Cost-effectiveness of an in-development adult-formulated 21-valent pneumococcal conjugate vaccine in US adults aged 50 years or older.

Indirect effects of childhood pneumococcal conjugate vaccines (PCV) have diminished the cost-effectiveness of current adult vaccine recommendations. An in-development adult-formulated 21-valent pneumococcal conjugate vaccine (PCV21) may play a critical role in reducing pneumococcal illness by targeting a larger number of serotypes responsible for adult pneumococcal infections. This study assesses the cost-effectiveness of PCV21 in US adults aged 50 years or older compared with currently recommended pneumococcal vaccines, from both the societal and healthcare perspectives. A Markov model evaluated the lifetime cost-effectiveness of PCV21 (given at age 50 years only, at ages 50/65 years, and risk-based at ages < 65 years plus age-based at age 65 years) compared to no vaccination and to currently recommended pneumococcal vaccines given either as currently recommended or routinely at ages 50/65 years. The analysis was conducted in hypothetical Black and non-Black cohorts aged 50 years or older, with and without considering childhood pneumococcal vaccination indirect effects. Model parameters were based on US data. Parameter uncertainty was assessed using 1-way and probabilistic sensitivity analyses. From the societal perspective, PCV21 at ages 50/65 years compared to PCV21 at age 50 years cost $7,410 per quality adjusted life year (QALY) gained in Black cohort analyses and $85,696/QALY gained in the non-Black cohort; PCV21 at ages 50/65 years had the most favorable public health outcomes. From the healthcare perspective, compared to no vaccination, PCV21 at age 50 years cost $46,213/QALY gained in the Black cohort and $86,629/QALY in non-Blacks. All other strategies were dominated in both cohorts and from both perspectives. When considering childhood pneumococcal vaccination indirect effects, costs of PCV21 at ages 50/65 years remained less than $140,000/QALY gained from the societal perspective in both populations. PCV21 is potentially cost-effective compared to currently approved pneumococcal vaccines in adults aged 50 years or older from both the societal and healthcare perspectives.

Pneumococcal Vaccination Strategies in 50-Year-Olds to Decrease Racial Disparities: A US Societal Perspective Cost-Effectiveness Analysis.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Societal Cost of Racial Pneumococcal Disease Disparities in US Adults Aged 50 Years or Older.

OBJECTIVE: This study aimed to estimate the societal cost of racial disparities in pneumococcal disease among US adults aged ≥  50 years. METHODS: In a model-based analysis, societal costs of invasive pneumococcal disease (IPD) and hospitalized nonbacteremic pneumococcal pneumonia (NBP) were estimated using (1) direct medical costs plus indirect costs of acute illness; (2) indirect costs of pneumococcal mortality; and (3) direct and indirect costs of related disability. Disparities costs were calculated as differences in average per-person pneumococcal disease cost between Black and non-Black adults aged ≥  50 years multiplied by the Black population aged ≥  50 years. Costs were in 2019 US dollars (US$), with future costs discounted at 3% per year. RESULTS: Total direct and indirect costs per IPD case were US$186,791 in Black populations and US$182,689 in non-Black populations; total hospitalized NBP costs per case were US$100,632 (Black) and US$96,781 (non-Black). The difference in population per-person total pneumococcal disease costs between Black and non-Black adults was US$47.85. Combined societal costs of disparities for IPD and hospitalized NBP totaled US$673.2 million for Black adults aged ≥  50 years. Disease and disability risks, life expectancy, and case-fatality rates were influential in one-way sensitivity analyses, but the lowest cost across all analyses was US$194 million. The 95% probability range of racial disparity costs were US$227.2-US$1156.9 million in a probabilistic sensitivity analysis. CONCLUSIONS: US societal cost of racial pneumococcal disease disparities in persons aged ≥ 50 years is substantial. Successful pneumococcal vaccination policy and programmatic interventions to mitigate these disparities could decrease costs and improve health.

