Welcome to the Population Approach Group in Europe

Support tools

Census 2: is a comprehensive project manager for NONMEM, providing detailed summary, comparison and overview of the runs comprising a given project, including the display of output data and post-run processing. The new version is a complete rewrite of Census from the ground up. In addition to adding cross-platform support, Census 2 incorporates a number of interface changes, including flexible run tagging and filtering, report output in HTML and LaTeX, a portable database file format, and too many others to mention. It is, however, no longer maintained.
Finch Studio: Finch Studio is an integrated modeling environment for pharmacometricians, clinical pharmacologists, data scientists, and other team members to visualize, understand, develop, and organize population PK/PD models and data. The goal of Finch Studio is to increase the modeler’s efficiency, lower the bar to entry and increase productivity for new pharmacometricians, and make PK/PD data and models more interpretable to non-modeler team members during interdisciplinary meetings. It includes a powerful NONMEM code editor and workbench, a library of > 100 PK/PD models, and interactive data visualizations to help guide decision making during the analysis. Finch Studio is released under a free academic license for students and instructors, as well as a commercial license for organizations.
Improve: The main concept behind Improve is to cover control and traceability over your complete modeling and simulation workflow while retaining the simplicity and ease of use of a standard file explorer. No matter which analysis, from noncompartmental to multicompartmental models, you choose, Improve will keep track of the "who what when where and why" of your data, while you are completely free to make decisions for the analysis you want to perform and which actions you want to take within your 3rd party tool of choice. In one sentence: Whatever you perform with your data, Improve will help you to keep track of your files AND your decisions.
InSysBio: is provider of Quantitative Systems Pharmacology (QSP) modeling services and developer of QSP modeling tools since 2004. The range of tools of QSP software infrastructure embraces Heta language, Heta compiler, Heta Simulator, Immune Response Template (IRT), CYTOCON DB, fIVE DB, DBSolveOptimum, and SbmlViewer. Heta project is an initiative for the development of infrastructure for modeling in pharmacology and systems biology. IRT is a platform of immune system, efficient and useful tool aimed to boost and facilitate the development of QSP models in immunology and immuno-oncology therapeutic areas. CYTOCON is a database of human baseline concentrations of cytokines and cells measured in different tissues of healthy subjects and patients suffering from various pathologies. fIVE DB is InSysBio’s project for in vitro experiments information collection and processing.
For more information about the tools, please visit: https://insysbio.com/services-and-tools/tools.
IQR Tools: is an R package that allows for seamless and efficient modeling across systems biology, systems pharmacology and pharmacometrics. It interfaces NONMEM, MONOLIX, and NLMIXR, enabling the user to fluently switch between parameter estimation platforms. In addition, it provides a world-leading powerful estimation method for systems pharmacology type of modeling, non-compartmental analysis functionality, and seamlessly interfaces with optimal experiment design R packages.
IQReport: is the innovative solution for reproducible research and efficient reporting in Microsoft Word. It allows writing of reports in a powerful extended markdown language and the final Word documents can match any desired corporate Word style through the use of customized reporting templates. With a shallow learning curve and user-friendly interface, IQReport speeds up the report writing process and allows for more time to focus on science and interpretation of the results.
jinko: is an in-silico trial design and simulation platform. Clinical trials are run through computer modeling with a disease model and a virtual population representative of any specific context or geographical location.; With jinko knowledge any scientist can extract, classify, summarize and collaborate around their literature review, publication and experimental process. That knowledge is the building block for model creation.; With jinko modeling QSP modelers can build, calibrate, and package their models. In collaboration with their colleagues they can then use jinko trial design and simulation to design any trial and experiment at scale and simulate how their candidate treatment will behave before recruiting a single patient. Treatment effects can be modeled across an unlimited range of digital patients, with no constraints over study length or the number of hypotheses tested.; With jinko content modelers and clinicians can get a head-start by benefiting from a library of existing curated models for both disease and treatments without having to start the modeling process from scratch.; In silico models don't replace in-person trials; instead, they generate insights that enable smaller and more targeted studies. Where no data from previous trials are available, control arms can be simulated to generate synthetic data.
Metrum Research Group Open Science: Tools, Courses, and Models: Metrum Research Group (Metrum RG) is a strong proponent of open-source software development efforts. Many of the tools we’ve developed for our own work are available as free, open-source software under GPL (most notably mrgsolve and Torsten). See this link for more information. Metrum RG also participates in training and education through various industry and academic M&S research efforts.
N.I.M.R.O.D.: is a Fortran program (Normal approximation Inference in Models with Random effects based on Ordinary Differential equations) devoted to the estimation in Ordinary Differential Equations (ODE) models with random effects. Although maximum likelihood based approaches are valuable options, both numerical and identifiability issues favor a Bayesian approach which can incorporate prior knowledge in a flexible way. NIMROD estimations relies on a normal approximation of the posterior that can be obtained by computing the maximum of the posterior distribution (MAP) by maximizing a penalized likelihood. NIMROD can be downloaded freely together with libraries for Pharmacokinetics and HIV models.
Open Systems Pharmacology Suite (OSPS with PK-Sim and MoBi): is a free open-source software for whole-body physiologically-based pharmacokinetic (PBPK) and Quantitative Systems Pharmacology (QSP) modeling and simulation. The best-known tools of the suite are PK-Sim and MoBi, which allow development of sophisticated PBPK QSP models in an intuitive graphical user interface. The software comes with an extensive database of physiology (human and pre-clinical) and protein expression, allowing model creation across the whole pharmaceutical life-cycle, from pre-clinical PK to human trial simulation. Thanks to its open-source nature, the OSPS is supported by a growing community of industry and academia. For more info and to download the software, please visit: www.open-systems-pharmacology.org.
