A summary of the Advisory Committee for Immunization Practices (ACIP) use of a benefit-risk assessment framework during the first year of COVID-19 vaccine administration in the United States.

To inform Advisory Committee for Immunization Practices (ACIP) COVID-19 vaccine policy decisions, we developed a benefit-risk assessment framework that directly compared the estimated benefits of COVID-19 vaccination to individuals (e.g., prevention of COVID-19-associated hospitalization) with risks associated with COVID-19 vaccines. This assessment framework originated following the identification of thrombosis with thrombocytopenia syndrome (TTS) after Janssen COVID-19 vaccination in April 2021. We adapted the benefit-risk assessment framework for use in subsequent policy decisions, including the adverse events of myocarditis and Guillain-Barre syndrome (GBS) following mRNA and Janssen COVID-19 vaccination respectively, expansion of COVID-19 vaccine approvals or authorizations to new age groups, and use of booster doses. Over the first year of COVID-19 vaccine administration in the United States (December 2020-December 2021), we used the benefit-risk assessment framework to inform seven different ACIP policy decisions. This framework allowed for rapid and direct comparison of the benefits and potential harms of vaccination, which may be helpful in informing other vaccine policy decisions. The assessments were a useful tool for decision-making but required reliable and granular data to stratify analyses and appropriately focus on populations most at risk for a specific adverse event. Additionally, careful decision-making was needed on parameters for data inputs. Sensitivity analyses were used where data were limited or uncertain; adjustments in the methodology were made over time to ensure the assessments remained relevant and applicable to the policy questions under consideration.

Cost-Effectiveness Analysis of Vaccination With Recombinant Zoster Vaccine Among Hematopoietic Cell Transplant Recipients and Persons With Other Immunocompromising Conditions Aged 19 to 49 Years.

OBJECTIVES: This study aimed to estimate the cost-effectiveness of the use of recombinant zoster vaccine (RZV) (Shingrix), which protects against herpes zoster (HZ), among immunocompromised adults aged 19 to 49 years, as a contribution to deliberations of the Advisory Committee on Immunization Practices. METHODS: Hematopoietic cell transplant (HCT) recipients experience a high incidence of HZ, and the efficacy of RZV in preventing HZ has been studied in clinical trials. The cost-effectiveness model calculated incremental cost-effectiveness ratios that compared vaccination with RZV with a no vaccination strategy among adults aged 19 to 49 years. Costs and outcomes were calculated until age 50 years using the healthcare sector perspective and summarized as cost per quality-adjusted life-year (QALY) gained. The base case represents HCT recipients, with scenario analyses representing persons with other immunocompromising conditions, including hematologic malignancies, human immunodeficiency virus, and autoimmune and inflammatory conditions. Uncertainty was investigated using univariate, multivariate, and probabilistic sensitivity analyses. RESULTS: Base-case results indicated vaccination with RZV would avert approximately 35% of HZ episodes and complications, while saving approximately 11% of net costs. Compared with no vaccination, vaccination of HCT recipients with RZV generated cost-savings (ie, lower costs and improved health) in the base case and in 81% of simulations in the probabilistic analysis. In scenario analyses, vaccination cost US dollar ($) 9500/QALY among patients with hematologic malignancies, $79 000/QALY among persons living with human immunodeficiency virus, and $208 000/QALY among persons with selected autoimmune and inflammatory conditions. CONCLUSIONS: Generally favorable economic estimates supported recommendations for vaccination of immunocompromised adults with RZV to prevent episodes of HZ and related complications.

Health and Economic Impact of the United States Varicella Vaccination Program, 1996-2020.

BACKGROUND: The aim of this study was to evaluate the health and economic impact of the varicella vaccination program on varicella disease in the United States (US), 1996-2020. METHODS: Analysis was conducted using the Centers for Disease Control and Prevention or published annual population-based varicella incidence, and varicella-associated hospitalization, outpatient visit, and mortality rates in the US population aged 0-49 years during 1996-2020 (range, 199.5-214.2 million persons) compared to before vaccination (1990-1994). Disease costs were estimated using the societal perspective. Vaccination program costs included costs of vaccine, administration, postvaccination adverse events, and travel and work time lost to obtain vaccination. All costs were adjusted to 2020 US dollars using a 3% annual discount rate. The main outcome measures were the number of varicella-associated cases, hospitalizations, hospitalization days, and premature deaths prevented; life-years saved; and net societal savings from the US varicella vaccination program. RESULTS: Among US persons aged 0-49 years, during 1996-2020, it is estimated that more than 91 million varicella cases, 238 000 hospitalizations, 1.1 million hospitalization days, and almost 2000 deaths were prevented and 118 000 life-years were saved by the varicella vaccination program, at net societal savings of $23.4 billion. CONCLUSIONS: Varicella vaccination has resulted in substantial disease prevention and societal savings for the US over 25 years of program implementation.

