OBJECTIVE. The goal was to estimate the population effect of 7-valent pneumococcal conjugate vaccine on rates of acute otitis media-related ambulatory visits and antibiotic prescriptions for <2-year-old children enrolled in private insurance plans.
METHODS. We performed a retrospective analysis of a defined population by using the 1997–2004 MarketScan databases, which included an average of >500000 person-years of observations for children <2 years of age. Trends in rates of International Classification of Diseases, Ninth Revision-coded ambulatory visits and antibiotic prescriptions attributable to acute otitis media were evaluated, and the national direct medical expenditures for these outcomes were estimated.
RESULTS. In a comparison of 2004 with 1997–1999 (baseline period), rates of ambulatory visits and antibiotic prescriptions attributable to acute otitis media decreased from 2173 to 1244 visits per 1000 person-years (42.7% reduction) and from 1244 to 722 prescriptions per 1000 person-years (41.9% reduction), respectively. Total, estimated, national direct medical expenditures for acute otitis media-related ambulatory visits and antibiotic prescriptions for children <2 years of age decreased from an average of $1.41 billion during 1997 to 1999 to $0.95 billion in 2004 (32.3% reduction).
CONCLUSIONS. Acute otitis media-related health care utilization and associated antibiotic prescriptions for privately insured young children decreased more than expected (on the basis of efficacy estimates in prelicensure clinical trials) after the introduction of routine 7-valent pneumococcal conjugate vaccine immunization. Although other factors, such as clinical practice guidelines to reduce antibiotic use, might have contributed to the observed trend, 7-valent pneumococcal conjugate vaccine may play an important role in reducing the burden of acute otitis media, resulting in substantial savings in medical care costs.
- acute otitis media
- Streptococcus pneumoniae
- pneumococcal conjugate vaccine
- immunization program evaluation
- health care utilization
Acute otitis media (AOM) is the most common reason for physician office visits among preschool-aged children in the United States. Before 36 months of age, 83% of children experience ≥1 episode of AOM. Streptococcus pneumoniae is the most common bacterial cause of AOM, accounting for 30% to 50% of episodes. In the United States, before the introduction of 7-valent pneumococcal conjugate vaccine (PCV7), AOM was estimated to account for 24.5 million visits and $2 billion to $5.3 billion in annual costs.1–6 AOM is also the most common reason for antibiotic prescriptions among US children, resulting in an estimated 15 million antibiotic prescriptions annually, and therefore is an important contributor to antibiotic resistance.3,6–8
PCV7 was introduced in the routine childhood immunization schedule in the United States in 2000. The vaccine is recommended by the Advisory Committee on Immunization Practices for all children 2 to 23 months of age and for children 24 to 59 months of age who are at increased risk for pneumococcal disease.9 The National Immunization Survey indicated that uptake of ≥3 doses of PCV7 increased from 41% in 2002 to 83% in 2005 among children 19 to 35 months of age (children born in 1999–2004).10–13 Postlicensure studies showed that the immunization program has substantially reduced the incidence of invasive pneumococcal disease in children (76% decrease in 2005),14–16 as well as that of pneumonia.17,18
Prelicensure clinical trials suggested that, in addition to invasive diseases and pneumonia, PCV7 has the potential to reduce the incidence of AOM. By using a health maintenance organization computerized database, the Northern California Kaiser Permanente trial found that PCV7 recipients had 9% fewer medical visits resulting from otitis media and 7% fewer new episodes of AOM.19,20 These data suggest that widespread PCV7 immunization could have an effect on AOM rates, but few studies have evaluated the population impact of PCV7 on AOM rates21 and none has assessed the economic implications of potential reductions in AOM rates. We evaluated trends in ambulatory visits (emergency department and physician office visits) and antibiotic prescriptions resulting from AOM among enrollees in commercial insurance plans in 1997 to 2004 and used the MarketScan databases22 to estimate the potential effects of PCV7 on AOM-related ambulatory visits and medical care expenditures associated with AOM in children <2 years of age.
Data were obtained from the 1997–2004 MarketScan databases,22 which contain information from ∼40 self-insured employers each year, including large private employers and state governments. Together, these employers offer >100 health insurance plans, and data are available for >500 million claims for employees, retirees, and their dependants. All states except Alaska and Hawaii are included, as is Washington, DC. The 2004 MarketScan databases included data obtained from some health insurance plan contributors, combined with the data from the employer customers. More than 40000 covered children <2 years of age per year are represented. The databases contain patient demographic features, provider characteristics, dates of services for ambulatory and hospital visits, payments, diagnostic codes (International Classification of Diseases, Ninth Revision [ICD-9]), and procedure codes (Current Procedural Terminology, Fourth Edition). Total payments reported in the MarketScan databases represent the actual amounts paid by insurance companies and patients to providers (eg, physicians and hospitals).
