药物组合的均匀试验设计

发布时间：2018-07-26 14:52

【摘要】：现代医学研究表明,复杂疾病往往是由多个基因和蛋白质发生变异而引起的,其发病机制也可理解为多途径、多靶点的生物网络变化.随着人们对疾病的治疗效果的要求日益提高,特别是对复杂的疾病,仅靠单一靶点的药物治疗往往不能满足疾病的治疗需求.在现代临床试验中,药物组合在治疗疾病的过程中发挥着越来越重要的作用,具有广阔的开发和应用前景.每种药物单独作用于人体时,会产生各自的药理效应.多种药物组合在一起使用时,则可能会使药效增强并降低副作用.所以,药物组合的研究具有重要的医学价值.本文主要利用均匀试验设计来研究两个药和三个药的组合试验.两个药的组合试验,其试验区域为任意的四边形.为了在任意四边形上构造均匀试验设计,本文提出了一种新颖的方法,即构造任意四边形与单位方体[0:1]2之间的一一对应变换,利用该变换推导出试验区域上随机向量的分布表达式,随后给出了在任意四边形上均匀布点的算法.三个药的组合试验,其试验区域为任意的三棱柱.同样地,本文构造任意三棱柱与单位三棱柱之间的一一对应变换,并且产生了在任意三棱柱上均匀布点的算法.最后本文将所提出的方法应用于药物组合研究实例,可在试验区域上均匀布点,同时使单药可加模型的失拟检验的功效达到最大,得到了不错的效果.
[Abstract]:Modern medical studies have shown that complex diseases are often caused by mutations in multiple genes and proteins, and the pathogenesis can also be understood as a variety of biological networks with multiple pathways and targets. With the increasing demand for the therapeutic effect of diseases, especially for complex diseases, the single target drug therapy is often unable to meet the needs of the treatment of diseases. In modern clinical trials, drug combinations play a more and more important role in the treatment of diseases and have a broad prospect of development and application. When each drug acts alone on the human body, it produces its own pharmacological effects. Combination of multiple drugs may enhance the efficacy and reduce side effects. Therefore, the study of drug combination has important medical value. In this paper, the uniform test design is used to study the combination test of two drugs and three drugs. The combined test of the two drugs has an arbitrary quadrilateral region. In order to construct a uniform experimental design on an arbitrary quadrilateral, a novel method is proposed in this paper, which is to construct a one-to-one corresponding transformation between an arbitrary quadrilateral and a unit square [0:1] 2. The distribution expression of random vectors in the experimental region is derived by using this transformation, and then an algorithm for uniformly distributing points on an arbitrary quadrilateral is given. The test area of the three drugs was arbitrary prism. In the same way, the one-to-one corresponding transformation between an arbitrary triangular prism and a unit triangular prism is constructed, and an algorithm for uniform distribution of points on any triangular-prism is obtained. Finally, the method proposed in this paper is applied to the case study of drug combination, which can distribute the points evenly in the experimental area, and at the same time, the efficiency of the single additive model can be maximized, and the good results are obtained.
【学位授予单位】：广西师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R96

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