PFIM: PFIM is an R package available in CRAN for population designs evaluation and optimization, based on the expression of the Fisher information matrix (FIM) in nonlinear mixed effects models. A library of usual PK and PD models is available and other models can be written using an analytical form or using a differential equations system. It provides tools to evaluate the FIM with evaluation criteria derived from its determinant, to perform design optimization under given design constraints and display the results of clear graphical form. The Multiplicative algorithm and the Fedorov-Wynn algorithm can be used for design optimization in a discrete space, and the PSO, PGBO and Simplex algorithms in a continuous space. The current version PFIM 6.0 is the result of a complete refactoring of the previous version PFIM 5.0 using the formal object oriented system S4. This new version offers users a completely new and simplest possible usage script to facilitate design evaluation and optimization.
Pirana: is a modeling environment for NONMEM and PsN, and provides an easy-to-use toolkit for both novice and advanced modelers. Pirana can be used to run, manage and edit models, interpret output, and manage NONMEM installations. It supports modeling on a local system and on computer clusters, and is easily extendible with custom scripts, and integrates smoothly with R, Xpose, Excel and other software. Pirana supports all NONMEM versions and runs on Windows, Linux and Mac OSX.
PopED: computes optimal experimental designs for both population and individual studies based on nonlinear mixed-effect models. Often this is based on a computation of the Fisher Information Matrix. PopED is written in R and is available as a package via CRAN.
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 simpler tasks such as parameter estimate extraction from output files, data file sub setting and resampling, to advanced computer-intensive statistical methods. PsN includes both stand-alone tools as well as development libraries for method developers.
pyDarwin: pyDarwin is an open source all-Python solution for machine learning model selection in NONMEM. Algorithms for model selection include Genetic Algorithm, Bayesian Optimization/Gaussian Process, Random Forest, Random Tree with Gradient Boosting and Particle Swarm Optimization. A full exhaustive search is also available in addition to the machine learning methods. The method is quite flexible, and can include search on model structure (including ODEs), optional parameters, such as absorption lag times and zero order infusions, between subject, between occasion and residual variability as well as any hypothesized covariate effects. The selection process is based on a user defined fitness/reward function that can include -2LL, and penalties for parsimony, convergence, covariance step, correlations and condition number. In addition to the penalties available in standard NONMEM output, user defined R or python code can be included to add custom penalties to the search. Requirements include NONMEM 7.4.3 or later, python version 3.10 or later. The documentation and installation instructions are available here.
rxode2: rxode2 is a free and open-source, cross-platform R package for solving and simulating from ODE-based models. Models written in the rxode2 mini-language are converted to C to generate compiled libraries for rapid solving. rxode2 is the successor to RxODE, which is no longer in active development, and forms the computational core of nlmixr2.
Simcyp: is a simulation and data analysis tool for PB-PK-PD applications associated with small and large therapeutic molecules, offered by Certara. It offers a database with multiple system parameters related to physiology, biology, genetics and anatomy for specific disease groups and defined age bands in humans and experimental animals. Simcyp is widely used by over 25 leading pharmaceutical companies for model-based drug development; from discovery to late clinical phases. All simulations are stochastic; however either individual or POPPK analyses can be applied for fitting data. The user-friendly interface is designed to facilitate access of various levels of expertise in nonlinear mixed effects approaches.
Simulations Plus, Inc.: is the premier developer of modeling & simulation software and consulting services supporting drug discovery, development research and regulatory submissions. We partner with companies to provide a data-driven, strategic modeling methodology, starting in early discovery, continuing through preclinical/clinical development, and concluding with clinical trials/post approval. With our subsidiaries, Cognigen Corporation and DILIsym Services, we offer #1-ranked, easy-to-use software (GastroPlus™, ADMET Predictor™, KIWI™, DILIsym®, NAFLDsym®, PKPlus™, and more) to bridge data mining, compound library screening with QSAR models, PBPK/TK modeling & simulation in animals and humans following administration around the body, and quantitative systems pharmacology approaches. Simulations Plus technology is licensed to and used by regulatory agencies worldwide. For over 20 years, Simulations Plus has partnered with our clients to reduce costs and accelerate research and development productivity by improving the ways scientists use knowledge and data to predict the properties and outcomes of pharmaceutical & biotechnology agents. Simulations Plus’ team of over 80 dedicated scientists & professionals, with decades of experience, stands ready to help.
Wings for NONMEM: WFN is a set of DOS batch command files and awk scripts to help NONMEM® users be more productive. The first version of WFN (Wheels for NONMEM) was written in 1989 at UC San Francisco. The unix csh and awk scripts evolved and were eventually ported to DOS in order to support NONMEM as part of the RIDO (Right Dose First Time) project.
Xpose: is a model building aid for population analysis using NONMEM. Xpose produces various plots and analyses to facilitate data set checkout, goodness-of-fit analysis, model exploration and visualization, model diagnostics, candidate covariate identification and model comparison. Xpose is written in the programming language R and allows for integration into nearly any model building platform. Functionality in Xpose 4 allows the user to create simulation based reference diagnostics, compute the conditional weighted residuals and modify standard Xpose graphics to create publication quality figures. An older version, Xpose 4, is still available, but is no longer actively maintained. A converter package allowing Xpose to be used with nlmixr is also available.

