Modeling the potential public health and economic impact of different COVID-19 booster dose vaccination strategies with an adapted vaccine in the United Kingdom.

BACKGROUND: Updating vaccines is essential for combatting emerging coronavirus disease 2019 (COVID-19) variants. This study assessed the public health and economic impact of a booster dose of an adapted vaccine in the United Kingdom (UK). METHODS: A Markov-decision tree model estimated the outcomes of vaccination strategies targeting various age and risk groups in the UK. Age-specific data derived from published sources were used. The model estimated case numbers, deaths, hospitalizations, medical costs, and societal costs. Scenario analyses were conducted to explore uncertainty. RESULTS: Vaccination targeting individuals aged ≥ 65 years and the high-risk population aged 12-64 years was estimated to avert 701,549 symptomatic cases, 5,599 deaths, 18,086 hospitalizations, 56,326 post-COVID condition cases, and 38,263 lost quality-adjusted life years (QALYs), translating into direct and societal cost savings of £112,174,054 and £542,758,682, respectively. The estimated economically justifiable price at willingness-to-pay thresholds of £20,000 and £30,000 per QALY was £43 and £61, respectively, from the payer perspective and £64 and £82, respectively, from the societal perspective. Expanding to additional age groups improved the public health impact. CONCLUSIONS: Targeting individuals aged ≥ 65 years and those aged 12-64 years at high risk yields public health gains, but expansion to additional age groups provides additional gains.

Evaluation of pre-school pertussis booster vaccination in Shanghai, China: A cost-effectiveness analysis.

BACKGROUND: In recent years, notified pertussis cases have been increasingly documented in China. It raised a new public health concern of potential optimization in immunization strategy. This study was aimed to determine the cost-effectiveness of different immunization strategies against pertussis-containing vaccines for 6-year-old pre-school children in Shanghai. METHODS: A Markov-decision tree model was applied to evaluate two pertussis immunization strategies for 6-year-old pre-school children as following: (1) 1 dose of acellular pertussis (aP) contained vaccine (DTaP or Tdap) booster vaccinated at 6 years of age, and (2) no booster at 6 years of age regimen. Primary outcomes included quality-adjusted life years (QALYs), costs, and incremental cost-utility ratios (ICUR). Sensitivity analyses were performed. The analysis was conducted over a study period of 14 years from a societal perspective. RESULTS: Compared to no booster immunization strategy, administering 1 dose of acellular pertussis (aP) contained vaccine (DTaP or Tdap) booster at 6 years of age, resulted in an average cost reduction of CNY 814.16 (USD 116) per individual, an increase in QALYs by 0.00066, and a rise in per capita net monetary benefit (NMB) by CNY 933.51 (USD 132). The total costs over the study period were reduced by CNY 160.59 million (USD 23 million), utility increased by 130.49 QALYs, and NMB increased by CNY 184.14 million (USD 26 million). CONCLUSIONS: Implementing acellular pertussis booster immunization for 6-year-old pre-school children in Shanghai emerges as a cost-saving immunization strategy, with both cost savings and utility gains.

Economic evaluation of second measles containing vaccine (MCV) dose: a systematic review of available evidence.

INTRODUCTION: The global measles incidence has decreased from 145 to 49 cases per 1 million population from 2000 to 2018, but evaluating the economic benefits of a second measles-containing vaccine (MCV2) is crucial. This study reviewed the evidence and quality of economic evaluation studies to guide MCV2 introduction. METHODS: The systematic review of model-based economic evaluation studies was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search yielded 2231 articles, with 876 duplicates removed and 1355 articles screened, with nine studies included for final analysis. RESULTS: Six studies reported a positive benefit-cost ratio with one resulting in net savings of $11.6 billion, and two studies estimated a 2-dose MMR vaccination program would save $119.24 to prevent one measles case, and a second dose could prevent 9,200 cases at 18 months, saving $548.19 per case. The most sensitive variables were the discount rate and vaccination administration cost. CONCLUSIONS: Two MCV doses or a second opportunity with an additional dose of MCV were highly cost-beneficial and resulted in substantial cost savings compared to a single routine vaccine. But further research using high-quality model-based health economic evaluation studies of MCV2 should be made available to decision-makers. PROSPERO REGISTRATION: CRD42020200669.

Testing fractional doses of COVID-19 vaccines.

