PEDIATRICS Vol. 121 No. 4 April 2008, pp. 669-673 (doi:10.1542/peds.2007-1914)
ARTICLE |
Valuing Reduced Antibiotic Use for Pediatric Acute Otitis Media
Center for Clinical Epidemiology and Biostatistics, Center for Education and Research on Therapeutics, and Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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OBJECTIVE. The 2004 American Academy of Pediatrics acute otitis media guidelines urge parents to weigh the benefits of reduced antibiotic use, adverse drug events, and future resistance versus risks of extra costs and sick days resulting from guideline use. The value of decreased antibiotic resistance has not been quantified. The objective was to perform cost-utility analysis, estimating the resistance value of implementing the guidelines for acute otitis media treatment for children <2 years of age. Outcomes were described with a common denominator and the value of avoiding resistance was estimated using a parental perspective.
METHODS. Decision analysis results were used for outcome probabilities. Published utilities were used to describe outcomes in quality-adjusted life-day units. The minimum resistance benefit value, where the benefits of the American Academy of Pediatrics guidelines would at least balance their costs, was defined as the guidelines’ incremental costs minus their other benefits.
RESULTS. For a child 2 to <6 months of age presenting to a primary care physician with possible otitis media, parents would need to value the resistance benefit at 0.77 quality-adjusted life-days per antibiotic prescription avoided for the guidelines’ benefits to balance their costs. For the 6- to <24-month-old group, results were 0.67 quality-adjusted life-days per prescription avoided. Results were sensitive to the dollar cost utility; when willingness to pay ranged from $20000 to $200000 per quality-adjusted life-year, results ranged from 0.36 and 0.30 quality-adjusted life-days up to 4.10 and 3.57 quality-adjusted life-days for the 2- to <6-month-old and 6- to <24-month-old groups, respectively. Costs were driven by missed parent work days.
CONCLUSIONS. From a societal perspective, trading 0.30 to 4 quality-adjusted life-days to avoid 1 antibiotic course might be desirable; from a parental perspective, this may not be as desirable. Parent demand for antibiotics may be rational when driven by the value of parent time. Other approaches that have the potential to reduce antibiotic use, such as wider use of influenza vaccine and improved rapid viral diagnostic techniques, might be more successful.
Key Words: otitis media • child • drug resistance • bacterial • decision support techniques • cost/benefit analysis
Abbreviations: AAP—American Academy of Pediatrics • ADE—adverse drug event • AOM—acute otitis media • QALD—quality-adjusted life-day • QALY—quality-adjusted life-year
Antibiotic use influences bacterial resistance at both individual and community levels. Previous antibiotic use is a risk factor for carriage of and infection with resistant Streptococcus pneumoniae,1–6 and resistant organisms are associated with increased risks of treatment failure, complications, and death.7–10 Resistance is influenced by selective pressure related to the volume of community antimicrobial use11–15; pediatric antibiotic use is especially influential. Each US child receives, on average, 0.54 to 1.89 antibiotic prescriptions per year,16–18 and young children are a reservoir of resistant pneumococcal infection.1,4,19 Among colonized individuals in close quarters, such as out-of-home child care, upper respiratory tract infection symptoms increase the risk of spreading resistant organisms to other individuals and then to their families.1,20
Acute otitis media (AOM) accounts for 45% to 53% of antibiotics prescribed for US children and up to 62% in some settings.21,22 Children <2 years of age are less likely than older children to experience improvement without antibiotic treatment.23,24 The American Academy of Pediatrics (AAP) AOM guidelines23 were meant to reduce antibiotic use through more selectivity regarding which children are diagnosed as having AOM and which are given antibiotics. The guidelines could reduce community antibiotic use and consequently help slow the development of antimicrobial resistance. The guidelines urge clinicians to instruct parents to weigh the advantages and disadvantages of withholding antibiotics for AOM, "the clinician should share with parents/caregivers the degree of diagnostic certainty and consider their preference. The potential of antibacterial therapy at the initial visit to shorten symptoms ... can be compared with the avoidance of common antibacterial side effects, ... infrequent serious side effects, and the adverse effects of antibacterial resistance."23 Essentially, parents are asked to help choose a preferred strategy for managing AOM, considering all of the outcomes. This study takes a closer look at that decision-making process. Potential costs, or risks, of using fewer antibiotics under the AAP guidelines include extra sick days, hospitalizations for treatment of suppurative complications such