Measles, smallpox, and poliomyelitis

Transcription

1 Considerations for Implementing a New Combination Vaccine into Managed Care Lawrence Mullany, MD, MBA Abstract Background: The control and elimination of several deadly childhood diseases are a result of extensive vaccination efforts made by pediatricians, family practitioners, public health providers, and health outreach systems. Managed care can assist this effort through facilitating the delivery of affordable quality healthcare to patients. Objective: To describe the considerations made by managed care when implementing a new vaccine into practice. Results: Managed care plans often assess the medical necessity, consumer acceptance, and pharmacoeconomic benefits of a vaccine when considering whether it can be implemented into practice. DTaP-HepB-IPV (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B [Recombinant] and Inactivated Poliovirus Vaccine [Combined]), a new combination vaccine, has demonstrated similar immunogenicity and safety when compared with separately administered component vaccines. Use of this combination vaccine will help to simplify the current immunization schedule, and therefore decrease the number of injections infants receive in the first year of life, favorably influencing consumer perception of this new vaccine. A reduction in the number of office visits as a result of fewer injections and improved vaccine compliance may result in a positive pharmacoeconomic impact on parents, physicians, and payers. Reduced administration fees, fewer needed syringes, and decreased risk of needlestick injury resulting from the use of combination vaccines all may have a positive impact on acceptance of these vaccines by managed care organizations. Conclusion: DTaP-HepB-IPV is expected to meet the tests of medical appropriateness, consumer acceptance, and pharmacoeconomic reasonableness, thereby fulfilling the value proposition of a new combination vaccine for managed healthcare plans. (Am J Manag Care. 2002;9:S23-S29) Measles, smallpox, and poliomyelitis are now known historically in our culture rather than by their demonstrated devastation. Parents are no longer familiar with the heartache that infections with Haemophilus influenzae type b, diphtheria, or tetanus can inflict when a child becomes ill with one of these deadly diseases. This is a testament to the efforts and effectiveness of pediatricians and family practitioners and their respective nursing staffs, as well as public health providers and health outreach systems, to vaccinate our children. Managed care strives to facilitate the delivery of affordable high quality healthcare and to surmount barriers or hurdles that limit or restrict immunization successes. With the availability of a new vaccine, an analysis of the risks, benefits, barriers, and advantages of implementing this vaccine in managed care will need to determine the value of the vaccine. Value in this context is regarded as a formula that includes medical necessity, indication, and patient benefit divided by cost, both financial and human. The cost component of the value equation refers to the pharmacoeconomics of ingredient costs, administration costs, and cost impact on the community. DTaP-HepB-IPV (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B [Recombinant] and Inactivated Poliovirus Vaccine Combined) (Pediarix, GlaxoSmithKline Biologicals, Rixensart, Belgium) is a new combination vaccine composed of diphtheria-tetanusacellular pertussis (DTaP) vaccine, hepatitis B virus (HepB) vaccine, and inactivated VOL. 9, NO. 1, SUP. THE AMERICAN JOURNAL OF MANAGED CARE S23

2 poliovirus (IPV) vaccine in 1 vaccine that may be administered to infants in 3 injections to complete the required primary series of immunizations. Managed care plans will need to assess the medical necessity, consumer acceptance, and pharmacoeconomic benefits of this vaccine when considering whether it can be implemented in the respective plan s pediatric population. Assessing the Medical Necessity of a New Vaccine Assessing the medical necessity of a vaccine requires evaluation of its effectiveness in terms of immunogenicity, ease and simplicity of administration, and physician acceptance. The risk of failure in terms of side effects, unanticipated impacts, and unsolicited adverse perceptions also needs to be weighed. Additionally, the opinions of respected authorities and regulatory bodies are both significant and critical to the decision process of whether a vaccine is a medical necessity. DTaP-HepB-IPV has been studied extensively both in the United States and in Europe, where it has been in use since Much of the assessment by managed care of the immunogenicity