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Haemophilus influenzae Infections

PEDIATRICS Vol. 110 No. 4 October 2002, pp. 653-661

Impact of Universal Haemophilus influenzae Type b Vaccination Starting at 2 Months of Age in the United States: An Economic Analysis

Fangjun Zhou, PhD, Kristine M. Bisgard, DVM, MPH, Hussain R. Yusuf, MBBS, MPH, Robert R. Deuson, PhD1, Sue K. Bath, MS, MPH and Trudy V. Murphy, MD

From the National Immunization Program, Centers for Disease Control and Prevention, Public Health Service, US Department of Health and Human Services, Atlanta, Georgia

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   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Objective. To evaluate the economic impact of universal Haemophilus influenzae type b (Hib) vaccination starting at 2 months of age.

Methods. Decision-tree-based analysis was conducted of a hypothetical US birth cohort of 3 815 469 infants using population-based vaccination coverage and disease incidence data. All costs were estimated from both the direct cost (medical and nonmedical) and societal perspectives. Net present value, cost-effectiveness ratios, and benefit-cost ratios of the US Hib vaccination program were evaluated.

Results. The results of these analyses showed that the universal vaccination program using the Hib conjugate vaccines in the United States in 2000 was cost-saving from both the direct and societal perspectives, with the benefit of the Hib vaccination program (net present value) from the direct cost and societal perspectives of $0.95 billion and $2.09 billion, respectively. Without a Hib vaccination program, the direct and societal costs of Hib invasive cases would be $1.35 billion and $2.58 billion, respectively. The direct and societal costs of the Hib vaccination program were estimated at $0.39 billion and $0.48 billion, respectively. The direct and societal benefit-cost ratios for the Hib vaccination program were 3.4 and 5.4, respectively. Varying the proportion of vaccines purchased and administered in the public versus the private sector and the proportion of combination vaccine versus monovalent vaccine administered did not have much effect on the results.

Conclusions. Regardless of the perspective (direct cost or societal) and the assumptions used, the benefit-cost ratios of the US vaccination program are >1.0. Potential changes in the program, including use of more or less Hib combination vaccines, would not significantly alter the benefit-cost ratio. The national Hib vaccination program is highly cost beneficial and results in substantial cost savings.

Key Words: Haemophilus influenzae type b • vaccine • cost-effectiveness analysis • benefit-cost analysis

Abbreviations: Hib, Haemophilus influenzae type b • NIS, National Immunization Survey • NPV, net present value • CE, cost-effectiveness • ABCs, Active Bacterial Core Surveillance • CDC, Centers for Disease Control and Prevention • DTaP, diphtheria and tetanus toxoids and acellular pertussis vaccine • HepB, hepatitis B vaccine • QALY, quality-adjusted life-year


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Before the introduction of effective vaccines, Haemophilus influenzae type b (Hib) was the leading cause of meningitis among children younger than 5 years in the United States. Each year, approximately 20 000 cases of Hib invasive disease occurred, including 12 000 cases of meningitis. Most Hib invasive disease occurred among children younger than 12 months.1–9 In 1985, a Hib polysaccharide vaccine was licensed; in 1987, the first Hib conjugate vaccine was licensed. These 2 vaccines were initially recommended for use among US children older than 18 months. In late 1990, the first of 3 formulations of Hib conjugate vaccines was approved for use in infants, and Hib conjugate vaccine was recommended for all infants starting at 2 months of age.10 Subsequently, 2 additional Hib conjugate vaccines were licensed for infants. Since 1993, high Hib vaccination coverage rates have been achieved among US infants (>90% for 3 doses by 2 years of age), and the incidence of Hib invasive disease has declined by >95%.11,12

Economic analyses of the polysaccharide vaccine and the first conjugate vaccine conducted close to the time of licensure projected that universal Hib vaccination of US children older than 18 months would be both cost-effective and cost-beneficial.2,13,14 The strategy for vaccination of infants starting at 2 months of age with the Hib conjugate vaccines also was expected to be economically advantageous, but its economic impact had not been formally assessed. Since the initial economic analysis, several other changes that could affect the results of economic analysis have occurred. Health care costs for treating the complications of Hib invasive disease have increased substantially during the past 2 decades, and the private sector now delivers a greater proportion of Hib vaccines. From 1990 to 2000, the price of Hib vaccine increased from $4.80 per dose to more than $6 per dose, primarily from the addition of the federal excise tax for vaccine-related injury compensation. Previous analyses did not include rifampin prophylaxis for those exposed to Hib cases or the treatment of adverse effects of vaccination.

