In this post, I am reviewing the Phoenix® Connect package from Pharsight (A Certara™ Company). Over the past several years, Pharsight has made a significant effort to modernize the pharmacokinetic analysis software tools to aid in the drug development process. While many longtime users of the PCNonlin and WinNonlin software solutions are disappointed with the need to learn a new computer interface, I liken this change similar to the move from text entry computers (e.g. DOS) to the windows-based platforms we now use (e.g. Windows, Mac OSX). You can still find people who love command-line computing; however the vast majority of users are comfortable and even more efficient with the graphical user interfaces we now see on computers and other electronic devices.
The Phoenix platform consists of modular packages that fit together on the Phoenix whiteboard to provide an integrated solution for pharmacokinetic and pharmacodynamic analysis.
These software packages, each with a different purpose, fit together interchangeably, similar to the toy Lego’s. This review focuses on the Phoenix Connect product which is displayed as a Data Management tool; however it actually provides connectivity to a myriad of other external tools. I prefer to think of Phoenix Connect as the tool that connects items within Phoenix to the outside world. Phoenix Connect has 3 primary functions, which I will review in order:
- Connecting Phoenix with data sources
- Integration of external analysis tools into Phoenix workflows
- Exporting results for reporting
Connecting Phoenix with data sources
Pharmacokinetic analysis is one part of data analysis in a study. As such, data flows from one source to another with the final location a report or regulatory document. The Phoenix Connect tool provides seamless integration to connect incoming demographics and concentration data with pharmacokinetic analysis procedures. Phoenix Connect provides methods to connect to a variety of external data sources. One of those sources is the Pharsight Knowledgebase Server (PKS), a proprietary database for PK and PD analyses. Phoenix Connect also provides flexibility by allowing import of SAS transport files in SDTM formats, or other external database structures (e.g. Oracle’s ODBC).
While connectivity to external data sources is important, Phoenix amplifies this valuable feature of Phoenix Connect by allowing for creation of templates and data links to automate data import. This allows a user to set up a pharmacokinetic analysis procedure (e.g. handling of BLQ values, non-compartmental analysis, concentration-time plots, data summarization, etc.) that can be repeated by simply connecting to new data sources.
Integration of external analysis tools
Many users think of Phoenix as an updated version of Pharsight’s WinNonlin product. But Phoenix is really a whiteboard platform that can be used with a large number of analysis tools. Phoenix Connect permits analysis with NONMEM, R, S-Plus, SAS, and many other analytical tools. There are competing tools that Pharsight sells (e.g. Phoenix WinNonlin, and Phoenix NLME); however, the Phoenix platform can be used to conduct native analyses with other tools. With Phoenix Connect, the user can add a NONMEM object that includes the dataset, control stream, and all output files. The resulting output files can then be used in other Phoenix objects (tables, plots, etc.) including integrated R-scripts. Phoenix Connect allows the user to organize and standardize pharmacometric analysis. Instead of a myriad of files and directories, all pharmacometric files are consolidated in a single Phoenix project file.
This feature of Phoenix Connect allows for consolidation and harmonization of all pharmacokinetic and pharmacometric analyses using the Phoenix platform, while retaining the value of multiple analysis tools (e.g. WinNonlin, NONMEM, R, etc.). Analyses can be performed using the native environment, yet the advantages of Phoenix can be leveraged with any of these tools. Using Phoenix Connect with external analysis tools also provides an increased level of quality control that can improve compliance with regulations and company standard operating procedures.
Exporting results for reporting
Phoenix Connect also provides a reporter tool that can be used to export results for incorporation into study reports. This feature completes the connection of Phoenix from data to results. The reporter tool allows you to select tables, figures, or text (called “listings” in the Reporter object) from your workflow and output them into a Microsoft Word document using context-sensitive table/figure/listing titles. The reporter object functions like all other Phoenix objects in that it takes inputs (tables, figures and text) and operates on it to produce output (MS Word file).
This new Reporter object can be used to compile tables and figures for study reports easily and quickly. For example, let’s take a bioequivalence clinical study (2-period 2-way crossover study). Standard figures include individual concentration-time profiles, mean concentration-time profiles for each formulation, and dot plots comparing Cmax and AUC across formulations. Standard tables include a listing of concentration-time data by subject, listing of individual PK parameter estimates, mean concentration-time data by formulation, mean PK parameter estimates by formulation, and a statistical comparison of Cmax and AUC across formulations. All of these tables and figures can be produced using Phoenix objects (table objects and plot objects, respectively). Instead of exporting each one independently, these objects can be fed into a Reporter object with context-sensitive information (e.g. analyte name, formulation, period, subject ID, etc.) that can be included in the title of the table or figure. These separate objects can then be exported together into a Microsoft Word document that can be saved and directly imported into a clinical study report.
If the data is updated, then the Reporter object, like any other Phoenix object, will turn pink to notify you that it is not current with the preceding objects. You can quickly refresh the workflow and update the output document to reflect the changes. This new Reporter object can be used within templates to standardize output for different studies and reports.
The new Reporter tool is an exciting advancement for the Phoenix platform. While Phoenix has been an excellent analysis platform, it always lacked a quality method for exporting information in an easy and useful manner. Individual file exports were time consuming, and could not be tracked within the workflow. In addition, the output was simply a data dump rather than a series of organized outputs that are report-ready. By adding the ability to customize titles and footers, the Reporter tool allows Phoenix to fully execute analyses from input data to final output (tables, figures, listings) for pharmacokinetic and pharmacodynamic analyses.
Overall impression and recommendations for the future
The updates to the Phoenix Connect product have made it an indispensable part of the Phoenix experience. The data connections provide access to a wide range of data sources. As companies begin to standardize on SDTM data formats, the data connection tool will become increasingly important instead of requiring a separate PK analysis dataset to be created by a SAS programmer. The ability to execute 3rd party software within Phoenix is the hidden gem of the Phoenix Connect product. This permits incorporation of tools into a regulatory compliant workflow that can be controlled in a validated environment. It simplifies the collection of output, and clearly identifies whether the results are current by color coding (white for current, pink for not current). Using Phoenix to manage your pharmacometrics work may soon become the standard for NONMEM control file management in the future. Additional tools such as custom R or S-Plus scripts or even custom SAS code allow the pharmacokinetic scientist to execute programs independently in a way that permanently links the analysis to the inputs and outputs. Finally, the new reporter tool is a first step to providing quality, report-ready output for inclusion in study reports. The reporter tool’s context-sensitive titles and footnotes are simple, useful, and easy to create. Like other objects, the reporter confirms that the output is current by the same color coding (white and pink) used in all other Phoenix objects. Future additions of reporter outputs to PowerPoint files, font selections for titles, and footnote locations will further refine the reporter tool to make it even more useful.
I highly recommend using the Phoenix Connect tool in your standard pharmacokinetic analysis workflow. Also, addition of this tool turns Phoenix into a pharmacometrics platform, even if you use NONMEM exclusively for your nonlinear mixed-effects modeling work. You can learn more about Phoenix Connect at the Pharsight website (http://www.certara.com/products/pkpd/phx-connect).