Due to the enormous economic, health, and social costs of the COVID-19 pandemic, there are high expected social returns to investing in parallel in multiple approaches to accelerating vaccination. We argue there are high expected social returns to investigating the scope for lowering the dosage of some COVID-19 vaccines. While existing evidence is not dispositive, available clinical data on the immunogenicity of lower doses combined with evidence of a high correlation between neutralizing antibody response and vaccine efficacy suggests that half or even quarter doses of some vaccines could generate high levels of protection, particularly against severe disease and death, while potentially expanding supply by 450 million to 1.55 billion doses per month, based on supply projections for 2021. An epidemiological model suggests that, even if fractional doses are less effective than standard doses, vaccinating more people faster could substantially reduce total infections and deaths. The costs of further testing alternative doses are much lower than the expected public health and economic benefits. However, commercial incentives to generate evidence on fractional dosing are weak, suggesting that testing may not occur without public investment. Governments could support either experimental or observational evaluations of fractional dosing, for either primary or booster shots. Discussions with researchers and government officials in multiple countries where vaccines are scarce suggests strong interest in these approaches.

The burden of pertussis in older adults: what is the role of vaccination? A systematic literature review.

INTRODUCTION: Pertussis (whooping cough) is a vaccine-preventable disease; however, neither natural- nor vaccine-induced protection is life-long. Although generally not severe in adults, pertussis can be associated with complications in patients with chronic conditions such as asthma or chronic obstructive pulmonary disease, and can be readily transmitted to more vulnerable populations, including neonates before they complete their primary vaccination. Furthermore, as the global population ages, the health and economic burden of the disease is expected to rise. Areas covered: A systematic literature review was conducted to ascertain the current epidemiological and financial burden of pertussis in older adults and to discuss the potential value of a booster vaccination in this population. Expert commentary: Our review indicates a considerable underestimation of the pertussis burden amongst older adults. Seroprevalence studies consistently demonstrate that the reported incidence may be much lower than the actual incidence. Tetanus toxoid-reduced diphtheria toxoid and acellular pertussis vaccines are immunogenic in older adults, induce high booster responses and are well-tolerated. There is therefore a good rationale for the advocacy of booster pertussis vaccination throughout life to prevent pertussis infection and its transmission, especially in adults aged ≥50 years.

Early use of the HPV 2-dose vaccination schedule: Leveraging evidence to support policy for accelerated impact.

Although human papillomavirus (HPV) vaccines were initially licensed based on efficacy after three-dose regimens in women aged 15-26 years, it was recognized early in clinical development that comparable immunogenicity could be obtained after just two doses when administered to younger girls. In both Canada and Mexico, public health authorities made the decision to administer two doses 6 months apart with a planned additional dose at 60 months, while simultaneously doing further study to determine if the third dose would confer meaningful additional benefit. This delayed third dose approach permitted a more cost-effective program with opportunities for improved compliance while minimizing injections and leaving open the opportunity to provide a full three-dose vaccination series. It required close cooperation across many governmental and civil society leadership bodies and real-time access to emerging data on HPV vaccine effectiveness. Although still limited, there is increasing evidence that even one-dose vaccination is sufficient to provide prolonged protection against HPV infection and associated diseases. Ongoing clinical trials and ecological studies are expected to consolidate existing data regarding one dose schedule use. However, to accelerate the preventive effect of HPV vaccination some jurisdictions, in particular those with limited resources may already consider the initiation of a one dose vaccination with the possibility of giving the second dose later in life if judged necessary. Such an approach would facilitate vaccination implementation and might permit larger catch-up vaccination programs in older girls (or as appropriate, girls and boys), thereby accelerating the impact on cervical cancer and other HPV-associated diseases.

A cost-effectiveness analysis of revaccination and catch-up strategies with the 23-valent pneumococcal polysaccharide vaccine (PPV23) in older adults in Japan.

