Rethinking vaccine costs: how the “more expensive” vaccine can actually save health systems millions

An exclusive article authored by Ignacio Olivera, Eduardo Lopez, Carlos Grau Pérez, Luis Lazarov and Hugo Dibarboure.

A newly published cost-minimization analysis from Argentina offers one of the clearest economic assessments to date on how immunization budgets should be evaluated [1]. The study, conducted by the CINVE research group, compares two hypothetical hexavalent vaccination strategies, one containing whole-cell pertussis (wP) antigens, the other acellular pertussis (aP) antigens, and reaches a seemingly counterintuitive conclusion: the vaccine with the higher purchase price can result in lower total costs to the health system. These wP vaccines are known to have higher rates of side effects (adverse events), placing a significant additional burden on the healthcare system and society [2].

The findings of the study add to a growing body of evidence from previously published cost-minimization studies and go further than most, modelling wP and aP hexavalent strategies and highlighting the monetary benefits of lower reactogenicity.

A long-held assumption is now being challenged

Where the effectiveness of two strategies (or options) aiming to protect against the same pathogen is assumed to be similar, immunization budget holders will typically focus on acquisition cost alone. But a vaccination program’s costs extend well beyond the product: logistics, cold chain, additional appointments, staff time, adverse event management, and the productivity lost when parents take time off work or travel for care.

The evidence from Argentina suggests that this approach risks overlooking where the greatest costs actually occur: in adverse events and their subsequent consequences.

A global randomized controlled trial by Decker et al. assessed the risk of adverse events between wP and aP [3]. Many adverse events, such as pain, redness, and fever, are far more common among those who receive wP vaccines. Fever rates were between two and nearly five times higher among wP recipients [4]. Primary-series recipients are infants, many of these adverse events lead to primary care visits, generating direct costs to the system and households, along with distress that other studies link to reduced willingness among families to accept vaccination more broadly [2]. The impacts of these adverse events are often overlooked and not factored into budget considerations.

The long-held assumption that whole-cell vaccines are the economical choice is becoming increasingly difficult to defend. Assessed against total health care and societal costs rather than acquisition price alone, acellular hexavalent vaccination increasingly presents as the more favorable option.

The current vaccination situation in Argentina

Argentina’s public schedule currently uses three doses, and a single booster dose [CO1] [NP2] of a pentavalent wP-containing vaccine (combined with diphtheria, tetanus, Hib (Haemophilus influenzae type B), and hepatitis B antigens), alongside three IPV (Inactivated Poliovirus Vaccine) doses. This option is available through the public healthcare system; however, Argentina’s immunization program already recognizes the more favorable tolerability profile of acellular (aP) hexavalent vaccines by providing them to certain premature infants through Pan American Health Organization (PAHO) supported programs [5].

Those with the means to purchase the acellular vaccine, with its more favorable tolerability profile, can opt for it through the private market [5]. For most Argentinian infants, however, the wP vaccine remains the default option, as it is offered in the National Immunization Program. Families with private insurance have access to the better-tolerated aP formulation as a matter of course. The burden of adverse events and their associated costs falls disproportionately on the public system and the households it serves.

Can the ‘more expensive’ vaccine be the cheaper option?

The answer, according to the analysis of Argentina, is an unambiguous yes. The upfront acquisition cost of an aP hexavalent vaccine is substantially higher than its wP equivalent. In Argentina’s public sector, the PAHO Revolving Fund price is $21.54 per dose for the aP formulation, versus $4.90 per dose for the wP formulation. On a per-vial basis, the case for wP looks straightforward [1].

But the Argentina study exposes the flaw in this reasoning. The vaccine acquisition cost is only one line item in the budget. Modelling Argentina’s annual birth cohort of roughly 495,000 infants across the public sector (representing 94% of the birth cohort), [CO3] [NP4] [GU5] the wP program’s total societal cost was $70 million: $7 million in acquisition costs, $5 million in programmatic costs, and $58 million in adverse event management. The aP program’s acquisition cost was higher at $32 million, with similar programmatic costs ($5 million), but adverse event management fell to $24 million — enough to bring total societal cost down to $61 million [1].

