Public health impact and return on investment of Belgium’s pediatric immunization program

ObjectiveWe evaluated the public health impact and return on investment of Belgium’s pediatric immunization program (PIP) from both healthcare-sector and societal perspectives.MethodsWe developed a decision analytic model for 6 vaccines routinely administered in Belgium for children aged 0–10 years: DTaP-IPV-HepB-Hib, DTaP-IPV, MMR, PCV, rotavirus, and meningococcal type C. We used separate decision trees to model each of the 11 vaccine-preventable pathogens: diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type b, measles, mumps, rubella, Streptococcus pneumoniae, rotavirus, and meningococcal type C; hepatitis B was excluded because of surveillance limitations. The 2018 birth cohort was followed over its lifetime. The model projected and compared health outcomes and costs with and without immunization (based on vaccine-era and pre–vaccine era disease incidence estimates, respectively), assuming that observed reductions in disease incidence were fully attributable to vaccination. For the societal perspective, the model included productivity loss costs associated with immunization and disease in addition to direct medical costs. The model estimated discounted cases averted, disease-related deaths averted, life-years gained, quality-adjusted life-years gained, costs (2020 euros), and an overall benefit–cost ratio. Scenario analyses considered alternate assumptions for key model inputs.ResultsAcross all 11 pathogens, we estimated that the PIP prevented 226,000 cases of infections and 200 deaths, as well as the loss of 7,000 life-years and 8,000 quality-adjusted life-years over the lifetime of a birth cohort of 118,000 children. The PIP was associated with discounted vaccination costs of €91 million from the healthcare-sector perspective and €122 million from the societal perspective. However, vaccination costs were more than fully offset by disease-related costs averted, with the latter amounting to a discounted €126 million and €390 million from the healthcare-sector and societal perspectives, respectively. As a result, pediatric immunization was associated with overall discounted savings of €35 million and €268 million from the healthcare-sector and societal perspectives, respectively; every €1 invested in childhood immunization resulted in approximately €1.4 in disease-related cost savings to the health system and €3.2 in cost savings from a societal perspective for Belgium’s PIP. Estimates of the value of the PIP were most sensitive to changes in input assumptions for disease incidence, productivity losses due to disease-related mortality, and direct medical disease costs.ConclusionBelgium’s PIP, which previously had not been systematically assessed, provides large-scale prevention of disease-related morbidity and premature mortality, and is associated with net savings to health system and society. Continued investment in the PIP is warranted to sustain its positive public health and financial impact

Cost-Effectiveness of Nucleoside Reverse Transcriptase Inhibitor Pairs in Efavirenz-Based Regimens for Treatment-Naïve Adults with HIV Infection in the United States

AbstractObjectiveTo estimate the cost-effectiveness of once-daily tenofovir/emtricitabine compared with twice-daily zidovudine/lamivudine and once-daily abacavir/lamivudine in treatment-naïve adults with HIV-1 infection in the United States.MethodsA Markov model with four therapy lines and six health states based on CD4+ cell-count ranges was developed to estimate lifetime costs and health outcomes. Efficacy data (virologic response and CD4+ cell-count changes) for first-line therapy were from 144-week results of Study 934 comparing tenofovir/emtricitabine with zidovudine/lamivudine and 48-week results of Study CNA30024 comparing abacavir/lamivudine with zidovudine/lamivudine, all in combination with efavirenz. Data from Study CNA30024 for abacavir/lamivudine were adjusted to allow for an indirect comparison with tenofovir/emtricitabine. Subsequent therapy lines were based on likely baskets of antiretroviral therapy recommended by US treatment guidelines. Utility values, mortality rates, and costs (2009 US dollars) were obtained from published sources. Base-case results were tested in sensitivity and variability analyses.ResultsAverage discounted results showed that individuals using tenofovir/emtricitabine were predicted to remain on first-line therapy for 7.7 years, accrue lifetime costs of $747,327, and experience 15.75 quality-adjusted life-years (QALYs), compared with 6.0 years,$777,090, and 15.68 QALYs for individuals using abacavir/lamivudine and 5.8 years, $778,287, and 15.44 QALYs for individuals using zidovudine/lamivudine. Tenofovir/emtricitabine was cost-effective compared with the other two first-line regimens in more than 75$0 and $250,000 per QALY gained. Results were robust in variability and one-way sensitivity analyses.ConclusionsTenofovir/emtricitabine was predicted to be more effective and cost-saving compared with abacavir/lamivudine and zidovudine/lamivudine in treatment-naïve adults with HIV-1 infection in the United States. © 2011, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). All rights reserved

Cost-effectiveness of seasonal quadrivalent versus trivalent influenza vaccination in the United States: A dynamic transmission modeling approach

