer dropped from the Final Parameters Pivoted result (QC

17348): When an NCA object contained user-defined parameters and the Include in

Final Parameters option was turned on, carryalong variables were dropped from the

Final Parameters Pivoted result. (They still appeared in the Final Parameters and the

Summary Table results.) This issue has been fixed.

An issue where preferred units for Cmax or other “C” parameters (“Rate” and

“R” parameters for urine or PD models) were not used when projects from

Phoenix 7.0 or prior were used in Phoenix 8.0 has been resolved with Phoenix 8.1

(QC 17360).

The Dose Type option is now disabled when the model type is Urine (QC 17450):

Models 210-212 assume single-dose data and the final parameters do not depend on

the dose type.

Records in the Core output are now properly sorted when Sort keys are specified

(QC 17553).

User Defined Parameters using AUMC (or any parameter not included in the

output) are now correct (QC 17707).

Nonparametric Superposition

NPS now handles external dosing sheet correctly (QC 17497): NPS was not using

mapped dosing worksheets in the prior release. This issue has been fixed with Phoenix

8.1 and the external dosing worksheet is no longer ignored.

September 2020

Phoenix® 8.1 Release Notes Known Issues - WinNonlin

Revision 1 of 58

Known Issues

AutoPilot Toolkit ...............................................................................................................21

Administrative Module ................................................................................................. 21

Automation ................................................................................................................... 23

Business Rules .............................................................................................................. 24

Comparison ................................................................................................................... 25

Exclusions ..................................................................................................................... 26

Graphs ........................................................................................................................... 26

Output ........................................................................................................................... 28

Reporting ...................................................................................................................... 29

Run ................................................................................................................................ 30

Tables ............................................................................................................................ 30

Text ............................................................................................................................... 32

User Interface ................................................................................................................ 33

Data Tools and Plots ..........................................................................................................33

BQL .............................................................................................................................. 33

Column Transformation ................................................................................................ 33

Data ............................................................................................................................... 34

Data Interpolation ......................................................................................................... 35

Data Wizard .................................................................................................................. 35

Descriptive Statistics ..................................................................................................... 36

Edit in Excel .................................................................................................................. 36

Reporter ........................................................................................................................ 37

Tables ............................................................................................................................ 37

Word Export ................................................................................................................. 38

Framework .........................................................................................................................38

Dependencies ................................................................................................................ 38

File I/O .......................................................................................................................... 38

Grid Computing ............................................................................................................ 39

History .......................................................................................................................... 39

Licensing ....................................................................................................................... 40

Logging ......................................................................................................................... 40

Mapping ........................................................................................................................ 40

NONMEM .................................................................................................................... 40

PKS ............................................................................................................................... 41

Printing .......................................................................................................................... 42

Projects .......................................................................................................................... 43

PsN ................................................................................................................................ 43

R .................................................................................................................................... 43

Reporter ........................................................................................................................ 44

User Interface ................................................................................................................ 44

September 2020

Phoenix® 8.1 Release Notes Known Issues - AutoPilot Toolkit

Revision 1 of 58

Watson-LIMS ............................................................................................................... 44

IVIVC ................................................................................................................................44

Convolution .................................................................................................................. 44

Levy Plot ....................................................................................................................... 45

Wagner-Nelson & Loo-Riegelman ............................................................................... 46

Workflow ...................................................................................................................... 46

JMS ....................................................................................................................................50

Phoenix Licensing Wizard .................................................................................................50

NLME ................................................................................................................................50

Engines .......................................................................................................................... 51

Model Comparer ........................................................................................................... 51

User Interface ................................................................................................................ 52

WinNonlin..........................................................................................................................55

Bioequivalence .............................................................................................................. 55

LinMix .......................................................................................................................... 56

NCA .............................................................................................................................. 56

Nonparametric Superposition ....................................................................................... 56

WinNonlin Classic Modeling ....................................................................................... 57

AutoPilot Toolkit

AutoPilot Toolkit does not function as a native application in 64-bit environments

(QC 3565): The 32-bit Phoenix executable (i.e., phoenix32.exe) must be used when

working with AutoPilot Toolkit.

Error when using AutoPilot Toolkit with custom settings xml file in a template

(QC 3813): An AutoPilot Toolkit object with a custom xml settings file that is used

and saved as part of a template does not refresh correctly when the template is used in

a workflow, and, as a result, an error might occur during verification or execution of

the workflow, specifically if there are differences between the data used for template

creation and template usage (for example, if the list of concentration variables has

changed). As a workaround to avoid this problem, it is recommended to disconnect

the AutoPilot object and to apply the desired settings again, i.e., select the custom

settings file and make the desired selections in the user interface.

Administrative Module

Users cannot resize all parts of the Administrative Module (QC 1781): The

Administrator Module panel can be resized, but not all parts of the interface can be

resized in a useful manner. For example, some of the menus in the Administration

Module that contain long names are not resized, so the scroll bars must be used to see

the entire name.

AutoPilot Toolkit should not have alignment option for axis tick labels or the

legend (QC 1809): In the Administration Module, go to PK Automation (or PK

September 2020


Revision 1 of 58

Comparison) > Graph Data > Format and select the Text Elements tab. If a user

chooses Legend or Axis Tick Labels in the Name menu, the Alignment menu should

be hidden or otherwise unavailable to the user, but it is not.

Context Sensitive Footnotes cannot be deleted or changed in the output (QC

2020): When a user attempts to delete or change the standard Context Sensitive

footnotes in the Administration Module, the changes are not saved or reflected in

AutoPilot Toolkit output.

The configuration settings file does not retain the PK Parameter settings and

causes categorical graph creation to fail (QC 2256): The configuration settings file

does not retain the PK Parameter settings that are changed by the Administrator.

Changes to PK Parameters need to be made in the AP Automation object on a run-by-

run basis.

Setting gridlines in the Administrator Module does not work correctly (QC

2264): Select Config > PK Automation (or PK Comparison) > Graph Data > Format.

The Line Elements tab enables the administrator to set the display characteristics for

lines, error bars, and data points. However, the Gridlines option is non-functioning

and no gridlines are produced, regardless of setting changes.

Line thickness setting changes not applied (QC 2265): In the Administrator

Module, select PK Automation (or PK Comparison) > Graph Data > Format. On the

Line Elements tab, the Thickness setting has no effect and any changes made are not

represented in PK Automation or PK Comparison output.

Legend placement at bottom of graphs does not always operate correctly (QC

2458): When using the Administrator custom configuration tool to place time-

concentration and PK parameter plot legends at the bottom of graphs, it has been

found that not all cases will work as expected. Legends placed at the bottom of these

graphs and that are Right-aligned seem to work as expected, however aligning them

Center or Left can produce random results. When the system does not adhere to the

settings chosen, the legends will revert to the upper-right corner of the plot region as

though the default locations were in effect.

Column mapping is case-sensitive (QC 2521): AutoPilot Toolkit requires that the

case of column names match the case used by Client names. For example, mapping

the variable Gender to the Client name GENDER can create differences in the output,

such as placing male data before female data in graphs stratified by gender. Make

sure that the case of column names and Client names are the same.

Some text labels are truncated in the Administration Module on Chinese versions

of Windows (QC 3414): Depending on the replacement font that is used on a specific

machine when working with a Chinese operating system, some text entries in the

Administration Module can be truncated. This does not affect the functionality of the

Administration Module.

September 2020


Revision 1 of 58

Deleting context sensitive footnote in Administration Module does not delete it

when system XML is reloaded (QC 3852): To remove an additional BQL footnote,

the BQL entry is deleted from the contextual footnotes. When the configuration file is

saved and then assigned to a new AutoPilot Toolkit object, the additional footnote still

appears when the AutoPilot Toolkit object is executed. If the changed configuration

file is opened in the Admin module of the AutoPilot Toolkit, it also shows the deleted

BQL entry in the contextual footnote.

Automation

Reference treatment that exists in a study worksheet but does not exist in the

NCA model output causes an error (QC 2089): If a reference treatment exists in a

study worksheet but does not exist in the NCA model output (due to less than two time

points or invalid concentration values), then the PK Ratios and PK Statistics tables

cannot be created and an error occurs. This is because the tables are based on the

NCA model output.

Lambda_z table and regression fit Summary PK text not created (QC 2202): In

cases where Phoenix cannot create a regression line (for instance, when concentration

increases over time), AutoPilot Toolkit cannot generate any table based on regression

values like Lambda_z. To force a regression line, set the start and stop times larger

than TLast.

Discrete Variables tab selections do not affect graph output (QC 3159): 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.

PK Statistics table contains incorrect output when a very large number of PK

parameters are selected (QC 3388): When a large number of parameters are

included in a PK Statistics table, the output can be incorrect and the text string “CF

("convergence failure")” is added to the PK Statistics table.

Excluded points are missing in excluded concentration by treatment graphs (QC

3451): There is no visual representation of excluded points in the time and

concentration by treatment graphs as there are in the PK Parameter graphs.

AutoPilot Toolkit does not use PK Parameter names that are modified in an NCA

model in Phoenix WinNonlin (QC 3462): If PK parameter names are updated in the

NCA model, automation and comparison objects are unable to process them correctly.

Do not modify PK Parameter names in NCA models that are connected to AutoPilot

Toolkit automation or comparison objects.

PK Stats table fails if the AP Automation object is executed from the workflow

(QC 3784): When the AP Automation object is executed as part of a workflow

execution, the creation of the PK Stats table fails. As a workaround, the object should

be executed directly and not as part of the whole Phoenix workflow.

September 2020


Revision 1 of 58

Missing line in the second table when selecting Automatic Table Splitting (QC

3811): There is a known issue where automatic splitting on long tables can cause

border formatting issues. There is no known workaround for this issue.

Font setting for Individual plot is not applied to the first subject plot (QC 3812):

There is a known issue where formatting is not applied to the first subject plot but is

applied to all other plots. There is no known workaround for this issue.

AP Phoenix template does not remember all settings (QC 3817): There is a known

issue where the user configuration settings are not remembered in a Phoenix template.

The only workaround is to unselect the data source and reset configuration.

Setting LOQ can result in doubling the execution time (QC 3819): Setting LOQ

for an AutoPilot execution will extend the execution time when stacked data is

involved.

Not all SigmaPlot graphs are created on machines running Windows 8.1 and

Microsoft Office 2013 (QC 3824): There are known issues with all graphs not being

created on a Windows 8.1 machine with Office 2013. Depending on the performance

of a specific computer, this issue might occur on other platforms as well. Errors

encountered look like “Not all graphs of type XXXX created [Retrieving the COM

class factory for component with CLSID {6E73CA04-CE63-11CF-B59C-

0000929132CE} failed due to the following error: 80080005 Server execution failed

(Exception from HRESULT: 0x80080005 (CO_E_SERVER_EXEC_FAILURE)).]”

