摘要：We explored market factors that affect pediatric combination vaccine uptake in the US public-sector pediatric vaccine market. We specifically examined how Pediarix and Pentacel earned a place in the 2009–2012 lowest overall cost formulary. Direct competition between Pediarix and Pentacel is driven by the indirect presence of the Merck Haemophilus influenzae type b vaccine and the Recommended Childhood Immunization Schedule requirement for a hepatitis B birth dose. The resulting analysis suggests that Pentacel would never have earned a place in the lowest overall cost formulary for 2009–2012 federal contract prices for any cost of an injection unless the Merck H influenzae type b advantage was ignored and the hepatitis B birth dose administration cost was recognized by health care providers in designing the lowest overall cost formularies. A limited number of pharmaceutical companies manufacture vaccines for the US pediatric vaccine market. Over the past decade, numerous economic and regulatory factors have made vaccine manufacturing less profitable for such companies, resulting in many of them exiting the market. 1 One consequence of this situation is that production problems often translate into vaccine shortages in the market. Because maintaining high immunization levels is a vital societal need, public health administrators are motivated to sustain an adequate supply of vaccines through public health policies that encourage new companies to enter the market. 1 The Centers for Disease Control and Prevention (CDC) in the United States is the primary public health organization responsible for developing and applying disease prevention and control. The Advisory Committee on Immunization Practices (ACIP) is an independent panel of vaccine stakeholder representatives from the CDC, vaccine manufacturers, scientists, and physician groups. The ACIP reviews technical data on new vaccines, and then makes recommendations after the vaccines are approved by the Food and Drug Administration (FDA) for sale in the United States. The ACIP is also responsible for adding the vaccines to the Recommended Childhood Immunization Schedule (RCIS; Figure 1 2 ). The RCIS represents the recommended sequence and timing of pediatric vaccines to protect children from pediatric diseases. Open in a separate window FIGURE 1— United States 2012 Recommended Childhood Immunization Schedule for birth through age 6 years. Note. DTaP = diphtheria, tetanus, and pertussis; HepA = hepatitis A; HepB = hepatitis B; Hib = Haemophilus influenzae type b; IPV = inactivated poliovirus; MMR = measles, mumps, and rubella; PCV = pneumococcal conjugate vaccine; RV = rotavirus. Source. Centers for Disease Control and Prevention. The CDC is required by law to negotiate vaccine prices for the purchases made by state and local governments. The state and local government public health officials purchase vaccines for the immunization of the children in their administrative areas of responsibility. They seek to satisfy the RCIS for each child to ensure proper immunization coverage. They distribute the vaccines free of charge to the private physicians and public health clinics that are registered as Vaccines for Children (VFC) Program providers. 3 The VFC Program is designed to provide vaccines (at no charge) to children whose parents or guardians are not able to afford them. Pediatric vaccines purchased at the federal contract prices, as negotiated by CDC, account for approximately 57% of total pediatric purchases by volume. 3 Private vaccine providers who are not registered as VFC Program providers cannot purchase the vaccines through federal contract prices, and as such, purchase the vaccines at private-sector prices (typically higher than the federal contract prices). The private-sector prices are reported by vaccine manufacturers to the CDC. 4 In this analysis, we focused on federal contract prices, though the methodology employed could be adapted to separately analyze the private sector. Vaccines are said to compete when 2 or more vaccine manufacturers produce the same vaccine or vaccines that contain the same antigen that can be administered to satisfy the immunization requirements in a given time period. There are 4 competitive antigens: diphtheria, tetanus, and pertussis (DTaP); hepatitis B (HepB); Haemophilus influenzae type b (Hib); and inactivated poliovirus (IPV). In the United States, 3 pharmaceutical companies (Merck, GlaxoSmithKline, and Sanofi Pasteur) manufacture all the competing vaccines. Pediarix (DTaP–HepB–IPV) was the first pentavalent combination vaccine to gain FDA approval (in 2002). In 2008, a second pentavalent combination vaccine, Pentacel (DTaP–IPV/Hib), gained FDA approval for the US market. As Pediarix and Pentacel are the only vaccines that immunize against 5 diseases in a single injection, health care providers welcome them as part of the formulary (defined as a set of pediatric vaccines stocked to satisfy the immunization needs for a pediatric population cohort, as defined by a given set of immunization requirements). On the basis of the RCIS structure, Pediarix and Pentacel are not compatible for use in a single vaccine formulary. By design, the market will gravitate toward the combination vaccine that provides the best value (i.e., yields the lowest overall cost formulary [LOCF], the set of vaccines that satisfies the RCIS at the lowest overall formulary cost 5 ). Therefore, Pediarix and Pentacel are said to serve as the backbone of the LOCF. From the perspective of health care providers, the question to ask is: which pentavalent vaccine earns a place in the LOCF, given a fixed cost of an injection (defined as a constant vaccine administration cost)? Behzad et al. 6 reported and discussed the LOCFs across 3 years (2009–2011) for several fixed cost of an injection values. From Behzad et al., 6 Pentacel was not competitively priced compared with Pediarix in 2009–2011 (i.e., Pentacel did not earn a place in the LOCF for any cost of an injection). According to data provided by the CDC 7,8 (e-mail communication from Sarah Foster, Centers for Disease Control and Prevention, August 14, 2013), the net number of Pentacel doses distributed in 2009–2011 was greater than the number of Pediarix doses distributed. A natural question to ask is why the uptake by health care providers who administer Pediarix or Pentacel as the backbone of their pediatric formularies is not consistent with the results reported in Behzad et al. 6 This study answers this question by considering the effects of 2 issues: a special property of the Merck Hib (i.e., a month-6 dose of Hib is not required if Merck Hib is administered in months 2 and 4) and the HepB birth dose. Moreover, this study identifies the equilibrium cost of an injection (defined as the minimum cost of an injection for which Pentacel earns a place in the LOCF) for the 4 possible scenarios associated with recognizing or ignoring these 2 issues by health care providers in designing the LOCF. No attempt has been made before to characterize the effects of the special property of the Merck Hib and HepB birth dose on the uptake of Pediarix and Pentacel. Understanding the market factors that have an impact on the uptake of pediatric combination vaccines could interest those within the pediatric health care community, such as pharmaceutical companies seeking right pricing strategies for their products, as well as the CDC negotiating vaccine prices with manufacturers and government, and public health officials seeking the LOCF for the children in their administrative area.
