劣者淘汰两阶段自适应临床试验的设计和分析

项目名称： 劣者淘汰两阶段自适应临床试验的设计和分析

项目编号： No.11471239

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 数理科学和化学

项目作者： 杨贵军

作者单位： 天津财经大学

项目金额： 70万元

中文摘要： 为了缩短试验周期，减少试验成本，劣者淘汰两阶段自适应临床试验将试验过程分为两个阶段。在第一阶段试验结束后，利用第一阶段数据进行统计分析，或者做出最终决策并终止整个试验，或者劣者淘汰，只对优选的试验处理（水平）进行第二阶段试验。由于生物医药领域的迫切需求，劣者淘汰两阶段自适应临床试验已成为该领域的研究热点。目前，在过程设计和数据分析方面已有不少的文献发表，但还有必要进行深入研究。本项目将深入研究试验过程设计与数据分析方面的一些最新课题，主要内容包括（1）劣者淘汰两阶段自适应临床试验过程优化，（2）现有的估计和检验方法的更严谨的统计学刻画，（3）具有超饱和设计结构的劣者淘汰两阶段自适应临床试验及具有部分因析设计结构的劣者淘汰两阶段自适应临床试验的过程设计和数据分析，（4）劣者淘汰两阶段自适应临床试验数据缺失问题的解决办法及其敏感性分析。期望给出一系列的理论结果，并给出应用案例，以供实际使用。

中文关键词： 试验设计；临床试验；自适应；部分因析设计；超饱和设计

英文摘要： The two-stage adaptive drop-the-losers clinical trials have the experimental procedure with two stages such that it happens possible that the entire procedure shortens and the total cost reduces. After the first stage, the analysis with statistical decision is performed based on data obtained from the first stage. If the final decision is obtained, the experiment is finished. Otherwise, to drop the losers, i.e. the better experimental treatments (or factorial levels) will be chosen to continue the second stage experiments. Because of the urgent need of biology, medicine and pharmacy development, research on two-stage adaptive drop-the-losers clinic trials have attracted considerable attention for their ability to improve statistical efficiency. At present, there are a lot of literatures published on the procedure design and data analysis. It is still necessary to further research. The project focuses on the latest issues of the design and analysis of experimental process and statistical inference. It intends to investigate: (1) how to optimize the entire procedure of two-stage adaptive drop-the-losers clinic trials; (2) how to find more theoretical properties of the estimators and significant test methods provided by published literatures; (3) how to design two-stage adaptive drop-the-losers clinic trials with supersaturated design structure or ones with fractional factorial design structure; (4) how to analyze the missing data of two-stage adaptive drop-the-losers clinic trials. The project will provide more important theoretical results and the application cases for practical use.

英文关键词： Experimental Design;Clinic Trials;Adaptive;Fractional Factorial Design;Supersaturated Design