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Cost-effectiveness analysis of an intranasal influenza vaccine for the prevention of influenza in healthy children |
Luce B R, Zangwill K M, Palmer C S, Mendelman P M, Yan L H, Wolff M C, Cho I S, Marcy S M, Iacuzio D, Belshe R B |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology The use of a live, attenuated, trivalent, intranasal influenza vaccine was examined. The vaccine contained 10^6.7 to 10^7.0 tissue culture infective dose50/dose of each of three attenuated strains that matched the antigens for the 1996 to 1998 seasons.
Economic study type Cost-effectiveness analysis.
Study population The study population comprised healthy children aged 15 to 71 months.
Setting The setting was primary care or the community. The economic study was carried out in the USA.
Dates to which data relate The effectiveness data and some resource use data were gathered from fall 1996 to spring 1998. Other resource use and one clinical estimate were derived from studies published between 1976 and 1997. The price year was 1998.
Source of effectiveness data The effectiveness evidence was derived from a single study and one authors' assumption.
Link between effectiveness and cost data Some resource use data were prospectively gathered from the same sample of patients as that used in the clinical study.
Study sample Limited information on the method of sample selection was provided because the primary study had been published already. The study sample comprised 1,070 patients in year 1 and 917 patients in year 2 in the vaccine group, and 532 (year 1) and 441 (year 2) patients, respectively, in the placebo group. The mean age was 42 months at enrolment in year 1. Approximately 85% of children were white, 52% were female, 35% were in child care for 5 days/week at enrolment, and 85% had two adults in the home.
Study design This was a multi-centred, prospective, randomised, double-blind, placebo-controlled trial. More than 97% of the patients completed the study.
Analysis of effectiveness The outcome measures used in the analysis were influenza-like illness (ILI) fever days and frequency of vaccine-related adverse events. ILI was defined using the following criteria:
any child with a temperature of at least 101 degrees F (oral, or its equivalent);
any child who was younger than 36 months and had a temperature of at least 102 degrees F (oral, or its equivalent);
any child who was younger than 36 months and had two or more systemic symptoms, including irritability, vomiting, decreased activity, muscle aches, chills and headache;
any child who was younger than 36 months and had a temperature of at least 101 degrees F (oral, or its equivalent) and a cough and/or a sore throat;
any child who was 36 months of age or older and had three or more systemic symptoms, including irritability, vomiting, decreased activity, muscle aches, chills, headache, or temperature of 102 degrees F (oral, or its equivalent); or
any child of any age with wheezing, suspected otitis media, pulmonary congestion, or shortness of breath.
The study groups were comparable at baseline in both years of the study.
Effectiveness results During the 2-year study period, a total of 1,502 ILI visits were included in the analysis. Vaccinated children had an average of 1.2 fewer ILI fever days/child than unvaccinated children. No patients experienced vaccine-related adverse events.
Clinical conclusions The effectiveness analysis showed that intranasal influenza vaccination reduced the number of ILI fever days.
Methods used to derive estimates of effectiveness The rate of transmission of influenza from an infected child to at least one family member was derived from authors' assumptions (based on a published study).
Estimates of effectiveness and key assumptions The rate of transmission of influenza from an infected child to at least one family member was 18%.
Measure of benefits used in the economic analysis The summary benefit measure used was the reduction in ILI fever days with vaccination in comparison with no vaccination. The measure was derived directly from the clinical trial. The benefits in the second year of the study were discounted at an annual rate of 3%. In the base-case analysis, 80% of children received one dose of vaccine and 20% of children received two doses.
Direct costs The costs incurred in the second year of the study were discounted at an annual rate of 3%. The unit costs were presented separately from the quantities of resources used. The economic evaluation considered health services related to vaccine acquisition and administration, the treatment of vaccine-associated adverse events and ILI, and caregivers' travel for vaccination and to health care visits (for the treatment of vaccine-associated adverse events, ILI and culture-confirmed influenza). The categories of costs considered were outpatient health care provider visits (physician office and emergency room visits), outpatient tests or procedures, outpatient medications and hospitalisations. Outpatient tests and procedures included chest radiograph, other nonoperative measurements or procedures, throat or nose culture, and urinalysis.
