Alternative strategies for adult pneumococcal polysaccharide vaccination: A cost-effectiveness analysis

doi:10.1016/j.vaccine.2008.01.007

Vaccine

Volume 26, Issue 11, 10 March 2008, Pages 1420-1431

https://doi.org/10.1016/j.vaccine.2008.01.007 Get rights and content

Summary

Pneumococcal polysaccharide vaccination (PPV) to prevent invasive pneumococcal disease (IPD) is recommended at age 65 for most persons in the US. We used a Markov model to examine alternative PPV strategies, finding that vaccination at ages 50 and 65 prevented more IPD than present vaccination policies; four decennial vaccinations were most effective. The present vaccination policy costs $3341/QALY gained, vaccinations at 50/65 cost $23,120/QALY and four vaccinations (50/60/70/80) cost $54,451/QALY; results were sensitive to vaccine uptake assumptions, with current policy no longer favored at present vaccination rates. PPV at ages 50/65 may be clinically and, depending on cost-effectiveness criterion used, economically favored over present vaccination recommendations.

Introduction

Streptococcus pneumoniae causes a major proportion of invasive bacterial disease (i.e., bacteremia, meningitis, or infection in a normally sterile site) in all age groups, especially the elderly. Pneumococcal polysaccharide vaccine (PPV) to prevent invasive pneumococcal disease (IPD) has been recommended for all persons aged 65 or older and for younger persons with comorbidities. However, current recommendations do not prevent as many deaths from S. pneumoniae as possible, due to infections in persons who do not have an indication for vaccination [1] and to the waning of immunity after PPV [2], [3]. Recent analyses supporting vaccination at age 50 to protect more “healthy” persons who are at risk [1] and the demonstrated safety of repeated PPV vaccinations [4], [5] have led to research questions about lowering the initial vaccination age to 50 and consideration of scheduled revaccinations [6].

Changes in pneumococcal serotype epidemiology, due to the introduction of childhood pneumococcal conjugate vaccine (PCV), further complicate vaccine policy decision making [7], [8], [9], [10]. IPD in adults aged 50 or older has decreased substantially since PCV licensure, with 28% fewer cases in this age group in 2002–2003 compared to 1998–1999 [9]. In contrast, persons with comorbid conditions have benefited less, leading to relative increases in the proportion of IPD cases seen in persons with comorbid conditions [9]. Furthermore, IPD caused by penicillin-resistant strains among persons >65 years decreased by 49% from 1999 to 2004 [11]. Previous decision analyses have not accounted for these changes in epidemiology [12], [13], [14].

Clinical trials to test the effectiveness of various vaccination strategies would likely be: (1) unwieldy, due to the large number of patients and the length of follow up required to ascertain vaccine-related changes; and (2) unhelpful, given relatively rapid epidemiologic changes due to PCV. Decision analysis techniques, systematically synthesizing vaccine effectiveness and epidemiologic changes in patient cohorts as they age, could be useful in determining the desirability of expanding the routine PPV schedule to two or more doses and beginning vaccination earlier. We used Markov modeling to estimate the effectiveness and cost-effectiveness of alternative PPV strategies in adults.

Section snippets

Methods

We used a Markov state-transition model to examine the effectiveness and cost-effectiveness of eight PPV strategies: no vaccination, one vaccination (age 50 or 65), two vaccinations (50/65 or 65/80), three vaccinations (50/65/80) or four vaccinations (50/60/70/80), and also a strategy depicting present US adult vaccination policy (i.e., vaccination at age 65 unless a comorbid condition is diagnosed prior to that age, with vaccination then and a second vaccination at either age 65 or five years

Invasive pneumococcal disease (IPD) epidemiology

Vaccination strategy effects on IPD are summarized in Table 4. With no vaccination, population lifetime risk for IPD from age 50 onward was 0.86% and for death due to IPD was 0.19%; this translates, in the approximately 3.9 million US 50-year-olds in 2004 [31], to 33,788 IPD cases and 7439 IPD deaths in their lifetime, based on “no vaccine” IPD rates derived from ABCs data. In single-dose vaccination strategies, vaccination at age 50 was more effective than at age 65, with more significant

Discussion

We investigated several pneumococcal vaccination strategies for adults aged 50 and older using decision analysis techniques. We found that vaccinating at age 65 only was less effective than vaccinating at age 50 only, and that two vaccinations at ages 50 and 65 or four vaccinations at ages 50, 60, 70, and 80 were reasonable strategies for consideration, depending on the cost-effectiveness acceptability criterion used. The present policy of vaccinating healthy 65-year-olds and also vaccinating

Acknowledgements

The authors gratefully acknowledge the efforts of the Active Bacterial Core Surveillance team, CDC and the members of the expert panel.

