Department of Health Statistics, Faculty of Preventative Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China.
Contemp Clin Trials. 2010 May;31(3):242-50. doi: 10.1016/j.cct.2010.02.001. Epub 2010 Feb 19.
It is well known that flexibility is one of the major advantages of an adaptive two-stage design, and the intended adaptation should be as preplanned as possible to maintain the integrity of the clinical trial. The design of adaptive two-stage double-arm clinical trials for dichotomous variables was proposed by simulation and forecasting procedure at the planning stage. To further ensure the integrity of the clinical trial, the sample size scheme for each scenario, which was supposed to be based on the first stage, was provided in the protocol by Monte Carlo simulation. In addition, the study parameters were determined by comparing the assessment indexes such as total sample size, expected sample size and the test power at the first stage. Furthermore, Fisher's combination test and pooled data analysis were considered and compared through the simulation. The latter, which has the larger overall power and the better overall type I error control, with the same sample size was adopted for further simulation and statistical analysis in the clinical trial.
众所周知，灵活性是适应性两阶段设计的主要优势之一，并且预期的适应性应该尽可能预先规划，以保持临床试验的完整性。通过模拟和预测程序在规划阶段提出了二分类变量的适应性两阶段双臂临床试验设计。为了进一步确保临床试验的完整性，根据第一阶段的结果，在方案中通过蒙特卡罗模拟为每个方案提供了样本量方案。此外，通过比较第一阶段的总样本量、预期样本量和检验效能等评估指标来确定研究参数。此外，通过模拟考虑并比较了 Fisher 组合检验和汇总数据分析。在临床试验中，采用了具有更大总体效能和更好总体 I 类错误控制的后者，并且具有相同的样本量，用于进一步的模拟和统计分析。
