Recommendations on the use of conjugate pneumococcal vaccine – 15 valent (PNEUC15) and 20 valent (PNEUC20) in adults: Economic evidence supplementary appendix
An Advisory Committee Statement (ACS)
National Advisory Committee on Immunization (NACI)
Table of Contents
 Preamble
 I. Systematic Review
 II. CostUtility Analysis
 III. MultiModel Comparison
 List of Abbreviations
 References
Preamble
The National Advisory Committee on Immunization (NACI) is an External Advisory Body that provides the Public Health Agency of Canada (PHAC) with independent, ongoing and timely medical, scientific, and public health advice in response to questions from PHAC relating to immunization.
In addition to burden of disease and vaccine characteristics, PHAC has expanded the mandate of NACI to include the systematic consideration of programmatic factors in developing evidence based recommendations to facilitate timely decisionmaking for publicly funded vaccine programs at provincial and territorial levels.
The additional factors to be systematically considered by NACI include: economics, ethics, equity, feasibility, and acceptability. Not all NACI statements will require indepth analyses of all programmatic factors. While systematic consideration of programmatic factors will be conducted using evidenceinformed tools to identify distinct issues that could impact decisionmaking for recommendation development, only distinct issues identified as being specific to the vaccine or vaccinepreventable disease will be included.
This statement contains NACI's independent advice and recommendations, which are based upon the best current available scientific knowledge. This document is being disseminated for information purposes. People administering the vaccine should also be aware of the contents of the relevant product monograph. Recommendations for use and other information set out herein may differ from that set out in the product monographs of the Canadian manufacturers of the vaccines. Manufacturer(s) have sought approval of the vaccines and provided evidence as to its safety and efficacy only when it is used in accordance with the product monographs. NACI members and liaison members conduct themselves within the context of PHAC's Policy on Conflict of Interest, including yearly declaration of potential conflict of interest.
A systematic review, de novo modelbased economic evaluation, and a multimodel comparison were used as economic evidence to support decisionmaking for the use of 15valent (PNEUC15) and 20valent (PNEUC20) conjugate vaccines. Each component is described below.
Systematic Review
A systematic review of the costeffectiveness of PNEUC15 and PNEUC20 vaccines for preventing pneumococcal disease (PD) was conducted. The review included economic evaluations conducted in adults aged 18 or older, comparing currently used vaccines to prevent pneumococcal disease to PNEUC15 or PNEUC20. The components of the research question are:
 Population: Adults aged 18 years or older
 Intervention: PNEUC15 or PNEUC20 (alone or in series with other pneumococcal vaccines)
 Comparator: Current vaccines for pneumococcal disease (PNEUC7, PNEUC10, PNEUC13, PNEUP23 (23valent polysaccharide))
 Outcomes: Measures of costeffectiveness (incremental cost per qualityadjusted life year, incremental cost per disabilityadjusted life year, cost per life year, etc.)
A systematic literature search of Embase, International Pharmaceutical Abstracts, Ovid Medline, EBM Reviews, and Econlit was conducted for January 1, 2018, to September 30, 2021. Language of publication was restricted to English or French. Keywords used included: pneumococcal vaccine, conjugate vaccine, pneumococcal infection, PCV15, PCV20, economic evaluation, economic impact, and financial effect. The search strategy was developed in consultation with and validated by a librarian. A search of grey literature was also conducted, guided by recommendations put forth by the Canadian Agency for Drugs and Technologies in Health (CADTH) in their Grey Matters tool, which is a checklist of grey literature sources including both Canadian and international health technology assessment agencies^{Footnote 1}. Titles and abstracts of retrieved references were screened using DistillerSR systematic literature review software^{Footnote 2} by two reviewers. Inclusion and exclusion criteria were discussed prior to screening to ensure criteria would be applied consistently, and any discrepancies were resolved through discussion. The full texts of references that were eligible for inclusion after title and abstract screening were retrieved and assessed by the same two reviewers to determine final inclusion/exclusion. A standardized data extraction tool was used to record study characteristics, methods, and findings of included studies. ICERs are presented in 2021 US dollars and were inflated using the Health Care component of Personal Consumption Expenditures where necessary^{Footnote 3}. The Joanna Brigs Institute (JBI) Critical Appraisal Checklist for Economic Evaluations^{Footnote 4} was used to assess the overall quality of included studies. The applicability or transferability of included studies was assessed using Heyland's Generalizability Criteria^{Footnote 5}. No studies were excluded on the basis of these appraisals.
I.1 Description of Included Studies
Four modelbased costutility analyses were identified, all of which were conducted in the United States. Only one study was published in the peerreviewed literature at the time of the search^{Footnote 6}, with the remaining studies identified in a search of the grey literature. Results for three of the economic evaluations were included in a single report to the Advisory Committee on Immunization Practices (ACIP)^{Footnote 7}. To distinguish between these studies, the three economic evaluations from this single report are referred to by the names of the authors of the individual studies^{Footnote 8} ^{Footnote 9} ^{Footnote 10}. A version of one of the studies included in the ACIP report was also described in greater detail in a separate report^{Footnote 11}. Two of the four included studies were industry sponsored^{Footnote 8} ^{Footnote 9}. Two studies used a health system perspective^{Footnote 6} ^{Footnote 9} and two used a societal perspective^{Footnote 8} ^{Footnote 10}. All studies used a 3% discount rate for costs and outcomes, as recommended in the US. Costeffectiveness outcomes were reported as ICERs, presented as the incremental cost per QALY gained. All studies used a lifetime time horizon.
Two studies used Markov models that followed a single age cohort over time^{Footnote 6} ^{Footnote 10} and the other two used multicohort Markov models that followed a population consisting of multiple age cohorts over time^{Footnote 8} ^{Footnote 9}. Although the model structures varied, all used a similar approach to model the risk of PD, generally conceptualized as invasive pneumococcal disease (IPD) or nonbacteremic pneumococcal pneumonia (NBPP) and the potential for longterm sequelae following IPD. Risk of PD was dependent on age, vaccination status, and for some models, presence of immunocompromising conditions (IC) or chronic medical conditions (CMC). None of the models used were dynamic but some did evaluate indirect effects by assuming a reduction in vaccinetype PD incidence over time due to potential use of PNEUC15 or PNEUC20 in pediatric populations^{Footnote 9} ^{Footnote 10}.
The modelbased evaluations compared outcomes, including costs and QALYs, for vaccination strategies using PNEUC15 or PNEUC20 to current US recommendations. At the time the studies were conducted, the US pneumococcal vaccination guidance for adults aged 19 years or older included the following age and riskbased recommendations: PNEUP23 plus optional PNEUC13 under shared clinical decisionmaking for adults aged 65 years or older; PNEUP23 at diagnosis of chronic medical conditions (CMC) if under age 65 years; and PNEUC13 in series with PNEUP23 at diagnosis of IC if under age 65 years^{Footnote 12}. Different age, risk, or combined age and riskbased vaccination strategies were evaluated, which are discussed in turn below. Results are presented for both the health system and societal perspectives, with the perspective used noted in the tables.
I.2 Results of AgeBased Strategies
All four modelbased economic evaluations examined the costeffectiveness of agebased strategies, consisting of different approaches for the use of PNEUC15 or PNEUC20 either alone or in series with PNEUP23 in the population aged 50 or 65 years and older (Table 1).
The use of PNEUC15 alone in the population aged 65 years was evaluated in a single study and was found to have an ICER ranging from $250,434 to 479,494 per QALY gained compared to the current vaccine recommendations in this age group^{Footnote 6}. The ICER was higher when indirect effects of a potential pediatric vaccination program for reducing adult PD were included. There was variability across the three studies that reported results for use of PNEUC15 in series with PNEUP23 at age 65 years. One study estimated that use of PNEUC15 plus PNEUP23 would result in lower costs and improved health outcomes compared to current recommendations (i.e., was the dominant strategy)^{Footnote 10}. The two other studies estimated ICERs ranging from $237,000611,169 per QALY gained^{Footnote 6} ^{Footnote 8}, suggesting that this strategy was unlikely to be considered costeffective under commonly used thresholds.
Three studies evaluated the use of PNEUC20 alone at age 50 years compared to the current agebased recommendations. One study reported variable estimates of potential value, depending on assumptions, ranging from PNEUC20 dominating current recommendations when indirect effects were included, to use of PNEUC20 leading to lower costs and reduced health outcomes when indirect effects were ignored^{Footnote 10}. A second study estimated ICERs ranging from $174,000514,000 per QALY gained^{Footnote 8} and the third study reported an ICER of $18,000 per QALY gained^{Footnote 9}.
Four studies evaluated the use of PNEUC20 alone at age 65 years compared to the current agebased recommendations. Two studies reported PNEUC20 to be the dominant strategy, resulting in lower costs and improved outcomes compared to current recommendations^{Footnote 9} ^{Footnote 10}. In one study that included four scenario analyses, ICERs ranged from dominant to $39,000 per QALY gained^{Footnote 8}. In another study, the ICER estimates ranged from $187,761410,900 per QALY gained^{Footnote 6}.
The single study to evaluate PNEUC20 in series with PNEUP23 at age 65 years showed the strategy was unlikely to be costeffective, with ICERs ranging from $488,716704,702 per QALY gained^{Footnote 6}.
Vaccine  Strategy  Age  Indirect effects included  Smith et al.^{Footnote 6}, health system perspective ICER ($/QALY)  Stoecker et al.^{Footnote 10}, societal perspective ICER ($/QALY)  OwusuEdusei et al.^{Footnote a}^{Footnote 8}, societal perspective ICER ($/QALY)  Weycker et al.^{Footnote 9}, health system perspective ICER ($/QALY) 

PNEUC15  Alone  65  No  250,434^{Footnote b}       
Yes  479,492^{Footnote b}        
PNEUC15  In series with PNEUP23  65  No  490,302^{Footnote b}  Dominant  237,000282,000   
Yes  611,169^{Footnote b}  Dominant      
PNEUC20  Alone  50  No    Lower costs and lower QALYs (5,300,000)  174,000514,000  18,000 
Yes    Dominant      
PNEUC20  Alone  65  No  187,761  Dominant  Dominant to 39,000  Dominant 
Yes  410,900  Dominant      
PNEUC20  In series with PNEUP23  65  No  488,716       
Yes  704,702        

I.3 Results of RiskBased Strategies
Three studies evaluated the costeffectiveness of riskbased strategies in people aged 19 to 49 or 1964 years with IC or CMC, population groups for whom different pneumococcal vaccination recommendations apply in the US, where the studies were conducted (Table 2).
The two studies that evaluated riskbased use of PNEUC15 in series with PNEUP23 in the population aged 1964 years found this strategy unlikely to be costeffective under commonly used thresholds, with ICERs ranging from $250,000656,000 per QALY gained^{Footnote 8} ^{Footnote 10}.
There was variability across the three studies that evaluated the use of PNEUC20 alone for the population aged 1949 years. In scenario analyses, one study reported that the use of PNEUC20 would range from dominating current recommendations to an ICER of $25,000 per QALY gained^{Footnote 8}. The other two studies reported a range from $94,000$483,000 per QALY gained^{Footnote 9} ^{Footnote 10}.
Riskbased use of PNEUC20 in the population aged 1964 years also produced variable results across studies, with one study suggesting that the strategy could be costeffective or dominate current recommendations^{Footnote 9}, and the other two studies estimating ICERs ranging from $58,999$292,000 per QALY gained^{Footnote 8} ^{Footnote 10}. Overall, riskbased use of PNEUC20 was estimated to result in lower ICERs when the strategy was used in the population aged 1964 years compared to its use in the population aged 1949 years.
Vaccine  Strategy  Age  Indirect effects included  Stoecker et al.^{Footnote 10}, societal perspective ICER ($/QALY)  OwusuEdusei et al.^{Footnote a}^{Footnote 8}, societal perspective ICER ($/QALY)  Weycker et al.^{Footnote 9}, health system perspective ICER ($/QALY) 

PNEUC15  In series with PNEUP23  1964  No  656,000^{Footnote b}  250,000312,000   
PNEUC20  Alone  1949  No  483,000^{Footnote c}  94,000273,000  Dominant 
Yes      25,000  
PNEUC20  Alone  1964  No  292,000^{Footnote d}  58,000183,000  Dominant 
N/A  Yes      11,000  

I.4 Results of Combined Age and RiskBased Strategies
Two studies evaluated combined age and riskbased strategies (Table 3). Overall, evaluations that combined age and riskbased strategies tended to result in more favourable ICER estimates compared to riskbased only strategies.
PNEUC15 use in series with PNEUP23 for people with CMC or IC aged 1964 years and at age 65 years for the general population was not likely to be costeffective under commonly used thresholds in the single study that evaluated this strategy (ICER of $338,000 per QALY gained)^{Footnote 10}.
The use of PNEUC20 alone for people aged 1949 years with CMC or IC and the general population at age 50 years resulted in estimates ranging from dominant to $11,000 per QALY gained^{Footnote 9} ^{Footnote 10}. The use of PNEUC20 alone for people aged 1964 years with CMC or IC and the general population at age 65 years was estimated to dominate current recommendations in both studies^{Footnote 9} ^{Footnote 10}. This finding was consistent with the ageonly and riskbased only comparisons, where the interventions appeared more costeffective at age 65 years compared to at 50 years.
Vaccine  Strategy  Age  Indirect effects included  Stoecker et al.^{Footnote 10}, societal perspective ICER ($/QALY)  Weycker et al.^{Footnote 9}, health system perspective ICER ($/QALY) 

