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The race to develop combination vaccines – and the importance of indirect effects

A development race is currently underway in the field of combination vaccines, with a number of influential pharmaceutical and biotech companies pursuing combination vaccines targeting influenza and COVID-19.1

The benefits of new combination vaccines are numerous – fewer injections mean simplified vaccination schedules, reduced pressure on health care systems, and less disruption to people receiving vaccines, with the additional potential benefit of boosting vaccine uptake. 

However, for any new combination vaccine to be adopted, public health decision makers rely on health technology assessments (HTAs) to systematically assess the impact of introducing a new health technology from a multidisciplinary perspective. As part of an HTA, the costs and benefits (cost-effectiveness) of introducing a novel health technology must be assessed in relation to existing health technologies in use. 

The costs of a novel health technology can be divided into a number of categories which include medical costs (e.g., the cost of a vaccine, and its storage and delivery), non-medical costs (e.g., transportation costs for the patient to and from a healthcare facility) and other costs such as productivity losses due to illness.

Because infectious disease spreads from person to person, vaccines provide both direct and indirect protection to the population at large. Individuals who receive a vaccine benefit from direct protection against disease, whilst the consequential reduction in the spread of disease confers indirect protection to the entire population. These indirect effects increase as more of the population is vaccinated and can be particularly important for infectious diseases that circulate at significant levels such as influenza and COVID-19.

To account for these indirect effects within traditional cost-effectiveness analyses, disease transmission models are used to understand how different levels of vaccine coverage impact the amount of disease spreading within a population. In the case of a combination vaccine targeting both influenza and COVID-19, such a transmission model must consider the impact of the vaccine on the circulation of both pathogens being targeted in the vaccine. 

Although the benefits of introducing combination vaccines may seem clear, it is important for both public health overall, and for maintaining the social contract between populations and public health decision makers, that evidence-based decisions are made which consider direct and indirect effects, take a multidisciplinary approach, and adequately capturing any uncertainty. 

The consequences of not capturing indirect effects can lead to health technologies or interventions being misvalued, resulting in poor decision making. In the past this has had catastrophic consequences – a failure to properly account for the relationship between the probability of infection and the mean age of first infection with rubella had significant health outcomes, leading to increases in congenital disease in Greece in 1993.2

At ICON Health Economics & Epidemiology, we have a broad range of expertise in infectious disease modelling. We model the clinical impact of a health technology or public health intervention like a vaccine, ensuring direct and indirect effects are considered, and use this as the basis for an economic evaluation. Stepping back to the broader economic perspective means we work in concert with other Health Economics & Epidemiology colleagues with expertise in evidence synthesis, cost-effectiveness analysis, and budget impact, to provide a comprehensive evaluation of the value of any new health technology.

To learn more about infectious disease modelling and vaccine commercialisation, please contact us.

References

1 Two-in-one flu and Covid jab passes advanced trial, BBC News, 10 June 2024 https://www.bbc.com/news/articles/ck55l4rk8z1o

2 Increase in congenital rubella occurrence after immunisation in Greece: retrospective survey and systematic review, BMJ, 04 December 1999 https://www.bmj.com/content/319/7223/1462.long

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