Group sequential control of overall toxicity incidents in clinical trials – non-Bayesian and Bayesian approaches
Group sequential control of overall toxicity incidents in clinical trials – non-Bayesian and Bayesian approaches
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DOI：
10.1177/0962280212440535
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发表时间：
2016-02
影响因子：
2.3
通讯作者：
Jihnhee Yu;A. Hutson;A. Siddiqui;Mary A Kedron
中科院分区：
文献类型：
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作者：
Jihnhee Yu;A. Hutson;A. Siddiqui;Mary A Kedron
在一些小型临床试验中，毒性不是主要终点;然而，它往往对患者的生活质量产生可怕的影响，甚至危及生命。对于此类临床试验，需要严格控制不良事件的总体发生率，同时收集安全性信息。在这篇文章中，我们提出了组序贯毒性监测策略，以控制总体毒性事件低于一定水平，而不是进行假设检验，这可以纳入现有的研究设计的基础上的主要终点。我们考虑两个顺序的方法：一个非贝叶斯方法，其中停止规则的基础上获得的“未来”的概率过高的毒性率;和贝叶斯适应修改拟议的非贝叶斯方法，它可以使用在中期分析获得的信息。通过一个广泛的蒙特卡罗研究，我们表明，贝叶斯方法往往提供了更好的控制比非贝叶斯方法的总体毒性率。我们还调查了充分的毒性评估后的研究。我们证明了我们提出的方法在控制急性缺血性卒中患者症状性颅内出血率方面的适用性。
In some small clinical trials, toxicity is not a primary endpoint; however, it often has dire effects on patients’ quality of life and is even life-threatening. For such clinical trials, rigorous control of the overall incidence of adverse events is desirable, while simultaneously collecting safety information. In this article, we propose group sequential toxicity monitoring strategies to control overall toxicity incidents below a certain level as opposed to performing hypothesis testing, which can be incorporated into an existing study design based on the primary endpoint. We consider two sequential methods: a non-Bayesian approach in which stopping rules are obtained based on the ‘future’ probability of an excessive toxicity rate; and a Bayesian adaptation modifying the proposed non-Bayesian approach, which can use the information obtained at interim analyses. Through an extensive Monte Carlo study, we show that the Bayesian approach often provides better control of the overall toxicity rate than the non-Bayesian approach. We also investigate adequate toxicity estimation after the studies. We demonstrate the applicability of our proposed methods in controlling the symptomatic intracranial hemorrhage rate for treating acute ischemic stroke patients.