Vaccine effectiveness of recombinant and standard dose influenza vaccines against influenza related hospitalization using a retrospective test-negative design.

BACKGROUND: Relative effectiveness of various vaccine formulations provide important input for vaccine policy decisions and provider purchasing decisions. We used electronic databases to conduct a test-negative case control study to determine relative vaccine effectiveness (rVE) of recombinant influenza vaccine (RIV4) compared with standard dose vaccines (SD-IIV4) against influenza hospitalization. METHODS: Adults 18-64 and ≥65 years of age hospitalized in a large U.S. health system (19 hospitals) in 2018-2019 and 2019-2020 who were clinically tested for influenza using reverse transcription polymerase chain reaction (RT-PCR) assays were included. The hospital system electronic medical record (EMR) and the state immunization registry were used to confirm influenza vaccination. Propensity scores with inverse probability weighting were used to adjust for potential confounders and determine rVE. RESULTS: Of the 14,590 individuals included in the primary analysis, 3,338 were vaccinated with RIV4 and 976 were vaccinated with SD-IIV4, with the balance of 10,276 being unvaccinated. Most participants were white (80 %), most (70 %) had a high-risk condition, just over half were female (54 %) and age 65 years or older (53 %). Overall RIV4 rVE was significant when adjusted for propensity scores with inverse probability weights (rVE = 31; 95 % CI = 11 %, 46 %). Among younger adults (18-64 years-old), overall rVE of RIV4 was significant (rVE = 29; 95 % CI = 4 %, 47 %). CONCLUSIONS: Over all adults, both RIV4 and SD-IIV4 were effective against influenza hospitalization, with RIV4 providing better protection compared with SD-IIV4 overall, for females, younger adults, and those with no high-risk conditions.

Vaccine effectiveness of recombinant and standard dose influenza vaccines against outpatient illness during 2018-2019 and 2019-2020 calculated using a retrospective test-negative design.

Newer influenza vaccine formulations have entered the market, but real-world effectiveness studies are not widely conducted until there is sufficient uptake. We conducted a retrospective test-negative case-control study to determine relative vaccine effectiveness (rVE) of recombinant influenza vaccine or RIV4, compared with standard dose vaccines (SD) in a health system with significant RIV4 uptake. Using the electronic medical record (EMR) and the Pennsylvania state immunization registry to confirm influenza vaccination, VE against outpatient medically attended visits was calculated. Immunocompetent outpatients ages 18-64 years seen in hospital-based clinics or emergency departments who were tested for influenza using reverse transcription polymerase chain reaction (RT-PCR) assays during the 2018-2019 and 2019-2020 influenza seasons were included. Propensity scores with inverse probability weighting were used to adjust for potential confounders and determine rVE. Among this mostly white and female cohort of 5,515 individuals, 510 were vaccinated with RIV4 and 557 were vaccinated with SD, with the balance of 4,448 (81%) being unvaccinated. Adjusted influenza VE estimates were 37% overall (95% CI = 27, 46), 40% (95% CI = 25, 51) for RIV4 and 35% (95% CI = 20, 47) for standard dose vaccines. Overall, rVE of RIV4 compared to SD was not significantly higher (11%; 95% CI = -20, 33). Influenza vaccines were moderately protective against medically attended outpatient influenza during the 2018-2019 and 2019-2020 seasons. Although the point estimates are higher for RIV4, the large confidence intervals around VE estimates suggest this study was underpowered to detect significant rVE of individual vaccine formulations.

Agent-based model of the impact of higher influenza vaccine efficacy on seasonal influenza burden.

