The impact of vaccine procurement methods on public health in selected European countries.

Introduction: Across Europe, immunization programs have brought immense benefits to the prevention of infectious diseases. The vaccines used are procured through a variety of models such as tenders and Pricing & Reimbursement. However, to date, the impact of the procurement method on the performance and sustainability of vaccination programs and on public health has received little attention.Areas covered: Drawing on a review of the academic and policy literature, complemented by an interview program with stakeholders involved in the procurement of vaccines, the authors have documented the relationship between procurement method dynamics and the level of protection against vaccine-preventable diseases in Germany, Italy, Spain and Romania for, measles-containing vaccines, hexavalent and influenza vaccines.Expert opinion: Price-based tenders can contribute to vaccine supply issues, discourage the provision of value-added services supporting vaccination coverage and disincentives future R&D. Although it is observed that price-based tenders can intensify competition in the short term, there can be unintended consequences such as damage to long-term competition. As European countries are committed to strengthen their immunization programs, they should consider the implications of current vaccine procurement models on the vaccine ecosystem and on public health.

Estimated costs attributable to events of "out-of-temperature" in the stockpiling of hexavalent vaccines occurring in Italy.

BACKGROUND: Antigens contained in vaccines are inherently unstable biologically; such a characteristic is conferred by their three-dimensional structure. Preserving the ability of the vaccines to protect against disease is necessary to ensure the supervision and monitoring of all steps of the cold chain. DTPa-HBV-IPV/Hib vaccine (Infanrix hexaTM, GSK Vaccines, Belgium) is designed to prevent disease due to diphtheria, tetanus, pertussis (DTP), hepatitis B virus (HBV), poliomyelitis and Haemophilus influenzae type b (Hib); it was first licensed for use in Europe in 2000 and is currently licensed in at least 95 countries. Since October 2013, more than 102 million doses of GSK's DTPa-HBV-IPV/Hib vaccine have been distributed globally, with nearly 15 million doses distributed in Italy. DTPa-HBV-IPV/Hib components are stable up to a temperature of 25°C for 72 hours. Lacking of officially approved stability data may generate some concern in case of cold chain accidents. METHODS: An analysis based on collected data was carried out to estimate potential costs attributable to events of "out-of-temperature" in the stockpiling of hexavalent vaccines occurring in Italy in 2014. RESULTS: The analysis, based on real data, documented that the loss for the National Health Service (NHS) was in the range of 100,000 - 400,000 euros in one year. However, the amount of money that in principle could have been lost would have ranged between nearly half and one million euros/year. CONCLUSIONS: A substantial loss of money was avoided thanks to the availability of officially approved stability data for GSK's DTPa-HBV-IPV/Hib vaccine.

Changes in immunization program managers' perceptions of programs' functional capabilities during and after vaccine shortages and pH1N1.

OBJECTIVES: We surveyed U.S. immunization program managers (IPMs) as part of a project to improve public health preparedness against future emergencies by leveraging the immunization system. We examined immunization program policy and Immunization Information System (IIS) functionality changes as a result of the Haemophilus influenzae type B (Hib) vaccine shortage and pandemic influenza A(H1N1) (pH1N1). Evaluating changes in immunization program functionalities and policies following emergency response situations will assist in planning for future vaccine-related emergencies. METHODS: We administered three consecutive surveys to IPMs from 64 state, city, and territorial jurisdictions in 2009, 2010, and 2012. We compared IPMs' responses across either two or three years (e.g., changes in response or consistent responses across years) using McNemar's test. RESULTS: Immunization programs maintained increases in functionality related to communication systems with health-care providers during this period. Immunization programs often did not maintain changes to IIS functionalities made from 2009 to 2010 (e.g., identifying high-risk and priority populations, tracking adverse events, and mapping disease risk) in the post-pandemic period (2010-2012). About half of IPMs reporting additional IIS functionality in identifying high-risk populations from 2009 to 2010 reported no longer having this function in 2012. There was an 18% decline in respondents reporting geographic information systems risk-mapping capability in IIS from 2010 to 2012. CONCLUSIONS: Because of the Hib vaccine shortage and pH1N1, immunization program needs and efforts changed to address evolving situations. The lack of sustained increases in resources or system functions after the pandemic highlights the need for comprehensive, sustainable public health emergency preparedness systems and related resources.