OBJECTIVE: In Japan, the National Immunization Program (NIP) includes PPV23 as the primary vaccination for adults and catch-up cohorts. The Japanese Association for Infectious Diseases recommends revaccination for older adults who received primary vaccination ≥5 years earlier. The cost-effectiveness of adding revaccination and/or continuing catch-up vaccination in the NIP was evaluated from the public payer perspective in Japan. METHODS: The Markov model included five health states: no pneumococcal disease, invasive pneumococcal diseases (IPD), non-bacteremic pneumococcal pneumonia (NBPP), post-meningitis sequelae, and death. Cohorts of adults aged 65-95 were followed until age 100 or death: 2014 cohort (aged 65-95, vaccinated: 2014); 2019 cohort (aged 65: 2019); and 2019 catch-up cohort (aged 70-100: 2019, unvaccinated: 2014). Strategies included: (1) vaccinate 2014 and 2019 cohorts; (2) vaccinate 2014 and 2019 cohorts and revaccinate both; (3) strategy 1 and vaccinate 2019 catch-up cohort; (4) strategy 2 and vaccinate 2019 catch-up cohort; and (5) strategy 4 and revaccinate 2019 catch-up cohort. Parameters were retrieved from global and Japanese sources, costs and QALYs discounted at 2%, and incremental cost-effectiveness ratios (ICERs) estimated. RESULTS: Strategy 1 had the highest number of IPD and NBPP cases, and strategy 5 the lowest. Strategies 3-5 dominated strategy 1 and strategy 2 was cost-effective compared to strategy 1 (ICER: ¥1,622,153 per QALY gained). At a willingness-to-pay threshold of ¥5 million per QALY gained, strategy 2 was cost-effective and strategies 3-5 were cost-saving compared to strategy 1. CONCLUSIONS: Strategies including revaccination, catch-up, or both were cost-effective or cost-saving in comparison to no revaccination and no catch-up. Results can inform future vaccine policies and programs in Japan.

Combined effect of PCV10 and meningococcal C conjugate vaccination on meningitis mortality among children under five years of age in Brazil.

The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in the Brazilian National Immunization Program in March 2010, scheduled at 2, 4, and 6 months, with a booster at 12-15 months of age. The meningococcal C conjugate vaccine (MCC) was introduced in November 2010, scheduled at 3 and 5 months, with a booster dose at 12-15 months of age and no catch-up for older age groups. In this interrupted time-series analysis study, we used Brazilian mortality data from 2005 to 2015 for children under five years of age (excluding data from the state of Bahia) to assess the combined impact of these vaccines on the overall burden of meningitis mortality among children aged 0-23 months and 2-4 years, as defined using meningitis and meningococcemia specific International Classification of Diseases - tenth revision codes. Secular trends and seasonality were taken into account. We found significant reductions for both age groups relative to those observed for the comparison group of diseases, with immediate effects after the transition period (2010-2011) of 29.2% and 27.5% for children aged 0-23 months and 2-4 years, respectively. These immediate effects were sustained throughout the post-vaccination period (2012-2015). In total, 337 deaths were averted by the combined effect of both vaccines, 238 (95%CI 169-319) for children aged 0-23 months and 99 (95%CI 56-144) for those aged 2-4 years. These results add strong evidence in support of investments in these vaccines by low and middle-income countries.

Frequency and Cost of Vaccinations Administered Outside Minimum and Maximum Recommended Ages-2014 Data From 6 Sentinel Sites of Immunization Information Systems.

OBJECTIVE: To quantify vaccinations administered outside minimum and maximum recommended ages and to determine attendant costs of revaccination by analyzing immunization information system (IIS) records. STUDY DESIGN: We analyzed deidentified records of doses administered during 2014 to persons aged <18 years within 6 IIS sentinel sites (10% of the US population). We quantified doses administered outside of recommended ages according to the Advisory Committee on Immunization Practices childhood immunization schedule and prescribing information in package inserts, and calculated revaccination costs. To minimize misreporting bias, we analyzed publicly funded doses for which reported lot numbers and vaccine types were consistent. RESULTS: Among 3 394 047 doses with maximum age recommendations, 9755 (0.3%) were given after the maximum age. One type of maximum age violation required revaccination: 1344 (0.7%) of 194 934 doses of the 0.25-mL prefilled syringe formulation of quadrivalent inactivated influenza vaccine (Fluzone Quadrivalent, Sanofi Pasteur, Swiftwater, PA) were administered at age ≥36 months (revaccination cost, $111 964). We identified a total of 7 529 165 childhood, adolescent, and lifespan doses with minimum age recommendations, 9542 of which (0.1%) were administered before the minimum age. The most common among these violations were quadrivalent injectable influenza vaccines (3835, or 0.7% of 526 110 doses administered before age 36 months) and Kinrix (GlaxoSmithKline Biologicals, Rixensart, Belgium; DTaP-IPV) (2509, or 1.2% of 208 218 doses administered before age 48 months). The cost of revaccination for minimum age violations (where recommended) was $179 179. CONCLUSION: Administration of vaccines outside recommended minimum and maximum ages is rare, reflecting a general adherence to recommendations. Error rates were higher for several vaccines, some requiring revaccination. Vaccine schedule complexity and confusion among similar products might contribute to errors. Minimization of errors reduces wastage, excess cost, and inconvenience for parents and patients.