Cost-effectiveness of an in-development adult-formulated pneumococcal vaccine in older US adults.

INTRODUCTION: CDC pneumococcal vaccination recommendations for older adults now include either 15- or 20-valent pneumococcal conjugate vaccine (PCV15/PCV20). However, an in-development 21-valent vaccine (PCV21), formulated based on adult pneumococcal disease epidemiology, could substantially increase coverage of disease-causing pneumococcal serotypes, particularly in Black older adults, who are at greater risk. The potential public health impact and cost-effectiveness of PCV21 compared to currently recommended vaccines in older adults is unclear. METHODS: A Markov decision model compared current pneumococcal vaccination recommendations to PCV21 use in Black and non-Black 65-year-old cohorts. CDC Active Bacterial Core surveillance data informed population and serotype-specific pneumococcal disease risk. Vaccine effectiveness was estimated using Delphi panel estimates and clinical trial data, with variation in sensitivity analyses. Potential indirect effects on adult disease from PCV15 childhood vaccination were examined. All model parameters were varied individually and collectively in sensitivity analyses. Scenarios with decreased PCV21 effectiveness and potential COVID-19 pandemic effects were also examined. RESULTS: In the Black cohort, the PCV21 strategy cost $88,478 per quality adjusted life-year (QALY) gained without and $97,952/QALY with childhood PCV15 indirect effects. PCV21 in the non-Black cohort cost $127,436/QALY gained without and $141,358/QALY with childhood PCV15 effects. Current recommendation strategies were economically unfavorable, regardless of population or indirect childhood vaccination effects. Results favoring PCV21 use were robust in sensitivity analyses and alternative scenarios. CONCLUSION: An in-development PCV21 vaccine would likely be economically and clinically favorable compared to currently recommended pneumococcal vaccines in older adults. While PCV21 was more favorable in Black cohort analyses, results for both Black and non-Black populations were economically reasonable, highlighting the potential importance of adult-specific pneumococcal vaccine formulations and, pending further investigation, potentially justifying a future general population recommendation for PCV21 use in older adults.

Cost-effectiveness of revised US pneumococcal vaccination recommendations in underserved minority adults < 65-years-old.

BACKGROUND: The 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recently recommended for US adults, giving either PCV20 alone or PCV15 followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) to all 65 + -year-olds and to high-risk younger adults. However, general population recommendations to vaccinate all 50-year-olds could reduce racial pneumococcal disease disparities given greater risk in underserved minority populations. METHODS: A Markov model examining hypothetical 50-year-old Black cohorts (serving as a proxy for underserved minorities) and non-Black cohorts estimated the incremental cost effectiveness of US adult pneumococcal vaccination recommendations compared to PCV20 or PCV15/PPSV23 for all 50-year-olds with no vaccination thereafter, or PCV20 or PCV15/PPSV23 for all at ages 50 and 65 years (50/65). Model parameters came from US databases, clinical trials, and Delphi panels. Cohorts were followed over their lifetimes from a healthcare perspective discounted at 3 %/year. RESULTS: PCV15/PPSV23 given at ages 50/65 had greatest public health impact. In Black cohorts, PCV15/PPSV23 at age 50 cost $104,723/quality adjusted life year (QALY) gained compared to PCV20 at age 50, while PCV15/PPSV23 at 50/65 cost $240,952/QALY gained compared to PCV15/PPSV23 at age 50. Both current recommendation options were more expensive and less effective than other strategies in both cohorts. In sensitivity analyses, age-based PCV20 or PCV15/PPSV23 use at ages 50 or 50/65 could be favorable depending on vaccine effectiveness or differential vaccine uptake, while current recommendations remained unfavorable. CONCLUSION: Recent risk-based US adult pneumococcal vaccination recommendations for adults < 65-years-old, were economically and clinically unfavorable compared to general population vaccination of all 50-year-olds in Black and non-Black cohorts. An age-based pneumococcal vaccination recommendation at age 50 years may reduce inequities in pneumococcal disease burden.

