GENERAL PURPOSE POPULATION ANALYSIS MODULE FOR SAAM II

描述：人口分析是用于量化 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，申请人建议制定一个一般人口分析 软件包并将该软件包与SAAM-II软件系统连接。 该系统通常用于人口建模， 使用示踪剂的药代动力学/药效学系统和代谢研究 动力学 群体分析广泛用于药代动力学研究，因为它 了解药物在人类和动物体内作用的关键。 它提供 智能设计治疗剂量方案的基础 疾病过程。 在代谢研究中，它被用来识别 当正常受试者群体被 与具有已知病理状况的受试者群体相比。 在这种建模工作中存在三个重大障碍：（i） 没有一个软件包同时包含参数和非参数 （二）目前使用的某些方法没有严格的 统计和数字分析，人们可以期望，和（iii）目前 软件要么在建模能力方面受到限制，要么对用户不友好。 该项目汇集了一组独特的研究人员，以克服这些问题。 通过制定和纳入SAAM-II的一般目的， 人口分析模块。 具体而言，以下三个目标是 建议：1）开发收敛的数值算法的参数和 非参数方法 2)证明Aim-1中算法的一致性。 通过仿真研究这些方法的效率和鲁棒性 并与现有的其他方法进行了比较。 3)界面 Aim-1中的算法，具有通用模型构建/图形用户界面 SAAM-II。 其结果将是一个人口分析程序与一般模型的建设 功能和图形用户界面，功能强大，灵活， 容易使用. 目前还没有这样的方案。 这样的一揽子计划将 改善临床试验的分析，以及由此产生的药物治疗， 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.