CMA and BIA analyses of replacing the current scheme with a hexavalent vaccine resulted in a net increase in costs of 8.7% and 15.5%, respectively. This was primarily driven by the higher acquisition cost per dose of the hexavalent vaccine compared with the other three vaccines, which impacted considerably the healthcare costs to administer the vaccine. When analyzing other activities related to the immunization process, savings were found on logistics costs and costs associated with treatment of adverse reactions.
Compared with the CMA, the BIA estimated a smaller reduction in costs related to treatment of adverse reactions in the alternative scheme versus the current scheme. This is likely because of the low risk of developing vaccine-derived polio across the entire population, minimizing the budget impact of this costly adverse reaction. The CMA also considered the broader perspective of social costs, showing that the alternative scheme would result in an overall saving of time parents spent on medical appointments to immunize their child and treating any adverse reaction, translating into a total cost saving of 24.3%. In this sense, it would be of interest to analyze other indirect impacts of substituting the current scheme with the hexavalent vaccine.
Logistics
Replacement of the current vaccination scheme with the hexavalent vaccine was found to result in a logistical cost saving of 59.8% (equivalent in total to more than $1.7 million), as well as freeing of ~ 18.0% of the required Peruvian vaccines storage capabilities. This additional benefit is associated with the smaller volume and weight of the hexavalent vaccine compared with the pentavalent vaccine, IPV, and OPV combined.
Freeing transportation and storage space would increase the efficiency of the supply chain and avoid bottlenecks caused by an insufficient capacity to receive supplies at a national and local level [
40].
The smaller hexavalent vaccine dimensions could potentially generate savings during vaccination campaigns outside healthcare facilities, particularly in rural areas where cold storage space may be more limited and vaccination campaigns more frequent because of geographic dispersion.
Local and systemic adverse reactions
As reflected by the 33.1% lower adverse reaction costs (equivalent in total to ~ $5.8 million), the alternative scheme is expected to be associated with fewer events than the current scheme. In terms of local and systemic reactions, this effect is largely due to the aP component of the hexavalent vaccine, [
17,
41] which replaces the wP component included in the pentavalent vaccine of the current scheme [
2]. wP is more reactogenic than aP, and has a higher incidence of injection site and systemic adverse reactions, such as fever, erythema, swelling, and drowsiness [
42,
43]. A previous study carried out in Peru found that the hexavalent vaccine results in 20% fewer episodes of fever > 38 °C and a considerably lower incidence of local and systemic reactions than a vaccination scheme based on a pentavalent vaccine and OPV [
43].
Vaccine-derived polio
A further contributor to the reduced adverse reaction costs associated with the hexavalent vaccine is the elimination of the risk of OPV-derived polio. Although rare, [
44] acute paralytic polio is an extremely serious and debilitating disease, with no cure and mortality rates of 5–10% [
8]. The last recorded case of wild poliovirus-derived disease in the Americas occurred in 1991 [
44]. However, in Peru, 81 cases of acute flaccid paralysis were investigated in 2011, with three considered acute paralytic polio [
44]. In 2017, according to the MINSA National Centre of Disease Epidemiology, Prevention and Control, 55 cases of suspected acute flaccid paralysis were notified in Peru [
45].
Given that identifying, monitoring, and confirming suspected polio cases, as well as treating confirmed cases, entail a substantial cost to the Peruvian Government (estimated as ~ $0.5 million [S/ 1.8 million] per annum in the current study), the ability of the hexavalent vaccine to replace OPV and, thereby, eradicate the risk of vaccine-associated polio, is a substantial benefit; particularly, if it is considered the burden of disease that could be prevented. Prior studies have documented that, for upper-middle income countries (as Peru has been classified by the World Bank), 14 disability-adjusted life years (DALY) are lost per VAPP case [
46,
47]. Although, country-specific estimations varied across regions. In Shanghai, it was estimated that switching from a four trivalent oral polio vaccine (tOPV) schedule to a four-IPV schedule could prevent 1.35 VAPP cases and 18.96 DALYs annually [
48]. Whereas, a study in Colombia found that using OPV could cause between 2 and 4 VAPP cases during the two years of follow-up of the study and, consequently, introducing IPV could avoid 64 DALYs [
49]. Given its sociodemographic similarities, the last study may better reflect the burden of disease averted in Peru; though it is still of high interest for future research to estimate the health benefits of adopting and IPV-containing schedule, that considers country-specific epidemiological and vaccination coverage data.
