Randomization for the susceptibility effect of an infectious disease intervention.
Randomization for the susceptibility effect of an infectious disease intervention.
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DOI：
10.1007/s00285-022-01801-8
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发表时间：
2022-09-20
影响因子：
1.9
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中科院分区：
文献类型：
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传染病干预措施（例如疫苗）的随机试验通常侧重于相互关联或潜在相互作用的个体群体。当感兴趣的病原体在研究对象之间传播时，可能会发生干扰：个体感染结果可能取决于其他人接受的治疗。流行病学家将感兴趣的主要参数（称为“易感性效应”）定义为在保持传染性暴露不变的情况下，接受治疗与未接受治疗的感染风险的对比。相关量——“直接效应”——被定义为治疗与未治疗的感染风险之间的无条件对比。本文的目的是表明，在广泛推荐的随机化设计下，当结果具有传染性时，直接效应可能无法恢复随机试验中干预措施的真实易感性效应的迹象。该分析方法利用传染病传播的结构特征来定义易感性效应。一种新的概率耦合论证揭示了不同治疗分配下潜在感染结果之间的随机优势关系。结果表明，当结果具有传染性时，估计随机化下的直接效果可能会对干预措施（例如疫苗）的效果得出误导性结论。估计直接影响的研究人员可能会错误地得出保护受治疗者免受感染的干预措施是有害的，或者有害的治疗是有益的结论。
Randomized trials of infectious disease interventions, such as vaccines, often focus on groups of connected or potentially interacting individuals. When the pathogen of interest is transmissible between study subjects, interference may occur: individual infection outcomes may depend on treatments received by others. Epidemiologists have defined the primary parameter of interest—called the “susceptibility effect”—as a contrast in infection risk under treatment versus no treatment, while holding exposure to infectiousness constant. A related quantity—the “direct effect”—is defined as an unconditional contrast between the infection risk under treatment versus no treatment. The purpose of this paper is to show that under a widely recommended randomization design, the direct effect may fail to recover the sign of the true susceptibility effect of the intervention in a randomized trial when outcomes are contagious. The analytical approach uses structural features of infectious disease transmission to define the susceptibility effect. A new probabilistic coupling argument reveals stochastic dominance relations between potential infection outcomes under different treatment allocations. The results suggest that estimating the direct effect under randomization may provide misleading conclusions about the effect of an intervention—such as a vaccine—when outcomes are contagious. Investigators who estimate the direct effect may wrongly conclude an intervention that protects treated individuals from infection is harmful, or that a harmful treatment is beneficial.