Intradermal Administration of Fractional Doses of Inactivated Poliovirus Vaccine: A Dose-Sparing Option for Polio Immunization.

A fractional dose of inactivated poliovirus vaccine (fIPV) administered by the intradermal route delivers one fifth of the full vaccine dose administered by the intramuscular route and offers a potential dose-sparing strategy to stretch the limited global IPV supply while further improving population immunity. Multiple studies have assessed immunogenicity of intradermal fIPV compared with the full intramuscular dose and demonstrated encouraging results. Novel intradermal devices, including intradermal adapters and disposable-syringe jet injectors, have also been developed and evaluated as alternatives to traditional Bacillus Calmette-Guérin needles and syringes for the administration of fIPV. Initial experience in India, Pakistan, and Sri Lanka suggests that it is operationally feasible to implement fIPV vaccination on a large scale. Given the available scientific data and operational feasibility shown in early-adopter countries, countries are encouraged to consider introducing a fIPV strategy into their routine immunization and supplementary immunization activities.

Cutaneous varicella zoster virus infection following zoster vaccination: report of post-vaccination herpes zoster skin infection and literature review of zoster vaccination efficacy and guidelines.

BackgroundHerpes zoster vaccine is currently recommended in the United States for immune competent individuals ≥60 years. The efficacy of the herpes zoster vaccine decreases with age and with time following vaccination.PurposeAn elderly man with herpes zoster following vaccination is described. The guidelines for vaccination and issues regarding re-vaccination are reviewed. METHODS: PubMed was used to search the following terms: efficacy, elderly, herpes zoster, herpes zoster incidence, herpes zoster recurrence, and vaccination. The papers and relevant citations were reviewed. The clinical features of a patient with post-vaccination herpes zoster skin infection are presented; in addition, vaccine efficacy and guidelines are reviewed.ResultsA 91-year-old man, vaccinated for herpes zoster 10 years earlier, presented with crusted erosions on his face corresponding to the area innervated by the ophthalmic division of the left trigeminal nerve. Evaluation using polymerase chain reaction confirmed the diagnosis of herpes zoster.ConclusionsHerpes zoster vaccine decreases in efficacy with both age and number of years following vaccination. Therefore, booster shots or revaccination in the older population may be of benefit.

Cost effectiveness of a targeted age-based West Nile virus vaccination program.

BACKGROUND: West Nile virus (WNV) is the leading cause of domestically-acquired arboviral disease in the United States. Several WNV vaccines are in various stages of development. We estimate the cost-effectiveness of WNV vaccination programs targeting groups at increased risk for severe WNV disease. METHODS: We used a mathematical model to estimate costs and health outcomes of vaccination with WNV vaccine compared to no vaccination among seven cohorts, spaced at 10year intervals from ages 10 to 70years, each followed until 90-years-old. U.S. surveillance data were used to estimate WNV neuroinvasive disease incidence. Data for WNV seroprevalence, acute and long-term care costs of WNV disease patients, quality-adjusted life-years (QALYs), and vaccine characteristics were obtained from published reports. We assumed vaccine efficacy to either last lifelong or for 10years with booster doses given every 10years. RESULTS: There was a statistically significant difference in cost-effectiveness ratios across cohorts in both models and all outcomes assessed (Kruskal-Wallis test p<0.0001). The 60-year-cohort had a mean cost per neuroinvasive disease case prevented of $664,000 and disability averted of $1,421,000 in lifelong model and $882,000 and $1,887,000, respectively in 10-year immunity model; these costs were statistically significantly lower than costs for other cohorts (p<0.0001). Vaccinating 70-year-olds had the lowest cost per death averted in both models at around $4.7 million (95%CI $2-$8 million). Cost per disease case averted was lowest among 40- and 50-year-old cohorts and cost per QALY saved lowest among 60-year cohorts in lifelong immunity model. The models were most sensitive to disease incidence, vaccine cost, and proportion of persons developing disease among infected. CONCLUSIONS: Age-based WNV vaccination program targeting those at higher risk for severe disease is more cost-effective than universal vaccination. Annual variation in WNV disease incidence, QALY weights, and vaccine costs impact the cost effectiveness ratios.

