A Cost-Effectiveness Analysis of the Switch to 20-Valent Pneumococcal Conjugate Vaccine from Lower-Valent Pneumococcal Conjugate Vaccines in the French Pediatric Population

Abstract

Introduction

The pneumococcal conjugate vaccine (PCV) with valency of 20 (PCV20) was approved for pediatric use by the European Commission in 2024. However, PCV20 is not yet implemented into the French infant National Immunization Program (NIP). In this cost-effectiveness analysis, we compared PCV20 under a 3 + 1 schedule to the current standard of care (13-valent PCV [PCV13]) or 15-valent PCV (PCV15), both under a 2 + 1 schedule, for infant vaccination in France.

Methods

The study adopted a multiple-cohort population-level model under the French Collective perspective over a 10-year time horizon. Inputs were sourced from published and unpublished studies conducted in the French population, where available. Clinical outcomes included disease cases (i.e., invasive pneumococcal disease [IPD], inpatient pneumonia, and otitis media [OM]) and deaths. Incremental cost-effectiveness ratios were calculated on the basis of estimated costs and quality-adjusted life years (QALY) for PCV20 3 + 1 versus PCV15 2 + 1 and PCV13 2 + 1 in separate pairwise comparisons.

Results

Compared with PCV13 2 + 1 and PCV15 2 + 1, PCV20 3 + 1 was estimated to be dominant, resulting in improved public health and economic outcomes. PCV20 was predicted to prevent more disease cases versus PCV13 (IPD: 13,510; hospitalized pneumonia: 317,136; hospitalized OM: 66,579) and PCV15 (IPD: 11,187; hospitalized pneumonia: 255,790; hospitalized OM: 53,733) and provide cost-savings of €1,567,052,379 and €1,134,653,266 versus PCV13 and PCV15, respectively.

Conclusions

This study predicted that infant immunization with PCV20 was the most cost-effective option compared with PCV13 and PCV15. These results could help decision-makers implement the optimal PCV strategy in the French pediatric NIP.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40121-025-01209-z.

Key Summary Points

Why carry out this study?

Although pneumococcal conjugate vaccine (PCV) with valency of 13 (PCV13) reduced pneumococcal disease in France, recent studies show a resurgence mainly due to non-PCV13 serotypes covered by 20-valent PCV (PCV20).

Infants in France are currently vaccinated against pneumococcal disease using PCV13 or 15-valent PCV (PCV15), while PCV20 is approved by the European Commission.

What was learned from the study?

A French cost-effectiveness model compared PCV20 with PCV13 and PCV15 over 10 years.

Infant vaccination with PCV20 was more effective and less costly than PCV13/PCV15.

Introduction

In France the 7-valent pneumococcal conjugate vaccine (PCV7) was recommended for widespread use among healthy children in 2003, making it the first European country to do so [1]. Subsequently, the 13-valent pneumococcal conjugate vaccine (PCV13) was implemented in the French National Immunization Program (NIP) in 2010, with the aim of tackling the emergence of non-vaccine-type serotypes, such as serotype 19A, and increasing protection against pneumococcal disease [2]. This transition to PCV13 led to a shift in pneumococcal epidemiology in France, including reduction in the incidence of invasive pneumococcal disease (IPD) and non-invasive pneumococcal disease among children alongside lower burden of pneumococcal disease among adults through indirect protection [2]. The French pediatric NIP has included PCV13 under a 2 + 1 schedule for children aged < 2 years, achieving an uptake of > 90% since 2010 [1].

Although the transition from PCV7 to PCV13 led to a decrease in pneumococcal disease incidence in France during the first 5 years following implementation, recent studies have indicated a resurgence of disease cases in both children and adults, primarily driven by non-PCV13 serotypes such as serotypes 8, 10A, 15B (covered by 20-valent pneumococcal conjugate vaccine [PCV20]), 24F, 15A, and 15C among children aged 0 to 23 months, highlighting the importance of developing and implementing higher-valent next-generation pneumococcal conjugate vaccines (PCV) [3, 4].

The recent approvals of next-generation PCVs including 15-valent PCV (PCV15) and the broader/higher-valent PCV20 by the European Commission (EC) provide an opportunity to reduce the remaining pneumococcal disease burden in Europe [5, 6]. In July 2023, the French National Authority for Health (Haute Autorité de santé, HAS) recommended PCV15 as an alternative to PCV13 in the NIP for infants aged < 2 years, and endorsed PCV20 for at-risk adults, followed by PCV20 endorsement for all people aged ≥ 65 years in 2025 (i.e., not for infants) [7–9].

