Resources

AAPS: www.aaps.org American Association of Pharmaceutical Scientists. Developing science, impacting health.

ACCP: www.accp1.org American College of Clinical Pharmacology. Advancing clinical care through pharmacology.

ACoP: www.go-acop.org The American Conference on Pharmacometrics had its first meeting in March 2008. It was formed to bring together other regional groups in the USA such as MUFPADA, ECPAG and BMSR. Participation at last ACoP meeting involved more than 500 participants.

ASCPT: www.ascpt.org  American Society for Clinical Pharmacology and Therapeutics. Advancing the science and practice of clinical pharmacology for the therapeutic benefit of patients and society.

CAMD: https://www.c-path.org/camd.cfm Coalition against Major Diseases.

DDMoRe Foundation: https://www.ddmore.foundation  The Drug Disease Model Resources (DDMoRe) Foundation maintains and drives development of a universally applicable, open source, model based framework, intended as the gold standard for future collaborative drug and disease Modelling & Simulation. Work is performed by the following Community Groups:

• The DDMoRe Model Repository provides a community-driven, fully-searchable hub for storing published and unpublished pharmacometric models.
• The DDMoRe Language Community provides a resource for encoding models with MDL, helps with understanding MDL structure and features, and provides a place for logging bugs, issues, feature requests and suggestions.
• The DDMoRe Thoughtflow Community maintains the Thoughtflow provenance standard for recording, storing and reporting the results of pharmacometric analyses, and drives its implementation in software.

NMusers: www.iconplc.com The NMusers email discussion list is an active international community with interests in all aspects of pharmacometrics but especially focused on the use of NONMEM.

PAGANZ: www.paganz.org A group of individuals with a common interest in data analysis using the population approach . It is based in the Australasian region and holds meetings in either New Zealand or Australia. It has been in existence since 1999. It numbers around 60 people who mainly come from the Australasian region with a smaller number of regular visitors from Asia (especially Korea).

PAGE: www.page-meeting.org Describing itself as a community, PAGE is based in Europe but the community includes people from around the world. It has been in existence since 1992. Participation at PAGE meetings involved more than 500 participants.

PAGIN: psgimsr.in/pagin.html The goal of PAGIN is to bring together individuals who share the passion to learn, train, and use model-based population approach methods for data analysis. It is based in India and has been in existence since 2008.

PAGJA: www.pagja.org Describing itself as a study group, PAGJA is based in Japan and holds meetings in Japanese although there was a joint meeting with PAGANZ in English in 2006. It has been in existence since 2006. Around 150 people attend the annual meeting.
PAGK: www.pagk.or.kr Describing itself as a study group, PAGK is based in Korea and holds meetings in Korean. It has been in existence since 2007. Around 130 people attend the annual meeting.

PaSiPHIC: www.pasiphic.calpoly.edu Pacific Coast Statisticians and Pharmacometricians Innovation Conference. Narrowing the distribution between stochastic scientists
by bringing Statisticians and Pharmacometricians together.

PKUK: www.pkuk.org.uk An open forum for discussing all PKPD issues in drug development as well as clinical implications of PKPD studies . It appears to be oldest pharmacometric community with meetings first held in the 1980s.

PharmML: www.pharmml.org PharmML stands for “Pharmacometrics Markup Language” – a new exchange format for encoding of models, associated tasks and their annotation as used in pharmacometrics. It was developed by the DDMoRe consortium, an European Innovative Medicines Initiative (IMI) project.

PharmPK: www.boomer.org The pharmpk email discussion list is an active international community with interests in all aspects of pharmacometrics.

WCoP: www.go-wcop.org The first World Conference on Pharmacometrics has its first meeting in September 2012.

This is not an exhaustive list, but aims to cover most tools of interest, both commercial and free.

GNU Octave: www.gnu.org/software/octave A free, but less fully-featured alternative to MATLAB.

Julia: julialang.org Julia is a high-level, high-performance dynamic programming language for numerical computing. It provides a sophisticated compiler, distributed parallel execution, numerical accuracy, and an extensive mathematical function library. Julia’s Base library, largely written in Julia itself, also integrates mature, best-of-breed open source C and Fortran libraries for linear algebra, random number generation, signal processing, and string processing.

MATLAB: www.mathworks.com/products/matlab A heavily-optimized platform for performing complex mathematical computing tasks.

Monolix: lixoft.com Easy, fast and powerful tool for parameter estimation in non-linear mixed effect models, model diagnosis and assessment, and advanced graphical representation. Accompanied by supporting products Datxplore, Mlxplore and Simulx.

nlmixr: www.nlmixr.org nlmixr is an R package for fitting general dynamic models, pharmacokinetic (PK) models and pharmacokinetic-pharmacodynamic (PKPD) models in particular, with either individual data or population data. It’s free and open source, and will remain so.