The MarketScan enrollment databases contain complete, individual-level, enrollment records for most enrollees (from an average of 73% in 1997–1999 to >99% in 2004). We included all enrollees <2 years of age in the MarketScan enrollment databases in the analyses of ambulatory visits (emergency department and physician office visits) and antibiotic prescriptions per 1000 person-years. Children who were not included in the enrollment databases or did not have prescription drug information were excluded (an average of ∼18% of enrolled children did not have prescription drug information). This study was reviewed by the human subjects coordinator at the Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases and, as an analysis of secondary data without identifiers, was determined not to require institutional review board review.
Rates of Ambulatory Visits and Antibiotic Prescriptions
The study sample included all ambulatory visits and drug records for January 1997 to December 2004. An AOM-related visit was defined as a record in the MarketScan databases with a primary diagnosis (first-listed diagnosis) of one of the following ICD-9 codes: 381.00, 381.01, 381.02, 381.03, 381.04, 381.05, 381.06, 381.4, 382.00, 382.01, 382.02, 382.3, or 382.9. Some of these visits also had Current Procedural Terminology, Fourth Edition-coded tympanostomy and pressure-equalizing tube insertion-related procedures, that is, code 69420 (myringotomy including aspiration and/or eustachian tube inflation), code 69421 (myringotomy including aspiration and/or eustachian tube inflation requiring general anesthesia), code 69433 (tympanostomy requiring insertion of ventilating tube, with local or topical anesthesia), or code 69436 (tympanostomy requiring insertion of ventilating tube, with general anesthesia). AOM-related visits were linked to the drug database by using a 3-day window to estimate the use of antibiotic prescriptions for AOM. The antibiotic classes were (1) aminoglycosides, (2) cephalosporin and related agents, (3) β-lactam antibiotics, (4) erythromycin and macrolide antibiotics, (5) penicillins, (6) tetracyclines, (7) miscellaneous antibiotics, (8) quinolones, not else classified, (9) sulfonamides and combinations, not else classified, and (10) sulfones, not else classified.
Stratified analyses of AOM-related ambulatory visits were conducted according to year, gender, and insurance plan type. We compared AOM-related ambulatory visit rates between managed care and non–managed care insurance plans. Five types of insurance plans were categorized as managed care (exclusive provider organizations, health maintenance organizations, noncapitated point-of-service plans, preferred provider organizations, and capitated or partially capitated point-of-service plans).23 Two types of insurance were categorized as non–managed care (basic/major medical insurance and comprehensive insurance).
We used a generalized linear model to assess changes in AOM-related ambulatory visit rates over time, by using Proc Glimmix in SAS. We used sandwich variance estimators to account for possible multiple visits per patient. The covariates included gender, insurance plan type (managed care versus non–managed care), and 2 interaction terms (gender-year and insurance-year). P values of ≤.05 were considered significant. As the prevaccination baseline, we used data from 1997, 1998, and 1999, to reduce the effects of year-to-year variations in rates.24 We calculated the percentage decreases in ambulatory visits attributable to AOM from the baseline period to 2004. The 95% confidence intervals (CIs) for all of these decreases were computed by using the delta method.25 Analyses were performed with the SAS 9.1 statistical package (SAS Institute, Cary, NC).
To evaluate the possibility of shifts in coding practices for diagnoses, we also assessed the trends in ambulatory visit rates attributable to other acute respiratory infections (excluding pneumonia) during the study period. The ICD-9 codes used for acute respiratory infections and asthma were codes 460 (acute nasopharyngitis), 461 (acute sinusitis), 462 (acute pharyngitis), 463 (acute tonsillitis), 464 (acute laryngitis and tracheitis), 465 (acute upper respiratory infections of multiple or unspecified sites), 466 (acute bronchitis and bronchiolitis), 478.9 (other and unspecified diseases of the upper respiratory tract), 487.1 (influenza with other respiratory manifestations), 487.8 (influenza with other manifestations), 490 (bronchitis, not specified as acute or chronic), 491.21 (obstructive chronic bronchitis with acute exacerbation), and 493 (asthma).
