Structured Literature Review to Identify Human Papillomavirus's Natural History Parameters for Dynamic Population Models of Vaccine Impacts.

Human papillomavirus (HPV) is a common sexually transmitted virus that can cause cervical cancer and other diseases. Dynamic transmission models (DTMs) have been developed to evaluate the health and economic impacts of HPV vaccination. These models typically include many parameters, such as natural history of the disease, transmission, demographic, behavioral, and screening. To ensure the accuracy of DTM projections, it is important to parameterize them with the best available evidence. This study aimed to identify and synthesize data needed to parametrize DTMs on the natural history of HPV infection and related diseases. Parameters describing data of interest were grouped by their anatomical location (genital warts, recurrent respiratory papillomatosis, and cervical, anal, vaginal, vulvar, head and neck, and penile cancers), and natural history (progression, regression, death, cure, recurrence, detection), and were identified through a systematic literature review (SLR) and complementary targeted literature reviews (TLRs). The extracted data were then synthesized by pooling parameter values across publications, and summarized using the range of values across studies reporting each parameter and the median value from the most relevant study. Data were extracted and synthesized from 223 studies identified in the SLR and TLRs. Parameters frequently reported pertained to cervical cancer outcomes, while data for other anatomical locations were less available. The synthesis of the data provides a large volume of parameter values to inform HPV DTMs, such as annual progression rates from cervical intraepithelial neoplasia (CIN) 1 to CIN 2+ (median of highest quality estimate 0.0836), CIN 2 to CIN 3+ (0.0418), carcinoma in situ (CIS) 2 to local cancer+ (0.0396), and regional to distant cancer (0.0474). Our findings suggest that while there is a large body of evidence on cervical cancer, parameter values featured substantial heterogeneity across studies, and further studies are needed to better parametrize the non-cervical components of HPV DTMs.

Comparison of a static cohort model and dynamic transmission model for respiratory syncytial virus intervention programs for infants in England and Wales.

BACKGROUND: A recent study comparing results of multiple cost-effectiveness analyses (CEAs) in a hypothetical population found that monoclonal antibody (mAb) immunoprophylaxis for respiratory syncytial virus (RSV) in infants averted fewer medically attended cases when estimated using dynamic transmission models (DTMs) versus static cohort models (SCMs). We aimed to investigate whether model calibration or parameterization could be the primary driver of inconsistencies between SCM and DTM predictions. METHODS: A recently published DTM evaluating the CEA of infant mAb immunoprophylaxis in England and Wales (EW) was selected as the reference model. We adapted our previously published SCM for US infants to EW by utilizing the same data sources used by the DTM. Both models parameterized mAb efficacy from a randomized clinical trial (RCT) that estimated an average efficacy of 74.5% against all medically attended RSV episodes and 62.1% against RSV hospitalizations. To align model assumptions, we modified the SCM to incorporate waning efficacy. Since the estimated indirect effects from the DTM were small (i.e., approximately 100-fold smaller in magnitude than direct effects), we hypothesized that alignment of model parameters should result in alignment of model predictions. Outputs for model comparison comprised averted hospitalizations and averted GP visits, estimated for seasonal (S) and seasonal-with-catchup (SC) immunization strategies. RESULTS: When we aligned the SCM intervention parameters to DTM intervention parameters, significantly more averted hospitalizations were predicted by the SCM (S: 32.3%; SC: 51.3%) than the DTM (S: 17.8%; SC: 28.6%). The SCM most closely replicated the DTM results when the initial efficacy of the mAb intervention was 62.1%, leading to an average efficacy of 39.3%. Under this parameterization the SCM predicted 17.4% (S) and 27.7% (SC) averted hospitalizations. Results were similar for averted GP visits. CONCLUSIONS: Parameterization of the RSV mAb intervention efficacy is a plausible primary driver of differences between SCM versus DTM model predictions.

Cost-Effectiveness Analysis of Routine Use of 15-Valent Pneumococcal Conjugate Vaccine in the US Pediatric Population.