Introduction: Current influenza vaccines have limited effectiveness. COVID-19 vaccines using mRNA technology have demonstrated very high efficacy, suggesting that mRNA vaccines could be more effective for influenza. Several such influenza vaccines are in development. FRED, an agent-based modeling platform, was used to estimate the impact of more effective influenza vaccines on seasonal influenza burden. Methods: Simulations were performed using an agent-based model of influenza that included varying levels of vaccination efficacy (40-95 % effective). In some simulations, level of infectiousness and/or length of infectious period in agents with breakthrough infections was also decreased. Impact of increased and decreased levels of vaccine uptake were also modeled. Outcomes included number of symptomatic influenza cases estimated for the US. Results: Highly effective vaccines significantly reduced estimated influenza cases in the model. When vaccine efficacy was increased from 40 % to a maximum of 95 %, estimated influenza cases in the US decreased by 43 % to > 99 %. The base simulation (40 % efficacy) resulted in âˆ¼ 28 million total yearly cases in the US, while the most effective vaccine modeled (95 % efficacy) decreased estimated cases to âˆ¼ 22,000. Discussion: Highly effective vaccines could dramatically reduce influenza burden. Model estimates suggest that even modest increases in vaccine efficacy could dramatically reduce seasonal influenza disease burden.

Impact of Low Rates of Influenza on Next-Season Influenza Infections.

INTRODUCTION: Interventions to curb the spread of COVID-19 during the 2020-2021 influenza season essentially eliminated influenza during that season. Given waning antibody titers over time, future residual population immunity against influenza will be reduced. The implication for the subsequent 2021-2022 influenza season is unknown. METHODS: An agent-based model of influenza implemented in the Framework for Reconstructing Epidemiological Dynamics simulation platform was used to estimate cases and hospitalizations over 2 successive influenza seasons. The impact of reduced residual immunity owing to protective measures in the first season was estimated over varying levels of similarity (cross-immunity) between influenza strains over the seasons. RESULTS: When cross-immunity between first- and second-season strains was low, a decreased first season had limited impact on second-season cases. High levels of cross-immunity resulted in a greater impact on the second season. This impact was modified by the transmissibility of strains in the 2 seasons. The model estimated a possible increase of 13.52%-46.95% in cases relative to that in a normal season when strains have the same transmissibility and 40%-50% cross-immunity in a season after a very low one. CONCLUSIONS: Given the light 2020-2021 influenza season, cases may increase by as much as 50% in 2021-2022, although the increase could be much less, depending on cross-immunity from past infection and transmissibility of strains. Enhanced vaccine coverage or continued interventions to reduce transmission could reduce this high season. Young children may have a higher risk in 2021-2022 owing to limited exposure to infection in the previous year.

Estimating the Impact of Low Influenza Activity in 2020 on Population Immunity and Future Influenza Seasons in the United States.

BACKGROUND: Influenza activity in the 2020-2021 season was remarkably low, likely due to implementation of public health preventive measures such as social distancing, mask wearing, and school closure. With waning immunity, the impact of low influenza activity in the 2020-2021 season on the following season is unknown. METHODS: We built a multistrain compartmental model that captures immunity over multiple influenza seasons in the United States. Compared with the counterfactual case, where influenza activity remained at the normal level in 2020-2021, we estimated the change in the number of hospitalizations when the transmission rate was decreased by 20% in 2020-2021. We varied the level of vaccine uptake and effectiveness in 2021-2022. We measured the change in population immunity over time by varying the number of seasons with lowered influenza activity. RESULTS: With the lowered influenza activity in 2020-2021, the model estimated 102 000 (95% CI, 57 000-152 000) additional hospitalizations in 2021-2022, without changes in vaccine uptake and effectiveness. The estimated changes in hospitalizations varied depending on the level of vaccine uptake and effectiveness in the following year. Achieving a 50% increase in vaccine coverage was necessary to avert the expected increase in hospitalization in the next influenza season. If the low influenza activity were to continue over several seasons, population immunity would remain low during those seasons, with 48% of the population susceptible to influenza infection. CONCLUSIONS: Our study projected a large compensatory influenza season in 2021-2022 due to a light season in 2020-2021. However, higher influenza vaccine uptake would reduce this projected increase in influenza.

Agreement among sources of adult influenza vaccination in the age of immunization information systems.

