title: Propagation of population pharmacokinetic information using a Bayesian approach: comparison with meta-analysis.
abstract: We investigated the propagation of population pharmacokinetic information across clinical studies by applying Bayesian techniques. The aim was to summarize the population pharmacokinetic estimates of a study in appropriate statistical distributions in order to use them as Bayesian priors in consequent population pharmacokinetic analyses. Various data sets of simulated and real clinical data were fitted with WinBUGS, with and without informative priors. The posterior estimates of fittings with non-informative priors were used to build parametric informative priors and the whole procedure was carried on in a consecutive manner. The posterior distributions of the fittings with informative priors where compared to those of the meta-analysis fittings of the respective combinations of data sets. Good agreement was found, for the simulated and experimental datasets when the populations were exchangeable, with the posterior distribution from the fittings with the prior to be nearly identical to the ones estimated with meta-analysis. However, when populations were not exchangeble an alternative parametric form for the prior, the natural conjugate prior, had to be used in order to have consistent results. In conclusion, the results of a population pharmacokinetic analysis may be summarized in Bayesian prior distributions that can be used consecutively with other analyses. The procedure is an alternative to meta-analysis and gives comparable results. It has the advantage that it is faster than the meta-analysis, due to the large datasets used with the latter and can be performed when the data included in the prior are not actually available.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Oxford Road, Manchester, M13 9PL, UK.
authors.forename: Aristides
authors.initials: A
authors.lastname: Dokoumetzidis
authors.forename: Leon
authors.initials: L
authors.lastname: Aarons
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001499:Bayes Theorem; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003198:Computer Simulation; D006801:Humans; D007275:Injections, Intravenous; D015201:Meta-Analysis as Topic; D008874:Midazolam / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008954:Models, Biological; D010627:Phenethylamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D010627:Phenethylamines; D013449:Sulfonamides; C063533:dofetilide; D008874:Midazolam