Estimating the Health and Economic Burden of Pneumococcal Diseases Attributable to PCV21 Versus PCV20 or PPSV23 Serotypes Among Adults in Norway

Abstract

Introduction

Routine childhood immunization programs using pneumococcal conjugate vaccines (PCVs) significantly reduce the burden of pneumococcal disease (PD). PCV21, a 21-valent PCV, was recently approved and recommended by the European Commission for use in Norway. The objective of this study was to quantify the health and economic burden of invasive PD (IPD) and non-bacteremic pneumococcal pneumonia (NBPP) attributable to PCV21, PCV20, and PPSV23 serotypes among adults in Norway.

Methods

A published Markov model was adapted to estimate lifetime IPD/NBPP cases, deaths, and direct medical costs (in 2023 Norwegian kroner [NOK]) associated with PCV21, PCV20, and PPSV23 serotypes in Norway. Results were disaggregated by age and risk groups. A one-way sensitivity analysis examined changes in disease costs (± 20%).

Results

The projected number of PD cases and deaths attributable to PCV21 serotypes was substantially higher than those attributable to PCV20 and PPSV23 serotypes. PD cases and deaths attributable to PCV21 serotypes vs. PCV20 and PPSV23 were ~ 41% and ~ 26% higher, respectively, in adults aged 65+ years, ~ 39% and ~ 25% higher in those aged 50–64 years, and ~ 37% and ~ 22% higher in those aged 18–64 years with risk factors. Within each age group, cases and total lifetime costs increased progressively as risk categorization increased. Estimated lifetime direct treatment costs for PD attributable to PCV21 serotypes were higher than those associated with PCV20 or PPSV23, at 3.9 billion NOK, 3.5 billion NOK, and 4.4 billion NOK in adults aged 65+, 50–64, and 18–64 years with risk factors, respectively.

Conclusions

Compared with PCV20 and PPSV23, PCV21 serotypes are associated with a higher health and economic burden in Norway. The inclusion of PCV21 into national vaccine recommendations in Norway can further alleviate the burden associated with PD in adults.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40121-025-01275-3.

Plain Language Summary

Pneumococcal disease is a serious bacterial infection that remains a public health concern globally and in Norway. Vaccines are available to protect against this disease, but they cover different groups of pneumococcal serotypes (i.e., strains of the bacteria). A new adult-targeting vaccine, PCV21, was recently approved in Europe, which protects against 21 serotypes, including 8 that are not covered by the other vaccines currently used in Norway (PCV20 and PPSV23). In this study, we used a published state transition Markov model to estimate the number of pneumococcal disease cases, deaths, and medical costs attributable to PCV21, PCV20, and PPSV23 serotypes among adults in Norway. Overall, we found that PCV21 serotypes were associated with a higher health and economic burden than those covered by PCV20 or PPSV23. Across all age groups, about one in four cases and one in four deaths were attributable to the eight unique PCV21 serotypes. Over a lifetime, pneumococcal diseases caused by PCV21 serotypes were estimated to cost about 12 billion Norwegian kroner in direct medical treatment, compared with 8.5 billion for PCV20 serotypes and 9.5 billion for PPSV23 serotypes. These findings suggest that including PCV21 in Norway’s adult vaccination program could prevent more illness and deaths and reduce healthcare costs by protecting against additional strains of pneumococcal disease.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40121-025-01275-3.

Key Summary Points

Why carry out this study?

Pneumococcal disease (PD) is a significant cause of morbidity, mortality, and healthcare costs in Norway.

PCV21, a recently approved 21-valent pneumococcal conjugate vaccine, protects against more serotypes than PCV20 and PPSV23 vaccines, but its potential health and economic impact in Norway is not fully understood.

This study evaluated the projected health and economic burden of PD attributable to PCV21, PCV20, and PPSV23 serotypes among adults in Norway, disaggregated by age and risk groups.

What was learned from the study?

PCV21 serotypes, including the 8 unique serotypes not found in other vaccines, were associated with substantially more PD cases, deaths, and higher lifetime direct treatment costs compared with PCV20 and PPSV23 serotypes.

The addition of PCV21 to the vaccine recommendations in Norway has the potential to prevent a considerable additional burden of disease and costs.

