Davis Sonia M, Koch Gary G, Davis C E, LaVange Lisa M
Quintiles, Inc., 5927 South Miami Boulevard, Morrisville, NC 27560, USA.
Schizophr Bull. 2003;29(1):73-80. doi: 10.1093/oxfordjournals.schbul.a006993.
The design of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia and Alzheimer's disease studies pose several statistical challenges, including issues related to performing multiple comparisons, defining effectiveness outcomes, and collecting and analyzing data from a design with multiple outcome-driven re-randomizations. We discuss the CATIE strategy for addressing many hypotheses within the context of one clinical trial while controlling the overall type I error rate. We provide motivation for the use of two effectiveness outcomes: time to all-cause discontinuation and composite endpoints that combine outcomes from multiple domains, such as efficacy, safety, cost-effectiveness, and quality of life. Methods for statistical analysis of an outcome-driven re-randomization trial are compared and evaluated. We describe analysis within each phase, analysis based on the first randomization or treatment algorithms, and repeated measures modeling. Finally, strategies are described for designing an electronic data collection system for trials with repeated outcome-driven re-randomizations.
临床抗精神病药物干预有效性试验（CATIE）中精神分裂症和阿尔茨海默病研究的设计带来了若干统计挑战，包括与进行多重比较、定义有效性结局以及从具有多个结局驱动再随机化的设计中收集和分析数据相关的问题。我们讨论了在一项临床试验的背景下控制总体I型错误率时应对多个假设的CATIE策略。我们阐述了使用两个有效性结局的动机：全因停药时间以及综合多个领域结局（如疗效、安全性、成本效益和生活质量）的复合终点。对结局驱动再随机化试验的统计分析方法进行了比较和评估。我们描述了每个阶段的分析、基于首次随机化或治疗算法的分析以及重复测量建模。最后，介绍了为具有重复结局驱动再随机化的试验设计电子数据收集系统的策略。
