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Current Pharmacogenomics and Personalized Medicine
(Formerly Current Pharmacogenomics)
ISSN (Print): 1875-6921
ISSN (Online): 1875-6913
VOLUME: 10
ISSUE: 1
DOI: 10.2174/1875692111201010022









Role of Statistical Random-Effects Linear Models in Personalized Medicine

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Author(s): Francisco J. Diaz, Hung-Wen Yeh and Jose de Leon
Pages 22-32 (11)
Abstract:
Some empirical studies and recent developments in pharmacokinetic theory suggest that statistical randomeffects linear models are valuable tools that allow describing simultaneously patient populations as a whole and patients as individuals. This remarkable characteristic indicates that these models may be useful in the development of personalized medicine, which aims at finding treatment regimes that are appropriate for particular patients, not just appropriate for the average patient. In fact, published developments show that random-effects linear models may provide a solid theoretical framework for drug dosage individualization in chronic diseases. In particular, individualized dosages computed with these models by means of an empirical Bayesian approach may produce better results than dosages computed with some methods routinely used in therapeutic drug monitoring. This is further supported by published empirical and theoretical findings that show that random effects linear models may provide accurate representations of phase III and IV steady-state pharmacokinetic data, and may be useful for dosage computations. These models have applications in the design of clinical algorithms for drug dosage individualization in chronic diseases; in the computation of dose correction factors; computation of the minimum number of blood samples from a patient that are necessary for calculating an optimal individualized drug dosage in therapeutic drug monitoring; measure of the clinical importance of clinical, demographic, environmental or genetic covariates; study of drug-drug interactions in clinical settings; the implementation of computational tools for web-site-based evidence farming; design of pharmacogenomic studies; and in the development of a pharmacological theory of dosage individualization.
Keywords:
Chronic diseases, dosage individualization, drug mixed linear models, effect sizes, empirical Bayesian feedback, evidence farms, pharmacokinetic modeling, random-effects linear models
Affiliation:
3901 Rainbow Blvd, Mail Stop 1026, Kansas City, KS 66160, United States.