New Vaccine Platforms-Novel Dimensions of Economic and Societal Value and Their Measurement.

The COVID-19 pandemic's dramatic impact has been a vivid reminder that vaccines-especially in the context of infectious respiratory viruses-provide enormous societal value, well beyond the healthcare system perspective which anchors most Health Technology Assessment (HTA) and National Immunization Technical Advisory Group (NITAG) evaluation frameworks. Furthermore, the development of modified ribonucleic acid-based (mRNA-based) and nanoparticle vaccine technologies has brought into focus several new value drivers previously absent from the discourse on vaccines as public health interventions such as increased vaccine adaptation capabilities, the improved ability to develop combination vaccines, and more efficient vaccine manufacturing and production processes. We review these novel value dimensions and discuss how they might be measured and incorporated within existing value frameworks using existing methods. To realize the full potential of next-generation vaccine platforms and ensure their widespread availability across populations and health systems, it is important that value frameworks utilized by HTAs and NITAGs properly reflect the full range of benefits for population health and well-being and cost efficiencies that these new vaccines platforms provide.

A systematic literature review of the economic and healthcare resource burden of cytomegalovirus.

OBJECTIVE: Cytomegalovirus (CMV) can infect individuals at any age, including infants, who may contract it from infected mothers (congenital CMV [cCMV]). Whereas CMV infection is typically asymptomatic or causes mild illness in healthy individuals, infection can result in severe outcomes in immunocompromised individuals and in infants with cCMV. This systematic review aims to characterize the economic impact of CMV and cCMV infections. METHODS: Medline, Embase, and LILACS databases were searched for publications reporting the economic impact of cCMV and CMV infections across all age groups. Manuscripts published between 2010 and 2020 from Australia, Latin America, Canada, Europe, Israel, Japan, the United States, and global (international, worldwide) studies were included; congress materials were excluded. Outcomes of interest included cCMV- and CMV-attributable direct costs/charges, resource utilization, and indirect/societal costs. RESULTS: Of 751 records identified, 518 were excluded based on duplication, population, outcome, study design, or country. Overall, 55 articles were eligible for full-text review; 25 were further excluded due to population, outcome, study design, or congress abstract. Two publications were additionally identified, resulting in economic impact data compiled from 32 publications. Of these, 24 publications reported cost studies of cCMV or CMV, including evaluation of direct costs/charges, healthcare resource utilization, and indirect/societal costs, and 7 publications reported economic evaluations of interventions. The populations, methods and outcomes used across these studies varied widely. CONCLUSIONS: CMV and cCMV infections impose a considerable economic impact on different countries, populations, and outcomes. There are substantial evidence gaps where further research is warranted.

Factors associated with receipt of mRNA-1273 vaccine at a United States national retail pharmacy during the COVID-19 pandemic.

INTRODUCTION: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prompted accelerated vaccine development of novel messenger RNA (mRNA)-based vaccines by Moderna and Pfizer, which received FDA Emergency Use Authorization in December 2020. The purpose of this study was to examine trends in primary series administration and multi-dose completion rates with Moderna's mRNA-1273 vaccine administered at a United States retail pharmacy. METHODS: Walgreens pharmacy data were joined to publicly available data sets to examine trends in mRNA-1273 primary series and multi-dose completion across patient race/ethnicity, age, gender, distance to first vaccination, and community characteristics. Eligible patients received their first dose of mRNA-1273 administered by Walgreens between December 18, 2020 and February 28, 2022. Variables significantly associated with on-time second dose (all patients) and third dose (immunocompromised patients) in univariate analyses were included in linear regression models. A subset of patients in selected states were studied to identify differences in early and late vaccine adoption. RESULTS: Patients (N = 4,870,915) who received ≥ 1 dose of mRNA-1273 were 57.0% White, 52.6% female, and averaged 49.4 years old. Approximately 85% of patients received a second dose during the study period. Factors associated with on-time second dose administration included older age, race/ethnicity, traveling ≤ 10 miles for the first dose, higher community-level health insurance, and residing in areas with low social vulnerability. Only 51.0% of immunocompromised patients received the third dose as recommended. Factors associated with third dose administration included older age, race/ethnicity, and small-town residence. Early adopters accounted for 60.6% of patients. Factors associated with early adoption included older age, race/ethnicity, and metropolitan residence. CONCLUSION: Over 80% of patients received their on-time second dose of mRNA-1273 vaccine per CDC recommendations. Patient demographics and community characteristics were associated with vaccine receipt and series completion. Novel approaches to facilitate series completion during a pandemic should be further studied.

