Various extensions of the isotonic regression problems and its applications

等渗回归问题的各种扩展及其应用

基本信息

批准号：
14580351
负责人：
HIROTSU Chihiro
金额：
$ 2.3万
依托单位：
Meisei University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580351/
关键词：
Comparative clinical study Dose - response analysis Life science and statistical science Non-inferiority test Multiple decision processes Superiority test 凹凸パターン拡張max t検定血圧24時間値最適実験計画 max min検定プロファイル解析クラスタリングアルゴリズム血圧日内リズム /

项目摘要

1.A unifying approach to non-inferiority, equivalence and superiority tests via multiple decision processesIn the comparative clinical study of a new drug against an active control the simultaneous testing of the non-inferiority hypothesis and the superiority hypothesis has been of great interest. In Japan the significance level of these two tests was set commonly at α=0.05 but the α for the non-inferiority hypothesis has been altered to 0.025 by the International Guideline introduced in 1999. It naturally gives a very big impact on the Japanese practice of clinical trial since according to the International Guideline approximately 1.3 times the sample size is required as compared with the old Japanese practice for proving the non-inferiority of a test drug which is truly equivalent to the control. This is indeed a very serious problem to be discussed carefully, see also Hirotsu and Hothorn (2003). In this research we succeeded in unifying the old Japanese Guideline and the International Guideline by applying the partitioning principle of the parameter space. This method is particularly attractive changing the strength of the evidence of relative efficacy of the test drug against a control according to the achievement of the clinical trial. It includes the decisions 1. weak non-inferiority, 2. strong non-inferiority, 3. at least equivalence, and 4. superiority. The weak non-inferiority corresponds to the Japanese practice and the strong non-inferiority to the International Guideline. Yet another approach has also been proposed taking the advantages of both of the Japanese and International practices.2.Dose - response analysisIn the dose-response analysis a new approach of estimating the dose - response patterns is proposed replacing the classical estimation of dose-response function. This idea is very useful in the phase 2 clinical trial whose purpose is to decide the recommended dose for the clinical treatment.

1.在新药的比较临床研究中，通过多个决策过程进行了一种非差异，等效性和优越性检验的统一方法，反对对非效率假设的简单检验和优越性假设的简单测试的主动控制一直具有极大的兴趣。在日本，这两项测试的显着性水平通常设定为α= 0.05，但非劣效率假设的α已通过1999年引入的国际准则将其更改为0.025。它自然地对日本的临床试验产生了很大的影响，因为根据国际指南的规定，与旧级别相比，这是对旧级别的典范，这是在旧日本的典范中提供的，而不是提供1.3次的典范。控制。这确实是一个非常严重的问题，需要仔细讨论，另请参见Hiratsu和Hothorn（2003）。在这项研究中，我们通过应用参数空间的分区原则成功地统一了日本旧准则和国际指南。这种方法特别有吸引力，改变了根据临床试验的实现，测试药物相对效率相对效率的证据的强度。它包括决策1。弱的非效率，2。强烈的非效率，3。至少等效，4。优越性。弱的不介绍性与日本实践相对应，对国际准则的强烈不介绍。还提出了另一种方法来利用日本和国际实践的优势。2。剂量反应分析在剂量反应分析中，提出了一种估计剂量响应模式的新方法，以取代剂量回应功能的经典估计。这个想法在第二阶段临床试验中非常有用，其目的是确定建议的临床治疗剂量。