TB Vaccine Modeling: A discussion with Dr. Richard White
By: Ye Eun Grace Jung, MD, MPH
Vaccine production, from the product concept to development to licensure to deployment is inherently costly and risky for manufacturers, particularly for vaccines against diseases where the burden lies predominantly in lower- and middle-income countries (LMICs). Thus, vaccine manufacturers frequently prioritize high-income markets that offer higher immediate return on investment. The World Health Organization has been funding a series of Full Value of Vaccines Assessments (FVVA) to reduce the uncertainty in investment and incentivize potential introduction decisions. These FVVAs provide a framework and methodology to evaluate the broad direct and indirect impacts and value of a vaccine. Recently, the WHO published a case for new TB vaccines under the FVVA series.
Often when evaluating the benefit of a potential vaccine, we assess only the direct medical benefits such as the number of deaths or illness averted. Through conversation with Dr. Richard White, professor of infectious disease modelling at the London School of Hygiene and Tropical Medicine (LSHTM), he revealed there are many more benefits to new TB vaccines than these. “There are wider benefits of new TB vaccines to societies and other decision makers, such as keeping people healthy so that they can bring up their kids, they can go to school, and they can keep employed and feed their families. TB is also a large proportion of global antimicrobial resistance, so new TB vaccines could help avert that. Also, different decision makers value different things, a Minister of Finance may value ‘return on investment’ in addition to the health benefits” said Dr. White.
How do we capture different benefits of a vaccine? The answer lies in mathematical infectious disease and economic modeling. “Models are just simplifications of reality, like a picture on a wall”, said Dr. White. They allow us to create a representation of a real-world scenario to make a prediction, such as predicting the potential health and economic impact of a new vaccine. Typically, with vaccines we see a high upfront cost, but the benefits accrue over a long time, sometimes decades. Given this, when evaluating the impact of a new vaccine over a short period of time, it may initially appear as poor value for money, but when evaluated over a longer period, the same vaccine can look like a good investment. The TB vaccine FVVA team’s goal was to model the impact of a vaccine over a longer period to capture the wider benefits. The health impact modeling was led by Dr. White and Rebecca Clark at LSHTM while the economic impact modeling was led by Dr. Nick Menzies and Dr Allison Portnoy at the Harvard T.H. Chan School of Public Health.
The findings of the FVVA for new TB vaccines made a compelling case for the need to invest in TB vaccines through four key messages. Firstly, TB vaccines could significantly reduce TB incidence and mortality as well as the development of antimicrobial resistance, an ever-growing global health problem. In particular, a vaccine targeting adults and adolescents can have a more immediate and larger impact given the higher burden and transmission rates from this group. This will also benefit children, who are largely infected from adults. Secondly, there is a strong economic argument for investing in new TB vaccines, with the rollout being cost saving in many countries when societal benefits are taken into account. The return on investment, unsurprisingly, was shown to be highest in countries with higher TB burden. Thirdly, TB vaccines can improve health equity and contribute to the achievement of several sustainable development goals (SDGs) by protecting poor, vulnerable groups from TB-related costs. Finally, moving forward there needs to be more investment in research and development in order to ensure the rapid development and availability of effective TB vaccines.
What is needed next in the world of modeling to continue to shape the political discussion around investing in TB vaccines? Country-level models, Dr. White noted, so that governments and political stakeholders can understand the direct and wider benefits of adopting a new TB vaccine in their unique environment. He encouraged readers who may be early career researchers to enter the TB vaccine world, which has been the most active and robust that it has been in decades with numerous vaccine candidates in preclinical and clinical development, bringing hope to achieve the true value of a new TB vaccine.
For more information on modeling, WGNV has a 2-page summary, which is linked here.
Grace is currently an internal medicine resident at Oregon Health & Science University in Portland, OR. Prior to this, she graduated from the Ben Gurion University of the Negev in Israel with an M.D. and the Harvard T.H. Chan School of Public Health with an M.P.H. in Global Health. Grace is interested in using clinical and health services research to ask health equity questions in respiratory health and critical care.