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 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.

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.

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.

National survey of pharmacy-based immunization services.

INTRODUCTION: Pharmacists in the United States (U.S.) are authorized to administer vaccines. This study described: how and to what extent immunization services are offered, promoted, and documented in community pharmacies; reasons for referral to other locations for vaccination; and perceived barriers to immunization services. METHODS: A mixed-mode (mail/electronic) survey of a stratified random sample of 1999 nationally-representative community pharmacies in the U.S. was conducted in April-July 2017. Survey instrument development was informed by validated scales and 10 in-depth interviews with community pharmacists; content and face validity were ensured via pre- (n = 5) and pilot-tests (n = 26) among community pharmacists. Potential non-response bias was investigated and descriptive statistics were used to analyze survey responses. RESULTS: Of the 1999 community pharmacies, 119 pharmacies were deemed ineligible. Of those eligible pharmacies, complete responses were provided by 292 respondents, each representing a unique pharmacy (15.5% response rate). Respondents were evenly split male/female (52.5/47.5%) and about half were pharmacy managers (51.3%). The majority (79.5%) reported offering at least one type of vaccine in 2016, with the most commonly administered vaccine types (average doses in 2016) being: Influenza (484), Pneumococcal 13-valent conjugate (55), Herpes Zoster (41), and Pneumococcal polysaccharide (39). Two-thirds (66.7%) of immunizing pharmacies provided adolescent vaccinations. Most frequently reported referral reasons were patients' insurance not covering vaccine administration at the pharmacy and patients' age not within approved protocol, policy or state law. The majority of respondents did not perceive organizational and environmental factors as barriers; however, they reported patient-related factors, especially cost and insurance coverage, as important barriers. CONCLUSIONS: The majority of U.S. community pharmacies reported offering at least one type of vaccine. The scope of pharmacy engagement in immunization services varied in terms of how and to what extent they were offered and documented. Addressing patient-related barriers is needed to further enhance pharmacy-based immunization services.

A Retrospective Cohort Study of the Incidence, Health Care Resource Utilization and Costs of International Classification of Diseases, Clinical Modification, 9th Revision Diagnosed Influenza and Related Complications in US Children.

BACKGROUND: There is a paucity of data on the clinical and economic impact of seasonal influenza in children. This study estimated the incidence of diagnosed influenza and related complications and associated health care resource utilization and costs in US children. METHODS: Children ≥6 months and <18 years old diagnosed with influenza using International Classification of Diseases, Clinical Modification, 9th revision codes and enrolled in a health plan during at least one influenza season between 2010 and 2014 were matched to similar patients without diagnosed influenza (GSK study identifier: HO-15-15728). Outcomes included incidence of influenza and complications, health care resource utilization frequency and health care costs during 21 days of follow-up. Adjusted costs were estimated using generalized linear models. RESULTS: Incidence (per 1000) of influenza was 20.3 (commercially insured) and 32.6 (Medicaid), with the highest incidence among 6-35 months old (Commercial: 26.8; Medicaid: 47.9). Approximately 12%-17% of influenza patients experienced complications, with the 6-35 months group having the highest percentage (25%-30%). The 6-35-month-old influenza patients with complications had the highest proportion with hospitalizations (5%-6%) and emergency room visits (Commercial: 19%; Medicaid: 36%). Influenza patients with (vs. without) complications had greater adjusted mean influenza-specific costs (Commercial: $1161 vs. $337; Medicaid: $1199 vs. $354; P<0.05), and influenza cases (vs. controls) had greater adjusted mean all-cause costs (Commercial: $688 vs. $470; Medicaid: $818 vs. $453; P < 0.05). CONCLUSIONS: Pediatric patients with influenza incurred higher health care costs compared with matched controls, and influenza-specific costs were greater among those with complications.

Burden of asthma with elevated blood eosinophil levels.