as mastoiditis, and monetary costs. Potential benefits include fewer adverse drug events (ADEs) (common mild ADEs and rarer but more-severe ADEs) and a decreased drive for additional resistance. Parents are most likely to consider their own child's or other family members’ decreased probability of a future resistant infection, but altruistic parents also might consider the societal benefits of decreased community-level resistance. For a parent to favor implementing the AAP guidelines, any adverse outcomes resulting from implementation need to be at least offset by the benefits of using fewer antibiotics, including the combined child-, family-, and community-level benefits of decreasing the drive for additional resistance. The objective of this study was to perform a cost-utility analysis by describing AOM outcomes, using a common denominator of quality-adjusted life-days (QALDs), and then estimating the value of avoiding antibiotic resistance with the AAP guidelines, using a parental perspective.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Event Probabilities
AOM outcome probability estimates (Table 1) were based on the results of our decision analysis.25 Outcomes modeled included antibiotic use, mild ADEs, ADE deaths, sick days, mastoiditis hospitalizations, and dollar costs. For example, a child 2 to <6 months of age presenting to a primary care physician with possible AOM, we estimated that implementing the AAP guidelines would predict 12.7% less antibiotic use, compared with a baseline strategy that was less restrictive with antibiotic use. Accordingly, we estimated fewer antibiotic-associated ADEs and greater risks of sick days, mastoiditis, and dollar costs.
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Estimating the benefit of decreasing antibiotic resistance is not straightforward. With reduced antibiotic use, fewer organisms would be killed and there would be decreased selection pressure for additional antibiotic resistance. These factors help determine how resistant organisms spread through the community.12,13,20 These relationships are quite complex, time-dependent, and influenced by many factors not included in our model, such as seasonality, family density, and the pneumococcal conjugate vaccine. The extent and timing of any expected decrease in resistance resulting from reduced antibiotic use are not known. Previous large-scale interventions showed variable success in influencing resistance levels and suggested that periods of
5 years are required for substantial decreases in resistance to be observed.12 Mathematical models suggest that the key parameter determining the rate of resistance decreases is the "fitness cost" of antimicrobial resistance, defined as the difference in transmissibility between an antibiotic-susceptible organism and a non–antibiotic-susceptible organism.12 In other words, pathogens with greater resistance are usually but not always less "catchy," and the relative robustness of these various clones helps determine their dissemination throughout the community. It is not possible to determine directly how parents value, or should value, this complex resistance benefit; however, by considering AOM outcomes with the use of a common denominator, the minimal value at which the benefits of the AAP guidelines would at least balance their costs (which is necessary for successful implementation of the guidelines) can be estimated. In other words, the value of the resistance benefit would be equal to the costs minus the other benefits.
Utility Values
The concept of a quality-adjusted life-year (QALY) provides a common denominator for different illness outcomes, quantifying the value of both the length and quality of life. Although they are sometimes judged to be subjective, QALYs, when used carefully, are not necessarily more subjective than many other assumptions used in research design, and they are at least a starting point in making these values explicit. Results of this study are more easily considered in days rather than years, and AOM outcomes were described by using a common denominator of QALDs (Table 2). Bennett et al26 published parent utilities for pediatric bacteremia outcomes using a standard gamble technique. These were used to define a disutility value for 1 sick day, 1 mild ADE, and 1 mastoiditis hospitalization. Results for parents of febrile and afebrile children were similar, and the combined utility results were used. For the sick day and mild ADE disutilities, the local infection value reported by Bennett et al26 was used, estimating local infection duration at 2 days. The sum of the values for hospitalization and meningitis with complete recovery reported by Bennett et al26 was used for the mastoiditis disutility for base-case analysis. Life tables27 and health-related quality of life,28 discounted at 3% per year, were used to define a disutility value for 1 ADE death in each age group. For dollar costs, base-case analysis used a willingness-to-pay threshold of $100000 per QALY.29 Utilities are experienced during the acute illness year and are not discounted, with the exception of ADE death as described above.