and reactogenicity of this vaccine can be based on these clinical studies, as follows. A study conducted by Schmitt and colleagues 1 demonstrated that a high degree of seroprotection is attained against diphtheria, tetanus, hepatitis B, and the 3 poliovirus strains when DTaP-HepB-IPV is administered separately but concomitantly with Haemophilus influenzae type b vaccine (Hib) at 2, 3, and 4 months of age. In addition, at least 97% of study participants had a vaccine response to pertussis ( 5 ELISA [enzyme-linked immunosorbent assay] units per ml), and all subjects who received DTaP-HepB-IPV and Hib separately had postvaccination Hib anti-polyribosylribitol phosphate antibody concentrations of 0.15 µg/ml or higher. Usonis and Bakasenas 7 also evaluated the reactogenicity and immunogenicity of DTaP-HepB-IPV concomitantly administered with 3 licensed Hib vaccines at 3, 4.5, and 6 months of age. This study also demonstrated that DTaP-HepB-IPV did not interfere with the immunogenicity of Hib vaccines when administered separately. Both studies found the separate administration of DTaP-HepB-IPV and Hib to be safe and well tolerated. 1,7 In a randomized study comparing DTaP- HepB-IPV coadministered with Hib vaccine, and diphtheria-tetanus-whole-cell pertussis (DTwP)-IPV/Hib vaccine coadministered with HepB at 6, 10, and 14 weeks of age, DTaP-HepB-IPV + Hib was found to be at least as immunogenic as DTwP-IPV/Hib + HepB. 2 All infants received HepB within 48 hours of birth. However, there was a notable difference in the anti-hepatitis B surface antigen response postdose 2 between the 2 groups (98.6% of infants in the DTaP-HepB- IPV + Hib group vs 88.7% of infants in the DTwP-IPV/Hib + HepB group). A lower incidence of adverse events occurred following the administration of DTaP-HepB-IPV + Hib compared with DTwP-IPV/Hib + HepB, most likely because of the lower reactogenicity of DTaP-based vaccines compared with DTwPbased vaccines. 8 In summary, DTaP-HepB- IPV + Hib was demonstrated to be safe and well tolerated and similar in immunogenicity to DTwP-IPV/Hib vaccine coadministered with HepB. Even though DTaP-HepB-IPV was compared with a combination vaccine containing DTwP, these data may still be examined by managed care plans when evaluating the effectiveness of DTaP-HepB-IPV. Safety and immunogenicity also were studied in a head-to-head trial comparing DTaP-HepB-IPV with separate administration of DTaP, HepB, and oral poliovirus vaccine (OPV) at 2, 4, and 6 months of age, 3 described in further detail by Partridge and Yeh 9 elsewhere in this supplement. In this study, DTaP-HepB-IPV also was compared with DTaP-HepB + IPV at 2, 4, and 6 months of age. All infants received separate administration of Hib at 2, 4, and 6 months of age. No vaccine-related serious adverse events were noted and there were no significant differences in minor local or systemic adverse events among any of the cohorts after any dose. Immune response rates were not different among the groups for diphtheria, tetanus, pertussis, hepatitis B, Hib, or polio types 1, 2, and 3. This study further supports the conclusion that the safety and immunogenicity of DTaP-HepB-IPV is equiv- S24 THE AMERICAN JOURNAL OF MANAGED CARE JANUARY 2003

3 Considerations for Implementing a New Combination Vaccine into Managed Care alent to standard individually administered vaccines. The safety of DTaP-HepB-IPV coadministered with Hib vaccine at a separate site also was compared with individually administered DTaP, Hib, and OPV in a study published by Zepp and colleagues. 4 In this study of 5472 infants, reactogenicity of DTaP-HepB-IPV administered concomitantly with 1 of 4 different Hib vaccines given at separate injection sites was similar to that occurring with commercially available individual vaccines in terms of defined end points of safety. The trial demonstrated that a complex strategy of simultaneous administration of up to 6 different antigens can be achieved without increased risk of clinically significant adverse events. Therefore, assuming acceptance by physicians and regulatory bodies, these studies demonstrate that DTaP-HepB-IPV meets the medical necessity criteria for implementing a new combination vaccine into managed care. Consumer Acceptance of a New Vaccine Currently, 7 vaccines that protect against 11 diseases are administered in 20 injections during the first 2 years of life in order to comply with the immunization schedule recommended by the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP). 