Introduction

Pneumococcal diseases (PDs) are symptomatic infections caused by the bacterium Streptococcus pneumoniae, which can be classified as either invasive PD (IPD) or non-invasive, non-bacteremic pneumococcal pneumonia (NBPP) [1, 2]. Infants, older adults (65+ years), and individuals with chronic conditions or who are immunocompromised are at an increased risk of PD [3, 4]. PDs are common and contribute a significant health and economic burden to healthcare systems, and this burden increases with age and the presence of underlying conditions [5]. In 2022, 17,700 confirmed cases of IPD were reported in the European Union (EU)/European Economic Area, and 539 cases were reported in Norway [6].

Vaccination strategies incorporating pneumococcal conjugate vaccines (PCVs) have substantially reduced the incidence of PD among children in Norway [7, 8]. PCV7 was introduced in the Norwegian childhood immunization program in 2006, which was later replaced by PCV13 in 2011 [9]. This program provided indirect protection among adults, and adult vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) has helped address residual disease in the adult population [10]. The Norwegian Institute of Public Health (NIPH) recommends pneumococcal vaccination with PCV20, PCV21 (approved in 2025), and PPSV23 for all adults over 65 years of age and for those in medical risk groups that increase their risk of PD [11, 12].

Despite a reduction in IPD attributed to pneumococcal vaccination in Norway, non-vaccine serotypes have emerged through serotype replacement, leading to an increase in IPD cases caused by serotypes not contained in previously available vaccines [7, 14, 15]. For example, in 2023, 13.3% of the population over 18 years old in Norway were vaccinated with any vaccine, and the pneumococcal vaccination coverage rate (VCR, defined as vaccination with PPSV23 alone, any conjugate alone, or any conjugate followed by PPSV23) was 2.3%, 8.7%, and 43.8% among adults aged 18–49 years, 50–64 years, and over 65 years, respectively [16]. Higher-valency PCVs, such as PCV21, have been developed to address this residual burden and expand the coverage of existing vaccines by including additional serotypes.

PCV21 is a 21-valent PCV that contains 8 unique serotypes which are not included in any currently licensed vaccines (15A, 15C [generated from deOAc-15B], 16F, 23A, 23B, 24F, 31, and 35B) along with 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 17F, 19A, 20A, 22F, and 33F. In March 2025, the European Commission approved PCV21 for use in all 27 EU member states as well as Norway, Iceland, and Liechtenstein. In 2021–2023, disease coverage for PCV21, PCV20, and PPSV23 in Norway for those aged 65 years or more was 83.7%, 59.3%, and 66.4%, respectively [17]. However, the eight unique serotypes in PCV21 accounted for 22.3% of all IPD cases [17], highlighting the potential for additional protection with PCV21 in Norway.

The current study was conducted to quantify the lifetime health and economic burden of PD attributable to PCV21, PCV20, and PPSV23 serotypes among adults in Norway. We hypothesized that PCV21 serotypes would be associated with a greater projected burden of cases, deaths, and costs compared to PCV20 and PPSV23 serotypes.

Methods

Model Overview

A published Markov model [18, 19] was adapted to the Norwegian healthcare perspective to estimate IPD/NBPP cases, deaths, and direct medical costs associated with PCV21, PCV20, and PPSV23 serotypes among adults aged 65 years and older, 50–64 years, and 18–64 years with risk factors. Three health states were modeled: no pneumococcal disease (PD), PD (divided into two groups: IPD and NBPP), and death (Fig. 1). For NBPP disease, there was a distinction between inpatient and outpatient.

Fig. 1.

Markov model structure. AR at-risk, HR high-risk, IPD invasive pneumococcal disease, LR low-risk, NBPP non-bacteremic pneumococcal pneumonia, PD pneumococcal disease

Adults entered the model at risk for infection, which was defined by age and risk level. Adults exited the model at death, at a background mortality rate adjusted by the case fatality rate associated with the PD state. The number of cases of IPD and NBPP, deaths from IPD and inpatient NBPP, and direct costs were estimated for a cohort of adults aged 18–100 years in annual cycles over a lifetime horizon. Costs were discounted after introduction by 4% annually for the first 40 years, by 3% from 40 to 74 years, and by 2% after 74 years [20].