PCV20 covered over 50% of serotypes that were responsible for IPD in 2022 among children aged < 15 years, representing three times the coverage of PCV13 [4]. Preliminary data for 2023 estimated the serotype distribution of PCV20 at 46%, 36%, and 60% among children aged < 2 years, 2 to 4 years, and 5 to 15 years, respectively, corresponding to 9.2, 2.8, and 2.9 times the coverage of PCV13 and 3.3, 2.4, and 2.1 times the coverage of PCV15, respectively [4]. However, despite this and the marketing authorization for pediatric use received by the EC in March 2024, PCV20 is not currently reimbursed or recommended by HAS.

A study by Perdrizet et al. published in 2025 highlighted that considerable health and economic benefits could be forgone as a result of delayed transitioning from lower-valent vaccines such as PCV13 and PCV15 to PCV20 in the pediatric NIP in multiple countries, indicating an urgent need for decision-making around which PCV should be implemented and the importance of prioritizing the replacement of lower-valent PCVs with higher-valent alternatives [10].

This study sought to assess the potential health and economic impact of introducing PCV20 under a 3 + 1 schedule, as per the European label, into the French pediatric NIP, and compare its cost-effectiveness with PCV13 and PCV15, both under 2 + 1 schedules [11].

Methods

Model Structure

The cost-effectiveness model utilized a multiple-cohort population-level structure to assess the clinical and economic impact of different PCV pediatric vaccination strategies (PCV20 3 + 1, PCV15 2 + 1, and PCV13 2 + 1) on the French population over a 10-year time horizon. This model structure has been previously used in PCV20 cost-effectiveness studies in other countries [12–16].

To simulate temporal dynamics, a new birth cohort entered the model at the start of each annual cycle for 9 years following the baseline year, which was eligible for vaccination. All individuals (new birth cohorts and the existing population) benefited from indirect effects and remained in the model throughout the model time horizon or until they died from pneumococcal disease or other causes (general mortality).

Within any annual cycle, both vaccinated and unvaccinated individuals could transition between an active-disease state and a non-disease state, with death representing an absorbing state. The active-disease state comprised various clinical events including IPD (meningitis or bacteremia), all-cause hospitalized pneumonia, and all-cause hospitalized otitis media (OM). The model considered sequelae following meningitis to account for possible long-term consequences. Meningitis, bacteremia, and hospitalized pneumonia were associated with some fatality, modeled as increased risk of mortality among individuals experiencing these events; however, OM was assumed to not be linked to any disease-related mortality. Disease fatality and general mortality were considered for the whole population. The model represented pneumococcal disease states as non-mutually exclusive, enabling individuals to encounter multiple clinical events concurrently rather than being restricted to a single outcome.

Model Population

The target population (i.e., vaccinated cohort) consisted of healthy children aged < 2 years, who could benefit from vaccine direct effects. In addition, the population-based approach allowed for the broad impact of the pediatric vaccination program to be reflected in the model, with older (unvaccinated) age groups benefiting from indirect effects.

Different age groups were modeled to account for age-specific aspects, such as epidemiological risks of pneumococcal disease, disease fatality, costs, quality of life, and vaccine effectiveness, as follows: < 1, 1, 2, 3, 4, 5 to 17, 18 to 34, 35 to 49, 50 to 64, and ≥ 65 years.

The total population and projected birth cohort inputs/sources used in the model are reported in Supplementary Tables 1 and 2.

Epidemiology, Cost, and Quality of Life Data

Supplementary Table 3 presents the key inputs used in the base case, for which French-specific inputs were prioritized; if these were not available, inputs were sourced from data originating from other European countries.

The analysis only considered IPD, hospitalized pneumonia, and hospitalized OM as a result of the lack of available incidence data for non-hospitalized non-invasive pneumococcal diseases in France. Sequelae were considered in the case of meningitis only.

