Structural identifiability in mixed-effects models : two different approaches

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Abstract

Structural identifiability analysis is a theoretical concept that ascertains whether unknown model parameters can be uniquely determined for a given experimental setup. If this condition is not fulfilled numerical parameter estimates will be meaningless and the model prediction may not necessarily be reliable. Therefore, structural identifiability should be considered a prerequisite in any project where model predictions are a part of the decision making process. For models defined by ordinary differential equations, there are several methods developed both for the linear and nonlinear cases. In systems pharmacology pharmaceutical drug development projects there is, apart from an interest in understanding the biological mechanisms, also an interest in subject variability. For this, mixed-effects models are typically used. However, despite the wide use of mixed-effects models and being a part of the decision making process in pharmaceutical drugs projects, very little has been done on developing methods for structural identifiability analysis of mixed-effects models. In this paper, we propose and compare two methods for performing such an analysis. The first method is based on applying a set of established statistical theorems while in the second method the system is augmented to yield a random differential equation system format followed by subsequent analysis.

Item Type: Journal Article
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculty of Science, Engineering and Medicine > Engineering > Engineering
Library of Congress Subject Headings (LCSH): Pharmacology -- Statistics, Pharmaceutical industry, Drugs -- Research
Journal or Publication Title: IFAC-PapersOnLine
Publisher: Elsevier
ISSN: 2405-8963
Official Date: 10 November 2015
Dates:
Date
Event
10 November 2015
Available
11 May 2015
Accepted
Volume: 48
Number: 20
Page Range: pp. 563-568
DOI: 10.1016/j.ifacol.2015.10.201
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Date of first compliant deposit: 11 May 2016
Date of first compliant Open Access: 10 November 2016
Funder: Seventh Framework Programme (European Commission) (FP7)
Grant number: Marie Curie People ITN European Industrial Doctorate (EID) project, , IMPACT (Innovative Modelling for Pharmacological Advances through CollaborativeTraining).
URI: https://wrap.warwick.ac.uk/79002/

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