PNEUC15  In series with PNEUP23  1964 for people with CMC/IC; 65 for general population  No  338,000   
PNEUC20  Alone  1949 for people with CMC/IC; 50 for general population  No  Dominant  11,000 
PNEUC20  Alone  1964 for people with CMC/IC; 65 for general population  No  Dominant  Dominant 
I.5 Generalizability
Given that all of the studies were conducted in the US, the transferability of the costeffectiveness estimates was assessed. The clinical generalizability, analysis type, costing method, outcome measure method, and use of a preferencebased measure instrument to obtain utility values were aligned with the NACI guidelines for the conduct of economic evaluations in the Canadian setting^{Footnote 13}. The discount rate (3%) was higher than the recommended discount rate of 1.5%.The US vaccination recommendations at the time of the analyses differed from Canadian pneumococcal vaccination recommendations, such that the comparator used in the included analyses may not reflect the Canadian context. For instance, in the US, PNEUP23 plus optional PNEUC13 under shared clinical decisionmaking was recommended for adults aged 65 years or older, while in Canada, populationlevel recommendations were for PNEUP23 for this age group.
I.6 Influential Parameters and Assumptions
Model parameters that were reported to influence the estimated costeffectiveness included: overall effectiveness of the conjugate vaccines; effectiveness of the conjugate vaccines against serotype 3 disease; waning of vaccine effectiveness; incidence of pCAP, and vaccine price. The assumption of declines in vaccinetype disease in the adult population associated with a putative infant vaccination program generally resulted in higher ICERs than scenarios that did not consider these potential indirect effects.
ICER estimates from Smith et al.^{Footnote 6} tended to be higher than in the other models, with results generally less favourable toward to use of PNEUC15 or PNEUC20 relative to current vaccine recommendations. Although reasons for this difference are uncertain, the Smith et al. study differed from the others by not modelling people with IC. It also used less recent data for vaccine serotype coverage and PD incidence^{Footnote 7}. This model, along with that of Weycker et al.^{Footnote 9} used the health system perspective; the use of a narrower perspective (compared to the societal one) that does not account for the full range of benefits associated with vaccination programs may also have contributed to less favourable costeffectiveness estimates.
I.7 Conclusions
A review of the peerreviewed and grey literature identified four costutility studies of PNEUC15 and PNEUC20 compared to current vaccination recommendations. The studies generally found that PNEUC20 use in older adults was associated with increased QALYs, with lower ICERs when the vaccine was used in adults aged 65 years and older compared to programs in adults aged 50 years and older. ICER estimates for PNEUC15 use in series with PNEUP23 at age 65 years showed variability across studies. The estimated impact of adding riskbased programs for younger adults with IC/CMC to an agebased strategy depended on the vaccine product, with more favourable costeffectiveness estimates for PNEUC20 than for PNEUC15 in series PNEUP23.
Costutility Analysis
II.1 Economic Model Description
A costutility model was developed to evaluate the costeffectiveness of PNEUC15 and PNEUC20 vaccines in the Canadian population. The model compared the health and economic outcomes of different vaccination strategies. Summaries of the methods and results are provided below.
The economic analysis incorporated the following considerations: recommended age at vaccination and whether PNEUC15 or PNEUC20 should be used alone or in series with PNEUP23. Given higher rates of PD in circumpolar regions of Canada, separate analyses were conducted for the Northern Territories (Northwest Territories, Yukon, and Nunavut) and the provinces, referred to as "North" and "Rest of Canada" (ROC), respectively. Due to data limitations, the model only evaluated agebased vaccination strategies and did not separately model risk in population groups known to experience higher risk of PD, including people with immunocompromising conditions and chronic medical conditions.
The model followed a single cohort of people aged 50, 65, or 75 years without a history of previous pneumococcal vaccination over their lifetime. The age at model entry was varied to evaluate different possible age recommendations for vaccination. The current Canadian populationlevel recommendation of PNEUP23 use for older adults was compared to PNEUC15 or PNEUC20 alone or in series with PNEUP23. When used in series, the conjugate vaccine was assumed to be given first, followed by PNEUP23 one year later. Vaccine was assumed to be administered on model entry.
People did not have PD on model entry but could develop invasive pneumococcal disease (IPD) or pneumococcal communityacquired pneumonia (pCAP) over their lifetimes (Figure 1). pCAP could be treated outside of the hospital (outpatient) or require hospitalization (inpatient). There was a risk of death associated with PD and mortality from other causes was also modelled^{Footnote 14}. People recovering from IPD (all assumed to require hospitalization) could experience longterm consequences associated with their infection (neurologic or auditory sequelae). Vaccination was assumed to reduce the risk of pneumococcal disease due to serotypes included in the vaccine. The cohort model was static and did not incorporate dynamic feedbacks. It used a lifetime time horizon, a discount rate of 1.5% for costs and outcomes, and assessed costeffectiveness from the health system and societal perspectives. The model was programmed using R 4.0 and the data.table package and used the approach described by Krijkamp et al. (2020)^{Footnote 15} ^{Footnote 16} ^{Footnote 17}.
Model outcomes included cases of IPD and pCAP, deaths due to PD, life years, qualityadjusted life years (QALYs), and costs. QALYs and costs were used to estimate incremental costeffectiveness ratios (ICERs). Model estimates were based on 2,000 simulations with parameters drawn from distributions. Conventional probability distributions were used: beta distributions were used for parameters constrained between zero and one, such as probabilities and utilities; Dirichlet distributions were used for multivariate probabilities, such as the proportion of PD cases attributable to serotype groups; gamma and lognormal distributions were used for parameters constrained to positive values, such as costs and rate ratios. Because multiple vaccine products and strategies were evaluated, sequential analyses were conducted, to determine if certain strategies would result in a more efficient use of resources. For a given age group and geographic region, sequential ICERs were calculated by ordering the strategies by lowest to highest cost and comparing the incremental costs and QALYs gained for a given strategy to the next less costly strategy. In the sequential analysis, strategies could be eliminated because there were other strategies that were projected to result in more QALYs gained at lower costs (i.e., the strategy was dominated) or there was a combination of other strategies that would result in more QALYs gained for lower costs, such that the excluded strategy would never be the optimal intervention, regardless of the costeffectiveness threshold used (i.e., the strategy was subject to extended dominance).
II.2 Model Parameters
Model parameters describing PD epidemiology (Table 4), vaccine characteristics (Table 5), costs (Tables 6 and 7), and health utilities (Table 8) were derived from available data and literature, wherever possible, and by assumption otherwise. Canadian data were used preferentially, when available. In the absence of vaccine effectiveness (VE) data for PNEUC15 and PNEUC20, VE was assumed to be equal to that reported for PNEUC13 but extended to cover additional serotypes not included in PNEUC13. VE for preventing PD caused by serotype 3 was assumed lower than for other serotypes for the conjugate and polysaccharide vaccines^{Footnote 11} ^{Footnote 18}. Protection was assumed to be more durable for the conjugate vaccines than for PNEUP23^{Footnote 10}.
Data on age and regionspecific incidence of IPD were obtained from the International Circumpolar Surveillance program and the Canadian Notifiable Disease Surveillance System^{Footnote 19}. Incidence of communityacquired pneumonia (CAP) was estimated using records of hospitalizations with pneumonia from the Discharge Abstract Database in 20182019. Data from the Serious Outcomes Surveillance (SOS) Network was used to estimate the proportion of hospitalized CAP cases due to S. pneumoniae^{Footnote 20}. The incidence of outpatient pCAP cases was estimated from studies reporting the proportion of CAP cases that are hospitalized^{Footnote 21} ^{Footnote 22} ^{Footnote 23} ^{Footnote 24}. The proportion of PD cases attributable to serotypes contained in the vaccines was obtained from Canadian surveillance data^{Footnote 19} ^{Footnote 20}. Estimates of casefatality^{Footnote 20} ^{Footnote 25} and risk of longterm sequelae^{Footnote 26} ^{Footnote 27} ^{Footnote 28} ^{Footnote 29} ^{Footnote 30} ^{Footnote 31} ^{Footnote 32} ^{Footnote 33} ^{Footnote 34} ^{Footnote 35} were obtained from the literature.
Costs of IPD and hospitalizations with pneumonia were estimated using Resource Intensity Weights obtained from the Discharge Abstract Database (20152019)^{Footnote 36} ^{Footnote 37} ^{Footnote 38} ^{Footnote 39} and the cost of a standard hospital stay^{Footnote 40}. Costs of outpatient pneumonia were assumed to comprise either a physician office visit or an emergency department visit. Costs of longterm sequelae were based on costs of auditory or neurologic complications of bacterial meningitis^{Footnote 41}. Vaccination costs included administration costs^{Footnote 42} and vaccine price. The prices of PNEUP23 and PNEUC13 were based on contract prices communicated in confidence by PHAC Vaccine Supply and Assurance. Prices for PNEUC15 and PNEUC20 were based on the relative US incremental prices of these vaccines compared to PNEUC13^{Footnote 43}. Based on the US data, the incremental price for PNEUC20 was higher than that for PNEUC15. For the societal perspective, costs included productivity loss due to illness, caregiver costs, and outofpocket medical costs. Productivity loss was estimated using the human capital method.
Agespecific utilities for the Canadian general population were based on EQ5D5L index scores of residents from Alberta, Canada^{Footnote 44}. Utilities of IPD, pCAP, and longterm sequelae were derived by applying utility multipliers for each condition^{Footnote 45} ^{Footnote 46} ^{Footnote 47} ^{Footnote 48} ^{Footnote 49} ^{Footnote 50} against utility norms for the general population.
Parameter  Base  Range  Reference 

IPD incidence (per 100,000)  
5064 years 


Northern Canada  38.97  23.10 – 58.93  
Rest of Canada  14.45  13.83 – 15.09  
6574 years  
Northern Canada  71.30  34.20 – 121.79  
Rest of Canada  20.61  19.52 – 21.72  
75+ years  
Northern Canada  105.01  38.55 – 204.12  
Rest of Canada  31.06  29.51 – 32.65  
CAP (inpatient) incidence (per 100,000)  
5064 years  DAD 20182019^{Footnote 39}  
Northern Canada  568.81  502.43 – 639.22  
Rest of Canada  347.81  344.46 – 351.17  
6574 years  
Northern Canada  1777.32  1568.36 – 1998.91  
Rest of Canada  871.48  863.81 – 879.20  
75+ years  
Northern Canada  5104.13  4555.27 – 5682.02  
Rest of Canada  2845.89  2829.84 – 2861.97  
Proportion of CAP cases attributed to S. pneumoniae (%)  
5064 years  19.4  17.4 – 21.6  LeBlanc et al 2022^{Footnote 20} 
6574 years  13.9  12.1 – 15.8  
75+ years  9.5  8.3 – 10.7  
Odds CAP case managed in outpatient setting  
5064 years  2.6  0.8 – 6.5 

6574 years  1.2  0.5 – 2.5  
75+ years  1.0  0.4 – 2.1  
Vaccinetype serotype distribution (%)  
5064 years  National Microbiology Laboratory 2019^{Footnote 19}  
ST3  11.5  9.6 – 13.5  
PNEUC13/nonST3  21.3  18.8 – 23.8  
PNEUC15/nonPNEUC13  12.2  10.3 – 14.3  
PNEUC20/nonPNEUC15  19.2  16.9 – 21.7  
PNEUP23/nonPNEUC20  15.7  13.5 – 18.0  
NVT  20.1  17.7 – 22.6  
65+ years  
ST3  13.2  11.6 – 15.0  
PNEUC13/nonST3  16.0  14.2 – 17.9  
PNEUC15/nonPNEUC13  15.4  13.6 – 17.3  
PNEUC20/nonPNEUC15  13.5  11.8 – 15.3  
PNEUP23/nonPNEUC20  10.1  8.6 – 11.7  
NVT  31.7  29.3 – 34.1  
Proportion of IPD survivors with longterm sequelae (%)  
Auditory sequelae  2.1  1.8 – 2.5 

Neurologic sequelae  1.9  1.6 – 2.2  
Case fatality (%)  
IPD  
5064 years  10.9  9.9 – 12.0  Wijayasri 2019^{Footnote 25} 
65+ years  17.2  16.2 – 18.3  
pCAP (inpatient)  
5064 years  4.8  2.9 – 7.1  LeBlanc et al 2022^{Footnote 20} 
65+ years  9.9  7.7 – 12.3  

Parameter  Base  Range  Reference 

Vaccination coverage (%)  
5064 years  48.3  43.7 – 53.0  Used same value as 6574 years 
6574 years  48.3  43.7 – 53.0  Seasonal Flu Survey 2021^{Footnote 51} 
75+ years  65.4  59.6 – 71.2  Seasonal Flu Survey 2021^{Footnote 51} 
PNEUC effectiveness at age 65 (%)  
VTIPD  60.0  34.0 – 76.0  Assumption based on Farrar et al 2021 and Bonten et al 2015^{Footnote 52} ^{Footnote 53} 
ST3IPD  26.0  0 – 53.4  Stoecker 2020 ^{Footnote 11} 
VTCAP  45.0  14.0 – 65.0  Assumption based on Childs et al 2021 and Bonten et al 2015^{Footnote 53} ^{Footnote 54} 
ST3CAP  15.6  0 – 22.7  Stoecker 2020^{Footnote 11} 
PNEUP23 effectiveness at age 65 (%)  
VTIPD  47.0  32.0 – 63.0  Djennad et al 2018^{Footnote 18} 
ST3IPD  2.0  0 – 21.0  Djennad et al 2018^{Footnote 18} 
VTCAP  20.0  0 – 40.0  Lawrence et al 2020^{Footnote 55} 
ST3CAP  2.0  0 – 21.0  Assumption of similar effect used for ST3IPD 
Vaccine effectiveness at age 50  1.1 x effectiveness at age 65  N/A  Assumption 
Vaccine effectiveness at age 75  0.9 x effectiveness at age 65  N/A  Assumption 
Duration of protection  
PNEUC  15 years: stable for 5 years, linear decline to 0 over 10 years  12 years: stable for 5 years, linear decline to 0 over 7 years  Stoecker 2020^{Footnote 10} 
PNEUP23  15 years: linear decline to 0 over 15 years  7 years: linear decline to 0 over 7 years  

Parameter  Base  Range  Reference 

Cost of vaccine administration  16.77  12.58 – 20.96  NACI 2018^{Footnote 42} 
Cost per IPD case  
5064 years  29,146  27,363 – 30,984  DAD 20152019^{Footnote 36} ^{Footnote 37} ^{Footnote 38} ^{Footnote 39} 
6574 years  28,955  26,727 – 31,271  
75+ years  21,501  20,001 – 23,054  
Cost per inpatient CAP case  
5064 years  DAD 20152019^{Footnote 36} ^{Footnote 37} ^{Footnote 38} ^{Footnote 39}  
Northern Canada  11,725  10,575 – 12,933  
ROC  9,813  9,730 – 9,897  
6574 years  
Northern Canada  10,297  9,466 – 11,163  
ROC  9,992  9,910 – 10,074  
75+ years  
Northern Canada  12,200  11,143 – 13,304  
ROC  10,043  9,997 – 10,089  
Cost per outpatient CAP case  
5064 years  109.58  82.19 – 136.98^{Footnote *} 

65+ years  125.84  94.38 – 157.30 

Outofpocket medication costs (<65 years)  18.06  13.55 – 22.58^{Footnote *}  Ontario Drug Benefit^{Footnote 60} 
Annual cost of care for those with auditory sequelae  2,783.33  2,087.50 – 3,479.16^{Footnote *}  Christensen 2014^{Footnote 41} 
Annual cost of care for those with neurologic sequelae  9,262.42  6946.82 – 11,578.03^{Footnote *}  
Cost of transportation to inpatient care  
Northern Canada  7,573  3,001 – 12,189^{Footnote *} 

ROC  396  199 – 592^{Footnote *} 

Cost of transportation to outpatient care  
Northern Canada  122  91 – 152^{Footnote *} 

ROC  0  N/A  Assumed to be outofpocket 
Daily cost of travel subsidy for overnight stay  
Northern Canada  155  78 – 310^{Footnote *}  Government of Yukon^{Footnote 71} 
ROC  0  N/A  N/A 

Parameter 
Base  Range  Reference 

Productivity loss  
Hospitalization  
5064 years  3,237  2,427 – 4,046^{Footnote *} 

65+ years  338  254 – 423^{Footnote *}  
Outpatient (CAP)  
5064 years  965  724 – 1,206^{Footnote *} 

65+ years  101  76 – 126^{Footnote *}  
Auditory sequelae (annual)  
5064 years  19,004  14,253 – 23,755^{Footnote *} 

65+ years  1,983  1,487 – 2,479^{Footnote *}  
Neurologic sequelae (annual)  
5064 years  54,228  40,671 – 67,785^{Footnote *} 

65+ years  5,660  4,245 – 7,075^{Footnote *}  
Cost of caregiver support  
Recovering inpatient  1,233  925 – 1,541^{Footnote *} 