Moreover, not only could OPV cause isolated paralytic polio cases, but it also has the potential to cause cases of cVDPV, developing polio outbreaks in areas previously free of the disease [
50]. For this reason, since the Polio Eradication and Endgame Strategic Plan 2013–2018 was elaborated by the Global Polio Eradication Initiative (GPEI) and approved by the WHO Executive Board, efforts towards a phased removal of all types of OPVs have been taken place globally [
51,
52]. In 2016, a coordinated switch from the tOPV to the bivalent oral polio vaccine (bOPV) was implemented, preceded by the introduction of at least one dose of IPV vaccine in national immunization programs; with the aim to reduce the risk of OPV-derived polio cases associated with the type 2 component of the tOPV vaccine. However, the risk of type 2 polio outbreaks is growing (64 type 2 cVDPV outbreaks have been reported since the switch through 2020, affecting 33 countries) and there is still the risk to develop type 1 and 3 cVDPV cases. Thus, in its last updated Polio Eradication Strategic Plan 2022–2026, the goal to complete the phase out of all OPV vaccines and the transition to IPV exclusive use was reinforced, whether as a standalone vaccine or as part of a combination vaccine [
20]. Likewise, the Latin American Society for Pediatric Infectious Disease (Sociedad Latinoamericana de Infectología Pediátrica) recommends a regional transition away from OPV and towards IPV [
53] and many national healthcare services have already discontinued use of OPV altogether, including the US, Uruguay, and Chile [
12,
54,
55]. Including the hexavalent vaccine in the National Immunization Program of Peru would be an option to achieve this objective.
Efficiency
In addition to the aforementioned cost advantages, reducing adverse reaction rates and eliminating OPV-derived polio by use of the alternative scheme would decrease the amount of time a healthcare professional must dedicate to solve adverse reactions, as well as time spent by parents caring for a sick child.
Furthermore, as a combination vaccine, the hexavalent vaccine could reduce the risk of vaccination sequence disruption and delayed vaccination, contributing to improved vaccination coverage. Under the current scenario, according to the Endes 2017, there is a fraction of children under one year of age who only complete the primary polio vaccination schedule but not the primary pentavalent scheme (~ 3%), and vice versa (~ 2%). By using a more combine scheme, these children lost to follow-up could have been fully protected, increasing the vaccination coverage rate for both vaccines (i.e., children who received three doses of pentavalent and polio vaccine) from 75.2% to ~ 80% [
56]. However, more integrated vaccination schemes may be more sensitive to supply interruptions, negatively affecting vaccination coverage. Hence, a balance between both effects should be considered.
Finally, it is important to mention that there are other alternative vaccination schemes that the country could adopt which could mitigate the risk of developing adverse reactions such as the replacement of the existing third dose of OPV with the IPV vaccine or the introduction of a pentavalent acellular vaccine instead of a whole cellular one. Even if these alternatives could be less costly in terms of vaccine administration (as the vaccine acquisition cost may be lower), they could represent a higher logistic cost and a greater complexity to be implemented due to a greater storage space requirement. Also, the efficiency gain and the social benefits that brings more integrated vaccination schemes would be lose. All of these factors should be evaluated when deciding to transition to a new immunization scheme.
Limitations
From a payer perspective, CMAs and BIAs are essential for the comprehensive economic assessment of a novel healthcare intervention, and are important evidence for reimbursement authorities [
39]. Nevertheless, while conducted in line with ISPOR recommendations using the most appropriate data sources available, the present analysis was based on a number of assumptions and results should be interpreted as best estimates of real-world outcomes. For example, the vaccine uptake rates for the hexavalent vaccines and the current scheme were assumed to be the same; however, this may not be representative of clinical practice and requires further investigation. In addition, the study had a limited time horizon of 1 year and only considered vaccine effects in infants < 1 year of age; thus, any long-term effects (such as long-term costs associated with polio rehabilitation and the long-term economic return of disease prevention at a population level) were not captured.
It should also be noted that BIAs are not intended to capture aspects such as productivity and costs outside of the healthcare system [
39]. Although this study incorporated the differences in cost of time society would assume under both scenarios, it does not recognize other intangible impacts, such as the potential effects on the utilization of human and physical resources.