Haemophilus influenzae type b disease and vaccine booster dose deferral, United States, 1998-2009.

BACKGROUND: Since the introduction of effective vaccines, the incidence of invasive Haemophilus influenzae type b (Hib) disease among children <5 years of age has decreased by 99% in the United States. In response to a limited vaccine supply that began in 2007, Hib booster doses were deferred for 18 months. METHODS: We reviewed national passive and active surveillance (demographic and serotype) and vaccination status data for invasive H. influenzae disease in children aged <5 years before (1998-2007) and during (2008-2009) the vaccine shortage years to assess the impact of the vaccine deferral on Hib disease. We estimated the average annual number of Hib cases misclassified as unknown (not completed or missing) serotype. RESULTS: From 1998 to 2007 and 2008 to 2009, the annual average incidence of Hib disease per 100000 population was 0.2 and 0.18, respectively; no significant difference in incidence was found by age group, gender, or race. Among Hib cases in both time periods, most were unvaccinated or too young to have received Hib vaccine. During 2001 to 2009, there were <53 Hib cases per year, with an estimated 6 to 12 Hib cases misclassified as unknown serotype. CONCLUSIONS: The booster deferral did not have a significant impact on the burden of invasive Hib disease in children <5 years of age. Continued surveillance and serotype data are important to monitor changes in Hib incidence, especially during vaccine deferrals. Hib booster deferral is a reasonable short-term approach to a Hib vaccine shortage.

Lessons learned from the 2007 to 2009 Haemophilus influenzae type B vaccine shortage: implications for future vaccine shortages and public health preparedness.

OBJECTIVE: To understand immunization programs' experience managing the 2007 to 2009 Haemophilus influenzae type B (Hib) vaccine shortage and identify ways in which the US immunization system can be improved to assist in responses to future shortages of routine vaccines and large-scale public health emergencies. METHODS: An Internet-based survey was conducted from July 2009 to October 2009 among the 64 city, state, and territorial immunization program managers (IPMs). RESULTS: Fifty-eight percent (37 of the 64) of IPMs responded. Forty percent of responding IPMs indicated not having enough Hib vaccine within their Vaccines for Children program to fulfill the temporary 3-dose recommendation issued in December 2007 in response to the Hib vaccine shortage. While 73% of IPMs indicated success in monitoring provider inventory and 68% indicated success in monitoring doses administered during the shortage, fewer than half indicated success in monitoring providers' compliance with shortage-specific recommendations regarding Hib vaccine. Forty-six percent of IPMs used their immunization information system (IIS) to monitor provider compliance with recommendations regarding Hib vaccine use, and of these, nearly 60% reported success in monitoring provider compliance with recommendations compared with 35% of IPMs who did not use their IIS in this way. Forty-two percent of IPMs felt that the Centers for Disease Control and Prevention (CDC) was successful in determining stockpiled vaccine allocations to their program, and 56% felt that the CDC was successful in communicating its rationale for their immunization program's Hib allocation during the shortage. CONCLUSIONS: Experiences from the 2007 to 2009 Hib vaccine shortage offer insights on how the US immunization system and system-wide response to vaccine shortages can be improved. Results from this survey suggest that improving vaccine transfer between jurisdictions and using IIS to track provider compliance with shortage recommendations are 2 ways that can help the US immunization system respond to future vaccine shortages and large-scale public health emergencies like influenza pandemics.

Determining the optimal vaccine vial size in developing countries: a Monte Carlo simulation approach.