BACKGROUND: Asthma is a common chronic condition with an economic burden of almost $56 billion annually in the US. Biologic markers like blood eosinophils, that help predict the risk of exacerbation could help guide more optimal treatment plans and reduce cost. The purpose of this study was to determine whether healthcare resource use and expenditures vary by eosinophil level among patients with asthma. METHODS: Patients with a diagnosis of asthma defined by ICD-9-CM code 493.xx between January 2004 and July 2011 were extracted from EMRClaims + database (eMAX Health, White Plains NY). Patients were classified as mild, moderate, or severe by medication use following diagnosis, based on recommendations of National Institutes of Health Expert Panel Report 3. Patients were classified as those with elevated eosinophils (≥400 cells/µL) and normal eosinophil level (<400 cells/µL). Patients were followed for resource use, defined as hospitalizations, ER visits and outpatient visit and associated costs were calculated to assess whether an economic difference exists between eosinophil groups. Non-parametric tests were used to compare resource use and associated cost between elevated and normal eosinophil groups. Multivariate modeling was performed to assess the contribution of eosinophil level on the likelihood of study outcomes among patients with severe asthma. RESULTS: Among the 2,164 patients meeting eligibility criteria, 1,144 had severity designations. Of these, 179(16 %) of patients had severe asthma of which 20 % (n = 35) had elevated eosinophils. Seventeen percent of patients with elevated eosinophils were admitted to the hospital during the follow-up period, significantly greater than patients with normal eosinophil levels (12 %; p = 0.011). Overall, compared to patients with normal eosinophil levels (n = 1734), patients with elevated eosinophil levels (n = 430) had significantly greater mean annual hospital admissions (0.51 vs. 0.21/year, p = 0.006) and hospital costs (2,536 vs. $1,091, p = 0.011). Logistic regressions showed that elevated eosinophil level was associated with 5.14 times increased odds of all cause admissions (95 % CI:1.76-14.99, p = 0.003) and 4.07 times increased odds of asthma related admissions (95 % CI: 1.26-13.12, p = 0.019). CONCLUSION: Eosinophil elevation was associated with greater healthcare resource use in patients with asthma.

ReCAP: Treatment Patterns and Cost of Care Associated With Initial Therapy Among Patients Diagnosed With Operable Early-Stage Human Epidermal Growth Factor Receptor 2-Overexpressed Breast Cancer in the United States: A Real-World Retrospective Study.

PURPOSE: Overexpression of the human epidermal growth factor receptor 2 (HER2) protein negatively affects survival in breast cancer. This study aimed to assess real-world treatment patterns and costs associated with resected nonmetastatic HER2-positive breast cancer in the United States. PATIENTS AND METHODS: Commercially insured patients with HER2-positive breast cancer were identified from oncology registry data linked to a large US commercial administrative claims database. Treatment patterns and health care use and costs in the initial phase of care were examined. RESULTS: Among the 915 patients who met the study criteria, 662 (72%) were hormone receptor (HR) positive, and 253 (28%) were HR negative. Overall, 72% (n = 662) of patients received HER2-targeted therapy (HR positive, 69% v HR negative, 80%; P < .01), specifically trastuzumab. The most common treatment regimens, regardless of HR status, were carboplatin, docetaxel, and trastuzumab (47% of patients) during neoadjuvant therapy and carboplatin, docetaxel, and trastuzumab ± hormone therapy (30% of patients) during adjuvant therapy. Overall unadjusted cost of treatment per patient per month (HR positive, $11,906 v HR negative, $14,367; P < .001) was mainly cancer related (HR positive, $10,513 v HR negative, $13,073; P < .001). Adjusted 12-month cost was $176,779 (HR positive, $167,088 v HR negative, $180,226; P > .05). CONCLUSION: Although trastuzumab-based therapy is considered standard of care among patients with HER2-positive early-stage breast cancer, approximately 28% of these patients did not receive HER2-targeted therapy. Additional studies are warranted to examine whether patients who have not received targeted therapy are eligible for and would benefit from an HER2-targeted approach.

