The American Journal of Managed Care March 2010
Economics of Influenza Vaccine Administration Timing for Children
Vaccinating children earlier (ie, September or October) can provide net economic benefit to society and to third-party payers. Vaccination of children remained cost-effective through December.
Objectives: To determine how much should be invested each year to encourage and operationalize the administration of influenza vaccine to children before November and how late the vaccine should be offered each year.
Study Design: Monte Carlo decision analytic computer simulation models.
Methods: The children’s influenza vaccination timing model quantified the incremental economic value of vaccinating a child earlier in the influenza season and the incremental cost of delaying vaccination. The children’s monthly influenza vaccination decision model evaluated the cost-effectiveness of vaccinating versus not vaccinating for every month of the influenza season.
Results: Getting children vaccinated by the end of October rather than when they are currently getting vaccinated could save society between $6.4 million and $9.2 million plus 653 and 926 quality-adjusted life-years (QALYs) and third-party payers between $4.1 million and $6.1 million plus 647 to 942 QALYs each year. Decision makers may want to continue offering influenza vaccination to children at least through the end of December. Vaccinating with trivalent inactivated virus vaccine was more cost-effective than vaccinating with live attenuated influenza vaccine for every month.
Conclusion: Policymakers could invest up to $6 million to $9 million a year to get children vaccinated in September or October without expending any net costs.
(Am J Manag Care. 2010;16(3):e75-e85)
The 2009 influenza A(H1N1) pandemic, as well as past influenza seasons, demonstrated the feasibility of administering seasonal influenza vaccine to children by September or October.
- Getting children vaccinated by the end of October rather than when they are currently getting vaccinated could save society between $6.4 million and $9.2 million plus 653 and 926 quality-adjusted life-years (QALYs) and third-party payers between $4.1 million and $6.1 million plus 647 to 942 QALYs each year.
- Trivalent inactivated virus vaccine (TIV) would be more cost-effective than live attenuated influenza vaccine (LAIV) for every month.
- Administration of TIV would remain cost-effective through December, and administration of LAIV would remain cost-effective through November.
The 2009 H1N1 pandemic demonstrated the feasibility of manufacturing, delivering, and administering seasonal influenza vaccine by September or October.3 Manufacturers and the supply chain were able to expeditiously produce and distribute seasonal influenza vaccine, despite manufacturing H1N1 influenza vaccine concurrently.4-6 In fact, studies6,7 have shown that in past years more than 70% of seasonal influenza vaccines have been available for administration by October. With evidence suggesting that earlier vaccination is possible, the next question is how much should be invested to ensure timely vaccination? The answer to this question depends in large part on the economic effect of delaying vaccination. Investment could occur all along the supply chain, from the very beginning (eg, investing to expand vaccine production capacity or to use antigen-sparing technology) to the very end (eg, investing to improve access to immunization clinics, school-based programs, health fairs, and healthcare provider visits). To address these issues, we constructed the following 2 sets of computer simulation models for children aged 2 to 18 years: (1) the children’s influenza vaccination timing model, to quantify the incremental economic value of vaccinating a child earlier in the influenza season and the incremental cost of delaying vaccination, and (2) the children’s monthly influenza vaccination decision model, to determine the cost-effectiveness of vaccinating versus not vaccinating a child for every month of the influenza season.
We used TreeAge Pro 2009 (TreeAge Software, Williamstown, MA) to develop 2 models (the children’s influenza vaccination timing model and the children’s monthly influenza vaccination decision model) that each fed into a pediatric influenza outcomes subtree. The models depicted 1 full influenza season, with the baseline scenario assuming a societal perspective (accounting for direct and indirect illness costs), and an additional scenario assuming the third-party payer perspective (direct illness costs only). Details of the models are as follows.
Children’s Influenza Vaccination Timing Model
The children’s influenza vaccination timing model Monte Carlo decision analytic computer simulation model determined the incremental cost-effectiveness of administering influenza vaccine to a child at different months of the influenza season (September to June) (Figure 1). Each vaccinated patient has a probability of experiencing local adverse effects (requiring 1 day of ibuprofen treatment) or systemic adverse effects (requiring 3 days of ibuprofen treatment). Vaccination confers immunity 2 weeks after administration. Vaccinated patients have a decreased probability of contracting influenza if exposed. Exposure to influenza is a function of the time left in the influenza season. Patients who contract influenza then proceed through the pediatric influenza outcomes subtree.
Children’s Monthly Influenza Vaccination Decision Model
The children’s monthly influenza vaccination decision model characterized the decision of whether to vaccinate a patient in a specific given month (Figure 2). For example, if a patient is seen in February, is it still cost-effective to vaccinate the patient? Separate models were created for each month of the year from September to June, encompassing the influenza season. Similar to the children’s influenza vaccination timing model, patients who are vaccinated have chances of developing local or systemic adverse effects. Vaccination confers immunity after 2 weeks and reduces the probability of contracting influenza if exposed. Exposure to influenza is a function of the time left in the influenza season. Patients who contract influenza then proceed through the pediatric influenza outcomes subtree.
