论文标题
在存在多种病原体变异和多种疫苗的情况下，疫苗有效性测量的时间特性
Temporal Properties of Vaccine Effectiveness Measures in Presence of Multiple Pathogen Variants and Multiple Vaccines
论文作者
论文摘要
疫苗有效性（VE）通常定义为发病率比，累积风险比或优势比。众所周知，基于发病率比的VE在研究期间的泄漏作用疫苗中存在时间不变，并且基于累积风险比率的VE对于全或无人行动疫苗都是时间不变的。因此，建议将这些VE措施分别用于泄漏和全或无人疫苗的适当措施。但是，在具有多种病原体变异和多种疫苗的疾病中，研究人员也可能对疫苗的变异特异性VE感兴趣，疫苗的相对VE疫苗针对两种变异型，或针对给定变体的不同疫苗的相对VE。在这种多变体和多疫苗情况下，尚未完全研究上述VE措施的时间特性。此外，任何打算估计变异特异性VE或相对VE的研究都没有通用样本量计算器。作为解决方案，我们在考虑多种竞争病原体变体的同时定义了变异特异性和相对VE度量。然后，我们在多变化的环境中为全或无疫苗提出了一种通用的作用方式。随后，我们评估了各种VE措施可能与之变化的条件和程度。我们表明，在多变量和多疫苗场景中，每种VE度量都是全或单位作用疫苗的时间变化。对于泄漏的疫苗，我们表明，基于发病率比的所有测量都随时间变化。我们在常用的队列，累积病例对照和测试阴性研究设计的背景下讨论了这些结果对VE研究的实际意义。最后，对于多变量和多疫苗情况，我们在R软件包和在线计算器中实现了变体特异性和相对VE的样本量计算。
Vaccine effectiveness (VE) is typically defined as incidence rate ratio, cumulative-risk ratio, or odds ratio. The VE based on incidence rate ratio is known to be time-invariant over the study period for leaky action vaccines and, the VE based on cumulative-risk ratio is time-invariant for all-or-none action vaccines. Consequently, these VE measures are recommended as appropriate measures of VE for leaky and all-or-none vaccines, respectively. However, in diseases with multiple pathogen variants and multiple vaccines, investigators may also be interested in variant-specific VE of a vaccine, the relative VE of a vaccine against two variants, or the relative VE of different vaccines against a given variant. In this multi-variant and multi-vaccine scenario, the temporal properties of the aforementioned VE measures have not been studied entirely yet. Furthermore, no general-purpose sample size calculator is available for either studies that intend to estimate variant-specific VE or relative VE. As a solution, we define variant-specific and relative VE measures while accounting for multiple competing pathogen variants. We then propose a generic mode of action for all-or-none vaccines in a multi-variant setting. Subsequently, we evaluate the conditions and the extent to which various VE measures can be time-varying. We show that every VE measure is time-varying for all-or-none action vaccines in a multi-variant and multi-vaccine scenario. For leaky vaccines, we show that all measures other than those based on incidence rate ratios are time-varying. We discuss the practical implications of these results on VE studies in the context of the commonly used cohort, cumulative case-control, and test-negative study designs. Lastly, for the multi-variant and multi-vaccine scenario, we implement sample size calculations for both variant-specific and relative VE in an R package and an online calculator.
