Therefore, alongside the development of NONMEM, many third‐party tools have been developed that facilitate the use of NONMEM by providing tools for organization and automation. In addition, at its core, NONMEM performs only model estimation (or simulation), and the implementation of essential diagnostic tools such as bootstrap analyses and the creation of goodness‐of‐fit plots are left to the modeler. This is partially because of the fact that NONMEM is invoked from the command line, and models are implemented using a Fortran‐derived syntax (NM‐TRAN). Modeling and simulation (M&S) in clinical pharmacology, and the use of NONMEM in particular, however, has a steep learning curve for most starting researchers. Development of the NONMEM software continues, and although over time several other modeling software tools have become available, NONMEM is still regarded as the gold standard within the pharmacometric community: a recent survey identified NONMEM (together with PsN) as the most frequently used software tool by far. CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e50 doi: advance online publication 26 June 2013.īACKGROUND Started in the early 1980s with the development of the NONMEM (acronym based on “NON‐linear Mixed‐Effects Modeling”) software, “population analysis” has proven to be extremely useful within pharmacometrics, both in the development of new drugs and the improvement of therapy with approved drugs. During the tutorial, we provide some guidance on what diagnostics we consider most useful in pharmacokinetic model development and how to construct them using these tools. This tutorial shows how three commonly used and freely available tools, Pirana, PsN, and Xpose, form a tightly integrated workbench for modeling and simulation with NONMEM. Several software tools are available that facilitate the use of the NONMEM software and extend its functionality.
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