This study evaluated the clinical and economic impact of routine pediatric vaccination with the 15-valent pneumococcal conjugate vaccine (PCV15, V114) compared with the 13-valent PCV (PCV13) from a societal perspective in the United States (US). A Markov decision-analytic model was constructed to estimate the outcomes for the entire US population over a 100-year time horizon. The model estimated the impact of V114 versus PCV13 on pneumococcal disease (PD) incidence, post meningitis sequalae, and deaths, taking herd immunity effects into account. V114 effectiveness was extrapolated from the observed PCV13 data and PCV7 clinical trials. Costs (2021$) included vaccine acquisition and administration costs, direct medical costs for PD treatment, direct non-medical costs, and indirect costs, and were discounted at 3% per year. In the base case, V114 prevented 185,711 additional invasive pneumococcal disease, 987,727 all-cause pneumonia, and 11.2 million pneumococcal acute otitis media cases, compared with PCV13. This led to expected gains of 90,026 life years and 96,056 quality-adjusted life years with a total saving of $10.8 billion. Sensitivity analysis showed consistent results over plausible values of key model inputs and assumptions. The findings suggest that V114 is a cost-saving option compared to PCV13 in the routine pediatric vaccination program.

Modeling the Impact of Exogenous Boosting and Universal Varicella Vaccination on the Clinical and Economic Burden of Varicella and Herpes Zoster in a Dynamic Population for England and Wales.

Universal varicella vaccination (UVV) in England and Wales has been hindered by its potential impact on exogenous boosting and increase in herpes zoster (HZ) incidence. We projected the impact of ten UVV strategies in England and Wales on the incidence of varicella and HZ and evaluated their cost-effectiveness over 50 years. The Maternal-Susceptible-Exposed-Infected-Recovered-Vaccinated transmission model was extended in a dynamically changing, age-structured population. Our model estimated that one- or two-dose UVV strategies significantly reduced varicella incidence (70-92%), hospitalizations (70-90%), and mortality (16-41%) over 50 years. A small rise in HZ cases was projected with UVV, peaking 22 years after introduction at 5.3-7.1% above pre-UVV rates. Subsequently, HZ incidence steadily decreased, falling 12.2-14.1% below pre-UVV rates after 50 years. At a willingness-to-pay threshold of 20,000 GBP/QALY, each UVV strategy was cost-effective versus no UVV. Frontier analysis showed that one-dose UVV with MMRV-MSD administered at 18 months is the only cost-effective strategy compared to other strategies. HZ incidence varied under alternative exogenous boosting assumptions, but most UVV strategies remained cost-effective. HZ vaccination decreased HZ incidence with minimal impact on the cost-effectiveness. Introducing a UVV program would significantly reduce the clinical burden of varicella and be cost-effective versus no UVV after accounting for the impact on HZ incidence.

Modeling the health and economic implications of adopting a 1-dose 9-valent human papillomavirus vaccination regimen in a high-income country setting: An analysis in the United Kingdom.

Although no human papillomavirus (HPV) vaccine is indicated for single-dose administration, some observational evidence suggests that a 1-dose regimen might reduce HPV infection risk to that achieved with 2 doses. This study estimated the potential health and economic outcomes associated with switching from a 2-dose HPV vaccination program for girls and boys aged 13-14 years to an off-label 9-valent (9vHPV), 1-dose regimen, accounting for the uncertainty of the effectiveness and durability of a single dose. A dynamic HPV transmission infection and disease model was adapted to the United Kingdom and included a probabilistic sensitivity analysis using estimated distributions for duration of protection of 1-dose and degree of protection of 1 relative to 2 doses. One-way sensitivity analyses of key inputs were performed. Outcomes included additional cancer and disease cases and the difference in net monetary benefit (NMB). The 1-dose program was predicted to result in 81,738 additional HPV-related cancer cases in males and females over 100 years compared to the 2-dose program, ranging from 36,673 to 134,347 additional cases (2.5% and 97.5% quantiles, respectively), and had a 7.8% probability of being cost-effective at the £20,000/quality-adjusted life years willingness-to-pay (WTP) threshold. In one-way sensitivity analyses, the number of additional cancer cases was sensitive to the median of the duration of protection distribution and coverage rates. The differences in NMBs were sensitive to the median of the duration of protection distribution, dose price and discount rate, but not coverage variations. Across sensitivity analyses, the probability of 1 dose being cost-effective vs 2 doses was < 50% at the standard WTP threshold. Adoption of a 1-dose 9vHPV vaccination program resulted in more vaccine-preventable HPV-related cancer and disease cases in males and females, introduced substantial uncertainty in health and economic outcomes, and had a low probability of being cost-effective compared to the 2-dose program.