Model Inputs

Demographic Inputs

The risk of PD was defined into three mutually exclusive risk groups: low-risk, at-risk, or high-risk based on categories for vaccine recommendation as defined by the NIPH [12]. Risk distributions were determined from national data on age and comorbidities (Supplemental Table S1) [11, 21]. In brief, those experiencing any of the following comorbid conditions or characteristics were considered at-risk: chronic liver disease, primary or secondary immune deficiency (except B cell deficiency), cancer (except hematologic), chronic kidney disease, homelessness, drug abuse, iatrogenic immune suppression (except solid organ transplant), diabetes mellitus, celiac disease, reduced ventilation capacity, chronic lung disease, chronic heart disease, previous IPD, alcoholism, smoking, and welder/professional exposure to risk. Those with functional or anatomic splenectomy, cerebrospinal fluid leak, HIV, B cell deficiency, hematopoietic stem cell transplant, hematologic cancers (leukemia, lymphoma, myelomatosis), solid organ transplant, or cochlear implantation (during implant) were considered high-risk.  Other demographic inputs were age-specific population sizes and mortality rates (Supplemental Table S2).

Epidemiological Inputs

Table 1 summarizes the epidemiological inputs used in the model. Epidemiological inputs were the incidence and case fatality rates of IPD (inpatient only) and NBPP (both inpatient and outpatient). Case fatality rates in Norway were obtained from the European Centre for Disease Prevention and Control (ECDC) Surveillance Atlas of Infectious Diseases (Supplemental Table S2) [22]. The IPD fatality rate (8.6%) was obtained from ECDC for adults aged 65+ years and was assumed for other groups. Age- and risk status-specific IPD incidence rates were derived by applying the incidence rates for each age group (18–49, 50–64, and 65+) from the ECDC [22] to the incidence rates per risk group in Winje et al. (2021) [7]. For NBPP inpatient fatality rates, the incidence rates for each age group were derived by applying the incidence rates from Nymark et al. (2022) [14] to the incidence rates per risk group in Winje et al. (2021) [7].

Table 1.

Epidemiological and cost inputs

Input category	Low-risk	At-risk	High-risk	Source(s)
Epidemiological inputs
IPD incidence (per 100,000)				ECDC (2022) [22]; Winje et al. (2021) [7]
Ages 18–49	2.5	9.2	71.0
Ages 50–64	9.7	24.3	113.0
Ages 65+	20.0	32.0	87.6
IPD case fatality rate, %	8.6			ECDC (2022) [22]
NBPP inpatient incidence (per 100,000)				Winje et al. (2021) [7]; Nymark et al. (2022) [14]
Ages 18–49	16.7	60.9	171.8
Ages 50–64	65.7	164.5	763.5
Ages 65+	176.7	283.0	774.5
NBPP inpatient case fatality rate				Huang et al. (2011) [30]
Ages 18–49	0.016 (all risk groups)
Ages 50–64	0.032 (all risk groups)
Ages 65+	0.067 (all risk groups)
NBPP outpatient incidence (per 100,000)				Winje et al. (2021) [7]; Nymark et al. (2022) [14]
Ages 18–49	21.6	78.6	607.1
Ages 50–64	84.8	212.3	985.6
Ages 65+	228.1	365.3	999.8
Disease coverage in 65+				NIPH (2024) [23]
PCV21	84.4%
PCV20	59.9%
PPSV23	66.4%
Cost inputs (NOK)				Nymark et al. (2022) [14]
IPD, per episode	135,285 (all risk groups)
NBPP inpatient, per episode	64,179 (all risk groups)
NBPP outpatient, per incidence	495 (all risk groups)

ECDC European Centre for Disease Prevention and Control, IPD invasive pneumococcal disease, NBPP non-bacteremic pneumococcal pneumonia, NIPH Norwegian Institute of Public Health, NOK Norwegian kroner

Serotype distribution [23] was used to calculate the percentages of IPD and NBPP cases attributed to each serotype (Supplemental Table S3). Disease coverage by each vaccine is included in Table 1.

Economic Inputs

The economic inputs were the direct costs of IPD and NBPP (Table 1). Costs were derived from Nymark et al. (2022) [14] and adjusted to 2023 Norwegian kroner (NOK).

Model Outcomes and Sensitivity Analysis

Model outcomes included the number of cases of IPD and NBPP, deaths from IPD and inpatient NBPP, and direct costs associated with IPD and NBPP. Results were summarized by age group and risk level for each vaccine, along with the eight unique serotypes in PCV21. A one-way sensitivity analysis was undertaken to test the robustness of the results to individual inputs (± 20%). Throughout the entire time horizon, the lower and upper bounds for discounting rates were assumed to be 0% and 6%, respectively.

Results

Burden of Disease

Figure 2 depicts the cumulative number of PD cases in adults by age and risk level over a lifetime horizon as predicted by the model. For all age groups, the number of PD cases attributable to PCV21 serotypes was greater than the number of cases attributable to PCV20 and PPSV23 serotypes for all risk levels.

