Abstract:
:Bioequivalence or interaction trials are commonly studied in crossover design and can be analysed by nonlinear mixed effects models as an alternative to noncompartmental approach. We propose an extension of the population Fisher information matrix in nonlinear mixed effects models to design crossover pharmacokinetic trials, using a linearisation of the model around the random effect expectation, including within-subject variability and discrete covariates fixed or changing between periods. We use the expected standard errors of treatment effect to compute the power for the Wald test of comparison or equivalence and the number of subjects needed for a given power. We perform various simulations mimicking crossover two-period trials to show the relevance of these developments. We then apply these developments to design a crossover pharmacokinetic study of amoxicillin in piglets and implement them in the new version 3.2 of the r function PFIM.
journal_name
Stat Medjournal_title
Statistics in medicineauthors
Nguyen TT,Bazzoli C,Mentré Fdoi
10.1002/sim.4390subject
Has Abstractpub_date
2012-05-20 00:00:00pages
1043-58issue
11-12eissn
0277-6715issn
1097-0258journal_volume
31pub_type
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