Relative Vaccine Effectiveness Research Articles

14. A Comprehensive Real-World Analysis to Compare Adjuvanted Trivalent Influenza Vaccine and Trivalent High Dose Influenza Vaccine by Age and Period of High Influenza Activity for the 2018–19 Season among U.S. Elderly

BackgroundInfluenza vaccine effectiveness decreases with increasing age due to the senescence of immune function and a reduced immune response to antigens. There is also considerable vaccine effectiveness heterogeneity depending on the influenza activity time period, especially in seasons where two different circulating strains predominated, such as the 2018–19 season. This research aimed to assess the effect of age and high influenza activity period (HIAP) on the relative vaccine effectiveness (rVE) of adjuvanted trivalent influenza vaccine (aTIV) vs. trivalent high-dose influenza vaccine (HD-TIV) among elderly (≥65y) recipients in the U.S.MethodsDuring the 2018–19 influenza season, a retrospective cohort analysis was conducted using professional fee, prescription claims and hospital charge master data in the U.S. The first sub-analysis evaluated rVE for different age groups (65–74 years, 75–84 years, ≥85 years). The second sub-analysis evaluated rVE overall, restricting the observation period from to HAIP: Dec 2018-Mar 2019 (August 2018-July 2019 in the main analysis). Adjusted analyses were conducted through inverse probability of treatment weighting (IPTW) to control for selection bias. Poisson regression was used to estimate the adjusted pairwise rVE for influenza-related hospitalizations/emergency room (ER) visits and office visits.ResultsFollowing IPTW, 561,315 recipients of aTIV and 1,672,779 of TIV-HD were identified. Following IPTW adjustment and Poisson regression, aTIV was more effective in reducing influenza-related office visits compared to TIV-HD (7.0%; 95% CI: 2.6%-11.2%) in the HIAP sub-analysis. In the age sub-analysis, the rVE favoring aTIV ranged from 5.1% (95% CI: -0.17%-10.1%) for the youngest group (65–74) up to 11.4% (95% CI: 0.6%-21.1%) for the eldest group (≥85y) for influenza-related office visits. No statistically significant differences were found for aTIV compared to TIV-HD for prevention of influenza-related hospitalizations/ER visits in the sub-analyses evaluated.ConclusionIn adjusted analyses, aTIV reduced influenza-related office visits compared to TIV-HD within the two older age groups and HIAP sub-analysis. aTIV and TIV-HD demonstrated comparable reductions in influenza-related hospitalizations/ER visits.Disclosures Maarten Postma, Dr., IQVIA (Consultant) Stephen I. Pelton, MD, Merck vaccine (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support)Sanofi Pasteur (Consultant, Other Financial or Material Support, DSMB)Seqirus Vaccine Ltd. (Consultant) Victoria Divino, PhD, Seiqrus Vaccines Ltd. (Consultant) Joaquin F. Mould-Quevedo, PhD, Seqirus Vaccines Ltd. (Employee, Shareholder) Drishti Shah, PhD, Seqirus Vaccines Ltd. (Consultant) Mitchell DeKoven, PhD, Seqirus Vaccines Ltd. (Consultant)

Relative vaccine effectiveness of adjuvanted trivalent influenza vaccine compared to egg-based trivalent high dose and other egg-based vaccines

Relative vaccine effectiveness of adjuvanted trivalent influenza vaccine compared to egg-based trivalent high dose and other egg-based vaccines

PRS25 Budget IMPACT Analysis of the CELL-Based Quadrivalent Influenza Vaccine in the German Population Using a Dynamic Transmission MODEL Approach

Cell-based influenza vaccine production can avoid egg-adaptation in vaccine viruses, particularly the H3N2 strain, enabling closer match between vaccine antigens and anticipated circulating strains. A closer match to circulating virus strains potentially increases effectiveness of cell-based influenza vaccine. The study aimed to evaluate the budget impact of a national immunization program based on the progressive use of cell-based quadrivalent influenza vaccine (QIVc) versus the current scenario of vaccinating exclusively with standard egg-based quadrivalent influenza vaccines (QIVe) in Germany (aged 9yrs+). The individual-based dynamic transmission model (4Flu) with German demography and contact structure was used to provide realistic estimates of the impact of QIVc over QIVe on age-specific influenza infections. The model was calibrated on German influenza attack rate using national vaccination rates, and combined with a decision tree structure. Relative vaccine effectiveness of QIVc over QIVe was assumed from a US retrospective cohort study. Egg-adapted mismatch was assumed to occur each year, although more conservative scenarios were assessed. Influenza-related probabilities of outpatient visit, hospitalization, mortality, and direct and indirect costs were extracted from published literature. The budget impact model includes a moderate increasing penetration of QIVc over the next 3 years in the German market. Over the 3-year period, switching gradually from QIVe to QIVc produces slightly higher vaccination costs of about €4.1M (+0.2%). The total savings derived from fewer influenza events and complications resulted in significant net budget savings of €131.1M (0.4%) from a societal perspective. Budget savings were mainly driven by the avoidance of complication costs (€14.1M, 0.5%); non-complicated symptomatic cases (€117.5M, 0.4%) and premature death costs (€3.6M, 0.3%). Considering the assumption of egg-adaptation related mismatch occurring 55% of the years, the net budget savings will be €61.3M. Based on the epidemiological and economic models, the introduction of QIVc would be economically favorable in the German immunization program.

