论文标题

贝叶斯响应自适应随机设计具有复合终点的死亡率和发病率

Bayesian response adaptive randomization design with a composite endpoint of mortality and morbidity

论文作者

Xu, Zhongying, Bandos, Andriy I., Ma, Tianzhou, Tang, Lu, Talisa, Victor B., Chang, Chung-Chou H.

论文摘要

根据决策点之前观察到的反应以及该分配的顺序适应,将患者分配给治疗臂,可以最大程度地减少预期的失败数量或最大程度地对患者的总收益。在这项研究中,我们开发了针对接受重症监护病房(ICU)的患者的贝叶斯反应自适应随机化(RAR)设计,该设计针对无器官支撑天(OSFD)。 OSFD是死亡率和发病率的混合物,该混合物是通过预定的随机后的预定时间窗口中自由器官支撑的天数进行评估的。过去,研究人员将OSFD视为最低类别是死亡的序数变量。我们通过使用Markov Chain Carlo采样的贝叶斯混合模型来估算OSFD的后验可能性,并确定每个中期的治疗率,我们提出了一种新颖的RAR设计,例如死亡率和发病率的复合终点,例如OSFD。进行了模拟,以比较我们提出的设计在各种随机规则和不同α支出功能下的性能。结果表明,与其他现有的自适应规则相比,我们使用贝叶斯推理的RAR设计将更多的患者分配给了表现更好的手臂,同时确保了足够的功率和I型错误率控制一系列合理的临床场景。

Allocating patients to treatment arms during a trial based on the observed responses accumulated prior to the decision point, and sequential adaptation of this allocation,, could minimize the expected number of failures or maximize total benefit to patients. In this study, we developed a Bayesian response adaptive randomization (RAR) design targeting the endpoint of organ support-free days (OSFD) for patients admitted to the intensive care units (ICU). The OSFD is a mixture of mortality and morbidity assessed by the number of days of free of organ support within a predetermined time-window post-randomization. In the past, researchers treated OSFD as an ordinal outcome variable where the lowest category is death. We propose a novel RAR design for a composite endpoint of mortality and morbidity, e.g., OSFD, by using a Bayesian mixture model with a Markov chain Monte Carlo sampling to estimate the posterior probability of OSFD and determine treatment allocation ratios at each interim. Simulations were conducted to compare the performance of our proposed design under various randomization rules and different alpha spending functions. The results show that our RAR design using Bayesian inference allocated more patients to the better performing arm(s) compared to other existing adaptive rules while assuring adequate power and type I error rate control for the across a range of plausible clinical scenarios.

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