We estimated expenditures for ambulatory visits and antibiotic prescriptions from the total payments to providers. Expenditures were standardized to 2004 US dollars by using the medical Consumer Price Index.26 We calculated mean payments per ambulatory visit and antibiotic prescription. We multiplied the average of 1997 to 1999 and 2004 US Census data27,28 by the observed rates and mean payments from the MarketScan databases to estimate national medical expenditures (ambulatory visits and antibiotic prescriptions only) for AOM in children <2 years of age in the prevaccine years of 1997 to 1999 and in 2004.
The number of covered children <2 years of age who met the inclusion criteria in the MarketScan databases increased from ∼20000 in 1997 to 150000 in 2004 (Table 1), as more companies were included in the MarketScan databases. Throughout the study period, there were slightly more enrolled boys (51%) than girls (49%). The proportion of enrollees covered by managed care plans increased gradually over time (from 67.4% in 1997 to 93.0% in 2004).
AOM-Related Ambulatory Visits
Annual ambulatory visit rates for AOM from 1997 to 2004 are shown in Fig 1. Comparing the rate in 2004 with the average rate for the baseline period (1997–1999), we observed 929 fewer ambulatory visits (95% CI: 917–940 visits) for AOM per 1000 person-years in children <2 years of age, that is, a 42.7% decrease from 2173 visits per 1000 person-years to 1244 visits per 1000 person-years (P < .001) (Table 2). On average, 2.1% of these ambulatory AOM visits were associated with tympanostomy and related procedures; this proportion did not change substantially over time. Annual ambulatory visit rates for other acute respiratory infections also decreased from 1997 to 2004 (Fig 1).
To assess whether reductions in AOM-related ambulatory visits might have been associated with secular trends in health care utilization during the study period, we calculated the proportions of total ambulatory visits that were AOM-related. We hypothesized that major secular trends would likely have affected all ambulatory visits. On average, AOM-related ambulatory visits constituted 15.7% of all annual ambulatory visits made by enrollees in the database during 1997 to 1999, compared with 10.6% in 2004 (a decrease of 32.4%).
Rates of AOM-related ambulatory visits decreased significantly among enrollees in both managed care and non–managed care plans (Fig 2). Among children enrolled in non–managed care plans, the rate of ambulatory visits decreased from an average of 2429 visits per 1000 person-years in the prevaccination years to 1231 visits per 1000 person-years in 2004 (a 49.3% reduction) (Table 2). For children enrolled in managed care plans, the corresponding decrease was from 2032 visits per 1000 person-years to 1244 visits per 1000 person-years (a 38.8% reduction). In 2004, there was no statistically significant difference in AOM visit rates between children enrolled in managed care plans and those enrolled in non–managed care plans.
Statistically significant decreases in the rates of AOM-related ambulatory visits were seen among enrollees of both genders. Among boys, the rate of ambulatory visits decreased from 2310 visits per 1000 person-years in the prevaccination years to 1348 visits per 1000 person-years in 2004 (a 41.6% reduction). For girls, the corresponding decrease was from 2028 visits per 1000 person-years to 1134 visits per 1000 person-years (a 44.1% reduction).
Controlling for the covariates and interaction terms in the multivariate model, the AOM-related ambulatory visit rate decreased significantly over time (P < .0.001). All of the covariates (gender and insurance plan type) and interactions (gender-time and insurance-time) were significant in the model. One of the significant interactions, the insurance-time interaction, suggested that the decreases among children enrolled in non–managed care plans occurred earlier than the decreases among children enrolled in managed care plans.
Annual rates of antibiotic prescriptions for AOM from 1997 to 2004 are shown in Fig 1. On average, 58% of AOM-related ambulatory visits resulted in antibiotic prescriptions during the study period. Comparing rates in 2004 with those in the baseline period (1997–1999), we observed 522 fewer antibiotic prescriptions (95% CI: 513–530 prescriptions) for AOM per 1000 children <2 years of age, a 41.9% decrease from 1244 prescriptions per 1000 children to 722 prescriptions per 1000 children (P < .001). Rates of AOM-related antibiotic prescriptions decreased significantly among enrollees in both managed care and non–managed care plans (Fig 2).
We calculated the proportion of total antibiotic prescriptions that were AOM-related. AOM-related antibiotic prescriptions constituted an average of 52.3% of all annual antibiotic prescriptions for children <2 years of age enrolled in the database during 1997 to 1999, compared with 42.2% in 2004 (a decrease of 19.2%). In 2004, the most commonly prescribed antibiotic categories for AOM were penicillins (66.3%), cephalosporins (20.8%), erythromycin and macrolides (11.0%), and sulfonamides and combinations (1.7%); in 1997, the categories were penicillins (49.3%), cephalosporins (21.8%), erythromycin and macrolides (14.9%), sulfonamides and combinations (11.2%), and β-lactam antibiotics (2.8%).
