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

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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