The cost/resource boundary of the third-party payer was adopted in the analysis of the direct costs. Some resource use data were estimated from the clinical trial. However, the authors stated that the resource use behaviour of patients enrolled in the trial could have been higher than that of the general population. Thus, some assumptions reflecting real-world treatment patterns were made and were explicitly reported. Further, other published sources such as national surveys were used. The costs came from authors' assumptions and published evidence, including the National Center for Health Statistics, the Red Book and published studies. Extensive details of the sources used were provided. When necessary, the costs were inflated to 1998/99 values using the medical component of the Consumer Price Index.
Statistical analysis of costs The costs were treated deterministically.
Indirect Costs The indirect costs were included in the economic evaluation because a societal perspective was adopted. Days of missed work due to care for a child with ILI were derived from the clinical trial, while primary caregivers' missed usual activity (at home and in the workforce) was based on authors' assumptions and published evidence. The unit cost came from the average hourly US wage rate for full-time workers. Discounting, the price year, and the provision of unit costs were similar to those in the analysis of the direct costs.
Sensitivity analysis An extensive sensitivity analysis was carried out to examine the robustness of the base-case cost-effectiveness ratios to variations in cost, resource use and clinical data. A breakeven analysis showing the vaccine/administration cost below which its use would be cost-saving was conducted. One- and two-way sensitivity analyses were performed. The ranges of values used were explicitly reported. The cost-effectiveness analysis was based on two scenarios. In scenario 1 (individual-based vaccination), all caregivers were assumed to initiate a visit to a health care facility specifically for vaccination of the child. In scenario 2 (group-based vaccination), the vaccination was performed in a group setting, such as a school or a child care facility, thus eliminating all caregivers' loss of time, productivity, and transportation costs associated with vaccination visits. The intranasal vaccine could be administered in the group-based vaccination setting by someone with very little training. In addition, vaccine cold chain requirements for transport and storage, proper screening methods, and authority and liability for vaccine administration were not at issue.
Estimated benefits used in the economic analysis See the 'Effectiveness Results' section.
Cost results The total costs were not reported.
Synthesis of costs and benefits An incremental cost-effectiveness ratio (ICER; i.e. the cost per ILI fever day avoided) was calculated to combine the costs and benefits of the vaccination strategy over the option of no vaccination.
From a societal perspective, the ICER was $29.67 with individual-based vaccination. Vaccination was dominant (more effective and less costly) in the scenario of group-based vaccination.
From a third-party payer perspective, the ICER was $19.10 in both scenarios.
The breakeven analysis showed that, from a societal perspective, the vaccine/administration cost below which its use would be cost-saving was $28 for group-based vaccination and $4.93 for the individual-based. From the perspective of the third-party payer, this cost was $10.29.
The univariate sensitivity analysis showed that the ICER with individual-based vaccination varied from $9.98 to $69.03 from a societal perspective, with the vaccine costs having the greatest impact on the base-case ICER. When group-based vaccination was considered, vaccine was dominant under a variety of scenarios considered in the sensitivity analysis.
The two-way sensitivity analysis suggested that, from a societal perspective in the individual-based scenario, if 10% of children receive 2 doses per year, the ICER would range from $4.68 to $63.84 for vaccine/administration costs of $10 and $40, respectively. When all children received only 1 dose of the vaccine, the ICER ranged from dominance to $40.59 at $10 to $40/dose, respectively.
From a societal perspective in the group-based scenario, if 10% of children received 2 doses per year, the base-case results remained dominant for a vaccine/administration cost of $10 to $25/dose. At $40/dose, the ICER was $18.52. When all children received only 1 dose per year, vaccination remained dominant for a vaccine cost of $10 to $30/dose. At $40/dose, the cost per ILI fever day avoided was $11.96.
