论文标题
响应者分层指数生存模型中的分析和样本量计算
Analysis and sample size calculation within the responder stratified exponential survival model
论文作者
论文摘要
肿瘤学的主要终点通常是总体生存,在这些年后,疗法之间的差异才能观察到。为了避免预扣有前途的疗法,可以基于替代终点的初步批准。批准可以在稍后通过评估同一研究中的总体生存率来确认。在这些试验中,必须考虑样本量计算和分析,替代终点与整体生存之间的相关性。对于二进制替代端点,可以通过Xia,Cui和Yang(2014)提出的响应者分层指数生存(RSES)模型来对此关系进行建模。我们根据最大似然估计器得出模型和置信区间的性能。此外,我们提出了生存差异的近似和精确检验。对于两个新开发的测试的I型错误率,功率和所需的样本量,都可以准确确定。将这些特征与Logrank检验的特征进行比较。我们证明确切的测试表现最好。在某些情况下,Logrank测试的功率大大降低。我们得出的结论是,不应在RSES模型中使用Logrank测试。提出的样本量计算方法效果很好。讨论了我们提出的方法的解释性。
The primary endpoint in oncology is usually overall survival, where differences between therapies may only be observable after many years. To avoid withholding of a promising therapy, preliminary approval based on a surrogate endpoint is possible. The approval can be confirmed later by assessing overall survival within the same study. In these trials, the correlation between surrogate endpoint and overall survival has to be taken into account for sample size calculation and analysis. For a binary surrogate endpoint, this relation can be modeled by means of the responder stratified exponential survival (RSES) model proposed by Xia, Cui, and Yang (2014). We derive properties of the model and confidence intervals based on Maximum Likelihood estimators. Furthermore, we present an approximate and an exact test for survival difference. Type I error rate, power, and required sample size for both newly developed tests are determined exactly. These characteristics are compared to those of the logrank test. We show that the exact test performs best. The power of the logrank test is considerably lower in some situations. We conclude that the logrank test should not be used within the RSES model. The proposed method for sample size calculation works well. The interpretability of our proposed methods is discussed.