Recovering outpatient  0  N/A  Assumption 
Neurologic sequelae  60,048  45,036 – 75,060^{Footnote *} 


Parameter  Base  Range  Reference 

Hospitalization  0.8659  0.8323 – 0.8963  Mangen et al 2017^{Footnote 45} 
Outpatient pCAP*  0.9938  0.9917 – 0.9956 

Auditory sequelae  0.6850  0.6214 – 0.7451  Galante et al 2011^{Footnote 50} 
Neurologic sequelae  0.3441  0.2725 – 0.4164  Galante et al 2011^{Footnote 50} 
II.3 Base Case
Health outcomes, compared to projected outcomes with use of PNEUP23 in the population, are displayed graphically in Figure 2 by cohort age and region. For all age cohorts and geographic regions, use of PNEUC20, alone or in series with PNEUP23 and use of PNEUC15 in series with PNEUP23, were projected to avert cases of IPD, pCAP, as well as pneumococcalattributable hospitalizations and deaths, compared to continued use of PNEUP23. In the age 50 cohort, use of PNEUC15 alone was projected to result in more cases of IPD than use of PNEUP23. For all other ages and outcomes, PNEUC15 was projected to result in fewer cases of IPD, pCAP, hospitalizations, and deaths compared to PNEUP23.
Figure 2  Text description
Figure two is a multipanel bar graph that shows averted health outcomes per 100,000 population. The figure is arranged in three rows and each row has four graphs. Each row shows results for a different age cohort. The top row shows results for the age 50 cohort, the middle row for the age 65 cohort and the bottom row for the age 75 cohort. The four graphs for each row are labelled "IPD", "pCAP", "Hospitalization" and "Death". For each graph, the xaxis is labelled "Mean lifetime outcomes averted per 100,000 population (compared to PNEUP23). The numeric scale of the xaxis varies across the row for the different outcomes, with maximum values of 30 for IPD, 300 for pCAP, 200 for hospitalization, and 20 for death. The yaxis is labelled with the names of the vaccination strategies: "PNEUC15", "PNEUC20", "PNEUC15 + PNEUP23", and "PNEUC20 + PNEUP23". For each strategy on the yaxis there are two bars, a blue one for Northern Canada and a yellow one for Rest of Canada. For the rows displaying the age 50 and age 65 years cohorts, the bars for the number of health events averted are longer for Northern Canada than Rest of Canada, indicating that more health outcomes are averted in this population group. For the age 75 cohort, except for IPD cases, there are more cases averted for the rest of Canada compared to Northern Canada. All of the values on the graph are positive except for the graph showing IPD cases averted in the age 50 years cohort using PNEUC15, which has small negative values, indicating fewer IPD cases occur when using PNEUP23. For all age cohorts and geographic regions, the rates of health outcomes averted are lowest for PNEUC15 and highest for PNEUC20 + PNEUP23. There is some variability for PNEUC20 and PNEUC15+PNEUP23 but in general, the rates of averted outcomes are similar.
Outcome  Strategy  Mean lifetime outcomes averted per 100,000 population 

IPD  PNEUC15  1.71825 
IPD  PNEUC20  17.93882 
IPD  PNEUC15 + PNEUP23  21.99199 
IPD  PNEUC20 + PNEUP23  29.06004 
pCAP  PNEUC15  111.5491 
pCAP  PNEUC20  260.824 
pCAP  PNEUC15 + PNEUP23  214.6381 
pCAP  PNEUC20 + PNEUP23  309.6834 
Hospitalization  PNEUC15  28.53096 
Hospitalization  PNEUC20  89.20836 
Hospitalization  PNEUC15 + PNEUP23  81.0254 
Hospitalization  PNEUC20 + PNEUP23  114.0592 
Death  PNEUC15  1.27263 
Death  PNEUC20  5.397521 
Death  PNEUC15 + PNEUP23  5.312283 
Death  PNEUC20 + PNEUP23  7.330628 
Outcome  Strategy  Mean lifetime outcomes averted per 100,000 population 

IPD  PNEUC15  0.64397 
IPD  PNEUC20  7.549912 
IPD  PNEUC15 + PNEUP23  9.343773 
IPD  PNEUC20 + PNEUP23  12.26972 
pCAP  PNEUC15  78.89242 
pCAP  PNEUC20  182.3706 
pCAP  PNEUC15 + PNEUP23  150.6069 
pCAP  PNEUC20 + PNEUP23  216.7382 
Hospitalization  PNEUC15  20.76439 
Hospitalization  PNEUC20  56.97985 
Hospitalization  PNEUC15 + PNEUP23  50.25161 
Hospitalization  PNEUC20 + PNEUP23  71.10063 
Death  PNEUC15  0.950296 
Death  PNEUC20  3.190357 
Death  PNEUC15 + PNEUP23  3.025681 
Death  PNEUC20 + PNEUP23  4.198087 
Outcome  Strategy  Mean lifetime outcomes averted per 100,000 population 

IPD  PNEUC15  4.897155 
IPD  PNEUC20  22.06517 
IPD  PNEUC15 + PNEUP23  24.90282 
IPD  PNEUC20 + PNEUP23  30.94968 
pCAP  PNEUC15  119.8787 
pCAP  PNEUC20  217.1269 
pCAP  PNEUC15 + PNEUP23  185.7728 
pCAP  PNEUC20 + PNEUP23  247.1149 
Hospitalization  PNEUC15  59.21648 
Hospitalization  PNEUC20  120.5447 
Hospitalization  PNEUC15 + PNEUP23  109.21 
Hospitalization  PNEUC20 + PNEUP23  143.0488 
Death  PNEUC15  6.206004 
Death  PNEUC20  13.5131 
Death  PNEUC15 + PNEUP23  12.60291 
Death  PNEUC20 + PNEUP23  16.38384 
Outcome  Strategy  Mean lifetime outcomes averted per 100,000 population 

IPD  PNEUC15  2.75027 
IPD  PNEUC20  10.16716 
IPD  PNEUC15 + PNEUP23  11.57536 
IPD  PNEUC20 + PNEUP23  14.20708 
pCAP  PNEUC15  100.2026 
pCAP  PNEUC20  176.5893 
pCAP  PNEUC15 + PNEUP23  152.5603 
pCAP  PNEUC20 + PNEUP23  201.1869 
Hospitalization  PNEUC15  48.79631 
Hospitalization  PNEUC20  91.27524 
Hospitalization  PNEUC15 + PNEUP23  81.75827 
Hospitalization  PNEUC20 + PNEUP23  106.6863 
Death  PNEUC15  4.980975 
Death  PNEUC20  9.702638 
Death  PNEUC15 + PNEUP23  8.881972 
Death  PNEUC20 + PNEUP23  11.5212 
Outcome  Strategy  Mean lifetime outcomes averted per 100,000 population 

IPD  PNEUC15  2.40475 
IPD  PNEUC20  21.21687 
IPD  PNEUC15 + PNEUP23  25.10092 
IPD  PNEUC20 + PNEUP23  31.30868 
pCAP  PNEUC15  139.4398 
pCAP  PNEUC20  261.0044 
pCAP  PNEUC15 + PNEUP23  224.0451 
pCAP  PNEUC20 + PNEUP23  299.4194 
Hospitalization  PNEUC15  71.49773 
Hospitalization  PNEUC20  150.7938 
Hospitalization  PNEUC15 + PNEUP23  136.4431 
Hospitalization  PNEUC20 + PNEUP23  180.0896 
Death  PNEUC15  7.235044 
Death  PNEUC20  16.43263 
Death  PNEUC15 + PNEUP23  15.30166 
Death  PNEUC20 + PNEUP23  20.06082 
Outcome  Strategy  Mean lifetime outcomes averted per 100,000 population 

IPD  PNEUC15  3.895045 
IPD  PNEUC20  15.52716 
IPD  PNEUC15 + PNEUP23  17.56409 
IPD  PNEUC20 + PNEUP23  21.69746 
pCAP  PNEUC15  187.6316 
pCAP  PNEUC20  333.7505 
pCAP  PNEUC15 + PNEUP23  285.8358 
pCAP  PNEUC20 + PNEUP23  379.074 
Hospitalization  PNEUC15  98.20861 
Hospitalization  PNEUC20  183.3103 
Hospitalization  PNEUC15 + PNEUP23  161.2181 
Hospitalization  PNEUC20 + PNEUP23  212.2464 
Death  PNEUC15  9.899365 
Death  PNEUC20  19.11666 
Death  PNEUC15 + PNEUP23  17.11785 
Death  PNEUC20 + PNEUP23  22.42586 
Outcomes are summed across the lifespan of the individuals in the indicated age cohort for the different vaccination strategies and compared to rates in a cohort vaccinated with PNEUP23. Results are shown separately for the North and rest of Canada. For the vaccinate at age 50 strategy, use of PNEUC15 was projected to result in more IPD cases than current recommendations (outlined in red). Note that the xaxes vary across graphs.
Unless noted otherwise, results are presented for the health system perspective. Mean costs, QALYs, and ICERs from the base case health system perspective are presented in Table 9. Incremental costeffectiveness ratios show the costs per QALY gained when comparing each vaccination strategy directly to current recommendations (PNEUP23). The sequential ICERs compare all of the different possible vaccination strategies for a given age cohort and geographic region, excluding those that are either dominated or subject to extended dominance. In the sequential analysis, strategies that, when compared to the current recommendation only, may have ICERs considered costeffective by commonly used thresholds, may be excluded because there are other strategies that represent better value for money, regardless of the costeffectiveness threshold used. For instance, for the rest of Canada, the ICER for vaccinating at age 65 with PNEUC15 compared to PNEUP23 is $34,852 per QALY gained. However, compared to PNEUC20 use in the same population, PNEUC15 is dominated, because it is more costly and results in fewer QALYs gained than PNEUC20. If PNEUC20 is available, it would be the preferred option based on the parameters and assumptions used for this analysis.
Mean costs and QALYs are also displayed graphically in Figure 3 by cohort age, region, and perspective. Across cohort ages, regions, and perspective, the efficiency frontier consisted of PNEUP23 and PNEUC20 (either alone or in series with PNEUP23). ICERs ranging from $6,529 to $113,514 per QALY from the health system perspective. ICERs were higher in younger age cohorts due to lower risk of disease and waning vaccine protection as risk increased with age. ICERs were generally lower in Northern Canada due to the higher burden of disease and higher costs associated with illness. Higher ICERs in the Northern Canada age 75 years cohort were likely due to lower life expectancy in this region.
Strategy  Cost (per 100,000) ($)  QALYs (per 100,000)  Sequential ICER ($/QALY)  ICER (vs PNEUP23) ($/QALY) 

Vaccinate at age 50 years, ROC  
PNEUP23  50,484,326  2,077,705  N/A  N/A 
PNEUC20  52,597,378  2,077,765  35,619  35,619 
PNEUC20 + PNEUP23  54,143,528  2,077,784  81,866  46,787 
PNEUC15  52,591,732  2,077,722  Subject to extended dominance between PNEUP23 and PNEUC20  127,065 
PNEUC15 + PNEUP23  53,877,523  2,077,762  Dominated by PNEUC20  60,515 
Vaccinate at age 50 years, Northern Canada  
PNEUP23  61,632,445  1,115,424  N/A  N/A 
PNEUC20  62,514,745  1,115,478  16,300  16,300 
PNEUC20 + PNEUP23  63,619,038  1,115,498  57,003  27,028 
PNEUC15  63,439,141  1,115,436  Dominated by PNEUC20  153,970 
PNEUC15 + PNEUP23  63,818,745  1,115,477  Dominated by PNEUC20  41,367 
Vaccinate at age 65 years, ROC  
PNEUP23  46,833,041  1,369,927  N/A  N/A 
PNEUC20  48,602,290  1,370,029  17,379  17,379 
PNEUC20 + PNEUP23  50,151,922  1,370,049  80,344  27,409 
PNEUC15  48,613,991  1,369,979  Dominated by PNEUC20  34,852 
PNEUC15 + PNEUP23  49,909,479  1,370,020  Dominated by PNEUC20  33,077 
Vaccinate at age 65 years, Northern Canada  
PNEUP23  52,151,455  552,531  N/A  N/A 
PNEUC20  52,563,675  552,594  6,529  6,529 
PNEUC20 + PNEUP23  53,667,380  552,608  79,986  19,704 
PNEUC15  53,367,564  552,559  Dominated by PNEUC20  43,038 
PNEUC15 + PNEUP23  53,815,043  552,590  Dominated by PNEUC20  28,178 
Vaccinate at age 75 years, ROC  
PNEUP23  39,732,906  907,517  N/A  N/A 
PNEUC20  41,603,714  907,652  13,854  13,854 
PNEUC20 + PNEUP23  43,602,551  907,676  83,788  24,353 
PNEUC15  41,848,301  907,586  Dominated by PNEUC20  30,817 
PNEUC15 + PNEUP23  43,428,274  907,638  Dominated by PNEUC20  30,551 
Vaccinate at age 75 years, Northern Canada  
PNEUP23  44,082,577  295,298  N/A  N/A 
PNEUC20  44,871,091  295,348  15,757  15,757 
PNEUC20 + PNEUP23  46,136,622  295,359  113,514  33,567 
PNEUC15  45,820,090  295,320  Dominated by PNEUC20  79,463 
PNEUC15 + PNEUP23  46,299,566  295,344  Dominated by PNEUC20  47,582 
Figure 3  Text description
Figure 3 is a multipanel figure showing mean costs and QALYs for different vaccination strategies, with results separated by age cohort, region, and perspective. The figure consists of 6 scatter plots arranged in two rows and three columns. Each graph shows results for an age cohort (50, 65, or 75 years) and geographic region (Rest of Canada or Northern Canada). The xaxis is labelled "Total QALYs (per capita)" and the yaxis is labelled "Total costs (per capita)". The scales for the x and yaxis are different across the graphs. There are symbols on the graphs that represent the total QALYs and total costs for a specified vaccination strategy. The vaccination strategies are: PNEUP23 (red), PNEUC15 (yellow), PNEUC20 (green), PNEUC15+PNEUP23 (blue), and PNEUC20+PNEUP23 (purple).There are two symbols representing the health system perspective (triangle) and societal perspective (square). The total costs are higher for the societal perspective than the health system perspective. There are solid lines connecting some of the symbols on the graph. The line is known as the efficiency frontier and the symbols on the efficiency frontier have numbers associated with them, representing the incremental costeffectiveness ratios. In all of the graphs, the efficiency frontier includes PNEUP23, PNEUC20, and PNEUC20+PNEUP23. PNEUC15 and PNEUC20+PNEUP23 are not on the efficiency frontier. The values of the incremental costeffectiveness ratios are provided in Table 9 for the health system perspective.
Perspective  Strategy  Total costs (per capita)  Total QALYs (per capita)  ICER  Sequential ICER 

Health system  PNEUP23  504.84  20.77705  0  0 
Health system  PNEUC20  525.97  20.77765  35618.87  35618.87 
Health system  PNEUC20 + PNEUP23  541.44  20.77784  46786.72  81866.14 
Health system  PNEUC15  525.92  20.77722  127064.8  Weakly dominated 
Health system  PNEUC15 + PNEUP23  538.78  20.77762  60515.2  Dominated 
Societal  PNEUP23  734.32  20.77705  0  0 
Societal  PNEUC20  751.07  20.77765  28232.13  28232.13 
Societal  PNEUC20 + PNEUP23  838.41  20.77784  133096.7  462487.8 
Societal  PNEUC15  754.62  20.77722  122418.8  Dominated 
Societal  PNEUC15 + PNEUP23  837.43  20.77762  183888.4  Dominated 
Perspective  Strategy  Total costs (per capita)  Total QALYs (per capita)  ICER  Sequential ICER 