A systematic literature review on the humanistic burden of cytomegalovirus.

OBJECTIVE: Cytomegalovirus (CMV) infection is typically asymptomatic in healthy individuals; however, certain populations are vulnerable to infection and may develop serious sequelae. CMV infection may also have a broad impact on humanistic outcomes, including patient health status and quality of life (QoL). We conducted a systematic literature review (SLR) to describe the global humanistic burden of CMV and congenital CMV (cCMV) infections across all age groups. METHODS: Medline, Embase, and LILACS were searched to identify studies on humanistic outcomes following CMV infection, including health status/QoL and any outcomes in domains such as auditory performance, cognitive ability, developmental status, intelligence, language, memory, mental health, motor performance, social communication, speech, and vocabulary. The SLR included articles published from 2000 to 2020 and focused geographically on Australia, Europe, Israel, Japan, Latin America, and North America. RESULTS: Sixty-three studies met the inclusion criteria. In general, individuals with symptomatic cCMV infection experience a greater burden of disease and more substantial impact on QoL versus those with asymptomatic cCMV infection. Children with hearing loss due to cCMV infection, both symptomatic and asymptomatic, showed improved auditory outcomes following cochlear implantation. Newborns, infants, and children with cCMV infections had worse cognitive outcomes in psychological development, sequential and simultaneous processing, phonological working memory, and attention control versus age-matched controls without cCMV infection. CMV infection was also associated with cognitive decline in elderly populations. CONCLUSIONS: CMV infection can have substantial, lifelong, heterogenous impacts on humanistic outcomes, including health status and QoL, which should be considered when developing and implementing treatment and prevention strategies.

Hepatitis A and B vaccination in adults at risk: A survey of US healthcare providers' attitudes and practices.

This study aimed to evaluate the attitudes and practices of US healthcare professionals (HCPs) regarding the Advisory Committee on Immunization Practices (ACIP) vaccination recommendations on HepA and HepB for adult patients at risk of contracting these infections or experiencing complications of hepatitis disease. This cross-sectional, web-based survey of 400 US HCPs, which included nurse practitioners and family medicine, internal medicine, infectious disease, emergency department, and gastroenterology physicians, assessed HCPs' attitudes and practices regarding the ACIP recommendations for adult patients at risk for hepatitis disease. HCP participants were identified via a survey research panel. A recruitment quota of 400 HCPs was set, including 50 NPs, 100 FMs, 100 IMs, 50 GIs, 50 EDs, and 50 IDs. The most frequently reported reasons for not recommending either HepA or HepB vaccines were "I think the risk of HepA infection is low in this patient population" and "I am uncertain about what the guidelines say about vaccinating this population." The most reported factors considered when determining eligibility for either vaccine were medical history and the patient's willingness/motivation to be vaccinated. Most reported it was extremely or moderately important to prevent hepatitis disease by vaccinating adult patients at risk, and most also reported recommending a HepA vaccine or HepB vaccine to patients at risk. Although most HCPs reported recommending HepA and HepB vaccines to patients at risk, these findings contrast with the low reported vaccination rates among these populations, and improved awareness of the ACIP recommendations among HCPs is needed.