Comparative Effectiveness of Influenza Vaccines Among US Medicare Beneficiaries Ages 65 Years and Older During the 2019-2020 Season.

Approximately 50 000 influenza-associated deaths occur annually in the United States, overwhelmingly among individuals aged ≥65 years. Although vaccination is the primary prevention tool, investigations have shown low vaccine effectiveness (VE) in recent years, particularly among the elderly. We analyzed the relative VE (RVE) of all influenza vaccines among Medicare beneficiaries aged ≥65 years to prevent influenza hospital encounters during the 2019-2020 season. Retrospective cohort study using Poisson regression and inverse probability of treatment weighting (IPTW). Exposures included egg-based high-dose trivalent (HD-IIV3), egg-based adjuvanted trivalent (aIIV3), egg-based standard dose (SD) quadrivalent (IIV4), cell-based SD quadrivalent (cIIV4), and recombinant quadrivalent (RIV4) influenza vaccines. We studied 12.7 million vaccinated beneficiaries. Following IPTW, cohorts were well balanced for all covariates and health-seeking behavior indicators. In the adjusted analysis, RIV4 (RVE, 13.3%; 95% CI, 7.4-18.9%), aIIV3 (RVE, 8.2%; 95% CI, 4.2-12.0%), and HD-IIV3 (RVE, 6.8%; 95% CI, 3.3-10.1%) were significantly more effective in preventing hospital encounters than the reference egg-based SD IIV4, while cIIV4 was not significantly more effective than IIV4 (RVE, 2.8%; 95% CI, -2.8%, 8.2%). Our results were consistent across all analyses. In this influenza B-Victoria and A(H1N1)-dominated season, RIV4 was moderately more effective than other vaccines, while HD-IIV3 and aIIV3 were more effective than the IIV4 vaccines, highlighting the contributions of antigen amount and adjuvant use to VE. Egg adaptation likely did not substantially affect our RVE evaluation. Our findings, specific to the 2019-2020 season, should be evaluated in other studies using virological case confirmation.

Evaluating the Relative Vaccine Effectiveness of Adjuvanted Trivalent Influenza Vaccine Compared to High-Dose Trivalent and Other Egg-Based Influenza Vaccines among Older Adults in the US during the 2017-2018 Influenza Season.

The influenza-related disease burden is highest among the elderly. We evaluated the relative vaccine effectiveness (rVE) of adjuvanted trivalent influenza vaccine (aTIV) compared to other egg-based influenza vaccines (high-dose trivalent (TIV-HD), quadrivalent (QIVe-SD), and standard-dose trivalent (TIVe-SD)) against influenza-related and cardio-respiratory events among subjects aged ≥65 years for the 2017–2018 influenza season. This retrospective cohort analysis used prescription claims, professional fee claims, and hospital charge master data. Influenza-related hospitalizations/ER visits and office visits and cardio-respiratory events were assessed post-vaccination. Inverse probability of treatment weighting (IPTW) and Poisson regression were used to evaluate the adjusted rVE of aTIV compared to other vaccines. In an economic analysis, annualized follow-up costs were compared between aTIV and TIV-HD. The study was composed of 234,313 aTIV, 1,269,855 TIV-HD, 212,287 QIVe-SD, and 106,491 TIVe-SD recipients. aTIV was more effective in reducing influenza-related office visits and other respiratory-related hospitalizations/ER visits compared to the other vaccines. For influenza-related hospitalizations/ER visits, aTIV was associated with a significantly higher rVE compared to QIVe-SD and TIVe-SD and was comparable to TIV-HD. aTIV was also associated with a significantly higher rVE compared to TIVe-SD against hospitalizations/ER visits related to pneumonia and asthma/COPD/bronchial events. aTIV and TIV-HD were associated with comparable annualized all-cause and influenza-related costs. Adjusted analyses demonstrated a significant benefit of aTIV against influenza- and respiratory-related events compared to the other egg-based vaccines.

