Adaptive Designs and Sequential Monitoring

临床试验是复杂的，通常涉及多个目标，如控制I类错误，增加检测治疗差异的能力，分配更多的患者接受更好的治疗等。在文献中，已经提出了适应性设计（通过顺序地改变设计过程）和顺序监测（通过顺序地改变分析过程），以在一定程度上实现这些目标。本项目将这两种序贯程序相结合，研究序贯监测反应适应性随机临床试验的优点。研究者首先推导出联合过程序贯检验统计量的渐近分布。基于渐近性质，研究者选择适当的边界的组合程序，以实现多个目标。此外，他还调查了联合程序在一些真实的临床试验中的实施情况。临床试验通常涉及多个相互竞争的目标，如检测治疗之间的临床差异，最小化总成本和保护更多的人免受可能的劣质治疗。自适应设计动态地使用顺序累积的数据来收集未来的数据，以实现这些目标。在进行临床试验时，顺序监测是一种标准技术，可以平衡早期停止试验的伦理和经济优势与错误结论的风险。该建议涉及将自适应设计和顺序监测相结合。研究者将首先研究反应适应性随机临床试验的序贯监测，然后研究该联合程序的优点。本计画完成后，可将序贯监测应用于适应性随机临床试验，以达成多重目标。这些研究项目将产生先进的统计工具，用于分析按顺序收集的数据。这些工具可以应用于许多领域，包括药物开发，医学研究，工业实验，经济和金融。

Clinical trials are complicated and usually involve multiple objectives such as controlling type I error, increasing power of detecting treatment difference, assigning more patients to better treatment, and more. In literature, both adaptive designs (by changing design procedure sequentially) and sequential monitoring (by changing analysis procedure sequentially) have been proposed to achieve these objectives to some degree. In this project, the investigator combines these two sequential procedures and studies the advantages of sequential monitoring response-adaptive randomized clinical trial. The investigator first derives the asymptotic distribution of the sequential test statistics of the combined procedure. Based on the asymptotic properties, the investigator selects appropriate boundaries for the combined procedure to achieve multiple objectives. Further, he investigates the implementation of the combined procedure to some real clinical trials.Clinical trials usually involve multiple competing objectives such as detecting clinical difference among treatments, minimizing total cost and protecting more people from possibly inferior treatments. Adaptive designs dynamically use sequentially accruing data in decisions for collecting future data in order to achieve these objectives. In conducting clinical trials, sequential monitoring is a standard technique to balance the ethical and financial advantages of stopping a trial early against the risk of an incorrect conclusion. This proposal is concerned with combining adaptive designs and sequential monitoring. The investigator will first investigate sequential monitoring of a response-adaptive randomized clinical trial and will then study the advantages of this combined procedure. Upon completion of this project, one can apply sequential monitoring to an adaptive randomized clinical trial to achieve multiple objectives. The research projects will produce advanced statistical tools for analyzing data which is sequentially collected. These tools may be applied in many fields including drug development, medical studies, industrial experiments, economics and finance.