Activity Number:
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477
- SPEED: Bayesian Methods and Applications in the Life and Social Sciences
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Type:
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Contributed
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Date/Time:
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Wednesday, August 1, 2018 : 8:30 AM to 10:20 AM
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Sponsor:
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Section on Bayesian Statistical Science
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Abstract #329054
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Presentation
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Title:
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A Novel Bayesian PK/PD Model for Synergy: Challenges and Opportunities for Sequential Knowledge Integration
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Author(s):
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Fabiola La Gamba* and Tom Jacobs and Helena Geys and Christel Faes
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Companies:
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and Janssen R&D and Janssen R&D and Hasselt University
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Keywords:
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Bayesian inference;
Nonlinear Mixed Models;
Pharmacodynamics;
Pharmacokinetics;
Sequential integration;
Meta-analysis
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Abstract:
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Studies on pharmacodynamic interactions are usually performed in an in-vitro setting. In this work the co-administration of a novel molecule with a marketed treatment is studied through in-vivo studies performed sequentially. The body temperature change over time is expressed through a turnover model where a virtual pharmacokinetic profile of the marketed treatment drives the effect. A pharmacodynamic interaction is assumed at IC50. The aim of this work is to discuss the implications of performing the model in a Bayesian sequential manner, so that the posteriors resulting from a study are used to determine the priors of the next study. The assessed modelling aspects are: 1.Impact of prior elicitation; 2.Specification of random effect; 3.Impact of different Bayesian sequential integrations. The model worked well with informative priors, random baseline and when a wide dose range was investigated in each study. The integration of studies where one or few dose combinations were assessed produced biased results. This highlights the importance of a careful design of experiment for a successful sequential integration.
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Authors who are presenting talks have a * after their name.