Health system  PNEUP23  468.33  13.69927  0  0 
Health system  PNEUC20  486.02  13.70029  17379.41  17379.41 
Health system  PNEUC20 + PNEUP23  501.52  13.70049  27408.62  80343.78 
Health system  PNEUC15  486.14  13.69979  34852.38  Dominated 
Health system  PNEUC15 + PNEUP23  499.09  13.70020  33077.01  Dominated 
Societal  PNEUP23  568.23  13.69927  0  0 
Societal  PNEUC20  583.69  13.70029  15180.3  15180.3 
Societal  PNEUC20 + PNEUP23  609.45  13.70049  34040.85  133588.7 
Societal  PNEUC15  585.14  13.69979  33082.75  Dominated 
Societal  PNEUC15 + PNEUP23  607.64  13.70020  42364.2  Dominated 
Perspective  Strategy  Total costs (per capita)  Total QALYs (per capita)  ICER  Sequential ICER 

Health system  PNEUP23  397.33  9.07517  0  0 
Health system  PNEUC20  416.04  9.07652  13853.65  13853.65 
Health system  PNEUC20 + PNEUP23  436.03  9.07676  24353.21  83787.72 
Health system  PNEUC15  418.48  9.07586  30816.98  Dominated 
Health system  PNEUC15 + PNEUP23  434.28  9.07638  30550.64  Dominated 
Societal  PNEUP23  474.48  9.07517  0  0 
Societal  PNEUC20  489.73  9.07652  11295.77  11295.77 
Societal  PNEUC20 + PNEUP23  519.81  9.07676  28527.96  126073.7 
Societal  PNEUC15  494.09  9.07586  28573.77  Dominated 
Societal  PNEUC15 + PNEUP23  519.03  9.07638  36829.13  Dominated 
Perspective  Strategy  Total costs (per capita)  Total QALYs (per capita)  ICER  Sequential ICER 

Health system  PNEUP23  616.32  11.15424  0  0 
Health system  PNEUC20  625.15  11.15478  16299.63  16299.63 
Health system  PNEUC20 + PNEUP23  636.19  11.15498  27027.56  57003.37 
Health system  PNEUC15  634.39  11.15436  153969.7  Dominated 
Health system  PNEUC15 + PNEUP23  638.19  11.15477  41367.37  Dominated 
Societal  PNEUP23  843.42  11.15424  0  0 
Societal  PNEUC20  845.40  11.15478  3668.979  3668.979 
Societal  PNEUC20 + PNEUP23  927.35  11.15498  114188  422998.3 
Societal  PNEUC15  860.37  11.15436  144467.5  Dominated 
Societal  PNEUC15 + PNEUP23  931.99  11.15477  167588.6  Dominated 
Perspective  Strategy  Total costs (per capita)  Total QALYs (per capita)  ICER  Sequential ICER 

Health system  PNEUP23  521.51  5.52531  0  0 
Health system  PNEUC20  525.64  5.52594  6528.941  6528.941 
Health system  PNEUC20 + PNEUP23  536.67  5.52608  19703.73  79986.27 
Health system  PNEUC15  533.68  5.52559  43038.09  Dominated 
Health system  PNEUC15 + PNEUP23  538.15  5.52590  28178.42  Dominated 
Societal  PNEUP23  589.83  5.52531  0  0 
Societal  PNEUC20  591.21  5.52594  2190.275  2190.275 
Societal  PNEUC20 + PNEUP23  612.41  5.52608  29351.2  153628.7 
Societal  PNEUC15  600.89  5.52559  39141.45  Dominated 
Societal  PNEUC15 + PNEUP23  614.66  5.52590  42058.08  Dominated 
Perspective  Strategy  Total costs (per capita)  Total QALYs (per capita)  ICER  Sequential ICER 

Health system  PNEUP23  440.83  2.95298  0  0 
Health system  PNEUC20  448.71  2.95348  15756.56  15756.56 
Health system  PNEUC20 + PNEUP23  461.37  2.95359  33567.12  113514 
Health system  PNEUC15  458.20  2.95320  79463.2  Dominated 
Health system  PNEUC15 + PNEUP23  463.00  2.95344  47582.26  Dominated 
Societal  PNEUP23  492.23  2.95298  0  0 
Societal  PNEUC20  497.26  2.95348  10046.29  10046.29 
Societal  PNEUC20 + PNEUP23  520.09  2.95359  45527.47  204793.1 
Societal  PNEUC15  508.42  2.95320  74040.71  Dominated 
Societal  PNEUC15 + PNEUP23  522.55  2.95344  65077.3  Dominated 
Each plot shows the efficiency frontier from the health system perspective (▲) and the societal perspective (■). The efficiency frontier is marked by a solid line connecting the set of potentially costeffective strategies, depending on the costeffectiveness threshold value. ICERs are labelled below each strategy on the efficiency frontier and are represented by the slope of the line connecting the strategy with the next most effective strategy on the frontier. Strategies that are not on the efficiency frontier are not considered costeffective at any threshold value and for this reason, ICERs are not shown. Note that the scales for the x and yaxes vary across graphs.
Figure 4 displays the proportion of simulations for which each strategy was the optimal strategy over a range of costeffectiveness threshold values. In Northern Canada, PNEUC20 was the optimal strategy in greater than 50% of simulations at threshold ranges of $16,70058,800, $7,40087,100, and $16,600125,600, in the age 50, 65, and 75 years cohorts, respectively. In ROC, PNEUC20 was the optimal strategy in greater than 50% of simulations at threshold ranges of $36,00085,100, $17,40087,900, and $14,10093,100, in the age 50, 65, and 75 years cohorts, respectively. In Northern Canada, PNEUC20 in series with PNEUP23 was the optimal strategy in the majority of simulations at thresholds above $67,100 (age 50 years), $92,800 (age 65 years), and $141,000 (age 75 years). In ROC, PNEUC20 in series with PNEUP23 was the optimal strategy in the majority of simulations at thresholds above $92,800 (age 50 years), $90,700 (age 65 years), and $97,100 (age 75 years). PNEUC15 did not appear as the optimal strategy in any of the simulations. PNEUC15 in series with PNEUP23 was the optimal strategy in <12% of simulations and at thresholds >$100,000 per QALY gained.
Results are shown for each age cohort and geographic region.
Figure 4  Text description
Figure 4 is a multipanel line graph. There are two rows. The top row shows results for the rest of Canada and the bottom row for Northern Canada. The columns show results for the age 50 years, 65 years, and 75 years cohorts. The xaxis is labelled "Costeffectiveness threshold, Canadian dollars per QALY gained" and the scale ranges from 0 to 200,000. The yaxis is labelled "Percent of simulations each strategy is optimal" and ranges from 0 to 100. Lines on the graph are colored by vaccination strategy: PNEUP23 (red), PNEUC15 (yellow), PNEUC20 (green); PNEUC15+PNEUP23 (blue); and PNEUC20+PNEUP23 (purple) and show percent of simulations that a given strategy is optimal for a given costeffectiveness threshold. At low threshold values, PNEUP23 has the highest values for percent of simulations that it is the optimal strategy. At threshold values in the $20,000 to $100,000 range, PNEUC20 is most frequently the strategy with the highest values for percent of simulations for which it is the optimal strategy. Above the $100,000 to $150,000 threshold, PNEUC20+PNEUP23 is most frequently the optimal strategy. The precise values vary across age cohorts and regions.
Costeffectiveness threshold ($ per QALY gained)  Strategy  % of simulations each strategy is optimal 

0  PNEUP23  100% 
10000  PNEUP23  100% 
20000  PNEUP23  85% 
30000  PNEUP23  62% 
40000  PNEUP23  43% 
50000  PNEUP23  32% 
60000  PNEUP23  23% 
70000  PNEUP23  17% 
80000  PNEUP23  12% 
90000  PNEUP23  9% 
100000  PNEUP23  7% 
110000  PNEUP23  5% 
120000  PNEUP23  4% 
130000  PNEUP23  3% 
140000  PNEUP23  2% 
150000  PNEUP23  1% 
160000  PNEUP23  1% 
170000  PNEUP23  1% 
180000  PNEUP23  1% 
190000  PNEUP23  0% 
200000  PNEUP23  0% 
0  PNEUC15  0% 
10000  PNEUC15  0% 
20000  PNEUC15  0% 
30000  PNEUC15  0% 
40000  PNEUC15  0% 
50000  PNEUC15  0% 
60000  PNEUC15  0% 
70000  PNEUC15  0% 
80000  PNEUC15  0% 
90000  PNEUC15  0% 
100000  PNEUC15  0% 
110000  PNEUC15  0% 
120000  PNEUC15  0% 
130000  PNEUC15  0% 
140000  PNEUC15  0% 
150000  PNEUC15  0% 
160000  PNEUC15  0% 
170000  PNEUC15  0% 
180000  PNEUC15  0% 
190000  PNEUC15  0% 
200000  PNEUC15  0% 
0  PNEUC20  0% 
10000  PNEUC20  1% 
20000  PNEUC20  15% 
30000  PNEUC20  38% 
40000  PNEUC20  57% 
50000  PNEUC20  67% 
60000  PNEUC20  71% 
70000  PNEUC20  66% 
80000  PNEUC20  57% 
90000  PNEUC20  45% 
100000  PNEUC20  33% 
110000  PNEUC20  22% 
120000  PNEUC20  14% 
130000  PNEUC20  9% 
140000  PNEUC20  6% 
150000  PNEUC20  4% 
160000  PNEUC20  2% 
170000  PNEUC20  1% 
180000  PNEUC20  1% 
190000  PNEUC20  0% 
200000  PNEUC20  0% 
0  PNEUC15 + PNEUP23  0% 
10000  PNEUC15 + PNEUP23  0% 
20000  PNEUC15 + PNEUP23  0% 
30000  PNEUC15 + PNEUP23  0% 
40000  PNEUC15 + PNEUP23  0% 
50000  PNEUC15 + PNEUP23  0% 
60000  PNEUC15 + PNEUP23  0% 
70000  PNEUC15 + PNEUP23  0% 
80000  PNEUC15 + PNEUP23  0% 
90000  PNEUC15 + PNEUP23  0% 
100000  PNEUC15 + PNEUP23  0% 
110000  PNEUC15 + PNEUP23  0% 
120000  PNEUC15 + PNEUP23  0% 
130000  PNEUC15 + PNEUP23  0% 
140000  PNEUC15 + PNEUP23  0% 
150000  PNEUC15 + PNEUP23  0% 
160000  PNEUC15 + PNEUP23  0% 
170000  PNEUC15 + PNEUP23  1% 
180000  PNEUC15 + PNEUP23  1% 
190000  PNEUC15 + PNEUP23  1% 
200000  PNEUC15 + PNEUP23  1% 
0  PNEUC20 + PNEUP23  0% 
10000  PNEUC20 + PNEUP23  0% 
20000  PNEUC20 + PNEUP23  0% 
30000  PNEUC20 + PNEUP23  0% 
40000  PNEUC20 + PNEUP23  0% 
50000  PNEUC20 + PNEUP23  1% 
60000  PNEUC20 + PNEUP23  6% 
70000  PNEUC20 + PNEUP23  17% 
80000  PNEUC20 + PNEUP23  31% 
90000  PNEUC20 + PNEUP23  47% 
100000  PNEUC20 + PNEUP23  61% 
110000  PNEUC20 + PNEUP23  73% 
120000  PNEUC20 + PNEUP23  82% 
130000  PNEUC20 + PNEUP23  88% 
140000  PNEUC20 + PNEUP23  92% 
150000  PNEUC20 + PNEUP23  94% 
160000  PNEUC20 + PNEUP23  96% 
170000  PNEUC20 + PNEUP23  97% 
180000  PNEUC20 + PNEUP23  98% 
190000  PNEUC20 + PNEUP23  99% 
200000  PNEUC20 + PNEUP23  99% 
Outcome  Strategy  Mean lifetime outcomes averted per 100,000 population 

0  PNEUP23  100% 
10000  PNEUP23  81% 
20000  PNEUP23  42% 
30000  PNEUP23  23% 
40000  PNEUP23  15% 
50000  PNEUP23  10% 
60000  PNEUP23  7% 
70000  PNEUP23  5% 
80000  PNEUP23  3% 
90000  PNEUP23  2% 
100000  PNEUP23  1% 
110000  PNEUP23  1% 
120000  PNEUP23  0% 
130000  PNEUP23  0% 
140000  PNEUP23  0% 
150000  PNEUP23  0% 
160000  PNEUP23  0% 
170000  PNEUP23  0% 
180000  PNEUP23  0% 
190000  PNEUP23  0% 
200000  PNEUP23  0% 
0  PNEUC15  0% 
10000  PNEUC15  0% 
20000  PNEUC15  0% 
30000  PNEUC15  0% 
40000  PNEUC15  0% 
50000  PNEUC15  0% 
60000  PNEUC15  0% 
70000  PNEUC15  0% 
80000  PNEUC15  0% 
90000  PNEUC15  0% 
100000  PNEUC15  0% 
110000  PNEUC15  0% 
120000  PNEUC15  0% 
130000  PNEUC15  0% 
140000  PNEUC15  0% 
150000  PNEUC15  0% 
160000  PNEUC15  0% 
170000  PNEUC15  0% 
180000  PNEUC15  0% 
190000  PNEUC15  0% 
200000  PNEUC15  0% 
0  PNEUC20  0% 
10000  PNEUC20  19% 
20000  PNEUC20  58% 
30000  PNEUC20  77% 
40000  PNEUC20  84% 
50000  PNEUC20  86% 
60000  PNEUC20  82% 
70000  PNEUC20  72% 
80000  PNEUC20  60% 
90000  PNEUC20  47% 
100000  PNEUC20  37% 
110000  PNEUC20  28% 
120000  PNEUC20  20% 
130000  PNEUC20  14% 
140000  PNEUC20  10% 
150000  PNEUC20  7% 
160000  PNEUC20  6% 
170000  PNEUC20  4% 
180000  PNEUC20  2% 
190000  PNEUC20  2% 
200000  PNEUC20  1% 
0  PNEUC15 + PNEUP23  0% 
10000  PNEUC15 + PNEUP23  0% 
20000  PNEUC15 + PNEUP23  0% 
30000  PNEUC15 + PNEUP23  0% 
40000  PNEUC15 + PNEUP23  0% 
50000  PNEUC15 + PNEUP23  0% 
60000  PNEUC15 + PNEUP23  0% 
70000  PNEUC15 + PNEUP23  0% 
80000  PNEUC15 + PNEUP23  1% 
90000  PNEUC15 + PNEUP23  1% 
100000  PNEUC15 + PNEUP23  2% 
110000  PNEUC15 + PNEUP23  2% 
120000  PNEUC15 + PNEUP23  2% 
130000  PNEUC15 + PNEUP23  2% 
140000  PNEUC15 + PNEUP23  2% 
150000  PNEUC15 + PNEUP23  1% 
160000  PNEUC15 + PNEUP23  1% 
170000  PNEUC15 + PNEUP23  1% 
180000  PNEUC15 + PNEUP23  1% 
190000  PNEUC15 + PNEUP23  1% 
200000  PNEUC15 + PNEUP23  1% 
0  PNEUC20 + PNEUP23  0% 
10000  PNEUC20 + PNEUP23  0% 
20000  PNEUC20 + PNEUP23  0% 
30000  PNEUC20 + PNEUP23  0% 
40000  PNEUC20 + PNEUP23  1% 
50000  PNEUC20 + PNEUP23  4% 
60000  PNEUC20 + PNEUP23  11% 
70000  PNEUC20 + PNEUP23  22% 
80000  PNEUC20 + PNEUP23  36% 
90000  PNEUC20 + PNEUP23  49% 
100000  PNEUC20 + PNEUP23  61% 
110000  PNEUC20 + PNEUP23  70% 
120000  PNEUC20 + PNEUP23  78% 
130000  PNEUC20 + PNEUP23  84% 
140000  PNEUC20 + PNEUP23  88% 
150000  PNEUC20 + PNEUP23  91% 
160000  PNEUC20 + PNEUP23  93% 
170000  PNEUC20 + PNEUP23  95% 
180000  PNEUC20 + PNEUP23  97% 
190000  PNEUC20 + PNEUP23  97% 
200000  PNEUC20 + PNEUP23  98% 
Outcome  Strategy  Mean lifetime outcomes averted per 100,000 population 