Resources

ClinicalTrials.gov: is a database of privately and publicly funded clinical studies conducted around the world.
discuss.go-isop.org: is a pharmacometrics discussion forum hosted by the International Society of Pharmacometrics (ISoP).
DDMoRe Model Repository: The DDMoRe Model Repository contains more than 150 pharmacometric models (PK, PD and PK/PD) shared and curated by the pharmacometric community, and continues to grow.
EMA: The European Medicines Agency.
EudraCT: is the European database for all interventional clinical trials on medicinal products authorized in the European Union (EEA) and outside the EU/EEA if they are part of a Paediatric Investigation Plan (PIP) from 1 May 2004 onwards. It has been established in accordance with Directive 2001/20/EC. Protocol and results information on interventional clinical trials are made publicly available through the European Union Clinical Trials Register since September 2011.
FDA: The U.S. Food and Drug Administration.
INRIA: A web animation: developed by Inria about the Population Approach is now available online. The objective of this animation is to explain that this approach is relevant in many fields (biology, agronomy, toxicology, pharmacology,…) and to show an application in PK modelling in a little more detail.
International Society of Pharmacometrics (ISoP): The mission of ISoP is the promotion and advancement of the discipline of pharmacometrics, through Integration, Innovation, and Impact: quantitative integration of multisource data and knowledge of clinical, biomedical, biological, engineering, statistical, and mathematical concepts, resulting in continuous methodological and technological innovation enhancing scientific understanding and knowledge, which in turn has an impact on discovery, research, development, approval, and utilization of new therapies. ISoP organizes the annual American Conference on Pharmacometrics (ACoP).
NMusers: The NONMEM Users Network is maintained by ICON Clinical Research LLC. Requests to subscribe to the network should be sent to: nmusers-request@iconplc.com. Once subscribed, you may contribute to the discussion by emailing: nmusers@globomaxnm.com.
NMusers Archive: The NONMEM Users Network Archive is maintained by Cognigen and contains a searchable database of every NMusers message sent since its inception.
Pharmacokinetic and Pharmacodynamic Resources: maintained by David Bourne, OUHSC College of Pharmacy. The purpose of this page is to provide links to information about the discipline of Pharmacokinetics.
PopDesign: is an e-mail list server for questions and comments about the design of population PK and PKPD studies. The PopDesign mailing list would be an appropriate place to ask questions and post comments about the design of any study for which nonlinear mixed effects modelling is the proposed analysis tool. Members of the list includes those who have developed nonlinear mixed effects models design software: PFIM, PFIM_OPT, PkStamp, PopDes, PopED, POPT, WinPOPT.
WikiPopix: is wiki dedicated to mixed effects models for the population approach.

Please send comments, requests for changes or additions and other questions related to this list to Justin Wilkins.