Medical Expenditures Associated with AOM
The mean payment per AOM-related ambulatory visit during the prevaccination years was $70.88 (95% CI: $69.63–$72.13). The corresponding value for 2004 was $77.97 (95% CI: $77.26–$78.68), a significant change (P < .001, t test). The mean total payment for AOM-related antibiotic prescriptions during the prevaccination years was $26.30 (95% CI: $26.16–$26.45), and the corresponding value for 2004 was $28.33 (95% CI: $28.20–$28.47; P < .001). When the MarketScan AOM data were projected to the whole US population by using 1997 to 1999 and 2004 census data, the estimated annual national medical expenditures for ambulatory visits and antibiotic prescriptions attributable to AOM in children <2 years of age decreased from an average of $1.41 billion during 1997 to 1999 to $0.95 billion in 2004 (a 32.3% decrease).
We conducted a comprehensive evaluation of AOM-related health care utilization by young children, including trends in ambulatory visits, antibiotic prescriptions, and related expenditures, over a period that spanned the introduction and maturation of the pneumococcal conjugate vaccination program in the United States. We found that, in a privately insured population, rates of ambulatory visits, antibiotic prescriptions, and resulting medical expenditures for AOM had decreased markedly by 2004, compared with prevaccination years. These results add to the growing evidence base of benefits of PCV7 vaccination and suggest that the vaccine may have contributed substantially to reducing the burden of AOM and associated medical costs.
AOM is a significant cause of outpatient visits and antibiotic prescriptions for children, and estimations of the burden of vaccine-preventable AOM and other pneumococcal disease-related syndromes have important implications for immunization policy. Although several studies have documented reductions in the rates of invasive pneumococcal disease (including drug-resistant infections) with routine PCV7 use,14,15,16 population-level data on the immunization program's effect on AOM are currently limited.22 We found that, between 1997 to 1999 and 2004, rates of ambulatory visits and antibiotic prescriptions attributable to AOM decreased by 43% and 42%, respectively. Although other factors, such as clinical practice guidelines to reduce inappropriate antibiotic use, also might have contributed to the observed trend, this finding is consistent with studies that suggested that S pneumoniae was a major contributor to the burden of AOM-related ambulatory visits and antibiotic prescriptions in children <2 years of age.1 The observed decrease in AOM rates after the introduction of PCV7 was gradual and consistent with increasing vaccination coverage during the study period.10–13
The decreases in rates of AOM-related visits observed in our study exceeded vaccine efficacy estimates (6%–9%) reported in prelicensure clinical trials19,20 but were consistent with results of other postmarketing national database studies evaluating the population impact of the PCV7 program. A national study showed that, already by 2002 to 2003, rates of otitis media-related outpatient medical care visits by children <2 years of age had decreased by 20%, compared with rates before PCV7 introduction.21 A clinic-based study found a ∼35% reduction in S pneumoniae isolates among bacterial isolates causing AOM, which suggests that the microbiologic features of AOM also might have changed since PCV7 introduction.29 It is possible that the herd effects that have been demonstrated for invasive pneumococcal disease and pneumonia17 extend to other noninvasive pneumococcus-related diseases and benefit unvaccinated and partially vaccinated children through reduced carriage and transmission of vaccine serotypes.30 By preventing the first episode of AOM, PCV7 may protect children against later susceptibility to frequent otitis media, complications, and ambulatory visits.31,32 Several other factors, however, also might have influenced the observed reductions in visits. First, although we were unable to measure it in our study, uptake of PCV7 in this privately insured population might have been higher than in the general population.33 Second, the trend of decreasing antibiotic use for children in the past decade may be continuing.6,7,34 Third, the definition of AOM we used (AOM-related visits) was based on ICD-9-coded diagnoses of AOM and was different from case definitions used in clinical trials (episodes of AOM).19,35
It is also possible that awareness of PCV7 vaccination status might have had an indirect effect on physician practices of diagnosing and coding AOM and other acute respiratory infections in vaccinated children. However, we found no compensatory increase in visit rates for non–AOM-related acute respiratory infections during the decrease in AOM visits, making it unlikely that a shift in diagnostic and coding practices would explain the observed decrease. The impact of educational efforts to promote judicious antibiotic prescribing is another important, potential, contributing factor.6 However, rates of antibiotic prescriptions for non-AOM visits did not change during the study period, which suggests that changes in practice patterns of prescribing antibiotics might not explain the observed decreases in AOM visits and related antibiotic prescriptions. Finally, because the largest absolute reductions in rates of AOM visits and prescriptions in the MarketScan databases had occurred already by 2002, it is unlikely that the 2004 American Academy of Pediatrics clinical practice guideline3 to consider deferring antibiotic treatment for some children with AOM had an effect on the trends observed in our study.