NONMEM: www.iconplc.com/innovation/nonmem/ The gold standard software in Population Pharmacokinetic and Pharmacokinetic-Pharmacodynamic modelling.

Perl-speaks-NONMEM (PsN): uupharmacometrics.github.io/PsN/ Perl-speaks-NONMEM (PsN) is a collection of Perl modules and programs aiding in the development of non-linear mixed effect models using NONMEM. The functionality ranges from solutions to simpler tasks such as parameter estimate extraction from output files, data file subsetting and resampling, to advanced computer-intensive statistical methods. PsN includes stand-alone tools for the end-user as well as development libraries for method developers.

Phoenix NLME: www.certara.com/software/pkpd-modeling-and-simulation/phoenix-nlme Phoenix NLME software is a population modeling and simulation solution for scientists with all levels of experience—from the most advanced modelers to novice PK/PD scientists. This comprehensive package includes integrated data preparation, modeling, and graphics tools, and uses the same GUI as Phoenix WinNonlin.

Pirana: www.pirana-software.com Pirana offers a powerful workbench for pharmacometric modeling, on your desktop or in the cloud.

PMXStan: github.com/yxiong1/pmxstan PMXStan is an R package aiming at facilitating Stan-based modeling building, fitting, diagnosis, and simulations for pharmacometrics uses.

Pumas: juliacomputing.com/products/pumas/ Pumas is a one-stop integrated modelling and simulation platform powered by the Julia language. It can perform non-compartmental analysis (NCA), nonlinear mixed-effects modelling (NLME), Bioequivalence (BE), in vitro-in vivo correlation (IVIVC) and clinical trial simulations (CTS). Further, Pumas provides convenient way of handling of multi-scale PBPK, QSP models. DeepNLME is the state-of-the-art product of Pumas that seamlessly integrates NLME and Deep Learning, via scientific machine learning. Pumas comes with a full suite of productivity tools to pre- and post-process your analyses in an interactive manner. Scientists can easily convert complex models to dashboards effortlessly to collaborate with interdisciplinary teams. Pumas was developed as a cloud-first technology that allows scientists scale to thousands of CPUs and GPUs with a single click. The software is free for non-commercial research and training..

R: www.r-project.org R is a free software environment for statistical computing and graphics. It compiles and runs on a wide variety of UNIX platforms, Windows and MacOS.

Stan: mc-stan.org Stan provides a full Bayesian platform for statistical modeling, data analysis, and prediction. Users specify log density functions in Stan’s probabilistic programming language and get full Bayesian statistical inference with MCMC sampling (NUTS, HMC), approximate Bayesian inference with variational inference (ADVI), penalized maximum likelihood estimation with optimization (L-BFGS), amongst other features. Stan’s math library provides differentiable probability functions & linear algebra (C++ autodiff). Additional R packages provide expression-based linear modeling, posterior visualization, and leave-one-out cross-validation.

xpose: github.com/UUPharmacometrics/xpose xpose was designed as a ggplot2-based update to xpose4. xpose aims to reduce the post processing burden and improve diagnostics commonly associated the development of non-linear mixed effect models.

Useful Textbooks and Literature

A Basic understanding of Pharmacokinetic and Clinical Pharmacology principles may be useful prior to more in depth study of pharmacometrics. The following are some online resources in these two disciplines.

Pharmacokinetic Courses: A First Course in Pharmacokinetics. A course by David Bourne from the University of Oklahoma.

Clinical Pharmacology Course: Principles of Clinical Pharmacology. This is a comprehensive course sponsored by NIH Clinical Center given in 2010. It has videos of lectures and downloadable slides.

Clinical Pharmacology Course: Interactive Clinical Pharmacology. Interactive teaching videos developed by Hitlab NZ and Christchurch Hospital/University of Otago Christchurch New Zealand.

Introduction to Pharmacometrics

DDMore Model Repository

The DDMoRe Foundation (DDMoRe) Repository enables access to curated and shared knowledge for the benefit of model-informed drug discovery, development and usage. The Model Repository is an open, publicly-available, free-to-use platform that is community-driven, indexed, fully searchable and supported by peer-review. Together with DDMoRe’s unique interoperability framework, these tools facilitate the collaborative development of computational models.

Users can submit their models in a number of formats, but to benefit from all of the repository’s features will need to use the PharmML representation.

Basic Pharmacokinetics and Pharmacodynamics Models For Teaching

Most of the commonly used pharmacokinetics and pharmacodynamic models may be found here and used to visualize drug response. The models were created in Stella® and each can be downloaded from this site: https://forio.com/simulate/sarar/

Excel Worksheet For Simple Non-compartmental Analysis

A Microsoft Excel Worksheet for simple non-compartmental analysis.