Cost-Effectiveness of Newly Recommended Pneumococcal Vaccination Strategies in Older Underserved Minority Adults in the USA.

INTRODUCTION: US pneumococcal vaccination recommendations for adults aged 65 years or older recently changed, with options for either 20-valent pneumococcal conjugate vaccine (PCV20) or the combination of 15-valent conjugate vaccine (PCV15) followed by 23-valent polysaccharide vaccine (PPSV23) 1 year later. Underserved minority adults are at higher risk for pneumococcal disease. METHODS: A Markov decision analysis model estimated the incremental cost-effectiveness of the newly adopted general population pneumococcal vaccination strategies in older underserved minority adults. The model examined hypothetical 65-year-old US Black cohorts (serving as a proxy for underserved minorities) and non-Black cohorts receiving PCV20 or PCV15/PPSV23, or no vaccination. Main outcome measures included incremental cost-effectiveness per quality-adjusted life year (QALY) gained and pneumococcal disease public health outcomes. RESULTS: Black cohorts had a greater risk of pneumococcal disease hospitalization compared to non-Black cohorts. In Black cohorts, total per person PCV20 strategy costs, compared to no vaccination, were $124 higher while gaining 0.00073 QALY, or $169,540/QALY gained. PCV15/PPSV23 cost $535,797/QALY compared to PCV20. In the non-Black cohort, PCV20 cost $210,529/QALY gained compared to no vaccination and PCV15/PPSV23 cost $728,423/QALY. Plausible variation of vaccine effectiveness minimally affected PCV20 strategy results and made PCV15/PPSV23 more unfavorable. In scenarios where the simpler one-vaccine PCV20 strategy increased absolute vaccine uptake by 10%, PCV20 cost-effectiveness changed minimally while PCV15/PPSV23 cost in excess of $6 million/QALY in the Black cohort. In probabilistic sensitivity analyses that varied all parameters simultaneously, PCV15/PPSV23 was unlikely to be favored at thresholds less than $500,000/QALY gained. CONCLUSION: General population recommendations for PCV20 use are substantially more economically reasonable in Black and non-Black older adult populations than PCV15/PPSV23. If using a single vaccine increases uptake, which is potentially more likely in the underserved, then PCV20 use becomes even more favorable.

Higher-Valency Pneumococcal Conjugate Vaccines: An Exploratory Cost-Effectiveness Analysis in U.S. Seniors.

INTRODUCTION: Use of the 13-valent pneumococcal conjugate vaccine in nonimmunocompromised adults aged ≥65 years is controversial. Higher-valency conjugate vaccines (15-valent and 20-valent ) are under development; their potential cost effectiveness in older adults is unknown, particularly when potential indirect (herd immunity) effects from childhood vaccination are considered. METHODS: A Markov model estimated the cost effectiveness of current U.S. recommendations and alternative strategies using currently available and in-development pneumococcal conjugate vaccines in seniors. Separately, strategies using a hypothetical 20-valent vaccine adding the 7 most common disease-causing non-13-valent vaccine serotypes were considered. Sensitivity analyses were performed and alternative scenarios were examined. Data were gathered and the analyses were performed in 2020. RESULTS: In analyses considering only existing and in-development vaccines, sole 20-valent vaccine use cost $172,491/quality-adjusted life year gained compared with current U.S. recommendations under baseline assumptions (equal serotype effectiveness and no childhood vaccination indirect effects). Strategies using 15-valent vaccine were more costly and less effective. When 13-valent/20-valent vaccines were assumed ineffective against pneumococcal serotype 3 and 15-valent vaccine was fully effective, 15-valent vaccine cost $237,431/quality-adjusted life year gained. With indirect effects considered, 15-valent or 20-valent vaccine cost >$449,000/quality-adjusted life year gained. When adding hypothetical 20-valent vaccine under baseline assumptions, hypothetical 20-valent vaccine cost $139,348/quality-adjusted life year gained. CONCLUSIONS: In-development pneumococcal conjugate vaccines may be economically unreasonable in older adults, regardless of serotype effectiveness assumptions, particularly when considering potential indirect effects from use of those vaccines in children. Adult vaccines containing high-risk serotypes not contained in childhood vaccines may be more promising.