Economic analysis addressing current costs and vaccination schedules is useful for making future policy decisions regarding Hib vaccination, including, for example, an anticipated increased use of combination vaccines that contain a Hib component. In addition, it is useful for countries considering adding a Hib conjugate vaccination program to perform an economic analysis. We used a decision analysis model using surveillance- and population-based data to determine whether the current Hib vaccination program is cost-effective and cost-beneficial compared with the absence of vaccination.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Decision Analysis Model
We developed a decision tree as the basis for our model (Fig 1). The effect of the Hib vaccination program on a hypothetical US birth cohort of 3 815 469 children (the estimated number of births in 2000 [www.census.gov/population/estimates/nation/e90s/e0001rmp.txt]) was evaluated from birth through 5 years of age. Depending on the vaccine formulation, 3 or 4 doses of Hib conjugate vaccine are recommended (ages 2, 4, and 12–15 months or 2, 4, 6, and 12–18 months).10 Our analysis estimated the total doses of Hib vaccine administered across all formulations using vaccination coverage level data from the National Immunization Survey (NIS). The NIS is a quarterly survey conducted nationwide among children aged 19 to 35 months.15 We calculated a net present value (NPV), cost-effectiveness (CE), and benefit-cost ratios. The analyses were performed from both direct cost (direct medical plus direct nonmedical costs) and societal (direct plus indirect costs) perspectives. All costs were inflated to year 2000 dollars, and all costs and benefits in the future were discounted at a 3% annual rate for the base case analysis.16



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  		Fig 1. Hib vaccination decision tree.

 
Estimating the Burden of Hib Disease Without Vaccination
The age-specific incidence rate (Table 1) of Hib invasive disease in the United States in the prevaccine era was obtained from the literature.1–9,17 Hib invasive disease was defined to include meningitis, epiglottitis, bacteremia, pneumonia, cellulitis, arthritis, and other invasive disease with isolation of Hib (eg, peritonitis). In the base case analysis, the case-fatality ratio was estimated at 3.78% for Hib invasive disease.2 Possible long-term consequences for children with meningitis in our model included mental retardation, severe hearing loss, epilepsy, and spasticity/hemiplegia; the probabilities of these outcomes were 6.1%, 6.7%, 6.1%, and 5.1%, respectively.18 The incidence and fatality ratios were applied to the entire birth cohort to derive the expected number of cases that would occur in the absence of a Hib vaccination program.


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  		TABLE 1. Average Estimated Age-Specific Incidence (Per 100 000) of Hib Invasive Disease Among Children Aged <5 Years, in the Prevaccine Era (1976–1984)1–9,17 and Vaccination Era (1995–1999)*

 
Estimating the Burden of Hib Invasive Disease With Vaccination
To determine the age-specific number of Hib cases occurring in the presence of a Hib vaccination program, we used the average of the age-specific annual number of reported Hib cases between 1995 and 1999 in the United States (Table 1). Hib invasive disease is defined as illness clinically compatible with invasive disease such as meningitis or sepsis, and isolation of the Hib from a normally sterile body fluid or tissue. Because the Hib conjugate vaccine provides some herd immunity (ie, provides some protection against Hib invasive disease to unvaccinated individuals), the herd immunity effect is taken into account by using national incidence data. Hib invasive disease has been nationally reportable since 1991.11,12,19 Three sources of surveillance data were used to determine the number of reported Hib cases: the National Notifiable Diseases Surveillance System, the National Bacterial Meningitis and Bacteremia Reporting System, and the Active Bacterial Core Surveillance (ABCs). These surveillance systems have been described in detail elsewhere.11,12,19,20 Hib cases identified by the ABCs (active, laboratory-based surveillance) system were reported to the Centers for Disease Control and Prevention (CDC) through the ABCs; and Haemophilus influenzae isolates were reserotyped at the CDC. Cases identified by the ABCs were also reported to state health departments. State health agencies and the District of Columbia provide weekly reports of provisional cases of Hib invasive disease to the CDC through the National Notifiable Diseases Surveillance System.