PK Summary text is not always created when using a XenApp/Citrix client (QC

3829): There is a known issue with appendices in a Citrix environment not being

created at times. There is no known workaround for this issue.

Font setting is not applied to Plots for axis labels and axis tick marks (QC 3830):

There is a known issue that font settings are not always applied to the axis labels and

axis tick labels for all graph output. There is no known workaround for this issue.

Specified ordering for Analytes is not followed in the concentration tables (QC

3867).

Incorrect font style in the Footnote (QC 3868): There is a known issue where font

settings are not being applied to footnotes for Intext table output. There is no known

workaround for this issue.

Business Rules

Comparisons do not handle differing units between reference and test files (QC

2063): The reference and test data sets used in a comparison project must contain

matching units. AutoPilot Toolkit will produce incorrect output if the units for a

variable in the reference data set do not match the units used for the same variable in

the test data set.

September 2020


Revision 1 of 58

Small Sample Size value forced to 1 when loading the configuration XML (QC

2586/CRM 65480): The Administration Module has two settings that are

incompatible. The first setting controls the summary statistics that are displayed by

default. This setting allows users to add statistics for display and to remove them.

Users navigate to this setting by selecting Config > General > Variable Data >

Statistics > User Default Selection. 32389

The second setting controls how AutoPilot Toolkit handles small sample sizes. Users

navigate to this setting by selecting Config > General > Business Rules > General >

Summary Stats Display Calculation Criteria. Users can select the minimum sample

count required before a summary statistic is computed.

The incompatibility occurs when a user selects the first setting to remove a summary

statistic from the default list or add a new statistic to that list. After making the

change, the minimum required sample size for one or more of the summary statistics is

frozen at one, even for statistics that require more than one sample.

The user interface allows users to change this value. However, if a user makes the

change, saves the system XML file, and reopens the Administration Module, then the

value has been set back to 1.

Comparison

Comparison graphs display the LOQ for the reference input only (QC 2271):

LOQ lines cannot be turned on and off for comparison projects because the LOQ

column is not displayed as an output option in AutoPilot Toolkit comparison objects

user interface.

AutoPilot Toolkit does not detect when input data are not using the same analyte

for Accumulation and Absolute Bioavailability projects (QC 2450): For

Accumulation and Absolute Bioavailability projects, the same analyte must be used

for the reference and the test data sets or an error occurs and not all graphs are created.

Analyte information is missing in the title of some Absolute Bioavailability

comparison graphs (QC 2534): The Categorical Box & Whisker graphs for Fabs do

not have analyte information displayed in the title. The categorical and continuous

demographic graphs for Fabs, DoseIV, and DoseExt are also missing analyte

information in the graph titles.

In Analyte - Trough comparisons, tables and graphs report missing stratification

variables in different ways (QC 2538): In a comparison between two replicated

trough studies that are stratified by gender and race, missing values for gender and

race are reported as NR in tables and Missing in graphs.

The X-axis is not correctly labeled in demographically-stratified summary

concentration graphs with missing values (QC 2539): In Analyte - Trough

comparisons, summary concentration graphs stratified by race and gender have

September 2020


Revision 1 of 58

incorrectly labeled X-axes when demographic data is missing. The graphs are created

correctly even when there are no points to plot, but the X-axis only displays the first

day in the study. For example, if data in a study is sampled on days 4, 8, and 11, then

summary concentration graphs stratified by race and gender that have no points to plot

only display day 4 on the X-axis.

Incorrect Y-axis labels are being displayed for urine graphs when the Matrix

column contains both plasma and urine (QC 2562/CRM 65041): If an input

dataset contains both plasma and urine matrices, and the plasma profiles are excluded,

the plasma profiles are incorrectly used to generate the Y-axis labels for the amount

excreted by subject graphs.

The workaround is to use the Multi-Transform tool in Phoenix WinNonlin to remove

the plasma profiles and create the NCA model against the Multi-Transform output

workbook. The Y-axis matrix information is then correctly displayed in these graphs.

X-axis angled labels overlap and are illegible in Comparison Categorical graphs

(QC 3238): The X-axis labels can overlap when there are too many entries on the X-

axis. For example, this could happen in stratified comparison graphs with multiple

stratifications and too many values for each categorical variable.

Saving a project that contains several comparison objects can cause Phoenix to

fail due to an out-of-memory error (QC 3457): A Phoenix project might fail to save

if the application runs out of memory.

Exclusions

LOQ values are treated as missing when they should be treated as zero (QC

3820): There is a known issue where the LOQ rule is not applied to the excluded

tables for stacked-by-analyte data. There is no known workaround for this issue.

Graphs

Categorical Standard graphs do not have a "None" option for Error Value (QC

1629): The Time Concentration graphs allow the user to select "None" for the Error

Value instead of SD, SE, etc. However, the Categorical Standard graphs do not have

"None" listed as an option.

First X-axis tick mark might be clipped (QC 1797): The first tick mark on X-axes

might be clipped from the graph output if the label text is very long and is displayed at

an angle to the X-axis. As a workaround, the .jnb file can be edited and the start value

of the range for the X-axis can be set to a smaller value. As a result, the first tick mark

and the label will move to the left and the whole text will be displayed.

Setting an unusually high LOQ value prevents concentration graphs from being

created (QC 1840): If the LOQ is set to a value that exceeds all concentration values,

no concentration graphs are created.

September 2020


Revision 1 of 58

The legend includes symbols for values that do not have any data plotted, such as

when values are all NC (QC 1913): The legend for graphs that contain summary

information will show symbols for values that are not calculated (NC) because the

sample size is too small. The NC values are shown only in the legend, and not in the

graphs.

LOQ legend text entry does not align with other legend information (QC 2401):

In order to accommodate the LOQ legend symbol, the LOQ text displayed in graph

legends (LOQ = X ug/mL) is not aligned with the rest of the legend text. The user can

manually adjust the width of the symbols in the legend in order to correctly align the

text with the following steps:

Right-click on any text in the legend and select Edit. The Edit Text window

opens.

Click Symbol to open the Symbols window.

Adjust the width of all symbols and/or lines to an equal width, for example

0.25".

Click OK.

Close the Edit Text window.

Legend text extends beyond frame in EMF and JNB images (QC 2478): There are

cases where one or more legend text entries either touch or overlap the right edge of

the box that surrounds the legend information. The problem is caused by the length of

the legend entry as well as the font attributes applied. Depending on the affected

graph, the workaround is to either decrease the length of the information that appears

within the legend box (for example, decrease length of analyte or treatment

descriptions where applicable) or use a smaller font for the legend text via

Administration Module settings.

Continuous Demographic graph option is available in the user interface even if

the study has no demographic variables (QC 2595): The user interface by default

attempts to create continuous demographic graphs. When a study does not contain

continuous demographic variables, AutoPilot Toolkit will crash under these default

settings with an error stating "Subscript out of range." Subsequent to this error

message, viewing the error log file will show an entry stating "An error has occurred

while creating Continuous_Demographic." The workaround is to be sure to unset the

checkboxes for these graphs when processing this type of data.

Continuous Dose Box & Whisker graph cannot be created when the option

“Group by Analyte” is selected (QC 3064).

Time concentration graphs do not use the display name for concentration (QC

3077): The graphs do not use the display name for concentration and it is always set

to Concentration.

September 2020


Revision 1 of 58

The x-axis label is cut off in the summary graphs (QC 3583): When Geometric

Mean is used in the creation of summary graphs and all data values are less than LOQ

for a subject, the x-axis label is only partially visible.

The functionality for changing Y-scaling and X-scaling on graph by graph or

flexible lin/log does not work in all instances (QC 3860):

For Y scaling:

Graph by graph for linear and uniform for log works as expected.

Uniform for linear and graph by graph for log is not working for IV infusion

study with those exclusions.

For graph by graph, only linear plots are adjusted, log plots all have the same

Y scaling.

For X scaling on individual:

Graph by graph or uniform, in combination with any of the three options

above, is not working, the X axis scale does not adjust nor does it adjust for lin

or log.

Output

On Chinese and Japanese systems, an asterisk is used to represent multiplication

sign instead of dot in all output generated from automation and comparison

objects (QC 2009, 3412).

The units in a data set and the units set in the NCA model’s Options Units tab

must match to get coherent output in AutoPilot Toolkit (QC 2216): If the units

specified in a data set and in a NCA mode’s Options tab do not match, the output

generated by AutoPilot Toolkit might not make sense. For example, if the time data is

in hours and the preferred time units in the NCA model are set to day, then the output

data will be in hours, but the units will indicate day.

Trough Individual time-concentration graphs can have X-axis tick mark labels

that overlap (QC 2496/CRM 64187): If X-axis tick-mark labels are too long, they

might overlap. This problem can also occur when there are time values that are

closely grouped together.

Discrepancy in reported values between tables and plots of urine amount

excreted (QC 2516): If one or more subjects in a data set have a negative relative

actual time value, AutoPilot does not display mean values in the plots when the

relative actual end time is used as the X-axis variable. If the default X-axis variable

Midpoint Time is used, then the mean values in the table are plotted.

September 2020


Revision 1 of 58

In Kanji (Japanese) versions of Windows, u (micro) in variable units is not

replaced with µ in the table output (QC 2719): This defect only applies to Japanese

versions of Microsoft Windows and only affects the units "uIU" and "u".

Partial Areas are NOT reported in AutoPilot Toolkit when using the Label for

Partial Areas in the NCA model (QC 3465): There is a feature in Phoenix

WinNonlin NCA models that allows users to enter a Label when defining Partial

Areas. When a label is entered in the Label field, no Partial Areas are reported by

AutoPilot Toolkit.

Subject IDs with a large number of digits display with exponential format in the

AutoPilot Toolkit output (QC 3866): Subject IDs with 12 digits were reported as

being display using an exponential format (e.g., 1.23457E+11). There is no known

workaround at this time.

Reporting

A large table can be incomplete when inserted to a new Word document (QC

2925): If a table is too large to fit on a page, it is shrunk and/or truncated in the Word

document. This could cause the table to be incomplete in the document. As a

workaround, the automatic table splitting feature can be used in an automation project

to avoid creating tables that would be too large to fit on a page.

Order is not maintained when the UP or DOWN button is used in the Selection

list of the Reporting tab (QC 2986).

Open Existing Word Document and Open Existing PowerPoint Presentation

buttons remain disabled after an output insert is completed (QC 3021): After

inserting objects into an existing Word or PowerPoint document, the user has to click

somewhere in the Reporting tab to re-enable the Open Existing Word Document and

Open Existing PowerPoint Presentation buttons.