Cost inputs were obtained from French claims databases considering a collective perspective for medical cost per episode of pneumococcal events including meningitis, bacteremia, hospitalized pneumonia, and hospitalized OM, while costs associated with sequelae were taken from studies that reported French data. All costs were actualized to 2024 pricing. Costs associated with sequelae were calculated using total costs over a 5-year duration because of some uncertainty related to cost calculations and to approach the inclusion of sequelae conservatively. Annual costs for each reported sequela were aggregated over 5 years and weighted by their probability of occurrence to derive an average cost.

Baseline utilities were based on French tariff EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) data, and quality-adjusted life year (QALY) decrements were sourced from previous cost-effectiveness studies in PCVs and pneumococcal disease publications, which distinguished between children and adults. QALY decrements associated with sequelae were applied as a lifetime decrement. The analysis did not consider disutilities linked to any vaccine adverse events as the approvals of PCV15 and PCV20 were based on immunogenicity data with similar safety profiles as PCV13 of which side effects are generally mild and require no treatments [17–19].

The model conducted cost analyses from the French Collective perspective [20]. In line with French guidelines, the model considered an annual discount rate of 2.5% for costs and health outcomes, as the time horizon was less than 30 years [20].

Vaccine Effectiveness, Serotype Coverage, and Vaccine Uptake

The analysis considered both direct effects on the vaccinated cohort and indirect effects on the unvaccinated population. Vaccine effectiveness was calculated in relation to vaccine serotype coverage. In the absence of detailed serotype distribution data stratified by age for non-invasive diseases, the same distribution as for IPD was used. Vaccine direct effect was also dependent on vaccine uptake, which was assumed at 95.7% for a complete mandatory schedule in France [21].

Direct effects on vaccine-type IPD were estimated using PCV13 vaccine effectiveness data from Savulescu et al. [22], assuming the same across vaccine serotypes but distinguishing by schedule: 78.2% (2 + 1) and 89.7% (3 + 1) [22].

For non-invasive disease, PCV7 trial efficacy data were utilized (25.5% against all-cause hospitalized pneumonia and 12.3% against all-cause hospitalized OM) instead of PCV13 data because of variability in study designs, endpoint definitions, and outcomes reported in PCV13 studies [23, 24]. To reflect serotype distribution changes since the pre-PCV7 period, PCV7 efficacy data were adjusted using the ratio of recent serotype coverage in France to the PCV7 original trial coverage (80.6%). Direct vaccine effects were assumed to remain at maximum levels up to 5 years following completion of the full schedule and then begin waning at an annual rate of 10% until year 10.

Although the French recommendations are to administer the booster dose at 11 months of age, in practice, some children receive it from month 12 onwards. Since the primary doses are administered before the age of 1 year, the analysis assumed that the protection for individuals aged < 1 year was 67% of the maximum reduction in disease incidence for the 2 + 1 schedule (i.e., 2 out of 3 doses) and 75.6% for the 3 + 1 schedule, based on Prasad et al. [25]. A summary of inputs used to estimate direct effect is provided in Supplementary Table 4.

Indirect effects were estimated for the additional serotypes covered by PCV15 and PCV20 versus PCV13 based on a hybrid approach using French-specific data to estimate the maximum reduction in IPD incidence and accrual rates [26–28]. To estimate indirect effects against non-invasive diseases, PCV7 clinical trial data were used, following a similar approach as the estimation of direct effect against pneumonia and OM [29–33]. Indirect effect was assumed to gradually reach a steady state, after which no additional benefits were expected. Details of the indirect effect data and estimations were discussed in a 2025 study assessing the consequences of delayed PCV20 implementation into the French pediatric NIP and a summary table can be found in Supplementary Table 5 [34].

Ethical Approval

The data used in this model was non-identifiable. This model and its analysis was based on previously published literature and does not contain any new data with human participants or animals. Therefore, no ethical approval was needed.

Sensitivity and Scenario Analyses

Sensitivity analyses, including a deterministic sensitivity analysis (DSA; default variance ± 20%) and a probabilistic sensitivity analysis (PSA; default standard error 20% with 1000 iterations), as well as additional scenario assessments were carried out to assess the robustness of the results in relation to variation of inputs and key model assumptions.