Cost­Effectiveness Risk­Aversion Curves: Comparison of Risk-Adjusted Performance Measures and Expected-Utility Approaches.

Accounting for risk attitudes in medical decision making under uncertainty has attracted little research. A recent proposal recommended using the results of a cost-effectiveness analysis to construct a cost-effectiveness risk-aversion curve (CERAC) to inform risk-averse decision makers choosing among healthcare programs with uncertain costs and effects. The CERAC is based on a risk-adjusted performance measure widely used in financial economics called the Sortino ratio. This paper evaluates the CERAC based on the Sortino ratio, derives its various properties, discusses the implications of using it to inform decision making under uncertainty, and compares it with the expected-utility approach. Analytic formulae for the CERAC, relating it to the means and standard deviations of costs and effects of a healthcare program, are derived for both approaches. Compared with the expected-utility approach, the CERAC based on the Sortino ratio implicitly assumes that the decision maker is highly risk averse.

Vaccination and herd immunity thresholds in heterogeneous populations.

It has been suggested, without rigorous mathematical analysis, that the classical vaccine-induced herd immunity threshold (HIT) assuming a homogeneous population can be substantially higher than the minimum HIT obtained when considering population heterogeneities. We investigated this claim by developing, and rigorously analyzing, a vaccination model that incorporates various forms of heterogeneity and compared it with a model that considers a homogeneous population. By employing a two-group vaccination model in heterogeneous populations, we theoretically established conditions under which heterogeneity leads to different HIT values, depending on the relative values of the contact rates for each group, the type of mixing between the groups, the relative vaccine efficacy, and the relative population size of each group. For example, under biased random mixing assumption and when vaccinating a given group results in disproportionate prevention of higher transmission per capita, we show that it is optimal to vaccinate that group before vaccinating the other groups. We also found situations, under biased assortative mixing assumption, where it is optimal to vaccinate more than one group. We show that regardless of the form of mixing between the groups, the HIT values assuming a heterogeneous population are always lower than the HIT values obtained from a corresponding model with a homogeneous population. Using realistic numerical examples and parametrization (e.g., assuming assortative mixing together with vaccine efficacy of 95% and the value of the basic reproduction number, [Formula: see text], of the model set at [Formula: see text] 2.5), we demonstrate that the HIT value generated from a model that considers population heterogeneity (e.g., biased assortative mixing) is significantly lower (40%) compared with a HIT value of 63% obtained if the model uses homogeneous population.

Cost-effectiveness of routine catch-up hepatitis a vaccination in the United States: Dynamic transmission modeling study.

BACKGROUND: Despite routine vaccination of children against hepatitis A (HepA), a large segment of the United States population remains unvaccinated, imposing a risk of hepatitis A virus (HAV) to adolescents and adults. In July of 2020, the Advisory Committee on Immunization Practices recommended that all children and adolescents aged 2-18 years who have not previously received a HepA vaccine be vaccinated. We evaluated the public health impact and cost-effectiveness of this HepA catch-up vaccination strategy. METHODS: We used a dynamic transmission model to compare adding a HepA catch-up vaccination of persons age 2-18 years to a routine vaccination of children 12-23 months of age with routine vaccination only in the United States. The model included various health compartments: maternal antibodies, susceptible, exposed, asymptomatic infectious, symptomatic infectious (outpatient, hospitalized, liver transplant, post- liver transplant, death), recovered, and vaccinated with and without immunity. Using a 3% annual discount rate, we estimated the incremental cost per quality-adjusted life year (QALY) gained from a societal perspective over a 100-year time horizon. All costs were converted into 2020 US dollars. FINDINGS: Compared with the routine vaccination policy at 12-23 months of age over 100 years, the catch-up program for unvaccinated children and adolescents aged 2-18 years, prevented 70,072 additional symptomatic infections, 51,391 outpatient visits, 16,575 hospitalizations, and 413 deaths. The catch-up vaccination strategy was cost-saving when compared with the routine vaccination strategy. In scenario analysis allowing administering a second dose to partially vaccinated children, the cost-effectiveness of was not favorable at a higher vaccination coverage ($196,701/QALY at 5% and $476,241/QALY at 50%). INTERPRETATION: HepA catch-up vaccination in the United States is expected to reduce HepA morbidity and mortality and save cost. The catch-up program would be optimized when focusing on unvaccinated children and adolescents and maximizing their first dose coverage.