Although hepatitis A and hepatitis B are vaccine-preventable diseases, not enough adults at risk are vaccinated in the United States (US). The Advisory Committee on Immunization Practices (ACIP) makes recommendations on the use of vaccines in the US. The ACIP recommendations identify groups of people at risk of contracting hepatitis A infection or experiencing complications of hepatitis A disease (e.g., people with chronic liver disease) and hepatitis B infection or its related complications (e.g., people with diabetes).To identify potential barriers to vaccination, we surveyed 400 US healthcare professionals to evaluate their views about the ACIP recommendations on hepatitis A and hepatitis B vaccination for patients at risk of infection or complications. Most reported it was extremely or moderately important to prevent hepatitis A or hepatitis B infection by vaccinating these adult patients. The most commonly reported reasons for not recommending either vaccine were "I am uncertain about what the guidelines say about vaccinating this population" and "I think the risk of hepatitis A or hepatitis B infection is low in this patient population".Our findings show that improved awareness of the guidelines among healthcare professionals is needed, particularly of the importance of hepatitis A vaccination, and hepatitis B vaccination in adults with diabetes. In addition to helping the ongoing multi-state hepatitis A outbreaks, this could aid in the successful implementation of the recent ACIP recommendation for hepatitis B vaccination in all adults that is expected to reduce barriers to vaccination.

The potential clinical impact of implementing different COVID-19 boosters in fall 2022 in the United States.

OBJECTIVE: Emerging SARS-COV-2 variants are spurring the development of adapted vaccines as public health authorities plan for fall vaccinations. This study estimated the number of infections and hospitalizations prevented by three potential booster strategies for adults (≥18 years) in the United States: boosting with either Moderna's (1) licensed first generation monovalent vaccine mRNA-1273 (ancestral strain) or (2) candidate bivalent vaccine mRNA-1273.214 (ancestral + BA.1 variant of concern [VOC]) starting in September 2022, or (3) Moderna's updated candidate bivalent vaccine mRNA-1273.222 (ancestral + BA.4/5 VOC) starting November 2022 due to longer development time. METHODS: An age-stratified, transmission dynamic, Susceptible-Exposed-Infection-Recovered (SEIR) model, adapted from previous literature, was used to estimate infections over time; the model contains compartments defined by SEIR and vaccination status. A decision tree was used to estimate clinical consequences of infections. Calibration was performed so the model tracks the actual course of the pandemic to present time. RESULTS: Vaccinating with mRNA-1273(Sept), mRNA-1273.214(Sept), and mRNA-1273.222(Nov) is predicted to reduce infections by 34%, 40%, and 18%, respectively, and hospitalizations by 42%, 48%, and 25%, respectively, over 6 months compared to no booster. Sensitivity analyses around transmissibility, vaccine coverage, masking, and waning illustrate that boosting with mRNA-1273.214 in September prevented more cases of infection and hospitalization than the other vaccines. LIMITATIONS AND CONCLUSIONS: With the emergence of new variants, key characteristics of the virus that affect estimates of spread and clinical impact also evolve, making parameter estimation difficult. Our analysis demonstrated that boosting with mRNA-1273.214 was more effective over 6 months in preventing infections and hospitalizations with a BA.4/5 subvariant than the tailored vaccine, simply because it could be deployed 2 months earlier. We conclude that there is no advantage to delay boosting until a more effective BA.4/5 vaccine is available; earlier boosting with mRNA-1273.214 will prevent the most infections and hospitalizations.

A systematic literature review of the global seroprevalence of cytomegalovirus: possible implications for treatment, screening, and vaccine development.