Outreach immunization services, in which health workers immunize children in their own communities, are indispensable to improve vaccine coverage in rural areas of developing countries. One of the challenges faced by these services is how to reduce high levels of vaccine wastage. In particular, the open vial wastage (OVW) that result from the vaccine doses remaining in a vial after a time for safe use -since opening the vial- has elapsed. This wastage is highly dependent on the choice of vial size and the expected number of participants for which the outreach session is planned (i.e., session size). The use single-dose vials results in zero OVW, but it increases the vaccine purchase, transportation, and holding costs per dose as compared to those resulting from using larger vial sizes. The OVW also decreases when more people are immunized in a session. However, controlling the actual number of people that show to an outreach session in rural areas of developing countries highly depends on factors that are out of control of the immunization planners. This paper integrates a binary integer-programming model to a Monte Carlo simulation method to determine the choice of vial size and the optimal reordering point level to implement an (nQ, r, T) lot-sizing policy that provides the best tradeoff between procurement costs and wastage.

Modeling insights into Haemophilus influenzae type b disease, transmission, and vaccine programs.

In response to the 2007-2009 Haemophilus influenzae type b (Hib) vaccine shortage in the United States, we developed a flexible model of Hib transmission and disease for optimizing Hib vaccine programs in diverse populations and situations. The model classifies population members by age, colonization/disease status, and antibody levels, with movement across categories defined by differential equations. We implemented the model for the United States as a whole, England and Wales, and the Alaska Native population. This model accurately simulated Hib incidence in all 3 populations, including the increased incidence in England/Wales beginning in 1999 and the change in Hib incidence in Alaska Natives after switching Hib vaccines in 1996. The model suggests that a vaccine shortage requiring deferral of the booster dose could last 3 years in the United States before loss of herd immunity would result in increasing rates of invasive Hib disease in children <5 years of age.

Effects of a nationwide Hib vaccine shortage on vaccination coverage in the United States.

BACKGROUND: A shortage of Haemophilus influenzae type b (Hib) vaccine that occurred in the United States during December 2007 to September 2009 resulted in an interim recommendation to defer the booster dose, but to continue to vaccinate as recommended with the primary series during the first year of life. OBJECTIVES: To quantify effects of the Hib shortage on vaccination coverage and to determine if any demographic subgroups were disproportionately affected. METHODS: Data from the 2009 National Immunization Survey (NIS) were divided based on child's age at the onset of the shortage. Comparisons were made in primary series coverage by 9 months between children <7 months versus ≥7 months at the start of the shortage. Comparisons in primary series plus booster dose completion by 19 months were made between children who were <12 months versus ≥12 months at the start of the shortage. RESULTS: Nationally, there was a difference in Hib primary series completion by 9 months among children age <7 months versus ≥7 months at the start of the shortage (73.9% versus 81.2%, P<0.001). There was a large difference in the percentage of children fully vaccinated with the primary series plus booster dose by 19 months among children age <12 months versus ≥12 months at the start of the shortage (39.5% versus 66.0%, P<0.001). There were differential effects of the shortage on primary series coverage among states and for some demographic characteristics. CONCLUSIONS: As expected booster dose coverage was reduced consistent with interim recommendations, but primary series coverage was also reduced by 7 percentage points nationally.

Accelerating introduction of new vaccines: barriers to introduction and lessons learned from the recent Haemophilus influenzae type B vaccine experience.

Adoption of new vaccines in developing countries is critical to reducing child mortality and meeting Millennium Development Goal 4. However, such introduction has historically suffered from significant delays that can be attributed to various factors including (i) lack of recognition of the value of a vaccine, (ii) factors related to weak health systems, and (iii) policy considerations. Recently, the Global Alliance for Vaccines and Immunization (GAVI) supported efforts to accelerate the introduction of Haemophilus influenzae type b (Hib) vaccines in developing countries, which resulted in a significant surge in vaccine adoption by these countries. The experience with Hib vaccines, as well as similar efforts by GAVI to support the introduction of new pneumococcal and rotavirus vaccines, provides a strategy for new vaccine adoption that is reviewed in this paper, providing a useful model to help accelerate the uptake of other life-saving vaccines. This strategy addresses barriers for vaccine adoption by focusing on three major areas: (i) communications to increase awareness about the various factors needed for evidence-based decisions that meet a country's health goals; (ii) research activities to answer key questions that support vaccine introduction and long-term programme sustainability; and (iii) coordination with the various stakeholders at global, regional and country levels to ensure successful programme implementation.