Treatment Patterns and Health Resource Utilization Among Patients Diagnosed With Early Stage Resected Non-Small Cell Lung Cancer at US Community Oncology Practices.

UNLABELLED: Data on adjuvant therapy in resected non-small cell lung cancer (NSCLC) in routine practice are lacking in the United States. This retrospective observational database study included 609 community oncology patients with resected stage IB to IIIA NSCLC. Use of adjuvant therapy was 39.1% at disease stage IB and 64.9% to 68.2% at stage II to IIIA. The most common regimen at all stages was carboplatin and paclitaxel. BACKGROUND: Platin-based adjuvant chemotherapy has extended survival in clinical trials in patients with completely resected non-small cell lung cancer (NSCLC). There are few data on the use of adjuvant therapy in community-based clinical practice in the United States. MATERIALS AND METHODS: This was a retrospective observational study using electronic medical record and billing data collected during routine care at US community oncology sites in the Vector Oncology Data Warehouse between January 2007 and January 2014. Patients aged ≥ 18 years with a primary diagnosis of stage IB to IIIA NSCLC were eligible if they had undergone surgical resection. Treatment patterns, health care resource use, and cost were recorded, stratified by stage at diagnosis. RESULTS: The study included 609 patients (mean age, 64.8 years, 52.9% male), of whom 215 had stage IB disease, 130 stage IIA/II, 110 stage IIB, and 154 stage IIIA. Adjuvant systemic therapy after resection was provided to 345 (56.7%) of 609 patients, with lower use in patients with stage IB disease (39.1%) than stage II to IIIA disease (64.9-68.2%) (P < .0001). The most common adjuvant regimen at all stages was the combination of carboplatin and paclitaxel. There were no statistically significant differences in office visits or incidence of hospitalization by disease stage. During adjuvant treatment, the total monthly median cost per patient was $17,389.75 (interquartile range, $8,815.61 to $23,360.85). CONCLUSION: Adjuvant systemic therapy was used in some patients with stage IB NSCLC and in the majority of patients with stage IIA to IIIA disease. There were few differences in regimen or health care resource use by disease stage.

Medical costs and adherence in patients receiving aqueous versus pressurized aerosol formulations of intranasal corticosteroids.

Intranasal corticosteroid (INS) formulations have different sensory attributes that influence patient preferences, and thereby possibly adherence and health outcomes. This study compares health care use and costs and medication adherence in matched cohorts of patients with allergic rhinitis (AR) using a chlorofluorocarbon-propelled pressurized metered-dose inhaler (pMDI) or aqueous intranasal corticosteroid (A-INS). Florida Medicaid retrospective claims analysis was performed of enrollees aged ≥12 years with at least 1 year of continuous enrollment before their initial AR diagnosis, 1 year for continuous enrollment before their index INS claim, and 18 months of continuous enrollment after their index INS claim during which they received either pMDI or A-INS. pMDI and A-INS patients were matched 1:2 using propensity scores. Nonparametric analyses compared outcomes between matched cohorts at 6, 12, and 18 months of follow-up. A total of 585 patients were matched (pMDI = 195, A-INS = 390). pMDI patients were more adherent to INS, as reflected in their higher median medication possession ratio (53.2% versus 32.7%; p < 0.0001) and fewer median days between fills (73 days versus 111 days; p = 0.0003). Significantly lower median per patient pharmacy fills (34.0 versus 50.5; p < 0.05) and costs ($1282 versus $2178; p < 0.01) were observed among pMDI patients versus A-INS patients 18 months after INS initiation and were maintained when analyses excluded INS fills. Adherence to INS and health care utilization and costs following INS initiation for AR differed by type of formulation received. Our findings suggest patient preferences for INS sensory attributes can drive adherence and affect disease control, and ultimately impact health care costs.