INTRODUCTION: Many vaccination studies rely on self-reported vaccination status, with its inherent biases. Accuracy of influenza vaccination self-report has been evaluated periodically, typically using the medical record as the gold standard. The burgeoning of electronic medical records (EMRs) and immunization information systems (IISs) and the rise of adult vaccine administration in community pharmacies suggest the need for a reevaluation of self-reported vaccination status. METHODS: Vaccination data from self-report, the state IIS, the health system EMR and other sources were compared for participants in outpatient and inpatient influenza vaccine effectiveness studies for four seasons (2016-2017 to 2019-2020). Agreement among the sources was calculated along with sensitivity and specificity. Tests for trend assessed changes in completeness of the Pennsylvania - Statewide IIS (PA-SIIS) data over time. RESULTS: With self-report as the gold standard, agreement with the local EMR, PA-SIIS, and all sources was 62%, 77% and 85%, respectively. Sensitivity of the EMR was 42% (95% CI = 41, 43) and specificity was 91% (90, 92). With PA-SIIS-as the gold standard, agreement with the local EMR and all sources was 77% and 78%, respectively. Sensitivity of all sources combined was 96% (95, 97) and specificity was (63% (62, 64). Capture of influenza vaccinations in the IIS has not consistently improved over time, with a significant increase among children (P = 0.001), no change among working-age adults and a decrease among older adults (P = 0.004). However, PA-SIIS provided the largest percentage of verified vaccines (69.3%) compared with EMR (43.3%) and other sources (12.4%). CONCLUSION: Both self-report and PA-SIIS are good estimates of actual vaccine uptake. When high accuracy data are required, such as for vaccine effectiveness studies, triangulation using multiple sources should be conducted.

Exploring the potential public health benefits of universal influenza vaccine.

Background: Broadly protective, long-lasting universal influenza vaccines are under development in response to low-moderate seasonal vaccine effectiveness, frequent genetic changes in circulating viruses and extended turnaround for vaccine manufacture. Because a long-lasting vaccine might be less effective than a seasonal vaccine that has been matched to current circulating strains, the public health impact of its introduction should be evaluated.Methods: A modified agent-based model (ABM) examined multi-year effects of a universal vaccine among 18 to 49-year-olds, given in Year 1 only. The proportion of vaccinated 18 to 49-year-olds who received universal vaccine was varied from 0% to 100%. Model parameters were drawn from US databases and the medical literature. Outcomes were 4-year cumulative and annual influenza cases as well as annual cases averted/100,000 population for 3 age groups, 0-17 years, 18-49 years and 50+ years.Results: In Year 1 when universal vaccine was given to 50% or 100% of all vaccinated 18 to 49-year-olds, more influenza cases occurred, compared to no universal vaccine, but fewer cases occurred in Years 2-4 as overall protection increased. Cumulative averted cases over 4 years in 18 to 49-year-olds were 892/100,000 and 1,687/100,000 population for the 50% and 100% universal vaccine for 18 to 49-year-olds scenarios, respectively, with additional benefits to children and older adults through indirect effects.Conclusions: In ABM, the universal vaccine with a conservative VE estimate given once to 18 to 49-year-olds reduced influenza cases among all age groups in Years 2-4 following its introduction. Reduced influenza burden may occur sooner if VE of universal vaccines exceeds that assumed in these models.

Compressed Influenza Vaccination in U.S. Older Adults: A Decision Analysis.