0  PNEUP23  98% 
10000  PNEUP23  64% 
20000  PNEUP23  35% 
30000  PNEUP23  21% 
40000  PNEUP23  15% 
50000  PNEUP23  11% 
60000  PNEUP23  8% 
70000  PNEUP23  7% 
80000  PNEUP23  5% 
90000  PNEUP23  3% 
100000  PNEUP23  2% 
110000  PNEUP23  1% 
120000  PNEUP23  1% 
130000  PNEUP23  0% 
140000  PNEUP23  0% 
150000  PNEUP23  0% 
160000  PNEUP23  0% 
170000  PNEUP23  0% 
180000  PNEUP23  0% 
190000  PNEUP23  0% 
200000  PNEUP23  0% 
0  PNEUC15  0% 
10000  PNEUC15  0% 
20000  PNEUC15  0% 
30000  PNEUC15  0% 
40000  PNEUC15  0% 
50000  PNEUC15  0% 
60000  PNEUC15  0% 
70000  PNEUC15  0% 
80000  PNEUC15  0% 
90000  PNEUC15  0% 
100000  PNEUC15  0% 
110000  PNEUC15  0% 
120000  PNEUC15  0% 
130000  PNEUC15  0% 
140000  PNEUC15  0% 
150000  PNEUC15  0% 
160000  PNEUC15  0% 
170000  PNEUC15  0% 
180000  PNEUC15  0% 
190000  PNEUC15  0% 
200000  PNEUC15  0% 
0  PNEUC20  2% 
10000  PNEUC20  36% 
20000  PNEUC20  65% 
30000  PNEUC20  79% 
40000  PNEUC20  84% 
50000  PNEUC20  85% 
60000  PNEUC20  82% 
70000  PNEUC20  74% 
80000  PNEUC20  63% 
90000  PNEUC20  53% 
100000  PNEUC20  44% 
110000  PNEUC20  36% 
120000  PNEUC20  28% 
130000  PNEUC20  21% 
140000  PNEUC20  16% 
150000  PNEUC20  12% 
160000  PNEUC20  10% 
170000  PNEUC20  7% 
180000  PNEUC20  6% 
190000  PNEUC20  5% 
200000  PNEUC20  4% 
0  PNEUC15 + PNEUP23  0% 
10000  PNEUC15 + PNEUP23  0% 
20000  PNEUC15 + PNEUP23  0% 
30000  PNEUC15 + PNEUP23  0% 
40000  PNEUC15 + PNEUP23  0% 
50000  PNEUC15 + PNEUP23  0% 
60000  PNEUC15 + PNEUP23  0% 
70000  PNEUC15 + PNEUP23  0% 
80000  PNEUC15 + PNEUP23  1% 
90000  PNEUC15 + PNEUP23  1% 
100000  PNEUC15 + PNEUP23  1% 
110000  PNEUC15 + PNEUP23  1% 
120000  PNEUC15 + PNEUP23  2% 
130000  PNEUC15 + PNEUP23  2% 
140000  PNEUC15 + PNEUP23  2% 
150000  PNEUC15 + PNEUP23  2% 
160000  PNEUC15 + PNEUP23  2% 
170000  PNEUC15 + PNEUP23  2% 
180000  PNEUC15 + PNEUP23  1% 
190000  PNEUC15 + PNEUP23  1% 
200000  PNEUC15 + PNEUP23  1% 
0  PNEUC20 + PNEUP23  0% 
10000  PNEUC20 + PNEUP23  0% 
20000  PNEUC20 + PNEUP23  0% 
30000  PNEUC20 + PNEUP23  0% 
40000  PNEUC20 + PNEUP23  1% 
50000  PNEUC20 + PNEUP23  4% 
60000  PNEUC20 + PNEUP23  10% 
70000  PNEUC20 + PNEUP23  20% 
80000  PNEUC20 + PNEUP23  32% 
90000  PNEUC20 + PNEUP23  43% 
100000  PNEUC20 + PNEUP23  52% 
110000  PNEUC20 + PNEUP23  62% 
120000  PNEUC20 + PNEUP23  69% 
130000  PNEUC20 + PNEUP23  76% 
140000  PNEUC20 + PNEUP23  82% 
150000  PNEUC20 + PNEUP23  86% 
160000  PNEUC20 + PNEUP23  89% 
170000  PNEUC20 + PNEUP23  91% 
180000  PNEUC20 + PNEUP23  93% 
190000  PNEUC20 + PNEUP23  94% 
200000  PNEUC20 + PNEUP23  95% 
Outcome  Strategy  Mean lifetime outcomes averted per 100,000 population 

0  PNEUP23  84% 
10000  PNEUP23  61% 
20000  PNEUP23  45% 
30000  PNEUP23  33% 
40000  PNEUP23  25% 
50000  PNEUP23  18% 
60000  PNEUP23  13% 
70000  PNEUP23  10% 
80000  PNEUP23  7% 
90000  PNEUP23  5% 
100000  PNEUP23  4% 
110000  PNEUP23  3% 
120000  PNEUP23  2% 
130000  PNEUP23  1% 
140000  PNEUP23  1% 
150000  PNEUP23  1% 
160000  PNEUP23  1% 
170000  PNEUP23  0% 
180000  PNEUP23  0% 
190000  PNEUP23  0% 
200000  PNEUP23  0% 
0  PNEUC15  0% 
10000  PNEUC15  0% 
20000  PNEUC15  0% 
30000  PNEUC15  0% 
40000  PNEUC15  0% 
50000  PNEUC15  0% 
60000  PNEUC15  0% 
70000  PNEUC15  0% 
80000  PNEUC15  0% 
90000  PNEUC15  0% 
100000  PNEUC15  0% 
110000  PNEUC15  0% 
120000  PNEUC15  0% 
130000  PNEUC15  0% 
140000  PNEUC15  0% 
150000  PNEUC15  0% 
160000  PNEUC15  0% 
170000  PNEUC15  0% 
180000  PNEUC15  0% 
190000  PNEUC15  0% 
200000  PNEUC15  0% 
0  PNEUC20  16% 
10000  PNEUC20  39% 
20000  PNEUC20  55% 
30000  PNEUC20  64% 
40000  PNEUC20  65% 
50000  PNEUC20  60% 
60000  PNEUC20  48% 
70000  PNEUC20  35% 
80000  PNEUC20  26% 
90000  PNEUC20  18% 
100000  PNEUC20  13% 
110000  PNEUC20  8% 
120000  PNEUC20  6% 
130000  PNEUC20  4% 
140000  PNEUC20  3% 
150000  PNEUC20  2% 
160000  PNEUC20  1% 
170000  PNEUC20  1% 
180000  PNEUC20  1% 
190000  PNEUC20  0% 
200000  PNEUC20  0% 
0  PNEUC15 + PNEUP23  0% 
10000  PNEUC15 + PNEUP23  0% 
20000  PNEUC15 + PNEUP23  0% 
30000  PNEUC15 + PNEUP23  0% 
40000  PNEUC15 + PNEUP23  0% 
50000  PNEUC15 + PNEUP23  0% 
60000  PNEUC15 + PNEUP23  0% 
70000  PNEUC15 + PNEUP23  0% 
80000  PNEUC15 + PNEUP23  0% 
90000  PNEUC15 + PNEUP23  0% 
100000  PNEUC15 + PNEUP23  0% 
110000  PNEUC15 + PNEUP23  0% 
120000  PNEUC15 + PNEUP23  0% 
130000  PNEUC15 + PNEUP23  0% 
140000  PNEUC15 + PNEUP23  0% 
150000  PNEUC15 + PNEUP23  0% 
160000  PNEUC15 + PNEUP23  0% 
170000  PNEUC15 + PNEUP23  1% 
180000  PNEUC15 + PNEUP23  0% 
190000  PNEUC15 + PNEUP23  0% 
200000  PNEUC15 + PNEUP23  1% 
0  PNEUC20 + PNEUP23  0% 
10000  PNEUC20 + PNEUP23  0% 
20000  PNEUC20 + PNEUP23  1% 
30000  PNEUC20 + PNEUP23  3% 
40000  PNEUC20 + PNEUP23  11% 
50000  PNEUC20 + PNEUP23  22% 
60000  PNEUC20 + PNEUP23  39% 
70000  PNEUC20 + PNEUP23  55% 
80000  PNEUC20 + PNEUP23  67% 
90000  PNEUC20 + PNEUP23  77% 
100000  PNEUC20 + PNEUP23  83% 
110000  PNEUC20 + PNEUP23  89% 
120000  PNEUC20 + PNEUP23  92% 
130000  PNEUC20 + PNEUP23  94% 
140000  PNEUC20 + PNEUP23  96% 
150000  PNEUC20 + PNEUP23  97% 
160000  PNEUC20 + PNEUP23  98% 
170000  PNEUC20 + PNEUP23  98% 
180000  PNEUC20 + PNEUP23  99% 
190000  PNEUC20 + PNEUP23  99% 
200000  PNEUC20 + PNEUP23  99% 
Outcome  Strategy  Mean lifetime outcomes averted per 100,000 population 

0  PNEUP23  66% 
10000  PNEUP23  45% 
20000  PNEUP23  30% 
30000  PNEUP23  21% 
40000  PNEUP23  15% 
50000  PNEUP23  12% 
60000  PNEUP23  9% 
70000  PNEUP23  7% 
80000  PNEUP23  6% 
90000  PNEUP23  5% 
100000  PNEUP23  4% 
110000  PNEUP23  3% 
120000  PNEUP23  2% 
130000  PNEUP23  2% 
140000  PNEUP23  2% 
150000  PNEUP23  1% 
160000  PNEUP23  1% 
170000  PNEUP23  1% 
180000  PNEUP23  0% 
190000  PNEUP23  0% 
200000  PNEUP23  0% 
0  PNEUC15  0% 
10000  PNEUC15  0% 
20000  PNEUC15  0% 
30000  PNEUC15  0% 
40000  PNEUC15  0% 
50000  PNEUC15  0% 
60000  PNEUC15  0% 
70000  PNEUC15  0% 
80000  PNEUC15  0% 
90000  PNEUC15  0% 
100000  PNEUC15  0% 
110000  PNEUC15  0% 
120000  PNEUC15  0% 
130000  PNEUC15  0% 
140000  PNEUC15  0% 
150000  PNEUC15  0% 
160000  PNEUC15  0% 
170000  PNEUC15  0% 
180000  PNEUC15  0% 
190000  PNEUC15  0% 
200000  PNEUC15  0% 
0  PNEUC20  34% 
10000  PNEUC20  55% 
20000  PNEUC20  69% 
30000  PNEUC20  77% 
40000  PNEUC20  80% 
50000  PNEUC20  78% 
60000  PNEUC20  73% 
70000  PNEUC20  66% 
80000  PNEUC20  56% 
90000  PNEUC20  48% 
100000  PNEUC20  39% 
110000  PNEUC20  32% 
120000  PNEUC20  25% 
130000  PNEUC20  20% 
140000  PNEUC20  15% 
150000  PNEUC20  12% 
160000  PNEUC20  9% 
170000  PNEUC20  7% 
180000  PNEUC20  6% 
190000  PNEUC20  5% 
200000  PNEUC20  3% 
0  PNEUC15 + PNEUP23  0% 
10000  PNEUC15 + PNEUP23  0% 
20000  PNEUC15 + PNEUP23  0% 
30000  PNEUC15 + PNEUP23  0% 
40000  PNEUC15 + PNEUP23  0% 
50000  PNEUC15 + PNEUP23  0% 
60000  PNEUC15 + PNEUP23  0% 
70000  PNEUC15 + PNEUP23  0% 
80000  PNEUC15 + PNEUP23  0% 
90000  PNEUC15 + PNEUP23  0% 
100000  PNEUC15 + PNEUP23  0% 
110000  PNEUC15 + PNEUP23  1% 
120000  PNEUC15 + PNEUP23  1% 
130000  PNEUC15 + PNEUP23  1% 
140000  PNEUC15 + PNEUP23  1% 
150000  PNEUC15 + PNEUP23  1% 
160000  PNEUC15 + PNEUP23  1% 
170000  PNEUC15 + PNEUP23  1% 
180000  PNEUC15 + PNEUP23  1% 
190000  PNEUC15 + PNEUP23  1% 
200000  PNEUC15 + PNEUP23  1% 
0  PNEUC20 + PNEUP23  0% 
10000  PNEUC20 + PNEUP23  0% 
20000  PNEUC20 + PNEUP23  0% 
30000  PNEUC20 + PNEUP23  2% 
40000  PNEUC20 + PNEUP23  4% 
50000  PNEUC20 + PNEUP23  10% 
60000  PNEUC20 + PNEUP23  17% 
70000  PNEUC20 + PNEUP23  26% 
80000  PNEUC20 + PNEUP23  38% 
90000  PNEUC20 + PNEUP23  47% 
100000  PNEUC20 + PNEUP23  57% 
110000  PNEUC20 + PNEUP23  65% 
120000  PNEUC20 + PNEUP23  72% 
130000  PNEUC20 + PNEUP23  77% 
140000  PNEUC20 + PNEUP23  82% 
150000  PNEUC20 + PNEUP23  86% 
160000  PNEUC20 + PNEUP23  89% 
170000  PNEUC20 + PNEUP23  91% 
180000  PNEUC20 + PNEUP23  93% 
190000  PNEUC20 + PNEUP23  94% 
200000  PNEUC20 + PNEUP23  95% 
Outcome  Strategy  Mean lifetime outcomes averted per 100,000 population 

