Two combination vaccines (measles-rubella- and diphtheria-tetanus-pertussis-containing vaccines) are the cornerstones of pediatric immunization programs worldwide. Additional combination vaccines could help ease crowded immunization programs and facilitate the adoption of exciting new vaccines on the horizon. However, vaccine manufacturers have lacked clear guidance for their development, and policy bodies have faced challenges in making informed decisions about their introduction and use.
One reason for this may be that traditional economic evaluations often fail to capture the full array of benefits and challenges of combination vaccines. This hinders decision-makers from considering their full value, potentially limiting their development and prioritization in immunization strategies.
As part of a broader effort to identify and prioritize high-potential new routine combination vaccines for children, PATH and the World Health Organization (WHO) researched and identified new approaches to measure the full economic value of combination vaccines. The resulting new checklist tool provides analysts with a way to more clearly, consistently, and comprehensively evaluate these vaccines.
Building a new tool
PATH and WHO determined that a new tool was needed to capture the unique benefits, costs, and risks of combination vaccines more effectively, which can differ from those for single-antigen vaccines. For example, existing economic evaluations may not quantify how decreases in the number of separate injections provided at a single immunization visit affect acceptability, which can impact timely immunization coverage.
To start, the team reviewed the literature on economic evaluations of combination vaccines to more precisely identify and define current gaps in value assessment, followed by consultations with numerous immunization stakeholders. This led to the creation of a list of value drivers and their associated metrics for potential inclusion in future evaluations.
In this context, a “value driver” is an attribute that highlights the advantage or disadvantage of a specific benefit or cost. For example, the benefit of reducing the number of injections can be realized through the value drivers of reduced discomfort and/or improved coverage through reduced hesitancy. In turn, each value driver can be measured by distinct “metrics;” for example, the value driver of reduced discomfort can be measured by the willingness to pay to avoid that discomfort.
Next, the team engaged with immunization and health economics experts to prioritize and categorize the list of value drivers and metrics based on specific criteria. This prioritization was further refined at a convening of health economics experts in June 2025. After this careful process, the new checklist approach emerged, which the team organized using a traffic-light-style classification system.
Value drivers were ranked according to their resonance (perceived alignment with policy priorities) and their magnitude (estimated impact on overall value). Metrics were classified by their quantifiability (can they be measured?) and ease of integration within the existing economic evaluation frameworks (are there existing methodologies or will innovation be required?).
The combination vaccine checklist
The complete checklist, recently published in a manuscript in Vaccine and shared in a new brief, is meant to complement other analyses and provide a helpful tool for determining the relevant value drivers and metrics when evaluating a specific combination vaccine.
Following the traffic-light system, the value drivers and metrics classified as green across all four dimensions indicate a high priority for inclusion in combination vaccine evaluations. If a value driver is green for resonance and magnitude, but orange or red for quantifiability and framework fit, it signifies strong interest from decision-makers but uncertain feasibility for inclusion and a potential research gap. Conversely, value drivers rated as orange or red for resonance and magnitude, combined with a green for quantifiability and framework fit, indicate low to moderate interest but higher feasibility of inclusion in analyses.
The matrix below shows an illustrative example of what an assessment of one combination vaccine could look like using the new checklist.
This figure shows an illustrative example of a matrix showing value drivers and metrics alongside their score based on the various prioritization dimensions.
While some of the value drivers and metrics correspond to those used in evaluations of single-antigen vaccines, others are unique to combination vaccines. The inclusion of additional and potentially lower magnitude value drivers and metrics may change the findings of some economic evaluations of single-antigen vaccines, resulting in markedly different outcomes.
Putting it to use
As a next step, the team is now collaborating with additional partners to formally model the potential impact and cost-effectiveness of a few specific future combination vaccines that resulted from the broader work PATH and WHO are doing to identify and prioritize high-potential combinations.
Ideally, analysts should implement this checklist tool for all new combination vaccines under consideration to ensure these vaccines are more comprehensively assessed by decision-makers to inform investment decisions or adoption. The tool can also enhance the valuation of new combination vaccines to support manufacturers with prioritizing their development.
Immunization programs face increasing pressure to achieve more with limited resources. This checklist could help support the development and adoption of new combination vaccines by easing this stress and making it easier to determine which combinations are the most valuable to pursue.