Details of the scenario analyses are presented in Supplementary Table 6. To explore the impact of including non-hospitalized pneumonia and non-hospitalized OM in the model, the use of proxy data was tested. In another scenario, the vaccinated adult population was excluded from experiencing indirect effects. Various cost assumptions were explored by adjusting pricing per strategy (i.e., matching the total vaccine cost for PCV20 3 + 1 with PCV20 2 + 1) and excluding the administration cost for PCV20. In addition, a scenario was tested focusing on pneumococcal outcomes (i.e., cases caused by Streptococcus pneumoniae) as opposed to all-cause outcomes considered in the base case. Other scenarios involved testing different QALY decrement input data for sequelae and assuming a linear reduction of 5% and 10% for newly covered serotypes by PCV15 and PCV20. In the latter, we assumed that PCV13-serotypes have reached a steady state and would remain unchanged, while the distribution of serotypes unique to PCV15 and PCV20 would decline gradually, both at 5% and 10% annually, until a new steady state was reached for the indirect effect (i.e., 6 years post implementation). The reduction in the newly covered serotypes under PCV15 and PCV20 compared to PCV13 would reflect in the emergence of non-vaccine-type serotypes, ultimately reducing the additional benefits of PCV15 and PCV20 over time. The final scenario focused on the impact of the new coming birth cohort on the results, in which a 10.9% lower birth cohort size compared with the base case was assumed, as France recently experienced a reduced birth rate.

Results

Base Case

The base case model estimated that PCV20 3 + 1 would be the dominant strategy versus both lower-valent alternatives, PCV13 2 + 1 and PCV15 2 + 1 (Table 1).

Table 1.

Base case discounted results

	PCV13 2 + 1	PCV15 2 + 1	PCV20 3 + 1	Incremental
				PCV20 3 + 1 versus PCV13 2 + 1	PCV20 3 + 1 versus PCV15 2 + 1
Clinical and health-related outcomes
IPD cases	46,257	43,934	32,747	− 13,510	− 11,187
Meningitis cases	14,180	13,478	9840	− 4340	− 3637
Bacteremia cases	32,077	30,456	22,906	− 9171	− 7550
Hospitalized pneumonia cases	4,392,997	4,331,651	4,075,861	− 317,136	− 255,790
Hospitalized OM cases	573,633	560,788	507,055	− 66,579	− 53,733
Pneumococcal disease-related deaths	538,572	531,255	501,346	− 37,226	− 29,909
Total QALYs	1,906,321,757	1,906,466,221	1,907,103,470	781,713	637,249
Total LYs	1,992,383,090	1,992,457,979	1,992,783,920	400,830	325,941
Total vaccine doses	20,344,540	20,344,585	27,126,280	6,781,740	6,781,695
Economic outcomes, EUR
Total cost	€32,465,849,214	€32,033,450,101	€30,898,796,835	− €1,567,052,379	− €1,134,653,266
Vaccination cost	€1,559,114,869	€1,559,118,238	€2,308,057,825	€748,942,956	€748,939,586
Total direct cost of disease	€30,772,444,704	€30,346,333,867	€28,495,707,144	− €2,276,737,560	− €1,850,626,722
Lifetime cost associated with sequelae	€134,289,642	€127,997,996	€95,031,866	− €39,257,776	− €32,966,130
ICER, EUR per QALY	–	–	–	PCV20 is dominant	PCV20 is dominant

EUR euros, ICER incremental cost-effective ratio, IPD invasive pneumococcal disease, LY life year, OM otitis media, PCV13 13-valent pneumococcal conjugate vaccine, PCV15 15-valent pneumococcal conjugate vaccine, PCV20 20-valent pneumococcal conjugate vaccine, QALY quality-adjusted life year

Over 10 years, PCV20 3 + 1 was associated with greater prevention of pneumococcal disease cases and deaths versus PCV13 2 + 1 across all age groups (Fig. 1). The public health benefits of PCV20 resulted in 781,713 QALYs gained versus PCV13. Despite higher vaccination costs, mainly driven by the extra dose under the 3 + 1 versus the 2 + 1 schedule, PCV20 was estimated to provide total cost-savings of €1,567,052,379, driven by reductions in medical costs and expenses associated with meningitis-related sequelae.

Fig. 1.

Predicted disease cases by vaccine and age group. IPD invasive pneumococcal disease, OM otitis media, PCV13 13-valent pneumococcal conjugate vaccine, PCV15 15-valent pneumococcal conjugate vaccine, PCV20 20-valent pneumococcal conjugate vaccine

Similar results were observed for the comparison of PCV20 3 + 1 with PCV15 2 + 1, with a total QALY gain of 637,249 and total cost-savings of €1,134,653,266.

