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Supplements A Managed Care Perspective on the Importance of Optimizing Influenza Vaccinations in Older Adults
Influenza in Older Patients: A Call to Action and Recent Updates for Vaccinations
Miranda Wilhelm, PharmD
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Managed Care Considerations and Economic Implications of Vaccination Practices
Mary Patricia Nowalk, PhD, RD
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Managed Care Considerations and Economic Implications of Vaccination Practices

Mary Patricia Nowalk, PhD, RD
Influenza is an acute viral respiratory disease caused by the influenza A and B viruses. The epidemiologic characteristics of influenza are in constant flux as the viruses mutate frequently, and the subsequent spread of illness depends on the affected population’s susceptibility to the new antigens. These viral mutations necessitate frequent updates to the annual seasonal influenza vaccine. Those most at risk for serious complications of influenza are young children and elderly persons. Although influenza vaccination rates are highest among adults 65 years or older, vaccine effectiveness in this age group is often less than among younger persons. Thus, vigilance in efforts to increase vaccine uptake is warranted through a concerted effort across the entire healthcare and public health spectrum of providers and agencies, including clinicians, health systems, government, and community agencies. Managed care organizations are an excellent case study for implementing systemwide efforts to prevent influenza disease and its consequences.
Am J Manag Care. 2018;24:-S0
The Economic Burden of Influenza in the United States

The public health burden of influenza is enormous, with outbreaks creating significant morbidity and mortality annually. Attendant to the significant morbidity and mortality is a considerable economic burden. In a landmark 2007 study, Molinari et al undertook a systematic analysis of the total costs of influenza. Using data from health insurance claims, the investigators estimated the direct medical costs for outpatient visits, hospitalizations, and mortality, along with projections of either earnings or statistical life-values for indirect costs of illness-related work absenteeism or premature death. They then estimated healthcare resource usage associated with influenza. Results of the study showed that annual influenza epidemics led to approximately 610,660 life-years lost, along with 3.1 million patient-hospitalized days and 31.4 million outpatient visits. The economic burden of influenza across all age groups was $87.1 billion annually, including $10.4 billion in direct medical costs alone, and projected lost earnings due to illness and death were approximately $16.3 billion. Significantly, 64% of the total cost  ($55.7 billion) was incurred by illnesses in older adults, due to their increased rates of hospitalizations and deaths associated with influenza, although older adults comprised only 13% of the US population at the time.1

Since the Molinari study, other research has explored the economic burden of influenza. In 2012, Mao et al assessed the annual economic costs of seasonal influenza for 3143 counties in the United States based on the 2010 US Census. The study researched spatial variations among counties regarding population size, age structure, income level, and influenza activity. Results showed that the annual economic costs of influenza varied from $13.9 thousand to $957.5 million across counties in the United States, with a median cost of $2.47 million. The authors suggested that prioritizing the distribution of influenza vaccines to counties with higher influenza rates may lead to fewer influenza cases and better net outcomes.2

A recently published study by Yan et al estimated the number of healthcare encounters and related costs attributable to influenza A and B in the United States during the 2001-2002 to 2008-2009 seasons. Over the 8 influenza seasons, 11.3 million to 25.6 million projected influenza-related healthcare encounters occurred. Related healthcare costs ranged from $2.0 billion to $5.8 billion.3

A new study by Young-Xu et al used electronic medical records (EMRs) from the Veterans Health Administration of the Department of Veterans Affairs (VA) and respiratory viral surveillance data from the CDC to estimate the disease and economic burdens of influenza among the US military veteran population from 2010 to 2014. An estimated 10,674 VA emergency department (ED) visits, 2538 VA hospitalizations, and 3793 underlying respiratory or circulatory deaths were attributed to influenza annually. Lost productivity during each year cost $27 million, with yearly costs for ED visits estimated at $6.2 million. Overall, the estimated annual economic burden related to seasonal influenza was $1.2 billion, with premature death being the largest cost driver, followed by hospitalization. The largest proportion of the burden of influenza affected those 65 years or older. Most of the lost productivity and hospitalization costs were incurred by older veterans.4

Cost-Effectiveness of Different Influenza Vaccines

The primary preventive strategy against the health and economic burden attributable to influenza is annual influenza vaccination. However, the reduction in influenza burden depends on vaccine coverage, effectiveness, and relative effectiveness of various vaccine formulations (eg, trivalent or quadrivalent; inactivated or live attenuated; standard-dose or high-dose; and cell-based, egg grown, or adjuvanted), as well as the relative uptake of the different vaccine types.

Over 5 recent influenza seasons, overall vaccine coverage has ranged from a low of 41.8% in 2011-2012 to a high of 47.1% in 2014-2015. In 2016-2017, coverage was 49.9% among those 6 months to 17 years, 33.6% among those 18 to 49 years, 45.4% among those 50 to 64 years, and 65.3% among those 65 years or older.5,6 During these years, the US Influenza Vaccine Effectiveness (VE) Network reported that the overall influenza VE was 47% in 2011-2012, 49% in 2012-2013, 52% in 2013-2014, 19% in 2014-2015, and 48% in 2015-2016. These factors, including uptake, VE, costs of vaccine and administration, and costs of disease are essential components of analyses to determine whether and under what scenarios vaccination is cost-effective.7 Ting et al recently reviewed 31 studies of influenza vaccination cost-effectiveness across diverse population subgroups. Vaccination was found to be cost-effective for children, adolescents, pregnant and postpartum women, and high-risk groups, such as those with comorbid conditions and the elderly, from both societal and health-system perspectives.8

