Part 2 of the WinNonlin review will cover the non-compartmental and PK modeling functions of Phoenix WinNonlin. To many people, these two features have defined WinNonlin for many years. And the updated software does not disappoint with significant improvements to the functionality, ease of use, automated graphics, and other features.
As I discussed in Part 1 of my review, the new Phoenix platform allows integration of data and analysis methods. The “WinNonlin” feature includes the non-compartmental analysis and individual PK modeling features. These features were the basis for the previous versions of standalone WinNonlin versions 3, 4, and 5. Thus using the term “Phoenix WinNonlin” signifies the use of the new Phoenix platform to execute analyses with WinNonlin. This confusing nomenclature for the products is not helpful to the user, but it can be fixed very easily.
The non-compartmental analysis workflow object is shown here.
Within this workflow object you can select the options for the non-compartmental analysis, including the type of model, if sparse data is included, the AUC calculation method, and the terminal slope method. One change in the non-compartmental analysis engine from previous versions of WinNonlin is that Cmax is no longer included in the terminal slope calculation.
In addition to the analysis options, the concentration-time data to be used is identified in the “Main” item, dosing information can be imported from a data set or by manual entry, slopes can be selected by the WinNonlin algorithm (maximize adjusted r2) or manually, partial areas can be defined, units can be specified, and parameter names can be selected or modified. A new feature of the non-compartmental engine is the ability to define a therapeutic response window. Lower and upper bounds can be specified by treatment or by subject. These bounds then appear on plots of concentration-time data. This feature is great for identifying either efficacy levels or toxicity margins.
After all of the input options have been selected, the model can be executed to produce the desired output. The results are presented in a set of tables under the results option. These include parameter estimates, exclusions, dosing information, and various settings. An example of the parameters table, in CDISC-like format is shown below:
Each of the output worksheets can be sent to other Phoenix objects such as tables or plots. If standard tables and plots templates have been created prior to analysis, the delivery of report-ready tables and graphics can be instantaneous. Although it appears that little has changed with the NCA engine, there have been a few modifications that simplify data analysis. First, the number of models has been reduced to three basic model types (plasma, urine, drug effect) with separate selections for the dosing input profile, and steady-state settings. The second improvement is the improved plotting engine which provides report-ready graphics without having to leave the application. And finally, the dosing input is simplified and can be automatically populated using study design features.
The pharmacokinetic model workflow object is shown here.
The model can be selected by double-clicking the “PK Model” workflow object icon shown at the top of the image to the right. This pulls up the different models that can be selected. It also permits selection of weighting options, the ability to select initial estimates, and minimization options.
The model requires 4 inputs: The study data (time and concentration), dosing information, initial parameter estimates, and units. The Main input includes the concentration-time data and any unique identifiers (e.g. subject ID, sex, weight, etc.). The Dosing input can be entered by the user or added from a data file. The initial estimates are entered by the user, and the units for both input and output parameters can be adjusted as needed.
After the workflow is set, the user can execute the model by running the workflow. The results include standard modeling output such as parameter estimates, residuals, model diagnostics, variance estimates and predicted values. All of these results are presented in worksheets and can be converted to report-ready tables using the Table workflow object. The user also receives the settings and model fits in the text output. Finally, diagnostic plots are automatically produced using the new plotting engine. These plots are fully customizable and can include data from multiple data sets. One example of these plots is shown here:
Any of the results files can be sent to a plot, table, or other workflow object. This powerful feature provides easy communication of modeling results for study reports or even presentations. This workflow makes individual model fits simple and easy. And since these PK models can be integrated with other objects, you could take mean concentration-time output from a large data set and send it to a PK Model object to generate initial estimates of the PK model before embarking on a population analysis.
For many users of WinNonlin versions 3 through 5, the new Phoenix WinNonlin interface presented an unexpected learning curve; however, I believe the improvements are well worth the time required to relearn how to interact with the software. Minor modifications have been made in the non-compartmental and PK modeling features of WinNonlin. The modifications (mentioned above) are nice, but for me, there are two key features of the new software that make my life easier. First, the graphics rival those produced within R or SigmaPlot with little or no effort to learn a different software package. These plots can be linked to output so that they are automatically updated if the output changes, and the whole package (analysis and plots) can be set up as a template for repetitive analyses. The second feature is the ability to “send” a result object (e.g. parameter worksheet) to another workflow object. Before Phoenix WinNonlin, I would export output from WinNonlin into another application to create tables and figures. Now, I can simply send the results from either my NCA or PK Model output to a table or plot workflow object within the Phoenix platform.
Overall, the non-compartmental and PK modeling features of WinNonlin are of high quality and include the desired features. Operation is simple and straightforward. And added features such as the improved plotting engine and the workflow interactivity have created a single platform for pharmacokinetic data analysis and reporting.
You can learn more about Phoenix WinNonlin by calling your local Certara representative, or by requesting information from Certara.
Today’s pharmacokineticists and PK/PD modelers are under more pressure than ever to quickly and accurately characterize the safety and efficacy profiles of investigational drugs. They need the right tools to perform non-compartmental analysis (NCA), build pharmacometric models, and generate reports that communicate their findings.
Phoenix 7.0’s new features and enhancements are the direct result of user feedback we received to make the world’s most advanced PK/PD software package even better.
Watch this webinar to learn how Phoenix 7.0 helps you handle bigger datasets, perform lightning-fast NCA, and make gorgeous plots.