Pediatric Influenza Outcomes Subtree
For both sets of models, patients who develop influenza have probabilities of self-medicating with over-the-counter medications, visiting an outpatient clinic, or being hospitalized. Hospitalized patients have a probability of not surviving. Vaccination status affects these probabilities.
Trivalent Inactivated (Killed) and Live Attenuated Influenza Virus Vaccines
Different scenarios looked at trivalent inactivated virus vaccine (TIV) and live attenuated influenza vaccine (LAIV). This involved changing the costs and the efficacy variable values to match each vaccine, as summarized in Table 1.
The following equation computed the incremental costeffectiveness ratio (ICER) of vaccine administration in a given month versus another comparison month: (Cost of Vaccinating in Baseline Month − Cost of Vaccinating in Comparison Month)/(Effectiveness of Vaccinating in Baseline Month − Effectiveness of Vaccinating in Comparison Month).
To assess if vaccinating is cost-effective, the threshold used in our model was $50,000/quality-adjusted life-year (QALY), which is a frequently cited criterion for cost-effectiveness analysis in the United States.21 Based on nonparametric estimates by Shiroiwa et al,22 this US cost-effectiveness threshold was similar to previously reported thresholds.
National Investment Using the Children’s Influenza Vaccination Timing Model
Using the children’s influenza vaccination timing model, we then constructed a model to project the potential economic value (from the societal and third-party payer perspectives) of moving the current timing of pediatric vaccination to October throughout the United States. The US Census data (http://www.census.gov/) from 2008 provided the sizes of the different age groups as follows: 2 to 4 years (21,005,852 children), 5 to 9 years (20,065,249 children), 10 to 14 years (20,054,627 children), and 15 to 18 years (21,514,358 children). Vaccination coverage among children was obtained from previous studies23,24 by the Centers for Disease Control and Prevention (CDC).
Table 1 lists the models’ data inputs, their respective distributions, and their sources. The cost of vaccine was the average wholesale price of TIV and LAIV, respectively.8 The cost of over-the-counter medications comprised the average wholesale price of acetaminophen (triangular distribution).8 The cost of hospitalization for influenza was obtained from the National Inpatient Survey of the Healthcare Cost and Utilization Project (HCUP).9 The cost of death was derived from differences in invasive pneumococcal disease costs in adults discharged alive versus those not surviving, which varied from $3700 to $14,000 based on HCUP data.10,25 The cost of an outpatient visit was obtained from a systemic review article11 regarding the effectiveness of vaccinating healthy children. The cost of vaccine adverse effects consisted of the average wholesale price of ibuprofen, assuming 1 to 3 days of ibuprofen treatment.8 Productivity losses from an outpatient visit comprised 4 hours of lost median wages (incurred by a parent missing 4 hours of work to bring a child to the clinic).12
Durations of clinic visits (in hours) and influenza (in days) were obtained from previous studies.10,13,14 Cochrane15,16 systematic reviews provided probabilities of influenza and vaccine efficacy (in preventing influenza, hospitalization, and death). Probabilities of various influenza outcomes were obtained from a CDC study.17 Probabilities of vaccine adverse effects were obtained from a 2007 study.18
All utility variables drew from triangular distributions and are expressed in QALYs; all other variables drew from normal and beta distributions.19,20,26 When possible, data inputs were obtained from published meta-analyses. The CDC27 monthly influenza surveillance data from 2000 to 2008 were used to generate the distribution of monthly influenza risk. Each simulation run randomly drew from 1 of 9 influenza seasons from 2000 to 2008.
A 3% discount rate converted costs and effectiveness measures into 2009 values. Effectiveness was expressed in QALYs. Each patient who experienced neither vaccine adverse effects nor influenza accrued 1.00 QALY.26 The occurrence of vaccine adverse effects, influenza, or hospitalization each caused relative QALY reductions.19,20 Death resulted in a QALY loss based on the QALY-adjusted life expectancy of that patient’s age.28
Sensitivity analyses varied variable values across the ranges listed in Table 1. We also looked specifically at how the age of the vaccine recipient (2-18 years) affected our results. This involved cohorts of the following age groups: 2 to 4, 5 to 9, 10 to 14, and 15 to 18 years. In addition, specific scenarios examined how much could be invested per child to encourage earlier vaccination with vaccination still remaining cost-effective.
Probabilistic (Monte Carlo) sensitivity analyses examined the effects of varying all variables simultaneously using all distributions in Table 1.
Children’s Influenza Vaccination Timing Model
Each simulation run comprised sending 5000 simulated patients 1000 times through the model, for a total of 5 million trials. Simulations found September and October to be the optimal months for vaccination, dominating other months (ie, yielding lower costs and greater effectiveness than other months).
For TIV, delaying vaccination until November cost society an additional $0.13 to $0.26 and 0.000016 to 0.000018 QALY per patient and cost third-party payers an additional $0.08 to $0.16 and up to 0.000017 QALY per patient. For LAIV, delays were even more costly for society (an additional $0.18-$0.37 and 0.000024-0.000025 QALY per patient) and for third-party payers (an additional $0.10-$0.27 and 0.000024-0.000026 QALY per patient).