HIV预防事件驱动试验的交叉和重复随机化:解决试验设计中风险异质性的影响

C. D. Domínguez Islas, E. Brown
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引用次数: 1

摘要

有效的HIV暴露前预防(PrEP)的可用性为检测新型按需、用户控制的HIV预防产品带来了新的挑战,包括较低的安慰剂组发生率和增加的参与者之间的HIV风险变异性。在本文中,我们讨论了低艾滋病毒发病率如何导致更长时间的试验,其中参与者风险的可变性可能影响风险降低的估计。我们引入了一种可能比按需产品发生率降低在人群水平上更相关的暴露效能测量方法,并探索了平行臂设计的替代方法,可以更好地针对这一感兴趣的参数:交叉和再随机化设计。我们提出了三种不同的方法,可以在事件驱动试验中实现干预分配的交叉和再随机化。我们通过仿真研究评估了这些设计的性能,发现它们比传统的事件驱动并行臂设计具有更好的估计和更高的功率。最后,我们讨论了未来的工作、实际的挑战和需要解决的道德问题,以使这些设计更接近实现。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Crossover and Repeated Randomization in Event Driven Trials for HIV Prevention: Addressing the Impact of Heterogeneity in Risk in the Trial Design
Abstract The availability of effective Pre-Exposure Prophylaxis (PrEP) for HIV introduces new challenges for testing novel on-demand, user-controlled HIV prevention products, including lower placebo arm incidence and increased between-participant variability in HIV risk. In this paper, we discuss how low HIV incidence may result in longer trials in which the variability in participants' risk may impact the estimate of risk reduction. We introduce a measure of per-exposure efficacy that may be more relevant than the population level reduction in incidence for on demand products and explore alternatives to the parallel arm design that could target better this parameter of interest: the crossover and the re-randomization designs. We propose three different ways in which crossover and re-randomization of intervention assignments could be implemented in event-driven trials. We evaluate the performance of these designs through a simulation study, finding that they allow for better estimation and higher power than the traditional event-driven parallel arm design. We conclude by discussing future work, practical challenges and ethical considerations that need to be addressed to take these designs closer to implementation.
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