A confusing error message is issued when the AutoPilot Toolkit Reporting tab is

accessed and no Phoenix license is available (QC 3061): If no Phoenix license is

available, a user can still load a project that includes AutoPilot Toolkit workflow

objects. However, when trying to use the AutoPilot Toolkit Reporting tab, users will

get an error message that states “Unable to retrieve xml settings for loading this

object” and the export of generated objects will fail. This defect does not affect the

functionality of the product.

Graphs do not completely get exported from SigmaPlot 12.x as editable objects

into Word or PowerPoint (QC 3449): In some instances, the plot itself was missing

in the exported graph but the legend and footnote are present.

Category and Sub Category field in the Reporting tab is displaying all options

when only chart or table is chosen (QC 3450).

September 2020


Revision 1 of 58

There are problems inserting results into Word and PowerPoint in the Reporting

tab if more than one document is open (QC 3452): When inserting Automation or

Comparison results into an existing Word or PowerPoint document in the Reporting

tab, it is recommended that only one document is open at the time.

Error exporting results to a new PowerPoint presentation after working with an

existing PowerPoint Presentation in the Reporting tab (QC 3453): After inserting

Automation or Comparison results into an existing PowerPoint presentation from the

Reporting tab and closing the PowerPoint presentation, errors will occur if the user

makes an immediate attempt to export results into a new PowerPoint presentation.

Error exporting files to Word in the Reporting tab (QC 3781): The Reporting tab

can generate a null result error when handling AutoPilot Toolkit templates that have

been executed prior to creating a template. Workarounds are to try to re-execute the

object, to use the Reporter plugin instead of the Reporter tab in AutoPilot Toolkit, or

to setup the AutoPilot node and create the template before executing the node.

Saving a Word document to disk can cause Phoenix to shut down (QC 3831): Sometimes, when saving a Word 2010 document created by the AutoPilot reporting

tool to disk, Phoenix will shut down unexpectedly. To work around the problem, save

the Word document to Phoenix first and then export the document to disk.

Run

Dosing information is required in the NCA model (QC 2347): If dosing

information is not entered in the NCA model, then the AutoPilot Automation Object

cannot be configured correctly and will not execute.

Nested sub-workflow AP objects execute even when the “Execute as Part of

Workflow” check box in Preferences is unchecked (QC 3671): Automation and

Comparison objects contained within a sub-workflow may execute when a parent

workflow is executed even if the Execute as Part of Workflow check box is

unchecked in Edit > Preferences > AutoPilot. The only workaround is to cancel the

execution.

Tables

The treatment description text is truncated in

Comparison_PK_ParameterA_Ratios table (QC 1196): The table does not display

the entire treatment description in some instances if table splitting is applied.

PK Stats table is not split when the option is selected (QC 1413): The table-

splitting option does not currently work for the PK Stats table. Choosing a large

number of PK Parameters can generate a table that will not fit on a single page. As a

workaround, choose only 7 or 8 parameters for this table. If more parameters are

required to be listed, perform additional Automation runs and choose the additional

desired parameters and generate only the PK Stats table.

September 2020


Revision 1 of 58

Multiplication symbol displays as extended ASCII code 201 symbol (QC 1949):

AutoPilot Toolkit uses a bullet (Unicode character 2022) instead of an asterisk as the

multiplication symbol. On some systems the bullet is displayed incorrectly. This is a

rare event as most computer configurations are capable of correctly displaying

Unicode symbols.

Discrepancies can occur between the numbers of subjects in each sequence in the

Intext PK Parameter table (QC 1976): This is an effect of an AutoPilot Toolkit

enhancement that allows Day to be blank in a data set. AutoPilot Toolkit is now able

to handle blank Day data, and since AutoPilot Toolkit needs Day to be an integer, a

missing or blank Day value is automatically set to 1. Therefore, if a subject has a

missing or blank Day value, the value is set to 1, and the subject will be counted in

Day 1 of a study but not in the next Day of a study. This defect affects both graph and

table output. This defect only occurs when there are missing Day values in a data set.

The Lambda_z table can contain missing subjects if the value for the day

variable is missing (QC 1977): This is an effect of an AutoPilot Toolkit

enhancement that allows Day to be blank in a data set. AutoPilot Toolkit is now able

to handle blank data, and since AutoPilot Toolkit needs day to be an integer, a missing

or blank day value is automatically set to 1. If a subject in a data set is missing a day

value, AutoPilot Toolkit will assign a value of 1 to the missing day value, which

causes the subject to be counted on day one of a study, but not counted on subsequent

days. This can cause Lambda_z tables to display a subject with a missing day value

on day one, but not display the subject for subsequent days in the study.

PK_Summary_Text.doc does not contain values for parameters from stratified

and excluded tables (QC 2006): Summary text output only includes values for

parameters from non-excluded tables (PK Parameter, Intext, Lambda_z tables). If

only stratified and excluded tables are created, the Summary PK document will not

include the table of PK parameters per profile.

Spacing in table footnotes is inconsistent (QC 2031): Under certain circumstances

(mainly depending on the font and font size), the spacing before and after the source

footnote can vary from table to table. This is caused by Excel's internal calculation of

the height for the cell that contains the footnote. As a workaround, the height of the

respective cells can be adjusted in the Excel file.

If a concentration table splits to the right, the units for Nominal Time are hidden

(QC 2184): If a concentration table is split to the right, the units for nominal time are

truncated when the table is viewed in Microsoft Excel. The units are displayed

correctly when the table is printed. To correct the display issue, select the column that

includes concentration over nominal time, and use the mouse pointer to expand the

column width.

September 2020


Revision 1 of 58

AutoPilot Toolkit tables display incorrect decimal alignment when cells contain

negative values (QC 2979): In tables where Excel worksheet cells have negative

values, the decimal alignment is not applied correctly to the cell.

Treatment Description is wrong in Tables when the description name includes a

symbol (QC 3779): AutoPilot Toolkit does not handle a Greek symbol “mu” in the

treatment description column when creating tables.

The whole footnote for the ‘Intext PK Parameter I’ table is being super-scripted,

instead of only the flag (QC 3853).

The functionality for changing Y-scaling and X-scaling on graph, by graph or

flexible lin/log does not work in all instances (QC 3860):

For Y scaling:

o Graph by graph for linear and uniform for log works as expected.

o Uniform for linear and graph by graph for log is not working for IV

infusion study with those exclusions.

o For graph by graph, only linear plots are adjusted, log plots all have the

same Y scaling.

For X scaling on individual:

Graph by graph or uniform, in combination with any of the three options above, is not

working, the X axis scale does not adjust nor does it adjust for lin or log.

Text

The table in Summary PK document does not fit in the page (QC 1882):

Sometimes the individual PK parameter values calculated for each subject can cause

the tables beneath each graph to exceed the page width of the Summary_PK_Text

document.

The graphs in the Summary PK document do not use display names (QC 2501):

Display name settings from the custom settings file for variables used in the graphs in

the Summary PK document (for example for HL_Lambda_z or Subject) are not used

by AutoPilot Toolkit. There is no workaround for this issue. Due to limitations in the

third party graphing control of Phoenix, display names that include superscripts and

subscripts are not properly applied to the graph titles in these documents.

Y-axis scaling settings applied to WinNonlin charts in Summary PK text

document (QC 2587): The Administration Module and AP Automation object allow

the user to select various scaling options for the time-concentration and summary

concentration charts. Settings to force the Y-axis scaling of these chart groups to be

uniform across all graphs, or to be calculated on a graph-by-graph basis, are also

applied to the charts that appear in the Summary_PK_Text appendix.

September 2020

Phoenix® 8.1 Release Notes Known Issues - Data Tools and Plots

Revision 1 of 58

However, any selections made to the X-axis scaling, including uniform vs. non-

uniform scaling, user-defined tick mark settings, and any options to start the X-axis at

time=0, are only applied to the JNB, WMF, and EMF output objects and not to the

charts in the Summary_PK_Text document, no matter what is selected in the user

interface.

User Interface

Clearing the "Create Graph" check box only prevents the summary portion of

graphs from being created (QC 1892): When the user clears a Create Graph check

box in the graph output detail screen in the Administrator module, only the summary

portion of the graph is not created; the graph itself is still produced.

Intext PK Parameter I and II Analyte tables in automation and comparison

studies copy each other's settings (QC 2540): If a user selects an Intext table in the

Tables tab of an automation or comparison object, and makes changes in the default

selections for non-time dependent and time dependent statistics, the changes are

copied to the other Intext table. For example, if a user selects Comparison Intext PK

Parameter II Analyte in the Tables tab and changes the settings for A and B in the Non

Time Dependent Stats area, the changes are automatically applied to the Comparison

Intext PK Parameter I Analyte table.

Phoenix is slow when handling projects with multiple automation objects,

automation objects with many results, or comparison objects (QC 2810):

Copying and pasting AutoPilot Toolkit operational objects within a project or

workflow can take a long time.


BQL

On some occasions, BQL does not replace “BQL” with 0 during a conditional

substitution (QC 17720/CRM 00167215).

Column Transformation

Blank data produces nulls or data depending on the formula (QC 11574): Custom column transformations can produce different arithmetic results based on the

order of operations if the data contains null values. The problem stems from

ambiguous behavior of doing math with null values. Currently Phoenix can add a

number and a null value and interprets it as addition of 0 or appending an empty value

since + can be used to append text data. However, since null is ambiguous, Phoenix

interprets the result as null.

Example: 0.5*(T1+T2)-0.5*(R1+R2) will always produce a numeric value as long as

either R1 or R2 is not null.

September 2020


Revision 1 of 58

If R1 or R2 is null then this equation 0.5*(T1+T2-R1-R2) will produce null for those

lines because of the order in which it is computed. If R1 is null then T1+T2-R1 is null

and consequently the entire evaluation. If R2 is null then the result is still null because

you have a value – null.

A workaround may be to first replace null values with 0.

The custom column transformation Adjacent option is not working (QC 11728):

For custom transformations, the option to place the new column Adjacent to a column

being used in the transformation is not working and the new column is always

appended at the end of the worksheet.

Data

The Unit Builder does not correctly convert units involving the prefix deca [dk]

(QC 12027): When the prefix deca [dk] is used in unit conversion, the results are

incorrect. The conversion process is using 1.E+2 instead of 1.E+1. In addition, the

abbreviation of [dk] is incorrect and should be [da].

Two unique numbers that are identical out to the 14th significant digit or greater

are treated as the same number (QC 12034, QC 13582): Computer accuracy is

limited to about 14 significant digits. This can cause two unique numbers with more

than 14 significant digits to be treated as the same number. As an example, using the

NCA Slopes Selector when the time data has more than 14 significant digits, and two

points differ at the 14th digit (e.g., 240.333333333333 and 240.333333333334), one

point appears selected for the time range but it is not used in the Slopes Select.