Trivalent inactivated influenza vaccines (IIV3s) protect against 2 A strains and one B lineage; quadrivalent versions (IIV4s) protect against an additional B lineage. The objective was to assess projected health and economic outcomes associated with IIV4 versus IIV3 for preventing seasonal influenza in the US. A cost-effectiveness model was developed to interact with a dynamic transmission model. The transmission model tracked vaccination, influenza cases, infection-spreading interactions, and recovery over 10 y (2012–2022). The cost-effectiveness model estimated influenza-related complications, direct and indirect costs (2013–2014 US$), health outcomes, and cost-effectiveness. Inputs were taken from published/public sources or estimated using regression or calibration. Outcomes were discounted at 3$599 million; 5.7%) are predicted to be more than offset by reduced influenza treatment costs ($699 million; 12.2$100 million; 0.6%). Including indirect costs, savings with IIV4 are predicted to be $7.1 billion (5.6%). Scenario analyses predict IIV4 to be cost-saving in all scenarios tested apart from low infectivity, where IIV4 is predicted to be cost-effective. In summary, seasonal influenza vaccination in the US with IIV4 versus IIV3 is predicted to improve health outcomes and reduce costs

Cost calculator for mass vaccination response to a US college campus outbreak of serogroup B meningococcal disease

Serogroup B (MenB) is the leading cause of meningococcal disease among 16- to 23-year-olds in the United States and has been responsible for all 10 college outbreaks between 2011 and 2017. Outbreak-associated costs levy a substantial and unforeseen burden on colleges/universities and surrounding communities, in part because they involve collaboration with local and state health departments to develop points-of-dispensing (PODs) outbreak response plans and rapid mass vaccination of a large at-risk student population. The MenB outbreak at Providence College in 2015 was used as a case study to develop an Excel-based Meningococcal Outbreak Cost Calculator that uses target populations for mass vaccination to estimate the costs and resources associated with a meningococcal disease outbreak response. Resources include labor, medical supply, and other nonlabor costs (eg, vaccine-related adverse event costs) over an 18-month period following the outbreak declaration. Based on the actual Providence College population partially or fully vaccinated with MenB-FHbp (Trumenba®, Bivalent rLP2086) (3-dose schedule), the calculator estimated aggregate direct costs of $1,350,963 over 18 months post-outbreak for 4,418 individuals. For planned full vaccination of the enrolled undergraduate population (4,795 individuals), the tool estimated total costs of$1,798,399. In both cases, the majority of costs were for medical supplies (88%–89%) and contract services (7%–9%). This calculator can help to plan a mass vaccination campaign for MenB outbreak control, and underscores the need to vaccinate pre-emptively against diverse disease-causing strains before an outbreak occurs

Understanding the role of exogenous boosting in modeling varicella vaccination

Introduction: The exogenous boosting (EB) hypothesis posits that cell-mediated immunity is boosted for individuals reexposed to varicella-zoster virus (VZV). Historically, mathematical models of the impact of universal childhood varicella vaccination (UVV) have used limited data to capture EB and often conclude that UVV will temporarily increase herpes zoster (HZ) incidence. Areas covered: We updated a 2013 systematic literature review of 40 studies to summarize new evidence from observational or modeling studies related to EB and its parameterization. We abstracted data on observational study designs and mathematical model structures, EB frameworks, and HZ-related parameter values. Expert commentary: This review identified an additional 41 studies: 22 observational and 19 modeling studies. Observational analyses generally reported pre-UVV increases in HZ incidence, making it difficult to attribute post-UVV increases to UVV versus other causes. Modeling studies considered a range of EB frameworks, from no boosting to full permanent immunity. Mathematical modeling efforts are needed in countries with long-standing vaccination programs to capture the dynamics of VZV transmission and temporal changes that may affect HZ incidence. Use of real-world pre-/postvaccination data on varicella and HZ incidence to validate model predictions may improve approaches to EB parameterization and understanding of the effects of varicella vaccination programs

Impact of population aging on the burden of vaccine-preventable diseases among older adults in the United States