Mathematical assessment of the impact of cohort vaccination on pneumococcal carriage and serotype replacement.

Although pneumococcal vaccines are quite effective in reducing disease burden, factors such as imperfect vaccine efficacy and serotype replacement present an important challenge against realizing direct and herd protection benefits of the vaccines. In this study, a novel mathematical model is designed and used to describe the dynamics of two Streptococcus pneumoniae (SP) serotypes, in response to the introduction of a cohort vaccination program which targets one of the two serotypes. The model is fitted to a pediatric SP carriage prevalence data from Atlanta, GA. The model, which is rigorously analysed to investigate the existence and asymptotic stability properties of the associated equilibria (in addition to exploring conditions for competitive exclusion), is simulated to assess the impact of vaccination under different levels of serotype-specific competition and illustrate the phenomenon of serotype replacement. The calibrated model is used to forecast the carriage prevalence in the pediatric cohort over 30 years.

A primer on using mathematics to understand COVID-19 dynamics: Modeling, analysis and simulations.

The novel coronavirus (COVID-19) pandemic that emerged from Wuhan city in December 2019 overwhelmed health systems and paralyzed economies around the world. It became the most important public health challenge facing mankind since the 1918 Spanish flu pandemic. Various theoretical and empirical approaches have been designed and used to gain insight into the transmission dynamics and control of the pandemic. This study presents a primer for formulating, analysing and simulating mathematical models for understanding the dynamics of COVID-19. Specifically, we introduce simple compartmental, Kermack-McKendrick-type epidemic models with homogeneously- and heterogeneously-mixed populations, an endemic model for assessing the potential population-level impact of a hypothetical COVID-19 vaccine. We illustrate how some basic non-pharmaceutical interventions against COVID-19 can be incorporated into the epidemic model. A brief overview of other kinds of models that have been used to study the dynamics of COVID-19, such as agent-based, network and statistical models, is also presented. Possible extensions of the basic model, as well as open challenges associated with the formulation and theoretical analysis of models for COVID-19 dynamics, are suggested.

Public health impact and cost-effectiveness of catch-up 9-valent HPV vaccination of individuals through age 45 years in the United States.

The Advisory Committee on Immunization Practices (ACIP) recommended catch-up 9-valent Human Papillomavirus (HPV) vaccination through age 26 years, and shared clinical decision-making for adults aged 27-45 years, compared with catch-up through age 26 years and 21 years for females and males, respectively (status quo; pre-June-2019 recommendations). This study assessed the public health impact and cost-effectiveness of expanded catch-up vaccination through age 45 years (expanded catch-up) compared with status quo. We used an HPV dynamic transmission infection and disease model to assess disease outcomes and incremental cost-effectiveness ratio (ICER) of expanded catch-up compared with status quo. Costs (2018 USD), calculated from a healthcare sector perspective, and quality-adjusted life years (QALY) were discounted at 3% annually. Historical vaccination coverage was estimated using NIS-TEEN survey data (NHANES data for sensitivity analysis). Alternative scenario analyses included restricting upper age of expanded catch-up through 26 years (June-2019 ACIP recommendation), 29 years, and further 5-year increments. Our results show expanded catch-up vaccination would prevent additional 37,856 cancers, 314,468 cervical intraepithelial neoplasia-2/3s, 1,743,461 genital warts, and 10,698 deaths compared with status quo over 100 years at cost of $141,000/QALY. With NHANES coverage, the ICER was $96,000/QALY. The June-2019 ACIP recommendation also provided public health benefits with an ICER of $117,000/QALY, compared with status quo. The ICER for expanded vaccination through age 34 years was $107,000/QALY. Expanding catch-up vaccination program through age 45 years-old in the US is expected to provide public health benefits, and cost-effectiveness improves with expanding catch-up through age 34.

Public health impact and cost effectiveness of routine and catch-up vaccination of girls and women with a nine-valent HPV vaccine in Japan: a model-based study.