Should older adult pneumococcal vaccination recommendations change due to decreased vaccination in children during the pandemic? A cost-effectiveness analysis.

BACKGROUND: The COVID-19 pandemic is causing declines in childhood immunization rates. We examined potential COVID-19-related changes in pediatric 13-valent pneumococcal conjugate vaccine (PCV13) use, subsequent impact on childhood and adult pneumococcal disease rates, and how those changes might affect the favorability of PCV13 use in non-immunocompromised adults aged ≥65 years. METHODS: A Markov model estimated pediatric disease resulting from decreased PCV13 use in children aged <5 years; absolute decreases from 10 to 50% for 1-2 years duration were examined, assuming no catch-up vaccination and that decreased vaccination led to proportionate increases in PCV13 serotype pneumococcal disease in children and seniors. Integrating pediatric model output into a second Markov model examining 65-year-olds, we estimated the cost effectiveness of older adult pneumococcal vaccination strategies while accounting for potential epidemiologic changes from decreased pediatric vaccination. RESULTS: One year of 10-50% absolute decreases in PCV13 use in <5-year-olds increased pneumococcal disease by an estimated 4-19% in seniors; 2 years of decreased use increased senior rates by 8-38%. In seniors, a >53% increase in pneumococcal disease was required to favor PCV13 use in non-immunocompromised seniors at a $200,000 per quality-adjusted life-year gained threshold, which corresponded to absolute decreases in pediatric PCV13 vaccination of >50% over a 2-year period. In sensitivity analyses, senior PCV13 vaccination was unfavorable if absolute decreases in pediatric PCV13 receipt were within plausible ranges, despite model assumptions favoring PCV13 use in seniors. CONCLUSION: COVID-19-related decreases in pediatric PCV13 use would need to be both substantial and prolonged to make heightened PCV13 use in non-immunocompromised seniors economically favorable.

Is further research on adult pneumococcal vaccine uptake improvement programs worthwhile? Α value of information analysis.

BACKGROUND: Pneumococcal vaccination policy for US adults is evolving, but previous research has shown that programs to increase vaccine uptake are economically favorable, despite parameter uncertainty. Using value of information (VOI) analysis and prior analyses, we examine the value of further research on vaccine uptake program parameters. METHODS: In US 50-64-year-olds, current vaccine recommendations with and without an uptake program were analyzed. In older adults, current recommendations and an alternative strategy (polysaccharide vaccine for all, adding conjugate vaccine only for the immunocompromised) with and without uptake programs were examined. Uptake program parameters were derived from a clinical trial (absolute uptake increase 12.3% [range 0-25%], per-person cost $1.78 [range $0.70-$2.26]), with other parameters obtained from US databases. VOI analyses incorporated probabilistic sensitivity analysis outputs into R-based regression techniques. RESULTS: In 50-64-year-olds, an uptake program cost $54,900/QALY gained compared to no uptake program. For ages ≥65, the program cost $287,000/QALY gained with the alternative strategy and $765,000/QALY with current recommendations. In younger adults, population-level expected value of perfect information (EVPI) was $59.7 million at $50,000/QALY gained and $2.8 million at $100,000/QALY gained. In older adults, EVPI values ranged from ~$1 million to $34.5 million at $100,000 and $200,000/QALY thresholds. The population expected value of partial perfect information (EVPPI) for combined uptake program cost and uptake improvement parameters in the younger population was $368,700 at $50,000/QALY and $43,900 at $100,000/QALY gained thresholds. In older adults, population EVPPI for vaccine uptake program parameters was $0 at both thresholds, reaching a maximum value of $445,000 at a $225,000/QALY threshold. Other model parameters comprised larger components of the global EVPI. CONCLUSION: VOI results do not support further research on pneumococcal vaccine uptake programs in adults at commonly cited US cost-effectiveness benchmarks. Further research to reduce uncertainty in other aspects of adult pneumococcal vaccination is justifiable.

