Just because a vaccine is proven to be effective at preventing a disease, that doesn’t necessarily mean it will be widely (or even narrowly) accepted and used. Beyond safety and efficacy, there are many other factors that determine whether a vaccine is perceived as a public health priority, introduced, and employed.
There needs to be sufficient commercial interest from manufacturers to develop and test the vaccine, as well as investors who are willing to pay for this work. Global and regional advisory bodies need to make formal recommendations about the vaccine’s use to help drive real-world demand. For many low- and middle-income countries, a global funder, such as Gavi, the Vaccine Alliance, needs to be willing to purchase the vaccine, at least initially. And finally, country decision-makers must determine if the vaccine makes sense for their respective immunization programs. Beyond just considering health benefits, those country decision-makers need to look closely at costs, cold chain requirements, available supply, and potential public acceptance of the vaccine.
All these elements factor into measuring a vaccine’s value. In practice, however, the full public health value of a vaccine is not always determined or widely understood prior to its availability.
Several vaccines have been developed and proven highly effective, but then took decades to be used—typhoid conjugate vaccines are one such example, which were shown to be highly effective in 2001 but didn’t start being introduced in endemic countries in Africa and Asia until 2019.
Vaccine value propositions
“If you build it, will they come?” asks William (Bill) Hausdorff, PhD, value proposition lead for PATH’s Center for Vaccine Innovation and Access. “I often reference this quote from the US film Field of Dreams since it so perfectly illustrates the question of measuring the value of vaccines. We cannot assume that even if someone creates a ‘perfect’ vaccine that anyone will actually use it.”
“PATH recognizes the importance of understanding and communicating to international agencies, funders, manufacturers, and country decision-makers the real public health value of vaccines,” continues Bill. “We want to help pave the way for the introduction of appropriate new vaccines into the low-resource areas where they are needed the most.”
“We want to help pave the way for the introduction of appropriate new vaccines into the low-resource areas where they are needed the most.”— Bill Hausdorff, value proposition lead, PATH
For many of the vaccines we’re working on, PATH is conducting a variety of activities to develop value propositions across the product life cycle—from preclinical to late-stage clinical trials. Countries are faced with a wide range of demands for budgetary and logistic support to cover an array of health interventions. Similarly, manufacturers can pursue any number of vaccine development opportunities. Value propositions can help countries prioritize health spending, as well as assist manufacturers to weigh opportunity costs of investing in one vaccine over another.
The World Health Organization (WHO) has been developing Full Value of Vaccine Assessments to better elucidate the overall value of specific vaccines. These assessments consider not only the public health and economic value of vaccines but provide a broader understanding of where a given class of vaccines “fits” in the immunization landscape and address societal and other benefits.
“PATH works closely with WHO to ensure that we are covering key issues in our value propositions, but we provide a more critical assessment by using more product-specific aspects in our assessments,” says Bill. “We also try to focus on a few key questions that we need to answer around a particular vaccine, as opposed to conducting an exhaustive summary of all the issues.”
Value propositions often involve several types of studies because each vaccine requires a customized package. These may include health economic analyses, demand forecasts, feasibility and acceptability studies, market assessments, expert consultations, literature reviews, and more. This comprehensive approach to examining a broad array of evidence, projections, and perspectives can result in a rich and complex picture about the value of a vaccine.
Input from local stakeholders is critical
In conducting this work, PATH has learned it is of key importance to hold structured consultations with different country stakeholders—not just global experts—regarding vaccine preferences.
“Gathering input directly from local vaccine decision-makers and health care workers seems like an obvious step, yet it’s too often overlooked by vaccine developers and donors,” says Chris Odero, PhD(c), MSc, PMP, technical advisor with PATH’s Center for Vaccine Innovation and Access and principal investigator for two recent PATH-led stakeholder consultations in Kenya. “Guidance from these groups must be prioritized for all future attempts to understand the public health value of vaccines, especially those destined primarily for low- and middle-income country markets.”
“Gathering input directly from local decision-makers seems like an obvious step, yet it’s too often overlooked by vaccine developers and donors.”— Chris Odero, technical advisor, PATH
PATH conducts feasibility and acceptability studies to capture input directly from national stakeholders and health care providers in countries where a vaccine might be used to better understand local preferences. These interview-based studies offer a way to identify which product attributes are most prioritized by different stakeholders. Understanding the relative priority of these attributes can inform vaccine design and clinical evaluation, and ultimately could facilitate vaccine recommendations and uptake.
It’s also interesting that sometimes the preferences expressed by local stakeholders don’t match the preconceptions or views of global experts, pointing to how critical it is to capture inputs from country-level voices.
PATH is currently wrapping up results from a value proposition focused on injectable next-generation rotavirus vaccine candidates, which included a study gathering stakeholder preferences from six countries. We’re also about to embark on another multicountry stakeholder preferences study about Shigella vaccine candidates alongside a range of other value proposition work. And we recently concluded an informal series of interviews with low- and middle-income country experts to better understand the potential value—and limitations—of monoclonal antibodies designed to provide protection against malaria.
PATH’s value propositions have the potential to help drive donor investments and vaccine developers' research priorities, as well as to influence clinical trial designs. Our work in this area to date has also raised interest in exploring the concept of combination vaccines—those that provide protection against multiple diseases in just one vaccine—in more depth.
Several combination vaccines are already in broad use. In fact, the “pentavalent vaccine,” as it is commonly called—which protects against diphtheria, tetanus, pertussis, Haemophilus influenzae type b (Hib), and hepatitis B—is widely regarded as the reason behind current high immunization coverage levels for Hib and hepatitis B. With an increasingly crowded childhood immunization schedule, a finite number of limbs for injections, and a plethora of new injectable childhood vaccines in development, combination vaccines are likely to play a critical role in the future.
Although countries and vaccine manufacturers are highly interested in new multipathogen combination vaccines, the development and regulatory pathways remain quite complex and could likely be streamlined. In addition, there’s a dearth of global policy guidance informed by the perspectives of country-level stakeholders regarding which new combinations represent public health priorities. Value proposition analyses that critically address these and other combination vaccine issues may be a way to increase the feasibility of pursuing these types of vaccines in the near term.
“While measuring the value of a vaccine may be more complex than it first seems on the surface, improving health and saving lives remain a steadfast goal,” says Chris. “But broadening our understanding of how decisions about vaccines are made at a local level can help make vaccines better for everyone.”
For media inquiries about Bill Hausdorff, Chris Odero, or PATH's vaccine development efforts, contact email@example.com.