Scenario Analyses

As shown in Table 2, scenario analyses for PCV20 3 + 1 versus PCV13 2 + 1 and PCV15 2 + 1 typically demonstrated minimal deviation from the base case, with PCV20 3 + 1 remaining dominant in all but one scenario. In the scenario considering disease cases caused by S. pneumoniae only, proportions of cases caused by S. pneumoniae of 11.54% and 7.4% were applied to incidence in hospitalized pneumonia and hospitalized OM; in addition, specific vaccine-type vaccine effects of 77% and 57% were used for pneumococcal hospitalized pneumonia and hospitalized OM, respectively [35–38]. The results implied that PCV20 averted more cases and deaths but at a higher total cost, resulting in incremental cost-effectiveness ratios (ICER) of €2002 and €3090 per QALY versus PCV13 and PCV15, respectively.

Table 2.

Scenario analysis results

Analysis	Incremental results: PCV13 2 + 1 versus PCV20 3 + 1			Incremental results: PCV15 2 + 1 versus PCV20 3 + 1
	QALY	Costs (EUR)	ICER (EUR per QALY)	QALY	Cost (EUR)	ICER (EUR per QALY)
Base case	781,713	− €1,567,052,379	Dominant	637,249	− €1,134,653,266	Dominant
1. Consider non-hospitalized pneumonia (Ouldali et al. [46]) and non-hospitalized (Mohanty et al. [47])	782,650	− €1,574,646,415	Dominant	637,999	− €1,140,731,590	Dominant
2. Excluding 0.88% (18–64 years) and 2.76% (≥ 65 years) of vaccinated adult population (i.e., adults at risk, not receiving indirect effects) [48]	762,981	− €1,517,482,026	Dominant	622,259	− €1,094,978,127	Dominant
3. Using different QALY decrement for sequelae (− 0.27 from Erickson et al. [49])	778,767	− €1,567,052,379	Dominant	634,736	− €1,134,653,266	Dominant
4a. Adjust pricing per strategy (i.e., total vaccine cost for PCV20 3 + 1 the same as PCV20 2 + 1)	781,713	− €1,927,552,065	Dominant	637,249	− €1,495,152,952	Dominant
4b. Excluding admin cost for PCV20	781,713	− €2,433,111,461	Dominant	637,249	− €2,000,712,348	Dominant
5. Proportion of cases by S. pneumoniae: 11.54% in hospitalized pneumonia (CAPHOSPI study) and 7.4% in hospitalized OM (Levy et al. [35, 36]). Vaccine-type vaccine effect on pneumococcal community-acquired pneumonia 77% (Lewnard et al. 2021), vaccine-type vaccine effect on pneumococcal community-acquired OM 57% (Eskola et al. [37, 38])	147,902	€296,108,270	€2002	122,173	€377,488,849	€3090
6a. Linear reduction at 5% in newly covered serotypes by PCV15 and PCV20	596,325	− €1,023,937,287	Dominant	486,176	− €692,998,232	Dominant
6b. Linear reduction at 10% in newly covered serotypes by PCV15 and PCV20	410,981	− €480,963,599	Dominant	335,145	− €251,478,567	Dominant
7. Assuming 10.9% lower birth cohort size per year based on actual data in 2024 compared to INSEE projections	779,271	− €1,621,810,924	Dominant	635,355	− €1,195,280,225	Dominant
8. Assuming 20% reduction in indirect effect against all disease for all ages	602,881	− €1,062,450,714	Dominant	490,574	− €721,610,414	Dominant

EUR euros, ICER incremental cost-effective ratio, INSEE Institut National de la Statistique et des Études Économiques, OM otitis media, PCV13 13-valent pneumococcal conjugate vaccine, PCV15 15-valent pneumococcal conjugate vaccine, PCV20 20-valent pneumococcal conjugate vaccine, QALY quality-adjusted life year, S. Pneumoniae Streptococcus pneumoniae

Sensitivity Analyses

The DSA identified the 10 key drivers of costs and QALYs in each pairwise comparison (Fig. 2).

Fig. 2.