10 As a result, 5 injections may be administered at a single visit. Introduction of DTaP-HepB-IPV into the immunization schedule at 2, 4, and 6 months of age would simplify administration of these vaccines by decreasing the necessary injections to 15 in the first 2 years of life, assuming a HepB birth dose is administered. From a member or parent perspective, this reduction in the number of injections administered is a major benefit of using DTaP-HepB-IPV in clinical practice. Of note, managed care organizations need to be aware of the perceptions about vaccines that exist among contemporary families. In a recent telephone survey conducted by Gellin and colleagues, 11 23% of parents stated that infants receive more vaccines than are good for them and 25% of parents believed that too many immunizations can overwhelm an infant s immune system, causing the infant to be susceptible to other diseases (Table 1). In addition, there is a large volume of unsubstantiated information available to parents that perpetuates myths about vaccines, resulting in poor healthcare practices because of fear. Allegations abound of vaccines causing diabetes, autism, infections, and a host of unsolicited adverse events. 12 Many websites amplify these claims by relying heavily on emotion- Table 1. Parents Perceptions About Immunizations* % Agree % Disagree (% Strongly (% Strongly Perception Agree) Disagree) Children should only be immunized 39 (20) 55 (31) against serious diseases. Children get more immunizations than 23 (10) 68 (37) are good for them. Immunizations are always proven safe 71 (33) 19 (7) before they are approved for use. I am concerned that my child s immune 25 (9) 63 (33) system could be weakened by too many immunizations. I am more likely to trust immunizations that 88 (64) 8 (3) have been around for a while. Immunizations are one of the safest forms 78 (41) 10 (4) of medicine ever developed. Immunizations are getting better and safer 89 (60) 4 (2) all the time, as a result of medical research. Vaccines strengthen the immune system. 71 (41) 11 (5) I have access to all the information I need 92 (70) 7 (4) to make good decisions about immunizing my children. Parents should be allowed to send their child 14 (6) 79 (63) to school even if not immunized. I am opposed to immunization requirements because: They go against freedom of choice. 18 (10) 75 (52) Only I know what is best for my child. 18 (9) 75 (47) Immunization requirements protect my child 84 (54) 11 (5) from getting diseases from unimmunized children. *Response scale for these questions is: strongly agree, agree, neither agree nor disagree, disagree, and strongly disagree. Source: Reproduced with permission from Gellin BG. 11 VOL. 9, NO. 1, SUP. THE AMERICAN JOURNAL OF MANAGED CARE S25

4 al appeal to convey their messages of distrust and vaccination avoidance. 13 However, good science and evidence-based reviews exist that disprove these allegations. The Institute of Medicine has published a report, Immunization Safety Review: Multiple Immunizations and Immune Dysfunction, 14 which concludes that such allegations are baseless. The availability of new vaccines will require practitioners to review the benefits of immunization with parents and describe the consequences of not being vaccinated. Although there has been a dramatic decline in many of the diseases children are vaccinated against, 300 children die annually from vaccine-preventable diseases. 15 Additionally, vaccine-preventable childhood diseases can cause other serious consequences, including deafness, decreased motor function, liver damage, and coma. 16 More important, some of these diseases continue to occur in our communities. In the United States, an analysis of data on notifiable diseases demonstrated that more than 7000 cases of pertussis and more than 1000 cases of invasive H influenzae occurred in Although extremely rare, diphtheria carries a 10% mortality rate and a 50% hospitalization rate. 18 Tetanus kills 30% of those affected. Five percent of children with mumps develop meningitis or encephalitis. From a household perspective, a child with chicken pox misses 8 to 9 days of school and the parent misses 1 to 2 days of work. 19 Therefore, the use of DTaP-HepB-IPV in a managed care organization, with an overall reduction in the number of inoculations needed, may provide practitioners with more time to address any issues that parents might have about vaccination. Pharmacoeconomic Assessment of a New Vaccine With reductions in the number of visits needed to achieve a similar immune status, saved days of employment missed by parents, and reduced copays for fewer vaccinerelated office visits, there are obvious direct and indirect pharmacoeconomic benefits of using a combination vaccine, such as DTaP- HepB-IPV, for the member. There are also benefits and costs that must be weighed for the managed care plan when implementing a new vaccine in practice. Physicians currently incur costs in nursing time associated with vaccine preparation, injection, and administrative recording. This time expands with infant crying and distress in the office. A time-motion study published in 2000 clearly demonstrated a savings in time with the use of a combination vaccine, which may result in better quality of care and savings of administrative dollars spent in the office. 