Abstract：
:There has been little evaluation of maximum likelihood approximation methods for non-linear mixed effects modelling of count data. The aim of this study was to explore the estimation accuracy of population parameters from six count models, using two different methods and programs. Simulations of 100 data sets were performed in NONMEM for each probability distribution with parameter values derived from a real case study on 551 epileptic patients. Models investigated were: Poisson (PS), Poisson with Markov elements (PMAK), Poisson with a mixture distribution for individual observations (PMIX), Zero Inflated Poisson (ZIP), Generalized Poisson (GP) and Negative Binomial (NB). Estimations of simulated datasets were completed with Laplacian approximation (LAPLACE) in NONMEM and LAPLACE/Gaussian Quadrature (GQ) in SAS. With LAPLACE, the average absolute value of the bias (AVB) in all models was 1.02% for fixed effects, and ranged 0.32-8.24% for the estimation of the random effect of the mean count (lambda). The random effect of the overdispersion parameter present in ZIP, GP and NB was underestimated (-25.87, -15.73 and -21.93% of relative bias, respectively). Analysis with GQ 9 points resulted in an improvement in these parameters (3.80% average AVB). Methods implemented in SAS had a lower fraction of successful minimizations, and GQ 9 points was considerably slower than 1 point. Simulations showed that parameter estimates, even when biased, resulted in data that were only marginally different from data simulated from the true model. Thus all methods investigated appear to provide useful results for the investigated count data models.
journal_name
J Pharmacokinet Pharmacodynjournal_title
Journal of pharmacokinetics and pharmacodynamicsauthors
Plan EL,Maloney A,Trocóniz IF,Karlsson MOdoi
10.1007/s10928-009-9126-8subject
Has Abstractpub_date
2009-08-01 00:00:00pages
353-66issue
4eissn
1567-567Xissn
1573-8744journal_volume
36pub_type
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