A 2017 review by deBoer et al used medical databases to identify economic evaluations of trivalent influenza vaccine (IIV3) versus quadrivalent influenza vaccine (IIV4) formulations. They found that the comparative benefits of the IIV4 formulation can vary by influenza season, because the VE of  IIV3 depends on how well the B virus contained in IIV3 matches with the circulating B virus, and on the level of cross-protection provided by IIV3 against the influenza B virus not included in the vaccine. Additionally, the price difference between IIV3 and IIV4 is a factor in the cost-effectiveness potential of IIV4. Results suggested that switching from a IIV3 to IIV4 formulation could be both clinically and economically beneficial; however, the authors recommended that the impact of the 2 formulations should be studied from multiple influenza seasons to better assess and reflect the circulation of the B strains from one season to another.9

Cost-effectiveness studies specific to adults 65 years or older have focused on use of the high-dose influenza vaccine versus the standard-dose influenza vaccine. One 2015 study based on US influenza-related health outcome data assessed the cost-effectiveness of high-dose inactivated influenza (IIV3-HD) versus standard-dose IIV3 and the standard-dose quadrivalent inactivated influenza (IIV4) vaccines. Results demonstrated that IIV3-HD vaccine compared with standard-dose influenza vaccine would avert 195,958 cases of influenza, 22,567 influenza-related hospitalizations, and 5423 influenza deaths among the US elderly. IIV3-HD generated 29,023 more quality-adjusted life-years (QALYs) and a net societal budget impact of $154 million, with an incremental cost-effectiveness ratio for this comparison of $5299 per QALY. The investigators concluded that the high-dose influenza vaccine is expected to achieve significant reductions in influenza-related morbidity and mortality and is a cost-effective alternative to the standard-dose influenza vaccines studied.10

Using Markov state transition decision analysis modeling, Raviotta et al compared vaccination strategies using the standard-dose influenza vaccine, IIV3-HD, and IIV4 vaccines in persons 65 years or older to assess their cost-effectiveness and public health benefits. Cost analyses showed that the cost of standard-dose inactivated, trivalent influenza vaccine was $3690 per QALY gained when compared with no vaccination at all. IIV4 cost $20,939 per  QALY gained compared with standard-dose inactivated, trivalent influenza vaccine, and IIV3-HD cost $31,214 per QALY when compared with IIV4. Overall differences of 83,775 fewer influenza cases and 980 fewer deaths were projected with the IIV3-HD formulation compared with IIV4. The investigators concluded that IIV3-HD would be the favored vaccination strategy if the actual willingness to pay for the formulation is greater than or equal to $25,000 per QALY gained. This compares with standard willingness-to-pay thresholds of $50,000 to $100,000 per QALY gained used in US literature. This study also examined the cost-effectiveness of an adjuvanted influenza vaccine (aIIV3). The cost-effectiveness of aIIV3 would depend on its price and effectiveness, which are still under study, but this formulation might be considered more favorable if its relative effectiveness is at least 15% greater than that of the standard IIV3 vaccine.11

Increasing the Rate and Cost-Effectiveness of Adult Influenza Immunization: The 4 Pillars Practice Transformation Program

Despite variability in its effectiveness from year to year, the case for vaccination against seasonal influenza is well established. Yet, vaccination uptake remains suboptimal, even among those most vulnerable to its complications, such as elderly persons and those with chronic health conditions. The reasons for influenza vaccine hesitancy are myriad and have features that differ from other vaccines. A lack of confidence in the vaccine was found to be the most important barrier to receipt of seasonal influenza vaccine, exemplified by negative attitudes, misconceptions about the disease or the vaccine, and its low perceived effectiveness. In addition, for elderly persons living alone, low perceived risk of disease and access to vaccination were important barriers to vaccine uptake.12

Although vaccination rates among the elderly population are higher than among other adult age groups, there are disparities in uptake by race, with vaccination rates among older Caucasians at 67.7%, Hispanics at 66.8%, and African Americans at 56.1% in 2010.13 A decision-analysis model has been examined to estimate the cost-effectiveness of a hypothetical national vaccination program aimed at eliminating the disparities in the vaccination rates among these populations. A proposed cost of $10 per targeted person per year was assumed, with all groups reaching 70% vaccination uptake within 10 years. The vaccination intervention program compared with no intervention program cost $48,617 per QALY saved. At willingness-to-pay thresholds of $50,000 and $100,000 per QALY saved, the likelihood of the vaccination program being cost-effective was shown to be 38% and 92%, respectively. Overall, the investigators concluded that such a hypothetical model would have a moderate to high likelihood of being cost-effective in resolving current disparities in vaccination rates among the different racial/ethnic populations studied.14

Although hypothetical models such as those highlighted above provide potentially promising data for establishing public policy to maximize influenza immunization’s cost-effectiveness, every influenza season presents a renewed challenge to achieve the updated Healthy People 2020 goals to increase the number of adults  aged 18 years and older vaccinated against seasonal influenza.15 The Community Preventive Services Task Force has recommended multi-strategy, evidence-based interventions to increase vaccination rates in the United States through enhanced access to vaccination services, increased community demand for vaccinations, and improved provider- and system-based vaccine-related interventions. Moreover, the Task Force recommended that 1 or more strategies from each of the interventions be used in combination for the best outcomes.16,17

 
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