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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/11000

Title: A Latent Pharmacokinetic Time Profile to Model Dose-Response Survival Data
Authors: Jacobs, Tom
Straetemans, Roel
Molenberghs, Geert
Bouwknecht, Adriaan J.
Bijnens, Luc
Issue Date: 2010
Abstract: The accelerating rotarod test is a preclinical pharmacodynamic test to assess the effect of a treatment on an animal's motor coordination. Two models are proposed to analyze the dose-response time-to-event data that typically result from such experiments: (1) a linear regression model and (2) an Emax model with latent drug concentration at the site of action. Both cope with the survival character of the data. The latter model allows a direct comparison of compounds, but raises the question of whether the study design would benefit from the inclusion of additional mice for plasma concentration sampling on the one hand or whether additional time-to-event data without plasma concentration sampling should be ascertained from these additional mice on the other hand. A simulation study explores the impact on operational characteristics of this change of study design.
Notes: [Jacobs, Tom] Hasselt Univ, Ctr Stat, Interuniv Inst Biostat & Stat Bioinformat, B-3590 Diepenbeek, Belgium. [Jacobs, Tom; Molenberghs, Geert] Katholieke Univ Leuven, Louvain, Belgium. [Straetemans, Roel; Bouwknecht, J. Adriaan; Bijnens, Luc] Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. tom.jacobs@uhasselt.be
URI: http://hdl.handle.net/1942/11000
DOI: 10.1080/10543401003618249
ISI #: 000278003200004
ISSN: 1054-3406
Category: A1
Type: Journal Contribution
Validation: ecoom, 2011
Appears in Collections: Research publications

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