Cost-Effectiveness of Pneumococcal Vaccination Policies and Uptake Programs in US Older Populations.

BACKGROUND/OBJECTIVES: Recently revised vaccination recommendations for US adults, aged 65 years and older, include both 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13), with PCV13 now recommended for immunocompetent older people based on shared decision making. The public health impact and cost-effectiveness of this recommendation or of pneumococcal vaccine uptake improvement interventions are unclear. DESIGN: Markov decision analysis. SETTING AND PARTICIPANTS: Hypothetical 65-year-old general and black population cohorts. INTERVENTION: Current pneumococcal vaccination recommendations for US older people, an alternative policy omitting PCV13 in immunocompetent older people, and vaccine uptake improvement programs. RESULTS: The current pneumococcal vaccination recommendation was the most effective strategy, but afforded slight public health benefits compared to an alternative (PPSV23 for all older people plus PCV13 for the immunocompromised) and cost greater than $750 000 per quality-adjusted life-year (QALY) gained in either population group with a vaccine uptake improvement program (absolute uptake increase = 12.3%; cost = $1.78/eligible patient) in place. The alternative strategy was more economically favorable, but cost greater than $100 000/QALY in either population, with or without an uptake intervention. Results were robust in sensitivity analyses; however, in black older people, the alternative strategy with an uptake program was most likely to be favored in probabilistic sensitivity analyses at a $150 000/QALY gained threshold. CONCLUSION: Current pneumococcal vaccination recommendations for US older people are economically unfavorable compared to an alternative strategy omitting PCV13 in the immunocompetent. The alternative recommendation with an uptake improvement program may be economically reasonable in black population analyses and could be worth considering as a population-wide recommendation if mitigating racial disparities is a priority. J Am Geriatr Soc 68:1271-1278, 2020.

Pneumococcal Vaccination in Adults Aged ≥65 Years: Cost-Effectiveness and Health Impact in U.S. Populations.

INTRODUCTION: 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). METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.

Cost-Effectiveness of Pneumococcal Vaccination and Uptake Improvement Programs in Underserved and General Population Adults Aged < 65 Years.

In US adults aged < 65 years, pneumococcal vaccination is recommended when high-risk conditions are present, but vaccine uptake is low. Additionally, there are race-based differences in illness risk and vaccination rates. The cost-effectiveness of programs to improve vaccine uptake or of alternative vaccination policies to increase protection is unclear. A decision analysis compared, in US black and general population cohorts aged 50 years, the public health impact and cost-effectiveness of pneumococcal vaccination recommendations, without and with a vaccine uptake improvement program, and alternative population vaccine policies. Program-based uptake improvement (base case: 12.3% absolute increase, costing $1.78/eligible patient) was based on clinical trial data. US data informed population-specific pneumococcal risk. Vaccine effectiveness was estimated using Delphi panel and trial data. In both black and general population cohorts, an uptake improvement program for current vaccination recommendations was favored, costing $48,621 per QALY gained in black populations ($54,929/QALY in the general population) compared to current recommendations without a program. Alternative vaccination policies largely prevented less illness and were economically unfavorable. In sensitivity analyses, uptake programs were favored, at a $100,000/QALY threshold, unless they improved absolute vaccine uptake < 2.1% in blacks or < 2.6% in the general population. Results were robust in sensitivity analyses. Programs to increase adult pneumococcal vaccination uptake are economically reasonable compared to changes in vaccination recommendations, and more favorable in underserved minorities than in the general population. If addressing race-based health disparities is a priority, evidence-based programs to increase vaccination should be considered.

Racial Disparities in Adult Pneumococcal Vaccination Indications and Pneumococcal Hospitalizations in the U.S.