Furthermore, the point representing a number, such as 240.333333333333, is

selectable in the Slopes Selector and can show as the End Time for a user-specified

range, but will not be used in the slope calculation, causing Lambda_Z_Lower and

Lambda_Z_Upper in the output to be off by 1e-14.

One workaround is to click on Slopes and paste the full number. Another possibility

is, prior to NCA, to round the time data so it has 14 significant digits or fewer (use a

custom transformation in the Data Wizard with a formula such as round(time,10)) or

roundsig(time,14)).

The Unit Builder incorrectly treats spaces in units as valid characters (QC

12055): The Unit Builder incorrectly treats spaces as valid characters with no curly

brackets around the units.

Numeric columns that contain more than 17 digits/characters are not displayed

correctly (QC 12164): The workaround is to change the column type to Text.

Numbers cannot be treated as text (QC 12513): This issue has presented itself in

three ways: 1) Columns with numbers as purely text will sort differently than numeric

columns; 2) Very large integers will lose precision due to rounding of significant

digits; 3) Preceding zeroes will be lost in the case of numeric subject identifiers that

September 2020


Revision 1 of 58

start with zeroes. Importing csv files will default strings of numeric values as a

numeric value.

Dataset is deleted when "Refresh from Source" is used after Edit in Excel with

formulas saved (QC 15105): The workaround is to right-click the dataset in the

Object Browser and select Edit in Excel again, make a change to the dataset (this is

important) and then save the changes back to Phoenix, the worksheet will be restored.

Subject IDs with many digits get changed to G8 format, even if imported as text

(QC 15528): Numeric subject IDs with many digits (e.g., 100010901) are changed by

the grids to G8 format by default (e.g., 1.0001090E+08) even if they are imported as

text. Using the G9 format retains the subject ID digits.

Data Interpolation

Interpolation tool fails to interpolate when input is text column (QC 14391): An

extra row in an input dataset containing text will cause entire columns to be treated as

text. The workaround for this defect is to change the columns to numeric.

Data Wizard

Show Dependents option does not show intermediate/secondary output, only final

output (QC 11654): In the Object Browser, Show Dependents will not correctly

show the dependents of IVIVC, Data Wizard, and Levy Plots.

A new “Selection (Exclude)” filter cannot be added after executing Data Wizard;

Filter Selection worksheet is empty (QC 11771): In Data Wizard Filter steps, in

order to create selection-based exclusions, check Retain intermediate results, or the

selection worksheet may be blank when attempting to make the selections.

Data Wizard Execution Warning dialog appears endlessly when using F7 several

times to execute (QC 11806): When executing a workflow with a Data Wizard

object, Phoenix can get into a state where a warning dialog appears every time the

object is executed. Users should use the Execute Locally button instead of F7 when

executing workflows with Data Wizard objects.

Entering a DF value for the Column Transformation tinv that is negative or zero

causes incorrect output (QC 13876): When an invalid DF (i.e., a negative or zero

DF) is entered for the custom function tinv (t-inverse), the output should be blank but

is reported as 1.

Unexpected spaces in formulas cause improper display of the mapping panel (QC

14167): The workaround is to remove spaces in custom transformation formulas.

History worksheet contains the source worksheet history when using “Copy to

Data Folder” from Data Wizard Results (QC 14255): The History sheet of a Data

September 2020


Revision 1 of 58

Wizard result worksheet that has been copied to the Data folder contains all of the

history records from the source worksheet that was mapped into the Data Wizard.

‘IF’ custom function does not work correctly when text mapped to column

exactly matches a word in phrase being tested (QC 15545): The ‘if’ statement in a

custom transformation does not work correctly when the text being mapped to a data

column exactly matches an entire word in the phrase being checked by the ‘if’

statement. For example, the following ‘if’ statement will not correctly match the data

to the given phrase:

if(Form='Form 1234 x 10 days', “Matched”, “”)

where Form is mapped to the dataset column to test. The workaround is either to use

text that is not in the phrase being tested or to use text that is a match to only part of a

word. For example, either of the following will work correctly:

if(Frm='Form 1234 x 10 days', “Matched”, “”)

if(Form='Form1234 x 10 days', “Matched”, “”)

Division by ln(1) does not work properly (QC 17522): Entering the custom formula

of 1+ln(2)/ln(1) produces the incorrect answer of 1.

Descriptive Statistics

Due to statistic name change from “CV% Geometric Mean” to “Geometric

CV%”, backward compatibility is not maintained and the column becomes

unmapped in referencing objects (QC 17436).

Edit in Excel

Editing an HTML Table a second time creates multiple entries on the History tab

(QC 11560): When editing HTML in Excel, it is possible for duplicate history entries

to be generated when changes are applied in Phoenix.

Some numbers are not exported to Excel correctly (QC 12028/CRM 137012): Using Excel format options is problematic, because different columns have different

levels of decimals or significant figures. To work around this issue, send your input

spreadsheet to a Table Object. Set up the table layout, specifying decimals or

significant figures for each table column, and then execute the table. Here is an

example procedure that describes how to export a Table result to Excel:

On the Results tab of the Table object, right-click the Table (Internet Explorer

logo), and select Copy to Tables folder.

Expand the Tables folder in the Object browser (left pane within Phoenix).

Right-click the TableHTMLResult and select Edit in Excel.

Use File > Save As to save the Excel file.

September 2020


Revision 1 of 58

Reporter

Table row statistics appear differently in the Microsoft Word document than in

the Reporter Object (QC 12336): Table row statistics that are emboldened when

displayed within Phoenix appear in regular type in the Microsoft Word report.

The Phoenix Object Browser generates an exception after the Reporter Object is

executed using input from the AutoPilot Toolkit (QC 12341): When the AutoPilot

Toolkit preference Execute as part of a Workflow is checked, and a Workflow

containing a Reporter Object using input from an AutoPilot Toolkit Object is

executed, the Reporter Object will execute successfully. However, a Phoenix error

dialog will appear and the Workflow diagram will fail to display. The user is left in

control and it is strongly recommended that the user save the project. After saving and

reopening the project, the Workflow diagram displays properly.

Formatting is not retained if a caption contains Asian characters (QC 12345): When a caption is created that contains Asian characters, any bold, italics, superscript,

subscript, or underline formatting that is applied to all or part of the caption is not

retained in the report. The Asian characters, however, appear in the report as

expected.

Reporter output for a PK parameter table created from joined worksheets with 2

stratification columns might be missing some data (QC 12416): If stratified tables

are generated in Phoenix from sparse data and the resulting tables have a different

number of columns due to the Remove Empty Column and the Page Break on Row

Stratification options both being checked, the table in the Reporter-generated Word

document can miss some columns when table splitting is applied because the table is

too wide for the document page. The workaround is to uncheck either the Remove

Empty Column or the Page Break on Row Stratification or both.

Mismatch between Reporter captions and plot titles (QC 12491): When there are

multiple plots in the output and one of the plots cannot be generated (e.g., there are not

enough data points to plot), the plot titles may not match the Reporter captions for

those plots.

Reporter generates an error and does not complete if a page is missing from the

plot output (QC 17486): This issue occurred with Phoenix 8.0, but not with releases

prior to 8.0.

Tables

Poor performance has been reported when navigating between the Table object

and data set after executing with a large data set (QC 5322): A significant

slowdown has been shown for projects that contain extremely large tables when trying

to view different project components. The workaround for this issue is to use Page

Break on Row Stratification for extremely large tables.

September 2020

Phoenix® 8.1 Release Notes Known Issues - Framework

Revision 1 of 58

HTML type tables do not use case-sensitive comparisons when determining to

combine rows together in a table (QC 6540): The Table object does not use case-

sensitive comparisons when sorting and grouping data.

Issue with subscripts appearing as superscripts when Tahoma or Courier font is

used (QC 7891): When defining subscripts in the Table object, using the font

Tahoma bold or Courier bold results in the infinity symbol looking like a superscript

when it is not. This is a problem with the font itself and not Phoenix, as it can be

reproduced in Word. The current work-around is to use a different font or disable

bold to get better looking infinity subscripts.

The Table object incorrectly becomes marked as out-of-date (red) when the Style

tab is selected (QC 10919): Just selecting the Style tab will mark a Table object as

out-of-date (red). The Table can be re-executed to return to an up-to-date-status.

Unable to execute Tables after migrating from Windows 7 to Windows 10 (QC

17604): After installing Phoenix 8.0, then upgrading from Windows 7 to Windows

10, it was reported that adding a table to an existing project resulted in the error,

“Failure to create table. Access to the path … denied.” A workaround is to log in as

the administrator.

Word Export

The “Start Table Numbers at” option is ignored when exporting a Table (QC

8023): When exporting html tables created in Phoenix using File > Word Export,

the Worksheet option Start Table Numbers at is ignored. This functionality is

available for worksheets and graphs. Additionally, exporting tables to Word does not

preserve the table formatting. A workaround to preserve formatting (for example,

borders) is to edit table in Excel and copy/paste Excel.

Framework

Dependencies

Workflow-Dependencies report does not contain all charts if > 100 chart tabs

(QC 8682): Right clicking on a workflow in the object browser and selecting

Dependencies exports all objects within a project file and an additional .xml file. The

.xml file contains links for all dependencies. This option can be used to view the work

done in Phoenix outside of the Phoenix system. However, plots containing more than

100 chart tabs will only output the first 100 chart tabs.

File I/O

Rounding issues can on rare occasions cause display issues with time values in

SAS transport files (QC 15729): Due to a defect in a third-party tool, time values

with 59 seconds on occasion have displayed as 60 seconds, whereas in Excel they

September 2020


Revision 1 of 58

have rounded to the next minute, e.g., 9:04:59 has displayed as 9:04:60 but in Excel

displayed as 9:05:00.

Grid Computing

Two unique numbers that are identical out to the 14th significant digit or greater

are treated as the same number (QC 12034, 13582): Computer accuracy is limited

to about 14 significant digits. This can cause two unique numbers with more than 14

significant digits to be treated as the same number. As an example, using the NCA

Slopes Selector when the time data has more than 14 significant digits, and two points

differ at the 14th digit (e.g., 240.333333333333 and 240.333333333334), one point

appears selected for the time range but it is not used in the Slopes Select.

Furthermore, the point representing a number, such as 240.333333333333, is

selectable in the Slopes Selector and can show as the End Time for a user-specified

range, but will not be used in the slope calculation, causing Lambda_Z_Lower and

Lambda_Z_Upper in the output to be off by 1e-14.

Subject IDs with many digits get changed to G8 format, even if imported as text

(QC 15528): Numeric subject IDs with many digits (e.g., 100010901) are changed by

the grids to G8 format by default (e.g., 1.0001090E+08) even if they are imported as

text. Using the G9 format retains the subject ID digits.

