A weighted log-rank test and associated effect estimator for cancer trials with delayed treatment effect.
A weighted log-rank test and associated effect estimator for cancer trials with delayed treatment effect.
复制标题
用于具有延迟治疗效果的癌症试验的加权对数秩检验和相关效应估计器。
DOI：
10.1002/pst.2092
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发表时间：
2021
影响因子：
1.5
通讯作者：
He,Philip
中科院分区：
文献类型：
--
作者：
Yu,Chang;Huang,Xiang;Nian,Hui;He,Philip
通过采用各种权重函数扩展了标准对数秩检验。癌症疫苗或免疫疗法试验已经显示出实验疗法的延迟起效。这表现为存活曲线的延迟分离。这项工作提出了新的加权对数秩检验来解释这种延迟。权重函数由实验和对照治疗之间的时变风险比驱动。我们实现了数值评估的舍恩菲尔德近似（NESA）的平均值的检验统计量。NESA使我们能够评估把握度并计算样本量，以检测此类延迟治疗效应，并对试验中的非比例风险进行更一般的规范。我们进一步表明我们提出的测试和加权考克斯回归之间的连接。然后获得使用相同权重的平均风险比作为治疗效果的估计量。进行了广泛的模拟研究，以比较所提出的测试与标准对数秩检验的性能，并评估其对模型错误规范的鲁棒性。我们的测试在一般情况下优于G ρ，γ类，并且具有接近最优测试的性能。我们在两项癌症免疫治疗试验中展示了我们的方法。
The standard log‐rank test has been extended by adopting various weight functions. Cancer vaccine or immunotherapy trials have shown a delayed onset of effect for the experimental therapy. This is manifested as a delayed separation of the survival curves. This work proposes new weighted log‐rank tests to account for such delay. The weight function is motivated by the time‐varying hazard ratio between the experimental and the control therapies. We implement a numerical evaluation of the Schoenfeld approximation (NESA) for the mean of the test statistic. The NESA enables us to assess the power and to calculate the sample size for detecting such delayed treatment effect and also for a more general specification of the non‐proportional hazards in a trial. We further show a connection between our proposed test and the weighted Cox regression. Then the average hazard ratio using the same weight is obtained as an estimand of the treatment effect. Extensive simulation studies are conducted to compare the performance of the proposed tests with the standard log‐rank test and to assess their robustness to model mis‐specifications. Our tests outperform theGρ,γclass in general and have performance close to the optimal test. We demonstrate our methods on two cancer immunotherapy trials.