Recombinant Zoster Vaccine Uptake and Risk of Flares Among Older Adults With Immune-Mediated Inflammatory Diseases in the US.

OBJECTIVE: Persons with immune-mediated inflammatory diseases (IMIDs) are at an increased risk of herpes zoster (HZ). In 2018, the Centers for Disease Control and Prevention recommended a highly efficacious vaccine, recombinant zoster vaccine (RZV), for prevention of HZ in immunocompetent patients ≥50 years of age. This study was undertaken to estimate RZV vaccination among adults ages ≥50 years with IMIDs during 2018-2019 and to examine possible vaccine-related flares following RZV. METHODS: We identified a cohort of IMID patients using medical claims data from the IBM MarketScan (ages 50-64 years) and Centers for Medicare and Medicaid Services Medicare (ages ≥65 years) databases. Presumed flares were defined as hospitalization/emergency department visit for their respective IMIDs, or steroid treatment with a short-acting oral glucocorticoid or parenteral glucocorticoid injection. We conducted a self-controlled case series (SCCS) analysis to examine a temporal association between RZV and flares. RESULTS: Among enrollees with IMIDs, 14.8% of 55,654 MarketScan enrollees and 43.2% of 160,545 Medicare enrollees received ≥1 dose of RZV in 2018-2019. Two-dose series completion rates were 76.6% in MarketScan enrollees and 85.4% in Medicare enrollees. In the SCCS analysis, 10% and 13% developed flares in the control window, compared to 9% and 11-12% in the risk window following 1 or 2 doses of RZV among MarketScan and Medicare enrollees, respectively. We found no statistically significant increase in flares following RZV administration for any IMID in either age group following RZV dose 1 or dose 2. CONCLUSION: We did not find an increase in presumed flares following RZV vaccination. Among adults ages ≥50 years with IMIDs, a substantial proportion received RZV compared to general zoster coverage estimates, and series completion rates were high.

Projected risks and health benefits of vaccination against herpes zoster and related complications in US adults.

The Advisory Committee on Immunization Practices (ACIP) recommends recombinant zoster vaccine (RZV) to prevent against herpes zoster (HZ) and related complications in immunocompetent adults ≥50 y and immunocompromised adults ≥19 y. In 2019, a statistical safety signal for Guillain-Barré syndrome (GBS) following RZV was identified using data from the Vaccine Safety Datalink (VSD). Subsequently, the U.S. Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and collaborators undertook additional analyses using Centers for Medicare & Medicaid Services (CMS) Medicare data to further investigate the potential risk of GBS following RZV. Concurrently, epidemiologic data suggested a potentially elevated risk of GBS following HZ in U.S. adults. Using data from these sources and a published simulation model, this study evaluated the health benefits and risks associated with vaccinating immunocompetent adults ≥50 y with RZV compared to no vaccination. In the base case analysis, RZV vaccination averted 43,000-63,000 cases of HZ, including GBS complications, per million vaccinated per 10-y age cohort compared to 3-6 additional cases of GBS projected following RZV per million vaccinated in the same population. This analysis highlights the projected health benefits of RZV vaccination compared to the relatively low potential risk of GBS following RZV.

Risk of Guillain-Barré syndrome following herpes zoster, United States, 2010-2018.

