Tutorials on the Foundations of Pharmacometrics and Systems Pharmacology

In addition to perspectives, reviews, and original research articles, CPT:PSP welcomes a special type of articles in the fields of Pharmacometrics and Systems Pharmacology: Tutorials. A CPT:PSP tutorial is intended as an “educational article providing practical tutorial on tools, methodologies, and approaches.” Tutorials aim to increase the awareness and potential of Pharmacometrics and Systems Pharmacology outside the disciplines, introduce methodology to newcomers interested in model-based approaches, and provide further training and specialized guides to those already working in the field. Tutorials are thereby one way for CPT:PSP to fulfill its objectives of being a “publication platform for Pharmacometrics and Systems Pharmacology, which will contribute to the further growth of the disciplines and a broader application” and in creating “a dedicated forum for the exchange of information essential to the practice of these emerging disciplines.”1 We do believe that there is a demand for educational articles in Pharmacometrics and Systems Pharmacology and that tutorials will facilitate the sharing of the advances and views of experts in the fields. The open-access format of CPT:PSP also provides an excellent platform by allowing efficient distribution to researchers worldwide. Pharmacometrics is a growing field with continuous development of methods and techniques for model building and evaluation. Research articles, text books,2,3 courses, and discussion forums provide insights into current standards and into new developments of population-based approaches. However, for novice modelers, it can be difficult to get access and select the most relevant literature to acquire an up-to-date overview of aspects to consider in the application of modeling and simulation. Tutorials may also facilitate the communication and connection between different fields applying model-based approaches. Moreover, the CPT:PSP tutorials are in line with the vision of the International Society of Pharmacometrics (ISOP), which is “to promote and advance the discipline of Pharmacometrics and broaden its impact” (http://go-isop.org/). Mould and Upton published the very first CPT:PSP tutorial,4 which was an introduction to the basic concepts on population-based modeling approaches aimed for readers with limited familiarity of Pharmacometrics. The tutorial provides a general background for the methods and explains common applications and capabilities. Since the inaugural tutorial by Mould and Upton, CPT:PSP has published three additional tutorials.5–7 Mould and Upton has followed up with a second tutorial “Basic concepts in population modeling, simulation and model-based drug development – Part 2: Introduction to population modeling methods,”5 where they discuss how to get started with population pharmacokinetic modeling, which is often the first type of population analysis novice modelers are exposed to, although much of the concepts and methodology presented also applies to pharmacodynamic analyses. The tutorial covers the most important steps in the development and evaluation of a population pharmacokinetic model, with valuable references for readers who wish to know more. The tutorial also serves as an example on how the online format of CPT:PSP can facilitate learning by integrating educational material as supplementary files such as graphics and model code. It is our hope that this tutorial can aid novice modelers with a quick start into the field and provide advice on commonly encountered problems. Although there are no definite standards set in the pharmacometric community on how to do modeling, and there are also differences in modeling strategies among experienced modelers, the tutorial by Mould and Upton provides a basis for the expected standards of a pharmacometric analysis in 2013. The concepts for applying time-to-event analysis in the field of Pharmacometrics were outlined in a tutorial by Holford,6 where the target audience are primarily those who already have some experience of population pharmacokinetic analysis. Holford makes the analogy of the hazard function and integration of the hazard with a one-compartment pharmacokinetic model and the integration of area under the curve. Berkeley Madonna code is provided as supplementary material for visual exploration of the impact of different parameter values on the hazard and survivor functions. His tutorial also emphasizes the value of parametric time-to-event models that allow for the incorporation of time-varying predictors, such as changes in drug or biomarker concentration, which are rarely made in traditional statistical analysis of time-to-event data. The tutorial will hopefully contribute to expanding the number of applications of survival analysis in pharmacometrics. That Pharmacometrics is an evolving field with different opinions and practices, even within the same company, is illustrated in the tutorial by Byon et al.7 at Pfizer. Their tutorial “Establishing Best Practices and Guidance in Population Modeling: an Experience with an Internal Population Pharmacokinetic Analysis Guidance” describes the in-house development of a best practice guide on how to perform population modeling. It should be noted that the developed guideline (provided to the readers as supplementary material) is based on these authors’ views and current opinions at Pfizer and not necessarily the view of other modelers or of CPT:PSP. The tutorial and guideline itself can, however, be a very useful starting point for other initiatives and for generating discussions. For example, at the wiki of the ISOP, anyone can contribute and discuss modeling practices, and this Wiki could develop into a dynamic global best practice guidance. In summary, CPT:PSP welcomes educational tutorials on various topics within the fields of Pharmacometrics and Systems Pharmacology and encourages authors CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e53; doi:10.1038/psp.2013.27; advance online publication 3 July 2013 Tutorials on the Foundations of Pharmacometrics and Systems Pharmacology EdiTorial