Advancing the Course of PK/PD Modeling
Throughout her career, Diane Mould has both advanced and spread the word on computer modeling.
By Linda C. Brown
As a scientist, researcher, entrepreneur, and educator, Diane Mould, Ph.D., FCP, FAAPS, has demonstrated her multiple talents. In addition to being the president of Projections Research, Inc., which offers pharmacokinetic and pharmacometric consulting services, she founded Baysient LLC, which develops systems to individualize doses of drugs that are difficult to manage. On the academic side, she is an adjunct professor at the University of Rhode Island (URI), Ohio State University (OSU), and the University of Florida, and teaches an annual class on disease progression modeling at the National Institutes of Health. She has taught courses at URI, OSU, and the State University of New York at Buffalo on specialized aspects of population pharmacokinetic and dynamic modeling. Her research includes understanding the pharmacokinetics and pharmacodynamics of therapeutic monoclonal antibodies and developing Bayesian adaptive dosing algorithms to improve patient response.
She applies particular importance to her research with applied pharmacometrics. “My colleagues and I have developed a software package to individualize the doses of biologic agents used in the treatment of rheumatoid arthritis, inflammatory bowel disease, and psoriasis,” Mould says. “Thanks to the wonderful support from our investigators, we are beginning to show substantial improvements in clinical outcomes with these agents.”
Mould received a doctorate degree in pharmaceutics and pharmaceutical chemistry at OSU’s College of Pharmacy after receiving a bachelor of science in chemical biology at Stevens Institute of Technology.
PK/PD and Modeling
Between college and her doctoral studies, Mould worked at Lederle Labs. “I worked for Vijay Batra, who introduced me to pharmacokinetics [PK],” she says. Batra had the most influence over her choice of career. “I think it was his delight in showing me aspects of PK that made him an excellent mentor,” she says. Batra supported Mould continuing in PK, which prompted her to consider the field as a career. She and Batra still meet up at professional meetings and exchange email. “I’d like to thank him for his help and support over the years,” she says.
An experience in graduate school inspired Mould to pursue computer modeling. “I was fortunate enough to attend a class held by Thomas Ludden on NONMEM [NONlinear Mixed Effects Modeling],” she says. NONMEM is a computer program that does population pharmacokinetic and pharmacokinetic/pharmacodynamic (PK/PD) modeling. “I also helped install and manage the system, which was a bit of an eye-opener.”
Before that, Mould used to do molecular modeling. “I started out in biophysics and spent a lot of time late at night running very big modeling programs,” she says. “Tom Ludden is a fantastic teacher with a great way of explaining the underlying aspects of population PK.”
After leaving school, she pursued population PK modeling at Hoffman LaRoche, which sent her to learn directly from Ludden, where she did her first modeling work under his direction. Thus, “I was again fortunate enough to work with Tom Ludden to learn more about population pharmacokinetics. Other notables in the field, including Lewis Sheiner and Stuart Beal, were kind enough to answer my questions and help me learn.” In addition to helping Mould get started in the field, Ludden has provided a lot of insight and advice throughout her career.
Ultimately, Mould hopes to change the way medicine is practiced in the future. She says, “It is thrilling to see how much the application of Bayesian dosing has improved the patients who are dosed using the software.”
An Accomplished Career
During her career, Mould conducted population PK/PD analyses of hematopoietic agents, monoclonal antibodies, anticancer, antiviral agents, antipsychotic, cardiovascular, and sedative/hypnotic agents. She has participated in clinical trial simulation and optimal study design in drug development and has reviewed and tested clinical trial simulation software.
Mould is a fellow of the American College of Clinical Pharmacology, and sits on its Board of Regents. In 2014, she was named a fellow of the American Association of Pharmaceutical Scientists (AAPS). She is an active member of the editorial board for the Journal of Pharmacokinetics and Pharmacodynamics, Clinical Pharmacology and Therapeutics, and Clinical Pharmacology and Therapeutics: Pharmacometrics and Systems Pharmacology.
Mould is a coinventor on five U.S. patent applications, regularly presents at national and international conferences on advanced modeling and simulation approaches, and has coauthored numerous peer-reviewed articles and book chapters.
As president of a company and founder of another, Mould believes that leadership involves balancing risk with reward. “It was a risk to leave a good job in the pharmaceutical industry to open a consulting company,” she says. “But while there were rough patches, the benefits have allowed me to associate with some truly great scientists and work in a wide range of therapeutic areas.” In addition to understanding risk, “I also think it helps to have a good sense of humor and the patience and flexibility to work through difficult situations.”
“Life is a continuous lesson,” she says. “I try to learn as much as I can about anything, even if it is not directly related to my field. Having a broad background has helped in building a business as well as in managing a diverse group of people more effectively. I also feel it’s important to develop an environment where employees feel free to offer critical opinions about my thoughts.”
Networking through AAPS
Mould is an active member of the AAPS Clinical Pharmacology and Translational Research section and chairs the AAPS Pharmacometrics focus group. As part of the focus group, she has worked with her colleagues to establish a newsletter to help inform Pharmacometrics focus group members of relevant meetings and learning opportunities, generate Web-based discussions on topics of interest to the group, and promote AAPS meeting symposia and webinars.
Mould says, “AAPS offers a good platform to engage with colleagues in your field. It also offers good scientific journals for publication opportunities as well as education. Participation in the various areas such as Clinical Pharmacology and Translational Research has been a good source for learning how others are solving problems.”
“I expect that successful people have wide ranges of skills and characteristics,” Mould says. “It’s just important to understand what you know and what you don’t and to learn where your strengths are so you can capitalize on them. It’s also helpful to love what you do.”
For college students or postdocs pursuing their careers, Mould advises, “Be willing to ask questions, take classes in areas that are not directly related to your field, and be open to new experiences. For example, I spent many years learning how to program in a variety of languages, which turned into a benefit when learning to deal with various modeling packages and developing useful output. Admittedly, I took classes in things I don’t use much now, but I appreciated the experience.”
As to where she thought she would be in her career, Mould says, “Personally, I was hoping to be a retired multimillionaire by now. I suspect I will still be working for years though.”
Linda C. Brown is the AAPS managing editor.