BACKGROUND: Combined with cancer screening programs, vaccination against human papillomavirus (HPV) can significantly reduce the high health and economic burden of HPV-related disease in Japan. The objective of this study was to assess the health impact and cost effectiveness of routine and catch-up vaccination of girls and women aged 11-26 years with a 4-valent (4vHPV) or 9-valent HPV (9vHPV) vaccine in Japan compared with no vaccination. METHODS: We used a mathematical model adapted to the population and healthcare settings in Japan. We compared no vaccination and routine vaccination of 12-16-year old girls with 1) 4vHPV vaccine, 2) 9vHPV vaccine, and 3) 9vHPV vaccine in addition to a temporary catch-up vaccination of 17-26 years old girls and women with 9vHPV. We estimated the expected number of disease cases and deaths, discounted (at 2% per year) future costs (in 2020 ¥) and discounted quality-adjusted life years (QALY), and incremental cost effectiveness ratios (ICER) of each strategy over a time horizon of 100 years. To test the robustness of the conclusions, we conducted scenario and sensitivity analyses. RESULTS: Over 100 years, compared with no vaccination, 9vHPV vaccination was projected to reduce the incidence of 9vHPV-related cervical cancer by 86% (from 15.24 new cases per 100,000 women in 2021 to 2.02 in 2121). A greater number of cervical cancer cases (484,248) and cancer-related deaths (50,102) were avoided through the described catch-up vaccination program. Routine HPV vaccination with 4vHPV or 9vHPV vaccine prevented 5,521,000 cases of anogenital warts among women and men. Around 23,520 and 21,400 diagnosed non-cervical cancers are prevented by catch-up vaccination among women and men, respectively. Compared with no vaccination, the ICER of 4vHPV vaccination was ¥975,364/QALY. Compared to 4vHPV, 9vHPV + Catch-up had an ICER of ¥1,534,493/QALY. CONCLUSIONS: A vaccination program with a 9-valent vaccine targeting 12 to 16 year-old girls together with a temporary catchup program will avert significant numbers of cases of HPV-related diseases among both men and women. Furthermore, such a program was the most cost effective among the vaccination strategies we considered, with an ICER well below a threshold of ¥5000,000/QALY.

Public health impact and cost-effectiveness of a nine-valent gender-neutral HPV vaccination program in France.

OBJECTIVES: In France, 9-valent HPV vaccination is recommended routinely for 11-14-years-old girls and as catch-up for 15-19-years-old girls. Recently, recommendation for gender-neutral vaccination (GNV) has been approved. The objectives of the study were to assess the public health impact and cost-effectiveness of a 9-valent GNV compared with girls-only vaccination program (GOV). METHODS: A published HPV disease transmission dynamic model accounting for herd protection effects with a 100-year time horizon was adapted and calibrated to French data. Epidemiological and economic outcomes included disease cases averted and quality-adjusted life years (QALY). Costs and incremental cost-effectiveness ratio (ICER) were measured in 2018 Euros (€). A coverage rate of 26.2% among girls and boys was assumed for the GNV program based on the current female coverage rate in France. The base case included genital warts, cervical, vulvar, vaginal, and anal cancers. Scenario analyses included all HPV-related diseases and considered higher vaccination coverage rate (60%). Deterministic sensitivity analyses on key inputs were performed. RESULTS: Over 100 years, GNV resulted in an additional reduction of 9,519 and 3,037 cervical cancer cases and deaths; 6,901 and 1,166 additional anal cancer cases and deaths; and a reduction of additional 1,284,077 genital warts compared with current GOV and an ICER of 24,763€/QALY. When including all HPV-related diseases, the ICER was 15,184€/QALY. At a higher coverage rate (60%), GNV would prevent 17,430 and 4,334 additional anogenital cancer cases and deaths and over two million genital warts compared with GOV with an ICER of 40,401€/QALY. Results were sensitive to a higher discount rate (6% versus 4%) and a shorter duration of protection (20 years versus lifetime). CONCLUSIONS: In France, GNV has a significant impact in terms of public health benefits and may be considered cost-effective compared with GOV at low and high coverage rates.

Correction to: Public health impact and cost effectiveness of routine childhood vaccination for hepatitis a in Jordan: a dynamic model approach.

Following publication of the original article1, the authors noted the following.

Alternative Conversion Methods for Transition Probabilities in State-Transition Models: Validity and Impact on Comparative Effectiveness and Cost-Effectiveness.

