Sample size calculation for the proportional hazards cure model.
Sample size calculation for the proportional hazards cure model.
复制标题
比例危害的样本量计算。
DOI：
10.1002/sim.5465
复制
发表时间：
2012-12-20
影响因子：
2
通讯作者：
Lu, Wenbin
中科院分区：
文献类型：
--
作者：
Wang, Songfeng;Zhang, Jiajia;Lu, Wenbin
在具有事件发生时间终点的临床试验中，很大一部分患者被治愈（或长期存活）的情况并不少见，例如非霍奇金淋巴瘤疾病的试验。根据比例风险 (PH) 模型得出的普遍使用的样本量公式可能不适合设计具有治愈分数的生存试验，因为可能违反 PH 模型假设。为了考虑治愈率，PH治愈模型在实践中被广泛使用，其中PH模型用于计算未治愈患者的生存时间，逻辑分布用于计算患者治愈的概率。在本文中，我们通过研究零假设和局部替代假设下标准加权对数秩统计量的渐近分布，开发了基于 PH 治愈模型的样本量公式。 PH 治愈模型下导出的样本量公式更加灵活，因为它可以用来测试短期生存和/或治愈分数的差异。此外，还作为数值示例研究了应计方法以及应计期间和后续期间对样本量计算的影响。结果表明，在样本量计算中忽略治愈率可能会导致研究动力不足或动力过大。通过模拟研究评估了所提出的公式的性能，并给出了一个使用黑色素瘤试验数据的例子来说明其应用。
In clinical trials with time-to-event endpoints, it is not uncommon to see a significant proportion of patients being cured (or long-term survivors), such as trials for the non-Hodgkins lymphoma disease. The popularly used sample size formula derived under the proportional hazards (PH) model may not be proper to design a survival trial with a cure fraction, since the PH model assumption may be violated. To account for a cure fraction, the PH cure model is widely used in practice, where a PH model is used for survival times of uncured patients and a logistic distribution is used for the probability of patients being cured. In this paper, we develop a sample size formula based on the PH cure model by investigating the asymptotic distributions of the standard weighted log-rank statistics under the null and local alternative hypotheses. The derived sample size formula under the PH cure model is more flexible since it can be used to test the differences in the short-term survival and/or cure fraction. Furthermore, the impacts of accrual methods and durations of accrual and follow-up periods on sample size calculation are also investigated as numerical examples. The results show that ignoring the cure rate in sample size calculation can lead to either underpowered or overpowered studies. The performance of the proposed formula is evaluated by simulation studies and an example is given to illustrate its application using data from a melanoma trial.
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影响因子：
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通讯作者：
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作者：
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