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

机译:从不完整的数据进行增量参数评估并将其应用于抗凝剂的人群药理学

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摘要

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.
机译:我们开发了一种从不完整数据进行参数评估的方法。使用贝叶斯方法和信息方法,逐步评估所需参数的改进估算,从实验到实验逐步进行。当实验仍在进行时,我们会做出动态的,改进的预测,并保留和解释有关局部波动的信息,这些信息在应用全局技术时会丢失。小数据包中的信息输入导致数据处理的半分析方法。推导了参数评估的进化准则,类似于人口选择的费舍尔定理。我们开发了可应用于低维系统的直接处理方法,基于对数或直接对数展开的半解析方法,最速下降方法,变化和摄动方法。通过根据有限的临床数据开发一种口服抗凝剂的长期治疗方法来说明该技术。口服抗凝剂的治疗效率在很大程度上取决于各种人体测量学和基因型因素,这会导致临床反应的巨大差异。我们使用从医疗咨询中积累的临床数据来提取有关给定患者动力学和人体测量参数的统计特性的改进的增量信息,进而将其用于随着治疗的进行做出反复的,改进的临床预测。

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