INTRODUCTION: Tradeoffs exist between efforts to increase influenza vaccine uptake, including early season vaccination, and potential decreased vaccine effectiveness if protection wanes during influenza season. U.S. older adults increasingly receive vaccination before October. Influenza illness peaks vary from December to April. METHODS: A Markov model compared influenza likelihood in older adults with (1) status quo vaccination (August-May) to maximize vaccine uptake or (2) vaccination compressed to October-May (to decrease waning vaccine effectiveness impact). The Centers for Disease Control and Prevention data were used for influenza incidence and vaccination parameters. Prior analyses showed that absolute vaccine effectiveness decreased by 6%-11% per month, favoring later season vaccination. However, compressed vaccination could decrease overall vaccine uptake. Influenza incidence was based on average monthly incidence with earlier and later peaks also examined. Influenza strain distributions from two seasons were modeled in separate scenarios. Sensitivity analyses were performed to test result robustness. Data were collected and analyzed in 2018. RESULTS: Compressed vaccination would avert ≥11,400 influenza cases in older adults during a typical season if it does not decrease vaccine uptake. However, if compressed vaccination decreases vaccine uptake or there is an early season influenza peak, more influenza can result. In probabilistic sensitivity analyses, compressed vaccination was never favored if it decreased absolute vaccine uptake by >5.5% in any scenario; when influenza peaked early, status quo vaccination was favored. CONCLUSIONS: Compressed vaccination could decrease waning vaccine effectiveness and decrease influenza cases in older adults. However, this positive effect is negated when early season influenza peaks occur and diminished by decreased vaccine uptake that could occur with shortening the vaccination season.

Potential Cost-Effectiveness of a Universal Influenza Vaccine in Older Adults.

BACKGROUND AND OBJECTIVES: "Universal" vaccines that could have multistrain and multiyear effectiveness are being developed. Their potential cost-effectiveness in geriatric populations is unknown. RESEARCH DESIGN AND METHODS: A Markov model estimated effects of a theoretical universal influenza vaccine compared with available seasonal vaccines in hypothetical cohorts of U.S. 65+-year olds followed over a 5-year time horizon to capture potential multiyear protection. Outcomes included costs per quality-adjusted life-year gained and influenza cases avoided. RESULTS: Using hypothetical universal vaccine parameter values (cost $100, vaccine effectiveness 39%, uptake 64%, effectiveness duration 5 years), universal vaccine was less costly than seasonal influenza vaccination strategies. High-dose trivalent influenza vaccine, compared with universal vaccine, gained 0.0028 quality-adjusted life-years and cost $82 more, or $28,700 per quality-adjusted life-year gained. Other seasonal vaccines were not favorable economically. Five-year influenza risk with universal vaccination was 32.3% under base case assumptions, compared with <30% with adjuvanted or high-dose vaccine use. In sensitivity analyses, universal vaccine was favored when uptake or vaccine effectiveness was greater than standard-dose influenza vaccine. If absolute universal vaccine effectiveness was 10% less than standard-dose vaccine, universal vaccine could be cost-saving but not more effective than other strategies. Universal vaccine was not favored if its effectiveness duration was <3 years. DISCUSSION AND IMPLICATIONS: Universal vaccine use in older persons could be either cost effective or cost saving when universal vaccine parameters are within plausible ranges. However, if its effectiveness is substantially less than current vaccines, its use would probably not be favored in geriatric populations.

Impact of seasonal influenza vaccination in the presence of vaccine interference.

BACKGROUND: Annual influenza vaccination is a key to preventing widespread influenza infections. Recent reports of influenza vaccine effectiveness (VE) indicate that vaccination in prior years may reduce VE in the current season, suggesting vaccine interference. The purpose of this study is to evaluate the potential effect of repeat influenza vaccinations in the presence of vaccine interference. METHODS: Using literature-based parameters, an age-structured influenza equation-based transmission model was used to determine the optimal vaccination strategy, while considering the effect of varying levels of interference. RESULTS: The model shows that, even in the presence of vaccine interference, revaccination reduces the influenza attack rate and provides individual benefits. Specifically, annual vaccination is a favored strategy over vaccination in alternate years, as long as the level of residual protection is less than 58% or vaccine interference effect is minimal. Furthermore, the negative impact of vaccine interference may be offset by increased vaccine coverage levels. CONCLUSIONS: Even in the presence of potential vaccine interference, our work provides a population-level perspective on the potential merits of repeated influenza vaccination. This is because repeat vaccination groups had lower attack rates than groups that omitted the second vaccination unless vaccine interference was at very high, perhaps implausible, levels.

