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Cost-Effectiveness of Live Attenuated Versus Inactivated Influenza Vaccine Among Children

Published Online: August 20, 2014
Lee J. Smolen, BSEE; Timothy M. Klein, BS; Christopher A. Bly, BA; and Kellie J. Ryan, MPH
Objectives: To model relative costs and benefits of trivalent live attenuated influenza vaccine (T/LAIV) versus trivalent inactivated influenza vaccine (T/IIV) in US children aged 2 to 17 years.

Study Design: Decision tree with 1-way and probabilistic sensitivity analysis functionality for analysis of the cost-effectiveness of T/LAIV versus T/IIV in children during mild, moderate, and severe influenza seasons.
 
Methods: Cost-effectiveness was modeled for US children aged 2 to 17 years using published efficacy data from randomized controlled trials comparing T/LAIV with T/IIV in children aged 6 months to 17 years. Model inputs were sourced from published literature and database analyses. Effectiveness was measured in quality adjusted life-years (QALYs), influenza cases, outpatient physician visits, and hospitalizations.
 
Results: Compared with T/IIV, T/LAIV reduced the number of influenza cases and healthcare resource utilization, and increased the QALYs for all modeled seasons. From a societal perspective, T/LAIV had a total cost increase per vaccinated child of $3.61 ($27,875 cost/QALY) for a mild season, and demonstrated cost savings versus T/IIV for moderate and severe seasons. From a payer perspective, T/LAIV had a total cost increase per vaccinated child of $7.50 ($57,986 cost/QALY), $6.04 ($23,338 cost/QALY), and $4.57 ($11,788 cost/QALY) for mild, moderate, and severe seasons, respectively.
 
Conclusions: T/LAIV reduced the number of influenza illnesses and healthcare resource utilization versus T/IIV in children aged 2 to 17 years. Use of T/LAIV versus T/IIV resulted in cost savings from a societal perspective in moderate and severe seasons, and was cost-effective from a societal perspective in mild seasons and from a payer perspective in all seasons.

Am J Pharm Benefits. 2014;6(4):171-182
Annual vaccination has been accepted as the most effective method for preventing influenza illness and its complications, and has been recommended in the United States for all individuals 6 months and older without contraindications to vaccination.1 Seasonal influenza epidemics lead to significant direct medical and societal costs in addition to heightened mortality risks.2,3 Previously published studies have demonstrated that vaccination reduces costs associated with influenza.4-9        

Currently, 2 types of influenza vaccines are available in the United States: live attenuated influenza vaccine (LAIV) and trivalent inactivated influenza vaccine (IIV). LAIV is approved for eligible individuals aged 2 to 49 years, and some IIV formulations are approved for use in eligible individuals 6 months and older (IIV products differ with respect to eligible populations).        

LAIV has demonstrated higher efficacy than IIV in 3 randomized controlled trials in children.10 Prior studies have examined the cost-effectiveness of vaccinating children with LAIV versus IIV. To the best of our knowledge, only 1 study has examined cost-effectiveness using efficacy data from a randomized trial that directly compared the 2 vaccines; this analysis was limited to children aged 24 to 59 months.4 New data on influenza mortality, resource utilization, and costs, along with the expanded recommendations for annual influenza vaccination, may impact previous results. We sought to evaluate the impact of this data on the relative cost-effectiveness of LAIV versus IIV.        

The objective of this analysis was to assess the cost-effectiveness of trivalent LAIV (T/LAIV) versus trivalent IIV (T/IIV) in children aged 2 to 17 years across differing influenza season severities from US societal and payer perspectives, using efficacy data from the 3 randomized controlled clinical trials that directly compared the 2 vaccines.

METHODS

Model Structure

A decision-tree model with probabilistic sensitivity analysis (PSA) functionality was developed in Microsoft Office Excel 2007 with Visual Basic for Applications macros to analyze the cost-effectiveness of influenza vaccination with T/LAIV versus T/IIV in United States children aged 2 to 17 years. The adapted model structure, based on published influenza models,4,11 is presented in Figure 1.