Up-to-date Haemophilus influenzae type b vaccination coverage during a vaccine shortage.

OBJECTIVES: We sought to assess Haemophilus influenzae type b (Hib) vaccination coverage in diverse areas of the United States during the 2008-2009 Hib vaccine shortage. Interim recommendations for Hib vaccination during the shortage called for deferral of the booster dose only among children not at high risk for disease; the primary series given during the first year of life continued to be recommended for all children. METHODS: Vaccination data on ∼123,000 children were collected from 8 Immunization Information System (IIS) sentinel sites. Completion of the primary Hib series (with 2 or 3 doses depending on vaccine type) by 9 months old during the vaccine shortage was compared with coverage of 2 vaccines given at similar ages (7-valent pneumococcal conjugate vaccine and diphtheria, tetanus acellular pertussis vaccine) in children born between November 1, 2007, and March 31, 2008. RESULTS: During the shortage period, Hib vaccination coverage for the primary series was 7.8 to 10.3 percentage points lower than diphtheria, tetanus acellular pertussis vaccine and 7-valent pneumococcal conjugate vaccine coverage for children by the age of 9 months in 7 of 8 sentinel sites. CONCLUSIONS: A significant decrease in Hib vaccination coverage for the primary series was observed and was consistent across several US localities. Close collaboration between the public health community and vaccine providers is essential during vaccine shortages to ensure that interim vaccination recommendations are clear, widely disseminated, and closely followed, and that access to available vaccine supplies is maintained.

Haemophilus influenzae type B meningitis in a previously healthy child.

Vaccines have proven successful in virtually eradicating certain infectious diseases that typically attack the pediatric population. Since 1988, when the conjugate vaccine was introduced, the incidence of invasive Haemophilus influenzae type B disease was reduced dramatically. However, immunization rates have decreased in certain parts of the country because of a combination of vaccine shortage and widespread parental perception that vaccines are harmful. We present the case of a previous healthy child, who ultimately succumbed to H. influenzae type B meningitis where multiple factors were likely responsible for his acquisition of the disease.

Changes in measurement of Haemophilus influenzae serotype b (Hib) vaccination coverage --- National Immunization Survey, United States, 2009.

The National Immunization Survey (NIS) has introduced a new method for measuring Haemophilus influenzae serotype b (Hib) vaccination coverage. Since its inception in 1994, NIS has considered a child aged 19-35 months to be fully vaccinated with Hib vaccine if the child had received 3 or more doses of any Hib-containing vaccine (3+Hib), regardless of vaccine product type received. However, for some Hib vaccine product types, 4 doses are needed to be fully vaccinated. Because NIS data have not distinguished between Hib vaccine product types, a child who received 3 doses of a vaccine product that requires 4 doses was misclassified as fully vaccinated. Since January 2009, NIS has requested that vaccination providers report data on Hib vaccine product types. Using this new information, two new measures were created: 1) primary series completed and 2) fully vaccinated (primary series completed plus booster dose). To determine the effects of the new method, CDC used preliminary data from the first half of 2009 NIS to compare the new measures with the previous 3+Hib measure. The findings, which were influenced by a nationwide shortage of certain Hib vaccine types, indicated that 92.9% of children aged 19-35 months in the United States had received the primary Hib series according to interim recommendations of the Advisory Committee on Immunization Practices (ACIP), and 56.9% were fully vaccinated. Using the previous method, 82.9% were fully vaccinated (3+Hib). When interpreting Hib vaccination coverage estimates and analyzing trends with NIS Hib vaccination coverage data in the future, analysts and state immunization programs should be aware of this change in Hib measurement.