Pneumococcal illnesses are associated with considerable economic burden in the United States and in other countries. One US study estimated that diseases associated with streptococcus pneumoniae caused $2.5 billion in direct medical costs and $3 billion in work-loss and productivity costs for each US birth cohort.36 Our data suggested that, compared with the prevaccination period, direct medical costs for AOM were reduced by an estimated $460 million annually. Approximately one fifth of direct AOM-related health care expenditures were attributable to antibiotic prescriptions. Our findings of benefits exceeded those of a prevaccine study that projected that implementation of pneumococcal conjugate vaccination in infants and young children could reduce annual direct medical costs of pneumococcus-associated diseases by $342 million.36 Because our analysis of the costs of AOM included complete outpatient visit and antibiotic prescription data for the patients with a diagnosis of AOM from the same data set, the estimates for direct medical costs attributable to these outcomes are likely to be reasonable and can be used to update cost-effectiveness studies for PCV7. The total net savings from the PCV7 program could be even greater if indirect costs such as costs of parents' loss of work time because of the child's illness were included. In our study, the overall prevaccine rates of AOM visits were similar to those reported in clinical studies20 and, as expected, were severalfold higher than the incidence of invasive pneumococcal disease (1.88 and 0.34 invasive cases per 1000 persons in <2-year-old children for the prevaccination period and 2004,37 respectively). If our findings are confirmed by other studies, then use of PCV7 to prevent pneumococcal disease is likely to be more cost-effective (or even cost-beneficial) than estimated previously.38,39
Several limitations to our analysis should be considered. Our estimates are based on data for privately insured persons, predominantly in managed-care health plans. Nationally, although most of the population is privately insured, utilization and medical expenditures per case of AOM may be greater for persons with Medicaid or without insurance,40 which makes these estimates conservative. However, because the proportion of the US population with private insurance did not change during the study period,41 any bias in our analysis is likely to have been consistent over time, and our estimates should reflect the degree of reduction in AOM-related health care utilization and expenditures among persons with employee-sponsored health insurance, predominantly in a managed care setting.
Our study might have missed some AOM-related health care utilization because of incompleteness of the databases, incomplete coding, or multiple insurance plans for some enrollees. In general, these later instances likely would be rare. Another limitation is that the MarketScan population almost tripled during our study period and trends for AOM-related outcomes could be affected by secular changes in the MarketScan population or in insurance or associated utilization patterns. However, the proportion of total ambulatory visits that were AOM-related among all MarketScan enrollees decreased by 32.4%, without a compensatory increase in other acute respiratory infection-related visits.42 Therefore, this analysis should control at least partially for potential changes in practice standards for ambulatory visits that might have occurred over time.
The multivariate model results also suggested that the decreases were unlikely to be artifacts of secular changes in insurance coverage. Decreases in ambulatory visits occurred among both managed care and non–managed care insurance plans, although earlier in non–managed care plans. In addition, although managed care organizations became more widespread during the course of the study, our finding that the AOM reduction was greater in non–managed care plans would have biased our results to be conservative. Additional study is needed to understand why changes for non–managed care plans were larger than those for managed care plans.
MarketScan obtains its data from employer-based insurance plans, particularly from larger employers. The study population is therefore somewhat homogeneous (eg, all of these children had private insurance). Nonetheless, the MarketScan population is large, draws from numerous medical settings, and represents a wide variety of geographic, social, and economic strata; the data complement and enhance available surveillance data.14,43 In conclusion, our data suggest that AOM-related health care utilization in children <2 years of age has been markedly reduced since the introduction of PCV7, highlighting the health and economic benefits of PCV7 vaccination in young children in the United States.
We thank Mark Messonnier, PhD, Pascale Wortley, MD, Cynthia Whitney, MD, and Trudy Murphy, MD, for their comments on the manuscript.
- Accepted July 23, 2007.
- Address correspondence to Fangjun Zhou, PhD, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mail Stop E-52, Atlanta, GA 30333. E-mail:
The authors have indicated they have no financial relationships relevant to this article to disclose.
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