Clinical Drug Investigation 2016 Jan; 36(1):41-53.

Cost-effectiveness of 13-valent conjugate pneumococcal vaccination program in COPD patients aged 50+ years in Spain

Rodríguez-GonzálezMoro JM1, Menéndez R2, Campins M3, Lwoff N4, Oyagüez I5, Echave M5, Rejas J4, Antoñanzas F6.

1Hospital Universitario Gregorio Marañón, Madrid, Spain; 2Hospital Universitario La Fe, Valencia, Spain; 3Hospital Universitari Vall d’Hebron. Barcelona, Spain; 4Pfizer SLU, Alcobendas (Madrid), Spain; 5Pharmacoeconomics & Outcomes Research Iberia, Madrid, Spain; 6University of La Rioja, Logrono, Spain.



Patients with chronic obstructive pulmonary disease (COPD) are at elevated risk of any form of pneumococcal disease (PD). A 13-valent-pneumococcal-conjugate vaccine (PCV13) was approved for adult protection against invasive disease and pneumonia caused by S. pneumonia as a consequence of CAPITA trial. In a former economic publication, we estimated the incremental cost-effectiveness ratio (ICER) of vaccinating COPD-patients ≥50-years with PCV13 compared to current vaccination policy (CVP) with 23-valent-pneumococcal-polysacharide vaccine (PPSV23) in subjects with COPD in Spain. Now, we inform of the efficiency of PCV13 in particular subpopulations of COPD subjects, mainly still smokers and patient with high-risk (1 or more comorbidities additionally to COPD) of suffering PD not previously analyzed. A Markov model accounting for risks and costs for all-cause non-bacteremic pneumonia (NBP) and invasive pneumococcal disease (IPD; bacteremic pneumonia or meningitis) was developed. The perspective of the analysis was that of a third-party payer (i.e., the Spanish National Health System), and the horizon of evaluation was lifetime in the base case scenario. We reported that over a lifetime horizon and for a 629,747 COPD total population, PCV13 would prevent 2,224 inpatient-NBP, 3,134 outpatient-NBP and 210 IPD extra cases in comparison with CVP. Additionally, 398 related deaths would be averted. ICER was €1,518 per quality adjusted life-year (QALY) gained for PCV13 versus CVP, which was considered to be a cost-effective strategy compared to vaccination with PPSV23 at the commonly accepted willingness-to-pay threshold of €30,000/QALY gained in Spain. Findings in both still smokers and high risk COPD patients were aligned with the base case showing ICERs for PCV13 vs. PPSV23, respectively, of €2,393/QALY gained or a dominant ICER (same cost and more effective), thus supporting its cost-effectiveness in additional COPD subpopulations.




Streptococcus pneumoniae is a major cause of morbidity, mortality and associated costs in the adult population. This bacterium causes different disease manifestations including invasive pneumococcal disease (IPD) and non-invasive mucosal infections (non-IPD), including non-bacteremic pneumonia (NBP). Older adults and those with certain clinical conditions such as those with immunocompromising conditions and immunocompetent patients with chronic diseases are at increased risk of developing pneumococcal disease (PD), particularly pneumonia, along with a higher risk of related mortality. In particular, one of the most relevant underlying conditions associated with increased risk for PD is chronic obstructive pulmonary disease (COPD), and certain related factors, as smoking or additional comorbidities, may increase substantially the burden of PD in those subjects. Particularly, and according to the Spanish National Health Survey, smoking is still present in near one third of patients diagnosed with COPD. Furthermore, more than half of the subjects with this disorder suffer one or more additional comorbidity (diabetes, heart disease, etc.) which, in turn, are factors increasing the risk for pneumococcal disease. The estimated total annual cost, likewise, of PD may be substantial from a third-party perspective. As the only health policy intervention that has proved to reduce the high burden of PD, vaccination strategies have been established in almost all European countries for at-high risk and/or the elderly population. In Spain, current adult vaccination policy (CVP) recommends 23-valent pneumococcal polysaccharide (PPSV23) and 13-valent pneumococcal conjugate (PCV13) vaccination for immunocompromised of all ages. PPSV23 is the unique recommended for adult with underlying chronic health disorders, such as COPD patients. At present, there is no evidence available regarding the cost-effectiveness of pneumococcal immunization with conjugate vaccines in adult patients at increased risk in Spain. The aim of this analysis was to evaluate the clinical and economic consequences of the use of a single dose of PCV13 among COPD adult population aged ≥50 years compared to CVP based on PPSV23. Also, in this analysis, we show data on the vaccine efficiency in particular subpopulations of COPD subjects with elevated risk of developing PD, such as still smokers and those with additional comorbidities to COPD (high risk patients).