This project was supported in part by funding from St. Margaret's Foundation, via a grant from Merck & Co, Inc. The sponsors had no role in the design and conduct of the study; in the collection, management, analysis, and interpretation of the data; or in the preparation or approval of the manuscript. The sponsors reviewed the manuscript, but had no authority to

References (42)

M.A. Mufson et al.
Pneumococcal antibody levels one decade after immunization of healthy adults
Am J Med Sci
(1987)
A.M. McBean et al.
Decreasing invasive pneumococcal disease in the elderly: a state-level analysis
Vaccine
(2006)
A. Melegaro et al.
Cost-effectiveness analysis of pneumococcal conjugate vaccination in England and Wales
Vaccine
(2004)
W.B. Kannel et al.
Demographics of the prevalence, incidence, and management of coronary heart disease in the elderly and in women
Ann Epidemiol
(1992)
A.M. Fry et al.
Comparing potential benefits of new pneumococcal vaccines with the current polysaccharide vaccine in the elderly
Vaccine
(2002)
K.L. O’Brien et al.
Combined schedules of pneumococcal conjugate and polysaccharide vaccines: is hyporesponsiveness an issue?
Lancet Infect Dis
(2007)
C.M. Greene et al.
Preventability of invasive pneumococcal disease and assessment of current polysaccharide vaccine recommendations for adults: United States, 2001–2003
Clin Infect Dis
(2006)
M.C. Rodriguez-Barradas et al.
Antibody to capsular polysaccharides of Streptococcus pneumoniae after vaccination of human immunodeficiency virus-infected subjects with 23-valent pneumococcal vaccine
J Infect Dis
(1992)
L.A. Jackson et al.
Safety of revaccination with pneumococcal polysaccharide vaccine
JAMA
(1999)
F.J. Walker et al.
Reactions after 3 or more doses of pneumococcal polysaccharide vaccine in adults in Alaska
Clin Infect Dis
(2005)

P. Gardner

A need to update and revise the pneumococcal vaccine recommendations for adults

Ann Intern Med

(2003)

G.T. Ray et al.

Cost-effectiveness of pneumococcal conjugate vaccine: evidence from the first 5 years of use in the United States incorporating herd effects

Pediatr Infect Dis J

(2006)

C.A. Lexau et al.

Changing epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine

JAMA

(2005)

M.H. Kyaw et al.

Effect of introduction of the pneumococcal conjugate vaccine on drug-resistant Streptococcus pneumoniae

N Engl J Med

(2006)

J.E. Sisk et al.

Cost-effectiveness of vaccination against pneumococcal bacteremia among elderly people

JAMA

(1997)

J.E. Sisk et al.

Cost-effectiveness of vaccination against invasive pneumococcal disease among people 50 through 64 years of age: role of comorbid conditions and race

Ann Intern Med

(2003)

A. Melegaro et al.

The 23-valent pneumococcal polysaccharide vaccine. Part II. A cost-effectiveness analysis for invasive disease in the elderly in England and Wales

Eur J Epidemiol

(2004)

K.K. Ho et al.

Survival after the onset of congestive heart failure in Framingham Heart Study subjects

Circulation

(1993)

R.J. Goldberg et al.

Factors associated with survival to 75 years of age in middle-aged men and women. The Framingham study

Arch Intern Med

(1996)

W.B. Kannel et al.

Profile for estimating risk of heart failure

Arch Intern Med

(1999)

Cited by (61)