A real-world study evaluating the relative vaccine effectiveness of a cell-based quadrivalent influenza vaccine compared to egg-based quadrivalent influenza vaccine in the US during the 2017–18 influenza season

BackgroundCell-based influenza vaccine manufacturing reduces egg adaptations that can decrease vaccine effectiveness. We evaluated the relative vaccine effectiveness (rVE) of cell-based quadrivalent influenza vaccine (QIVc) compared to standard-dose egg-based quadrivalent influenza vaccines (QIVe-SD) against influenza-related and serious respiratory events among subjects 4–64 years of age during the 2017–18 influenza season. MethodsA retrospective cohort analysis was conducted using administrative claims data in the US (IQVIA PharMetrics Plus® database). Subjects vaccinated with QIVc or QIVe-SD from 8/2017–1/2018 were identified (date of vaccination termed the index date). Influenza-related hospitalizations/ER visits, all-cause hospitalizations and serious respiratory hospitalizations/ER visits were assessed post-vaccination. Inverse probability of treatment weighting (IPTW) and Poisson regression were used to evaluate the adjusted rVE of QIVc compared to QIVe-SD. In a subgroup analysis, rVE was assessed for several subgroups of interest (4–17, 18–64 and 50–64 years, and subjects with ≥1 high-risk condition). In a secondary economic analysis, annualized all-cause costs over the follow-up were compared using propensity score matching (PSM) and generalized estimating equation (GEE) models. ResultsThe study sample comprised 555,538 QIVc recipients and 2,528,524 QIVe-SD recipients. Prior to adjustment, QIVc subjects were older and had higher total costs in the 6-months pre-index. Following IPTW-adjustment and Poisson regression, QIVc was more effective in reducing influenza-related hospitalizations/ER visits, all-cause hospitalizations, and hospitalizations/ER visits related to asthma/COPD/bronchial events and other respiratory events compared to QIVe-SD. Similar trends were generally observed in the subgroup analysis. Following PSM adjustment and GEE regression, QIVe-SD was associated with significantly higher annualized all-cause total costs compared to QIVc, driven by higher costs for outpatient medical services and inpatient hospitalizations. ConclusionsAfter adjustment for confounders and selection bias, QIVc reduced influenza-related hospitalizations/ER visits, all-cause hospitalizations, and serious respiratory hospitalizations/ER visits compared to QIVe-SD. QIVc was associated with significantly lower all-cause total costs.

Relative vaccine efficacy of high-dose versus standard-dose influenza vaccines in preventing probable influenza in a Medicare Fee-for-Service population

BackgroundHigh-dose (HD) influenza vaccine, currently the most commonly used vaccine among US seniors (aged ≥ 65 years), has been shown to be more efficacious than standard-dose (SD) vaccine in multiple randomized trials. This study evaluated the real-world relative vaccine effectiveness (rVE) of HD vs SD over four influenza seasons. MethodsThis study included Medicare Fee-for-Service enrollees who received HD or SD at an outpatient clinic or pharmacy during influenza seasons 2011–2012 through 2014–2015. Probable influenza (an inpatient stay with an influenza diagnosis on the claim, or an outpatient visit with a rapid influenza test/culture followed by an antiviral prescription) was assessed among HD recipients matched 1:1 with SD recipients by location, vaccination date, age, and sex. Fine-Gray subdistribution hazard models with competing risk of death were used to adjust for residual confounding. Analyses were stratified by outpatient vs pharmacy vaccination. ResultsAcross the four influenza seasons, there were 535,598, 1,017,552, 1,548,164, and 2,420,450 in the pharmacy cohort; and 821,662, 1,151,080, 1,559,488, and 2,421,758 in the outpatient cohort. During peak influenza season, rVEs for 2011–12 through 2014–15 were 21.8% (95% CI: −5.9%, 42.3%), 14.8% (9.3%, 19.9%), 16.9% (9.2%, 23.9%), and 17.2% (14.5%, 19.9%), respectively, in the pharmacy cohort; and 16.5% (−5.9%, 34.2%), 15.1% (10.9%, 19.1%), 10.0% (2.9%, 16.6%), and −0.2% (−3.0%, 2.5%), respectively, in the outpatient cohort. ConclusionHD was consistently associated with better protection against probable influenza. The lower treatment effect observed in the outpatient cohort could reflect provider bias due to physicians triaging HD to frailer patients.

High-dose influenza vaccination and mortality among predominantly male, white, senior veterans, United States, 2012/13 to 2014/15.

IntroductionIt is unclear whether high-dose influenza vaccine (HD) is more effective at reducing mortality among seniors.AimThis study aimed to evaluate the relative vaccine effectiveness (rVE) of HD. MethodsWe linked electronic medical record databases in the Veterans Health Administration (VHA) and Medicare administrative files to examine the rVE of HD vs standard-dose influenza vaccines (SD) in preventing influenza/pneumonia-associated and cardiorespiratory mortality among VHA-enrolled veterans 65 years or older during the 2012/13, 2013/14 and 2014/15 influenza seasons. A multivariable Cox proportional hazards model was performed on matched recipients of HD vs SD, based on vaccination time, location, age, sex, ethnicity and VHA priority level. ResultsAmong 569,552 person-seasons of observation, 207,574 (36%) were HD recipients and 361,978 (64%) were SD recipients, predominantly male (99%) and white (82%). Pooling findings from all three seasons, the adjusted rVE estimate of HD vs SD during the high influenza periods was 42% (95% confidence interval (CI): 24–59) against influenza/pneumonia-associated mortality and 27% (95% CI: 23–32) against cardiorespiratory mortality. Residual confounding was evident in both early and late influenza periods despite matching and multivariable adjustment. Excluding individuals with high 1-year predicted mortality at baseline reduced the residual confounding and yielded rVE of 36% (95% CI: 10–62) and 25% (95% CI: 12–38) against influenza/pneumonia-associated and cardiorespiratory mortality, respectively. These were confirmed by results from two-stage residual inclusion estimations.DiscussionThe HD was associated with a lower risk of influenza/pneumonia-associated and cardiorespiratory death in men during the high influenza period.