Fig. 2.

a–c Cumulative lifetime cases of pneumococcal disease due to vaccine serotypes by age and risk level. PCV20 20-valent pneumococcal conjugate vaccine, PCV21 21-valent pneumococcal conjugate vaccine, PPSV23 23-valent pneumococcal polysaccharide vaccine. Bold values on top of the PCV21 bars represent the sum of the total PCV21 cases (15A, 15C [generated from deOAc-15B], 16F, 23A, 23B, 24F, 31, and 35B] along with 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 17F, 19A, 20A, 22F, and 33F) which is the sum of less unique 8 and unique 8 serotypes (15A, 15C [generated from deOAc-15B], 16F, 23A, 23B, 24F, 31, and 35B)

In adults aged 65+ years, cases totaled 112,762 (3,229 IPD + 109,533 NBPP) for PCV21 serotypes, which accounted for ~ 41% more (32,872) IPD/NBPP cases vs. PCV20 serotypes and ~ 26% more cases (23,289) vs. PPSV23 serotypes (Supplemental Table S4). Among adults aged 50–64 years, cases totaled 101,035 (4,107 IPD + 96,928 NBPP) for PCV21 serotypes, which accounted for ~ 39% more IPD/NBPP cases (28,151) vs. PCV20 serotypes and ~ 25% more (20,258) vs. PPSV23 serotypes (Supplemental Table S5). In adults aged 18–64 years with risk factors, cases totaled 128,507 (5,928 IPD + 122,579 NBPP) for PCV21 serotypes, which accounted for ~ 37% more (34,437) IPD/NBPP cases vs. PCV20 serotypes and ~ 22% more cases (22,913) vs. PPSV23 serotypes (Supplemental Table S6). Among all age groups, ~ 25% of total cases were attributable to the eight serotypes unique to PCV21.

The projected number of deaths attributable to PCV21 serotypes was greater in all age groups and at all risk levels than deaths that were attributable to PCV20 and PPSV23 serotypes (Fig. 3). For adults aged 65+ years, deaths due to disease from serotypes in PCV21 totaled 2,859 (208 IPD + 2,651 NBPP) and were ~ 41% higher than deaths due to disease from PCV20 serotypes (2,026; 148 IPD + 1,878 NBPP) and ~ 26% higher than deaths from PPSV23 serotypes (2,269; 165 IPD + 2,104 NBPP). For adults aged 50–64 years, deaths due to disease from serotypes in PCV21 totaled 1,627 (223 IPD + 1,404 NBPP) and were ~ 39% higher than deaths due to disease from PCV20 serotypes (1,173; 164 IPD + 1,009 NBPP) and ~ 25% higher than deaths due to PPSV23 serotypes (1,300; 181 IPD + 1,119 NBPP). Among adults 18–64 years with risk factors, deaths due to disease from serotypes in PCV21 totaled 1,635 (294 IPD + 1,341 NBPP) and were ~ 37% higher than deaths due to disease from PCV20 serotypes (1,190; 220 IPD + 970 NBPP) and ~ 23% higher than deaths due to PPSV23 serotypes (1,334; 248 IPD + 1,086 NBPP). Among all age groups, ~ 25% of deaths were attributable to the eight unique serotypes in PCV21.

Fig. 3.

a–c Cumulative deaths from pneumococcal disease due to vaccine serotypes by age and risk level. 20-valent pneumococcal conjugate vaccine, PCV21 21-valent pneumococcal conjugate vaccine, PPSV23 23-valent pneumococcal polysaccharide vaccine. Bold values on top of the PCV21 bars represent the sum of the total PCV21 deaths (15A, 15C [generated from deOAc-15B], 16F, 23A, 23B, 24F, 31, and 35B] along with 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 17F, 19A, 20A, 22F, and 33F) which is the sum of less unique 8 and unique 8 serotypes (15A, 15C [generated from deOAc-15B], 16F, 23A, 23B, 24F, 31, and 35B)

Economic Burden

The estimated lifetime economic burden of PD due to serotypes PCV21, PCV20, and PPSV23 is shown in Fig. 4 across age groups and risk levels. PCV21 serotypes were associated with a higher economic burden compared to PCV20 and PPSV23 serotypes. The model estimated the lifetime direct treatment costs for PD attributable to PCV21 serotypes were 3.9 billion NOK in adults 65+ years old, 3.5 billion NOK in adults 50–64 years old, and 4.4 billion NOK in adults 18–64 years old with risk factors. Estimated lifetime direct costs associated with PCV20 and PPSV23 serotypes were 2.8 billion NOK and 3.1 billion NOK in adults 65+ years old, 2.5 billion NOK and 2.8 billion NOK in adults 50–64 years old, and 3.2 billion NOK and 3.6 billion NOK for adults 18–64 years old with risk factors. The 18–64 age group with risk factors (Supplemental Table S6) had the highest associated total direct lifetime cost, followed by the 65+age group (Supplemental Table S4) and the 50–64 age group (Supplemental Table S5). Within each age group, the high-risk population had the highest associated total direct lifetime costs, followed by the at-risk group.