BACKGROUND: Cytomegalovirus (CMV) is a common pathogen that affects individuals of all ages and establishes lifelong latency. Although CMV is typically asymptomatic in healthy individuals, infection during pregnancy or in immunocompromised individuals can cause severe disease. Currently, treatments are limited, with no prophylactic vaccine available. Knowledge of the current epidemiologic burden of CMV is necessary to understand the need for treatment and prevention. A systematic literature review (SLR) was conducted to describe the most recent epidemiologic burden of CMV globally. METHODS: Medline, Embase, and LILACS were searched to identify data on CMV prevalence, seroprevalence, shedding, and transmission rates. The SLR covered the time period of 2010-2020 and focused geographically on Australia, Europe, Israel, Japan, Latin America (LATAM), and North America. Studies were excluded if they were systematic or narrative reviews, abstracts, case series, letters, or correspondence. Studies with sample sizes < 100 were excluded to focus on studies with higher quality of data. RESULTS: Twenty-nine studies were included. Among adult men, CMV immunoglobulin G (IgG) seroprevalence ranged from 39.3% (France) to 48.0% (United States). Among women of reproductive age in Europe, Japan, LATAM, and North America, CMV IgG seroprevalence was 45.6-95.7%, 60.2%, 58.3-94.5%, and 24.6-81.0%, respectively. Seroprevalence increased with age and was lower in developed than developing countries, but data were limited. No studies of CMV immunoglobulin M (IgM) seroprevalence among men were identified. Among women of reproductive age, CMV IgM seroprevalence was heterogenous across Europe (1.0-4.6%), North America (2.3-4.5%), Japan (0.8%), and LATAM (0-0.7%). CMV seroprevalence correlated with race, ethnicity, socioeconomic status, and education level. CMV shedding ranged between 0% and 70.2% depending on age group. No findings on CMV transmission rates were identified. CONCLUSIONS: Certain populations and regions are at a substantially higher risk of CMV infection. The extensive epidemiologic burden of CMV calls for increased efforts in the research and development of vaccines and treatments. TRIAL REGISTRATION: N/A.

The Population-Wide Risk-Benefit Profile of Extending the Primary COVID-19 Vaccine Course Compared with an mRNA Booster Dose Program.

The vaccination program is reducing the burden of COVID-19. However, recently, COVID-19 infections have been increasing across Europe, providing evidence that vaccine efficacy is waning. Consequently, booster doses are required to restore immunity levels. However, the relative risk-benefit ratio of boosters, compared to pursuing a primary course in the unvaccinated population, remains uncertain. In this study, a susceptible-exposed-infectious-recovered (SEIR) transmission model of SARS-CoV-2 was used to investigate the impact of COVID-19 vaccine waning on disease burden, the benefit of a booster vaccine program compared to targeting the unvaccinated population, and the population-wide risk-benefit profile of vaccination. Our data demonstrates that the rate of vaccine efficacy waning has a significant impact on COVID-19 hospitalisations with the greatest effect in populations with lower vaccination coverage. There was greater benefit associated with a booster vaccination strategy compared to targeting the unvaccinated population, once >50% of the population had received their primary vaccination course. The population benefits of vaccination (reduced hospitalisations, long-COVID and deaths) outweighed the risks of myocarditis/pericarditis by an order of magnitude. Vaccination is important in ending the COVID-19 pandemic sooner, and the reduction in hospitalisations, death and long-COVID associated with vaccination significantly outweigh any risks. Despite these obvious benefits some people are vaccine reluctant, and as such remain unvaccinated. However, when most of a population have been vaccinated, a focus on a booster vaccine strategy for this group is likely to offer greater value, than targeting the proportion of the population who choose to remain unvaccinated.

Factors influencing series completion rates of recombinant herpes zoster vaccine in the United States: A retrospective pharmacy and medical claims analysis.

BACKGROUND/OBJECTIVES: Vaccination against herpes zoster (HZ) is an effective strategy in protecting the population against consequences of varicella zoster virus reactivation. Optimal immunogenicity with recombinant zoster vaccine (RZV) relies on completion of the 2-dose series within 2-6 months from the first dose. The objectives of this study were to estimate RZV completion rates and adherence with the recommended administration schedule in the general United States population aged at least 50 years and to evaluate factors influencing completion rates. METHODS: Longitudinal, open-source pharmacy and medical claims databases were analyzed for adults aged at least 50 years with a first RZV prescription filled between October 2017 and September 2019. The data were linked to Experian Marketing Services Consumer View data to obtain information regarding race. Completion rates and adherence were calculated overall and stratified according to claim source, age class, sex, and payer type. Logistic regression models were built for each subpopulation of interest to identify factors correlating with completion rates. RESULTS: Overall, cumulative completion rates were 70.41% and 81.80% at 6 and 12 months, respectively. Median time to second dose was approximately 4 months (4.08-5.13 months) and adherence 67.62%. Completion rates were lower in the medical claims database compared with the pharmacy claims database (48.98% vs. 73.23% at 6 months). Regression models confirmed that pharmacy claim was an independent factor for higher completion rates, while African American race and Medicaid status were associated with lower completion rates. Most comorbidities, including chronic obstructive pulmonary disease and type 2 diabetes mellitus, were associated with lower completion rates. CONCLUSION: Pharmacists contribute substantially to the overall high RZV completion rates in the United States. However, completion rates can be improved, especially in people receiving their first RZV dose at a physician's office. Future strategies should aim at lowering barriers to completing vaccination series in African Americans, Medicaid beneficiaries, and people with comorbidities.

