Fred Hutchinson Cancer Research Center, Seattle, WA 91809, USA.
Comput Math Methods Med. 2014;2014:813789. doi: 10.1155/2014/813789. Epub 2014 May 7.
"Leaky" vaccines are those for which vaccine-induced protection reduces infection rates on a per-exposure basis, as opposed to "all-or-none" vaccines, which reduce infection rates to zero for some fraction of subjects, independent of the number of exposures. Leaky vaccines therefore protect subjects with fewer exposures at a higher effective rate than subjects with more exposures. This simple observation has serious implications for analysis methodologies that rely on the assumption that the vaccine effect is homogeneous across subjects. We argue and show through examples that this heterogeneous vaccine effect leads to a violation of the proportional hazards assumption, to incomparability of infected cases across treatment groups, and to nonindependence of the distributions of the competing failure processes in a competing risks setting. We discuss implications for vaccine efficacy estimation, correlates of protection analysis, and mark-specific efficacy analysis (also known as sieve analysis).
“渗漏”疫苗是指那些在每次暴露的基础上降低感染率的疫苗，而不是“全有或全无”疫苗，后者使某些比例的受试者的感染率降低到零，而与暴露次数无关。因此，渗漏疫苗可以在较高的有效率下保护暴露次数较少的受试者，而不是暴露次数较多的受试者。这一简单的观察结果对依赖于疫苗效果在受试者中具有同质性假设的分析方法具有严重影响。我们通过示例进行了论证和说明，这种异质的疫苗效果会导致比例风险假设的违反，在治疗组之间使感染病例不可比，以及在竞争风险环境中使竞争失败过程的分布失去独立性。我们讨论了这对疫苗效力估计、保护相关因素分析和标记特异性效力分析（也称为筛选分析）的影响。