Fig. 4.

a–c Direct lifetime cost of PD due to vaccine serotypes by age and risk level. NOK Norwegian kroner, PCV20 20-valent pneumococcal conjugate vaccine, PCV21 21-valent pneumococcal conjugate vaccine, PPSV23 23-valent pneumococcal polysaccharide vaccine

Sensitivity Analysis

The one-way sensitivity analysis confirmed the robustness of the results; all scenarios showed a substantial lifetime direct medical cost that could potentially be offset by PCV21. A summary of the results, depicted in decreasing order of the top 10 inputs’ influence on the total discounted direct lifetime costs, is presented as a tornado diagram in Fig. 5a for adults aged 65+ years and in Fig. 5b for adults aged 50–64 years. Among both age populations, the discounting rate was the most influential input. The direct costs (upper to lower) associated with the discounting rates were 3.4 to 5.7 billion NOK for those aged 65+ and 2.6 to 7.1 billion NOK for those aged 50–64 years.

Fig. 5.

One-way sensitivity analysis results demonstrating the estimated lifetime discounted direct medical cost for PCV21 serotypes among adults aged a 65+ years and b 50–64 years in Norway. AR at-risk, HR high-risk, IPD invasive pneumococcal disease, LR low-risk, NBPP non-bacteremic pneumococcal pneumonia. Costs expressed in 2023 Norwegian kroner (NOK), millions

Discussion

Using a state transition Markov model and a multicohort approach to estimate the burden of PDs attributable to serotypes among adults, we found that PCV21 serotypes were associated with a considerably higher health and economic burden compared with PCV20 or PPSV23 serotypes in Norway. Generally, within each age group, the low-risk group had the lowest number of PD cases, deaths, and associated direct costs compared to the at-risk and high-risk groups. These findings align with the stated hypothesis.

This study adapted a published Markov model by Yi and colleagues (2024) [18], which examined the lifetime health and economic burden of IPD attributable to serotypes contained in PCV21 vs. PCV20 among adults in the USA, and applied it to the Norwegian healthcare setting. Similar to our study, Yi et al. found that PCV21 serotypes were associated with a substantially higher clinical and economic burden of IPD compared to PCV20 serotypes. Our analysis additionally examined the burden of PPSV23 serotypes, which were not included in the analysis by Yi et al. [18]. In the study by Yi et al., approximately one-third of the estimated lifetime number of cases of IPD and IPD-related deaths were attributed to the eight unique serotypes contained in PCV21 [18]. Similar findings were demonstrated in our study, with approximately 25% of PD cases and deaths attributed to the eight unique serotypes in PCV21. In contrast to the study by Yi et al., which only examined the burden of IPD, our analysis examined the health and economic burden of both IPD and NBPP. Since NBPP constitutes a large proportion of PDs, our study provides a more comprehensive understanding of the overall burden of PD in Norway.

Childhood vaccination programs have reduced the burden of IPD in children and have also led to indirect protection among adults [24]. Previously approved pneumococcal vaccines (e.g., PPSV23, PCV13, and PCV20) helped to address residual disease in adults; however, the durability of protection by vaccines like PPSV23 and PCV13 is limited, and non-PPSV23 serotypes have continued to circulate and cause PD in adults [10]. In Norway, the PCV21 serotypes account for a higher incidence of IPD compared to PCV20 serotypes [22]. Higher-valency PCVs, including PCV21, were specifically designed to address the residual disease burden among adults [10], which is reflected in our finding that PCV21 serotypes were associated with the greatest clinical and economic impact among adults in Norway, as compared to PCV20 and PPSV23 serotypes.

