The Societal Value of Vaccines: Expert-Based Conceptual Framework and Methods Using COVID-19 Vaccines as A Case Study

Health technology assessments (HTAs) of vaccines typically focus on the direct health benefits to individuals and healthcare systems. COVID-19 highlighted the widespread societal impact of infectious diseases and the value of vaccines in averting adverse clinical consequences and in maintaining or resuming social and economic activities. Using COVID-19 as a case study, this research work aimed to set forth a conceptual framework capturing the broader value elements of vaccines and to identify appropriate methods to quantify value elements not routinely considered in HTAs. A two-step approach was adopted combining a targeted literature review and three rounds of expert elicitation based on a modified Delphi method, leading to a conceptual framework of 30 value elements related to broader health effects, societal and economic impact, public finances, and uncertainty value. When applying the framework to COVID-19 vaccines in post-pandemic settings, 13 value elements were consensually rated highly important by the experts for consideration in HTAs. The experts reviewed over 10 methods that could be leveraged to quantify broader value elements and provided technical forward-looking recommendations. Limitations of the framework and the identified methods were discussed. This study supplements on-going efforts aimed towards a broader recognition of the full societal value of vaccines.

Impact of COVID-19 and Effects of Vaccination with BNT162b2 on Patient-Reported Health-Related Quality of Life, Symptoms, and Work Productivity Among US Adult Outpatients with SARS-CoV-2

BackgroundAlthough there is extensive literature on the clinical benefits of COVID-19 vaccination, data on humanistic effects are limited. This study evaluated the impact of SARS-CoV-2 infection on symptoms, Health Related Quality of Life (HRQoL) and Work Productivity and Impairment (WPAI) prior to and one month following infection, and compared results between individuals vaccinated with BNT162b2 and those unvaccinated. MethodsSubjects with [≥]1 self-reported symptom and positive RT-PCR for SARS-CoV-2 at CVS Health US test sites were recruited between 01/31/2022-04/30/2022. Socio-demographics, clinical characteristics and vaccination status were evaluated. Self-reported symptoms, HRQoL, and WPAI outcomes were assessed using questionnaires and validated instruments (EQ-5D-5L, WPAI-GH) across acute COVID time points from pre-COVID to Week 4, and between vaccination groups. Mixed models for repeated measures were conducted for multivariable analyses, adjusting for several covariates. Effect size (ES) of Cohens d was calculated to quantify the magnitude of outcome changes within and between vaccination groups. ResultsThe study population included 430 subjects: 197 unvaccinated and 233 vaccinated with BNT162b2. Mean (SD) age was 42.4 years (14.3), 76.0% were female, 38.8% reported prior infection and 24.2% at least one comorbidity. Statistically significant differences in outcomes were observed compared with baseline and between groups. The EQ-Visual analogue scale scores and Utility Index dropped in both cohorts at Day 3 and increased by Week 4, but did not return to pre-COVID levels. The mean changes were statistically lower in the BNT162b2 cohort at Day 3 and Week 4. The BNT162b2 cohort reported lower prevalence and fewer symptoms at index date and Week 4. At Week 1, COVID-19 had a large impact on all WPAI-GH domains: the work productivity time loss among unvaccinated and vaccinated was 65.0% and 53.8%, and the mean activity impairment was 50.2% and 43.9%, respectively. With the exception of absenteeism at Week 4, the BNT162b2 cohort was associated with statistically significant less worsening in all WPAI-GH scores at both Week 1 and 4. ConclusionsCOVID-19 negatively impacted HRQoL and work productivity among mildly symptomatic outpatients. Compared with unvaccinated, those vaccinated with BNT162b2 were less impacted by COVID-19 infection and recovered faster.

The impact of COVID-19 vaccination in the US: averted burden of SARS-COV-2-related cases, hospitalizations and deaths

By August 1, 2022, the SARS-CoV-2 virus had caused over 90 million cases of COVID-19 and one million deaths in the United States. Since December 2020, SARS-CoV-2 vaccines have been a key component of US pandemic response; however, the impacts of vaccination are not easily quantified. Here, we use a dynamic county-scale metapopulation model to estimate the number of cases, hospitalizations, and deaths averted due to vaccination during the first six months of vaccine availability. We estimate that COVID-19 vaccination was associated with over 8 million fewer confirmed cases, over 120 thousand fewer deaths, and 700 thousand fewer hospitalizations during the first six months of the campaign.

