Model‐based estimation of vaccine effects from community vaccine trials

Abstract

Community vaccine trials are becoming increasingly important to assess both the direct and indirect community level effects of vaccination. In this paper, we present statistical methods to analyse such trials, using a design with several matched pairs of communities. The communities are matched on similarities in infection transmission as reflected through the basic reproduction number. Two methods of analysis are presented and compared. The first is simple empirical estimation of vaccine effects. Summary measures of these effects are constructed by reciprocal variance weighted averages across the community pairs. The second is likelihood-based where we derive a mixed effects epidemic model. This model takes the intercommunity variability into account through a random effect on the basic reproduction number. With this model, we derive a distribution-free estimator for the variance of the random effect. We use simulated epidemics to explore the performance of the two estimation methods for different numbers of community pairs and different levels of inter-pair variability. Both methods provide acceptable estimates in terms of bias and precision under reasonable conditions. Although the empirical approach involves fewer assumptions than the model-based approach, the resulting vaccine effectiveness estimates are only applicable to the vaccination fraction tested in the trial. In contrast, the model-based approach can be used to predict the vaccine effectiveness at vaccination fractions other than those used in the trial. Thus, it can be used as a public health policy tool for predicting the community level effects of vaccination. We demonstrate such use by predicting total vaccine effectiveness for the whole range of vaccination fractions.

Long-standing influenza vaccination policy is in accord with individual self-interest but not with the utilitarian optimum

“…Latently infected individuals proceed to become infectious. The perceived duration of the infectious period is 5 days (Table 1), which is close to the actual value of 4-5 days (40).…”

The SIRS Model of Epidemic Spreading in Virtual Society

“…After vaccination, these individuals become unsusceptible (R) (to simplify the model we assume that the time necessary to develop immunity is very shortno longer than one day). It should be noted that introducing the probability p TV can be also treated as a simple model of chemoprophylaxis [16]. The value of the probability p TV is related to the time of identification of ill individuals in population by health services.…”

Ecological aspects in vaccine trials

“…A Phase III vaccine efficacy trial is typically designed to measure vaccine protective efficacy, which reflects direct effects of vaccines [6]. Individually randomized, placebo-controlled trials are considered 'gold standard' for evaluating such vaccine efficacy.…”