Costs Associated With Disease
Direct Costs
Direct health care costs include those associated with the treatment, complications, and sequelae of Hib invasive disease. Both outpatient and inpatient costs were included in the analysis. The frequency and cost of outpatient visits, average duration of hospital stay, and hospitalization costs for each Hib-related condition (Table 2) were obtained from Marketscan database21 and published studies.22 Marketscan is a large national insurance payment database that includes data from >200 payers and >4 million people. It includes inpatient and outpatient health care services, drug claims, and physician costs, as well as costs for supplies, laboratory tests, and other materials and procedures. All medical cost estimates for acute care were derived from the Marketscan database and were the 5-year (1993–1997) average costs for patients who were younger than 5 years.


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  		TABLE 2. Probabilities and Assumptions for Acute Care of Hib Invasive Disease Case-Patients and Sequelae Among Patients With Meningitis18,19

 
At least 7 drugs are acceptable for initial therapy for suspected Hib invasive disease, or to complete therapy for proven disease: cefuroxime, cefotaxime, ceftriaxone, chloramphenicol, ampicillin, vancomycin, and dexamethasone.23 It is recommended that patients with Hib invasive disease receive rifampin prophylaxis for 4 days after the therapy if ampicillin or choramphenicol was used for treatment.24 The medication costs were derived from a survey of children’s medical centers, and the price of each medication was the cost that a self-pay patient would be charged (CDC, unpublished data, 2001). Although some practitioners may administer different drugs, we used a commonly accepted guideline23 to determine the duration and frequency of the typical treatment regimens and the average costs of medications using the price derived from our survey. The average medication costs were estimated to be $2574 for meningitis, $808 for epiglottitis, $1250 for bacteremia, $1197 for pneumonia, $1077 for cellulitis, $1397 for arthritis, and $1060 for all other type of Hib invasive diseases.

Other direct costs included 1) institutional care for mental retardation, 2) special schooling for deafness and mental retardation, and 3) long-term care for epilepsy and hemiplegia. We assumed that the annual cost of epilepsy and hemiplegia was $1693 and that the average lifespan was 50 years for such individuals25; the annual special education cost for severely disabled children until 18 years of age was $16 26226; and the annual cost for the long-term care of individuals with mental retardation during a 50-year lifespan was $78 448.27

Indirect Costs
Our model estimated the economic value of life lost prematurely, indirect costs from permanent disability such as deafness and mental retardation, and indirect costs associated with parents who missed work and stayed at home to care for sick children. To estimate the economic value of life, we used the human capital approach, which assumes that the value to society of an individual’s life is measured by his or her future production potential. It equates the value of life to the present discounted value of lost earnings. This method ignores any other dimensions of illness and death. Average wages for men and women were used to estimate productivity losses and the economic value of life as a result of premature mortality. We also assigned a value to unpaid labor, such as caring for one’s children and home. These data were taken from published reports,28 the Bureau of Labor Statistics,29 and the Bureau of the Census.30

Prophylaxis Intervention
Household contacts of Hib cases in children who are younger than 4 years and unimmunized or incompletely immunized are at increased risk for Hib invasive disease after a case.24 Child care contacts who are younger than 2 years and unimmunized or incompletely immunized are at lesser but still increased risk for Hib invasive disease.24 Rifampin prophylaxis has been recommended for household contacts in households where at-risk infants or children reside. Rifampin prophylaxis has been recommended for all child care classroom contacts and their supervisory personnel when underimmunized children are in the classroom where 2 or more Hib cases have occurred within 60 days. Rifampin dosage is once a day for 4 days (in a dose of 20 mg/kg; maximum dose, 600 mg).24

In the model, we assumed that 39% of Hib case-patients attended child care facilities (CDC, unpublished data, 1999). On the basis of published data,31,32 we assumed an average of 14 child care contacts (6 children for family child care home, 12 children for group child care home, 18 children of a classroom for child care centers, and an average of 2 caregivers [Division of Child Care Licensing, Bureau of Regulatory Services, Michigan State Government]) and 5.4 household contacts per case. The retail medication cost for rifampin prophylaxis per contact was assumed to be $14.89 (4 days, retail price at 1 pharmacy, 2000). We assumed that the rifampin administration cost per household was $61 (1 physician visit) and per child care facility was $672 (4 days of work by a public health nurse whose hourly salary, including fringe and indirect costs, was estimated to be $21 in 2000).