PIN3 RELATIVE VACCINE EFFECTIVENESS OF QUADRIVALENT CELL-BASED VERSUS EGG-BASED INFLUENZA VACCINES AMONG ADULTS 50-64 YEARS OLD: A U.S. OBSERVATIONAL COHORT STUDY

Influenza puts subjects of 50-64 years old at an increased risk of pneumonia, heart attack, and stroke and can lead to worsening of comorbid conditions such as diabetes, heart disease, and asthma. Real-world evidence studies have indicated that cell-based quadrivalent influenza vaccine (QIVc) reduced physician office visits and hospitalizations due to influenza compared with conventional egg-based quadrivalent influenza vaccine (QIVe). This study aimed to assess the relative vaccine effectiveness (rVE) of QIVc compared to QIVe to prevent influenza-related and respiratory-related hospitalizations/emergency room (ER) visits and all-cause hospitalizations, among subjects 50-64 years old during the 2017/18 influenza season. A retrospective cohort analysis was conducted among subjects 50-64 years old vaccinated with QIVc or QIVe using administrative claims data in the U.S. (IQVIA’s Real-World Data Adjudicated Claims – US Database). Baseline characteristics included age, gender, payer type, geographic region, Charlson Comorbidity Index, comorbidities, month of flu vaccination, indicators of frail health status and pre-index hospitalization. The adjusted number of events and rates (per 1,000 vaccinated subject-seasons) of influenza-related hospitalizations/ER visits, respiratory-related hospitalizations/ER visits (e.g., pneumonia, asthma/COPD/bronchial and other respiratory events (e.g. sinusitis, respiratory tract infections, etc.)) and all-cause hospitalizations were calculated using inverse probability of treatment weighting (IPTW) and Poisson regression (following CMS/FDA statistical methodology). During the 2017/18 influenza season, an A/H3N2 predominant season; 245,316 recipients of QIVc and 831,368 of QIVe were identified following IPTW. Adjusted results show that rVE for QIVc was significantly higher compared to QIVe for influenza-related hospitalizations/ER visits (9.36% [95%CI: 0.31%-17.58%]) and all-cause hospitalization (5.09% [95%CI: 2.98%-7.16%]). Similar findings showed that QIVc was more effective than QIVe in preventing hospitalization/ER visits related to asthma/COPD/bronchial (6.49% [95%CI: 3.23%-9.64%]) and other respiratory events (5.80% [95%CI: 2.93%-8.59%]). QIVc reduced influenza-related and respiratory-related hospitalizations/ER visits and all-cause hospitalizations compared to QIVe in subjects 50-64 years old during 2017/18 influenza season.

Relative Effectiveness of the Cell-Cultured Quadrivalent Influenza Vaccine Compared to Standard, Egg-derived Quadrivalent Influenza Vaccines in Preventing Influenza-like Illness in 2017-2018.

BackgroundInfluenza antigens may undergo adaptive mutations during egg-based vaccine production. In the 2017–2018 influenza season, quadrivalent, inactivated cell-derived influenza vaccine (ccIIV4) vaccine was produced using A(H3N2) seed virus propagated exclusively in cell culture, thus lacking egg adaptive changes. This United States study estimated relative vaccine effectiveness (rVE) of ccIIV4 vs egg-derived quadrivalent vaccines (egg-derived IIV4) for that season.MethodsVaccination, outcome, and covariate data were ascertained retrospectively from a electronic medical record (EMR) dataset and analyzed. The study cohort included patients ≥ 4 years of age. rVE was estimated against influenza-like illness (ILI) using diagnostic International Classification of Diseases, Ninth or Tenth Revision codes. The adjusted odds ratios used to derive rVE estimates were estimated from multivariable logistic regression models adjusted for age, sex, race/ethnicity, geographic region, and health status.ResultsOverall, 92 187 individuals had a primary care EMR record of ccIIV4 and 1 261 675 had a record of egg-derived IIV4. In the ccIIV4 group, 1705 narrowly defined ILI events occurred, and 25 645 occurred in the standard egg-derived IIV4 group. Crude rVE was 9.2% (95% confidence interval [CI], 4.6%–13.6%). When adjusted for age, sex, health status, comorbidities, and geographic region, the estimated rVE changed to 36.2% (95% CI, 26.1%–44.9%).ConclusionsccIIV4, derived from A(H3N2) seed virus propagated exclusively in cell culture, was more effective than egg-derived IIV4 in preventing ILI during the 2017–2018 influenza season. This result suggests that cell-derived influenza vaccines may have greater effectiveness than standard egg-derived vaccines.