Using the 4 Pillars to increase vaccination among high-risk adults: who benefits?

OBJECTIVES: To compare changes in vaccination rates (pneumococcal polysaccharide vaccine [PPSV]; tetanus, diphtheria, and pertussis [Tdap] vaccine; and influenza vaccine) among high-risk adults following an intervention (June 1, 2013, to January 31, 2015) that used the 4 Pillars Practice Transformation Program (4 Pillars Program). STUDY DESIGN: Post hoc analysis of data from a randomized controlled cluster trial. METHODS: Eighteen primary care practices received staff education, guidance for using the 4 Pillars Program, and support for a practice immunization champion. Paired t tests were used to compare vaccination rates separately for those with diabetes, chronic lung or chronic heart disease, or other high-risk conditions. Student's t tests were used to compare vaccination rates across high-risk conditions. Generalized estimating equation modeling was used to determine the likelihood of vaccination. RESULTS: Based on International Classification of Diseases, Ninth Revision, Clinical Modification codes, 4737 patients aged 18 to 64 years were identified as having diabetes (n = 1999), chronic heart disease (n = 658), chronic lung disease (n = 1682), or another high-risk condition (n = 764). PPSV uptake increased by 12.2 percentage points (PP), Tdap vaccination increased by 11.4 PP, and influenza vaccination increased by 4.8 PP. In regression analyses, patients with diabetes (odds ratio [OR], 2.2; 95% CI, 1.80-2.73), chronic lung disease (OR, 1.50; 95% CI, 1.21-1.87), or chronic heart disease (OR, 1.32; 95% CI, 1.02-1.71) were more likely to receive PPSV than those without the respective high-risk condition. Those with diabetes (OR, 1.14; 95% CI, 1.01-1.28) or chronic lung disease (OR, 1.14; 95% CI, 1.01-1.30) were more likely to receive an influenza vaccine than those without the respective condition. The likelihood of Tdap vaccination was not significantly associated with any of the chronic conditions tested. CONCLUSIONS: An intervention including the 4 Pillars Program was associated with significant increases in vaccination of high-risk adults. However, the overall uptake of recommended vaccines for those with high-risk conditions remained below national goals.

Using the 4 Pillars™ Practice Transformation Program to increase adolescent human papillomavirus, meningococcal, tetanus-diphtheria-pertussis and influenza vaccination.

OBJECTIVES: To report the results of an intervention using the 4 Pillars™ Practice Transformation Program (4 Pillars™ Program) to increase adolescent vaccinations including human papillomavirus vaccine (HPV) and influenza vaccines, which remain underutilized in this population. STUDY DESIGN: Eleven pediatric and family medicine practices, previously control sites from a randomized controlled cluster trial, with ≥50 adolescent patients participated. The 4 Pillars™ Program was the foundation of the intervention. De-identified demographic, office visit and vaccination data were derived from electronic medical record extractions for patients whose date of birth was 4/1/1997 to 4/1/2004 (ages 11-17years at baseline). Vaccination rates for HPV, influenza, tetanus-pertussis-diphtheria (Tdap) and meningococcal (MenACWY) vaccines were determined for all eligible patients pre- and post intervention (i.e., vaccination rates on 4/1/2015 and 4/30/2016). RESULTS: Among 9473 patients ages 11-17years at baseline (4/1/2015), mean pre-intervention vaccination rates for HPV initiation and completion, meningococcal, Tdap and influenza vaccines were below national levels. Rates increased significantly post intervention (P<0.001) for HPV initiation which increased 17.1 percentage points (PP) from 51.4%; HPV completion increased 14.8PP from 30.7%, meningococcal vaccine uptake increased 16.6PP from 79.1%, Tdap vaccine uptake increased 14.6PP from 76.9%. Influenza vaccine uptake did not increase significantly (2.3PP from 40.1%). In the regression using generalized estimating equations, odds of vaccination were higher for younger, non-white adolescents for all vaccines; being in a smaller practice decreased the odds of Tdap vaccination but increased the odds of influenza vaccination. CONCLUSION: Clinically and statistically significant improvements in HPV series initiation and completion, and meningococcal and Tdap vaccinations were observed in primary care practices implementing the 4 Pillars™ Practice Transformation Program. Clinical Trial Registry Number: NCT02165722.

