Phoenix® WinNonlin® uses Phoenix Modeling Language (PML) to encode pharmacokinetic (PK) and pharmacodynamic (PD) models. Although most models can be built using the Phoenix graphical user interface (GUI), some models require custom coding with PML. During the latter part of 2016, Certara’s support team, led by Dr. Bernd Wendt, Director of Training and Support, introduced a new interactive education program focused on building PK/PD models: PML School. After 20 lessons on a range of topics, I caught up with Bernd to get his perspective on the program and find out what’s in store for the future.
Maria Saluta: Before we delve into PML School, let’s talk about your background in education. You performed computational chemistry research at Pharma and Research Institutes. Then, you switched to training and support when you joined Certara seven years ago. What attracted you to move from research into a role that combines customer interaction and education?
Bernd Wendt: Good question! I spent more than 15 years in discovery or pre-clinical research, and as with all research, I experienced successes and failures. While at Alara Pharmaceuticals, a virtual company, I moved into the PK/PD field. We went through the pre-clinical phases with our compounds, so I learned quite a bit through that. So I thought that I’d gained enough research experience, maybe I can share this with others. I started at Certara as a trainer in support and application science. When you support commercial and academic customers, especially in the application area, they describe modeling scenarios that you may or may not be familiar with. In most cases you knew about it… I’ve seen that before. So it helps you dive back into this kind of research and helps the customer to steer around potential problems. It is nice, too, to help them with their work so they can really make progress on their drug’s development.
MS: You’re no stranger to education. You have been a lecturer in Molecular Modeling and PK/PD for over 9 years at the Ludwig-Maximilians-Universität (Munich); you must enjoy teaching. What do you appreciate most about teaching and what have you learned as an educator?
BW: Yes, teaching is in my roots, my origins. Starting with my PhD work, I had the opportunity to run workshops and seminars. I was working in an area that was brand new at the university and others also wanted to learn. After I received my degree, I continued to hold seminars on several theoretical topics that were coming together and in which there was great interest. And, I continue to teach at LMU because I enjoy it.
What have I learned as an educator? Students give you direct and honest feedback right away. They tell you what they think. And that’s great because you’re teaching both the theory and practical aspects of PK/PD modeling because you have to apply these concepts to actual research projects. The students start to challenge you, and that broadens your perspective. Also, students are intellectually diverse so every seminar is different and the questions might be different. And new questions are always refreshing.
MS: Let’s now turn to PML School—your most recent educational venture. Why and how did this program begin? What were your goals for the program?
BW: The idea for PML School originated from conversations I had with customers at last year’s Phoenix Road Shows. Also, we’d accumulated a large collection of support cases concerning a range of modeling scenarios. So, we recognized the need for training in model building. Phoenix provides great flexibility. It gives users access to its library models, which can be selected using simple built-in options. When customers described the situation, it occurred to me that we have to provide two simple solutions for them. First, we need to provide a new library of models that users can pick from for their day-to-day work. It was really just very simple—sometimes very simple models, sometimes more complex ones, but they could still be easily built with a new interface. While providing these models, we wanted to explain in detail how the models are set up using PML. This has the nice side effect of highlighting how easy and straightforward the underlying modeling language is. It’s really easy to adopt once we get them to understand that knowing PML is a key qualification. It has never been so easy to become an expert modeler now because they can build fairly complex models with just a little understanding of some of the key functions and the language. You can pick this up in a week’s time or so. This was our key message. And it’s why we called the program Phoenix Modeling Language School because PML is really the differentiator. Of course, Phoenix also offers built-in options and the graphical model builder. But all together, these are just different representations of the same model.
MS: Let’s move on to the lesson topics. How did the team choose the lessons, how difficult was it to narrow down to 20 lessons, and how was the curriculum defined? That seemed to be a great undertaking.
BW: You’re right, it was difficult. Chris Mehl and I (previously with Support and now an instructor at Certara University) reviewed the past four years of support cases. Then, we ranked them on the basis of how frequent the question appeared in the Phoenix Support Forum. Next, Chris linked the inquiries with the exercises in the book by Johan Gabrielsson and Dan Weiner—5th edition of Pharmacokinetic and Pharmacodynamic Data Analysis Concepts and Applications—and we chose the top 10 PK model exercises and 10 PD model exercises, or PK/PD. Finally, we developed the modeling questions and assigned lessons for each modeling question based on a particular exercise in the book. Dan, a pioneer in PK/PD modeling, one of the original developers of WinNonlin, and a well-known educator, helped us attain permission to use the book as the basis of the PML lessons and also provided some lectures.
MS: The 20 PML school lessons covered topics ranging from 3-compartment modeling to allometric scaling to Michaelis-Menten—dose escalation to tumor growth inhibition. Which lessons resonated most with the students and why?
BW: The most popular topic was allometric scaling, an exciting topic in pre-clinical development. Extrapolating from animal data to human data is a crucial step. Most researchers at medical schools perform pre-clinical research. So, that’s why it resonated so well. And people ask whether there’s a standard approach available that they can apply it to their own data.
MS: What were your favorite topics to teach?
BW: Allometric scaling and target-mediated disposition model (TMDD) allowed Dan to dive into the details and the theory, not just showing “here’s what it is”, but “here’s how you do it and that’s what you get.” And TMDD is a topic where you can really dive into the theory and show the power of modeling. The Tumor Growth Inhibition model was my favorite since my research background is oncology.
MS: Do you plan to offer PML school lessons in the future? If so, what topics would you discuss? I am sure our blog readers will want to know!
BW: I’ve been getting some feedback from the community for topics. We will present three new sessions starting on November 16. In two lessons, our clients will share their modeling “tips and tricks” with the community. We will also provide a pre-clinical example to simulate a desired outcome. We have a bunch of models, maybe around 100 or so, so we have ample materials for potential future sessions.
MS: Although the first semester of PML School ended on August 10, how can our readers access archived sessions, files and information?
BW: The PML School landing page provides a list of the 2017 curriculum and upcoming sessions. All information, for each of the lessons, including the textual models, the slide deck, and Q&A is available in the Certara PML School User Forum.
MS: Any parting words you would like to share with our audience?
BW: I think the only thing that I would like to share is that this was the “birth” of PML School. We are very happy with the interest it attracted. On average, 300 people attended each class. So we would like to thank all the attendees and our lecturers who made PML school a success. We’ll see you in November!
To learn how we used Phoenix to help a client streamline designing early clinical studies based on pre-clinical data, please read this case study.