Improving methods to determine vaccine impact in low- and middle-income countries

衡量疫苗的影响，包括疫苗对人群健康的直接和间接影响，对于新疫苗是至关重要的。在公共卫生和社会福利干预措施迅速变化的背景下，将健康状况的改善归因于疫苗效果往往是有问题的，而且受到现有数据的限制。目前大多数疫苗影响测量方法依赖于使用疫苗前数据根据过去的趋势预测预期的疾病负担并与观察到的疾病负担进行比较，但改善对混淆和间接影响的理解对于提高这些估计的准确性至关重要。关键问题是如何从观测数据中更好地量化疫苗群体的影响，区分疫苗归因于其他公共卫生干预措施的影响？目的通过范围审查，描述在资源有限的情况下疫苗影响评估(VIE)的设计和分析方法。比较以S为金标准的疟疾RTS疫苗影响评估的现有方法的性能，并将其扩展到马拉维的肺炎球菌结合疫苗和轮状病毒疫苗的引入，并考虑合理的方法修改。通过将基于模拟的方法应用于目标2中调查的方法，确定改进的方法和最重要的混杂因素以及要纳入未来评估的间接益处。使用分组随机影响评估的实验方法对疟疾RTS、S疫苗和即将在马拉维进行的伤寒疫苗评估，我们将使用这项研究中关于5岁以下儿童死亡率的VIE作为金标准1)比较不同的观察方法的性能以及它们如何偏离金标准2)通过模拟研究调查混杂因素的作用和相对重要性3)重新分析来自已发表的肺炎球菌和轮状病毒疫苗评估的数据，以调查影响估计如何改变。新的将尖端传染病建模和模拟方法纳入低收入和中等收入国家(LMIC)的VIE，以确定更稳健和完整的有效性测量。利用正在进行的随机分组控制的RTS VIE的不同寻常的机会，S在马拉维对新方法进行基准和测试。使用这种方法从计划、剂量和对目标/高危人群的影响等方面回答关于优化RTS、S和伤寒疫苗实际交付的关键问题。关键词：全球卫生；公共卫生；感染和免疫

Measuring vaccine impact, both the direct and indirect effects of vaccines on population health, is essential for new vaccines. Attributing improvements in health to vaccine effects in a context with rapidly changing public health and social-welfare interventions often is problematic, and is limited by available data. Most current approaches to vaccine impact measurement rely on using pre-vaccine data to predict an expected burden of disease based on past-trends and compare to what is observed, but improved understanding of confounding and indirect effects is essential to improve the accuracy of these estimates. The key question is how to better quantify full vaccine population impacts from observational data, differentiating vaccine-attributable effects from those of other concurrent public health interventions?ObjectivesThrough a scoping review, describe the designs and analytical methods of vaccine impact evaluations (VIE) in resource limited settings.Compare the performance of existing impact assessment methods using VIEs of malaria RTS,S as a gold-standard, and extend to pneumococcal conjugate and rotavirus vaccine introduction in Malawi and consider logical method modification.Through simulation-based approach applied to the methods investigated in objective 2, identify improved methods and the most important confounding factors and indirect benefits to include in future evaluations.Experimental Approach Using the cluster randomised impact evaluation of malaria RTS,S vaccine and an upcoming evaluation of Typhoid vaccine in Malawi, we will use VIEs on under 5-child mortality from this study as a gold-standard to 1) compare different observational method performance and how they deviate from the gold-standard 2) investigate the role and relative importance of confounders through simulation studies 3) reanalyse data from published pneumococcal and rotavirus vaccine evaluations to investigate how impact estimates alter.NoveltyIncorporating cutting-edge infectious disease modelling and simulation approaches into VIEs in low and middle income countries (LMIC) to determine more robust and complete effectiveness measures.Utilising the unusual opportunity of an ongoing cluster-randomised controlled VIEs of RTS,S in Malawi to benchmark and test new methodology.Use this approach to answer key questions on optimising real-life delivery of the RTS,S and Typhoid vaccines in terms of scheduling, dosing, and impact on target/high-risk groups.Keywords: global health; public health; infections and immunity