Background. In state-transition models (STMs), decision problems are conceptualized using health states and transitions among those health states after predefined time cycles. The naive, commonly applied method (C) for cycle length conversion transforms all transition probabilities separately. In STMs with more than 2 health states, this method is not accurate. Therefore, we aim to describe and compare the performance of method C with that of alternative matrix transformation methods. Design. We compare 2 alternative matrix transformation methods (Eigenvalue method [E], Schure-Padé method [SP]) to method C applied in an STM of 3 different treatment strategies for women with breast cancer. We convert the given annual transition matrix into a monthly-cycle matrix and evaluate induced transformation errors for the transition matrices and the long-term outcomes: life years, quality-adjusted life-years, costs and incremental cost-effectiveness ratios, and the performance related to the decisions. In addition, we applied these transformation methods to randomly generated annual transition matrices with 4, 7, 10, and 20 health states. Results. In theory, there is no generally applicable correct transformation method. Based on our simulations, SP resulted in the smallest transformation-induced discrepancies for generated annual transition matrices for 2 treatment strategies. E showed slightly smaller discrepancies than SP in the strategy, where one of the direct transitions between health states was excluded. For long-term outcomes, the largest discrepancy occurred for estimated costs applying method C. For higher dimensional models, E performs best. Conclusions. In our modeling examples, matrix transformations (E, SP) perform better than transforming all transition probabilities separately (C). Transition probabilities based on alternative conversion methods should therefore be applied in sensitivity analyses.

Projected impact of elbasvir/grazoprevir in patients with hepatitis C virus genotype 1 and chronic kidney disease in Vietnam.

BACKGROUND: Hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in patients with chronic kidney disease (CKD). The objective of this study was to predict the impact of EBR/GZR on the incidence of liver and kidney related complications compared with no treatment (NoTx) and pegylated interferon plus ribavirin (pegIFN/RBV) in patients with CKD stage 4/5 in Vietnam. METHODS: We developed a mathematical model of the natural history of chronic HCV, CKD, and liver disease. Efficacy of EBR/GZR and pegIFN/RBV were derived from the C-SURFER trial and a meta-analysis, respectively. We calculated lifetime cumulative morbidity and mortality rates, including incidence of decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), and life expectancy. RESULTS: Estimated lifetime incidence of DC was significantly reduced in patients receiving EBR/GZR (3.47%) compared to NoTx (18.14%) and pegIFN/RBV (9.01%). Estimated incidence of HCC was 1.02%, 21.64%, and 8.90%, and 1.02% in patients receiving EBR/GZR, NoTx, and pegIFN/RBV. EBR/GZR was estimated to extend life expectancy by 4.2 and 2.0 years compared with NoTx and pegIFN/RBV. CONCLUSIONS: Our model predicted that EBR/GZR will significantly reduce the incidence of liver-related complications and prolong life in patients with chronic HCV GT1 infection and CKD compared with NoTx or pegIFN/RBV.

Public health impact and cost effectiveness of routine childhood vaccination for hepatitis a in Jordan: a dynamic model approach.

BACKGROUND: As the socioeconomic conditions in Jordan have improved over recent decades the disease and economic burden of Hepatitis A has increased. The purpose of this study is to assess the potential health and economic impact of a two-dose hepatitis A vaccine program covering one-year old children in Jordan. METHODS: We adapted an age-structured population model of hepatitis A transmission dynamics to project the epidemiologic and economic impact of vaccinating one-year old children for 50 years in Jordan. The epidemiologic model was calibrated using local data on hepatitis A in Jordan. These data included seroprevalence and incidence data from the Jordan Ministry of Health as well as hospitalization data from King Abdullah University Hospital in Irbid, Jordan. We assumed 90% of all children would be vaccinated with the two-dose regimen by two years of age. The economic evaluation adopted a societal perspective and measured benefits using the quality-adjusted life-year (QALY). RESULTS: The modeled vaccination program reduced the incidence of hepatitis A in Jordan by 99%, 50 years after its introduction. The model projected 4.26 million avoided hepatitis A infections, 1.42 million outpatient visits, 22,475 hospitalizations, 508 fulminant cases, 95 liver transplants, and 76 deaths over a 50 year time horizon. In addition, we found, over a 50 year time horizon, the vaccination program would gain 37,502 QALYs and save over $42.6 million in total costs. The vaccination program became cost-saving within 6 years of its introduction and was highly cost-effective during the first 5 years. CONCLUSION: A vaccination program covering one-year old children is projected to be a cost-saving intervention that will significantly reduce the public health and economic burden of hepatitis A in Jordan.