Pneumococcal Vaccination Strategies in 50-Year-Olds to Decrease Racial Disparities: A US Societal Perspective Cost-Effectiveness Analysis
2024, Value in Health
This study assesses the impact of expanding pneumococcal vaccination to all 50-year-olds to decrease racial disparities by estimating from the societal perspective, the cost-effectiveness of 20-valent pneumococcal conjugate vaccine (PCV20) and 15-valent conjugate vaccine followed by 23-valent polysaccharide vaccine (PCV15/PPSV23) for 50-year-olds.
A Markov model compared the cost-effectiveness of PCV20 or PCV15/PPSV23 in all general population 50- and 65-years-olds compared with current US recommendations and with no vaccination in US Black and non-Black cohorts. US data informed model parameters. Pneumococcal disease societal costs were estimated using direct and indirect costs of acute illness and of pneumococcal-related long-term disability and mortality. Hypothetical 50-year-old cohorts were followed over their lifetimes with costs and effectiveness discounted 3% per year. Deterministic and probabilistic sensitivity analyses assessed model uncertainty.
In Black cohorts, PCV20 for all at ages 50 and 65 was the least costly strategy and had greater effectiveness than no vaccination and current recommendation strategies, whereas PCV15/PPSV23 at 50 and 65 cost more than $1 million per quality-adjusted life year (QALY) gained compared with PCV20 at 50 and 65. In non-Black cohorts, PCV20 at 50 and 65 cost $62 083/QALY and PCV15/PPSV23 at 50 and 65 cost more than $1 million/QALY with current recommendations, again being more costly and less effective. In probabilistic sensitivity analyses, PCV20 at 50 and 65 was favored in 85.7% (Black) and 61.8% (non-Black) of model iterations at a $100 000/QALY gained willingness-to-pay threshold.
When considering the societal costs of pneumococcal disease, PCV20 at ages 50 and 65 years in the general US population is a potentially economically viable strategy, particularly in Black cohorts.
Cost-effectiveness of dual influenza and pneumococcal vaccination among the elderly in Shenzhen, China
2021, Vaccine
To assess the cost-effectiveness of dual influenza and pneumococcal vaccination for the elderly in Shenzhen, China.
A Markov state-transition model with a weekly cycle was developed to compare the outcomes of dual influenza and pneumococcal vaccination for the prevention of influenza and pneumococcal infections compared with no vaccination among 70–74 years old people in Shenzhen over 5 years. The model allowed seasonal variation of influenza activity. We calculated the incremental cost-effectiveness ratio (ICER) with costs and quality-adjusted life years (QALYs) discounted at 5% annually from the societal perspective. The impact of parameter uncertainty on the results was examined using one-way and probabilistic sensitivity analyses (PSA).
In the base case, dual vaccination prevented 5042 influenza infections, 26 IPD cases, 3 disabilities, 34 deaths, and cost US$7.1 per person while resulting in a net gain of 0.0026 QALYs compared with no vaccination. Using once the Chinese gross domestic product per capita in 2019 (US$10,289) as the willingness-to-pay threshold, dual vaccination was cost-effective with an ICER of US$2699 per QALY gained. One-way sensitivity analyses showed that the ICER was relatively sensitive to changes in influenza attack rates and influenza vaccine effectiveness. Based on the results of PSA with 1000 Monte Carlo simulations, receiving both vaccines was cost-effective in 100% of the repetitions.
The current study provides evidence that dual influenza and pneumococcal vaccination is a cost-effective disease prevention strategy for the elderly in Shenzhen, China.
Pneumococcal Vaccination in Adults Aged ≥65 Years: Cost-Effectiveness and Health Impact in U.S. Populations
2020, American Journal of Preventive Medicine
Recommending both the conjugate and polysaccharide pneumococcal vaccines to all U.S. seniors may have little public health impact and be economically unreasonable. Public health impact and cost-effectiveness of using both vaccines in all adults aged ≥65 years were estimated compared with an alternative strategy (omitting pneumococcal conjugate vaccine in the nonimmunocompromised) and with the newly revised recommendation (giving or omitting conjugate vaccine based on patient–physician shared decision making).
Strategies were examined in hypothetical U.S. 65-year-old population cohorts and segmented into health states based on age- and population-specific data in a Markov state-transition model with a lifetime time horizon from a healthcare perspective. Black population cohorts were examined separately given greater illness risk and lower vaccine uptake. Model parameters came from the Centers for Disease Control Active Core Bacterial Surveillance network, National Health Interview Survey, and Nationwide Inpatient Sample data. Outcomes included incremental costs per quality-adjusted life year gained and pneumococcal disease outcomes for each strategy. Data were gathered and analysis performed in 2018.
Giving both vaccines, either routinely or with shared decision making, was most effective, reducing pneumococcal disease incidence compared with no vaccination, but costing $765,000–$2.18 million/quality-adjusted life year gained. Depending on examined population and scenario, the alternative strategy cost $65,700–$226,700/quality-adjusted life year gained (less in black populations) and reduced cases and deaths by 0.3%–0.9%.
A vaccination strategy that omits pneumococcal conjugate vaccine in immunocompetent U.S. seniors may be economically reasonable, particularly for black seniors. Use of both pneumococcal vaccines was more effective but substantially more expensive.
Pneumococcal Disease: A Systematic Review of Health Utilities, Resource Use, Costs, and Economic Evaluations of Interventions
2019, Value in Health
Citation Excerpt :
In total, 178 articles included in the review were economic evaluations of interventions targeted at pneumococcal infections, of which 26 focused on the impact of antibiotic treatment on pneumococcal diseases, 12 focused on other diagnostic/operational interventions (for example, management, treatment guidelines, standing-order programs, and screening), and the largest number of studies (140) focused on vaccinations programs. The vaccination programs were further stratified into adult (Table 233-81) and pediatric (Table 382-172) categories. For both adult and pediatric programs, we report assessments of cost-effectiveness of different vaccines against no vaccination, vaccine use in different age groups, and head-to-head comparison of different vaccines.