Jobs canceled from Phoenix (while they are in a wait state in the queue) remain

in the queue (QC 17632): The number of available cores specified for a grid cannot

exceed the total number of cores for which the grid is configured. This might cause

the software to ask for more cores to do the computation than are available and result

in the job getting stuck in the queue.

History

When data is pasted into the * row of the data grid the history does not record

the row information (QC 7696): In order for a row-paste operation to be entered

into the history, the data to be copied must be selected by highlighting the individual

cells, and pasted by selecting the destination row number. The data can be pasted by

selecting the destination cells, but the history entry will not be created. Similarly, the

data can be copied by selecting a row number, and then pasted, but there will be no

history entry.

History for Paste event (for vertical range of cells) is incorrectly recorded, if only

one cell is highlighted and Ctrl+V is pressed to cover the entire vertical range of

cells (QC 10450): Selected ranges that are copied then pasted into a single range

might not correctly record the destination range.

Moving contents of selected rows to another set of rows does not get correctly

added as an event in the History tab (QC 12008): Audit events are not captured

correctly when rows are dragged from one location to another in a worksheet.

September 2020


Revision 1 of 58

Licensing

User is not warned before closing and loses project modifications if framework

license was lost and Phoenix left open (QC 8510): If a Named User Server license

is disconnected while there are still unsaved projects open, then the user must ensure

that a license has been retrieved before attempting to close Phoenix. If the user does

close Phoenix without first re-acquiring a license, there will be no ability to save, and

all changes will be lost.

Logging

Issue with logging service affects performance of Phoenix when starting up and

when accessing Edit > Preferences (QC 12450): Large log files cause problems

within the logging service which, in turn, affects the performance of Phoenix when

starting up or when accessing the Preference dialog. If the performance starts to slow

down, try deleting the Phoenix log files

Mapping

Copy-and-paste of operational objects maps Lower automatically even if it is not

mapped in the original object (QC 9875): When doing Copy and Paste of

operational objects, auto-mapping can take place. For example, a parameter

worksheet with a Lower or Upper column can be unexpectedly mapped when pasting

in a model. It is a good idea to check mappings after doing a Paste.

NONMEM

NONMEM control file does not ignore blanks or tabs (QC 9372): The NONMEM

shell in Phoenix does not recognize blanks or tabs before NONMEM commands. If

the user loads or copies a NONMEM control into the Phoenix NONMEM shell and it

contains blanks before the statements, they are not recognized. For example the first

statement below is ignored:

“ $input “

vs.

“$input “

The workaround is to remove any blanks or tabs before the commands in NONMEM

controls before executing them within Phoenix.

NONMEM TIME input required for Dose-effect model when not necessary for

analysis (QC 10052): When doing analysis with NONMEM shell using Dose-Effect

model, TIME is required as input field in data even though it is not used in analysis.

The workaround is to add a dummy TIME column and map it.

NONMEM Input statements containing equal signs are not recognized (QC

10658): If the NONMEM input statement contains equal signs like $INPUT ID TIME

DV=DROP LNDV=DV MDV AMT RATE EVID DOSE, the Phoenix mappings do

September 2020


Revision 1 of 58

not recognize the drop option and will still present a DV variable in the mappings. In

addition a statement like LNDV=DV will show up as LNDV_DV.

The workaround is to modify the input statement in the NONMEM control file by

manually removing any DROP variables (they will not be mapped and thus not used)

and just providing the name of the variable that is needed. For example, the example

above should be modified as $INPUT ID TIME DV MDV AMT RATE EVID DOSE

and the column LNDV mapped to DV.

NONMEM 7 local run executions do not use user-defined names from Control

file for Covariance and Correlation (QC 10733): This issue is only in the column

headers for the Covariance Matrix and Correlation Matrix worksheets, not the numeric

results.

NONMEM scripts with lowercase or mixed-case phxtbl cause problems in

PHXTBL output (QC 10799): Lower case or mixed case user specified tables

named phxtbl can result in duplicate NONMEM output files because Phoenix

generates a file named PHXTBL by default for use with the NONMEM comparison

tool. To work around the problem, rename the table.

NONMEM plug-in will not start the specified Development Environment unless a

dataset is specified already (QC 11931): The NONMEM plug-in requires that a

dataset is provided before the selected NONMEM development environment is

launched. In previous versions, the user was not informed why the development

environment was not launched. An error message is now displayed to indicate to the

user that a dataset needs to be provided.

NONMEM simulation script results in Scatterplot error (QC 12382/CRM

139546): Phoenix code that gets added to the script results in an incorrect

identification of a NONMEM comparison occurring, when the script is actually

calling for a NONMEM simulation only. As a result, Phoenix is looking for a table

from which to generate a scatterplot for the comparison. This table is not created by

the script and the script never successfully executes.

PKS

PKS Study View – leading zeroes and commas are dropped from values (QC

12248): When creating a PKS Study from Phoenix, if a source field contains comma-

separated numeric values and is mapped to a Sample, Dose, or Demographic in PKS,

the commas are erroneously stripped out and the value is stored as a single numeric

value. For example, if a field contains "01, 2, 3", the value will be stored in PKS as

123.

An apostrophe in the column name prevents the study from being created

correctly (QC 14676): If the PCTESTCD values (mapped to Analyte) contain an

apostrophe, it leads to an error when the study is created: Instead of adding the data to

the mapped columns, they are all joined together and added to the value in the column.

September 2020


Revision 1 of 58

Saving a new version of a PKS scenario can fail if the URL to the PKS middle-

tier is changed from the URL used when the scenario was saved (QC 15086): Loading a PKS scenario and submitting the workflow to the JMS for processing can

prevent the scenario from being saved if it was saved using the old PKS middle-tier

URL and then loaded using the new URL. The workaround is to load the scenario,

run it locally, and save it to the PKS again. The new URL is used to verify the

existence of objects in PKS prior to the save.

Error getting latest version of out-of-date dependent objects loaded from other

scenarios (QC 15362): If a scenario (A) has dependencies to ScenarioDatasets or

ScenarioObjects from other scenarios, and those objects go out-of-date by creating a

new version of the scenarios, then the scenario (A) will display the option to get the

latest versions, but it fails when trying to get the latest versions. The workaround is to

load the scenario and use Refresh from Source to get the latest version of the

dependent objects.

Printing

Printing -wide Table gets truncated (QC 5432): There is a known issue with

printing tables comprised of wide data directly from Phoenix. These wide tables will

be truncated in the printed output. While this is an Internet Explorer print limitation,

the following workaround will allow users to print data in wide tables:

Right click on the Result Tables -Table output, and select Copy to Tables

Folder.

Navigate to the Table folder in the Object Browser, right-click the

TableHtmlResult item and select Edit in Excel.

Click OK in the message dialog.

The table data is then displayed in Excel.

Users can format as desired and/or use the File > Page Setup > Fit to One Page

option to view the output.

File > Print All always prints using the default printer (QC 12153/CRM 137935):

When using the Print All function, regardless of the printer selected in the Print

dialog, the output will only go to the default printer. If the default printer happens to

be a Microsoft XPS Document or PDF and the selected study has hundreds of

thousands of records, there could be hundreds or thousands of Save PDF File As

windows popping up, which could lead to crashing the system.

Modifications to margins are lost when printing a table (html) from Phoenix (QC

12158/CRM 137981): Changing the margins does not get applied when printing

directly from the Table object. The workaround is to set margins in the Table object

and then right-click and select Copy to Table folder. Navigate to the Table folder in

the Object Browser, right-click the TableHtmlResult item, and select Print.

September 2020


Revision 1 of 58

Printed History truncates the description of column contents (QC 13900): The

Description column becomes truncated if:

the line of text is longer than the width of the cell, or

the description contains more than one line of text.

There is currently no known workaround for this issue.

Projects

Execution Error encountered after object is re-serialized to resolve conflict –

“The GetRows methods cannot be called while the view is inactive” (QC 14728): To work around, save, close and re-load the project and the object will execute

successfully.

PsN

PsN plug-in does not work with shortcuts to model files that contain spaces in

path (QC 11880): For PsN Shell objects, if the user selects to "Bring Model Files In

as Shortcuts" the path to the model file cannot contain any spaces, e.g., C:\Program

Files.

Performance issue when loading PsN bootstrap results (QC 14074): Bootstrap

PsN can generate thousands of results if the user has set the number of sub-directories

to traverse to a value greater than 2. It can take hours to load the results in some cases.

There is no known workaround for this issue. Note that loading the results as

shortcuts does not appear to improve the performance.

PsN Plug-in validates working folder location when submitting to JMS (QC

14324): Currently, when executing PsN on JMS, the working folder location must

exist both on the client and on the JPS server or PsN will fail validation. To work

around this issue, use a standard working folder location on all clients and make sure

that the standard path also exists on all JPS servers.

R

Start Development Environment is not working for Tinn-R unless Tinn-R is

already opened (QC 11450): To use the option Start Development Environment

with Tinn-R, start up Tinn_R outside of Phoenix first.

When datasource inputs are published by adding decorated attach statements

and later all of these statements are removed, the datasource inputs remain (QC

11839): If clearing all inputs published via attach statements, another dummy

attach statement must be added and mapped for execution.

R object does not re-execute a prior object in the workflow if needed (QC 12985): Other Phoenix objects in a workflow allow the user to click and execute the last object

September 2020

Phoenix® 8.1 Release Notes Known Issues - IVIVC

Revision 1 of 58

in a chain and it will re-run any necessary objects earlier in the workflow. With the R

object, the user must execute the earlier objects manually prior to executing the R

object.

Reporter

Table row statistics appear differently in the Microsoft Word document than in

the Reporter Object (QC 12336): Table row statistics that are emboldened when

displayed within Phoenix appear in regular type in the Microsoft Word report.

User Interface

Phoenix Model-Setup-Dosing-Grid does not allow input (QC 10725): When using

Copy Down in grids, sometimes the cells become read-only. To enter data, try

double-clicking in the cell or selecting the cell and then entering the data in the field

that displays the data for the cell at the top of the grid.

Resizing of Phoenix window and fonts on Windows 10, can lead to the inability to

select some buttons or tabs (QC 16904): Try changing the size of text, apps, and

other items to 100% (right-click on the Desktop and choose the Display menu item),

then restart your computer to apply changes.

Running Phoenix with Windows Text Size (DPI Scaling) greater than 100%

results in overlapping UI (QC 17302): This issue is caused by Phoenix not being

DPI aware and is most frequently seen on laptops. If you encounter overlapping

controls in Phoenix, try reducing the scaling to 100%.

Exception occurs when trying to “View Source” for created plot, and project

cannot be closed (QC 17728): An exception may occur when selecting View Source

for a Plot object to open the source data in a new window, then selecting the Windows

menu in the Phoenix main menu (not in the new Source window), and then selecting

the Close All menu option. The exception can be avoided by closing the Source

window through any other means, such as the “X” button or the Close All option in

the Windows menu of the Source window.

