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肿瘤新药Ⅱ期临床试验常用二阶段设计的样本含量估计及其SAS实现

Sample Size Calculation using SAS for PhaseⅡin Two-stage Clinical Trials of Anti-tumor Drugs

  • 摘要: 目的介绍肿瘤新药Ⅱ期临床试验常用Gehan 二阶段设计及Simon 二阶段设计的设计原理和样本含量估计问题,提供 SAS宏程序快速实现其样本含量估计。方法结合二项分布的确切概率原理说明单阶段设计、Gehan 二阶段设计及两种Simon二阶段设计样本含量计算过程。利用SAS宏程序,通过设置不同参数比较其优缺点。结果Simon极小极大设计与单阶段设计相比,不会增加最大样本含量;与Gehan 二阶段设计相比,保证了在实际有效率很低时早期终止试验。结论Simon 二阶段比单阶段设计和Gehan 二阶段设计更有优势,且极小极大设计在多数情况下比最优化设计受欢迎。

     

    Abstract: Objective To compare Gehan two-stage design and Simon two-stage design in sample size calculations for phase Ⅱ clinical trials of anti-tumor drugs. Methods We explained the sample size calculation methods with a single-stage design, Gehan two-stage design, and Simon optimal two-stage and minimax two-stage designs in line with the principle of exact binomial probability. By setting up different parameters in SAS macro program, the advantages and disadvantages of these designs were compared. Results The minimax two-stage design does not increase the maximum sample size compared with the single-stage design. Compared with the Gehan two-stage design, the Simon two-stage design has the advantage of being able to determine an early termination of trials when no or low anti-tumor activities are evident. Conclusion Simon two-stage design is better than single-stage design and Gehan two-stage design. The minimax design is more popular than the optimal design.

     

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