DSA results PCV20 3 + 1 versus: a PCV13 2 + 1 2 + 1 and b PCV15 2 + 1. Costs are in euros. DSA deterministic sensitivity analysis, IPD invasive pneumococcal disease, PCV13 13-valent pneumococcal conjugate vaccine, PCV15 15-valent pneumococcal conjugate vaccine, PCV20 20-valent pneumococcal conjugate vaccine, QALY quality-adjusted life year

Overall, the parameters to which costs were the most sensitive included maximum indirect effect of PCV20 against hospitalized pneumonia, current serotype coverage by vaccine, medical costs and incidence of hospitalized pneumonia, and cost per dose of PCV20. These parameters, except for medical cost of hospitalized pneumonia and cost per dose of PCV20, were also key drivers for QALYs, followed by case fatality rate of hospitalized pneumonia and indirect effect accrual for PCV20.

The PSA results indicated that PCV20 was dominant in 96.9% of iterations versus PCV13 and in 93.8% of iterations versus PCV15 (Table 3; Fig. 3). PCV20 was estimated to be more effective in 100.0% of iterations versus both comparators but more costly in 3.1% of iterations versus PCV13 and in 6.2% of iterations versus PCV15.

Table 3.

PSA results: proportion of iterations per quadrant with PCV20 3 + 1 versus PCV13 2 + 1 and PCV15 2 + 1

	Proportion of iterations per quadrant, %
	PCV20 versus PCV13	PCV20 versus PCV15
More costly and more effective	3.1%	6.2%
More costly and less effective	0.0%	0.0%
Less costly and less effective	0.0%	0.0%
Less costly and more effective	96.9%	93.8%

PCV13 13-valent pneumococcal conjugate vaccine, PCV15 15-valent pneumococcal conjugate vaccine, PCV20 20-valent pneumococcal conjugate vaccine, PSA probabilistic sensitivity analysis

Fig. 3.

PSA scatterplots PCV20 3 + 1 versus: a PCV13 2 + 1, b PCV15 2 + 1. Costs are in euros. PCV13 13-valent pneumococcal conjugate vaccine, PCV15 15-valent pneumococcal conjugate vaccine, PCV20 20-valent pneumococcal conjugate vaccine, PSA probabilistic sensitivity analysis, QALY quality-adjusted life year

Discussion

The findings from this cost-effectiveness analysis indicated that adopting PCV20 3 + 1 in the French pediatric NIP would be a dominant strategy, providing greater health benefits and cost-savings, versus PCV13 2 + 1 and PCV15 2 + 1 over 10 years from the French Collective perspective. Improvements in health outcomes were observed across all age groups, with PCV20 implementation predicted to lead to fewer disease cases versus PCV13 and PCV15. The model estimated that PCV20 would also result in reduced disease fatality and lower disease-related medical costs compared with both lower-valent alternatives. Although PCV20 was associated with the highest vaccination costs, it remained the most cost-saving strategy among the three vaccine strategies considered in this analysis owing to notable savings in medical costs associated with pneumococcal events and sequelae. As a result, PCV20 was associated with QALY gains of 781,713 and 637,249 compared with PCV13 and PCV15, respectively. A total cost-saving of €1,567,052,379 was projected with PCV20 versus PCV13, whereas a €1,134,653,266 cost-saving was estimated with PCV20 versus PCV15 over 10 years.

Most sensitivity analyses and scenario assessments produced consistent results with the base case, identifying PCV20 as the dominant vaccine strategy compared with PCV13 and PCV15 for pediatric vaccination in France, demonstrating robustness of the results irrespective of uncertainties around assumptions and model inputs. The findings and conclusions of this analysis largely aligned with previous studies of PCV20 in pediatric vaccination programs across multiple European countries as well as North and South America, and Asia [12–16, 39–42].

The results of a recently published modeling study by Bakker et al. suggested that the incidence of IPD caused by PCV13 serotypes (“breakthrough” IPD) could increase if PCV20 is implemented in France [43]. However, this analysis used a very narrow focus by only estimating the impact of PCV15 and PCV20 on PCV13-type IPD in children aged up to 1 year. This approach is limited as it does not account for the potential effects of the five additional serotypes included in PCV20 versus PCV15, and we argue that modeled estimates of higher-valent PCV impact should consider the full spectrum of potential benefits to adequately inform decision-making. A similar study to Bakker et al. was recently performed in the USA. In contrast to Bakker et al., this study took a broader perspective, modeling the health and economic benefits of PCV15 and PCV20 in children aged up to 1 year, estimating that PCV20 would avert nearly 119,000 additional disease cases (IPD, pneumonia, and OM) over 5-year period compared with PCV15 [44]. Additionally, a systematic literature review of pediatric PCV cost-effectiveness analyses concluded that PCV20 would result in greater QALY gains and cost reductions (both direct medical costs and indirect cost attributed to productivity loss) versus PCV13 and PCV15 [45].

