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Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4627-32. doi: 10.1073/pnas.0711508105. Epub 2008 Mar 19.

Incremental parameter evaluation from incomplete data with application to the population pharmacology of anticoagulants.

Author information

1
Department of Chemistry, Stanford University, Stanford CA 94305-5080, USA. marceluc@stanford.edu

Abstract

We develop a method for parameter evaluation from incomplete data. Improved estimates of the desired parameters are evaluated step by step, from experiment to experiment by using both Bayesian and informational methods. We make dynamical, improved predictions while the experiments are still going on and keep and interpret information about local fluctuations, which is lost on applying global techniques. The input of information in small packets leads to semi-analytic methods for data processing. An evolution criterion for parameter evaluation, similar to Fisher's theorem of population selection, is derived. We develop direct processing methods, which can be applied to low dimensional systems, semi-analytic methods based on direct or double logarithmic phase expansions, steepest descent approaches, variation and perturbation methods. The techniques are illustrated by developing a method of long-term planning of treatments with oral anticoagulants based on limited clinical data. The efficiency of treatment by oral anticoagulants depends strongly on various anthropometric and genotypic factors, which lead to large variations of the clinical response. We use the clinical data, which accumulates from medical consultations, for extracting improved, incremental information about the statistical properties of the kinetic and anthropometric parameters for a given patient, which in turn is used for making repeated, improved clinical predictions as the treatment proceeds.

PMID:
18353988
PMCID:
PMC2290818
DOI:
10.1073/pnas.0711508105
[Indexed for MEDLINE]
Free PMC Article
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