GENERAL PURPOSE POPULATION ANALYSIS MODULE FOR SAAM II

描述：人口分析是用来量化的方法 动力学研究中的受试者间变异性。在这项修订后的研究中 项目中，申请者提议制定一项总体人口分析。 软件包，并将该软件包与SAAM-II软件系统接口。 该系统通常用于人口建模 利用示踪剂进行药代动力学/药效学系统和代谢研究 运动学。 群体分析被广泛应用于药代动力学研究，因为它是 了解药物在人类和动物体内的作用的关键。它提供了 治疗用药方案智能化设计的基础 疾病过程。在新陈代谢研究中，它被用来识别 当正常受试者的总体为 与一群患有已知疾病的受试者相比。 在这种建模工作中有三个重大障碍：(I) 不是同时包含参数和非参数的软件包 方法，(Ii)目前使用的某些方法没有得到严格的 人们所希望的统计和数值分析，以及(Iii)当前 软件要么在建模能力上受到限制，要么对用户不友好。 该项目汇集了一组独特的研究人员，以克服这些 制定和纳入SAAM-II的一般目的所造成的障碍 人口分析模块。更具体地说，以下三个目标是 提出：1)发展收敛的参数和参数的数值算法 非参数方法。2)证明了AIM-1算法的一致性。 通过仿真研究了这些方法的效率和稳健性 对现有的其他方法进行了研究和比较。3)接口 具有通用建模/图形用户界面的AIM-1中的算法 SAAM-II。 其结果将是一个具有一般模型建立的人口分析程序 功能和图形用户界面，功能强大、灵活 使用方便。这样的程序目前还不存在。这样的一揽子计划将 改进临床试验的分析，以及由此产生的药物治疗和 病人护理。

DESCRIPTION: Population analysis is the methodology used to quantify intersubject variability in kinetic studies. In this revised research project, the applicants propose to develop a general population analysis package and to interface this package with the SAAM-II software system. This system will typically be used for the population modeling of pharmacokinetic/pharmacodynamic systems and metabolic studies using tracer kinetics. Population analysis is widely used on pharmacokinetic studies since it is the key to understanding how drugs behave in human and animals. It provides the foundation for the intelligent design of dosage regiments to treat disease processes. In metabolic studies, it is used to identify which parameters in a model change when a population of normal subjects is compared to a population of subjects with a known pathological condition. There are three significant obstacles in such modeling efforts: (i) there is no software package that includes both parameteric and nonparameteric methods, (ii) certain methods currently in use have not had the rigorous statistical and numerical analyses that one could desire, and (iii) current software is either limited in modeling capabilities or is not user friendly. This project brings together a unique group of researchers to overcome these obstacles by developing and incorporating into the SAAM-II a general purpose population analysis module. More specifically, the following three aims are proposed: 1) Develop convergent numerical algorithms for parametric and nonparameteric methods. 2) Prove consistency of algorithm in Aim-1. Investigate efficiency and robustness of these methods via simulation studies and compare with other existing methods. 3) Interface the algorithms in Aim-1 with the general model building/graphical user interface of SAAM-II. The result will be a population analysis program with general model building capabilities and a graphical user interface that is powerful, flexible and easy to use. Such programs do not currently exists. Such a package will improve the analysis of clinical trials, and resulting drug therapy and patient care.