Approximation of the Fisher Information Matrix for Nonlinear Mixed Effects Models in Population PK/PD Studies

2013 ◽  
pp. 145-152
Author(s):  
Sergei Leonov ◽  
Alexander Aliev
Keyword(s):  
Fisher Information ◽  
Fisher Information Matrix ◽  
Information Matrix ◽  
Mixed Effects ◽  
Mixed Effects Models ◽  
Nonlinear Mixed Effects ◽  
Nonlinear Mixed Effects Models ◽  
Population Pk

scholarly journals Practical identifiability in the frame of nonlinear mixed effects models: the example of the in vitro erythropoiesis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ronan Duchesne ◽  
Anissa Guillemin ◽  
Olivier Gandrillon ◽  
Fabien Crauste
Keyword(s):  
Information Matrix ◽  
Mixed Effects ◽  
Individual Variability ◽  
Mixed Effects Models ◽  
Model Parameters ◽  
Nonlinear Mixed Effects ◽  
Nonlinear Mixed Effects Models ◽  
Erythroid Progenitors ◽  
Practical Identifiability

Abstract Background Nonlinear mixed effects models provide a way to mathematically describe experimental data involving a lot of inter-individual heterogeneity. In order to assess their practical identifiability and estimate confidence intervals for their parameters, most mixed effects modelling programs use the Fisher Information Matrix. However, in complex nonlinear models, this approach can mask practical unidentifiabilities. Results Herein we rather propose a multistart approach, and use it to simplify our model by reducing the number of its parameters, in order to make it identifiable. Our model describes several cell populations involved in the in vitro differentiation of chicken erythroid progenitors grown in the same environment. Inter-individual variability observed in cell population counts is explained by variations of the differentiation and proliferation rates between replicates of the experiment. Alternatively, we test a model with varying initial condition. Conclusions We conclude by relating experimental variability to precise and identifiable variations between the replicates of the experiment of some model parameters.

scholarly journals Practical Identifiability in the Frame of Nonlinear Mixed Effects Models: the Example of the in vitro Erythropoiesis

2021 ◽  
Author(s):  
Ronan Duchesne ◽  
Anissa Guillemin ◽  
Olivier Gandrillon ◽  
Fabien Crauste
Keyword(s):  
Information Matrix ◽  
Mixed Effects ◽  
Individual Variability ◽  
Mixed Effects Models ◽  
Model Parameters ◽  
Nonlinear Mixed Effects ◽  
Nonlinear Mixed Effects Models ◽  
Erythroid Progenitors ◽  
Practical Identifiability

Nonlinear mixed effects models provide a way to mathematically describe experimental data involving a lot of inter-individual heterogeneity. In order to assess their practical identifiability and estimate confidence intervals for their parameters, most mixed effects modelling programs use the Fisher Information Matrix. However, in complex nonlinear models, this approach can mask practical unidentifiabilities. Herein we rather propose a multistart approach, and use it to simplify our model by reducing the number of its parameters, in order to make it identifiable. Our model describes several cell populations involved in the in vitro differentiation of chicken erythroid progenitors grown in the same environment. Inter-individual variability observed in cell population counts is explained by variations of the differentiation and proliferation rates between replicates of the experiment. Alternatively, we test a model with varying initial condition. We conclude by relating experimental variability to precise and identifiable variations between the replicates of the experiment of some model parameters.

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