论文标题

使用两个阶段TMLE的聚类随机试验和观察性研究模糊,以解决子采样,丢失和最小独立单位

Blurring cluster randomized trials and observational studies using Two-Stage TMLE to address sub-sampling, missingness, and minimal independent units

论文作者

Nugent, Joshua R., Marquez, Carina, Charlebois, Edwin D., Abbott, Rachel, Balzer, Laura B.

论文摘要

集群随机试验(CRT)经常招募大量参与者,但是由于后勤和财政挑战,只能选择一部分参与者以测量某些结果,而被采样的人可能是故意或没有任何参与者的,对所有参与者都不明确。缺少的数据还带来了一个挑战:如果采样具有测量结果的个体与缺失结果的人不同,则对ARM特异性结果的未调整估计值以及干预效果可能会产生偏差。此外,CRT经常不需要限制和随机几个群集,限制统计能力并提高对有限样本性能的担忧。由搜索社区随机试验的子研究对结核病感染的发生,我们展示了解决这些挑战的互锁方法。首先,我们扩展了两个阶段的最小损失估计(TMLE),以说明三个缺失的来源:(1)子研究的抽样; (2)测量被采样的人之间的基线状态,以及(3)在发病率队列中的最终状态测量(即已知在基线处有风险的人)。其次,我们批判性地评估了可以将群集子单位视为有条件独立的单位的假设,从而提高了精度和统计能力,但也导致CRT的行为更像是一项观察性研究。我们对搜索的应用突出了不同假设对测量和依赖性的影响,以及我们降低偏见和效率提高方法的现实生活增长。

Cluster randomized trials (CRTs) often enroll large numbers of participants, but due to logistical and fiscal challenges, only a subset of participants may be selected for measurement of certain outcomes, and those sampled may, purposely or not, be unrepresentative of all participants. Missing data also present a challenge: if sampled individuals with measured outcomes are dissimilar from those with missing outcomes, unadjusted estimates of arm-specific outcomes and the intervention effect may be biased. Further, CRTs often enroll and randomize few clusters by necessity, limiting statistical power and raising concerns about finite sample performance. Motivated by a sub-study of the SEARCH community randomized trial on the incidence of TB infection, we demonstrate interlocking methods to handle these challenges. First, we extend Two-Stage targeted minimum loss-based estimation (TMLE) to account for three sources of missingness: (1) sampling for the sub-study; (2) measurement of baseline status among those sampled, and (3) measurement of final status among those in the incidence cohort (i.e., persons known to be at risk at baseline). Second, we critically evaluate the assumptions under which sub-units of the cluster can be considered the conditionally independent unit, improving precision and statistical power but also causing the CRT to behave more like an observational study. Our application to the SEARCH highlights the impact of different assumptions on measurement and dependence as well as the real-life gains of our approach for bias reduction and efficiency improvement.

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