Costs Associated With Vaccination
Hib vaccines are administered by both public- and private-sector providers. Several formulations of Hib vaccine are available in the US market, including combination vaccines that contain other antigens, eg, diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP)-Hib and hepatitis B vaccine (HepB)-Hib. The distributions of publicly purchased versus privately purchased vaccine and the distribution by vaccine formulations were derived from the CDC VACMAN database33 and from voluntary manufacturers’ reports to the CDC (CDC, unpublished data, 2000). VACMAN is a database management system used by 59 state, city, and territorial government immunization programs. The programs use VACMAN to order and optionally to track and record information relating to publicly funded (Vaccines for Children, 317 Grant, and state/other) vaccines. We assumed that the average total cost to distribute (transport from the manufacturer to the site where administered) a dose of public vaccine was $0.68.34 No extra distribution cost was associated with privately purchased vaccine. We assumed that the overall rate of vaccine wastage (public and private sectors) was 21.5%.35

The federal excise tax that supports the National Vaccine Injury Compensation Program was included in all vaccine prices ($0.75 for each Hib vaccine administered, $3.00 for DTaP-Hib, and $1.50 for HepB-Hib). The price for a Hib combination vaccine is higher than the sum of the prices for the separate vaccines. Therefore, we calculated the price of Hib in combination vaccines as a proportion based on the individual vaccine prices. For example, if Manufacturer A’s vaccine prices for DTaP, Hib, and DTaP-Hib were $9.25, $5.20, and $22.01, respectively, then we calculated the Hib price in DTaP-Hib as follows: $7.92 = (22.01 x [5.20/(9.25 + 5.20)]).

Vaccination coverage rates by age and number of doses administered were estimated for children in the cohort at 1 year of age and at 2 years of age, using data from the 2000 NIS. By 19 to 35 months of age, 93% of children had received >=3 doses of Hib-containing vaccines.15

Most vaccines for children are administered by private-sector providers. NIS data indicated that approximately 66% of surveyed children obtained their vaccines from private health care providers, 22% from public health clinics, 10% from hospital-based clinics, and 2% from other clinics (CDC, unpublished data, 2000). The administrative cost for vaccination during a visit to a public clinic was estimated at $5 (CDC, Houston mobile clinic study, unpublished data, 2000). In the private sector, the estimated administration cost was $15.09 (in 1995 dollars) in our model.36 Other costs of vaccination include the caregiver’s travel to the clinic at $3.50 (2 bus tickets in Atlanta for a round trip), and 2 hours of time off work to take the child for vaccination. We assumed that 85%37 of the caregivers were female and that the average wage for these caregivers was $8.25 per hour. We counted one third of the indirect caregiver costs in the base case analysis because Hib vaccine was almost always given simultaneously with DTaP and inactivated poliovirus vaccines in the first year of life and with DTaP; measles, mumps, and rubella; and varicella vaccines in the second year of life.

Vaccine-Associated Adverse Events
Hib vaccines have been found to be generally well tolerated.38,39 Reported rates of local reactions to Hib vaccines, such as pain, tenderness, swelling, and erythema at the site of injection, vary, but these symptoms typically are mild and last <24 hours.24 Temperature of 39°C (102.2°F) or higher has been reported in <2% of Hib vaccine recipients.38 We conservatively estimated that 2% of children who receive vaccinees will develop fever, and the children who experience fever will be treated with an antipyretic (eg, acetaminophen). Diagnostic tests for a 2-month-old child with fever (the recommended age of first vaccination) could be costly. However, we assumed that like DTaP, the expected characteristic fever would obviate the need for extensive laboratory tests and there would be no additional outpatient visit. We included indirect costs and assumed that caregivers would lose 1 day of work for each case of fever.

Quality-Adjusted Life-Years
The effect of Hib invasive disease on life expectancy and quality of life vary depending on the outcome of the disease. Quality-adjusted life-years (QALYs) can be estimated as a single outcome that accounts for morbidity and disability. The health utility index is a value assigned to quality of life. One life-year in optimal health is assigned a value of 1. Death is given a value of 0. The value of a year in less-than-perfect health is given a value between 0 and 1. We assume that the health utility indices are 0.840 for hemiplegia, epilepsy, and mental retardation and 0.977 for severe hearing loss.40 We also assumed that acute Hib infections without sequelae have only a transitory effect on patients’ quality of life.