Time and cost of administering COVID-19 mRNA vaccines in the United States.

In early 2020, the World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak a global pandemic. In response, two novel messenger RNA (mRNA)-based vaccines: mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) were rapidly developed. A thorough understanding of the differences in workflow requirements between the two vaccines may lead to improved efficiencies and reduced economic burden, both of which are crucial for streamlining vaccine deployment and minimizing wastage. Vaccine administration workflow costs are borne by providers and reimbursed separately from dose acquisition in the United States. Currently, mRNA-1273 and BNT162b2 are the most administered COVID-19 vaccines in the United States. In this study, US-licensed and practicing pharmacists were interviewed to collect data on differences in terms of labor costs associated with the workflows for mRNA-1273 and BNT162b2. Results suggest the cost differential for mRNA-1273 compared to BNT162b2 is -$0.82 (or -$1.01 when assuming volume equivalency). If extrapolated to even just a proportion of the remaining unvaccinated US population, this can amount to significant workflow efficiencies and lower vaccine administration costs. Further, as key differences in the vaccine workflow steps between the two vaccines would be similar in other settings/regions, these findings are likely transferable to health-care systems worldwide.

Vaccinating Adolescents and Children Significantly Reduces COVID-19 Morbidity and Mortality across All Ages: A Population-Based Modeling Study Using the UK as an Example.

Debate persists around the risk-benefit balance of vaccinating adolescents and children against COVID-19. Central to this debate is quantifying the contribution of adolescents and children to the transmission of SARS-CoV-2, and the potential impact of vaccinating these age groups. In this study, we present a novel SEIR mathematical disease transmission model that quantifies the impact of different vaccination strategies on population-level SARS-CoV-2 infections and clinical outcomes. The model employs both age- and time-dependent social mixing patterns to capture the impact of changes in restrictions. The model was used to assess the impact of vaccinating adolescents and children on the natural history of the COVID-19 pandemic across all age groups, using the UK as an example. The base case model demonstrates significant increases in COVID-19 disease burden in the UK following a relaxation of restrictions, if vaccines are limited to those ≥18 years and vulnerable adolescents (≥12 years). Including adolescents and children in the vaccination program could reduce overall COVID-related mortality by 57%, and reduce cases of long COVID by 75%. This study demonstrates that vaccinating adolescents and children has the potential to play a vital role in reducing SARS-CoV-2 infections, and subsequent COVID-19 morbidity and mortality, across all ages. Our results have major global public health implications and provide valuable information to inform a potential pandemic exit strategy.

Estimated Public Health Impact of the Recombinant Zoster Vaccine.