Epidemiologic data regarding the risk of Guillain-Barré syndrome (GBS) following herpes zoster (HZ) are limited. We conducted a self-controlled case series analysis using two large national data sources to evaluate the risk of GBS following HZ among U.S. adults. We analyzed medical claims from the IBM® MarketScan® Commercial Claims and Encounters (persons 18-64 years during 2010-2018) and Centers for Medicare and Medicaid Services Medicare (persons ≥65 years during 2014-2018) databases. HZ cases were defined as persons with an outpatient claim with a primary or secondary ICD-9 or ICD-10 diagnostic code for HZ. GBS cases were defined as persons with an inpatient claim with a principle diagnostic code for GBS and an associated procedural code. We compared the rates of GBS following HZ in the 1-42-day risk window versus primary (100-365-day) or secondary (43-99-day) control windows. We identified 489,516 persons 18-64 years of age and 650,229 persons ≥65 years of age with HZ, among whom 11 and 41, respectively, developed GBS 1-365 days following HZ. The risk of GBS following HZ was increased during the risk window as compared to the primary control window for both groups, with a rate ratio of 6.3 (95% CI, 1.8-21.9) for those 18-64 years and 4.1 (95% CI, 1.9-8.7) for those ≥65 years. This study provides new and methodologically rigorous epidemiologic support for an association between HZ and GBS, and useful context regarding the benefits versus potential risks of zoster vaccination.

Decline in Receipt of Vaccines by Medicare Beneficiaries During the COVID-19 Pandemic - United States, 2020.

On March 13, 2020, the United States declared a national emergency concerning the novel coronavirus disease 2019 (COVID-19) outbreak (1). In response, many state and local governments issued shelter-in-place or stay-at-home orders, restricting nonessential activities outside residents' homes (2). CDC initially issued guidance recommending postponing routine adult vaccinations, which was later revised to recommend continuing to administer routine adult vaccines (3). In addition, factors such as disrupted operations of health care facilities and safety concerns regarding exposure to SARS-CoV-2, the virus that causes COVID-19, resulted in delay or avoidance of routine medical care (4), likely further affecting delivery of routine adult vaccinations. Medicare enrollment and claims data of Parts A (hospital insurance), B (medical insurance), and D (prescription drug insurance) were examined to assess the change in receipt of routine adult vaccines during the pandemic. Weekly receipt of four vaccines (13-valent pneumococcal conjugate vaccine [PCV13], 23-valent pneumococcal polysaccharide vaccine [PPSV23], tetanus-diphtheria or tetanus-diphtheria-acellular pertussis vaccine [Td/Tdap], and recombinant zoster vaccine [RZV]) by Medicare beneficiaries aged ≥65 years during January 5-July 18, 2020, was compared with that during January 6-July 20, 2019, for the total study sample and by race and ethnicity. Overall, weekly administration rates of the four examined vaccines declined by up to 89% after the national emergency declaration in mid-March (1) compared with those during the corresponding period in 2019. During the first week following the national emergency declaration, the weekly vaccination rates were 25%-62% lower than those during the corresponding week in 2019. After reaching their nadirs of 70%-89% below 2019 rates in the second to third week of April 2020, weekly vaccination rates gradually began to recover through mid-July, but by the last study week were still lower than were those during the corresponding period in 2019, with the exception of PPSV23. Vaccination declined sharply for all vaccines studied, overall and across all racial and ethnic groups. While the pandemic continues, vaccination providers should emphasize to patients the importance of continuing to receive routine vaccinations and provide reassurance by explaining the procedures in place to ensure patient safety (3).

Recombinant Zoster Vaccine (Shingrix): Real-World Effectiveness in the First 2 Years Post-Licensure.

BACKGROUND: Shingrix (recombinant zoster vaccine) was licensed to prevent herpes zoster, dispensed as 2 doses given 2-6 months apart among adults aged ≥50 years. Clinical trials yielded efficacy of >90% for confirmed herpes zoster, but post-market performance has not been evaluated. Efficacy of a single dose and a delayed second dose and efficacy among persons with autoimmune or immunosuppressive conditions have not been studied. We aimed to assess post-market vaccine effectiveness of Shingrix. METHODS: We conducted a cohort study among Medicare Part D community-dwelling beneficiaries aged >65 years. Herpes zoster was identified using a medical office visit diagnosis with treatment, and postherpetic neuralgia was identified using a validated algorithm. We used inverse probability of treatment weighting to improve cohort balance and marginal structural models to estimate hazard ratios. RESULTS: We found a vaccine effectiveness of 70.1% (95% confidence interval [CI], 68.6-71.5) and 56.9% (95% CI, 55.0-58.8) for 2 and 1 doses, respectively. The 2-dose vaccine effectiveness was not significantly lower for beneficiaries aged >80 years, for second doses received at ≥180 days, or for individuals with autoimmune conditions. The vaccine was also effective among individuals with immunosuppressive conditions. Two-dose vaccine effectiveness against postherpetic neuralgia was 76.0% (95% CI, 68.4-81.8). CONCLUSIONS: This large real-world observational study of the effectiveness of Shingrix demonstrates the benefit of completing the 2-dose regimen. Second doses administered beyond the recommended 6 months did not impair effectiveness. Our effectiveness estimates were lower than the clinical trials estimates, likely due to differences in outcome specificity.

