1 Introduction

1.1 Contents of the bookdown

For details on installing the library, see section 2 Installation.

Sections 3 Statistical methods to 4 Diagnostic graphs present the statistical models and methods:

  • in section 3 Statistical methods, we describe the statistical models and the evaluation methods. We also give details on specific methods to handle censored data or the different decorrelation methods available

  • in section 4 Diagnostic graphs, we describe the diagnostic graphs available in the package

Section 5 Using the npde package shows a step-by-step example of using the library to produce default diagnostic plots for the theophylline data.

In section 6 Examples, we illustrate the use of the package through several examples, showcasing the various diagnostic graphs and their interpretation.

In section 7 Types of graphs in the npde library, we show which plot types are available (some depend on whether for instance covariates or data below the limit of quantification are present in the dataset) for a NpdeObject object. The options available for binning are also shown.

Section 8 Tayloring options for graphs shows all the arguments that can be passed on to the plot() functions to change layout, titles, colours, symbols, content, in order to personalise the plots.

Section 9 Types of graphs in the npde library describes the different kinds of plots that can be produced using the plot.type argument to the generic plot() function, as well as the corresponding specialised functions that are called to produce each type of graph.

Finally, section 11 References has a list of relevant references to the publications about npde and other diagnostic tools, while section 10 Structure of the npde package contains some technical details concerning the online help, S4 classes and methods of the package.

1.2 Citing npde

If you use this program in a scientific publication, we would like you to cite the following reference: Emmanuelle Comets, Brendel, and Mentré (2008). Additional references are: Brendel et al. (2006), Emmanuelle, Karl, and Mentré (2010), T. H. T. Nguyen, Comets, and Mentré (2012), Emmanuelle Comets, Nguyen, and Mentré (2013), Emmanuelle Comets and Mentré (2021).

References

Brendel, Karl, Emmanuelle Comets, Céline Laffont, Christian Laveille, and France Mentré. 2006. “Metrics for External Model Evaluation with an Application to the Population Pharmacokinetics of Gliclazide.” Pharmaceutical Research 23: 2036–49.
Comets, Emmanuelle, Karl Brendel, and France Mentré. 2008. “Computing Normalised Prediction Distribution Errors to Evaluate Nonlinear Mixed-Effect Models: The Npde Add-on Package for R.” Computer Methods and Programs in Biomedicine 90: 154–66.
Comets, Emmanuelle, and France Mentré. 2021. “Developing Tools to Evaluate Non-Linear Mixed Effect Models: 20 Years on the Npde Adventure.” AAPS Journal (Accepted for Publication).
Comets, Emmanuelle, Thi Huyen Tram Nguyen, and France Mentré. 2013. “Additional Features and Graphs in the New Npde Library for R.” Poster. 22\(^{th}\) Meeting of the Population Approach Group in Europe, Glasgow, United Kingdom.
Emmanuelle, Comets, Brendel Karl, and France Mentré. 2010. “Model Evaluation in Nonlinear Mixed Effect Models, with Applications to Pharmacokinetics.” Journal de La Société Française de Statistique 151: 106–28.
Nguyen, Thi Huyen Tram, Emmanuelle Comets, and France Mentré. 2012. “Extension of NPDE for Evaluation of Nonlinear Mixed Effect Models in Presence of Data Below the Quantification Limit with Applications to HIV Dynamic Model.” Journal of Pharmacokinetics and Pharmacodynamics 39: 499–518.