Relative Vaccine Efficacy of High-Dose Versus Standard-Dose Influenza Vaccines in Preventing Probable Influenza in a Medicare Fee-for-Service Population

Background: High-dose (HD) influenza vaccine, currently the most commonly used vaccine among US seniors (aged ≥ 65 years), has been shown to be more efficacious than standard-dose (SD) vaccine in multiple randomized trials. This study evaluated the real-world relative vaccine effectiveness (rVE) of HD vs SD over four influenza seasons. Methods: This study included Medicare Fee-for-Service enrollees who received HD or SD at an outpatient clinic or pharmacy during influenza seasons 2011-12 through 2014-15. Probable influenza (an inpatient stay with an influenza diagnosis on the claim, or an outpatient visit with a rapid influenza test/culture followed by an antiviral prescription) was assessed among HD recipients matched 1:1 with SD recipients by location, vaccination date, age, and sex. Fine-Gray subdistribution hazard models with competing risk of death were used to adjust for residual confounding. Analyses were stratified by outpatient vs pharmacy vaccination. Findings: Across the four influenza seasons, there were 535,598, 1,017,552, 1,548,164, and 2,420,450 in the pharmacy cohort; and 821,662, 1,151,080, 1,559,488, and 2,421,758 in the outpatient cohort. During peak influenza season, rVEs for 2011-12 through 2014-15 were 21·8% (95% CI: -5·9%, 42·3%), 14·8% (9·3%, 19·9%), 16·9% (9·2%, 23·9%), and 17·2% (14·5%, 19·9%), respectively, in the pharmacy cohort; and 16·5% (-5·9%, 34·2%), 15·1% (10·9%, 19·1%), 10·0% (2·9%, 16·6%), and -0·2% (-3·0%, 2·5%), respectively, in the outpatient cohort. Interpretation: HD was consistently associated with better protection against probable influenza. The lower treatment effect observed in the outpatient cohort could reflect provider bias due to physicians triaging HD to frailer patients. Funding Statement: This study was supported by Sanofi Pasteur (Swiftwater, PA). Declaration of Interests: A.C. is an employee of Sanofi Pasteur (Swiftwater, PA, USA), the funder of this study. M.P., A.B., S.K., D.V., and L.B. are employees of Optum (Eden Prairie, MN, USA), which was contracted by Sanofi Pasteur to conduct this study and provide medical writing support. SMM has received unrestricted research grants from Merck, GlaxoSmithKline, Sanofi Pasteur, Pfizer and Roche-Assurex for unrelated studies. SMM has received fees as an advisory board member for Sanofi Pasteur. Ethics Approval Statement: This study was approved by the New England Institutional Review Board (approval #120160896), with waived consent for analyses of deidentified administrative claims.

2747. Relative Vaccine Efficacy of High-Dose vs. Standard Dose Influenza Vaccines in Preventing Probable Influenza in a US Medicare Fee-for-Service Population

BackgroundHigh dose (HD) influenza vaccine has been shown to be more efficacious than standard dose (SD) vaccine in multiple randomized trials. HD is currently the most commonly used vaccine in US seniors (≥65 years of age). In this study, we evaluated the real-world relative vaccine effectiveness (rVE) of HD vs SD over 3 influenza seasons.MethodsThis study includes a cohort of Medicare fee-for-service enrollees during influenza seasons 2011–2012 to 2013–2014 who received either HD or SD at a pharmacy or an outpatient clinic. HD recipients were matched 1:1 to SD recipients based on location, date of vaccination, age, and gender. Fine-Gray subdistribution hazard models with competing risk of death were used to adjust for residual confounding. The study outcome of probable influenza was defined as any inpatient stay with an influenza diagnosis on the claim, or an outpatient medical encounter with a rapid influenza test/culture followed by an antiviral prescription. Analyses were stratified based on vaccination location (clinic vs pharmacy) as it is expected that physicians carrying both vaccines may prioritize HD to frailer patients, while pharmacists may not exercise clinical judgment.ResultsOver the influenza seasons 2011–2012, 2012/–2013, and 2013–2014, 1.6–2.2 million seniors were immunized at a pharmacy; and 3.3–3.5 million at a clinic. After matching, there were 535,598; 1,017,552; and 1,548,164 in the pharmacy cohort, and 821,662; 1,151,080; and 1,559,488 in the clinic cohort, across study years. The rVE over 2011/12, 2012/13, and 2013/14 during peak influenza circulation was 21.8% (95% CI: −5.9%, 42.3%), 14.8% (9.3%,19.9%), and 16.9% (9.2%, 23.9%), respectively, in the pharmacy cohort; and 16.5% (−5.9%, 34.2%), 15.1% (10.9%, 19.1%), 10.0% (2.9%, 16.6%), respectively, in the clinic cohort.ConclusionHD was consistently associated with better protection against probable influenza events requiring outpatient or inpatient care. The slightly lower treatment effects observed in the outpatient clinic cohort could be a result of confounding by indication due to physicians triaging HD to frailer patients.Disclosures All authors: No reported disclosures.