0  PNEUP23  71% 
10000  PNEUP23  57% 
20000  PNEUP23  46% 
30000  PNEUP23  38% 
40000  PNEUP23  32% 
50000  PNEUP23  28% 
60000  PNEUP23  23% 
70000  PNEUP23  19% 
80000  PNEUP23  16% 
90000  PNEUP23  14% 
100000  PNEUP23  12% 
110000  PNEUP23  10% 
120000  PNEUP23  9% 
130000  PNEUP23  8% 
140000  PNEUP23  6% 
150000  PNEUP23  6% 
160000  PNEUP23  5% 
170000  PNEUP23  4% 
180000  PNEUP23  4% 
190000  PNEUP23  3% 
200000  PNEUP23  3% 
0  PNEUC15  0% 
10000  PNEUC15  0% 
20000  PNEUC15  0% 
30000  PNEUC15  0% 
40000  PNEUC15  0% 
50000  PNEUC15  0% 
60000  PNEUC15  0% 
70000  PNEUC15  0% 
80000  PNEUC15  0% 
90000  PNEUC15  0% 
100000  PNEUC15  0% 
110000  PNEUC15  0% 
120000  PNEUC15  0% 
130000  PNEUC15  0% 
140000  PNEUC15  0% 
150000  PNEUC15  0% 
160000  PNEUC15  0% 
170000  PNEUC15  0% 
180000  PNEUC15  0% 
190000  PNEUC15  0% 
200000  PNEUC15  0% 
0  PNEUC20  29% 
10000  PNEUC20  43% 
20000  PNEUC20  54% 
30000  PNEUC20  62% 
40000  PNEUC20  66% 
50000  PNEUC20  70% 
60000  PNEUC20  72% 
70000  PNEUC20  73% 
80000  PNEUC20  71% 
90000  PNEUC20  67% 
100000  PNEUC20  63% 
110000  PNEUC20  58% 
120000  PNEUC20  53% 
130000  PNEUC20  48% 
140000  PNEUC20  43% 
150000  PNEUC20  39% 
160000  PNEUC20  34% 
170000  PNEUC20  31% 
180000  PNEUC20  28% 
190000  PNEUC20  24% 
200000  PNEUC20  21% 
0  PNEUC15 + PNEUP23  0% 
10000  PNEUC15 + PNEUP23  0% 
20000  PNEUC15 + PNEUP23  0% 
30000  PNEUC15 + PNEUP23  0% 
40000  PNEUC15 + PNEUP23  0% 
50000  PNEUC15 + PNEUP23  0% 
60000  PNEUC15 + PNEUP23  0% 
70000  PNEUC15 + PNEUP23  0% 
80000  PNEUC15 + PNEUP23  0% 
90000  PNEUC15 + PNEUP23  0% 
100000  PNEUC15 + PNEUP23  0% 
110000  PNEUC15 + PNEUP23  1% 
120000  PNEUC15 + PNEUP23  1% 
130000  PNEUC15 + PNEUP23  1% 
140000  PNEUC15 + PNEUP23  1% 
150000  PNEUC15 + PNEUP23  1% 
160000  PNEUC15 + PNEUP23  1% 
170000  PNEUC15 + PNEUP23  1% 
180000  PNEUC15 + PNEUP23  1% 
190000  PNEUC15 + PNEUP23  1% 
200000  PNEUC15 + PNEUP23  1% 
0  PNEUC20 + PNEUP23  0% 
10000  PNEUC20 + PNEUP23  0% 
20000  PNEUC20 + PNEUP23  0% 
30000  PNEUC20 + PNEUP23  1% 
40000  PNEUC20 + PNEUP23  1% 
50000  PNEUC20 + PNEUP23  3% 
60000  PNEUC20 + PNEUP23  5% 
70000  PNEUC20 + PNEUP23  9% 
80000  PNEUC20 + PNEUP23  13% 
90000  PNEUC20 + PNEUP23  19% 
100000  PNEUC20 + PNEUP23  25% 
110000  PNEUC20 + PNEUP23  31% 
120000  PNEUC20 + PNEUP23  38% 
130000  PNEUC20 + PNEUP23  43% 
140000  PNEUC20 + PNEUP23  50% 
150000  PNEUC20 + PNEUP23  55% 
160000  PNEUC20 + PNEUP23  60% 
170000  PNEUC20 + PNEUP23  64% 
180000  PNEUC20 + PNEUP23  68% 
190000  PNEUC20 + PNEUP23  72% 
200000  PNEUC20 + PNEUP23  75% 
II.4 Sensitivity Analysis
Deterministic univariate sensitivity analysis was performed for key model parameters by varying model parameters one at a time over the ranges listed in Tables 38 while holding all other parameter values at their base case values (Figures 5 and 6). Vaccine effectiveness parameters were tested differently, with values for PNEUC15/20 and PNEUP23 constrained to ensure that PNEUC15/20 would not be less effective than PNEUP23 during this test. The low effectiveness value of PNEUC15/20 was constrained to be no less than the base case value of the PNEUP23 and the high effectiveness value of PNEUP23 was constrained to be no greater than the base case value of PNEUC15/20. Vaccine prices were varied by ±50% of the base case value. Results are presented as ICERs of PNEUC15 + PNEUP23 or PNEUC20 compared to PNEUP23.
The model showed greater sensitivity to vaccination parameters, particularly when vaccine effectiveness against CAP was similar between the polysaccharide and conjugate vaccines. In addition, the model showed greater sensitivity to vaccine price and discount rate. Larger variations in the ICER were observed in Northern Canada compared to the rest of Canada.
Figure 5  Text description
Figure 5 is a multipanel figure showing tornado diagrams for a sensitivity analysis comparing PNEUC15 + PNEUP23 to PNEUP23. There are 2 rows. The top row shows results for the rest of Canada and the bottom row shows results for Northern Canada. There are three columns, with the following headings: Epidemiological parameters, Vaccination parameters, and Economic parameters. The xaxis shows the ICER and the yaxis is labelled with different model input parameters. For each figure, there is a bar for each model input parameter and the bar is colored to represent low (yellow) and high (blue) values of the input parameter values used. The bars are centered on the base case estimate of the ICER and the width of the bars represents the range of ICER values when a given parameter is varied from its low to high values. For each graph the bars are ordered by width, with the widest bars at the top, indicating parameters that when varied across their low and high values resulted in the largest change in the value of the ICER.
Parameter type  Parameter name  Base case ICER  ICER for low value  ICER for high value 

Epidemiological parameter  CFR, CAP  32943  37270.71  29239.03 
Epidemiological parameter  % pCAP/CAP  32943  36502.12  29751.33 
Epidemiological parameter  Incidence IPD  32943  33431.74  32459.01 
Epidemiological parameter  CFR, IPD  32943  33239.45  32622.09 
Epidemiological parameter  Incidence CAP (inpatient)  32943  33166.49  32719.63 
Epidemiological parameter  Prob sequelae (severe)  32943  33055.81  32829.86 
Epidemiological parameter  Odds CAP is outpatient  32943  32995.56  32850.81 
Epidemiological parameter  Prob sequelae (mild)  32943  32989.53  32880.13 
Vaccination parameter  VE CAP, PNEUC  32943  76814.58  20728.3 
Vaccination parameter  VE CAP, PNEUP  32943  23982.29  48534.51 
Vaccination parameter  VE IPD, PNEUC  32943  36931.66  28788.43 
Vaccination parameter  VE ST3CAP, PNEUC  32943  38539.65  30511.88 
Vaccination parameter  VE ST3IPD, PNEUC  32943  36016.26  29861.64 
Vaccination parameter  VE IPD, PNEUP  32943  30209.25  35566.29 
Vaccination parameter  VE ST3CAP, PNEUP  32943  32413.46  36911.21 
Vaccination parameter  VE ST3IPD, PNEUP  32943  32763.88  34708.83 
Vaccination parameter  Coverage  32943  32942.58  32942.58 
Economic parameter  Price, PNEUC15  32943  15274.56  50610.6 
Economic parameter  Discount rate  32943  25632.98  55067.23 
Economic parameter  Cost, vaccine administration  32943  30868.53  35016.62 
Economic parameter  Utility, inpatient  32943  30714.68  34768.91 
Economic parameter  Cost, IPD  32943  33127.13  32750.74 
Economic parameter  Cost, transportation (inpatient)  32943  33096.19  32789.74 
Economic parameter  Utility, outpatient  32943  32793.72  33041.2 
Economic parameter  Cost, sequelae (severe)  32943  33005.05  32880.11 
Economic parameter  Utility, sequelae (severe)  32943  32891.48  32994.34 
Economic parameter  Utility, sequelae (mild)  32943  32892.41  32990.12 
Economic parameter  Cost, CAP (inpatient)  32943  32982.3  32902.86 
Economic parameter  Cost, sequelae (mild)  32943  32963.33  32921.83 
Economic parameter  Cost, CAP (outpatient)  32943  32961.47  32923.68 
Parameter type  Parameter name  Base case ICER  ICER for low value  ICER for high value 

Epidemiological parameter  Incidence IPD  28087  41153.12  15760.63 
Epidemiological parameter  % pCAP/CAP  28087  33562.21  23196.25 
Epidemiological parameter  Incidence CAP (inpatient)  28087  33017.77  23594.88 
Epidemiological parameter  CFR, CAP  28087  31392.36  25194.08 
Epidemiological parameter  CFR, IPD  28087  28469.69  27677.09 
Epidemiological parameter  Odds CAP is outpatient  28087  28365.92  27606.4 
Epidemiological parameter  Prob sequelae (severe)  28087  28218.38  27955.72 
Epidemiological parameter  Prob sequelae (mild)  28087  28140.12  28015.62 
Vaccination parameter  VE CAP, PNEUC  28087  83621.18  10741.69 
Vaccination parameter  VE CAP, PNEUP  28087  14685.57  51440.06 
Vaccination parameter  VE IPD, PNEUC  28087  37394.81  19250.88 
Vaccination parameter  VE ST3IPD, PNEUC  28087  35143.63  21465.78 
Vaccination parameter  VE IPD, PNEUP  28087  21831.94  34599.04 
Vaccination parameter  VE ST3CAP, PNEUC  28087  35731.86  24709.27 
Vaccination parameter  VE ST3CAP, PNEUP  28087  27322.52  33816.3 
Vaccination parameter  VE ST3IPD, PNEUP  28087  27675.08  32257.08 
Vaccination parameter  Coverage  28087  28086.67  28086.67 
Economic parameter  Price, PNEUC15  28087  112.1939  56061.14 
Economic parameter  Discount rate  28087  22379.1  43535.62 
Economic parameter  Cost, transportation (inpatient)  28087  35821.56  20277.33 
Economic parameter  Utility, inpatient  28087  24254.93  31714.93 
Economic parameter  Cost, vaccine administration  28087  25056.75  31116.58 
Economic parameter  Cost, CAP (inpatient)  28087  29053.65  27078.96 
Economic parameter  Cost, IPD  28087  28825.34  27318.82 
Economic parameter  Utility, outpatient  28087  27829.56  28258.33 
Economic parameter  Cost, sequelae (severe)  28087  28166.88  28006.45 
Economic parameter  Utility, sequelae (severe)  28087  28030.24  28143.88 
Economic parameter  Utility, sequelae (mild)  28087  28031.27  28139.22 
Economic parameter  Cost, transportation subsidy (outpatient)  28087  28136.41  28038.53 
Economic parameter  Cost, accommodation subsidy (outpatient)  28087  28189.36  28091.48 
Economic parameter  Cost, CAP (outpatient)  28087  28132.06  28041.27 
Economic parameter  Cost, sequelae (mild)  28087  28113.31  28060.02 
Each parameter value was varied between a low and high value while holding all other parameters at their base case values. Differences in the base case ICERs compared to Table 9 are a result of deterministic (rather than probabilistic) estimates in the univariate sensitivity analysis.
 CAP
 communityacquired pneumonia
 CFR
 case fatality rate
 IPD
 invasive pneumococcal disease
 % pCAP/CAP
 proportion of CAP cases attributable to S. pneumoniae
 VE
 vaccine effectiveness
 PCV
 pneumococcal conjugate vaccine
 PPV
 pneumococcal polysaccharide vaccine
 ST3
 serotype 3
Figure 6  Text description
Figure 6 is a multipanel figure showing tornado diagrams for a sensitivity analysis comparing PNEUC20 to PNEUP23. There are 2 rows. The top row shows results for the rest of Canada and the bottom row shows results for Northern Canada. There are three columns, with the following headings: Epidemiological parameters, Vaccination parameters, and Economic parameters. The xaxis shows the ICER and the yaxis is labelled with different model input parameters. For each figure, there is a bar for each model input parameter and the bar is colored to represent low (yellow) and high (blue) values of the input parameter values used. The bars are centered on the base case estimate of the ICER and the width of the bars represents the range of ICER values when a given parameter is varied from its low to high values. For each graph the bars are ordered by width, with the widest bars at the top, indicating parameters that when varied across their low and high values resulted in the largest change in the value of the ICER.
Parameter type  Parameter name  Base case ICER  ICER for low value  ICER for high value 

Epidemiological parameter  % pCAP/CAP  16898  19253.44  14810.6 
Epidemiological parameter  CFR, CAP  16898  19294.71  14882.18 
Epidemiological parameter  Incidence IPD  16898  17162.11  16635.97 
Epidemiological parameter  Incidence CAP (inpatient)  16898  17045.35  16751.45 
Epidemiological parameter  CFR, IPD  16898  17021.27  16764.5 
Epidemiological parameter  Odds CAP is outpatient  16898  16945.35  16816.05 
Epidemiological parameter  Prob sequelae (severe)  16898  16960.16  16836.12 
Epidemiological parameter  Prob sequelae (mild)  16898  16921.98  16866.15 
Vaccination parameter  VE CAP, PNEUC  16898  67289.08  7922.267 
Vaccination parameter  VE CAP, PNEUP  16898  8487.277  41027.76 
Vaccination parameter  VE IPD, PNEUC  16898  20405.93  13445.22 
Vaccination parameter  VE IPD, PNEUP  16898  13881.84  20089.49 
Vaccination parameter  VE ST3CAP, PNEUC  16898  19974.86  15537.06 
Vaccination parameter  VE ST3IPD, PNEUC  16898  18715.62  15052.79 
Vaccination parameter  VE ST3CAP, PNEUP  16898  16601.19  19115.35 
Vaccination parameter  VE ST3IPD, PNEUP  16898  16791.19  17950.95 
Vaccination parameter  Coverage  16898  16898.02  16898.02 
Economic parameter  Price, PNEUC20  16898  1547.19  35343.24 
Economic parameter  Discount rate  16898  12628.76  30249.21 
Economic parameter  Utility, inpatient  16898  15734.19  17854.41 
Economic parameter  Cost, transportation (inpatient)  16898  17054.63  16742.21 
Economic parameter  Cost, IPD  16898  17049.34  16740.74 
Economic parameter  Utility, outpatient  16898  16817.3  16951.53 
Economic parameter  Cost, sequelae (severe)  16898  16948.29  16847.76 
Economic parameter  Cost, CAP (inpatient)  16898  16940.61  16855.44 
Economic parameter  Utility, sequelae (severe)  16898  16876.93  16919.38 
Economic parameter  Cost, CAP (outpatient)  16898  16918.28  16877.77 
Economic parameter  Utility, sequelae (mild)  16898  16877.32  16917.64 
Economic parameter  Cost, sequelae (mild)  16898  16914.72  16881.33 
Economic parameter  Cost, vaccine administration  16898  16898.02  16898.02 
Parameter type  Parameter name  Base case ICER  ICER for low value  ICER for high value 