Knowledge of interim recommendations and use of Hib vaccine during vaccine shortages.

OBJECTIVES: The goals were to determine among pediatricians and family physicians (1) knowledge of interim recommendations regarding Haemophilus influenzae type b (Hib) vaccine administration, (2) current practices, and (3) factors associated with nonadherence. METHODS: An Internet-based survey was conducted in April 2008 among national samples. RESULTS: Response rates were 68% (220 of 325 physicians) among pediatricians and 51% (153 of 302 physicians) among family physicians. Seventy-three percent of pediatricians and 45% of family medicine physicians reported insufficient Hib vaccine supplies, and 22% to 24% reported having to defer doses for infants 2 to 6 months of age > or =10% of the time. Ninety-eight percent of pediatricians and 81% of family physicians were aware of the interim recommendations (P < or = .0001), and virtually all knew that the booster dose should be deferred; however, 22% of pediatricians and 33% of family medicine physicians reported not deferring this dose. Physicians in both specialties were less likely to adhere to recommendations to defer in this age group if they thought that their practice had sufficient vaccine supplies (pediatricians, odds ratio: 0.01 [95% confidence interval: 0.003-0.03]; family medicine physicians, odds ratio: 0.10 [95% confidence interval: 0.03-0.33]). Family medicine physicians were less likely to adhere to recommendations if they had not heard about the interim recommendations (odds ratio: 0.04 [95% confidence interval: 0.01-0.21]). CONCLUSIONS: Most primary care physicians experienced Hib vaccine shortages, and many have had to defer doses for 2- to 6-month-old children. Most are knowledgeable regarding interim recommendations, but one-fifth to one-third reported nonadherence.

Licensure of a Haemophilus influenzae type b (Hib) vaccine (Hiberix) and updated recommendations for use of Hib vaccine.

On August 19, 2009, the Food and Drug Administration (FDA) licensed Hiberix (GlaxoSmithKline Biologicals, Rixensart, Belgium), a Haemophilus influenzae type b (Hib) conjugate vaccine composed of H. influenzae type b capsular polysaccharide (polyribosyl-ribitol-phosphate [PRP]) conjugated to inactivated tetanus toxoid (PRP-T). Hiberix is licensed for use as the booster (final) dose of the Hib vaccine series for children aged 15 months through 4 years (before the 5th birthday) who have received previously the primary series of Hib vaccination (consisting of 2 or 3 doses, depending on the formulation). The Advisory Committee on Immunization Practices (ACIP) recommends Hib booster vaccination for children at ages 12 through 15 months; however, because of the recent shortage of Hib vaccines, many children have deferred the booster dose and therefore require catch-up vaccination. This report summarizes the indications for Hiberix use and provides guidance on Hib booster dose administration based on increasing vaccine supplies. Vaccination recommendations in this report update the previous advisory on Hib booster administration (June 26, 2009), which advised that children with deferred booster doses receive it at the next regularly scheduled visit. Vaccination providers are now recommended to begin recall of children in need of the booster dose when feasible and monovalent Hib vaccine supply in the office is adequate.

Updated recommendations for use of Haemophilus influenzae type b (Hib) vaccine: reinstatement of the booster dose at ages 12-15 months.

On December 13, 2007, certain lots of Haemophilus influenzae type b (Hib) vaccine marketed as PedvaxHIB (monovalent Hib vaccine) and Comvax (Hib-HepB vaccine), and manufactured by Merck & Co., Inc., were recalled voluntarily, and the company temporarily suspended production of these vaccines. To conserve the limited supply of Hib-containing vaccines, CDC, in consultation with the Advisory Committee on Immunization Practices (ACIP), the American Academy of Family Physicians (AAFP), and the American Academy of Pediatrics (AAP), on December 18, 2007, recommended that vaccination providers temporarily defer the routine Hib vaccine booster dose administered to most healthy children at age 12-15 months.