Document Detail


Determination of an optimal dosage regimen using a Bayesian decision analysis of efficacy and adverse effect data.
MedLine Citation:
PMID:  12194536     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
One of the aims of Phase II clinical trials is to determine the dosage regimen(s) that will be investigated during a confirmatory Phase III clinical trial. During Phase II, pharmacodynamic data are collected that enables the efficacy and safety of the drug to be assessed. It is proposed in this paper to use Bayesian decision analysis to determine the optimal dosage regimen based on efficacy and toxicity of the drug oxybutynin used in the treatment of urinary urge incontinence. Such an approach results in a general framework allowing modeling, inference and decision making to be carried out. For oxybutynin, the repeated measurement efficacy and toxicity data were modeled using nonlinear hierarchical models and inferences were based on posterior probabilities. The optimal decision in this problem was to determine the dosage regimen that maximized the posterior expected utility given the prior information on the model parameters and the patient response data. The utility function was defined using clinical opinion on the satisfactory levels of efficacy and toxicity and then combined by weighting the relative importance of each pharmacodynamic response. Markov chain Monte Carlo (MCMC) methodology implemented in Win-BUGS 1.3 was used to obtain posterior estimates of the model parameters, probabilities and utilities.
Authors:
Gordon Graham; Suneel Gupta; Leon Aarons
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of pharmacokinetics and pharmacodynamics     Volume:  29     ISSN:  1567-567X     ISO Abbreviation:  J Pharmacokinet Pharmacodyn     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-08-26     Completed Date:  2003-03-12     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  101096520     Medline TA:  J Pharmacokinet Pharmacodyn     Country:  England    
Other Details:
Languages:  eng     Pagination:  67-88     Citation Subset:  IM    
Affiliation:
Centre for Applied Pharmacokinetic Research, School of Pharmacy and Pharmaceutical Sciences, Oxford Road, University of Manchester, Manchester M13 9PL, U.K. gordon.graham@man.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Aged
Bayes Theorem*
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
Humans
Male
Mandelic Acids / administration & dosage*,  adverse effects
Middle Aged
Monte Carlo Method
Nonlinear Dynamics*
Chemical
Reg. No./Substance:
0/Mandelic Acids; 5633-20-5/oxybutynin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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