NPV, Benefit-Cost, and CE Analyses
NPV is the most widely used technique in economic analysis to determine the return on any investment and, in this case, is the sum of the discounted benefits from the Hib vaccination program minus the sum of the discounted costs. NPV can be written as follows:

where Bt and Ct are the benefits and costs, respectively, T is the life expectancy, and r is the discount rate. Using a discount rate provides a method of adjusting the value of receiving benefits today versus receiving benefits in the future or of incurring costs in the present versus incurring costs in the future.

Three types of CE ratios were calculated: cost per case averted, cost per year of life saved, and cost per QALY gained. The CE ratio can be calculated as follows:

The costs in the numerator are limited to the costs associated with vaccination. Therefore, these CE ratios for this study give a measure of the vaccination cost associated with preventing each case of Hib infection or with each year of life saved. Some vaccination programs are funded separately from medical services in the United States. The decision maker in charge of vaccinations cannot benefit from calculated savings in health care costs that are attributable to fewer infections. At the different levels, there are many competing demands for dollars spent on health and these CE ratios will help decision makers to justify their expenditures. However, if we included the disease costs averted in the CE equation, the CE ratio (called average CE ratio) can also be calculated as follows:

On the basis of recommendations developed by the Panel on Cost-Effectiveness in Health and Medicine,16 to avoid double-counting benefits, we did not include productivity losses as a result of death in calculating dollar per (discounted) year of life saved.

Benefit-cost analysis provides outcome measures of cost per unit of health outcome by placing a dollar value on the health outcomes. In this analysis, the benefit-cost ratio is equal to the costs averted with the vaccination program divided by the vaccine program costs. It can be calculated as follows:

Sensitivity Analyses
Univariate sensitivity analyses were performed to assess the effect of varying 1) the proportion of vaccines purchased and administered in the public versus the private sector, 2) the administration cost, 3) the wastage rate, 4) the discount rate, 5) the Hib incidence rate, and 6) the proportion of combination vaccine versus monovalent vaccine administered.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Base Case
Without a Hib vaccination program, the model estimated that 17 589 Hib invasive disease cases and 665 deaths would occur among a cohort of 3 815 469 children. From the direct cost perspective, these cases would result in costs of $1.35 billion, including a cost of $7.6 million for rifampin prophylaxis used for household contacts and child care contacts. From the societal perspective, these cases would result in costs of $2.58 billion (Table 3). In the presence of a national Hib vaccination program, the number of Hib cases and deaths is reduced by 99.7% and 99.6%, respectively. The Hib vaccination program results in 97 878 years of life saved, 27 301 discounted years of life saved, and 113 644 QALYs gained. The direct and societal costs of the Hib vaccination program were estimated at $0.39 billion and $0.48 billion, respectively. The calculated NPVs (net savings) of the Hib vaccination program, from direct cost and societal perspectives, were $0.95 billion and $2.09 billion, respectively. From the societal perspective, we estimated that the Hib vaccination program spends $28 073 to prevent 1 Hib case, $743 209 to prevent 1 Hib-related death, $4903 to save 1 life-year, $17 577 to save 1 discounted life-year, and $4223 to gain 1 QALY (Table 4). From direct cost perspective, it would save $55 598 to prevent 1 Hib case, $1 471 888 to prevent 1 Hib-related death, $9710 to save 1 life-year, $34 811 to save 1 discounted life year, and $8363 to gain 1 QALY (Table 4). The direct and societal benefit-cost ratios for the Hib vaccination program were 3.4 (1.34 billion/0.39 billion) and 5.4 (2.57 billion/0.48 billion), respectively.


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  		TABLE 3. Summary of All Hib Disease and Vaccination Costs*

 

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  		TABLE 4. CE Ratios (Program Cost/Outcome and Average Cost [Savings]/Outcome)

 
Sensitivity Analyses
If 90% of the publicly purchased vaccines were administered by private providers, then the total vaccination program costs would increase to $507.1 million and the direct and societal benefit-cost ratios would decrease to 3.2 and 5.1, respectively (Table 5). If 80% of all Hib-related vaccines were purchased by the private sector, then the related direct and societal benefit-cost ratios would be 2.9 and 4.6, respectively. If the administration costs in the public and private sectors were doubled, then the related direct and societal benefit-cost ratios would be 2.4 and 3.9, respectively. With a lower or higher wastage rate, the benefit-cost ratios change only slightly (Table 5). With higher discount rates (eg, 5%, 8%), the benefit-cost ratios decrease significantly (Table 5).