Public Health Impact of the Pfizer-BioNTech COVID-19 vaccine (BNT162b2) in the first year of rollout in the United States

BackgroundAs the body of evidence on COVID-19 and post-vaccination outcomes continues to expand, this analysis sought to evaluate the public health impact of the Pfizer-BioNTech COVID-19 Vaccine, BNT162b2, during the first year of its rollout in the US. MethodsA combined Markov decision tree model compared clinical and economic outcomes of the Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) versus no vaccination in individuals aged [≥]12 years. Age-stratified epidemiological, clinical, economic, and humanistic parameters were derived from existing data and published literature. Scenario analysis explored the impact of using lower and upper bounds of parameters on the results. The health benefits were estimated as the number of COVID-19 symptomatic cases, hospitalizations and deaths averted, and Quality Adjusted Life Years (QALYs) saved. The economic benefits were estimated as the amount of healthcare and societal cost savings associated with the vaccine-preventable health outcomes. ResultsIt was estimated that, in 2021, the Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) contributed to averting almost 9 million symptomatic cases, close to 700,000 hospitalizations, and over 110,000 deaths, resulting in an estimated $30.4 billion direct healthcare cost savings, $43.7 billion indirect cost savings related to productivity loss, as well as discounted gains of 1.1 million QALYs. Scenario analyses showed that these results were robust; the use of alternative plausible ranges of parameters did not change the interpretation of the findings. ConclusionsThe Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) contributed to generate substantial public health impact and vaccine-preventable cost savings in the first year of its rollout in the US. The vaccine was estimated to prevent millions of COVID-19 symptomatic cases and thousands of hospitalizations and deaths, and these averted outcomes translated into cost-savings in the billions of US dollars and thousands of QALYs saved. As only direct impacts of vaccination were considered, these estimates may be conservative. KEY SUMMARY POINTSO_ST_ABSWhy carry out this study?C_ST_ABSO_LIAssessing the population-level health and economic impact of the Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) is important for policy makers and payers who support decision-making and investment in vaccination. C_LIO_LIThese analyses may be relevant to the public, especially those who remain hesitant to COVID-19 vaccination. C_LI What was learned from the study?O_LIThis study showed that Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) was an effective strategy that contributed to generating substantial public health impact and economic gains in the US in 2021 C_LIO_LIThe vaccine was estimated to prevent millions of COVID-19 symptomatic cases and thousands of hospitalizations and deaths, and these averted outcomes translated into cost-savings in the billions of US dollars and millions of QALYs saved C_LIO_LIThe study highlights the importance of continuing widespread uptake of the Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) to prevent COVID-19 related disease and generate substantial benefits from a broad, patient-centric, societal perspective C_LI

COVID-19-Associated Hospitalizations Among Children Less Than 12 Years of Age in the United States

ObjectivesTo describe the characteristics, healthcare resource use and costs associated with initial hospitalization and readmissions among pediatric patients with COVID-19 in the US. MethodsHospitalized pediatric patients, 0-11 years of age, with a primary or secondary discharge diagnosis code for COVID-19 (ICD-10 code U07.1) were selected from 1 April 2020 through 30 September 2021 in the US Premier Healthcare Database Special Release (PHD SR). Patient characteristics, hospital length of stay (LOS), in-hospital mortality, hospital costs, hospital charges, and COVID-19-associated readmission outcomes were evaluated and stratified by age groups (0-4, 5-11), four COVID-19 disease progression states based on intensive care unit (ICU) and invasive mechanical ventilation (IMV) usage, and three sequential calendar periods. Sensitivity analyses were performed using the US HealthVerity claims database and restricting the analyses to primary discharge code. ResultsAmong 4,573 hospitalized pediatric patients aged 0-11 years, 68.0% were 0-4 years and 32.0% were 5-11 years, with a mean (median) age of 3.2 (1) years; 56.0% were male, and 67.2% were covered by Medicaid. Among the overall study population, 25.7% had immunocompromised condition(s), 23.1% were admitted to the ICU and 7.3% received IMV. The mean (median) hospital LOS was 4.3 (2) days, hospital costs and charges were $14,760 ($6,164) and $58,418 ($21,622), respectively; in-hospital mortality was 0.5%. LOS, costs, charges, and in-hospital mortality increased with ICU admission and/or IMV usage. In total, 2.1% had a COVID-19-associated readmission. Study outcomes appeared relatively more frequent and/or higher among those 5-11 than those 0-4. Results using the HealthVerity data source were generally consistent with main analyses. LimitationsThis retrospective administrative database analysis relied on coding accuracy and inpatient admissions with validated hospital costs. ConclusionsThese findings underscore that children aged 0-11 years can experience severe COVID-19 illness requiring hospitalization and substantial hospital resource use, further supporting recommendations for COVID-19 vaccination.