20 The investigators were able to demonstrate a reduction of 2.4 minutes per shot in examination room settings and 1.7 minutes per shot in an immunization room setting when administering a combination vaccine (Table 2). This time savings may also assist in reducing the likelihood of a medication error within the process of medication administration and transcription. Although difficult to quantify, other impacts to managed care organizations include a reduction in office visits because of fewer injections. In addition, fewer syringes are needed and there is a decreased risk of needlestick injury by handling fewer syringes. This may help to defray the costs that are associated with following the Needlestick Safety and Prevention Act (H.R. 5178), which requires safety devices, employee training, and Sharps Injury Log maintenance. 21 The Occupational Safety and Health Administration estimates that the average expenses associated with needlestick injuries or other blood exposures range from $500 to $3000, with the majority falling between $500 and $1000. It was further noted that if the needlestick injury were to result in an actual infection such as hepatitis or human immunodeficiency virus, the cost could be hundreds of thousands of dollars or more. 22 This is consistent with the recommendations of the AAP Infection Control Guidelines to avoid these problems. 23 The actual incidence of needlestick injuries sustained annually is not clearly defined. In a US General Accounting Office estimate based on the CDC National Surveillance System for Health Care Workers, about percutaneous injuries occur annually in hospitals, with 60% from hollow-bore needlestick injuries. 24 Twenty-six percent of these hospital injuries were S26 THE AMERICAN JOURNAL OF MANAGED CARE JANUARY 2003

5 Considerations for Implementing a New Combination Vaccine into Managed Care Table 2. Time Required Based on Number of Injections in the Injection Room and Examination Room in a Managed Care Organization* Mean Time (Min) By No. of Injections Mean Change (Min) Per Time Element Site Extra Injection P Preparation Injection room Examination room Injection Injection room <.001 Examination room <.001 Paperwork/ Injection room administrative Examination room Other vaccine- Injection room related time Examination room NA NA Total nurse time Injection room <.001 Examination room Care center Injection room <.001 personnel time to Examination room process patient NA indicates not applicable. *Linear regression of time vs number of injections adjusted for age. Mean minutes per extra injection. P value for trend. Source: Reproduced with permission from Pellissier JM. 20 caused by sudden patient movement at the time of needle insertion, manipulation, or removal. However, these data did not include the ambulatory settings where 60% of all healthcare workers are employed. According to the International Health-care Worker Safety Center at the University of Virginia in Charlottesville, it has been estimated that there have been at least sharps and blood contacts annually during the past decade. 25 It is logical to postulate that a reduction in the number of injections required for vaccination would reduce the risk of needlestick injury and therefore reduce the costs associated with these events. As a result of improved vaccination rates with combination vaccines, managed care organizations can document these results as a performance measure, such as a Health Plan Employer Data and Information Set (HEDIS) score, to recruit new members. These performance measures also serve to meet consumer demands for meaningful information about a managed care plan, and act as a comparative basis for selecting a managed care plan. 26 An analysis of HEDIS 3.0 measures found that the administrative cost per measure to a managed care plan can range from $ to $ as a result of several tasks, including the cost of reviewing charts, linking different data sets, cleaning the data, doing the calculations, and writing the reports associated with a measure. 14 In terms of vaccinations, much of this cost is in the collection of the data, which can be complicated and thus increasingly expensive to obtain by manual chart reviews and variable compliance. A simplified immunization schedule with VOL. 9, NO. 1, SUP. THE AMERICAN JOURNAL OF MANAGED CARE S27