Cost-effectiveness and public health impact of alternative influenza vaccination strategies in high-risk adults.

PURPOSE: High-dose trivalent inactivated influenza vaccine (HD-IIV3) or recombinant trivalent influenza vaccine (RIV) may increase influenza vaccine effectiveness (VE) in adults with conditions that place them at high risk for influenza complications. This analysis models the public health impact and cost-effectiveness (CE) of these vaccines for 50-64year-olds. METHODS: Markov model CE analysis compared 5 strategies in 50-64year-olds: no vaccination; only standard-dose IIV3 offered (SD-IIV3 only), only quadrivalent influenza vaccine offered (SD-IIV4 only); high-risk patients receiving HD-IIV3, others receiving SD-IIV3 (HD-IIV3 & SD-IIV3); and high-risk patients receiving HD-IIV3, others receiving SD-IIV4 (HD-IIV3 & SD-IIV4). In a secondary analysis, RIV replaced HD-IIV3. Parameters were obtained from U.S. databases, the medical literature and extrapolations from VE estimates. Effectiveness was measured as 3%/year discounted quality adjusted life year (QALY) losses avoided. RESULTS: The least expensive strategy was SD-IIV3 only, with total costs of $99.84/person. The SD-IIV4 only strategy cost an additional $0.91/person, or $37,700/QALY gained. The HD-IIV3 & SD-IIV4 strategy cost $1.06 more than SD-IIV4 only, or $71,500/QALY gained. No vaccination and HD-IIV3 & SD-IIV3 strategies were dominated. Results were sensitive to influenza incidence, vaccine cost, standard-dose VE in the entire population and high-dose VE in high-risk patients. The CE of RIV for high-risk patients was dependent on as yet unknown parameter values. CONCLUSIONS: Based on available data, using high-dose influenza vaccine or RIV in middle-aged, high-risk patients may be an economically favorable vaccination strategy with public health benefits. Clinical trials of these vaccines in this population may be warranted.

Does cost-effectiveness of influenza vaccine choice vary across the U.S.? An agent-based modeling study.

BACKGROUND: In a prior agent-based modeling study, offering a choice of influenza vaccine type was shown to be cost-effective when the simulated population represented the large, Washington DC metropolitan area. This study calculated the public health impact and cost-effectiveness of the same four strategies: No Choice, Pediatric Choice, Adult Choice, or Choice for Both Age Groups in five United States (U.S.) counties selected to represent extremes in population age distribution. METHODS: The choice offered was either inactivated influenza vaccine delivered intramuscularly with a needle (IIV-IM) or an age-appropriate needle-sparing vaccine, specifically, the nasal spray (LAIV) or intradermal (IIV-ID) delivery system. Using agent-based modeling, individuals were simulated as they interacted with others, and influenza was tracked as it spread through each population. Influenza vaccination coverage derived from Centers for Disease Control and Prevention (CDC) data, was increased by 6.5% (range 3.25%-11.25%) to reflect the effects of vaccine choice. RESULTS: Assuming moderate influenza infectivity, the number of averted cases was highest for the Choice for Both Age Groups in all five counties despite differing demographic profiles. In a cost-effectiveness analysis, Choice for Both Age Groups was the dominant strategy. Sensitivity analyses varying influenza infectivity, costs, and degrees of vaccine coverage increase due to choice, supported the base case findings. CONCLUSION: Offering a choice to receive a needle-sparing influenza vaccine has the potential to significantly reduce influenza disease burden and to be cost saving. Consistent findings across diverse populations confirmed these findings.