There remains a substantial burden of preventable IPD in the older adult population in Norway [25]. A significant factor that has contributed to PD cases among adults in Norway is the suboptimal uptake of pneumococcal vaccines, which is observable across age groups, and thus leaves a significant number of adults more susceptible to PD [7, 16]. To address this, the NIPH implemented a limited adult immunization program in fall 2025, which includes pneumococcal vaccination for adults turning 65 years of age [13]. Although national recommendations for pneumococcal vaccination have existed for several years for adults aged 65 years and older, as well as at-risk and high-risk groups, reimbursement has previously been limited to a select few indications among the high-risk groups. The recently established age-based adult immunization program now provides partial reimbursement for pneumococcal vaccination for any individual 65 years and older [13]. The European Commission approved PCV21 in the EU in March 2025, and Norway follows the EU for approval of new medicines and vaccines. As demonstrated in the current study, the clinical and economic burden was highest for PCV21 serotypes compared to serotypes covered by PCV20 and PPSV23, suggesting that adding PCV21 to the vaccine recommendations for adults in Norway can help further alleviate the clinical and economic burden of PD.

Limitations

This study has several limitations. Firstly, the model assumed constant IPD and NBPP epidemiology; however, the incidence of IPD and NBPP would be expected to change over time due to both direct and indirect effects from current and evolving vaccines and vaccine recommendations in both pediatric and adult populations in Norway. This analysis assumes continued pediatric vaccination with PCV13, which would sustain indirect protection against PCV13 serotypes in adults. If pediatric vaccination practices were to change, the relative burden of these serotypes in adults may shift. Additionally, there is insufficient data to incorporate these effects into the current analysis, which is a common limitation of Markov/static models. Secondly, although serotype distributions varied by age and risk group, distributions were assumed to be the same for IPD and NBPP cases, despite data being available only for IPD. Thirdly, the model only examined the direct costs of PD. The inclusion of indirect costs of PD would have substantially increased the predicted burden of PD. Fourthly, the model did not include the long-term sequelae from meningitis (post-meningitis sequelae) because of a lack of data. If post-meningitis sequelae were included, the estimated incremental burden associated with PCV21 serotypes would be even greater compared with PCV20 or PPSV23. Lastly, the model assumed stable risk distributions within each age group. Assessing if the risk distribution has changed since the publication by Winje et al. (2021) [7], and assessing vaccination uptake by risk group would improve the current analysis.

Strengths

This model analyzed outcomes at the serotype level, an underrepresented area of research, using a published Markov model with a multicohort approach to evaluate health and economic benefits across three different age cohorts while accounting for population heterogeneity in risk of disease. This study contributes to the growing evidence base demonstrating the greater health and economic burden associated with PCV21 serotypes compared to other vaccine serotypes [18] in Norway. Previous studies indicate the substantial impact that using a single cohort versus a multicohort model has on results when examining health and cost burdens associated with PCVs [26, 27]. The model accounted for different risk distributions for different age groups, which provides a more accurate assessment of clinical and economic outcomes, given that the at-risk and high-risk categories are associated with higher IPD risk and costs [4, 28]. The model considered both IPD and NBPP, thus providing a more comprehensive representation of the overall burden of PD. Finally, sensitivity analyses confirmed the robustness of the base case results, which indicated that the significant lifetime direct medical costs of PCV21 could potentially be offset.

Conclusions

A substantial number of lifetime cases and deaths due to PD were projected among adults in Norway that were attributable to serotypes in PCV21, including the eight unique serotypes not found in other vaccines. The health and economic burden of PCV21-attributable disease exceeded that of PCV20- and PPSV23-attributable disease. These findings suggest that the addition of PCV21 to the vaccine recommendations in Norway can help further alleviate the clinical and economic burden of PD in adults.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contributions

Zinan Yi, Athar Ali Tajik, Søren Toksvig Klitkou, Eleana Tsoumani, and Kwame Owusu-Edusei contributed to the study conception, design, and scope of the study. Material preparation and data collection and analysis were performed by Søren Toksvig Klitkou. Zinan Yi performed the study analysis. Zinan Yi, Athar Ali Tajik, Søren Toksvig Klitkou, Eleana Tsoumani, and Kwame Owusu-Edusei commented on previous versions of the manuscript. All authors read and approved of the final manuscript.

Funding

This study was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, funded the journal’s publication fees.

Data Availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Declarations

Conflict of Interest

Zinan Yi and Kwame Owusu-Edusei are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Søren Toksvig Klitkou and Athar Ali Tajik are employees of MSD Norway. Eleana Tsoumani is an employee of MSD Greece. All authors may hold stock or stock options in Merck & Co., Inc., Rahway, NJ, USA.

Ethical Approval

As this was a modeling study using de-identified data as model inputs, ethical approval was not required.