A model with a Markov process was developed in Microsoft Excel 2007, to depict the risks and costs of IPD (bacteremic pneumonia or meningitis) and all-cause NBP in a ≥50 year-old Spanish COPD population. Expected total number of IPD cases, all-cause NBP, and expected number of deaths due to IPD and all-cause inpatient NBP; expected total costs of medical treatment for IPD and all-cause NBP; and total costs of vaccination were evaluated from model entry through the end of the modeling horizon. Cost-effectiveness was estimated based on the incremental cost-effectiveness ratio (ICER), which was calculated by dividing the differences in costs by the quality adjusted life-year (QALY) gained of PCV13 strategy versus CVP with PPSV23. Perspective of the economic evaluation was that of a third-payer; the Spanish National Health System (NHS). Population estimations were based on national figures from the Spanish National Institute of Statistics according with local prevalence of COPD and the Spanish National Health Survey years 2011-2012. Risk-specific incidence and case-fatality rates associated with PD were based on published data in chronic respiratory disease. The effectiveness of both pneumococcal vaccines were obtained from an investigation which aimed to evaluate the epidemiological impact of the PPSV23 vaccination program in the elderly in England and Wales, from a published meta-analyses and systematic reviews and from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) trial. In addition to COPD subjects above 50-years old, which findings have been recently published elsewhere (see Clin Drug Invest 2016, 36:41-53), we here analyze the efficiency of immunization with PCV13 in particular subjects with COPD, i.e. those still smokers and patients at high risk (patients above 50-years with a COPD diagnosis and one or more additional comorbidity).


The administration of PCV13 for Spanish ≥50 years COPD cohort, under base case assumptions, accounted for higher health benefits than CVP with PPSV23. Overall, compared to CVP the inclusion of one dose of PCV13, would avoid 210 IPD cases, 2,224 inpatient NBP and 3,134 outpatient NBP cases for a lifetime horizon. Additionally, 398 related deaths would be averted. Medical plus vaccination costs per patient obtained in the model would imply €682 and €686 for CVP and PCV13, respectively, for the NHS in a lifetime period in the whole population with COPD (see base case scenario in table 1). The resulting ICER was €1,245 per additional LYG and €1,844 per QALY gained for PCV13 compared to CVP with PPSV23 that were considered cost-effective values according with Spanish recommendations. Vaccination with PCV13 vs. PPSV23 in special COPD subpopulations showed findings completely aligned with what was observed in the base case scenario. In COPD still smokers, compared to PPSV23 the inclusion of one dose of PCV13, would avoid 53 IPD cases, 227 inpatient NBP and 320 outpatient NBP cases for a lifetime horizon. Additionally, 40 related deaths would be averted. PCV13 strategy would also be a cost-effective alternative to PPSV23 (see table 1) since incremental costs would be offset partially with substantial more PD cases avoided (see figure 1, graph A) yielding to acceptable ICERs of €1,720 per additional LYG and €2,393 per QALY gained, that should be considered cost-effective values according with Spanish recommendations. In COPD high-risk subjects, PCV13 vaccine this time would be a dominant option over PPSV23 vaccination strategy (table 1) since analysis showed that a vaccination policy with PCV13 would cost exactly the same as that with CVP while it would avert a meaningful number of PD cases (see figure 1, graph B). As such, compared to CVP, one dose of PCV13 would avoid 378 IPD cases, 1,033 inpatient NBP and 1,453 outpatient NBP cases for a lifetime horizon. Additionally, 277 related deaths would be averted in this high risk COPD subpopulation. Univariate and probabilistic sensitivity analyses confirmed results to be robust in both subpopulations.