Despite vaccination recommendations, the burden of vaccine-preventable diseases remains high in older adults in the United States (US), contributing to substantial morbidity, mortality, and health care resource use and costs. To adequately plan for health care resource needs and to help inform vaccination policies, burden of disease projections that account for population aging over the coming decades are needed. As a first step, this exploratory study projects the burden of influenza, pertussis, herpes zoster, and pneumococcal disease in adults aged 50 y and older in the US, using a population-based modeling framework with separate decision trees for each vaccine-preventable disease. The model uses projected population estimates from the US Census Bureau to account for changes in the US population over time and then calculates expected numbers of cases and associated costs for each disease, keeping current estimates of age-specific disease incidence, vaccine coverage, and efficacy constant over time. This approach was used to focus the exploratory analysis on the burden of disease that may be expected due to population changes alone, assuming that all else remains unchanged. Due to population growth and the shifting age distribution over the next 30 y, the annual societal economic burden for the four vaccine-preventable diseases is projected to increase from approximately $35 billion to$49 billion, resulting in cumulative costs of approximately $1.3 trillion, as well as more than 1 million disease-related deaths. Given such notable burden, further efforts to increase vaccination coverage and effectiveness in older adults are needed

Cost-effectiveness of Telaprevir Combination Therapy for Chronic Hepatitis C

<div><p>Objective</p><p>To explore the expected long-term health and economic outcomes of telaprevir (TVR) plus peginterferon alfa-2a and ribavirin (PR), a regimen that demonstrated substantially increased sustained virologic response (SVR) compared with PR alone in adults with chronic genotype 1 hepatitis C virus (HCV) and compensated liver disease in the Phase III studies ADVANCE (treatment-naïve patients) and REALIZE (relapsers, partial responders, and null responders to previous PR treatment).</p><p>Study Design</p><p>A decision-analytic model was developed to assess the cost-effectiveness of TVR+PR vs. PR in the United States (US).</p><p>Methods</p><p>Patients first moved through the 72-week decision-tree treatment phase of the model and then entered the cyclic Markov post-treatment phase. Clinical data (patient characteristics, SVR rates, and adverse event rates and durations) were obtained from ADVANCE and REALIZE. Health-state transition probabilities, drug and other costs (in 2012/2013 US dollars), and utility values were obtained from the trials, published studies, and publicly available sources. Outcomes were discounted at 3% per year.</p><p>Results</p><p>Regardless of treatment history, patients receiving TVR+PR were projected to experience fewer liver-disease complications, more life-years, and more quality-adjusted life-years (QALYs) than patients receiving PR. In prior relapsers, TVR+PR was dominant, with lower total medical costs and more QALYs. For the other patient subgroups, incremental costs per QALY gained were between $16,778 (treatment-naïve patients) and$34,279 (prior null responders). Extensive sensitivity analyses confirmed robust model results.</p><p>Conclusions</p><p>At standard willingness-to-pay thresholds, TVR+PR represents a cost-effective treatment option compared with PR alone for patients with chronic genotype 1 HCV and compensated liver disease in the US. Future analyses are needed to compare TVR+PR with all existing HCV treatment options.</p></div

Input Parameter Values, by Health State, Age, and Sex.

<p>DCC indicates decompensated cirrhosis; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; PR, peginterferon alfa-2a plus ribavirin; SVR, sustained virologic response; TVR, telaprevir; US, United States.</p>a<p>Annual probabilities of progression in METAVIR fibrosis score for patients with SVR and with no or mild fibrosis (F0–F2) were assumed to be zero, which was consistent with data reported in various published studies <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090295#pone.0090295-Poynard1" target="_blank">[18]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090295#pone.0090295-Poynard2" target="_blank">[34]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090295#pone.0090295-Camm2" target="_blank">[35]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090295#pone.0090295-Sherman1" target="_blank">[36]</a>.</p>b<p>Patients in the TVR+PR arm of the model received TVR for a total of 12 weeks and peginterferon alfa-2a plus ribavirin for a total of 24 or 48 weeks (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090295#pone-0090295-g001" target="_blank">Figure 1</a>).</p>c<p>Post-treatment costs for patients who did not achieve SVR represent incremental costs over those incurred by patients who achieved SVR. Therefore, the model assumed post-treatment costs for patients who achieved SVR were $0. These post-treatment costs do not include additional costs incurred by patients who progressed to DCC, HCC, or liver transplant, which are shown separately.</p>d<p>Consistent with the clinical trial protocols, anemia was managed with ribavirin dose reductions; therefore, costs of epoetin alfa were excluded from the analysis.</p

Base-Case Model Results: Average Per-Patient Lifetime Health and Cost Outcomes by Patient Subgroup.

<p>DCC indicates decompensated cirrhosis; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; ICER, incremental cost-effectiveness ratio; PR, peginterferon alfa-2a plus ribavirin; QALY, quality-adjusted life-year; TVR, telaprevir.</p>a<p>Modeled cases of cirrhosis that developed following treatment.</p>b<p>Due to rounding, ICERs differ slightly from calculations using costs, life-years, and QALYs shown in this table.</p>c<p>One treatment dominates another if it exhibits more QALYs at a lower total cost.</p