BACKGROUND: Racial disparities in U.S. adult pneumococcal vaccination rates persist despite reduced barriers to access. Consequently, racial and ethnic minorities experience pneumococcal disease at higher rates than whites. This study examined prevalence of high-risk conditions and pneumococcal hospitalizations among U.S. black and non-black populations aged ≥50 years. METHODS: National Health Interview Survey, National Center for Health Statistics and National Inpatient Sample data were used to create black and non-black population cohorts, determine risk factors for pneumococcal disease (pneumococcal vaccine indications) and assess the impact of pneumococcal hospitalization. Each racial cohort was segmented into groups based on the presence of immunocompromising or other pneumococcal high-risk conditions. Persons without those conditions were separated into smokers (also a pneumococcal vaccine indication) and nonsmokers. Mortality was estimated from NCHS life table data. NIS data provided length of stay and costs (calculated from cost to charge ratios) for admissions related to pneumococcal disease including bacteremia, meningitis and nonbacteremic pneumonia. RESULTS: There were similar proportions of immunocompromised (<5%) and smokers (14%) in both racial cohorts. Likelihood of non-immunocompromising pneumococcal high-risk conditions was higher for blacks than non-blacks at age 65, but higher for non-blacks than blacks at age 80 years (P < 0.001). Age-specific relative likelihood of mortality was 1.1%-12% higher in blacks than non-blacks (P < 0.001). Length of stay was significantly longer for blacks than non-blacks in all age and discharge status groups for non-bacteremic pneumonia and for blacks discharged alive with invasive pneumococcal disease. Costs were higher for blacks 65 years or older with invasive pneumococcal disease. CONCLUSION: Marked differences exist between U.S. black and non-black populations in likelihood of conditions conferring a high-risk of pneumococcal disease, and for length of stay and costs of pneumococcal disease hospitalizations. Further research is recommended to identify cost-effective policies or interventions to increase vaccine uptake in higher risk populations.

Cost-effectiveness of adult pneumococcal vaccination policies in underserved minorities aged 50-64 years compared to the US general population.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

An intervention to improve pneumococcal vaccination uptake in high risk 50-64 year olds vs. expanded age-based recommendations: an exploratory cost-effectiveness analysis.

In the U.S., pneumococcal polysaccharide vaccine (PPSV23) uptake among high-risk adults aged <65 years is consistently low and improvement is needed. One barrier to improved vaccine coverage is the complexity of the adult vaccination schedule. This exploratory analysis compared the cost-effectiveness of strategies to increase pneumococcal vaccine uptake in high-risk adults aged 50-64 years. We used a Markov model to compare strategies for non-immunocompromised 50-64 year olds: 1) current pneumococcal polysaccharide vaccine (PPSV23) recommendations; 2) current recommendations enhanced by an intervention; 3) PPSV23 plus pneumococcal conjugate vaccine (PCV13) for high-risk patients with no intervention; or 4) both vaccines for all 50-year-olds with no intervention. Parameters included CDC data and other US data, varied extensively in sensitivity analyses. In the analysis, vaccinating high-risk individuals with PPSV23/PCV13 was the least costly strategy, with total costs of $424/person. Vaccinating all 50 year olds with PPSV23/PCV13 cost $40 more and gained 0.00068 quality-adjusted life years (QALY), or $57,786/QALY gained. Current recommendations with or without an intervention program were more expensive and less effective than other strategies. In multi-way sensitivity analyses, the current recommendations/intervention program strategy was favored at a $100,000/QALY threshold only if non-bacteremic pneumococcal pneumonia rate or PCV13 serotype coverage were substantially lower than base case values. Thus, an intervention program to improve pneumococcal vaccine uptake among high-risk 50-64 year-olds was not cost-effective in most scenarios. High-risk individuals receiving both PCV13 and PPSV23 could be economically favorable, and vaccinating all 50-year-olds with both vaccines could be considered.