Epidemiological parameter  Incidence IPD  5851  12920  1286.28 
Epidemiological parameter  % pCAP/CAP  5851  9753.419  2418.012 
Epidemiological parameter  Incidence CAP (inpatient)  5851  9362.508  2695.969 
Epidemiological parameter  CFR, CAP  5851  6602.032  5206.31 
Epidemiological parameter  Odds CAP is outpatient  5851  6123.009  5382.365 
Epidemiological parameter  CFR, IPD  5851  5914.509  5781.997 
Epidemiological parameter  Prob sequelae (severe)  5851  5905.025  5796.534 
Epidemiological parameter  Prob sequelae (mild)  5851  5868.967  5826.295 
Vaccination parameter  VE CAP, PNEUC  5851  71930.16  7877.39 
Vaccination parameter  VE CAP, PNEUP  5851  7241.68  42075.76 
Vaccination parameter  VE IPD, PNEUC  5851  14591.63  1773.46 
Vaccination parameter  VE IPD, PNEUP  5851  1029.26  14068.75 
Vaccination parameter  VE ST3IPD, PNEUC  5851  10242.7  1666.169 
Vaccination parameter  VE ST3CAP, PNEUC  5851  10402.76  3812.619 
Vaccination parameter  VE ST3CAP, PNEUP  5851  5392.792  9261.133 
Vaccination parameter  VE ST3IPD, PNEUP  5851  5593.172  8446.69 
Vaccination parameter  Coverage  5851  5850.651  5850.651 
Economic parameter  Price, PNEUC20  5851  24028.8  35730.1 
Economic parameter  Cost, transportation (inpatient)  5851  13822.28  2197.69 
Economic parameter  Discount rate  5851  2360.459  15668.19 
Economic parameter  Cost, CAP (inpatient)  5851  6908.196  4748.564 
Economic parameter  Utility, inpatient  5851  5031.426  6632.717 
Economic parameter  Cost, IPD  5851  6457.344  5219.996 
Economic parameter  Cost, sequelae (severe)  5851  5915.764  5785.538 
Economic parameter  Cost, transportation subsidy (outpatient)  5851  5904.895  5798.157 
Economic parameter  Cost, accommodation subsidy (outpatient)  5851  5962.638  5855.901 
Economic parameter  Cost, CAP (outpatient)  5851  5900.297  5801.006 
Economic parameter  Utility, outpatient  5851  5792.29  5889.67 
Economic parameter  Cost, sequelae (mild)  5851  5872.277  5829.025 
Economic parameter  Utility, sequelae (severe)  5851  5841.11  5860.317 
Economic parameter  Utility, sequelae (mild)  5851  5841.284  5859.531 
Economic parameter  Cost, vaccine administration  5851  5850.651  5850.651 
Each parameter value was varied between a low and high value while holding all other parameters at their base case values. Differences in the base case ICERs compared to Table 9 are a result of deterministic (rather than probabilistic) estimates in the univariate sensitivity analysis.
 CAP
 communityacquired pneumonia
 CFR
 case fatality rate
 IPD
 invasive pneumococcal disease
 % pCAP/CAP
 proportion of CAP cases attributable to S. pneumoniae
 VE
 vaccine effectiveness
 PCV
 pneumococcal conjugate vaccine
 PPV
 pneumococcal polysaccharide vaccine
 ST3
 serotype 3
II.5 Scenario Analyses
Extensive scenario analyses were conducted to account for uncertainty in base case assumptions. Some key analysis are described below.
Indirect effects of a pediatric vaccination program with PNEUC15 and/or PNEUC20
Incidence of pneumococcal disease associated with serotypes unique to PNEUC15 or PNEUC20 were decreased to approximate indirect effects of a potential pediatric vaccination program with PNEUC15 or PNEUC20. Indirect effects were assumed to begin four years after vaccination of adults to account for a delay in initiating a pediatric program and time to observe an effect of reduced carriage. Indirect effects were modelled as a simple linear decline in PD incidence from unique PNEUC15/20 serotypes by 50% over 5 years. Potential serotype replacement was not modelled. Figure 7 shows that inclusion of indirect effects resulted in ICERs that were higher compared to the base case. No change to the strategies on the efficiency frontier was observed compared to the base case.
Figure 7  Text description
Figure 7 is a multipanel figure showing mean costs and QALYs for different vaccination strategies under a scenario analysis looking at the impact of indirect effects from a pediatric vaccination program. The graphs are separated by age cohort, region, and include the results for two perspectives. The figure consists of four scatter plots arranged in two rows and three columns. Each graph shows results for an age cohort (50 or 65 years) and geographic region (Rest of Canada or Northern Canada). The xaxis is labelled "Total QALYs (per capita)" and the yaxis is labelled "Total costs (per capita)". The scales for the x and yaxis are different across the graphs. There are symbols on the graphs that represent the total QALYs and total costs for a specified vaccination strategy. The vaccination strategies are: PNEUP23 (red), PNEUC15 (yellow), PNEUC20 (green), PNEUC15+PNEUP23 (blue), and PNEUC20+PNEUP23 (purple).There are two symbols representing the health system perspective (triangle) and societal perspective (square). The total costs are higher for the societal perspective than the health system perspective. There are solid lines connecting some of the symbols on the graph. The line is known as the efficiency frontier and the symbols on the efficiency frontier have numbers associated with them, representing the incremental costeffectiveness ratios. In all of the graphs, the efficiency frontier includes PNEUP23, PNEUC20, and PNEUC20+PNEUP23. PNEUC15 and PNEUC20+PNEUP23 are not on the efficiency frontier.
Perspective  Strategy  Total costs (per capita)  Total QALYs (per capita)  ICER  Sequential ICER 

Health system  PNEUP23  442.93  20.78185  0  0 
Health system  PNEUC20  464.97  20.78237  42251.9  42251.9 
Health system  PNEUC20 + PNEUP23  480.46  20.78255  53026.96  83231.79 
Health system  PNEUC15  463.97  20.78201  126552.6  Weakly dominated 
Health system  PNEUC15 + PNEUP23  477.32  20.78237  65527.74  Weakly dominated 
Societal  PNEUP23  655.73  20.78185  0  0 
Societal  PNEUC20  673.94  20.78237  34908.42  34908.42 
Societal  PNEUC20 + PNEUP23  761.33  20.78255  149192.8  469556.6 
Societal  PNEUC15 + PNEUP23  759.57  20.78237  197867.4  Weakly dominated 
Societal  PNEUC15  675.97  20.78201  121690.5  Dominated 
Perspective  Strategy  Total costs (per capita)  Total QALYs (per capita)  ICER  Sequential ICER 

Health system  PNEUP23  418.29  13.70260  0  0 
Health system  PNEUC20  437.39  13.70350  21316.42  21316.42 
Health system  PNEUC20 + PNEUP23  452.92  13.70369  31881.02  81612.41 
Health system  PNEUC15  436.46  13.70308  38018.23  Weakly dominated 
Health system  PNEUC15 + PNEUP23  449.92  13.70346  36932.73  Dominated 
Societal  PNEUP23  508.90  13.70260  0  0 
Societal  PNEUC20  526.05  13.70350  19143.66  19143.66 
Societal  PNEUC20 + PNEUP23  551.86  13.70369  39551.61  135619.3 
Societal  PNEUC15  526.21  13.70308  36234.83  Dominated 
Societal  PNEUC15 + PNEUP23  549.35  13.70346  47235.11  Dominated 
Perspective  Strategy  Total costs (per capita)  Total QALYs (per capita)  ICER  Sequential ICER 

Health system  PNEUP23  562.99  11.15560  0  0 
Health system  PNEUC20  573.14  11.15610  19975.74  19975.74 
Health system  PNEUC20 + PNEUP23  584.24  11.15630  30350.42  57806.58 
Health system  PNEUC15  581.02  11.15571  151839.4  Dominated 
Health system  PNEUC15 + PNEUP23  585.54  11.15611  44131.95  Dominated 
Societal  PNEUP23  780.56  11.15560  0  0 
Societal  PNEUC20  784.31  11.15610  7375.954  7375.954 
Societal  PNEUC20 + PNEUP23  866.32  11.15630  122490.8  427137.6 
Societal  PNEUC15  797.45  11.15571  142242.7  Dominated 
Societal  PNEUC15 + PNEUP23  870.04  11.15611  175110  Dominated 
Perspective  Strategy  Total costs (per capita)  Total QALYs (per capita)  ICER  Sequential ICER 

Health system  PNEUP23  501.31  5.52569  0  0 
Health system  PNEUC20  506.61  5.52629  8750.289  8750.289 
Health system  PNEUC20 + PNEUP23  517.66  5.52643  21989.27  80283.02 
Health system  PNEUC15  513.74  5.52596  44969.29  Dominated 
Health system  PNEUC15 + PNEUP23  518.65  5.52626  30139.73  Dominated 
Societal  PNEUP23  567.56  5.52569  0  0 
Societal  PNEUC20  570.25  5.52629  4440.515  4440.515 
Societal  PNEUC20 + PNEUP23  591.47  5.52643  32138.18  154096.2 
Societal  PNEUC15  578.92  5.52596  41082.05  Dominated 
Societal  PNEUC15 + PNEUP23  593.17  5.52626  44510.92  Dominated 
Each plot shows the efficiency frontier from the health system perspective (▲) and the societal perspective (■). The efficiency frontier is marked by a solid line connecting the set of potentially costeffective strategies, depending on the costeffectiveness threshold value. ICERs are labelled below each strategy on the efficiency frontier and are represented by the slope of the line connecting the strategy with the next most effective strategy on the frontier. Strategies that are not on the efficiency frontier are not considered costeffective at any threshold value.
Faster waning of vaccine protection
This scenario examined the potential impact of faster waning protection compared to the base case. In this scenario, protection by the polysaccharide vaccine declined linearly to 0% over seven years (compared to 15 years in the base case). Protection by the conjugate vaccine was assumed to remain stable for the first five years and then declined to 0% over the next seven years (compared to 10 years in the base case). Lower ICERs were observed compared to the base case (Figure 8) and PNEUP23 was dominated by PNEUC20 at age 65 years in Northern Canada and at age 50 years in Northern Canada from the societal perspective.
Figure 8  Text description
Figure 8 is a multipanel figure showing mean costs and QALYs for different vaccination strategies under a scenario analysis looking at the impact of faster waning of vaccine protection. The graphs are separated by age cohort, region, and include the results for two perspectives. The figure consists of four scatter plots arranged in two rows and two columns. Each graph shows results for an age cohort (50 or 65 years) and geographic region (Rest of Canada or Northern Canada). The xaxis is labelled "Total QALYs (per capita)" and the yaxis is labelled "Total costs (per capita)". The scales for the x and yaxis are different across the graphs. There are symbols on the graphs that represent the total QALYs and total costs for a specified vaccination strategy. The vaccination strategies are: PNEUP23 (red), PNEUC15 (yellow), PNEUC20 (green), PNEUC15+PNEUP23 (blue), and PNEUC20+PNEUP23 (purple).There are two symbols representing the health system perspective (triangle) and societal perspective (square). The total costs are higher for the societal perspective than the health system perspective. There are solid lines connecting some of the symbols on the graph. The line is known as the efficiency frontier and the symbols on the efficiency frontier have numbers associated with them, representing the incremental costeffectiveness ratios. In the graphs for the Rest of Canada, the efficiency frontier includes PNEUP23, PNEUC20, and PNEUC20+PNEUP23. PNEUC15 and PNEUC20+PNEUP23 are not on the efficiency frontier. In the graphs for Northern Canada, the efficiency frontier includes only PNEUC20 and PNEUC20+PNEUP23 for both perspectives for the age 65 years cohort and for the societal perspective for the age 50 years cohort. PNEUP23 is included on the efficiency frontier, along with PNEUC20 and PNEUC20+PNEUP23, for the age 50 cohort for the health system perspective.
Perspective  Strategy  Total costs (per capita)  Total QALYs (per capita)  ICER  Sequential ICER 

Health system  PNEUP23  509.49  20.7767  0  0 
Health system  PNEUC20  528.17  20.77748  23838.53  23838.53 
Health system  PNEUC20 + PNEUP23  544.83  20.77758  40209.17  174517 
Health system  PNEUC15  527.37  20.77711  43469.32  Weakly dominated 
Health system  PNEUC15 + PNEUP23  542.68  20.77732  53634.26  Dominated 
Societal  PNEUP23  742.23  20.7767  0  0 
Societal  PNEUC20  754.55  20.77748  15733.22  15733.22 
Societal  PNEUC20 + PNEUP23  843.89  20.77758  115686.5  935722.3 
Societal  PNEUC15  756.93  20.77711  35760.31  Dominated 
Societal  PNEUC15 + PNEUP23  843.83  20.77732  164211.1  Dominated 
Perspective  Strategy  Total costs (per capita)  Total QALYs (per capita)  ICER  Sequential ICER 

Health system  PNEUP23  473.63  13.69883  0  0 
Health system  PNEUC20  489.43  13.70002  13294.69  13294.69 
Health system  PNEUC20 + PNEUP23  506.08  13.70011  25243.49  171272.8 
Health system  PNEUC15  488.62  13.69958  19818.06  Weakly dominated 
Health system  PNEUC15 + PNEUP23  503.99  13.6998  31114.19  Dominated 
Societal  PNEUP23  574.98  13.69883  0  0 
Societal  PNEUC20  587.85  13.70002  10826.28  10826.28 
Societal  PNEUC20 + PNEUP23  615.08  13.70011  31188.54  280040.8 
Societal  PNEUC15  588.17  13.69958  17437.37  Dominated 
Societal  PNEUC15 + PNEUP23  613.73  13.6998  39707.12  Dominated 
Perspective  Strategy  Total costs (per capita)  Total QALYs (per capita)  ICER  Sequential ICER 

Health system  PNEUP23  628.62  11.1539  0  0 
Health system  PNEUC20  630.30  11.15466  2221.118  2221.118 
Health system  PNEUC20 + PNEUP23  644.40  11.15477  18164.03  129176.3 
Health system  PNEUC15  637.81  11.15427  24320.02  Dominated 
Health system  PNEUC15 + PNEUP23  647.89  11.15451  31277.33  Dominated 
Societal  PNEUC20  852.19  11.15466  10960.3  0 
Societal  PNEUC20 + PNEUP23  938.30  11.15477  89519.62  789172.1 
Societal  PNEUP23  860.52  11.1539  0  Dominated 
Societal  PNEUC15  864.87  11.15427  11510.01  Dominated 
Societal  PNEUC15 + PNEUP23  945.11  11.15451  137261.2  Dominated 
Perspective  Strategy  Total costs (per capita)  Total QALYs (per capita)  ICER  Sequential ICER 

