We review vaccine efficacy (VE) estimands for susceptibility in individual randomized trials with natural (unmeasured) exposure, where individual responses are measured as time from vaccination until an event (e.g., disease from the infectious agent). Common VE estimands are written as $1-θ$, where $θ$ is some ratio effect measure (e.g., ratio of incidence rates, cumulative incidences, hazards, or odds) comparing outcomes under vaccination versus control. Although the ratio effects are approximately equal with low control event rates, we explore the quality of that approximation using a nonparametric formulation. Traditionally, the primary endpoint VE estimands are full immunization (or biological) estimands that represent a subset of the intent-to-treat population, excluding those that have the event before the vaccine has been able to ramp-up to its full effect, requiring care for proper causal interpretation. Besides these primary VE estimands that summarize an effect of the vaccine over the full course of the study, we also consider local VE estimands that measure the effect at particular time points. We discuss interpretational difficulties of local VE estimands (e.g., depletion of susceptibles bias), and using frailty models as sensitivity analyses for the individual-level causal effects over time.

翻译：本文综述了在自然（未测量）暴露条件下的个体随机试验中针对易感性的疫苗效力（VE）估计目标，其中个体反应被测量为从接种疫苗到发生事件（例如，由感染源引起的疾病）的时间。常见的VE估计目标被表述为$1-θ$，其中$θ$是某种比较疫苗接种组与对照组结局的比率效应度量（例如，发病率比、累积发病率比、风险比或比值比）。尽管在对照组事件发生率较低时，这些比率效应近似相等，但我们使用非参数公式探讨了该近似的质量。传统上，主要终点的VE估计目标是完全免疫（或生物学）估计目标，它们代表了意向治疗人群的一个子集，排除了那些在疫苗能够充分发挥其全部效果之前就已发生事件的个体，这要求对正确的因果解释予以关注。除了这些总结疫苗在整个研究期间效应的主要VE估计目标外，我们还考虑了测量特定时间点效应的局部VE估计目标。我们讨论了局部VE估计目标的解释困难（例如，易感者耗竭偏倚），并讨论了使用脆弱模型作为个体层面随时间变化的因果效应的敏感性分析。