Potential Cost-Effectiveness of a Universal Influenza Vaccine in Older Adults.

BACKGROUND AND OBJECTIVES: "Universal" vaccines that could have multistrain and multiyear effectiveness are being developed. Their potential cost-effectiveness in geriatric populations is unknown. RESEARCH DESIGN AND METHODS: A Markov model estimated effects of a theoretical universal influenza vaccine compared with available seasonal vaccines in hypothetical cohorts of U.S. 65+-year olds followed over a 5-year time horizon to capture potential multiyear protection. Outcomes included costs per quality-adjusted life-year gained and influenza cases avoided. RESULTS: Using hypothetical universal vaccine parameter values (cost $100, vaccine effectiveness 39%, uptake 64%, effectiveness duration 5 years), universal vaccine was less costly than seasonal influenza vaccination strategies. High-dose trivalent influenza vaccine, compared with universal vaccine, gained 0.0028 quality-adjusted life-years and cost $82 more, or $28,700 per quality-adjusted life-year gained. Other seasonal vaccines were not favorable economically. Five-year influenza risk with universal vaccination was 32.3% under base case assumptions, compared with <30% with adjuvanted or high-dose vaccine use. In sensitivity analyses, universal vaccine was favored when uptake or vaccine effectiveness was greater than standard-dose influenza vaccine. If absolute universal vaccine effectiveness was 10% less than standard-dose vaccine, universal vaccine could be cost-saving but not more effective than other strategies. Universal vaccine was not favored if its effectiveness duration was <3 years. DISCUSSION AND IMPLICATIONS: Universal vaccine use in older persons could be either cost effective or cost saving when universal vaccine parameters are within plausible ranges. However, if its effectiveness is substantially less than current vaccines, its use would probably not be favored in geriatric populations.

Cost-effectiveness of increasing vaccination in high-risk adults aged 18-64 Years: a model-based decision analysis.

BACKGROUND: Adults aged 18-64 years with comorbid conditions are at high risk for complications of certain vaccine-preventable diseases, including influenza and pneumococcal disease. The 4 Pillars™ Practice Transformation Program (4 Pillars Program) increases uptake of pneumococcal polysaccharide vaccine, influenza vaccine and tetanus-diphtheria-acellular pertussis vaccine by 5-10% among adults with high-risk medical conditions, but its cost-effectiveness is unknown. METHODS: A decision tree model estimated the cost-effectiveness of implementing the 4 Pillars Program in primary care practices compared to no program for a population of adults 18-64 years of age at high risk of illness complications over a 10 year time horizon. Vaccination rates and intervention costs were derived from a randomized controlled cluster trial in diverse practices in 2 U.S. cities. One-way and probabilistic sensitivity analyses were conducted. RESULTS: From a third-party payer perspective, which considers direct medical costs, the 4 Pillars Program cost $28,301 per quality-adjusted life year gained; from a societal perspective, which adds direct nonmedical and indirect costs, the program was cost saving and more effective than no intervention. Cost effectiveness results favoring the program were robust in sensitivity analyses. From a public health standpoint, the model predicted that the intervention reduced influenza cases by 1.4%, with smaller decreases in pertussis and pneumococcal disease cases. CONCLUSION: The 4 Pillars Practice Transformation Program is an economically reasonable, and perhaps cost saving, strategy for protecting the health of adults aged < 65 years with high-risk medical conditions.

The impact of implementing a demand forecasting system into a low-income country's supply chain.