6 Table 3. Cost Benefit for Immunization of Infants Months of Age Cost Benefit Cost Benefit Vaccine Direct ($) * Indirect ($) Total ($) DTP Polio MMR Hib 1.4 # HepB 0.5** Varicella DTP indicates diphtheria and tetanus toxoids and pertussis vaccine; HepB, hepatitis B virus vaccine; Hib, Haemophilus influenzae type b vaccine; MMR, measles-mumps-rubella. *Direct costs include medical care savings from vaccination (physician fees, hospitalization, and disease sequelae). Indirect costs calculated as total minus direct costs. Total costs include medical care and nonmedical costs (direct costs plus costs for parent s loss of work time or transportation to the physician s office). Data are from reference 29. Data are from reference 30. Data are from reference 31. #Data are from reference 32. **Data are from reference 33. Data are from reference 34. Source: Adapted with permission from Gershon AA. 28 improved compliance may reduce the costs of acquiring these data as currently performed, and may enhance the collection and assessment of the data by allowing for administrative collection with a single code. In addition, simplifying the process may reduce the gap in children who should have received their scheduled immunizations by age 2 but have not. As noted in HEDIS 2002 national data (based on 2001 results), this gap ranges from 17% to 23% for 4DTP, 3IPV, and 3HepB immunizations specifically, and from 17% to 45% for most recommended vaccinations (4DTP, 3IPV, 3HepB, 1MMR, 3Hib, and 1Varicella). 27 When determining the overall economic value of a vaccine, the indirect savings of administering the vaccine must be weighed against the direct costs of the vaccine. For example, as shown in Table 3, every dollar spent on Hib vaccine saves $1.40 in direct costs and $0.80 in indirect costs (ratio, 2.2:1). 28 Likewise, every dollar spent on HepB vaccine saves $0.50 in direct costs and $1.50 in indirect costs (ratio, 2.0:1), and every $1.00 spent on varicella vaccine saves $0.90 in direct costs and $4.50 in indirect costs (ratio, 5.4:1). When using DTaP- HepB-IPV to complete the primary immunization series, an extra HepB dose may be administered if a HepB birth dose was given as recommended by the ACIP, AAP, and AAFP. Each managed care plan will need to examine the cost benefits of administering DTaP-HepB-IPV in relation to the cost of an extra HepB dose. There is no doubt as to the return on health and/or the return on investment of vaccinating when both the direct and indirect costs of a vaccine are taken into consideration. Conclusion In summary, DTaP-HepB-IPV should meet a managed care organization s tests for medical appropriateness, consumer acceptance, and pharmacoeconomic reasonableness, thereby fulfilling the value proposition for the vaccine. The immunogenicity and safety of this vaccine have been demonstrated in several clinical studies. The need for fewer injections with use of DTaP-HepB-IPV is expected to be well received by parents and healthcare providers, and should result in decreased costs for the parent, healthcare provider, and payer. In addition, better compliance with needed vaccinations should occur. DTaP-HepB-IPV will be a welcome addition to the vaccine armamentarium for managed care organizations. REFERENCES 1. Schmitt HJ, Knuf M, Ortiz E, Sänger R, Uwamwezi MC, Kaufhold A. Primary vaccination of infants with diphtheria-tetanus-acellular pertussis-hepatitis B virusinactivated polio virus and Haemophilus influenzae type b vaccines given as either separate or mixed injections. J Pediatr. 2000;137: Gylca R, Gylca V, Benes O, et al. A new DTPa-HBV- IPV vaccine co-administered with Hib, compared to a commercially available DTPw-IPV/Hib vaccine coadministered with HBV, given at 6, 10 and 14 weeks following HBV at birth. Vaccine. 2001;19: Yeh SH, Ward JI, Partridge S, et al. Safety and immunogenicity of a pentavalent diphtheria, tetanus, pertussis, hepatitis B and polio combination vaccine in infants. Pediatr Infect Dis J. 2001;20: S28 THE AMERICAN JOURNAL OF MANAGED CARE JANUARY 2003

