Fewer than half the respondents were willing to trade any time to prevent uncomplicated influenza in a hypothetical child, but many (73%) were willing to give up some time to prevent vaccination-related complications. Most participants indicated a willingness-to-pay to avoid uncomplicated influenza as well as a severe allergic reaction or Guillain-Barré syndrome due to vaccination, but there was substantial variation in the amounts they were willing to pay.
This study did not evaluate willingness-to-pay and time-tradeoff amounts for complications of influenza such as otitis media and hospitalization that should be included in an economic evaluation of influenza vaccine. They were not included because values for these conditions were collected in a previous study conducted on a random sample of adults in the United States. In this study, we found that the median time-tradeoff amount for acute otitis media was 4 days, non-hospitalized pneumonia was 65 days, and hospitalization due to pneumonia was 214 days .
For preventing a case of uncomplicated influenza in a 1-year-old and a 14-year-old, 51% and 60% of respondents were not willing to trade any time. For the same health states, far fewer respondents reported zero as their willingness-to-pay to prevent uncomplicated influenza in a 1-year-old (13%) and a 14-year-old (14%). Since the smallest unit respondents could trade was one day in the time-tradeoff questions, respondents that might have been willing to trade a fraction of a day might have responded with zero when the true tradeoff value could have been between 0 and 1 day. Allowing respondents to trade minutes or hours could have resulted in fewer non-zero responses. In this study, respondents were not asked about time periods of less than one day and willingness-to-pay appears to be a more sensitive metric for valuing temporary health states.
The willingness-to-pay results for the safer (hypothetical) vaccines should be interpreted cautiously. There is considerable evidence that people have difficulty valuing small risk reductions and also are willing to pay more in a hypothetical situation [13, 14]. In this study, using the responses from the risk reduction questions results in willingness-to-pay estimates orders of magnitude higher than when respondents directly valued the prevention of one case of either event. Differences could be attributable to (1) risk aversion (the second set of values ignores any premium respondents are willing to pay to avoid a risk), (2) overestimation of small probabilities, and/or (3) the voluntary nature of the risk (because parents voluntarily choose to expose their children to vaccines and may feel responsible for bad outcomes associated with them, they may be willing to pay more to reduce that risk than they would in a situation that included a similar risk of experiencing a condition in a way unrelated to any decision or action by the parent). In any case, the values for questions on risk reductions are sufficiently different to cause some concern about the incorporation of probabilities into contingent valuation questions.
There are a number of challenges in measuring the value of health for very young children including the use of parents as proxy respondents, the valuation of temporary health states, and whether or not to include family spillover effects [15–17]. Applying utilities from standardized instruments such as the Health Utilities Index (HUI) or the EQ-5D which were developed to value chronic health states in adults (and children 6 and older in the case of the HUI) are unlikely to be accurate for valuing temporary or transient health states in very young children [15, 18]. There is a small but growing body of literature in the area of valuing temporary health states. Alternatives such as the waiting-tradeoff, conjoint analysis, "chained" health states, and other modifications of the time-tradeoff method have been proposed without any clear consensus on a preferred method [19–22]. This study demonstrates the use of a modified time-tradeoff question that differs from that typically used to value chronic health states, in which respondents choose between years of life with and without a stated condition. (For a discussion of the appropriateness of using time-tradeoff questions to elicit utilities for economic evaluations, see Dolan P. Output measures and valuation in health. In: Economic evaluation in health care: Merging theory with practice. Eds: Drummond M, McGuire A. New York: Oxford University Press. 2001.) Approaches similar to the one used in this study have been employed in previous studies [12, 23, 24], but clearly more research is needed to reach consensus in the field regarding optimal methods for valuing temporary health states in young children.
There has been increasing recognition of family spillover effects (i.e., the effect of one family member's illness on other family members) on health-related quality-of-life. The potential importance of including these effects in economic analyses can be quite significant for illnesses in the very young and the very old [16, 17]. Our approach of valuing changes in health-related quality-of-life for both parent and child is consistent with the inclusion of family spillover effects in the economic evaluation. Our study evaluated the tradeoff between life in a parent and a temporary health state in their child. The inclusion of loss of quality-of-life for both parent and child prevents the time-tradeoff amounts from being directly comparable to utility values from generic utility instruments for measuring reductions in quality-of-life for chronic health states, such as the Health Utilities Index  or the EQ-5D . Clearly more research will be needed to establish the optimal method for valuing family spillover effects.
The generalizability of these study results are limited by the small sample size and a relatively homogeneous and geographically-limited respondent population whose characteristics differ from those of the general U.S. population. Sampling from the general membership of a large New England HMO resulted in a group of respondents with little variation in income, and that otherwise differed from characteristics of the general U.S. population. For example, more than 75% of respondents had an annual household income greater than $50,000. The response rate was somewhat low, but not atypical for similar telephone surveys. Given these limitations, the results are sufficiently robust to justify a larger study for validation that also included additional uncommon severe outcomes of influenza in children, including encephalopathy and death .
The annual probability of a one-year-old experiencing an influenza-related illness is approximately 16% in non-pandemic years [28–37] and varies from 0–23% in a non-pandemic year. The risk of an influenza-related hospitalization is about 3 per thousand for a child at low risk for influenza-related complication [1–3]. In contrast the risk of anaphylaxis from influenza vaccination is estimated at approximately 1 in 4 million  based on surveillance from the 1976 swine flu vaccine program. Guillain-Barré syndrome was associated with receipt of swine flu vaccine in 1976 with a risk of 1 per 100,000 persons vaccinated , although children were associated with a lower risk of GBS than adults , and studies since 1976 have not found a clear association of GBS with influenza vaccination [40, 41]. Most studies of an association of Guillain-Barré syndrome with influenza vaccination have been among adults and not children. Economic analyses can provide information useful in comparing the benefits of vaccination with the risks of adverse events.
The variability in preferences and willingness-to-pay observed in this study suggests that different community members may appraise the desirability or cost-effectiveness of influenza vaccination quite differently. The relatively low value many respondents attributed to uncomplicated influenza could provide insight into low coverage rates for influenza vaccination among children. Concern about the safety of vaccination is shown by the premium most respondents were willing to pay for a vaccine with lower risks of adverse events. Information on the costs, benefits, risks, and community preferences can aid policy decisions regarding influenza vaccination.