Watson-LIMS

The Watson Plug-in does not specify an Audit Reason when appending dosing

information to a PKS Study (QC 14914): The workaround is to generate a full audit

report using the PKS Web interface to see the records affected.

IVIVC

Convolution

When the number of Exponential terms in worksheet is less than the number in

the settings, the maximum number of defined exponential terms will be used (QC

September 2020


Revision 1 of 58

8801): The number of exponential terms used in convolution is limited by the number

of defined terms. For example, if the number of exponential terms is set to 3 in the

settings, and only 2 terms are defined, only two will be used.

The Exponential Terms values disappear from copy/paste when input data set

has a sort mapped (QC 8811): If the convolution input has a sort variable and the

UIR source is internal, copy/pasting the convolution object will result in the UIR

internal source being reset. The workaround is to publish the internal UIR source so

that it is now external, and then copy/paste will just point to the UIR source.

No results will be shown for a subject if the source data set has any blank or text

values (QC 10523): Convolution will not generate results for profiles that have any

non-numeric Cumulative_Input values. The workaround is to filter out non-numeric

values. This can be done be creating an x*n where n=1 transformation to create a new

column that contains NULLs for non-numeric values. Then use a filter to filter out the

non-numeric values.

Verification does not fail if Sort values in Input Function and UIR do not match

(QC 10697): Convolution does not verify that the input sort values match between

the Input and UIR sources. It will only use the UIR sorts that match the Input source.

This is only an issue when the UIR input is mapped to an external source.

IVIVC fails to give prediction errors when doses are in large numbers (QC

13350/CRM 142678): Very large numeric dosing values for InVivo (regardless of

unit) can result in small Fraction_Input result on deconvolution. This can prevent

Convolution in the prediction stage from producing non-zero concentrations.

Consequently, Validation and Prediction results will not be accurate. The workaround

is to change the dosing units to reduce the magnitude of the values.

Convolution fails execution when Time column is declared as type Text (QC

17732): If the input column used as the Time variable is declared as type Text, the

Convolution tool may yield the erroneous error message, “Time data must be sorted in

increasing order.” The workaround is to change the type to Numeric.

Levy Plot

Word Export in Phoenix takes a much longer time as compared to WinNonlin

and as a result, system becomes unresponsive (QC 9772): When using Word

Export on Levy Plots and IVIVC Workflow objects, the list of output includes all

internal objects, and the objects are not readily discernible. Work Export is not

recommended for IVIVC and Levy Plots.

Settings are missing in Settings text output and History tab (QC 10628): Settings

are not contained in the results; look at the Properties panel to see the settings.

September 2020


Revision 1 of 58

Levy plot created even if units in Values column are different (QC 10652): Levy

Plot does not prevent or warn the user if the units in the Values source columns do not

match.

Levy plot results are incorrect if data has sort variables, but sort variables are

not used (QC 10681): Duplicate time points for a given profile are not handled

properly for Levy Plots. The workaround is to use descriptive statistics to average the

profiles to ensure distinct unique time points per profile.

Problem using multiple sort variables and user-specified matched values (QC

10896): In a Levy Plot object, if sort variables and user-specified matched values are

used, the following error is encountered if the sort variables contain missing or null

values: Bad conversion from DBNULL to Boolean. The workaround is to fill in any

missing or null values.

Levy Plot - Output remains red when Workflow is executed, but object is black

(QC 11609): In some cases, the Levy Plot output may appear out-of-date after

executing. The workaround is to unmap and then re-map a column and re-execute the

Levy Plot object.

Levy plots can fail to execute if there is a blank in a Formulation column (QC

12370): Levy Plots do not support blank/empty cells in the Formulation column. It

will prevent execution of the Levy Plot object.

Wagner-Nelson & Loo-Riegelman

No settings provided in Settings text output and therefore not in History (QC

10348): Some settings are missing in the output of Wagner-Nelson and Loo-

Riegelman. To find the settings, look on the Options tab, the Slopes source and the

Parameters source (for Loo-Riegelman).

Workflow

IVIVC Validation fails when number of subjects in different studies is different

AND one of them has only one subject (QC 4873): If a crossover study, for

example, has multiple formulations and studies, and one study has a different number

of subjects and one study has one subject, the Validate Correlation process fails. The

failure occurs when the Mean option for Averaging is used for external validation.

Vivo.Deconvolution.Exponential Terms missing units for A and Alpha (QC

9708): Exponential terms output from Deconvolution does not contain units.

Prediction Dose units do not match In Vivo Dose units when external dosing

worksheet is used (QC 9809): If dosing units are specified by an external worksheet

for In Vivo and the Prediction Dosing is an internal worksheet, the Prediction Dosing

internal worksheet will not reflect the Dosing units of the External Dosing for In Vivo.

The dosing unit in the prediction stage is assumed to be the same as the In Vivo stage.

September 2020


Revision 1 of 58

Pred Conv Out plot - All plots are not on one page (QC 10245): For the IVIVC

Convolution Output Plots, the plots are not grouped by Formulation when there is a

sort variable. Each plot is displayed on a separate tab.

Executing IVIVC steps by buttons in Properties panel does not cause execution of

source feeders (QC 10419): The workaround is to use the execute button on the

IVIVC workflow object to ensure sources are executed prior to IVIVC workflow

verification.

Dependency output for a Partially Executed IVIVC Baseline project does not

match Execution Output (QC 10568): When exporting dependencies, if the text

output has the same name as a worksheet, only the worksheet is available in the

dependencies view in the browser. The actual result is exported to disk and can be

found in the folder where the dependencies were exported.

Settings missing in History tab description when workflow is executed (QC

10633): When the IVIVC object is executed, the settings are not recorded on the

History tab; however, they can be found in the Settings text output files:

Correlation.Correlation.Settings Validation.Conv.Settings

Prediction.Conv.Settings Validation.Corr.Sim.Settings

Prediction.Corr.Sim.Settings Validation.Observed.Baseline.Nca.Settings

Prediction.Diss.Settings Validation.Predicted PK.Nca.Settings

Prediction.Observed.Baseline.Nca.Settings Validation.Settings

Prediction.Predicted.Nca.Prediction.Settings Vitro.Dissolution.Settings

Validation.Average.Vivo.Settings Vivo.Deconvolution.Settings

Vivo.UIR.Settings.

Executions of individual steps are not recorded on the History tab (QC 10637): If

the IVIVC workflow is executed using the Execute button in the toolbar, the History

tab will record this event; however, when individual steps are executed (Fit

Dissolution, Validate Correlation, Predict PK, etc.), they are not recorded in the

History tab.

Levy Plot: Formulation column in data set used even if not mapped (QC 10689):

If the sources for Levy Plot have the column Formulation, and no columns are mapped

to Formulation in the sources, the columns called Formulation will be used even

though not mapped and the Levy Plot will fail if the formulations in the columns do

not match.

Unable to complete Validation if UIR step previously failed due to bad mapping

(QC 10832): If the UIR step previously failed due to incorrect column mappings (for

example, the Sort and Values column were inadvertently switched), the Validate

Correlation and Predict PK steps will continue to fail, even after the In Vivo Data

mappings are corrected. The workaround is to make a copy of the In Vivo data set,

September 2020


Revision 1 of 58

pre-fix all of the column names with X (Time column is renamed XTime), then map

this data set to the In Vivo Data setup and map columns appropriately. The Validate

Correlation and Predict PK steps will now execute successfully.

Prediction does not complete if Prediction Dissolution setup is completed before

Prediction Data setup (QC 11024): In an IVIVC object, the following error is

encountered in the Prediction step if an external worksheet is used for Prediction

Estimates and this mapping is completed before the mapping for Prediction Data:

Failed Validation

1 or more columns required for Name in Units

1 or more columns required for Preferred in Units

IVIVC tool can enter a broken state that cannot be fixed (QC 13266/CRM

142192): The IVIVC tool has restrictions on a column named Formulation. If this

column is mapped to a Sort variable in InVivo Data (even just temporarily), it will

cause the IVIVC object to break and not to be able to perform Prediction. If this

happens, the only solution is to create a new IVIVC object, reapply all the settings,

change any Sort input column named Formulation to another name, remap, and

execute.

Objects using results of partially executed IVIVC object fail verification (QC

13307): Even if Prediction is not being done, the Target Formulation may need to

be set in order to use output from IVIVC downstream. Not setting the Target

Formulation on the Prediction tab will prevent IVIVC from passing verification,

which will prevent use of output in other objects. Selecting any value in the Target

Formulation dropdown should get IVIVC to pass verification so that downstream

objects will execute using the IVIVC results.

Cannot generate Levy plots (QC 13844): If Formulation is mapped to the InVitro

Formulation, it can cause the Levy Plots to not be generated when requested. The

workaround is to recreate the IVIVC object and not map a column named Formulation

to the InVitro Formulation mapping.

Prediction and Validation Errors are different from Reference (QC 14353): If

columns mapped to IVIVC time mappings (i.e., InVitro Time, InVivo Independent,

and Prediction Time) have type Text, these columns will be sorted as text rather than

numerically when performing Validation and Prediction, which will cause errors in the

internal interpolation routine. Column mistyping could occur by importing time

values specified by an equation in another tool. To work around this, check that

numeric column types are mapped to the IVIVC time mappings and change the source

columns to type Numeric, if needed.

Re-executing Validate Correlation after publishing internal worksheets passes

verification, even though columns have not yet been mapped (QC 14692):

Publishing InVitro Estimates and then using the Validate Correlation button on the

Correlation tab should fail verification because the columns are not yet mapped.

However, the Validation Correlation step completes with no verification error,

September 2020


Revision 1 of 58

although a validation error is displayed in a pop-up. Users should confirm that

columns are mapped after publishing and before using the Validate Correlation

button.

Formulation data that is not mapped in the InVitro Formulation panel is still

included in the output plots (QC 14874): The IVIVC toolkit creates IVIVC plots by

default (Correlation overlay, Levy plot, and Fabs vs Fdiss). These plots are

incorrectly including other formulations (e.g., Target) that are checked to not be

included in the “InVitro Formulation” panel (i.e., set to None in mappings window).

This could lead to a confusing interpretation of those plots because, in some cases,

formulations displayed can be made using different technologies. (The IVIVC

correlation model itself and any results from it do not include these other formulations

if they are set to None.) As a workaround, the user can use the resulting worksheets

and create plots after filtering the formulation that should not be included (e.g., for the

Levy plot, filter unwanted data from the “Levy Plots.Tvivo vs Tvitro.Levy Plot

Values” worksheet; for the Correlation overlay plot, filter unwanted data from the

“Correlation.Abs vs Diss Data” worksheet). In addition, the user must specify the data

to plot the line of unity.