Health system  PNEUC20  529.55  5.525862  3599.2  0 
Health system  PNEUC20 + PNEUP23  542.63  5.525953  11225.58  143739.3 
Health system  PNEUP23  532.48  5.525049  0  Dominated 
Health system  PNEUC15  536.53  5.525534  8344.917  Dominated 
Health system  PNEUC15 + PNEUP23  545.40  5.525741  18666.65  Dominated 
Societal  PNEUC20  595.54  5.525862  8136.98  0 
Societal  PNEUC20 + PNEUP23  619.03  5.525953  18660.67  258195.9 
Societal  PNEUP23  602.16  5.525049  0  Dominated 
Societal  PNEUC15  604.05  5.525534  3882.236  Dominated 
Societal  PNEUC15 + PNEUP23  622.75  5.525741  29748.14  Dominated 
Each plot shows the efficiency frontier from the health system perspective (▲) and the societal perspective (■). The efficiency frontier is marked by a solid line connecting the set of potentially costeffective strategies, depending on the costeffectiveness threshold value. ICERs are labelled below each strategy on the efficiency frontier and are represented by the slope of the line connecting the strategy with the next most effective strategy on the frontier. Strategies that are not on the efficiency frontier are not considered costeffective at any threshold value.
PNEUC15 effectiveness versus serotype 3
This scenario examined the potential impact of higher effectiveness of PNEUC15 for preventing pneumococcal disease due to serotype 3, based on GMT ratios^{Footnote 78}. Vaccine effectiveness values for this scenario are listed in Table 10. Higher effectiveness of PNEUC15 against serotype 3 PD resulted in lower ICERs of PNEUC15 (alone or in series with PNEUP23) compared to PNEUP23 than in the base case analysis but did not result in PNEUC15 appearing on the efficiency frontier (Figure 9). No other changes to the strategies on the efficiency frontier were observed.
Parameter  Base Value  Range 

Vaccine effectiveness against serotype 3 IPD  
PNEUP23  2.0  0 – 21.0 
PNEUC15  46.0  18.1 – 75.5 
PNEUC20  26.0  0 – 53.4 
Vaccine effectiveness against serotype 3 CAP  
PNEUP23  2.0  0 – 21.0 
PNEUC15  27.6  18.4 – 37.9 
PNEUC20  15.6  0 – 22.7 
Figure 9  Text description
Figure 9 is a multipanel figure showing mean costs and QALYs for different vaccination strategies under a scenario analysis looking at the impact of higher PNEUCvaccine effectiveness against pneumococcal disease caused by serotype 3. The graphs are separated by age cohort, region, and include the results for two perspectives. The figure consists of four scatter plots arranged in two rows and two columns. Each graph shows results for an age cohort (50 or 65 years) and geographic region (Rest of Canada or Northern Canada). The xaxis is labelled "Total QALYs (per capita)" and the yaxis is labelled "Total costs (per capita)". The scales for the x and yaxis are different across the graphs. There are symbols on the graphs that represent the total QALYs and total costs for a specified vaccination strategy. The vaccination strategies are: PNEUP23 (red), PNEUC15 (yellow), PNEUC20 (green), PNEUC15+PNEUP23 (blue), and PNEUC20+PNEUP23 (purple). There are two symbols representing the health system perspective (triangle) and societal perspective (square). The total costs are higher for the societal perspective than the health system perspective. There are solid lines connecting some of the symbols on the graph. The line is known as the efficiency frontier and the symbols on the efficiency frontier have numbers associated with them, representing the incremental costeffectiveness ratios. In all of the graphs, the efficiency frontier includes PNEUP23, PNEUC20, and PNEUC20+PNEUP23. PNEUC15 and PNEUC20+PNEUP23 are not on the efficiency frontier.
Perspective  Strategy  Total costs (per capita)  Total QALYs (per capita)  ICER  Sequential ICER 

Health system  PNEUP23  504.84  20.77705  0  0 
Health system  PNEUC20  525.97  20.77765  35618.87  35618.87 
Health system  PNEUC20 + PNEUP23  541.44  20.77784  46786.72  81866.14 
Health system  PNEUC15  524.99  20.7773  83639.69  Weakly dominated 
Health system  PNEUC15 + PNEUP23  537.86  20.77769  52018.32  Weakly dominated 
Societal  PNEUP23  734.32  20.77705  0  0 
Societal  PNEUC20  751.07  20.77765  28232.13  28232.13 
Societal  PNEUC20 + PNEUP23  838.41  20.77784  133096.7  462487.8 
Societal  PNEUC15 + PNEUP23  835.85  20.77769  159986.5  Weakly dominated 
Societal  PNEUC15  753.03  20.7773  77688.08  Dominated 
Perspective  Strategy  Total costs (per capita)  Total QALYs (per capita)  ICER  Sequential ICER 

Health system  PNEUP23  468.33  13.69927  0  0 
Health system  PNEUC20  486.02  13.70029  17379.41  17379.41 
Health system  PNEUC20 + PNEUP23  501.52  13.70049  27408.62  80343.78 
Health system  PNEUC15  484.59  13.69993  24867.23  Weakly dominated 
Health system  PNEUC15 + PNEUP23  497.57  13.70035  27307.56  Weakly dominated 
Societal  PNEUP23  568.23  13.69927  0  0 
Societal  PNEUC20  583.69  13.70029  15180.3  15180.3 
Societal  PNEUC20 + PNEUP23  609.45  13.70049  34040.85  133588.7 
Societal  PNEUC15  583.18  13.69993  22862.02  Weakly dominated 
Societal  PNEUC15 + PNEUP23  605.71  13.70035  34999.91  Weakly dominated 
Perspective  Strategy  Total costs (per capita)  Total QALYs (per capita)  ICER  Sequential ICER 

Health system  PNEUP23  616.32  11.15424  0  0 
Health system  PNEUC20  625.15  11.15478  16299.63  16299.63 
Health system  PNEUC20 + PNEUP23  636.19  11.15498  27027.56  57003.37 
Health system  PNEUC15 + PNEUP23  635.68  11.15484  32138.56  Weakly dominated 
Health system  PNEUC15  631.85  11.15443  80821.26  Dominated 
Societal  PNEUP23  843.42  11.15424  0  0 
Societal  PNEUC20  845.40  11.15478  3668.979  3668.979 
Societal  PNEUC20 + PNEUP23  927.35  11.15498  114188  422998.3 
Societal  PNEUC15  856.80  11.15443  69666.38  Dominated 
Societal  PNEUC15 + PNEUP23  928.46  11.15484  141218.4  Dominated 
Perspective  Strategy  Total costs (per capita)  Total QALYs (per capita)  ICER  Sequential ICER 

Health system  PNEUP23  521.51  5.525308  0  0 
Health system  PNEUC20  525.64  5.525939  6528.941  6528.941 
Health system  PNEUC20 + PNEUP23  536.67  5.526077  19703.73  79986.27 
Health system  PNEUC15 + PNEUP23  534.42  5.525995  18760.1  Weakly dominated 
Health system  PNEUC15  529.89  5.525689  21951.39  Dominated 
Societal  PNEUP23  589.83  5.525308  0  0 
Societal  PNEUC20  591.21  5.525939  2190.275  2190.275 
Societal  PNEUC20 + PNEUP23  612.41  5.526077  29351.2  153628.7 
Societal  PNEUC15 + PNEUP23  610.45  5.525995  29989  Weakly dominated 
Societal  PNEUC15  596.62  5.525689  17809.61  Dominated 
Each plot shows the efficiency frontier from the health system perspective (▲) and the societal perspective (■). The efficiency frontier is marked by a solid line connecting the set of potentially costeffective strategies, depending on the costeffectiveness threshold value. ICERs are labelled below each strategy on the efficiency frontier and are represented by the slope of the line connecting the strategy with the next most effective strategy on the frontier. Strategies that are not on the efficiency frontier are not considered costeffective at any threshold value.
Vaccine price
Given the sensitivity of model results to vaccine prices and uncertainty about prices for PNEUC15 and PNEUC20, the influence of vaccine prices on optimal vaccination strategy was further explored in a twoway sensitivity analysis. We determined the point at which the prices for PNEUC15, PNEUC20, and PNEUP23 would have equivalent costeffectiveness (i.e., the use of one particular vaccination strategy was no longer preferred). The vaccine prices for PNEUC15 and PNEUC20 were varied relative to the assumed price for PNEUP23. The optimal strategies were determined for the age 50 and 65 years cohorts for costeffectiveness thresholds of $30,000 and $60,000 per QALY gained. At a threshold of $30,000 per QALY gained, PNEUP23, PNEUC15, and PNEUC20 would be equivalent costeffective strategies at incremental prices (relative to an assumed fixed price for PNEUP23) of PNEUC15 and PNEUC20 of $14 and $51 per dose, respectively, in the age 50 years cohort. In the age 65 years cohort, the strategies would be equivalent at incremental prices of $41 (PNEUC15) and $84 (PNEUC20) per dose. At a threshold of $60,000 per QALY gained, PNEUP23, PNEUC15 + PNEUP23, and PNEUC20 would be equivalent strategies at incremental prices of $46 (PNEUC15) and $88 (PNEUC20) per dose in the age 50 years cohort. In the age 65 years cohort, the strategies would be equivalent at incremental prices of $99 (PNEUC15) and $148 (PNEUC20) per dose. Based on this analysis, the price per dose of PNEUC15 may need to be approximately $4050 less than that of PNEUC20 for the use of PNEUC15 to be cost effective.
II.6 Study limitations
There are a number of limitations to this study. A significant limitation is the lack of comparative effectiveness data between PNEUC15 and PNEUC20. As a result, the dominance of PNEUC20 is driven by the broader serotype coverage under an assumption of equivalent effectiveness to PNEUC13 serotypes. In addition, the nature of waning protection with PNEUC15 and PNEUC20 are unknown. Although the model results appear robust in scenario analysis of vaccine waning, the strategies on the efficiency frontier may change if waning is markedly different between the two conjugate vaccines.
The effect of vaccination on transmission could not be assessed due to the static cohort design. There is considerable uncertainty associated with the possible future use of higher valency pneumococcal vaccines in pediatric vaccination programs, in terms of reduction in vaccinetype PD and potential serotype replacement, which could influence the costeffectiveness of an adult program.
The model did not stratify the population by underlying medical conditions or immunocompromised status due to limited data in these groups at the national level. These groups may have a higher burden of disease and higher medical costs per case. Costeffectiveness of the conjugate vaccines in groups without underlying medical or immunocompromising conditions may be overestimated as the costs and benefits are aggregated over the entire population.
There is some data suggesting that vaccination may reduce the occurrence of cardiac events following pneumonia^{Footnote 79} ^{Footnote 80}. Due to uncertainty about the nature of this protective effect, this outcome was not included in the model and this exclusion may underestimate the benefits of vaccination with PNEUC15 or PNEUC20. In this case, these study results would be a conservative estimate of the costeffectiveness of PNEUC15 and PNEUC20.
Societal costs were likely underestimated as nonmedical consumption and caregiver costs associated with auditory sequelae were not included due to uncertainty about the effect of pneumococcal disease and auditory sequelae on these costs. Given these limitations, the study results may be viewed as a conservative estimate of the costeffectiveness of PNEUC15 and PNEUC20 from a societal perspective.
II.7 Conclusions
The base case model and scenario analyses indicate that PNEUC20 (either alone or in series with PNEUP23) is likely a costeffective strategy at age 65 or age 75 years. In the base case, using a health system perspective, ICERs for the use of PNEUC20 alone ranged from $6530 to $17,400 per QALY gained in these age cohorts. Base case ICERs for PNEUC20 at age 50 years ranged from $16,300 to $35,600 per QALY gained using the health system perspective. PNEUC15 was dominated or subject to extended dominance across most scenarios and does not appear to be a costeffective strategy while PNEUP23 or PNEUC20 are available.
Multimodel Comparison
III.1 Approach
To evaluate the robustness of the costutility model described in Section 2, a multimodel comparison was conducted. Outputs from different economic models were compared to identify areas of consistency and difference across models with different structures and assumptions. Two additional costutility models were identified that were adapted to evaluate the costeffectiveness of agebased vaccination strategies in the Canadian population. Both models were funded by industry. Versions of the Merck^{Footnote 8} and Pfizer^{Footnote 9} models were described in the systematic review (Section 1) and were used in economic evaluations of PNEUC15 and/or PNEUC20 in the United States. Wherever possible, these models incorporated the same parameters as used in the previously described Canadian costutility model, although differences in the model structures required some modifications or simplifying assumptions, as described in Table 11. All models were adapted to represent a general population and did not include stratification by chronic medical or immunocompromising conditions.
Model feature  Merck  Pfizer  NACI 

Model type  Single cohort  Multipleage cohort  Single cohort 
Lower vaccine effectiveness for serotype 3 than other serotypes  Yes  No  Yes 
Costs and health consequences of postmeningitis sequelae included  Yes  No  Yes 
For the multimodel comparison, results from a single base case were generated and sensitivity analysis were not conducted. A health system perspective was adopted and all models used a lifetime time horizon. Indirect effects of a potential pediatric vaccination program were not included for this comparison. For a given age recommendation and region, sequential ICERs were calculated, to allow for a comparison across different vaccination strategies and identify options that would be most costeffective. Results for the multimodel comparison are summarized in aggregate below to avoid possible disclosure of confidential information.
III.2 MultiModel Comparison Results
Results were broadly consistent across the different models. Differences in estimates across models likely reflected differences in model structure and simplifying assumptions made for the purposes of the multimodel comparison. Despite quantitative variability in ICER estimates across models, qualitative results were consistent.
In the sequential analysis of all vaccination strategies, all models estimated that PNEUC15 or PNEUC15 in series with PNEUP23 would be dominated or subject to extended dominance by PNEUC20. This was consistent across ages and regions.
All three models indicated that use of PNEUC20 is likely a costeffective strategy at age 50 years and 65 years, with ICERs ranging from $5,000 to $40,000 per QALY across models and geographic regions. At age 75, results for the use of PNEUC20 were variable, with ICERs ranging from $11,000 to $105,000 per QALY gained. All models placed PNEUC20 in series with PNEUP23 on the efficiency frontier for all ages and regions, suggesting that this strategy could be considered costeffective, depending on the threshold used.
III.3 Conclusions
Three costutility models with harmonized parameter values showed qualitatively consistent results despite differing model structures and assumptions. The comparison supported the finding that, based on currently available data, PNEUC20, used alone or in series with PNEUP23 could be a costeffective strategy for use in the adult Canadian population.
List of Abbreviations
 ACIP
 Advisory Committee on Immunization Practices
 CADTH
 Canadian Agency for Drugs and Technologies in Health
 CAP
 Communityacquired pneumonia
 CFR
 Case fatality rate
 CMC
 Chronic medical conditions
 CNDSS
 Canadian Notifiable Disease Surveillance System
 DAD
 Discharge Abstract Database
 IC
 Immunocompromising conditions
 ICER
 Incremental costeffectiveness ratio
 ICS
 International Circumpolar Surveillance
 IPD
 Invasive pneumococcal disease
 NVT
 Nonvaccine type
 pCAP
 Pneumococcal Community Acquired Pneumonia
 PCV
 Pneumococcal conjugate vaccine
 PD
 Pneumococcal disease
 PNEUC13
 13valent pneumococcal conjugate vaccine
 PNEUC15
 15valent conjugate pneumococcal vaccine
 PNEUC20
 20valent conjugate pneumococcal vaccine
 PNEUP23
 23valent pneumococcal polysaccharide vaccine
 PPV
 Pneumococcal polysaccharide vaccine
 QALY
 Qualityadjusted life year
 ROC
 Rest of Canada
 ST3
 Serotype 3
 US
 United States
 VE
 Vaccine effectiveness
 VT
 Vaccinetype
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