Comput Math Methods Med - Leaky vaccines protect highly exposed recipients at a lower rate: implications for vaccine efficacy estimation and sieve analysis.

Tópicos

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Resumo

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).

Resumo Limpo

leaki vaccin vaccineinduc protect reduc infect rate perexposur basi oppos allornon vaccin reduc infect rate zero fraction subject independ number exposur leaki vaccin therefor protect subject fewer exposur higher effect rate subject exposur simpl observ serious implic analysi methodolog reli assumpt vaccin effect homogen across subject argu show exampl heterogen vaccin effect lead violat proport hazard assumpt incompar infect case across treatment group nonindepend distribut compet failur process compet risk set discuss implic vaccin efficaci estim correl protect analysi markspecif efficaci analysi also known siev analysi

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