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  		TABLE 5. Benefit-Cost Ratios: Univariate Sensitivity Analysis

 
Our base case analysis assumed that the estimates of the incidence of Hib invasive disease were accurate for US children during pre- and postvaccination eras. However, it is possible that these figures underestimate or overestimate the true incidence. To evaluate the extent to which underestimation of Hib incidence in the postvaccination era potentially could have had an impact on our analysis, we ran our model using a postvaccination Hib incidence rate that was 200% of the rate in the base case analysis. The direct and societal benefit-cost ratios did not change significantly (Table 5). To evaluate the potential impact of over- or underestimates of the prevaccination-era Hib incidence rate, we varied the incidence estimates from 50% to 200% of the base case assumptions. The direct and societal benefit-cost ratios of Hib vaccination program varied from 1.7 (50%) to 6.9 (200%) and from 2.7 (50%) to 10.7 (200%), respectively, indicating that the results were very sensitive to variation in the incidence of Hib disease without a national vaccination program (Table 1).

If only single-antigen Hib vaccines were used in the Hib immunization program, then the direct and societal benefit-cost ratios would be 3.2 and 5.0, respectively. As the number of routinely recommended vaccines has increased, infants now receive as many as 4 or 5 simultaneous injections at the 2-month clinic visit. If all Hib doses were administered in the form of combination vaccines, then the number of simultaneous injections at each visit would be decreased.41 The additional benefits of this reduction were not considered in our model. If all Hib vaccines were administered in combination vaccines, then the direct and societal benefit-cost ratios would be 4.7 and 7.5, respectively.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Soon after the publication of recommendations for universal Hib vaccination of children starting at 2 months of age, high coverage levels (>90% by 2 years of age in 1995) were achieved among US children. The dramatic reduction in the incidence of Hib invasive disease and decrease in pain and suffering to family and friends of the ill patient are a direct result of this achievement.11,12,19,42,43 Our study shows that the current Hib vaccination program is highly cost beneficial and results in substantial cost savings. Regardless of the perspective taken (direct cost or societal) or how the assumptions were varied, the benefit-cost ratios of the vaccination program (which measure the return for every dollar invested) were always >1.0. Our findings quantify the economic gains resulting from the current Hib vaccination program and add to the compelling case for maintaining the high vaccination coverage levels achieved among infants and young children.

A published review of nearly 500 life-saving interventions in the United States reported that median net cost (cost expended minus cost averted) per life-year saved for medical interventions was $19 000.44 Another recent report suggested $50 000 as an acceptable threshold value for life-year saved.45 Because the Hib vaccination program in the United States results in a significant net savings (NPV >$0.9 billion and >$2.0 billion from the direct cost and societal perspectives, respectively), it therefore compares very favorably with other medical interventions. In addition, the program cost per QALY gained was very low ($4223).

Sensitivity analysis is a useful instrument to assess the robustness of economic estimates. In this study, results were not strongly affected by most factors. Benefit-cost and CE ratios were found to be most sensitive to the discount rate. However, even at a high discount rate of 8%, the benefit-cost ratio was above 1. The benefit-cost ratios were also sensitive to lower base case incidence rate estimates. Even in the unlikely scenario that we substantially underestimated prevaccination era incidence rates (50% of base case incidence rate), our analysis yielded a favorable benefit-cost ratio (>1). In addition, our results remained stable over a wide range of wastage rate estimates.

Compared with the public sector, costs are higher with privately purchased and administered Hib vaccine. Our results confirm that the direct and societal benefit-cost ratios of the Hib vaccination program remain favorable (>1) with a greater role of the private sector in vaccine delivery. In recent years, there has been a shift in the delivery of childhood vaccines from the public sector to the private sector because of programs to reduce out-of-pocket costs for immunizations, such as the Vaccines for Children Program and State Child Health Insurance Program.46–48 Optimally, a greater role could be taken by the private sector in the purchase of vaccines. Insurance reform to improve vaccination coverage rates in children (eg, first dollar laws) and the increasing delivery of vaccines by managed care organizations is expected to increase the role of the private sector.49 In our sensitivity analysis, increasing the proportion of vaccines delivered or purchased by private providers did not substantially change the CE and benefit-cost ratios.