The Advisory Committee on Immunization Practices' Updated Interim Recommendation for Allocation of COVID-19 Vaccine - United States, December 2020.

The first vaccines for prevention of coronavirus disease 2019 (COVID-19) in the United States were authorized for emergency use by the Food and Drug Administration (FDA) (1) and recommended by the Advisory Committee on Immunization Practices (ACIP) in December 2020.* However, demand for COVID-19 vaccines is expected to exceed supply during the first months of the national COVID-19 vaccination program. ACIP advises CDC on population groups and circumstances for vaccine use.† On December 1, ACIP recommended that 1) health care personnel§ and 2) residents of long-term care facilities¶ be offered COVID-19 vaccination first, in Phase 1a of the vaccination program (2). On December 20, 2020, ACIP recommended that in Phase 1b, vaccine should be offered to persons aged ≥75 years and frontline essential workers (non-health care workers), and that in Phase 1c, persons aged 65-74 years, persons aged 16-64 years with high-risk medical conditions, and essential workers not recommended for vaccination in Phase 1b should be offered vaccine.** These recommendations for phased allocation provide guidance for federal, state, and local jurisdictions while vaccine supply is limited. In its deliberations, ACIP considered scientific evidence regarding COVID-19 epidemiology, ethical principles, and vaccination program implementation considerations. ACIP's recommendations for COVID-19 vaccine allocation are interim and might be updated based on changes in conditions of FDA Emergency Use Authorization, FDA authorization for new COVID-19 vaccines, changes in vaccine supply, or changes in COVID-19 epidemiology.

The Advisory Committee on Immunization Practices' Interim Recommendation for Allocating Initial Supplies of COVID-19 Vaccine - United States, 2020.

The emergence of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), has led to a global pandemic that has disrupted all sectors of society. Less than 1 year after the SARS-CoV-2 genome was first sequenced, an application* for Emergency Use Authorization for a candidate vaccine has been filed with the Food and Drug Administration (FDA). However, even if one or more vaccine candidates receive authorization for emergency use, demand for COVID-19 vaccine is expected to exceed supply during the first months of the national vaccination program. The Advisory Committee on Immunization Practices (ACIP) advises CDC on population groups and circumstances for vaccine use.† ACIP convened on December 1, 2020, in advance of the completion of FDA's review of the Emergency Use Authorization application, to provide interim guidance to federal, state, and local jurisdictions on allocation of initial doses of COVID-19 vaccine. ACIP recommended that, when a COVID-19 vaccine is authorized by FDA and recommended by ACIP, both 1) health care personnel§ and 2) residents of long-term care facilities (LTCFs)¶ be offered vaccination in the initial phase of the COVID-19 vaccination program (Phase 1a**).†† In its deliberations, ACIP considered scientific evidence of SARS-CoV-2 epidemiology, vaccination program implementation, and ethical principles.§§ The interim recommendation might be updated over the coming weeks based on additional safety and efficacy data from phase III clinical trials and conditions of FDA Emergency Use Authorization.

The Advisory Committee on Immunization Practices' Ethical Principles for Allocating Initial Supplies of COVID-19 Vaccine - United States, 2020.

To reduce the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) and its associated impacts on health and society, COVID-19 vaccines are essential. The U.S. government is working to produce and deliver safe and effective COVID-19 vaccines for the entire U.S. population. The Advisory Committee on Immunization Practices (ACIP)* has broadly outlined its approach for developing recommendations for the use of each COVID-19 vaccine authorized or approved by the Food and Drug Administration (FDA) for Emergency Use Authorization or licensure (1). ACIP's recommendation process includes an explicit and transparent evidence-based method for assessing a vaccine's safety and efficacy as well as consideration of other factors, including implementation (2). Because the initial supply of vaccine will likely be limited, ACIP will also recommend which groups should receive the earliest allocations of vaccine. The ACIP COVID-19 Vaccines Work Group and consultants with expertise in ethics and health equity considered external expert committee reports and published literature and deliberated the ethical issues associated with COVID-19 vaccine allocation decisions. The purpose of this report is to describe the four ethical principles that will assist ACIP in formulating recommendations for the allocation of COVID-19 vaccine while supply is limited, in addition to scientific data and implementation feasibility: 1) maximize benefits and minimize harms; 2) promote justice; 3) mitigate health inequities; and 4) promote transparency. These principles can also aid state, tribal, local, and territorial public health authorities as they develop vaccine implementation strategies within their own communities based on ACIP recommendations.