Pneumococcal diseases cause substantial mortality, morbidity, and economic burden. Evidence on data inputs for economic evaluations of interventions targeting pneumococcal disease is critical.
To summarize evidence on resource use, costs, health utilities, and cost-effectiveness for pneumococcal disease and associated interventions to inform future economic analyses.
We searched MEDLINE, Embase, Web of Science, CINAHL, PsycINFO, EconLit, and Cochrane databases for peer-reviewed studies in English on pneumococcal disease that reported health utilities using direct or indirect valuation methods, resource use, costs, or cost-effectiveness of intervention programs, and summarized the evidence descriptively.
We included 383 studies: 9 reporting health utilities, 131 resource use, 160 economic costs of pneumococcal disease, 95 both resource use and costs, and 178 economic evaluations of pneumococcal intervention programs. Health state utility values ranged from 0 to 1 for both meningitis and otitis media and from 0.3 to 0.7 for both pneumonia and sepsis. Hospitalization was shortest for otitis media (range: 0.1-5 days) and longest for sepsis/septicemia (6-48). The main categories of costs reported were drugs, hospitalization, and household or employer costs. Resource use was reported in hospital length of stay and number of contacts with general practitioners. Costs and resource use significantly varied among population ages, disease conditions, and settings. Current vaccination programs for both adults and children, antibiotic use and outreach programs to promote vaccination, early disease detection, and educational programs are cost-effective in most countries.
This study has generated a comprehensive repository of health economic evidence on pneumococcal disease that can be used to inform future economic evaluations of pneumococcal disease intervention programs.
Cost-effectiveness of adult pneumococcal vaccination policies in underserved minorities aged 50–64 years compared to the US general population
2019, Vaccine
Changing pneumococcal disease epidemiology due to childhood vaccination has prompted re-examination of US adult pneumococcal vaccination policies, as have considerations of greater pneumococcal disease incidence and higher prevalence of conditions that increase risk in underserved minority populations. Prior analyses suggest routine pneumococcal vaccination at age 50 could be considered, which could disproportionately benefit underserved populations.
A Markov cohort model estimated the cost-effectiveness of US pneumococcal vaccination policies in hypothetical 50-year-old underserved minority and general population cohorts. Strategies included receiving one or both available pneumococcal vaccines based on age- or chronic condition-specific criteria. US databases and medical literature data calibrated pneumococcal illness incidence, vaccine serotype distributions, age- and race-specific chronic condition distributions, and costs. Black population data were used as a proxy for underserved minorities. We took a US healthcare perspective, discounting at 3%/year. One-way and probabilistic sensitivity analyses were performed and scenarios modeling differing vaccine assumptions were examined.
In both black and general population 50-year-olds, giving both pneumococcal vaccines to all 50-year-olds prevented the most disease, but cost >$250,000 per quality adjusted life year (QALY) gained. Current CDC recommendations (both vaccines for the immunocompromised, polysaccharide vaccine for other high-risk conditions) were economically favorable in either population when analyses assumed polysaccharide vaccine was ineffective against nonbacteremic pneumococcal pneumonia (NBP). If polysaccharide vaccine is effective against NBP or if less complex age-based vaccination recommendations result in increased vaccine uptake, giving polysaccharide vaccine to all 50-year-olds cost <$100,000/QALY; this effect was more pronounced in black cohorts. Results were robust in 1-way and probabilistic sensitivity analyses.
Despite changes in pneumococcal epidemiology, current CDC recommendations were favored in underserved minority and general population cohorts. Polysaccharide vaccine for all 50-year-olds could be considered under some vaccine uptake and effectiveness assumptions, particularly if mitigating racial health disparities in pneumococcal disease is a priority.
Cost-effectiveness of adult vaccinations: A systematic review
2019, Vaccine
Citation Excerpt :
The 78 abstracted publications yielded 161 outcomes (Table 1). All the identified outcomes from the publications in the final set of records are summarized in the appendix [66–133]. The percent of outcomes associated with age-based vaccination recommendations by vaccine group was 75 for influenza, 62 for pneumococcal, 74 for HPV, 100 for HZ, and 72 for Td/Tdap.
Coverage levels for many recommended adult vaccinations are low. The cost-effectiveness research literature on adult vaccinations has not been synthesized in recent years, which may contribute to low awareness of the value of adult vaccinations and to their under-utilization. We assessed research literature since 1980 to summarize economic evidence for adult vaccinations included on the adult immunization schedule.
We searched PubMed, EMBASE, EconLit, and Cochrane Library from 1980 to 2016 and identified economic evaluation or cost-effectiveness analysis for vaccinations targeting persons aged ≥18 years in the U.S. or Canada. After excluding records based on title and abstract reviews, the remaining publications had a full-text review from two independent reviewers, who extracted economic values that compared vaccination to “no vaccination” scenarios.
The systematic searches yielded 1688 publications. After removing duplicates, off-topic publications, and publications without a “no vaccination” comparison, 78 publications were included in the final analysis (influenza = 25, pneumococcal = 18, human papillomavirus = 9, herpes zoster = 7, tetanus-diphtheria-pertussis = 9, hepatitis B = 9, and multiple vaccines = 1). Among outcomes assessing age-based vaccinations, the percent indicating cost-savings was 56% for influenza, 31% for pneumococcal, and 23% for tetanus-diphtheria-pertussis vaccinations. Among age-based vaccination outcomes reporting $/QALY, the percent of outcomes indicating a cost per QALY of ≤$100,000 was 100% for influenza, 100% for pneumococcal, 69% for human papillomavirus, 71% for herpes zoster, and 50% for tetanus-diphtheria-pertussis vaccinations.
The majority of published studies report favorable cost-effectiveness profiles for adult vaccinations, which supports efforts to improve the implementation of adult vaccination recommendations.