Potential Consequences of Not Using Live Attenuated Influenza Vaccine.

INTRODUCTION: Decreased live attenuated influenza vaccine (LAIV) effectiveness in the U.S. prompted the Advisory Committee on Immunization Practices in August 2016 to recommend against this vaccine's use. However, overall influenza uptake increases when LAIV is available and, unlike the U.S., LAIV has retained its effectiveness in other countries. These opposing countercurrents create a dilemma. METHODS: To examine the potential consequences of the decision to not recommend LAIV, which may result in decreased influenza vaccination coverage in the U.S. population, a Markov decision analysis model was used to examine influenza vaccination options in U.S. children aged 2-8 years. Data were compiled and analyzed in 2016. RESULTS: Using recently observed low LAIV effectiveness values, fewer influenza cases will occur if LAIV is not used compared with having LAIV as a vaccine option. However, having the option to use LAIV may be favored if LAIV effectiveness returns to prior levels or if the absence of vaccine choice substantially decreases overall vaccine uptake. CONCLUSIONS: Continued surveillance of LAIV effectiveness and influenza vaccine uptake is warranted, given their importance in influenza vaccination policy decisions.

Does Choice of Influenza Vaccine Type Change Disease Burden and Cost-Effectiveness in the United States? An Agent-Based Modeling Study.

Offering a choice of influenza vaccine type may increase vaccine coverage and reduce disease burden, but it is more costly. This study calculated the public health impact and cost-effectiveness of 4 strategies: no choice, pediatric choice, adult choice, or choice for both age groups. Using agent-based modeling, individuals were simulated as they interacted with others, and influenza was tracked as it spread through a population in Washington, DC. Influenza vaccination coverage derived from data from the Centers for Disease Control and Prevention was increased by 6.5% (range, 3.25%-11.25%), reflecting changes due to vaccine choice. With moderate influenza infectivity, the number of cases averaged 1,117,285 for no choice, 1,083,126 for pediatric choice, 1,009,026 for adult choice, and 975,818 for choice for both age groups. Averted cases increased with increased coverage and were highest for the choice-for-both-age-groups strategy; adult choice also reduced cases in children. In cost-effectiveness analysis, choice for both age groups was dominant when choice increased vaccine coverage by ≥3.25%. Offering a choice of influenza vaccines, with reasonable resultant increases in coverage, decreased influenza cases by >100,000 with a favorable cost-effectiveness profile. Clinical trials testing the predictions made based on these simulation results and deliberation of policies and procedures to facilitate choice should be considered.

Using a Mixed Methods Approach to Examine Practice Characteristics Associated With Implementation of an Adult Immunization Intervention Using the 4 Pillars Practice Transformation Program.

Adult immunization rates are consistently suboptimal, exacting significant human and financial burden of preventable disease. Practice-level interventions to improve immunization rates have produced mixed results. The context of change critically affects implementation of evidence-based interventions. We conducted a randomized controlled cluster trial of the 4 Pillars Practice Transformation Program to increase adult vaccination rates in primary care practices and used qualitative methods to test intervention effects and understand practice characteristics associated with implementation success. We conducted qualitative interviews with staff from 14 practices to assess implementation experiences. Thematic analysis of data pointed to the importance of quality improvement history, communication and practice leadership, Immunization Champion leadership effectiveness, and organizational flexibility. Practices were scored on these characteristics and grouped into four types: Low Implementers, Medium Implementers, High Implementers, and Public/University Practices. Intervention uptake and immunization rate changes were compared, and a significant increase in influenza vaccination rates (3.9 percentage points [PPs]; p = .038) was observed for High Implementers only. Significant increases in Tdap vaccination rates were observed for High Implementers (9.3 PP; p = 0.006) and the Public/University groups (6.5 PP; p = 0.012), but not other groups. Practice characteristics may be critical factors in predicting intervention success.