A Cost-Effectiveness Analysis of Vaccination for Prevention of Herpes Zoster and Related Complications: Input for National Recommendations.

Background: The U.S. Advisory Committee on Immunization Practices recently developed recommendations for use of a new recombinant zoster vaccine (RZV). Objective: To evaluate the cost-effectiveness of vaccination with RZV compared with zoster vaccine live (ZVL) and no vaccination, the cost-effectiveness of vaccination with RZV for persons who have previously received ZVL, and the cost-effectiveness of preferential vaccination with RZV over ZVL. Design: Simulation (state-transition) model using U.S. epidemiologic, clinical, and cost data. Data Sources: Published data. Target Population: Hypothetical cohort of immunocompetent U.S. adults aged 50 years or older. Time Horizon: Lifetime. Perspective: Societal and health care sector. Intervention: Vaccination with RZV (recommended 2-dose regimen), vaccination with ZVL, and no vaccination. Outcome Measures: The primary outcome measure was the incremental cost-effectiveness ratio (ICER). Results of Base-Case Analysis: For vaccination with RZV compared with no vaccination, ICERs ranged by age from $10 000 to $47 000 per quality-adjusted life-year (QALY), using a societal perspective and assuming 100% completion of the 2-dose RZV regimen. For persons aged 60 years or older, ICERs were less than $60 000 per QALY. Vaccination with ZVL was dominated by vaccination with RZV for all age groups 60 years or older. Results of Sensitivity Analysis: Results were most sensitive to changes in vaccine effectiveness, duration of protection, herpes zoster incidence, and probability of postherpetic neuralgia. Vaccination with RZV after previous administration of ZVL yielded an ICER of less than $60 000 per QALY for persons aged 60 years or older. In probabilistic sensitivity analyses, RZV remained the preferred strategy in at least 95% of simulations, including those with 50% completion of the second dose. Limitation: Few data were available on risk for serious adverse events, adherence to the recommended 2-dose regimen, and probability of recurrent zoster. Conclusion: Vaccination with RZV yields cost-effectiveness ratios lower than those for many recommended adult vaccines, including ZVL. Results are robust over a wide range of plausible values. Primary Funding Source: Centers for Disease Control and Prevention.

Cost-effectiveness of adult vaccinations: A systematic review.

BACKGROUND: Coverage levels for many recommended adult vaccinations are low. The cost-effectiveness research literature on adult vaccinations has not been synthesized in recent years, which may contribute to low awareness of the value of adult vaccinations and to their under-utilization. We assessed research literature since 1980 to summarize economic evidence for adult vaccinations included on the adult immunization schedule. METHODS: We searched PubMed, EMBASE, EconLit, and Cochrane Library from 1980 to 2016 and identified economic evaluation or cost-effectiveness analysis for vaccinations targeting persons aged ≥18 years in the U.S. or Canada. After excluding records based on title and abstract reviews, the remaining publications had a full-text review from two independent reviewers, who extracted economic values that compared vaccination to "no vaccination" scenarios. RESULTS: The systematic searches yielded 1688 publications. After removing duplicates, off-topic publications, and publications without a "no vaccination" comparison, 78 publications were included in the final analysis (influenza = 25, pneumococcal = 18, human papillomavirus = 9, herpes zoster = 7, tetanus-diphtheria-pertussis = 9, hepatitis B = 9, and multiple vaccines = 1). Among outcomes assessing age-based vaccinations, the percent indicating cost-savings was 56% for influenza, 31% for pneumococcal, and 23% for tetanus-diphtheria-pertussis vaccinations. Among age-based vaccination outcomes reporting $/QALY, the percent of outcomes indicating a cost per QALY of ≤$100,000 was 100% for influenza, 100% for pneumococcal, 69% for human papillomavirus, 71% for herpes zoster, and 50% for tetanus-diphtheria-pertussis vaccinations. CONCLUSIONS: The majority of published studies report favorable cost-effectiveness profiles for adult vaccinations, which supports efforts to improve the implementation of adult vaccination recommendations.