View all citing articles on Scopus

View full text

Alternative strategies for adult pneumococcal polysaccharide vaccination: A cost-effectiveness analysis

Summary

Introduction

Section snippets

Methods

Invasive pneumococcal disease (IPD) epidemiology

Discussion

Acknowledgements

Am J Med Sci

Vaccine

Vaccine

Ann Epidemiol

Vaccine

Lancet Infect Dis

Preventability of invasive pneumococcal disease and assessment of current polysaccharide vaccine recommendations for adults: United States, 2001–2003

Clin Infect Dis

Antibody to capsular polysaccharides of Streptococcus pneumoniae after vaccination of human immunodeficiency virus-infected subjects with 23-valent pneumococcal vaccine

J Infect Dis

Safety of revaccination with pneumococcal polysaccharide vaccine

JAMA

Reactions after 3 or more doses of pneumococcal polysaccharide vaccine in adults in Alaska

Clin Infect Dis

A need to update and revise the pneumococcal vaccine recommendations for adults

Ann Intern Med

Cost-effectiveness of pneumococcal conjugate vaccine: evidence from the first 5 years of use in the United States incorporating herd effects

Pediatr Infect Dis J

Changing epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine

JAMA

Effect of introduction of the pneumococcal conjugate vaccine on drug-resistant Streptococcus pneumoniae

N Engl J Med

Cost-effectiveness of vaccination against pneumococcal bacteremia among elderly people

JAMA

Cost-effectiveness of vaccination against invasive pneumococcal disease among people 50 through 64 years of age: role of comorbid conditions and race

Ann Intern Med

The 23-valent pneumococcal polysaccharide vaccine. Part II. A cost-effectiveness analysis for invasive disease in the elderly in England and Wales

Eur J Epidemiol

Survival after the onset of congestive heart failure in Framingham Heart Study subjects

Circulation

Factors associated with survival to 75 years of age in middle-aged men and women. The Framingham study

Arch Intern Med

Profile for estimating risk of heart failure

Arch Intern Med