Tjalke A. Westra

Cost-Effectiveness Analysis of Various Pertussis Vaccination Strategies Primarily Aimed at Protecting Infants in the Netherlands

BACKGROUND Pertussis is a highly contagious respiratory disease. Despite a high rate of vaccine coverage through the Dutch national immunization program, the incidence of pertussis remains high in the Netherlands and the risk of infection continues. Because pertussis is most severe in unimmunized infants and infants who have only received some of the recommended doses, new pertussis immunization strategies should be considered to protect this vulnerable population. OBJECTIVE This study was designed to estimate the cost-effectiveness of 3 new immunization strategies for possible addition to the current Dutch national immunization program: immunization of the infant at birth, immunization of the parents immediately after birth of the child (cocooning), and maternal immunization during the third trimester of pregnancy. METHODS A literature search was performed in the PubMed database for articles published in English, German, and Dutch using the following terms: pertussis, whooping cough, vaccination strategies, maternal immunization, cocooning, at birth, vaccine efficacy, mortality, underreporting, prevalence, incidence, and cost-effectiveness. A decision-tree model was developed for this analysis, and data on pertussis morbidity and costs were collected consistently for different age groups (infants <1 year of age and adults 25 to 34 years of age). The size of the infant cohort was set at 200,000 to approximate previous Dutch birth cohorts. The size of the adult cohort was set at 401,380 parents for the cocooning strategy and 201,380 mothers for the maternal immunization strategy. Health benefits (quality-adjusted life-years [QALYs]) and costs were estimated in both cohorts for each of the 3 immunization strate- gies. Incremental cost-effectiveness ratios were calculated from both a payers and a societal perspective. The robustness of the results was determined through sensitivity analysis. RESULTS In the base-case analysis, cocooning and maternal immunization were found to be effective in reducing the incidence of pertussis among infants (123 and 174 infant cases were expected to be prevented, respectively). Furthermore, cocooning and maternal immunization were estimated to be cost-effective from a payers perspective (euro4600 [US

Cost-Effectiveness of Adolescent Pertussis Vaccination for The Netherlands: Using an Individual-Based Dynamic Model

6400]/QALY and euro3500 [

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4900]/QALY, respectively) and even cost-saving from a societal perspective (savings of up to euro7200 [

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10,100] and euro5000 [

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7000], respectively). Sensitivity analyses revealed that favorable cost-effectiveness was generally robust. In the sensitivity analysis, the cost-effectiveness of cocooning and maternal immunization was mostly sensitive for changes in assumptions on underreporting (200-fold increase in reported number of symptomatic cases) of pertussis disease and infection. With no underreporting, the ICER was estimated at euro211,900 (

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296,700)/QALY for cocooning and euro81,600 (

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114,200)/QALY for maternal immunization from a payers perspective. However, even at much lower levels of underreporting (20- to 30-fold increase in incidence), cost-effectiveness remained favorable. The cost-effectiveness of the third strategy, at-birth immunization, was highly unfavorable (euro329,900 [

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461,900]/QALY from a payers perspective and euro330,100 [

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462,100]/ QALY from a societal perspective). CONCLUSIONS This study estimated that the addition of cocooning or maternal immunization to the current Dutch national immunization program likely would be cost-effective or even cost-saving. These estimates were mainly due to reduction in the number of cases among parents, which are likely to be mild and therefore would largely remain unreported. Immunization at birth was not a cost-effective strategy. Cocooning was the most expensive intervention to implement; however, it resulted in the highest number of QALYs gained (mainly in adults). Maternal immunization would offer better protection of infants, due to maternally acquired antibodies.

Accumulating evidence for the case of differential discounting

Background Despite widespread immunization programs, a clear increase in pertussis incidence is apparent in many developed countries during the last decades. Consequently, additional immunization strategies are considered to reduce the burden of disease. The aim of this study is to design an individual-based stochastic dynamic framework to model pertussis transmission in the population in order to predict the epidemiologic and economic consequences of the implementation of universal booster vaccination programs. Using this framework, we estimate the cost-effectiveness of universal adolescent pertussis booster vaccination at the age of 12 years in the Netherlands. Methods/Principal Findings We designed a discrete event simulation (DES) model to predict the epidemiological and economic consequences of implementing universal adolescent booster vaccination. We used national age-specific notification data over the period 1996–2000—corrected for underreporting—to calibrate the model assuming a steady state situation. Subsequently, booster vaccination was introduced. Input parameters of the model were derived from literature, national data sources (e.g. costing data, incidence and hospitalization data) and expert opinions. As there is no consensus on the duration of immunity acquired by natural infection, we considered two scenarios for this duration of protection (i.e. 8 and 15 years). In both scenarios, total pertussis incidence decreased as a result of adolescent vaccination. From a societal perspective, the cost-effectiveness was estimated at €4418/QALY (range: 3205–6364 € per QALY) and €6371/QALY (range: 4139–9549 € per QALY) for the 8- and 15-year protection scenarios, respectively. Sensitivity analyses revealed that the outcomes are most sensitive to the quality of life weights used for pertussis disease. Conclusions/Significance To our knowledge we designed the first individual-based dynamic framework to model pertussis transmission in the population. This study indicates that adolescent pertussis vaccination is likely to be a cost-effective intervention for The Netherlands. The model is suited to investigate further pertussis booster vaccination strategies.