Total public sector costs fell by $9.1 million (~13.0%) under the aP scheme, driven by a $33.6 million reduction in adverse event management costs. In practical terms, this translated to 533,110 fewer primary care visits, 308,687 fewer emergency department visits, 2,868 fewer hospitalizations, and 1,654,129 fewer missed working days for parents [1].

The cost of adverse events is higher than many assume

The study’s most important methodological contribution may be its rigorous quantification of the costs of adverse events. The paper effectively demonstrates that adverse events are not simply clinical inconveniences. They consume healthcare resources at a scale that is seriously underestimated.

Adverse events management costs accounted for 64% of total costs under the wP hexavalent scheme [1]. It reflects the real-world consequences of administering a more reactogenic vaccine to hundreds of thousands of infants. Pain, redness, fever, prolonged crying, and, in rare but serious cases, seizures and hypotonic-hyporesponsive episodes each generate healthcare resource use: medications, outpatient visits, emergency visits, hospitalizations, and the parental time and travel that accompany them.

Notably, the economic model used adverse event data from Decker et al. 1995 [3]. The estimates from this study report smaller differences between wP and aP vaccines compared with more recent analyses, such as Zhang et al. 2014 [2] and Patterson et al. 2018 [6], which suggest a higher risk in the adverse event profiles of wP vaccination. Consequently, the estimates of savings related to adverse events presented for aP vaccination may be rather conservative.

Argentina is unlikely to be an exception

Comparable findings are emerging across different health systems, procurement models, and income settings. A previous whitepaper from Algeria, discussed in Medika Life [7], demonstrated that acellular hexavalent vaccination has improved vaccination coverage and simplified the vaccination schedule by reducing the number of appointments from 10 to 6. Overall, the higher upfront cost of adopting the new vaccine was offset by around 73% through savings generated by managing adverse events, improved logistics and transportation, and increased parental productivity.

Peru and South Africa saw similar patterns after adopting hexavalent vaccines: higher initial costs were substantially offset by reduced adverse events, lower programmatic expenses, and logistical efficiencies. Peru reported a reduction in logistical costs of nearly 60%, with roughly 44% of the initial cost increase recovered [8]. South Africa achieved overall savings of about $10 per child [9]. Projections from Paraguay and Uruguay estimate overall system savings of $2 million and $16.1 million, respectively, when comparing wP vs aP hexavalent vaccination [10,11].

A potential, and very rare, “double-win” for the health system

Evidence indicates that vaccination should be viewed as an investment, rather than an upfront cost, yielding up to 54 times the initial investment according to the WHO [12]. Much of this return on investment is calculated over a very long period, taking into account costs incurred by the medical system after vaccination, not just acquisition costs. The figure demonstrates the power of vaccines, leading to better health outcomes throughout childhood, fewer missed school days, and, in turn, better prospects later in life.

For a policymaker, on the other hand, the initial cost of a new vaccination program must be justified against a host of other healthcare interventions competing for health system resources. Long-term benefits calculated over many years are often insufficient to justify the expenditure. Because most of the savings in this case come from reducing the direct impacts of adverse events, they are realized in the short term. In addition, the societal costs of adverse events are reduced, with fewer children hospitalized and fewer parents taking time off work to care for sick children.

Healthcare decision-makers are often asked to choose between better outcomes and lower costs. The emerging evidence surrounding acellular hexavalent vaccination increasingly suggests that this may be one of the very rare situations in which both objectives can be achieved simultaneously.

[This consensus paper is based on the findings of a white paper discussing the findings of a group of vaccination experts focusing on pediatric immunization, supported by Sanofi. Intended for professional use.]

