Statistical Power Calculations for Mixed Pharmacokinetic Study Designs Using a Population Approach
Journal Title: The AAPS Journal - Year 2014, Vol 16, Issue 5
Abstract
Simultaneous modelling of dense and sparse pharmacokinetic data is possible with a population approach. To determine the number of individuals required to detect the effect of a covariate, simulation-based power calculation methodologies can be employed. The Monte Carlo Mapped Power method (a simulation-based power calculation methodology using the likelihood ratio test) was extended in the current study to perform sample size calculations for mixed pharmacokinetic studies (i.e. both sparse and dense data collection). A workflow guiding an easy and straightforward pharmacokinetic study design, considering also the cost-effectiveness of alternative study designs, was used in this analysis. Initially, data were simulated for a hypothetical drug and then for the anti-malarial drug, dihydroartemisinin. Two datasets (sampling design A: dense; sampling design B: sparse) were simulated using a pharmacokinetic model that included a binary covariate effect and subsequently re-estimated using (1) the same model and (2) a model not including the covariate effect in NONMEM 7.2. Power calculations were performed for varying numbers of patients with sampling designs A and B. Study designs with statistical power >80% were selected and further evaluated for cost-effectiveness. The simulation studies of the hypothetical drug and the anti-malarial drug dihydroartemisinin demonstrated that the simulation-based power calculation methodology, based on the Monte Carlo Mapped Power method, can be utilised to evaluate and determine the sample size of mixed (part sparsely and part densely sampled) study designs. The developed method can contribute to the design of robust and efficient pharmacokinetic studies.
Authors and Affiliations
Frank Kloprogge, Julie A. Simpson, Nicholas P. J. Day, Nicholas J. White, Joel Tarning
Keywords
Related Articles
- EP ID EP681087
- DOI 10.1208/s12248-014-9641-4
- Views 95
- Downloads 0
Evaluation of the potential use of poly(ethylene oxide) as tablet- and extrudate-forming material
The purpose of this study was to assess the potential use of poly(ethylene oxide) (PEO) as matrix-forming mate-rial for tablets and extrudates. Raw materials were characterized for size, size distribution, and shape. Tab...
Glucocorticoid Receptor-Mediated Transcriptional Regulation of N-acetyltransferase 1 Gene Through Distal Promoter
Human arylamine N-acetyltransferase 1, (HUMAN)NAT1, is a phase II xenobiotic-metabolizing enzyme that plays an important role in drug and carcinogen biotransformation and cancer development. Its gene expression has been...
Population Pharmacokinetic Modeling of LY2189102 after Multiple Intravenous and Subcutaneous Administrations
Interleukin-1 beta (IL-1β) is an inflammatory mediator which may contribute to the pathophysiology of rheumatoid arthritis (RA) and type 2 diabetes mellitus (T2DM). Population pharmacokinetics (PK) of LY2189102,...
Mucoadhesive Microspheres for Gastroretentive Delivery of Acyclovir: In Vitro and In Vivo Evaluation
The aim of the present investigation was to evaluate the potential use of mucoadhesive microspheres for gastroretentive delivery of acyclovir. Chitosan, thiolated chitosan, Carbopol 71G and Methocel K15M were used as muc...
Stability: Recommendation for Best Practices and Harmonization from the Global Bioanalysis Consortium Harmonization Team
This paper provides a comprehensive overview of stability-related aspects of quantitative bioanalysis and recommends science-based best practices, covering small and large molecules as well as chromatographic and ligand-...