All scenarios analyzed in the model suggest that, from the Spanish NHS perspective, routine pneumococcal adult vaccination scheme with PCV13 would be a highly cost-effective or dominant intervention in COPD subjects regardless of their age strata, smoking status or underlying health conditions. Under base case analysis, PCV13 policy would cost €1,844 per additional QALY versus CVP in the general COPD population, increasing to €2,393 in smokers with COPD, which should be both considered highly cost-effective assuming the common willingness-to-pay threshold in Spain from around €30,000 per additional QALY. Nonetheless, PCV13 would even produce net monetary saving in oldest age strata (above 75 years-old) and would not cost more in COPD patients with one or more additional comorbidities while avoiding more pneumococcal disease cases. These last findings would be considered impacting since, from an epidemiological point of view, more than two thirds of the Spanish COPD population corresponds to patients at high-risk of suffering any type of pneumococcal disease.


Table 1. Cost-effectiveness lifetime results in the whole population with COPD and in the still smokers and high risk COPD subpopulations.

table 1ICER: incremental cost-effectiveness ratio; LYG: life-year gained; QALY: Quality-Adjusted Life-Years; PCV13: 13-valent pneumococcal conjugate vaccine; PPSV23: 23-valent pneumococcal polysaccharide vaccine; High risk COPD patients: COPD patients above 50 years-old with one or more additional comorbidity; dominant: PCV13 less costly and more effective than PPSV23.


As expected, the most influential parameters were vaccine effectiveness, time horizon and vaccine price. Herd effect, even considering high values that are out of the scope of the Spanish situation regarding current vaccination policy in childhood (still very limited), was of little impact in the model. It is worthy to highlight that crucial outcome for prophylactic measures are referred to averted cases and in this research, in all PD types assessed, PCV13 vaccination strategy scenario compared to CVP would avoid a substantial number of PD cases. In costs terms, for the lifetime horizon, the results of this study suggest that use of PCV13 would lead to a reduction in the total number of cases of pneumococcal disease as well as cost reduction via avoided health care services that would partially offset the incremental costs related to PCV13 vaccination in adults aged ≥50 years with COPD. On the other hand, while a 15% reduction in PCV13 price was associated with a dominant situation in favor of this vaccination strategy, the same reduction for PPV23 was of little effect upon the ICER value. This finding is of interest; as the model was populated with vaccine prices corresponding to only-one administration packages instead of the 10-administration package which is the usual acquisition form by the NHS, this costing around a 15% less.


Published cost-effectiveness analyses for pneumococcal vaccination are available for USA, England, Germany, Italy and Netherlands with a wide range of immunization strategies and different populations tested. Comparison of results between studies is difficult because of model assumptions, differences in healthcare system organizations, epidemiology, year cost values and other country-specific factors. Most of them showed the cost-effectiveness of PCV13 over the recommended PPSV23 vaccination strategy in adults above 65 years-old with different underlying health condition, but none of them were populating COPD subjects. Despite of any of these studies it is important to remark that this is the first evaluation addressing the question of cost-effectiveness for conjugate pneumococcal vaccination specially focused in COPD adults applying the vaccine efficacy data from the CAPiTA trial so no comparison with other studies in similar population is feasible.


Figure 1 

The importance of this study is, despite possible limitations (uncertainty surrounding waning of the vaccine protection over the long-term, indirect effects, perspective of a third-payer only, and lack of Spanish evidence on case fatality rate in pneumococcal disease in this specific group of patients) and assumptions carried out, that is the first time that two vaccines used in immunization programs against pneumococcus are compared in adult subjects with COPD from a health economical perspective, and also because we populated the model for subjects with this condition and special characteristics, such as still smokers and high risk patients. The administration of the 13-valent conjugate pneumococcal vaccine (PCV13) in a ≥50 years COPD cohort would account higher health benefits than current vaccination policy with the polysaccharide vaccine, irrespective of age strata, smoking or risk status. The incremental costs of this vaccination strategy are counterbalanced in part by savings from averted pneumococcal disease cases, resulting in an efficient strategy in Spain.



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