OBJECTIVE: To investigate the potential public health impact of adult herpes zoster (HZ) vaccination with the adjuvanted recombinant zoster vaccine (RZV) in the United States in the first 15 years after launch. METHODS: We used a publicly available model accounting for national population characteristics and HZ epidemiological data, vaccine characteristics from clinical studies, and anticipated vaccine coverage with RZV after launch in 2018. Two scenarios were modeled: a scenario with RZV implemented with 65% coverage after 15 years and a scenario continuing with zoster vaccine live (ZVL) with coverage increasing 10% over the same period. We estimated the numbers vaccinated, and the clinical outcomes and health care use avoided yearly, from January 1, 2018, to December 31, 2032. We varied RZV coverage and investigated the associated impact on HZ cases, complications, and health care resource use. RESULTS: With RZV adoption, the numbers of individuals affected by HZ was predicted to progressively decline with an additional 4.6 million cumulative cases avoided if 65% vaccination with RZV was reached within 15 years. In the year 2032, it was predicted that an additional 1.3 million physicians' visits and 14.4 thousand hospitalizations could be avoided, compared with continuing with ZVL alone. These numbers could be reached 2 to 5 years earlier with 15% higher RZV vaccination rates. CONCLUSION: Substantial personal and health care burden can be alleviated when vaccination with RZV is adopted. The predicted numbers of HZ cases, complications, physicians' visits, and hospitalizations avoided, compared with continued ZVL vaccination, depends upon the RZV vaccination coverage achieved.

Early examination of real-world uptake and second-dose completion of recombinant zoster vaccine in the United States from October 2017 to September 2019.

Shingrix (Recombinant zoster vaccine, RZV) was approved in October 2017 in the United States (US) for the prevention of herpes zoster in adults aged 50 years and older. The vaccine is administered in two doses, with the second dose administration recommended between two and six months after the first dose. Examination of uptake and series completion is important to ensure appropriate use, especially at the time of vaccine introduction. This report provides demographic characteristics of patients receiving RZV between October 2017 and September 2019, first- and second-dose uptake, and a cumulative estimation of second-dose completion by month for US adults aged 50 years and older. Monthly uptake increased rapidly since October 2017; overall, 7,097,441 first doses of RZV were administered along with 4,277,636 second doses during the observed timeframe. Among people with an observed first-dose administration, 70% and 80% completed the two-dose series within six and 12 months post initial dose, respectively. This evidence suggests that RZV has rapidly been adopted by a large population in the US and most are following manufacturer or policy recommendations regarding series completion. Further analyses are needed to explore potential patient, provider, and policy-relevant characteristics associated with second-dose completion that could serve as targets for further improvement.

Retrospective study of the use of an influenza disease two-tiered classification system to characterize clinical severity in US children.

In children <5 years, influenza is associated with higher risk of serious disease and hospitalization when compared with other age groups. Influenza vaccination reduces the risk of influenza and vaccination may attenuate the severity of disease. Recent studies in Europe suggest that classifying influenza disease as mild versus moderate-to-severe (M-S) using a novel definition may be clinically significant. We retrospectively evaluated whether this M-S definition also characterized influenza severity in a cohort of US children. We included children <18 years at Kaiser Permanente Northern California with PCR-confirmed influenza during the 2013-2014 influenza season. We classified children as M-S if they had ≥1 symptom: fever >39°C, acute otitis media, lower respiratory tract infection (LRTI), or extra-pulmonary complications; otherwise, they were classified as mild. We used multivariable log-binomial models to assess whether M-S influenza disease was associated with increased healthcare utilization. Nearly half of the 1,105 influenza positive children were classified as M-S. Children 6-35 months had the highest proportion of M-S disease (35.1%), mostly due to LRTI (63.2%) and fever (44.6%). Children ≥6 months who had M-S disease were associated with a 1.6 to 2.8 times increased likelihood of having had an emergency department or any follow-up outpatient visits. Those who had M-S disease were associated with an increased likelihood of receiving antibiotics, with the highest likelihood in children 6-35 months (RR 9.0, 95% CI 4.1, 19.8). While more studies are needed, an influenza classification system may distinguish children with more clinically significant disease.

Constrained Optimization for the Selection of Influenza Vaccines to Maximize the Population Benefit: A Demonstration Project.