From the third-party payer perspective, the ICERs varied from dominance to $55.14 when 10% of children received 2 doses per year, and from dominance to $45.35 when 0% of children received 2 doses per year. Again, the vaccine cost had the greatest impact on the ICERs.
Authors' conclusions An intranasal influenza vaccine in young healthy children reduced influenza-like illness (ILI) fever days. It also had the potential for being highly cost-effective, especially if delivered using a group-based vaccination approach.
CRD COMMENTARY - Selection of comparators The choice of the comparator (placebo) was based on the comparator used in the primary clinical trial. You should decide whether this is a valid comparator in your own setting.
Validity of estimate of measure of effectiveness The effectiveness evidence came from a randomised trial, which was appropriate for the study question. Limited information on the design of the study was reported, as the trial had been published already. However, the characteristics of the study (e.g. randomisation, double-blinding, data coming from multiple centres, baseline comparability of the study groups and high follow-up rate) enhanced the internal validity of the analysis. One estimate was based on an authors' assumption.
Validity of estimate of measure of benefit The summary benefit measure was specific to the study setting and is comparable only with the benefits of similar interventions. Discounting was applied. The authors stated that the number of ILI fever days averted was chosen to estimate the clinical impact of the intervention.
Validity of estimate of costs The authors adopted the broadest possible perspective in the cost analysis. A more restricted perspective was also adopted, because it could have been more relevant for decision-makers. Extensive information on resource use, unit costs and price year was provided, which enhances the possibility of replicating the study and reflating the results of the analysis in other settings. The authors justified all sources used and all assumptions made in the cost analysis. Some key cost estimates were varied in the sensitivity analysis. Discounting was applied using US rates. Overall, a robust cost analysis was carried out.
Other issues The authors stated that their study was the first one to evaluate an influenza vaccination strategy targeting young children and using data from a clinical trial. They also stated that their study supported the conclusions of earlier analyses on the cost-effectiveness of vaccination in young children. The study findings were compared extensively with the results of other studies examining other vaccination programmes in children. Some limitations to the validity of the analysis were noted. For example, the use of assumptions (especially on the resource use side), the exclusion of clinical and economic benefits associated with vaccine-based herd immunity, and the potential extra costs due to changes in logistics. In terms of the generalisability of the study results to other settings, the authors stressed that the results of the sensitivity analysis could be useful for extrapolation to other local and/or national settings.
Implications of the study The study results supported the use of an intranasal influenza vaccine in young healthy children.
Source of funding Funding from Aviron and the National Institute of Allergy and Infectious Diseases, National Institutes of Health (contract NO1-AI45249).
Bibliographic details Luce B R, Zangwill K M, Palmer C S, Mendelman P M, Yan L H, Wolff M C, Cho I S, Marcy S M, Iacuzio D, Belshe R B. Cost-effectiveness analysis of an intranasal influenza vaccine for the prevention of influenza in healthy children. Pediatrics 2001; 108(2): e24-e31 Other publications of related interest Belshe RB, Mendelman PM, Treanor J, et al. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine in children. New England Journal of Medicine 1998;338:1405-12.
McIntosh K, Lieu T. Is it time to give influenza vaccine to healthy infants? New England Journal of Medicine 2000;342:275-6.
Cohen GM, Nettleman MD. Economic impact of influenza in preschool children. Pediatrics 2000;106:973-6.
White T, Lavoie S, Nettleman MD, et al. Potential cost savings attributable to influenza vaccination of school-aged children. Pediatrics 1999;103(1).
Indexing Status Subject indexing assigned by NLM MeSH Administration, Intranasal; Child, Preschool; Cost of Illness; Cost-Benefit Analysis; Double-Blind Method; Drug Costs; Efficiency; Health Care Costs; Health Expenditures /statistics & Health Services /economics /utilization; Humans; Infant; Influenza Vaccines /administration & Influenza, Human /economics /prevention & Placebos; Prospective Studies; Vaccination /economics; control; dosage /economics /therapeutic use; numerical data AccessionNumber 22001001535 Date bibliographic record published 31/10/2005 Date abstract record published 31/10/2005 |
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