Erratum to: Effect of Age on Relative Effectiveness of High-Dose Versus Standard-Dose Influenza Vaccines Among US Medicare Beneficiaries Aged ≥65 Years.

BACKGROUND Studies have found that the high-dose influenza vaccine has a higher relative vaccine effectiveness (RVE) versus standard-dose vaccines in some seasons. We evaluated the effect of age on the RVE of high-dose versus standard-dose influenza vaccines among Medicare beneficiaries. METHODS A 6-season retrospective cohort study from 2012 to 2018 among Medicare beneficiaries aged ≥65 years was performed. Poisson regression was used to evaluate the effect of age on the RVE of high-dose versus standard-dose influenza vaccines in preventing influenza-related hospitalizations. RESULTS The study included >19 million vaccinated beneficiaries in a community pharmacy setting. The Poisson models indicated a slightly increasing trend in RVE with age in all seasons. The high-dose vaccine was more effective than standard-dose vaccines in preventing influenza-related hospital encounters (ie, influenza-related inpatient stays and emergency department visits) in the 2012-2013 (RVE, 23.1%; 95% confidence interval [CI], 17.6%-28.3%), 2013-2014 (RVE, 15.3%; 95% CI, 7.8%-22.3%), 2014-2015 (RVE, 8.9%; 95% CI, 5.6%-12.1%), and 2016-2017 (RVE, 12.6%; 95% CI, 6.3%-18.4%) seasons and was at least as effective in all other seasons. We also found that the high-dose vaccine was consistently more effective than standard-dose vaccines across all seasons for people aged ≥85 years. Similar trends were observed for influenza-related inpatient stays. CONCLUSIONS The RVE of high-dose versus standard-dose influenza vaccines increases with age.

Comparative effectiveness of high dose versus adjuvanted influenza vaccine: A retrospective cohort study

BackgroundAdults 65 years and older (seniors) experience more complications following influenza infection than younger adults. We estimated the relative vaccine effectiveness (rVE) of a trivalent high dose (HD-IIV3) versus an adjuvanted trivalent influenza vaccine (aIIV3) in seniors for respiratory-related hospitalizations. MethodsWe conducted a retrospective cohort study using claims data from Optum’s Clinformatics® Data Mart to compare outcome rates between seniors who received HD-IIV3 versus aIIV3 during the 2016/17 and 2017/18, predominantly A/H3N2 respiratory seasons. Rates were adjusted for demographic characteristics, comorbid conditions, previous influenza vaccination, and geography. We used the previous event rate ratio (PERR) approach to address bias by time-fixed unmeasured confounders. ResultsWe identified 842,282 HD-IIV3 and 34,157 aIIV3 recipients for the 2016/17 season and 1,058,638 HD-IIV3 and 189,636 aIIV3 recipients for the 2017/18 season. The pooled rVE of HD-IIV3 versus aIIV3 for respiratory-related hospitalizations over both seasons was 12% (95% confidence interval: 3.3%–20%); 13% (−6.4% to 32%) for the 2016/17 season and 12% (2.1%–21%) for the 2017/18 season. ConclusionsPooled over two predominantly A/H3N2 respiratory seasons, HD-IIV3 was associated with fewer respiratory hospital admissions than aIIV3 in senior members of large national managed health care company in the U.S.

Effect of Age on Relative Effectiveness of High-Dose Versus Standard-Dose Influenza Vaccines Among US Medicare Beneficiaries Aged ≥65 Years.

Studies have found that the high-dose influenza vaccine has a higher relative vaccine effectiveness (RVE) versus standard-dose vaccines in some seasons. We evaluated the effect of age on the RVE of high-dose versus standard-dose influenza vaccines among Medicare beneficiaries. A 6-season retrospective cohort study from 2012 to 2018 among Medicare beneficiaries aged ≥65 years was performed. Poisson regression was used to evaluate the effect of age on the RVE of high-dose versus standard-dose influenza vaccines in preventing influenza-related hospitalizations. The study included >19 million vaccinated beneficiaries in a community pharmacy setting. The Poisson models indicated a slightly increasing trend in RVE with age in all seasons. The high-dose vaccine was more effective than standard-dose vaccines in preventing influenza-related hospital encounters (ie, influenza-related inpatient stays and emergency department visits) in the 2012-2013 (RVE, 23.1%; 95% confidence interval [CI], 17.6%-28.3%), 2013-2014 (RVE, 15.3%; 95% CI, 7.8%-22.3%), 2014-2015 (RVE, 8.9%; 95% CI, 5.6%-12.1%), and 2016-2017 (RVE, 12.6%; 95% CI, 6.3%-18.4%) seasons and was at least as effective in all other seasons. We also found that the high-dose vaccine was consistently more effective than standard-dose vaccines across all seasons for people aged ≥85 years. Similar trends were observed for influenza-related inpatient stays. The RVE of high-dose versus standard-dose influenza vaccines increases with age.

