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    
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.
Gordon Graham; Suneel Gupta; Leon Aarons
Related Documents :
20543666 - Use of automated blood pressure measurements in clinical trials and registration studie...
17855116 - Epidemiologic methods developments: a look forward to the year 2032.
15702606 - A two-stage design for bridging studies.
2270186 - Effects of background symmetry on same-different pattern matching: a compromise-criteri...
25140216 - Selection of variables that influence drug injection in prison: comparison of methods w...
19322226 - Periodontal treatment could improve glycaemic control in diabetic patients.
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    
Centre for Applied Pharmacokinetic Research, School of Pharmacy and Pharmaceutical Sciences, Oxford Road, University of Manchester, Manchester M13 9PL, U.K.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Bayes Theorem*
Dose-Response Relationship, Drug
Drug Administration Schedule
Mandelic Acids / administration & dosage*,  adverse effects
Middle Aged
Monte Carlo Method
Nonlinear Dynamics*
Reg. No./Substance:
0/Mandelic Acids; 5633-20-5/oxybutynin

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

Previous Document:  Influence of arterial vs. venous sampling site on nicotine tolerance model selection and parameter e...
Next Document:  A note on sample size calculation in bioequivalence trials.