COVID-19 vaccine effectiveness among immunocompromised populations: a targeted literature review of real-world studies

IntroductionFrom July through October of 2021, several countries issued recommendations for increased COVID-19 vaccine protection for individuals with one or more immunocompromised (IC) conditions. It is critically important to understand the vaccine effectiveness (VE) of COVID-19 vaccines among IC populations as recommendations are updated over time in response to the evolving COVID-19 pandemic. Areas coveredA targeted literature review was conducted to identify real-world studies that assessed COVID-19 VE in IC populations between December 2020 and September 2021. A total of 10 studies from four countries were identified and summarized in this review. Expert opinion/commentaryVE of the widely available COVID-19 vaccines, including BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), Ad26.COV2.S (Janssen), and ChAdOx1 nCoV-19 (Oxford/AstraZeneca), ranged from 64%-90% against SARS-CoV-2 infection, 73%-84% against symptomatic illness, 70%-100% against severe illness, and 63%-100% against COVID-19-related hospitalization among the fully vaccinated IC populations included in the studies. COVID-19 VE for most outcomes in the IC populations included in these studies was lower than in the general populations. These findings provide preliminary evidence that the IC population requires greater protective measures to prevent COVID-19 infection and associated illness, hence should be prioritized while implementing recommendations of additional COVID-19 vaccine doses.

Evaluation of COVID-19 vaccine breakthrough infections among immunocompromised patients fully vaccinated with BNT162b2

ObjectiveTo evaluate COVID-19 vaccine breakthrough infections among immunocompromised (IC) individuals. MethodsIndividuals vaccinated with BNT162b2 were selected from the US HealthVerity database (12/10/2020-7/8/2021). COVID-19 vaccine breakthrough infections were examined in fully vaccinated ([≥]14 days after 2nd dose) IC individuals (IC cohort), 12 mutually exclusive IC condition groups, and a non-IC cohort. IC conditions were identified using an algorithm based on diagnosis codes and immunosuppressive (IS) medication usage. ResultsOf 1,277,747 individuals [≥]16 years of age who received 2 BNT162b2 doses, 225,796 (17.7%) were identified as IC (median age: 58 years; 56.3% female). The most prevalent IC conditions were solid malignancy (32.0%), kidney disease (19.5%), and rheumatologic/inflammatory conditions (16.7%). Among the fully vaccinated IC and non-IC cohorts, a total of 978 breakthrough infections were observed during the study period; 124 (12.7%) resulted in hospitalization and 2 (0.2%) were inpatient deaths. IC individuals accounted for 38.2% (N=374) of all breakthrough infections, 59.7% (N=74) of all hospitalizations, and 100% (N=2) of inpatient deaths. The proportion with breakthrough infections was 3 times higher in the IC cohort compared to the non-IC cohort (N=374 [0.18%] vs. N=604 [0.06%]; unadjusted incidence rates were 0.89 and 0.34 per 100 person-years, respectively. Organ transplant recipients had the highest incidence rate; those with >1 IC condition, antimetabolite usage, primary immunodeficiencies, and hematologic malignancies also had higher incidence rates compared to the overall IC cohort. Incidence rates in older ([≥]65 years old) IC individuals were generally higher versus younger IC individuals (<65). LimitationsThis retrospective analysis relied on coding accuracy and had limited capture of COVID-19 vaccine receipt. ConclusionsCOVID-19 vaccine breakthrough infections are rare but are more common and severe in IC individuals. The findings from this large study support FDA authorization and CDC recommendations to offer a 3rd vaccine dose to increase protection among IC individuals.