Rikard Nordgren (1), Andrew C. Hooker (1), Sebastian Ueckert (1), Stella Belin (1) and Mats O. Karlsson (1)
(1) Department of Pharmacy, Uppsala University, Sweden
The Uppsala University pharmacometrics group develops and maintains several different open source software packages.
assemblerr – Construction of pharmacometric models by combining pre-defined model components.
ncappc – can perform traditional non-compartmental analysis and simulation based posterior predictive checks for PK and PKPD models [1].
Pharmpy – A library for pharmacometric modelling. Has functionality for reading, parsing and transforming models and datasets as well as for retrieving and calculating results.
Pharmr – R interface to Pharmpy
piraid – An aid for development and diagnostics of pharmacometric IRT and composite score models
PopED – computes optimal experimental designs for population or individual studies based on non-linear mixed effects models. [2][3]
xpose4/xpose – Model building aids for nonlinear mixed-effects model analysis using NONMEM, facilitating data set checkout, exploration and visualization, model diagnostics, candidate covariate identification and model comparison [4].
PsN – is an open source toolbox for population PK/PD model building using NONMEM. It has broad functionality ranging from results extraction to advanced computer-intensive statistical methods. PsN simplifies the organization of NONMEM output files, helps with starting jobs on different types of clusters (i.e. slurm, torque, sge and lsf) and can perform a cornucopia of different statistical, computational and other methods, including: benchmark – combinatoric benchmarking of different NONMEM control stream settings, bootstrap – assessing uncertainty of parameter estimates, cdd – case deletion diagnostic to look for influential individuals, crossval – model cross validation, frem – full random effects modelling, linearize – generation of model approximation using linarization and second order approximation for likelihood models, llp – log likelihood profiling, mcmp – monte carlo mappend power for power compuations, nmoutput2so – converting NONMEM results into the standard output file format, parallel_retries – estimate the same model multiple times with different initial parameter estimates, qa – fast and automatic assumption assessment and quality assurance of models, resmod – residual modelling for quickly assessing appropriateness of structural and residual error models, scm – stepwise covariate model, simeval – simulation evaluation diagnostics of outliers, sir – sampling importance resampling for parameter uncertainty assessment, sse – stochastic simulation and estimation, transform – do changes to a model programmatically and vpc – visual predictive check. [5][6][7][8]
PsN is freely available at https://uupharmacometrics.github.io/PsN, xpose4 at https://uupharmacometrics.github.io/xpose4, xpose at https://uupharmacometrics.github.io/xpose4, PopED at https://andrewhooker.github.io/PopED, ncappc at https://github.com/UUPharmacometrics/ncappc, Pharmpy at https://pharmpy.github.io, assemblerr at https://github.com/UUPharmacometrics/assemblerr and piraid at https://github.com/UUPharmacometrics/piraid.
References:
[1] Chayan Acharya, Andrew C. Hooker, Gulbeyaz Y. Turkyilmaz, Siv Jonsson and Mats O. Karlsson (2016), A diagnostic tool for population models using non-compartmental analysis: The ncappc functionality for R, Computer Methods and Programs in Biomedicine, 127, 83-93.
[2] Nyberg J, Ueckert S, Stroemberg EA, Hennig S, Karlsson MO, Hooker AC (2012). “PopED: An extended, parallelized, nonlinear mixed effects models optimal design tool.” Computer Methods and Programs in Biomedicine, 108.
[3] Foracchia M, Hooker AC, Vicini P, Ruggeri A (2004). “POPED, a software for optimal experiment design in population kinetics.” Computer Methods and Programs in Biomedicine, 74.
[4] Jonsson EN, Karlsson MO. Xpose–an S-PLUS based population pharmacokinetic/pharmacodynamic model building aid for NONMEM. Computer Methods and Programs in Biomedicine. 58(1):51-64.
[5] Karlsson MO, Nordgren R et al., PsN: An open source toolkit for non-linear mixed effects modelling, 2004-, https://uupharmacometrics.github.io/PsN/ [Online; accessed 2021-04-22]
[6] Lindbom L, Ribbing J, Jonsson EN. Perl-speaks-NONMEM (PsN)–a Perl module for NONMEM related programming. Comput Methods Programs Biomed. 75(2):85-94.
[7] Lindbom L, Pihlgren P, Jonsson EN. PsN-Toolkit–a collection of computer intensive statistical methods for non-linear mixed effect modeling using NONMEM. Comput Methods Programs Biomed. 79(3):241-57.
[8] Keizer RJ, Karlsson MO, Hooker A. Modeling and Simulation Workbench for NONMEM: Tutorial on Pirana, PsN, and Xpose. CPT Pharmacometrics Syst Pharmacol. (2013) 2, e50.
Reference: PAGE 29 (2021) Abstr 9748 [www.page-meeting.org/?abstract=9748]
Poster: Software Demonstration