Economic assessment of a high-dose versus a standard-dose influenza vaccine in the US Veteran population: Estimating the impact on hospitalization cost for cardio-respiratory disease

ObjectiveTo compare the economic impact of high-dose trivalent (HD) versus standard-dose trivalent (SD) influenza vaccination on direct medical costs for cardio-respiratory hospitalizations in adults aged 65 years or older enrolled in the United States (US) Veteran’s Health Administration (VHA). MethodsLeveraging a relative vaccine effectiveness study of HD versus SD over five respiratory seasons (2010/11 through 2014/15), we collected cost data for healthcare provided to the same study population both at VHA and through Medicare services. Our economic assessment compared the costs of vaccination and hospital care for patients experiencing acute cardio-vascular or respiratory illness. ResultsWe analyzed 3.5 million SD and 158,636 HD person-seasons. The average cost of HD and SD vaccination was $23.48 (95% CI: $21.29 - $25.85) and $12.21 (95% CI: $11.49 - $13.00) per recipient, respectively, while the hospitalization rates for cardio-respiratory disease in HD and SD recipients were 0.114 (95% CI: 0.108–0.121) and 0.132 (95% CI: 0.132–0.133) per person-season, respectively. Attributing the average cost per hospitalization of $11,796 (95% CI: $11,685 - $11,907) to the difference in hospitalization rates, we estimated savings attributable to HD to be $202 (95% CI: $115 – $280) per vaccinated recipient. ConclusionsFor the five-season period of 2010/11 through 2014/15, HD influenza vaccination was associated with net cost savings due to fewer hospitalizations, and therefore lower direct medical costs, for cardio-respiratory disease as compared to SD influenza vaccination in the senior US VHA population.

Adjuvanted versus nonadjuvanted influenza vaccines and risk of hospitalizations for pneumonia and cerebro/cardiovascular events in the elderly

ABSTRACTBackground: The higher effectiveness of MF59®-adjuvanted trivalent influenza vaccine (MF59-TIV) vs. nonadjuvanted TIV in preventing influenza-related hospitalizations was found considering few influenza seasons, local and heterogeneous settings. This study evaluated the relative vaccine effectiveness (rVE) of MF59-TIV vs. nonadjuvanted TIV on the risk of hospitalization for pneumonia and cerebro/cardiovascular events across 15 consecutive influenza seasons.Research design and methods: Using Health Search Database, a case–control study was nested in a cohort of elderly vaccinated with MF59-TIV or TIV. Conditional logistic regression was used to estimate the odds ratio with 95% confidence intervals (CI) of hospitalizations potentially related to influenza in patients vaccinated with MF59-TIV or TIV.Results: Of 43,000 patients vaccinated with MF59-TIV (66.2%) and TIV (33.8%) for the first time, 103 cases of hospitalization for pneumonia or cerebro/cardiovascular events (0.11 per 1,000 person-weeks) during 15 influenza seasons were identified. The MF59-TIV was associated with a reduced risk of hospitalizations for pneumonia and cerebro/cardiovascular events vs. TIV [rVE: 39% (95% CI: 4–61%)].Conclusions: In a 15-season cohort of elderly, MF59-TIV seems to reduce the risk of hospitalizations for pneumonia and cerebro/cardiovascular events when compared with nonadjuvanted TIV. Our findings support the recommendation for MF59-TIV in the elderly population.

Analysis of relative effectiveness of high-dose versus standard-dose influenza vaccines using an instrumental variable method

BackgroundObservational studies of the relative effectiveness of influenza vaccines are essential for public health decision making. Their estimates, however, are subject to bias due to unmeasured confounders. Instrumental variable (IV) methods can control for observed and unobserved confounders. MethodsWe used linked electronic medical record databases in the Veterans Health Administration (VHA) as well as Medicare administrative files to examine the relative vaccine effectiveness (rVE) of high-dose influenza vaccine (HD) versus standard-dose influenza vaccines (SD) in preventing hospitalizations among VHA-enrolled Veterans ≥65 years of age during 5 influenza seasons (2010–2011 through 2014–2015). Using multivariable IV Poisson regression modeling to address unmeasured confounding and bias, we analyzed the data by each season and through longitudinal analysis of all five seasons. FindingsWe included 3,638,924 person–influenza seasons of observation where 158,636 (4%) were among HD vaccine recipients and 3,480,288 (96%) were among SD vaccine recipients. Of the 1,728,562 Veterans, 1,702,824 (98.5%) were male and 1,299,412 (75%) were non-Hispanic white. Based on the longitudinal analysis of all five seasons, the IV-adjusted rVE estimate of HD vs. SD was 10% (95% CI, 8–12%) against all-cause hospitalization; 18% (95% CI, 15–21%) against cardiorespiratory-associated hospitalization; and 14% (95% CI, 6–22%) against influenza/pneumonia-associated hospitalization. The findings by season were similar. InterpretationOur analysis of VHA clinical data collected from approximately 1.7 million Veterans 65 years and older during five seasons demonstrates that high-dose influenza vaccine is more effective than standard-dose influenza vaccines in preventing influenza- or pneumonia-associated hospitalizations, cardiorespiratory hospitalizations, and all-cause hospitalizations.