BACKGROUND: Influenza is an infectious disease causing a high annual economic and public health burden. The most efficient management of the disease is through prevention with vaccination. Many influenza vaccines are available, with varying efficacy and cost, targeting different age groups. Therefore, strategic decision-making about which vaccine to deliver to whom is warranted to improve efficiency. OBJECTIVE: We present the use of a constrained optimization (CO) model to evaluate targeted strategies for providing influenza vaccines in three adult age groups in the USA. METHODS: CO was considered for identifying an influenza vaccine provision strategy that maximizes the benefits at constrained annual budgets, by prioritizing vaccines based on return on investment. The approach optimizes a set of predefined outcome measures over several years resulting from an increasing investment using the best combination of influenza vaccines. RESULTS: Results indicate the importance of understanding the relative differences in benefits for each vaccine type within and across age groups. Scenario and threshold analyses demonstrate the impact of changing budget distribution over time, price setting per vaccine type, and selection of outcome measure to optimize. CONCLUSION: Significant gains in cost efficiency can be realized for a decision maker using a CO model, especially for a disease like influenza with many vaccine options. Testing the model under different scenarios offers powerful insights into maximum achievable benefit overall and per age group within the predefined constraints of a vaccine budget.

Maternal Immunization in the U.S.: A Nationwide Retrospective Cohort Study.

INTRODUCTION: At present, pregnant women in the U.S. are recommended to receive tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) and influenza vaccines. This study assessed maternal coverage of these 2 vaccinations. METHODS: Data for this retrospective cohort study were extracted from 2 large administrative claims databases, the MarketScan Commercial and Multi-State Medicaid Databases, for 2009-2017 and analyzed in 2018. Women aged 15-44 years on the date of pregnancy end were included. Pregnancies with gestational age of less than 23 weeks were excluded from the Tdap vaccination endpoint owing to the optimal recommended gestational age for Tdap vaccination. Multivariable logistic regression models identified predictors of vaccination. RESULTS: The Tdap vaccination subpopulation included 1,421,452 Commercial and 523,635 Medicaid pregnancies; the influenza vaccination subpopulation included 1,862,705 Commercial and 628,079 Medicaid pregnancies. There were marked increases in vaccination coverage from 2010 to 2017: from 1.0% to 56.3% (Commercial) and from 0.5% to 31.4% (Medicaid) for Tdap, and from 14.7% to 31.3% (Commercial) and from 9.7% to 17.5% (Medicaid) for influenza. The likelihood of Tdap/influenza vaccination increased significantly with receipt of the other vaccine and more pregnancy-related healthcare visits. CONCLUSIONS: Although maternal Tdap and influenza vaccination coverage increased substantially from 2010 to 2017 among large, geographically diverse U.S. cohorts, coverage remained suboptimal, potentially putting newborns at risk of pertussis and influenza. Strategies to increase maternal vaccination coverage could target women identified to have a reduced likelihood of vaccination: those who are younger, black, residing in rural areas, with multiple gestation, and a prepregnancy inpatient admission.

Is patient insurance type related to physician recommendation, administration and referral for adult vaccination? A survey of US physicians.

This study evaluated physician practices and perceived barriers for influenza, tetanus, diphtheria, pertussis (Tdap), and zoster vaccination of adults in the United States (US), with emphasis on patients with Medicare versus commercial insurance. A cross-sectional internet-based survey of board-certified general/family practitioners and internists (N = 1,000) recruited from a national US physician panel was conducted in May 2017. For influenza, rates of physician recommendation (84% of Medicare patients, 82% of commercially-insured patients), administration (80% Medicare, 78% commercial), and referral (11% Medicare, 11% commercial) were similar regardless of insurance type. Tdap recommendation was higher for commercial compared to Medicare patients (59% vs. 54%, p < 0.001); while zoster recommendation was higher for Medicare patients than commercial (59% vs. 55%, p < 0.001). For Tdap and zoster, higher administration rates were reported in commercial patients (64% Tdap, 36% zoster) than Medicare (56% Tdap, 32% zoster), and referral rates were higher for Medicare patients (19% Tdap, 49% zoster) than commercial (14% Tdap, 42% zoster). Over 40% of physicians would be much more likely to administer Tdap and zoster vaccines if they were covered under Medicare Part B, with more physicians indicating financial barriers as "major" or "moderate" for Medicare than commercial patients. These differences may be related to financial barriers associated with adult vaccinations that are covered under Medicare Part D and involve patient out-of-pocket costs. Efforts to reduce financial barriers associated with adult vaccinations covered under Medicare Part D and to improve patient and physician knowledge could positively impact physician recommendation, administration, and referral for adult vaccination in the US.