Our analysis found universal Hib vaccination to be cost-saving on the basis of the current proportional uptake of the various formulations of Hib vaccine available in the US market. We also assessed the potential impacts of using more or fewer Hib-containing combination vaccines. As an increasing number of vaccines are recommended for universal childhood administration, there will be greater pressure for use of combination vaccines, including Hib-containing combination vaccines. A recent study in the United States assessed the relative CE (direct costs only) of administering the combination HepB-Hib vaccine to all infants compared with using a monovalent HepB vaccine and monovalent Hib vaccine.45 The investigators reported that use of the combination HepB-Hib vaccine resulted in an incremental CE ratio of $17 000 per life-year saved as a result of potentially higher HepB vaccine coverage rates.45 Alternatively, availability of combination vaccines that do not contain Hib (eg, a pentavalent DTaP-inactivated poliovirus-HepB vaccine) in the future may potentially result in a greater use of monovalent Hib vaccine.50 Our findings indicate that a shift in either direction of the proportion of combination vaccines will not have a substantial impact on the benefit-cost and CE ratios of a national Hib vaccination program. However, use of more Hib-containing combination vaccines will make the Hib vaccination program more cost-beneficial (Table 5).

One potential limitation of our model was that base case and postvaccination Hib incidence rates were estimated using surveillance data and population-based studies and therefore may be subject to reporting biases. Such biases were likely to be small as a result of factors such as the seriousness of the disease and state disease reporting regulations.51 Another potential limitation was the assumption that the incidence rate of Hib disease among the current birth cohorts in the absence of vaccination would be the same as was observed in prevaccination birth cohorts. We believe that this was a reasonable assumption because there was no apparent decline in incidence of Hib invasive disease in the decade before vaccination programs were started.51 We attempted to account for the potential effects of these potential biases on our results in our sensitivity analysis.

The use of surveillance- and population-based data to estimate the burden of Hib invasive disease and its economic costs (rather than modeling these using vaccine efficacy estimates) is also a major strength of our analysis, especially as there is herd immunity effect from high a Hib vaccination level. We also conducted our analysis from both the direct cost perspective and the societal perspective, which had not been done before.

Economic analyses conducted in other countries have also reported favorable benefit-cost and CE ratios associated with Hib vaccination starting at 2 to 3 months of age.40,42,52,53 The Global Alliance for Vaccine and Immunization was recently established as an alliance of public- and private-sector partners involved in promoting health and immunization worldwide (www.vaccinealliance.org). The Global Alliance for Vaccine and Immunization provides technical assistance and financial support, through the Global Fund for Children’s Vaccine (now the Vaccine Fund), to 74 developing countries to introduce new and underused vaccines into their routine infant and childhood immunization programs, including Hib vaccine. Countries are expected eventually to assume the cost of these immunization programs. Economic evaluation of Hib and other immunization programs can help decision makers in these countries optimally allocate their limited resources. Our study can help to provide an example for such analyses as well as comparative contextual information.

The highly cost-beneficial Hib vaccination program for children in the United States dramatically reduced the incidence of meningitis and other serious Hib invasive diseases in <1 decade. Rising health care costs will continue the impetus to identify health care strategies that are cost-beneficial. In this context, universal Hib vaccination of infants starting at 2 months of age has been and remains an excellent societal investment. As new technologies and vaccines are developed, our experience with Hib should help guide policy formulation and adoption of strategies that have potential for reducing disease burden and saving costs.


   ACKNOWLEDGMENTS
 
We thank Bridget Lyons, MPH, Edith Gary, MT, Shawn McMahon, MD, Jeanne Santoli, MD, Nancy Rosenstein, MD, and Lance Rodewald, MD, for contributions to this study and review of the manuscript; and Mary McCauley, MTSC, for assistance in manuscript preparation.


   FOOTNOTES
 
Received for publication Jan 28, 2002; Accepted Apr 26, 2002.

Reprint requests to (F.Z.) National Immunization Program, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop E-52, Atlanta, GA 30333. E-mail: faz1{at}cdc.gov

1 R.R.D. is currently at Merck Co Inc. Back


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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PEDIATRICS (ISSN 1098-4275). ©2002 by the American Academy of Pediatrics



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