References

1. Ignacio Olivera, Eduardo Lopez, Carlos Grau Pérez et al. A cost-minimisation analysis: comparison of acellular versus whole-cell hexavalent paediatric vaccination strategies in Argentina, 16 September 2026, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-11039921/v1]
2. Zhang L, Prietsch SOM, Axelsson I, Halperin SA. Acellular vaccines for preventing whooping cough in children. Cochrane Database of Systematic Reviews 2014, Issue 9. Art. No.: CD001478. DOI: 10.1002/14651858.CD001478.pub6.
3. Decker MD, Edwards KM, Steinhoff MC, Rennels MB, Pichichero ME, Englund JA, Anderson EL, Deloria MA, Reed GF. Comparison of 13 acellular pertussis vaccines: adverse reactions. Pediatrics. 1995 Sep;96(3 Pt 2):557-66. PMID: 7659476.
4. Casabona, G., Shah, N., Choudhury, J., & Shah, U. (2026). Whole cell and acellular pertussis vaccines – rethinking the evidence. Expert Review of Vaccines, 25(1). https://doi.org/10.1080/14760584.2026.2689606
5. Olivera, I., Pérez, C.G., Lazarov, L. et al. Cost minimization analysis of a hexavalent vaccine in Argentina. BMC Health Serv Res 23, 1067 (2023). https://doi.org/10.1186/s12913-023-10038-0
6. Patterson, J., Kagina, B. M., Gold, M., Hussey, G. D., & Muloiwa, R. (2018). Comparison of adverse events following immunisation with acellular and whole-cell pertussis vaccines: A systematic review. Vaccine, 36(40), 6007-6016. https://doi.org/10.1016/j.vaccine.2018.08.022
7. Medika Life, An Expert Perspective from Algeria on Hexavalent Vaccine Adoption. https://medika.life/an-expert-perspective-from-algeria-on-hexavalent-vaccine-adoption/
8. Seinfeld J, Rosales ML, Sobrevilla A, López Yescas JG. Economic assessment of incorporating the hexavalent vaccine as part of the National Immunization Program of Peru. BMC Health Serv Res. 2022 May 16;22(1):651. doi: 10.1186/s12913-022-08006-1. PMID: 35570278; PMCID: PMC9109284.
9. Batson A, Glassman A, Federgruen A, et al. The world needs to prepare now to prevent polio resurgence post eradication. BMJ Global Health. 2022;7(12):e011485. doi: https://doi.org/10.1136/bmjgh-2022-011485
10. ID-308 – COST MINIMIZATION ANALYSIS OF THE HEXAVALENT VACCINE WITH ACELLULAR PERTUSSIS COMPONENT (HEXA PAC) VERSUS HEXAVALENT VACCINE WITH THE WHOLE CELL PERTUSSIS COMPONENT (HEXA PC). PARAGUAY 2025.Olivera Ignacio (1); Martínez Celia (2); Grau Carlos (1); Lazarov Luis (1); Dibarboure Hugo(1). Center for Economic Research, CINVE-Health, Montevideo, Uruguay; (2). Hospital de Clínicas, Asunción, Paraguay.
11. ID-307 – COST-MINIMIZATION ANALYSIS OF THE HEXAVALENT ACELLULAR PERTUSSIS COMPONENT VACCINE (HEXA PAC) VERSUS HEXAVALENT WHOLE-CELL PERTUSSIS COMPONENT (HEXA PC). URUGUAY 2025.Olivera Ignacio (1); Grau Carlos (1); Lazarov Luis (1); Dibarboure Hugo (1). Center for Economic Research, CINVE-Health, Montevideo, Uruguay.
12. WHO, Fully-funded Gavi, the Vaccine Alliance, is a lifeline for child survival, says WHO. https://www.who.int/news/item/28-03-2025-fully-funded-gavi–the-vaccine-alliance–is-a-lifeline-for-child-survival–says-who

 [CO1]It´s 3 doses primary scheme (2,4 & 6 months) +1 booster dose (18 months)

 [NP2]added the additional details

 [CO3]94% of all doses does not represent “really” administered doses. The 94% is the size of the cohort vaccinated in the public sector with wP pentavalente +IPV vaccines. Only 6% of the cohort get aP hexa vaccine in the private sector

 [NP4]addressed in the bracket to note these details

 [GU5]It’s not 94% of doses, but 94% of infants taken care in the public sector.