Determining the Optimal Vaccination Schedule for Herpes Zoster: a Cost-Effectiveness Analysis.

BACKGROUND: The Advisory Committee on Immunization Practices recommends a single dose of herpes zoster (HZ) vaccine in persons aged 60 years or older, but the efficacy decreases to zero after approximately 10 years. A booster dose administered after 10 years might extend protection, but the cost-effectiveness of a booster strategy has not been examined. OBJECTIVE: We aimed to determine the optimal schedule for HZ vaccine DESIGN: We built a Markov model to follow patients over their lifetime. From the societal perspective, we compared costs and quality-adjusted life years (QALYs) saved of 11 strategies to start and repeat HZ vaccine at different ages. SUBJECTS: Adults aged 60 years. INTERVENTION: HZ vaccine. MAIN MEASURES: Costs, quality-adjusted life years (QALYs), and incremental costs per QALY saved. KEY RESULTS: At a $100,000/QALY threshold, "vaccination at 70 plus one booster" was the most cost-effective strategy, with an incremental cost-effectiveness ratio (ICER) of $36,648/QALY. "Vaccination at 60 plus two boosters" was more effective, but had an ICER of $153,734/QALY. In deterministic sensitivity analysis, "vaccination at 60 plus two boosters" cost < $100,000/QALY if compliance rate was > 67 % or vaccine cost was < $156 per dose. In probabilistic sensitivity analysis, "vaccination at 70 plus one booster" was preferred at a willingness-to-pay of up to $135,000/QALY. CONCLUSIONS: Under current assumptions, initiating HZ vaccine at age 70 years with one booster dose 10 years later appears optimal. Future data regarding compliance with or efficacy of a booster could affect these conclusions.

Cost-effectiveness analysis of catch-up hepatitis A vaccination among unvaccinated/partially-vaccinated children.

BACKGROUND: Since 2006, the US Centers for Disease Control and Prevention has recommended hepatitis A (HepA) vaccination routinely for children aged 12-23months to prevent hepatitis A virus (HAV) infection. However, a substantial proportion of US children are unvaccinated and susceptible to infection. We present results of economic modeling to assess whether a one-time catch-up HepA vaccination recommendation would be cost-effective. METHODS: We developed a Markov model of HAV infection that followed a single cohort from birth through death (birth to age 95years). The model compared the health and economic outcomes from catch-up vaccination interventions for children at target ages from two through 17years vs. outcomes resulting from maintaining the current recommendation of routine vaccination at age one year with no catch-up intervention. RESULTS: Over the lifetime of the cohort, catch-up vaccination would reduce the total number of infections relative to the baseline by 741 while increasing doses of vaccine by 556,989. Catch-up vaccination would increase net costs by $10.2million, or $2.38 per person. The incremental cost of HepA vaccine catch-up intervention at age 10years, the midpoint of the ages modeled, was $452,239 per QALY gained. Across age-cohorts, the cost-effectiveness of catch-up vaccination is most favorable at age 12years, resulting in an Incremental Cost-Effectiveness Ratio of $189,000 per QALY gained. CONCLUSIONS: Given the low baseline of HAV disease incidence achieved by current vaccination recommendations, our economic model suggests that a catch-up vaccination recommendation would be less cost-effective than many other vaccine interventions, and that HepA catch-up vaccination would become cost effective at a threshold of $50,000 per QALY only when incidence of HAV rises about 5.0 cases per 100,000 population.

Cost-effectiveness of next-generation vaccines: The case of pertussis.