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For sensitivity analyses, the utility for hospitalization reported by Bennett et al26 without the meningitis value was used for the minimal mastoiditis disutility. For sick days, ADEs, and dollar costs, disutility values were varied from a minimum of 50% up to 200% of the values used for base-case analysis.
The incremental probability of each outcome between strategies was then multiplied by the disutility value for each AOM outcome type. In Table 3, each AOM outcome is expressed in terms of a common denominator of QALDs and weighted by its incremental probability of occurrence between strategies. For example, for a 2- to <6-month-old child presenting to a primary care physician with possible AOM, using the AAP guidelines versus the baseline strategy predicted increased sick days valued at 0.0003068 QALDs between strategies.
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RESULTS |
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Subtraction of other benefits from total costs yielded a resulting difference of 0.09814 QALDs for the 2- to <6-month-old group. This implies that, for a 2- to <6-month-old child presenting to a primary care physician with possible AOM, parents would need to value a 12.7% probability of reduced antibiotic use (Table 1) at almost 0.1 QALD or more for the benefits of the AAP guidelines to balance their costs, compared with the baseline strategy (ie, 0.77 QALDs per antibiotic prescription avoided).
Results for the 6- to <24-month-old group were quite similar, with a difference of 0.10420 QALDs. This implies that, for a 6- to <24-month-old child presenting to a primary care physician with possible AOM, parents would need to value a 15.6% probability of reduced antibiotic use (Table 1) at 0.1 QALD for the benefits of the AAP guidelines to balance their costs, compared with the baseline strategy (ie, 0.67 QALDs per antibiotic prescription avoided).
Results were most sensitive to the dollar cost utility. When willingness to pay was varied from $20000 to $200000 per QALY, results ranged from 0.36 to 4.10 QALDs for the 2- to <6-month-old group and from 0.30 to 3.57 QALDs for the 6- to <24-month-old group. The results were not as sensitive to variations in other values throughout a wide range. One-way sensitivity analysis results are shown in Table 4 to 2 decimal points, estimated as the limit of clinical significance. Except for ADE death, variation of outcome terms throughout the extremes of their ranges made essentially no difference in the estimated values of the resistance benefit. For ADE death, a rare but devastating outcome, results varied from 0.71 to 0.80 and from 0.61 to 0.70 for the 2- to <6-month-old and 6- to <24-month-old groups, respectively.
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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The AAP guidelines assume that parents, with the help of their pediatricians, will weigh complex trade-offs for each AOM treatment decision. This study estimated that parents would need to value the benefit of decreased antibiotic resistance resulting from 1 fewer antibiotic prescription using the AAP guidelines at least at
0.3 to 4 QALDs, depending on the age group, for the benefits of the AAP guidelines to at least balance the risks. These results were quite robust to sensitivity analysis throughout a wide range. Because dollar cost was the dominant term in the model and largely depended on missed parent work days,25 these results largely depend on how parent time is valued. Parent time has value, even for nonworking parents,30 and the sensitivity analysis included a wide range of values for parent time. Parents may be more likely to expect antibiotics if they feel pressure to return to work or to return their child to day care, and physicians are more likely to prescribe antibiotics if they perceive that parents expect them.31,32 This study has several limitations. The utilities described by Bennett et al26 that were used in this study have not been validated in other populations. However, the standard gamble technique they used incorporates an element of risk and is considered the standard method for preference assessment.30 Furthermore, the QALY value for simple AOM developed with the time-trade-off method by Prosser et al33 is within the range of values used for this study's sensitivity analysis, which is evidence that the values used here are reasonable. To the extent that the utility values reported by Bennett et al26 might have already included parents’ perceptions of the value of their missed work time, the value of parent missed work time might have been overestimated in at least the base-case analysis; however, the scenario descriptions given to parents in the study by Bennett et al26 did not mention missed work time. Current parental perceptions of the risks and costs of AOM treatment are not known and were not included in this