OBJECTIVE: To evaluate the potential impact and value of applications (e.g. adjusting ordering levels, storage capacity, transportation capacity, distribution frequency) of data from demand forecasting systems implemented in a lower-income country's vaccine supply chain with different levels of population change to urban areas. MATERIALS AND METHODS: Using our software, HERMES, we generated a detailed discrete event simulation model of Niger's entire vaccine supply chain, including every refrigerator, freezer, transport, personnel, vaccine, cost, and location. We represented the introduction of a demand forecasting system to adjust vaccine ordering that could be implemented with increasing delivery frequencies and/or additions of cold chain equipment (storage and/or transportation) across the supply chain during varying degrees of population movement. RESULTS: Implementing demand forecasting system with increased storage and transport frequency increased the number of successfully administered vaccine doses and lowered the logistics cost per dose up to 34%. Implementing demand forecasting system without storage/transport increases actually decreased vaccine availability in certain circumstances. DISCUSSION: The potential maximum gains of a demand forecasting system may only be realized if the system is implemented to both augment the supply chain cold storage and transportation. Implementation may have some impact but, in certain circumstances, may hurt delivery. Therefore, implementation of demand forecasting systems with additional storage and transport may be the better approach. Significant decreases in the logistics cost per dose with more administered vaccines support investment in these forecasting systems. CONCLUSION: Demand forecasting systems have the potential to greatly improve vaccine demand fulfilment, and decrease logistics cost/dose when implemented with storage and transportation increases. Simulation modeling can demonstrate the potential health and economic benefits of supply chain improvements.

Landscaping the structures of GAVI country vaccine supply chains and testing the effects of radical redesign.

BACKGROUND: Many of the world's vaccine supply chains do not adequately provide vaccines, prompting several questions: how are vaccine supply chains currently structured, are these structures closely tailored to individual countries, and should these supply chains be radically redesigned? METHODS: We segmented the 57 GAVI-eligible countries' vaccine supply chains based on their structure/morphology, analyzed whether these segments correlated with differences in country characteristics, and then utilized HERMES to develop a detailed simulation model of three sample countries' supply chains and explore the cost and impact of various alternative structures. RESULTS: The majority of supply chains (34 of 57) consist of four levels, despite serving a wide diversity of geographical areas and population sizes. These four-level supply chains loosely fall into three clusters [(1) 18 countries relatively more bottom-heavy, i.e., many more storage locations lower in the supply chain, (2) seven with relatively more storage locations in both top and lower levels, and (3) nine comparatively more top-heavy] which do not correlate closely with any of the country characteristics considered. For all three cluster types, our HERMES modeling found that simplified systems (a central location shipping directly to immunization locations with a limited number of Hubs in between) resulted in lower operating costs. CONCLUSION: A standard four-tier design template may have been followed for most countries and raises the possibility that simpler and more tailored designs may be warranted.

One size does not fit all: The impact of primary vaccine container size on vaccine distribution and delivery.

BACKGROUND: While the size and type of a vaccine container (i.e., primary container) can have many implications on the safety and convenience of a vaccination session, another important but potentially overlooked consideration is how the design of the primary container may affect the distribution of the vaccine, its resulting cost, and whether the vial is ultimately opened. METHODS: Using our HERMES software platform, we developed a simulation model of the World Health Organization Expanded Program on Immunization supply chain for the Republic of Benin and used the model to explore the effects of different primary containers for various vaccine antigens. RESULTS: Replacing vaccines with presentations containing fewer doses per vial reduced vaccine availability (proportion of people arriving for vaccines who are successfully immunized) by as much as 13% (from 73% at baseline) and raised logistics costs by up to $0.06 per dose administered (from $0.25 at baseline) due to increased bottlenecks, while reducing total costs by as much as $0.15 per dose administered (from $2.52 at baseline) due to lower open vial wastage. Primary containers with a greater number of doses per vial each improved vaccine availability by 19% and reduced logistics costs by $0.05 per dose administered, while reducing the total costs by up to $0.25 per dose administered. Changes in supply chain performance were more extreme in departments with greater constraints. Implementing a vial opening threshold reversed the direction of many of these effects. CONCLUSIONS: Our results show that one size may not fit all when choosing a primary vaccine container. Rather, the choice depends on characteristics of the vaccine, the vaccine supply chain, immunization session size, and goals of decision makers. In fact, the optimal vial size may vary among locations within a country. Simulation modeling can help identify tailored approaches to improve availability and efficiency.