Estimating Vaccine Efficacy Under the Heterogeneity of Vaccine Action in a Nonrandomly Mixing Population

Rahman, Mostafizur

doi:10.1080/10543406.2011.616974

Cited by 2 publications

(2 citation statements)

References 27 publications

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“…A ‘leaky’ vaccine provides the same partial reduction of susceptibility to every vaccinated individual, while an ‘AoN’ vaccine provides complete protection to a proportion of vaccinated individuals, with the remainder receiving no direct benefit. Despite the marked difference between these two approaches 38 39 , little previous work has explored the population level impact of these assumptions.…”

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confidence: 99%

Vaccination Programs for Endemic Infections: Modelling Real versus Apparent Impacts of Vaccine and Infection Characteristics

Ragonnet

Trauer

Denholm

et al. 2015

Sci Rep

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Vaccine effect, as measured in clinical trials, may not accurately reflect population-level impact. Furthermore, little is known about how sensitive apparent or real vaccine impacts are to factors such as the risk of re-infection or the mechanism of protection. We present a dynamic compartmental model to simulate vaccination for endemic infections. Several measures of effectiveness are calculated to compare the real and apparent impact of vaccination, and assess the effect of a range of infection and vaccine characteristics on these measures. Although broadly correlated, measures of real and apparent vaccine effectiveness can differ widely. Vaccine impact is markedly underestimated when primary infection provides partial natural immunity, when coverage is high and when post-vaccination infectiousness is reduced. Despite equivalent efficacy, ‘all or nothing’ vaccines are more effective than ‘leaky’ vaccines, particularly in settings with high risk of re-infection and transmissibility. Latent periods result in greater real impacts when risk of re-infection is high, but this effect diminishes if partial natural immunity is assumed. Assessments of population-level vaccine effects against endemic infections from clinical trials may be significantly biased, and vaccine and infection characteristics should be considered when modelling outcomes of vaccination programs, as their impact may be dramatic.

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confidence: 99%

Vaccination Programs for Endemic Infections: Modelling Real versus Apparent Impacts of Vaccine and Infection Characteristics

Ragonnet

Trauer

Denholm

et al. 2015

Sci Rep

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“…The difference between leaky and all-or-nothing vaccine models has been explored extensively by mathematically modelling their distinctive direct biological action mechanisms on individuals under various population mixing patterns and vaccine coverage [27][28][29][30]. It is known that when all infections are ascertained, VE Rate overstates the biological effect for all-or-nothing vaccines, while VE Risk understates the biological effect of leaky vaccines.…”

Section: Discussionmentioning

confidence: 99%

The influence of incomplete case ascertainment on measures of vaccine efficacy

Marsh

McBryde

et al. 2018

Vaccine

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Background Motivated by the unexplained variation in the performance of some vaccines across different settings, we extend previous theoretical work to consider the potential impact of incomplete case ascertainment on measures of vaccine effect (Change "effect" to "efficacy", being consistent with the term VE introduced in the second paragraph of Introduction.) (VE), which is more likely in subclinical or clinically unimportant infections, such as rotavirus gastroenteritis. Methods By simulating the measurement of VE under outbreak conditions using a discrete time stochastic SIR model, we compare three commonly used measures, VE Risk , VE Rate , and VE Hazard , calculated respectively based on risk ratio, rate ratio and hazard ratio of disease. We investigate how these measures are influenced by factors such as biological activity, action mechanism of vaccine, proportion of cases ascertained, and underlying force of infection. Results Under plausibly low levels of ascertainment, the group with the most infections, and therefore the most missed cases, has the most falsely inflated denominator, producing similar rates in the control and intervention groups. As a result, VE Rate and VE Hazard will underestimate the true VE compared to high case ascertainment scenarios. Furthermore, the extent of underestimation is greater for leaky vaccine models with lower biological protective effects and under conditions which are conducive to high transmission. Conclusions This study demonstrates that a biologically active vaccine may produce a low measured VE under a range of epidemiological, vaccine-related and logistical conditions. Low case ascertainment may partly explain the observed heterogeneity in the performance of rotavirus vaccine across different settings, and should be considered in the design and interpretation of future field trials.

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Estimating Vaccine Efficacy Under the Heterogeneity of Vaccine Action in a Nonrandomly Mixing Population

Cited by 2 publications

References 27 publications

Vaccination Programs for Endemic Infections: Modelling Real versus Apparent Impacts of Vaccine and Infection Characteristics

Vaccination Programs for Endemic Infections: Modelling Real versus Apparent Impacts of Vaccine and Infection Characteristics

The influence of incomplete case ascertainment on measures of vaccine efficacy

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