Cost-effectiveness of Bezlotoxumab Compared With Placebo for the Prevention of Recurrent Clostridium difficile Infection.

Background: Clostridium difficile infection (CDI) is the most commonly recognized cause of recurrent diarrhea. Bezlotoxumab, administered concurrently with antibiotics directed against C. difficile (standard of care [SoC]), has been shown to reduce the recurrence of CDI, compared with SoC alone. This study aimed to assess the cost-effectiveness of bezlotoxumab administered concurrently with SoC, compared with SoC alone, in subgroups of patients at risk of recurrence of CDI. Methods: A computer-based Markov health state transition model was designed to track the natural history of patients infected with CDI. A cohort of patients entered the model with either a mild/moderate or severe CDI episode, and were treated with SoC antibiotics together with either bezlotoxumab or placebo. The cohort was followed over a lifetime horizon, and costs and utilities for the various health states were used to estimate incremental cost-effectiveness ratios (ICERs). Both deterministic and probabilistic sensitivity analyses were used to test the robustness of the results. Results: The cost-effectiveness model showed that, compared with placebo, bezlotoxumab was associated with 0.12 quality-adjusted life-years (QALYs) gained and was cost-effective in preventing CDI recurrences in the entire trial population, with an ICER of $19824/QALY gained. Compared with placebo, bezlotoxumab was also cost-effective in the subgroups of patients aged ≥65 years (ICER of $15298/QALY), immunocompromised patients (ICER of $12597/QALY), and patients with severe CDI (ICER of $21430/QALY). Conclusions: Model-based results demonstrated that bezlotoxumab was cost-effective in the prevention of recurrent CDI compared with placebo, among patients receiving SoC antibiotics for treatment of CDI.

Cost-Utility of Elbasvir/Grazoprevir in Patients with Chronic Hepatitis C Genotype 1 Infection.

OBJECTIVE: To evaluate the cost-utility of treatment with elbasvir/grazoprevir (EBR/GZR) regimens compared with ledipasvir/sofosbuvir (LDV/SOF), ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (3D ± RBV), and sofosbuvir/velpatasvir (SOF/VEL) in patients with chronic hepatitis C genotype (GT) 1 infection. METHODS: A Markov cohort state-transition model was constructed to evaluate the cost-utility of EBR/GZR ± RBV over a lifetime time horizon from the payer perspective. The target population was patients infected with chronic hepatitis C GT1 subtypes a or b (GT1a or GT1b), stratified by treatment history (treatment-naive [TN] or treatment-experienced), presence of cirrhosis, baseline hepatitis C virus RNA (< or ≥6 million IU/mL), and presence of NS5A resistance-associated variants. The primary outcome was incremental cost-utility ratio for EBR/GZR ± RBV versus available oral direct-acting antiviral agents. One-way and probabilistic sensitivity analyses were performed to test the robustness of the model. RESULTS: EBR/GZR ± RBV was economically dominant versus LDV/SOF in all patient populations. EBR/GZR ± RBV was also less costly than SOF/VEL and 3D ± RBV, but produced fewer quality-adjusted life-years in select populations. In the remaining populations, EBR/GZR ± RBV was economically dominant. One-way sensitivity analyses showed varying sustained virologic response rates across EBR/GZR ± RBV regimens, commonly impacted model conclusions when lower bound values were inserted, and at the upper bound resulted in dominance over SOF/VEL in GT1a cirrhotic and GT1b TN noncirrhotic patients. Results of the probabilistic sensitivity analysis showed that EBR/GZR ± RBV was cost-effective in more than 99% of iterations in GT1a and GT1b noncirrhotic patients and more than 69% of iterations in GT1b cirrhotic patients. CONCLUSIONS: Compared with other oral direct-acting antiviral agents, EBR/GZR ± RBV was the economically dominant regimen for treating GT1a noncirrhotic and GT1b TN cirrhotic patients, and was cost saving in all other populations.