Using the 4 Pillars Practice Transformation Program to Increase Pneumococcal Immunizations for Older Adults: A Cluster-Randomized Trial.

OBJECTIVES: To test the effectiveness of a step-by step, evidence-based guide, the 4 Pillars Practice Transformation Program, to increase adult pneumococcal vaccination. DESIGN: Randomized controlled cluster trial (RCCT) in Year 1 (June 1, 2013 to May 31, 2014) and pre-post study in Year 2 (June 1, 2014 to January 31, 2015) with data analyzed in 2016. Baseline year was June 1, 2012, to May 31, 2013. Demographic and vaccination data were derived from deidentified electronic medical record extractions. SETTING: Primary care practices (n = 25) stratified according to metropolitan area (Houston, Pittsburgh), location (rural, urban, suburban), and type (family medicine, internal medicine), randomized to receive the intervention in Year 1 (n = 13) or Year 2 (n = 12). PARTICIPANTS: Individuals aged 65 and older at baseline (N = 18,107; mean age 74.2; 60.7% female, 16.5% non-white, 15.7% Hispanic). INTERVENTION: The 4 Pillars Program, provider education, and one-on-one coaching of practice-based immunization champions. Outcome measures were 23-valent pneumococcal polysaccharide vaccine (PPSV) and pneumococcal conjugate vaccine (PCV) vaccination rates and percentage point (PP) changes in vaccination rates. RESULTS: In the Year 1 RCCT, PPSV vaccination rates increased significantly in all intervention and control groups, with average increases ranging from 6.5 to 8.7 PP (P < .001). The intervention was not related to greater likelihood of PPSV vaccination. In the Year 2 pre-post study, the likelihood of PPSV and PCV vaccination was significantly higher in the active intervention sites than the maintenance sites in Pittsburgh but not in Houston. CONCLUSION: In a RCCT, PPSV vaccination rates increased in the intervention and control groups in Year 1. In a pre-post study, private primary care practices actively participating in the 4 Pillars Practice Transformation Program improved PPSV and PCV uptake significantly more than practices that were in the maintenance phase of the study.

Improving adolescent HPV vaccination in a randomized controlled cluster trial using the 4 Pillars™ practice Transformation Program.

OBJECTIVE: Uptake of meningococcal vaccine (MCV) and tetanus, diphtheria and pertussis (Tdap) vaccine among adolescents has approached Healthy People 2020 goals, but human papillomavirus (HPV) vaccination has not. This study evaluated an intervention using the 4 Pillars™ Practice Transformation Program to increase HPV, MCV and Tdap uptake among adolescents in primary care practices. METHODS: Practices with at least 50 patients 11-17years old with estimated vaccination rates less than national goals, were assigned to intervention (n=11) and control (n=11) groups in a randomized controlled cluster trial; 9 intervention and 11 control sites completed the study. The baseline and active study periods were 7/1/2013-6/30/2014 and 7/1/2014-3/31/2015, respectively. Vaccination and demographic data for patients who had a visit in both study periods were derived from de-identified EMR extractions. Primary outcomes were vaccination rates and percentage point (PP) changes. Data were analyzed in 2015-16. RESULTS: Among the cohort of 10,861 adolescent patients, 38% were 11-13years old; 50% were female; 18% were non-white; and 64% were commercially insured. Average baseline HPV initiation rates were 52.5% for intervention and 61.8% for control groups. After 9months, the intervention sites increased HPV initiation 10.2PP compared with 7.3PP in control sites (P<0.001); HPV series completion rates did not differ between groups. Implementation of >10 strategies to improve rates significantly increased the likelihood of HPV series initiation (OR=2.06, 95% CI=1.43, 2.96). CONCLUSIONS: Using >10 strategies from the 4 Pillars™ Practice Transformation Program is effective for increasing HPV series initiation among adolescents. Clinical trial registry number: NCT02165722.