7 Considerations for Implementing a New Combination Vaccine into Managed Care 4. Zepp F, Schuind A, Meyer C, Sänger R, Kaufhold A, Willems P. Safety and reactogenicity of a novel DTPa- HBV-IPV combined vaccine given along with commercial Hib vaccines in comparison with separate concomitant administration of DTPa, Hib, and OPV vaccines in infants. Pediatrics. 2002;109. Available at: http// 5. Blatter MM, Resinger K, Bottenfield GW, et al. Evaluation of the reactogenicity and immunogenicity of a new combined DTPa-HBV-IPV vaccine co-administered with Hib vaccine at 2, 4 & 6 months of age [abstract]. Clin Infect Dis. 1999;29: Bogaerts H. The future of childhood immunizations: examining the European experience. Am J Manag Care. 2002;8:S526-S Usonis V, Bakasenas V. Does concomitant injection of a combined diphtheria-tetanus-acellular pertussishepatitis B virus-inactivated polio virus vaccine influence the reactogenicity and immunogenicity of commercial Haemophilus influenzae type b conjugate vaccines? Eur J Pediatr. 1999;158: Brown F, Greco D, Mastrantonio P, Salmaso S, Wassilak S. Pertussis vaccine trials. Session IV: vaccine efficacy. Dev Biol Stand. 1997;89: Partridge S, Yeh SH. Clinical evaluation of a DTaP- HepB-IPV combined vaccine. Am J Manag Care. 2002;8:S509-S Centers for Disease Control and Prevention. Recommended childhood immunization schedule: United States, MMWR Morb Mortal Wkly Rep. 2002;51: Gellin BG, Maibach EW, Marcuse EK, for the National Network for Immunization Information Steering Committee. Do parents understand immunizations? A national telephone survey. Pediatrics. 2000;106: Offit PA, Quarles J, Gerber MA, et al. Address-ing parents concerns: do multiple vaccines overwhelm or weaken the infant s immune system? Pediatrics. 2002;109: Wolfe RM, Sharp LK, Lipsky MS. Content and design attributes of antivaccination web sites. JAMA. 2002;287: Stratton K, Wilson CB, McCormick MC, eds. Immunization Safety Review: Multiple Immunizations and Immune Dysfunction. Washington, DC: National Academy Press; National Committee for Quality Assurance. The state of managed care quality, 2001: childhood immunization status. Available at: somc2001/child_imm/somc_2001_cis.html. Accessed August 5, National Immunization Program. Vaccine-preventable childhood diseases. Available at: gov/nip/diseases/child-vpd.htm. Accessed August 5, Eberhardt MS, Ingram DD, Makuc DM, et al. Urban and Rural Health Chartbook. Health, United States, Hyattsville, Md: National Center for Health Statistics; Marquette County Health Department. Childhood immunization facts. Available at: marquette.localhealth.net/arcniiweek.htm. Accessed August 7, American Academy of Pediatrics. Varicella: the chickenpox vaccine. Available at: medem.com/search/article_display.cfm?path=n:&mstr=/ ZZZU7QBMH4C.html&soc=AAP&srch_typ=NAV_ SERCH. Accessed August 7, Pellissier JM, Coplan PM, Jackson LA, May JE. The effect of additional shots on the vaccine administration process: results of a time-motion study in 2 settings. Am J Manag Care. 2000;6: Environmental & Occupational Health & Safety Services. Safe medical devices. Available at: MedicalDevices. Accessed August 16, US Department of Labor Occupational Safety and Health Administration. Record summary of the request for information on occupational exposure to bloodborne pathogens due to percutaneous injury. Available at: Accessed August 16, American Academy of Pediatrics. AAP releases infection control guidelines for physicians offices. Available at: jun.inf.htm. Accessed August 12, US General Accounting Office. Occupational safety: selected costs and benefit implications of needlestick prevention devices for hospitals. Available at: Accessed August 16, Flaherty M. A hazard to your health? Available at: html. Accessed August 16, Kongstvedt PR, ed. Member services and consumer affairs. The Managed Health Care Handbook. 4th ed. New York, NY: Aspen Publishers, Inc; 2001:chap National Committee for Quality Assurance (NCQA). Quality Compass Washington DC: NCQA; Gershon AA, Gardner P, Peter G, Nichols K, Orenstein W. Guidelines from the Infectious Diseases Society of America: quality standards for immunization. Clin Infect Dis. 1997;25: Hatziandreu E, Palmer CS, Brown RE, Halpern MT. A cost benefit analysis of the diphtheria-tetanus-pertussis (DTP) vaccine. Arlington, Va: Batelle, Medical Technology, Assessment and Policy Research Program; Hatziandreu E, Palmer CS, Halpern MT, Brown RE. A cost benefit of the OPV vaccine. Arlington, Va: Batelle, Medical Technology, Assessment and Policy Research Program; Hatziandreu E, Brown RE, Halpern MT. A cost benefit analysis of measles-mumps-rubella (MMR) vaccine. Arlington, Va: Batelle, Medical Technology, Assessment and Policy Research Program; Hatziandreu EJ, Brown RE. A cost benefit analysis of the Haemophilus influenzae type b (Hib) vaccine. Arlington, Va: Batelle; Margolis HS, Coleman PJ, Brown RE, Mast EE, Sheingold DH, Arevalo JA. Prevention of hepatitis B virus transmission by immunization: an economic analysis of current recommendations. JAMA. 1995;274: Lieu TA, Cochi SL, Black SB, et al. Cost-effectiveness of a routine varicella vaccination program for US children. JAMA. 1994;271: VOL. 9, NO. 1, SUP. THE AMERICAN JOURNAL OF MANAGED CARE S29