Influenza Infection and Complication Rates

The T/LAIV and T/IIV influenza infection rates for our base case analysis were taken from 2 clinical trials12,13 performed in the 2002-2003 influenza season14 (Table 110,11,14-30). These trials provided a unique opportunity to evaluate T/LAIV and T/IIV in children aged 2 to 17 years in the same influenza season. There is no defined average influenza season in the United States. In a separate trial of T/LAIV versus T/IIV,18 attack rates in the T/IIV arm were 8.6% compared with the 5.8% seen in the T/IIV arm of the trials used in the current model. The influenza season of that study (2004-2005) has been referenced as mild to moderate by the US Vaccines and Related Biological Products Advisory Committee.31 Because the attack rate in the TIV arm used for our model was lower than that described by Belshe and colleagues,18 we considered the base case clinical trial–sourced scenario as mild. Because influenza severity can differ significantly by season and there is no defined attack rate for an average season, analyses were performed for hypothetical US moderate and severe influenza seasons to provide vaccine decision makers with estimates of the impact of T/LAIV and T/IIV across potential severity scenarios. T/LAIV versus T/IIV relative risk reductions from the clinical trials were applied to the defined moderate and severe influenza seasons. In the absence of clinical trial data, CDC surveillance data were used to estimate influenza attack rates. The CDC data provide the most comprehensive and quantitative information available on influenza seasons in the United States. The trial-based mild season attack rates were proportionally scaled using CDC influenza-like illness (ILI) count data for patients aged 0 to 24 years16 from more severe influenza seasons. Qualitative CDC surveillance influenza season descriptions were used to ensure that the ILI count data were reflective of season severity. The 2003-2004 season was designated as “moderately severe” and in the 2005-2006 season “activity remained elevated for a longer period of time.”14 The ILI counts for the 2003-2004 and 2005-2006 seasons were approximately double those of the 2002-2003 season,16 so the mild season attack rates were doubled to model the hypothetical moderate season. The 2007-2008 season was “associated with greater overall mortality, and higher rates of hospitalization.”14 The ILI counts for the 2007-2008 and 2008-2009 seasons were approximately 4 times those of the 2002-2003 season.16 To model the hypothetical severe season, the trial-based mild attack rates were multiplied by a factor of 3 to be conservative instead of the approximate ILI count-derived ratio of 4.        

The model implemented acute otitis media (AOM) and lower respiratory infection (LRI) complication rates given influenza infection differentiated by vaccine and age (Table 1). The model assumed that the complication rates were constant across influenza attack rates. AOM complication rates were taken from a pooled analysis of 2 T/LAIV versus T/IIV controlled trials.17 The rates for children aged 2 to 7 years were used for children aged 2 to 8 years. A postmarketing observational study (R. Baxter and S. L. Toback, MedImmune, unpublished observations, 2011) documented an incidence of medically attended AOM in older children (9-17 years) that was approximately 40% of the incidence for children aged 5 to 8 years. This proportion was applied to the published rates and used as the AOM complication rate for children aged 9 to 17 years. LRI complication rates were taken from a clinical trial of T/LAIV versus T/IIV in children aged 6 to 59 months.18 LRI given influenza values for children aged 6 months to 5 years were applied to children aged 2 to 5 years in the model. Prosser and colleagues11 noted a lower LRI infection rate for children aged 5 to 11 and 12 to 17 years compared with younger children. In the absence of LRI infection rates for older children from clinical trials, age-based ratios of LRI rates calculated from Prosser and colleagues’ data were used to approximate LRI rates for the older children.      

Adverse events associated with vaccination, such as reactogenicity, injection site events, and medically significant wheezing, were not included in the model. The most common adverse events associated with vaccination are low-cost, low-utility impact events such as runny nose, cough, or injection site pain or swelling.

Influenza Vaccine Efficacy

The influenza vaccine efficacies for children aged 2 to 5 and 6 to 17 years are from 2 randomized, open-label studies conducted in Europe and Israel during the 2002-2003 influenza season. The trial for the younger age group (2-5 years) was conducted in children aged 6 to 71 months with recurrent respiratory tract infections12; a meta-analysis compared T/LAIV and T/IIV influenza incidence rates in those trials for children aged 24 to 71 months, and the relative risk reduction reported for T/LAIV versus T/IIV was 48%.10 The trial for the older age group (6-17 years) was conducted in children and adolescents aged 6 to 17 years with medically stable asthma13; a meta-analysis was published comparing the T/LAIV versus T/IIV incidence rates for children aged 6 to 11 and 12 to 17 years, and the reported relative risk reductions for T/LAIV versus T/IIV were 31% and 30%, respectively. Although children with asthma had an increased risk of influenza complications, their risk of influenza illness was judged to be similar to that of healthy children of the same age.15 In the United States, T/LAIV currently is not recommended for use in children with recurrent wheezing or asthma.

Influenza Resource Utilization and Mortality

The model assumed that the utilization of medical resources given influenza infection is vaccine independent (Table 1). Uncomplicated influenza patients had an age-dependent risk of seeking outpatient medical care.11 Complicated influenza patients were assumed to seek outpatient care, and complicated influenza patients with LRI had an age-dependent risk of inpatient hospitalization.11 The model inputs estimated mortality rates for uncomplicated and complicated influenza.

Costs

Costs in the model included direct medical and indirect costs (Table 1). Costs were inflated to 2010 US dollars using the January 2010 values from the medical care component of the Bureau of Labor Statistics’ Consumer Price Index.32        

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