989. Clinical Effectiveness of High-Dose Trivalent vs. Quadrivalent Influenza Vaccination Among Veterans Health Administration Patients

BackgroundDespite the widespread availability of several injectable inactivated influenza vaccines (IIV), including the trivalent standard-dose (IIV3-SD) and high-dose (IIV3-HD), and the quadrivalent (IIV4), the US Advisory Committee on Immunization Practices does not currently recommend one over another. The objective of this study was to assess the relative vaccine effectiveness (rVE) of IIV3-HD and IIV4 vs. IIV3-SD.MethodsrVE was estimated from a retrospective cohort study of Veterans aged 65 years and older who received an IIV during the 2014–2015 influenza season. Veterans Health Administration (VHA) electronic medical records were linked with Centers for Medicare and Medicate Services administrative claims to capture the study outcomes of hospitalizations and baseline characteristics. The inverse probability of treatment weight (IPTW) method was used to adjust for potential confounding due to unmeasured factors associated with IIV3-SD, IIV3-HD, or IIV4 vaccination. The probability was estimated based on patient sociodemographic characteristics, comorbidities, pre-influenza season hospitalizations, prior season influenza vaccination, and use of immunosuppressive medication.ResultsOur study population included 782,346 VHA patients vaccinated during the 2014–2015 season. Of these, 10,543 (1%) received IIV4, while 59,536 (8%) received IIV3-HD and 712,267 (91%) received IIV3-SD. 11,626 (1.5%) were female and 588,324 (76%) were non-Hispanic white. Compared with those that received IIV3-SD vaccine, the IPTW-adjusted rVE for IIV3-HD was 7% (95% CI, 9%–21%) against all-cause, 15% (95% CI, 10%–17%) against cardiorespiratory associated, and 13% (95% CI, 8%–17%) against influenza/pneumonia-associated hospitalization. For those that received IIV4, the IPTW-adjusted rVE was 4% (95% CI, 1%–4%), 1% (95% CI, −2%–5%), and 0% (95% CI, −9%–8%), respectively.ConclusionIIV3-HD is more effective than, and IIV4 is as effective as, IIV3-SD vaccination in preventing influenza/pneumonia-associated, cardiorespiratory, and all-cause hospitalizations. Additional studies that employ methods to control for unmeasured confounding are warranted as the use of IIV4 expands.Disclosures All authors: No reported disclosures.

Reliability and validity of the World Health Organization reading standards for paediatric chest radiographs used in the field in an impact study of Pneumococcal Conjugate Vaccine in Kilifi, Kenya.

BackgroundRadiologically-confirmed pneumonia (RCP) is a specific end-point used in trials of Pneumococcal Conjugate Vaccine (PCV) to estimate vaccine efficacy. However, chest radiograph (CXR) interpretation varies within and between readers. We measured the repeatability and reliability of paediatric CXR interpretation using percent agreement and Cohen’s Kappa and the validity of field readings against expert review in a study of the impact of PCV on pneumonia.MethodsCXRs were obtained from 2716 children admitted between 2006 and 2014 to Kilifi County Hospital, Kilifi, Kenya, with clinically-defined severe or very-severe pneumonia. Five clinicians and radiologists attended a three-day training course on CXR interpretation using a WHO standard. All CXRs were read once by two local primary readers. Discordant readings and 13% of concordant readings were arbitrated by a panel of three expert radiologists. To assess repeatability, a 5% median random sample was presented twice. Sensitivity and specificity of the primary readers’ interpretations was estimated against the ‘gold-standard’ of the arbitrators’ results.ResultsOf 2716 CXRs, 2 were uninterpretable and 159 were evaluated twice. The percent agreement and Kappa for RCP were 89% and 0.68 and ranged between 84–97% and 0.19–0.68, respectively, for all pathological findings. Intra-observer repeatability was similar to inter-observer reliability. Sensitivities of the primary readers to detect RCP were 69% and 73%; specificities were 96% and 95%.ConclusionIntra- and inter-observer agreements on interpretations of radiologically-confirmed pneumonia are fair to good. Reasonable sensitivity and high specificity make radiologically-confirmed pneumonia, determined in the field, a suitable measure of relative vaccine effectiveness.