IVIVC freezes when executing from the Execute button but using all the

individual Run buttons works correctly (QC 15063): This appears to be a rare

occurrence. If it is encountered, try using the buttons in the IVIVC Workflow

individually (Generate UIR, Deconvolve, Build Correlation, Generate Plots, Validate

Correlation).

IVIVC item is marked out-of-date even though all results are up to date (QC

15110): In cases where a prediction has been partially set up at one time and then

removed, the IVIVC object will appear as being out-of-date, even though there is no

Prediction output yet.

Initial Estimates for InVitro and Prediction are not persistent after previously

executing with an external worksheet (QC 15153): In situations where an external

Initial Estimates worksheet is used and the user has made changes to the “Fixed or

Estimated” and Initial columns, switching to an internal worksheet resets those user-

specified settings to their default values. Users will need to make those changes again

for the internal worksheet.

In an IVIVC object, parameter FMAX in Makoid Banakar is not fixed to the

specified value as in other Dissolution models (QC 16373): One workaround is to

set the initial estimates option to User-Supplied Initial Parameter Values, and then

set initial estimates for any estimated parameters. Alternatively, you can create a

worksheet and use it as an external worksheet for the initial estimates. Another

workaround is to run the Dissolution Model separately from the IVIVC Workflow and

run it in WNL Classic Modeling, with FMAX set to 1.

September 2020

Phoenix® 8.1 Release Notes Known Issues - JMS

Revision 1 of 58

JMS

After merging a job from JMS, the user interface reflects a ready state even

though the Merge process is proceeding (QC 10328): For projects with a lot of data

(NLME), large objects (IVIVC), or many objects, the merging of a job from JMS can

take some time and the status window can indicate ready when it is actually still

processing the merge back into the local workspace.

Phoenix Licensing Wizard

Clean.log is not time stamped (QC 49).

Uninstalling previous versions of the PLW on Windows 7 (SP1) fails to remove a

registry entry, which causes the PLW installer to abort (QC 138): If you should

encounter this issue, please contact Support for assistance. (Note that the registry

entry is properly removed when PLW is uninstalled.)

Domain field should not be filled in when the machine does not reside on a

domain (QC 190): Currently, the Domain field defaults to the localhost machine

name when that machine does not reside on a domain. This field should be empty

under such conditions.

User Management - In the Add User(s) dialog, entering incorrect information in

the Domain Specification section and then using the Group pull-down causes an

exception (QC 203): When this exception occurs, users can click Continue and

return to the dialog where the domain information can be corrected.

Installing PLW 3.0 fails with “Runtime error in setup script” (QC 212): There is

a dll that is missing from the PLW 3.0 installer package, causing the installation to fail

with the message 'Runtime error in setup script, Source File:

PharsightLicensingServer, Line Number: 131'. If you encounter this problem, please

contact Certara Support.

Severe performance problem reported with PLW 3.0 user management that

involved over 200 users (QC 213): When adding a new user to a Group, opening the

Groups list and selecting a Group for the user, used multiple GB of memory and

eventually PLW froze. A possible workaround is to edit the lsreserv list directly.

NLME

NLME does not run if Windows 8dot3 short names are disabled (QC 16337): If

Windows 8dot3 short names are disabled on the machine, directories containing

spaces, such as “Program Files(x86)”, can be problematic. Re-enabling 8dot3 short

names is not easy to do and it is not recommended that users attempt it. The best

available solution identified thus far is to reinstall Phoenix to the root directory, i.e.

C:\Phoenix. This circumvents the C:\Program Files(x86) filepath and allows the

NLME models to compile.

September 2020

Phoenix® 8.1 Release Notes Known Issues - NLME

Revision 1 of 58

Some observables are not shown in Initial Estimates tab when there are more

than five observation variables in the model (QC 17719/CRM 00167162): The

Initial Estimates tab is unable to show all possible graphs with observable variables

when the number of observables exceeds five. The workaround is to switch to a

textual model.

Engines

Simulation table and Simulation output do not match; there is a small difference

at time of dose (QC 12109): When generating tables from model fitting runs, if

reporting times in a table are simultaneous with dosing times, the table reporting may

actually occur before the doses, even though they are at identical times. This is simply

an artifact of simultaneity, for which there is no clearly correct behavior.

No warnings are issued when improper case is used in column names for SS, etc.

(QC 12767): In SS and ADDL cycle definitions, if column names used for dose

amounts or delta-t do not precisely match the column names in the input dataset, the

results are incorrect and no warning is given.

Special characters in the ID column cause the NLME engine to crash (QC

13354): Special characters, such as the Greek letter “beta,” in the data can cause

NLME7.exe to abort. The user is advised to avoid include such special characters in

their data.

If a crash occurs while using MPI in NLME, other MPI processes may be left

running, which can cause unpredictable behavior in NLME (QC 14279): If one

of the MPI processes crashes, other MPI processes and the parent process mpiexec.exe

may be left running. This can leave NLME in an unpredictable state, such as being

unusually slow to execute or being unable to execute another model. To fix the

problem, mpiexec.exe must be stopped from the Task Manager. This will stop any

other MPI processes. The problem should only occur with an engine crash, not when

using the Stop Execution or Stop Early buttons, or when NLME ends with an error

message.

Posthoc table is not correct when the model is not time-based and covariates are

used for stparm (QC 17406): A workaround is to add a fake deriv statement and

map the apparent time to a fake variable.

Model Comparer

When a Sort variable is used, the Hide and Compare checkboxes do not maintain

their checked/unchecked status (QC 10765): Once a Hide or Compare checkbox is

checked or unchecked in the Phoenix Model Comparer, additional models can be

checked or unchecked by moving the mouse cursor over the checkboxes, even if not

selecting the checkboxes. This only happens when a Sort variable is used. The status

of the checkboxes may also revert to a prior status when Execute is selected.

September 2020


Revision 1 of 58

Comparison Result cannot be loaded into an R object, but works directly in R

(QC 13965): When using the R object for accessing the Model Comparer results for

NLME or NONMEM, the default .csv file generated for importing into R will not

work. The columns beginning with # are preventing the default .csv file from loading

into R. The workaround is to not have these output columns generated in the Model

Comparer or explicitly state the columns to import with acceptable names via the

commenting mechanism for mapping in the R tool. For example, to import all the

columns generated by the Model Comparer into an R script, use a script similar to the

following and map the columns:

attach(compare.df) #WNL_IN Hide Compare Name Sort Method

Description Lineage LogLik -2(LL) AIC BIC -2(LL)Delta

AICDelta BICDelta NumParms NumObs NumSubj pvalue

Incorrect identification of models (QC 17364): If multiple Phoenix Model objects

have the same names in different workflows, when the Model Comparer is used, all

models with the same names will be used in the comparison. Even if the models with

duplicated names are not checked, the checkboxes will be checked at execution. The

workarounds are to not use the same names for different model objects, or to check the

Hide checkboxes next to the model objects that are not wanted for the comparison.

User Interface

Categorical plots show 0, 1 but instead should correspond to the description

mapping (e.g., male and female) (QC 3645): For categorical covariates, the user has

the option to enter the categorical name that corresponds to the value in the covariate

column. However, this information is not used downstream and plots and worksheets

will still display the values of the categorical covariate instead of the categorical name.

There is no option for using sort keys in the internal worksheet for dosing (QC

6567): For Phoenix models, internal worksheets such as dosing require input for all

values of the sort variables. This is unlike other tools, which allow the same input to

be used across specified sort variables. To work around this, dose amounts and times

should be dragged into the worksheet.

Phoenix WinNonlin models generate TAD default plots when time and/or dose

are not in the model specification (QC 7573): Default plots from library Phoenix

models will always generate plots with Time After Dose (TAD) in the X-axis. These

plots are generated by default even if time is not the x-variable in the model (for

example pharmacodynamic Emax models) or if dose is an inappropriate concept in the

model. In these cases, these plots just duplicate the plots with IVAR in the x-axis.

Graphical editor, observation from the elimination compartment, model built is

over-parameterized (QC 7678): Changing the observation in the Graphical Editor

from the central compartment to the elimination compartment does not update the

September 2020


Revision 1 of 58

model parameters correctly. The model will be over-parameterized. The workaround

is to use a Textual model.

Maximum number of Sort and ID columns is not checked in the user interface,

which can lead to columns missing in the output (QC 7905): Although the total

number of mapped Sort and ID columns cannot be more than 5, this is not checked in

the UI, and more than 5 can be mapped, giving incorrect results.

Random Effects setup can change upon model update (QC 8140): The order of

the random effects and associated initial estimates can change if the user selects

different model parameterization after the random effects have been setup. The order

of the random effects is not remembered if the structural model is changed. Caution is

advised in double-checking the random effects entries after a model is changed.

Secondary parameter uses the last value for variant parameters (QC 8181): If a

secondary parameter definition is a function of a parameter that changes over time or

across subjects (for example, dose, concentration) the secondary parameter will be

calculated using the last value for that parameter. It is advised that definitions for

secondary parameters only involve invariant parameters.

Default plots from Phoenix models that are non-time-based can be sorted

incorrectly (QC 8442/CRM 147536): Phoenix models with an independent variable

(IVAR) that is not “time” might display default output graphs incorrectly. The

workaround is to manually sort the data prior to executing the model; this can be

accomplished directly from the mappings panel by clicking the new button View

Source and then selecting to sort the worksheet.

If Parameter.Mappings is forgotten when using a worksheet for initial estimates,

the values on the bottom tab are used without a warning (QC 8529).

When going from a PK/Emax or PK/Indirect Built-in Model to a Graphical

model, if Freeze PK is selected for Built-in, the parameters do not stay frozen in

the Graphical model (QC 8543): The workaround is to select the boxes in the

Graphical Editor to freeze the individual PK parameters.

Verification does not fail if values for Dosepoint, Amount, Delta Time, and Rate

are missing or not valid (QC 8805): If SS or ADDL input is specified, and if input

column names are given, the column names are case-sensitive and must match the

column names in the input data set. If they do not match, there is no warning, and the

result can be undefined behavior, as NA values are used.

Numbers typed in text fields with commas for decimals breaks PML (QC 8925):

Where numbers can be entered in data fields, generally either comma (,) or period (.)

can be used as a decimal point. (It will be converted to period.) However, there are

fields where sequences of numbers, separated by commas, can be entered, such as the

sequence of times in a table specification. In those fields, the comma character cannot

be used as a decimal point, because it acts as a delimiter between numbers.

September 2020


Revision 1 of 58

NLME cannot run when imported data is in a format that has commas (QC

9552): In Phoenix, the default display format is not one that uses commas as decimal

points. In general, US format numbers should be used in worksheets. That is, using

the period character (.) as a decimal point, and no thousands separator.