Despite steady vaccination coverage rates, pertussis incidence in the United States has continued to rise. This public health challenge has motivated calls for the development of a new vaccine with greater efficacy and duration of protection. Any next-generation vaccine would likely come at a higher cost, and must provide sufficient health benefits beyond those provided by the current vaccine in order to be deemed cost-effective. Using an age-structured transmission model of pertussis, we quantified the health and economic benefits of a next-generation vaccine that would enhance either the efficacy or duration of protection of the childhood series, the duration of the adult booster, or a combination. We developed a metric, the maximum cost-effective price increase (MCPI), to compare the potential value of such improvements. The MCPI estimates the per-dose price increase that would maintain the cost-effectiveness of pertussis vaccination. We evaluated the MCPI across a range of potential single and combined improvements to the pertussis vaccine. As an upper bound, we found that a next-generation vaccine which could achieve perfect efficacy for the childhood series would permit an MCPI of $18 per dose (95% CI: $12-$31). Pertussis vaccine improvements that extend the duration of protection to an average of 75 years would allow for an MCPI of $22 per dose for the childhood series (CI: $10-$33) or $12 for the adult booster (CI: $4-$18). Despite the short duration of the adult booster, improvements to the childhood series could be more valuable than improvements to the adult booster. Combining improvements in both efficacy and duration, a childhood series with perfect efficacy and average duration of 75 years would permit an MCPI of $39 per dose, the highest of any scenario evaluated. Our results highlight the utility of the MCPI metric in evaluating potential vaccines or other interventions when prices are unknown.

Impact and cost-effectiveness of a second tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine dose to prevent pertussis in the United States.

INTRODUCTION: The United States experienced a substantial increase in reported pertussis cases over the last decade. Since 2005, persons 11 years and older have been routinely recommended to receive a single dose of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine. The objective of this analysis was to evaluate the potential impact and cost-effectiveness of recommending a second dose of Tdap. METHODS: A static cohort model was used to calculate the epidemiologic and economic impact of adding a second dose of Tdap at age 16 or 21 years. Projected costs and outcomes were examined from a societal perspective over a 20-year period. Quality-adjusted Life Years (QALY) saved were calculated. RESULTS: Using baseline pertussis incidence from the National Notifiable Diseases Surveillance System, Tdap revaccination at either age 16 or 21 years would reduce outpatient visits by 433 (5%) and 285 (4%), and hospitalization cases by 7 (7%) and 5 (5%), respectively. The costs per QALY saved with a second dose of Tdap were approximately US $19.7 million (16 years) and $26.2 million (21 years). In sensitivity analyses, incidence most influenced the model; as incidence increased, the costs per QALY decreased. To a lesser degree, initial vaccine effectiveness and waning of effectiveness also affected cost outcomes. Multivariate sensitivity analyses showed that under a set of optimistic assumptions, the cost per QALY saved would be approximately $163,361 (16 years) and $204,556 (21 years). CONCLUSION: A second dose of Tdap resulted in a slight decrease in the number of cases and other outcomes, and that trend is more apparent when revaccinating at age 16 years than at age 21 years. Both revaccination strategies had high dollar per QALY saved even under optimistic assumptions in a multivariate sensitivity analysis.

Cost-effectiveness of using 2 vs 3 primary doses of 13-valent pneumococcal conjugate vaccine.

BACKGROUND AND OBJECTIVE: Although effective in preventing pneumococcal disease, 13-valent pneumococcal conjugate vaccine (PCV13) is the most expensive vaccine on the routinely recommended pediatric schedule in the United States. We examined the cost-effectiveness of switching from 4 total doses to 3 total doses by removing the third dose in the primary series in the United States. METHODS: We used a probabilistic model following a single birth cohort of 4.3 million to calculate societal cost savings and increased disease burden from removing the 6-month dose of PCV13. Based on modified estimates of 7-valent pneumococcal conjugate vaccine from randomized trials and observational studies, we assumed that vaccine effectiveness under the 2 schedules is identical for the first 6 months of life and largely similar after administration of the 12- to 15-month booster dose. RESULTS: Removing the third dose of PCV13 would annually save $500 million (in 2011$) but would also result in an estimated 2.5 additional deaths among inpatients with pneumonia or invasive pneumococcal disease. Such dose removal would also result in 261,000 estimated otitis media and 12,000 estimated pneumonia cases annually. These additional illnesses could be prevented through modest increases in coverage. Overall, societal savings per additional life-year lost would be ∼$6 million. When nonfatal outcomes are also considered, savings would range from $143,000 to $4 million per additional quality adjusted life-year lost, depending on the assumptions used for otitis media. CONCLUSIONS: Sizable societal cost savings and a moderate pneumococcal disease increase could be expected from removing the PCV13 primary series' third dose.