Cost-effectiveness of an adjuvanted recombinant zoster vaccine in older adults in the United States who have been previously vaccinated with zoster vaccine live.

Zoster Vaccine Live (ZVL) is marketed in the US since 2008, and a non-live adjuvanted Recombinant Zoster Vaccine (RZV) was approved in 2017. Literature suggests that waning of ZVL efficacy may necessitate additional vaccination. The Advisory Committee on Immunization Practices recommended vaccination with RZV in immunocompetent adults aged 50+ years old, including those previously vaccinated with ZVL. The objective of this study was to determine the cost-effectiveness of vaccinating US adults aged 60+ years old, previously vaccinated with ZVL. The ZOster ecoNomic Analysis (ZONA) model, a deterministic Markov model, was adapted to follow a hypothetical 1 million(M)-person cohort of US adults previously vaccinated with ZVL. Model inputs included demographics, epidemiology, vaccine characteristics, utilities and costs. Costs and quality-adjusted life-years (QALYs) were presented over the lifetimes of the cohort from the year of additional vaccination, discounted 3% annually. The model estimated that, vaccination with RZV 5 years after previous vaccination with ZVL, would reduce disease burden compared with no additional vaccination, resulting in a gain of 1,633 QALYs at a total societal cost of $96M (incremental cost-effectiveness ratio: $58,793/QALY saved). Compared with revaccinating with ZVL, vaccination with RZV would result in a gain of 1,187 QALYs and societal cost savings of almost $84M. Sensitivity, scenario, and threshold analyses demonstrated robustness of these findings. Vaccination with RZV is predicted to be cost-effective relative to no additional vaccination, assuming a threshold of $100,000/QALY, and cost-saving relative to ZVL revaccination of US adults aged 60+ years old who have been previously vaccinated with ZVL.

Age-appropriate compliance and completion of up to five doses of pertussis vaccine in US children.

Background: In the United States (US), diphtheria, tetanus, and acellular pertussis (DTaP) vaccination is recommended at 2, 4, and 6 months (doses 1-3), 15-18 months (dose 4), and 4-6 years (dose 5). The objective of this study (GSK study identifier: HO-14-14383) was to examine DTaP completion and compliance rates among commercially insured and Medicaid-enrolled children. Secondarily, the study aimed at identifying predictors of compliance/completion. Methods: Truven Health MarketScan Commercial and Multi-State Medicaid databases (2005-2013) were analyzed separately. Children born during 2005-2011 with ≥ 2 years continuous enrollment from birth provided data for doses 1-4; those with continuous enrollment from birth to their seventh birthday provided dose 5 data. Series compliance (each recommended dose by 3, 5, and 7 months; 19 months; seventh birthday) and completion (3 doses by 8 months; 4 by 24 months; 5 by seventh birthday) were calculated. Predictors of compliance/completion were identified using multivariable logistic regression. Results: A total of 367,493 commercially insured and 766,153 Medicaid-enrolled children were followed for ≥ 2 years; and 23,574 and 41,284, respectively, for ≥ 7 years. Series compliance to doses 1-3, 1-4, and 1-5 were 67.2%, 55.3%, 47.5% (commercial) and 37.4%, 27.3%, 14.4% (Medicaid), respectively. Predictors of better compliance/completion included: later birth year (commercial/Medicaid) and higher household income (commercial); predictors of worse compliance/completion included: Northeast residence (commercial), birth hospitalization ≥ 14 days (commercial/Medicaid), and Black race/ethnicity (Medicaid). Conclusions: DTaP series compliance/completion improved over time, but appear to be suboptimal. As this could increase pertussis risk, greater awareness of the importance of timely vaccination completion is needed. GSK study identifier: HO-14-14383.