Changing the PML code requires rebuilding of the dosing sheet (QC 11306):

When changing a model from individual to population or vice versa, and changing

between Sort and ID mapping, if there is a built-in dosing worksheet, care must be

taken to rebuild the worksheet. Otherwise, it retains the prior mapping, causing a

verification error when attempting to run the model.

When running in graphical mode, sequence blocks cannot be entered in the

procedure block (QC 11933).

NLME output should not show the missing value code 3.3E-151 (QC 12251):

When the value 3.3E-151 appears in the output, it signifies the absence of a number in

that location and the user should treat it as a missing value.

A fixed effect term involving a categorical covariate is not recognized in the

secondary parameter definition for a Built-in model (QC 14223): Secondary

parameters depending on categorical covariate effects do not work for Built-in or

Graphical models. The user interface does not accept them. However, they do work

for Textual models. For example, if “sex” is a categorical covariate having values 0

and 1, and it modifies column “V,” then there is a fixed effect named “dVdsex1.”

This fixed effect is not recognized in the secondary parameter definition; however it

will work in a Textual model.

Parsing of a model fails to remove fixef parameters if they are deleted from the

Textual model (QC 14256): When doing a Profile of a Textual model, it is possible

to get extra copies of fixed effects appearing in the “Fixed Eff” list. There does not

seem to be a way to recover from this, other than returning to a Built-in or Graphical

model.

When “Stop Early” is executed, the “Warnings and Errors” output does not

clearly state that the execution was stopped early (QC 14380): If the user reviews

this output later, the user should check the Overall output to see the Return Code of 6,

which will show that the fitting was not allowed to run to convergence.

Population Simulation can generate an unpopulated Table01 after executing a

Simple run with the Table option (QC 14407): If a Simple fitting run is done, and a

table is requested in the Run Options, it appears in worksheet Table01. If the Run

option is then changed to Sim./Pred Check and the model is run, Table01 also

appears, except it is empty. (If a Simulation Table is requested, its contents appear as

a .csv file, because it may well be too large for a worksheet.) If the contents of

Table01 are desired, one should switch back to Simple run mode, fit the mode, and

then capture the contents of Table01 into some other repository, like an Excel

spreadsheet.

September 2020


Revision 1 of 58

For a sequential model, the Initial Estimates tab does not show PD parameters

(QC 14435): When the Initial Estimates tab is used with a sequential model, PD

parameters are not shown in the parameter list, they cannot be adjusted, and plot

results for PD observations cannot be displayed. The workaround for this is:

1. Edit file Phoenix.exe.config and change the line <nlog globalThreshold="Trace">

to <nlog globalThreshold="Debug">

2. Make sure that the directory c:\PhxTemp exists.

When this directory exists, NLME will use it for all temporary files.

The plot will now work correctly.

Individual simulation in NLME is not reporting sort values in Rawsimout files

(QC 14447): When running simulation in an individual model, the Rawsimout.csv

file does not indicate which subject the simulation is for. Rather it makes multiple

copies of the file, one for each subject, but there is no indication which file goes with

which subject.

Using the Initial Estimates tool before adding a secondary parameter causes

inactive text boxes in the Secondary sub-tab (QC 16343): A workaround is to add

secondary parameters before using the Initial Estimates tab. Alternatively, clicking

the Add button a second time will display a second row of text boxes that are active.

Enter the secondary parameter definition in the second row and then delete the first

row, which is blank.

WinNonlin

Bioequivalence

Table using Bioequivalence output as the source is not updated correctly when

the Bioequivalence object is re-executed (QC 7724): When re-executing a

Bioequivalence object, new instances of the Ratio output worksheets are created,

rather than simply updating the existing instances. If another object, such as a table, is

linked to the original worksheets, after re-execution of the Bioequivalence object, the

downstream object will need to be re-linked to the new result worksheets.

Validation Suite

Phoenix Installation test case in Validation suite fails after Integral 1.1 or PKSubmit 1.1 are installed (QC 18053): The Integral 1.1 and PKSubmit 1.1 plugins have a separate installer from Phoenix that removes the Integral and PK Submit plugins original installed with Phoenix 8.1. As a result, installing the Integral 1.1 or PKSubmit 1.1 plugin causes the Phoenix Installation test case in the Validation Suite to report a false failure, since it cannot find the original plugins.

September 2020


Revision 1 of 58

Changing a column name after setting up Bioequivalence leaves the object in a

state where it cannot be re-executed (QC 13010): If the name of a classification

variable is changed, the prior column name still appears in the Classification Variables

field and cannot be removed, and this causes the execution to fail. The workaround is

to finalize the column names before sending data to the Bioequivalence or LinMix

objects.

LinMix

Loss of accuracy in LinMix confidence intervals for small sample sizes (NDF < 5)

(QC 4698): The CIs in Linear Mixed Effects Modeling use an approximation for the

t-value which is very accurate when the degrees of freedom is at least five, but loses

accuracy as the degrees of freedom approaches one. The degrees of freedom are the

number of observations minus the number of parameters being estimated (not counting

parameters that are within the singularity tolerance, i.e., nearly completely correlated).

NCA

One or more NCA result graphs have a mismatched lattice page condition (QC

9702/CRM 145998): In rare cases, NCA result plots fail to render with the error

message, “one or more graphs have a mismatched lattice page condition.” The exact

conditions that cause this issue are not known, but it only seems to happen in models

with carry along columns mapped. The problem can be worked around by unmapping

any carry along columns, executing NCA, remapping carry along columns, and re-

executing.

On rare occasions, Rsq or Lambda-Z will not appear in the plot title when a

Carry-Along variable is specified (QC 10517).

Best-fit Lambda Z range values are not reported consistently in the output when

multiple points are excluded at the start of the data or if there are zero-valued

points at the start of the range (QC 11227): When excluded or zero-valued points

are at the beginning of the Lambda_z range, Lambda_z_lower is reported in some

output as the earlier time value, which includes the unused initial points, yet in other

output, it is reported as the first point that is used. For example, if values range from

0.8 to 2 and points before 1.4 are excluded, some of the output reports the Lambda_z

range as (0.8, 2), whereas other output lists the range as (1.4, 2).

In a Bioequivalence object, any of the following actions will reset the model to the

default model: copy/paste, move-to-new-workflow, using a template, or map

source (QC 9641).

NCA, WNL Classic, Bioequivalence, and LinMix Core Status output exported as

RTF does not the same formatting as WNL ASCII output did (QC 10357): When

Core Status output is exported as an RTF file, the file when opened defaults to Sans

Serif, a non-uniform font size. To align the columns in the output, and make the

output the same as the WNL 5 defaults, change the font to Courier New 9 pt.

September 2020


Revision 1 of 58

three points fail to compute Lambda Z (such as the last three points going uphill).

This defect has existed in all versions of Phoenix. The workaround is to execute NCA

on the data using the default settings, and then use the NCA Slopes result and map it

to the Terminal Phase setup in the NPS object.

NPS and NCA Best-Fit Lambda Z calculations differ (QC 14394): In a case where

input data was given to significant precision (eight significant digits or more), the Best

Fit algorithms in NCA and in NPS (Nonparametric Superposition) were not generating

exactly the same Lambda Z values, although the results were very similar.

NPS does not use external worksheet mapping for Lambda Z setup (QC 17680):

The workaround is to set Lambda Z ranges using an internal worksheet.

WinNonlin Classic Modeling

Inconsistent behavior is possible when using external worksheets for a PK Model

object (QC 7122): When using a PK operational object, external worksheets for

stripping dose, units and initial estimates can be accessed in different ways. The

differences will occur if there is more than 1 row of information on these external

worksheets that correspond to one or more individual profiles of data of the Main

input worksheet.

In such cases, the stripping dose for PK models will be determined as the first value

found on that external worksheet whereas the units and initial parameters will be based

on the last row found on those external worksheets (for any given profile). To avoid

any confusion stemming from these differences it is suggested that external

worksheets maintain a one-to-one row-based correspondence to the Main input

profiles whenever possible.

Executing a PK Model object can lock up the system (QC 7148): In extremely rare

instances, the nonlinear modeling core computational engine can get into an infinite

loop during the minimization process. This infinite looping will cause Phoenix to

hang and the application must be shutdown using Task Manager. The problem

typically occurs when the parameter space in which the program is working within is

very flat.

To work around the problem, it is first suggested that the user change the minimization

algorithm found on the Engine Settings tab to Nelder-Mead and retry the problem. If

this fails to correct the problem, varying the initial estimates and/or using bounds on

the parameters can allow processing to complete as expected.

NPS quits trying to compute Lambda Z if the last three points fail to compute

Lambda Z, which is different than NCA (QC 13804): NCA and NPS behave

differently in computing Lambda Z for a specific case and they should be the same.

As NCA tries to compute Lambda Z, if the last 3 points fail to compute a Lambda Z, it

will continue checking further back in the dataset to see if a larger group of points

ending with the last point will yield a valid Lambda Z. NPS appears to quit if the last

Nonparametric Superposition

September 2020


Revision 1 of 58

Initial Estimates grid for Dissolution models does not accept new initial values after changing the Fixed option to Estimated (QC 9741): For the WinNonlin Generated Initial Parameter Values option with Dissolution models, to avoid getting pop-up warnings that “WinNonlin will determine initial estimate” when using the Initial Estimates internal worksheet setup, the user should delete the initial values and change the menu option from Estimated to Fixed before entering the initial estimate.Once the dropdown is changed from Fixed to Estimated, the user will not be

able to delete the initial value entered. However, it will not be used, and WinNonlin

will estimate the initial value as requested.

The WNL Classic Modeling output plot of observed and predicted data is

missing the observed data (QC 13947): The WNL Classic Modeling object in pre-

existing projects may sometimes load in Phoenix 1.4 or later with the observed data

missing from the “Observed Y and Predicted Y vs X” plot. If this occurs, map all data

to None, remap the data, and re-execute the object. This should correct the issue.

Loss of accuracy in WNL Classic Modeling univariate confidence intervals for

small sample sizes (NDF < 5) (QC 17448): The Univariate CIs in WNL use an

approximation for the t-value which is very accurate when the degrees of freedom is at

least five, but loses accuracy as the degrees of freedom approaches one. The degrees

of freedom are the number of observations minus the number of parameters being

estimated (not counting parameters that are within the singularity tolerance, i.e., nearly

completely correlated).

Deconvolution fails when Time is last column or after Conc column (QC 17729):

When the column mapped for Time is after the column mapped for Concentration,

Deconvolution may yield the error message "Time must be sorted in increasing order,"

even when the values actually are in increasing order. The workaround is to switch

the order of the Time and Conc columns in the input dataset.

September 2020

phoenix winnonlin 8.0 release notes - certara · 2021. 2. 10. · phoenix® 8.1 release notes...

Documents