study; these are likely to vary depending on the characteristics of the parents surveyed. This study assumed that the base-case results of our decision analysis apply to all children and that all parents are perfectly aware of these results. The sensitivity analyses of both studies reflect how sensitive these results are to changes in the risk estimates used for analysis. There are many strategies that were not modeled, including intermediate strategies that use only part of the AAP guidelines. The use of different strategies would predict different results. In particular, improving AOM diagnostic specificity, for example through better assessment of middle ear effusion or improved rapid viral diagnostic techniques, would allow withholding of antibiotics from select children with less risk of subsequent adverse consequences. It is also difficult to understand what the concept of a QALD means for a child with a self-limited illness. In the clinical setting, however, we routinely value these trade-offs more informally. Also, parents may not have as great a problem with this, because they may be more likely to consider these results in terms of the dollar costs they represent, such as missed work days; valued at $100000 per QALY, 0.7 to 0.8 QALDs would be equivalent to $192 to $219. The outcomes included do not represent the entirety of any clinical scenario and, with the assumptions made, certainly are not meant to be a definitive answer regarding how parents do value, or should value, this resistance benefit. However, this simple model helps make the benefits and risks explicit, provides a common denominator for outcomes, and considers outcomes within the context of the trade-offs involved.
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CONCLUSIONS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Many children with AOM fare well whether or not they receive antibiotics. It has been suggested that between 7 and 20 children must be treated with antibiotics for 1 child to derive benefit,23 and this study suggests a trade-off of
0.3 to 4 QALDs (7–96 hours) to avoid 1 course of antibiotics. Although this might be a desirable trade-off from a societal perspective, this might not be as desirable from a parental perspective, which could be a barrier to successful implementation of the AAP AOM guidelines. Parent desire for antibiotics can be considered rational within this context if it is driven by the value of parent time. These conclusions are similar to those of a recent Robert Wood Johnson Foundation report, which stated, "The barriers to addressing the problem of antibiotic resistance all involve conflict between the interest of individual decisionmakers and the interest of society as a whole. . . . Demand-side solutions that do not put patients at risk are most feasible now."34 Along this line, other approaches that have the potential to reduce antibiotic use might be more successful, such as wider use of influenza vaccine and improved rapid viral diagnostic techniques.35–37
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ACKNOWLEDGMENTS |
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This project was supported in part by an Agency for Healthcare Research and Quality Centers for Education and Research on Therapeutics Cooperative Agreement (grant HS10399), a Ruth L. Kirchstein National Research Service Award (F32-AI-073015-01A1), and an unrestricted educational grant from Amgen.
I thank David A. Asch, MD, MBA, Henry A. Glick, PhD, Brian L. Strom, MD, MPH, and Sankey V. Williams, MD, for valuable suggestions.
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FOOTNOTES |
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Accepted Aug 29, 2007.
Address correspondence to Sharon B. Meropol, MD, MSCE, University of Pennsylvania School of Medicine, Center for Clinical Epidemiology and Biostatistics, Room 108, Blockley Hall, 423 Guardian Dr, Philadelphia, PA 19104. E-mail: meropols{at}mail.med.upenn.edu
Financial Disclosure: Dr Meropol has served as a consultant for Wyeth Pharmaceuticals.
This work was presented, in part, at the annual meeting of the Pediatric Academic Societies, May 8, 2007, Toronto, Ontario, Canada.
| What's Known on This Subject The 2004 American Academy of Pediatrics otitis media guidelines urge parents to weigh the potential benefits of reduced antibiotic use versus the potential risks; however, the value of decreased antibiotic resistance has not been quantified.
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| What This Study Adds Parents would need to value the resistance benefit of one fewer antibiotic prescription at 0.3 to 4 quality-adjusted life days for the benefits of the AAP Guidelines to balance their risks. Parental desire for antibiotics can be rational within this context.
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PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics
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