This study sought to capture the current context along with the epidemiological and clinical characteristics specific to France by prioritizing the use of local data. However, there remained some limitations regarding available data and the use of some proxies in this analysis. Firstly, as a result of the lack of France-specific incidence rates for non-hospitalized pneumonia and non-hospitalized OM, these conditions were excluded from the model. Although excluding non-hospitalized pneumonia and non-hospitalized OM was not optimal, this approach was considered conservative, as it likely underestimated the health and economic advantages of PCV20 3 + 1 relative to alternatives. A scenario including non-hospitalized pneumonia and non-hospitalized OM using proxy data from other countries was tested, the results of which were in line with the base case. Secondly, the model assumed that the serotype distributions for IPDs were the same as those for non-invasive diseases as a result of lack of specific data, not only in France but in many other countries. However, this assumption has been used in many other cost-effectiveness and public health impact studies of PCVs [12–15, 39, 40, 42]. Thirdly, the estimates used for lifetime costs associated with sequelae were based on weighted average costs over a duration of 5 years because of uncertainties around the data, which also was considered a conservative approach. The vaccine effect estimated in this study relied on several assumptions because of the absence of real-world and trial efficacy data for PCV15 and PCV20. Estimates for direct and indirect effects were derived using data from lower-valent vaccines, such as PCV13 and PCV7. While some parameters, including vaccine-type effects against IPD, were informed by French data, other estimates (such as direct effects for all clinical events and indirect effects for non-invasive diseases) were sourced from large-scale studies conducted in other European countries. This hybrid methodology aimed to collect data that are representative of the burden of pneumococcal infections and apply these to the French context in order to provide a robust estimate of the impact of pediatric vaccination. The base case analysis assumed no serotype replacement for PCV15- and PCV20-unique serotypes compared with PCV13 because of the absence of long-term data. To address this uncertainty, two scenarios were explored, applying a 5% and 10% annual linear reduction until the new steady state was reached, reflecting a reduction in vaccine-type coverage and an increase in non-vaccine-type coverage, the findings of which were consistent with the base case.

Conclusion

The results of this cost-effectiveness study suggested that implementing PCV20 3 + 1 into the routine pediatric vaccination program in France would lead to reduced incidence of pneumococcal disease, yield QALY gains, and provide notable cost-savings compared with currently available lower-valent alternatives—PCV13 2 + 1 and PCV15 2 + 1—over a 10-year time horizon at the whole population level.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contributions

Stéphane Fiévez, Emmanuelle Blanc, Jessica Y. El Khoury, Maud Beillat, Ayman Sabra, Aleksandar Ilic, and Johnna Perdrizet contributed to the drafting/reviewing/editing of the manuscript (original and subsequent drafts). An Ta, Lucile Bellier and Marine Sivignon contributed to the formal analysis and drafting/reviewing/editing of the manuscript (original and subsequent drafts).

Funding

This study was sponsored by Pfizer. The sponsor was involved in the study design, analysis, and interpretation of the data. The journal’s Rapid Service Fee was funded by ICON Plc.

Data Availability

All data generated and analyzed in this study are reported in this published article/as supplementary information files.

Declarations

Conflict of Interest

An Ta is an employee of Cytel, which received funding from Pfizer in connection with the development of this manuscript and study. Marine Sivignon is employed by Putnam, and Lucile Bellier formally employed by Putnam, which received funding from Pfizer in connection with the development of this manuscript and study. Stéphane Fiévez, Emmanuelle Blanc, Jessica Y. El Khoury, Ayman Sabra, Aleksandar Ilic, and Johnna Perdrizet are employees of Pfizer. Maud Beillat is a former Pfizer employee.

Ethical Approval

The data used in this model was non-identifiable. This model and its analysis was based on previously published literature and does not contain any new data with human participants or animals. Therefore, no ethical approval was needed.