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.

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.

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.

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.

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-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.

The Impact of Enhanced Screening and Treatment on Hepatitis C in the United States.

BACKGROUND: The effectiveness of interferon-free direct-acting antivirals (DAA) in treating chronic hepatitis C virus (HCV) is limited by low screening and treatment rates, particularly among people who inject drugs (PWIDs). METHODS: To evaluate the levels of screening and treatment with interferon-free DAAs that are required to control HCV incidence and HCV-associated morbidity and mortality, we developed a transmission model, stratified by age and by injection drug use, and calibrated it to epidemiological data in the United States from 1992 to 2014. We quantified the impact of administration of DAAs at current and at enhanced screening and treatment rates, focusing on outcomes of HCV incidence, prevalence, compensated and decompensated cirrhosis, hepatocellular carcinoma, liver transplants, and mortality from 2015 to 2040. RESULTS: Increasing annual treatment of patients 4-fold-from the approximately 100 000 treated historically to 400 000-is predicted to prevent 526 084 (95% confidence interval, 466 615-593 347) cases of cirrhosis and 256 315 (201 589-316 114) HCV-associated deaths. By simultaneously increasing treatment capacity and increasing the number of HCV infections diagnosed, total HCV prevalence could fall to as low as 305 599 (222 955-422 110) infections by 2040. Complete elimination of HCV transmission in the United States through treatment with DAAs would require nearly universal screening of PWIDs, with an annual treatment rate of at least 30%. CONCLUSIONS: Interferon-free DAAs are projected to achieve marked reductions in HCV-associated morbidity and mortality. Aggressive expansion in HCV screening and treatment, particularly among PWIDs, would be required to eliminate HCV in the United States.

Public Health Impact and Cost-Effectiveness of Hepatitis A Vaccination in the United States: A Disease Transmission Dynamic Modeling Approach.

OBJECTIVE: To assess the population-level impact and cost-effectiveness of hepatitis A vaccination programs in the United States. METHODS: We developed an age-structured population model of hepatitis A transmission dynamics to evaluate two policies of administering a two-dose hepatitis A vaccine to children aged 12 to 18 months: 1) universal routine vaccination as recommended by the Advisory Committee on Immunization Practices in 2006 and 2) Advisory Committee on Immunization Practices's previous regional policy of routine vaccination of children living in states with high hepatitis A incidence. Inputs were obtained from the published literature, public sources, and clinical trial data. The model was fitted to hepatitis A seroprevalence (National Health and Nutrition Examination Survey II and III) and reported incidence from the National Notifiable Diseases Surveillance System (1980-1995). We used a societal perspective and projected costs (in 2013 US $), quality-adjusted life-years, incremental cost-effectiveness ratio, and other outcomes over the period 2006 to 2106. RESULTS: On average, universal routine hepatitis A vaccination prevented 259,776 additional infections, 167,094 outpatient visits, 4781 hospitalizations, and 228 deaths annually. Compared with the regional vaccination policy, universal routine hepatitis A vaccination was cost saving. In scenario analysis, universal vaccination prevented 94,957 infections, 46,179 outpatient visits, 1286 hospitalizations, and 15 deaths annually and had an incremental cost-effectiveness ratio of $21,223/quality-adjusted life-year when herd protection was ignored. CONCLUSIONS: Our model predicted that universal childhood hepatitis A vaccination led to significant reductions in hepatitis A mortality and morbidity. Consequently, universal vaccination was cost saving compared with a regional vaccination policy. Herd protection effects of hepatitis A vaccination programs had a significant impact on hepatitis A mortality, morbidity, and cost-effectiveness ratios.

Chronic hepatitis C virus (HCV) disease burden and cost in the United States.

UNLABELLED: Hepatitis C virus (HCV) infection is a leading cause of cirrhosis, hepatocellular carcinoma, and liver transplantation. A better understanding of HCV disease progression and the associated cost can help the medical community manage HCV and develop treatment strategies in light of the emergence of several potent anti-HCV therapies. A system dynamic model with 36 cohorts was used to provide maximum flexibility and improved forecasting. New infections incidence of 16,020 (95% confidence interval, 13,510-19,510) was estimated in 2010. HCV viremic prevalence peaked in 1994 at 3.3 (2.8-4.0) million, but it is expected to decline by two-thirds by 2030. The prevalence of more advanced liver disease, however, is expected to increase, as well as the total cost associated with chronic HCV infection. Today, the total cost is estimated at $6.5 ($4.3-$8.4) billion and it will peak in 2024 at $9.1 ($6.4-$13.3) billion. The lifetime cost of an individual infected with HCV in 2011 was estimated at $64,490. However, this cost is significantly higher among individuals with a longer life expectancy. CONCLUSION: This analysis demonstrates that US HCV prevalence is in decline due to a lower incidence of infections. However, the prevalence of advanced liver disease will continue to increase as well as the corresponding healthcare costs. Lifetime healthcare costs for an HCV-infected person are significantly higher than for noninfected persons. In addition, it is possible to substantially reduce HCV infection through active management. (HEPATOLOGY 2013;57:2164-2170).

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.

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.

Cost-effectiveness of boceprevir in patients previously treated for chronic hepatitis C genotype 1 infection in the United States.

OBJECTIVES: The phase 3 trial, Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol-2 (RESPOND-2), demonstrated that the addition of boceprevir (BOC) to peginterferon-ribavirin (PR) resulted in significantly higher rates of sustained virologic response (SVR) in previously treated patients with chronic hepatitis C virus (HCV) genotype-1 infection as compared with PR alone. We evaluated the cost-effectiveness of treatment with BOC in previously treated patients with chronic hepatitis C in the United States using treatment-related data from RESPOND-2 and PROVIDE studies. METHODS: We developed a Markov cohort model to project the burden of HCV disease, lifetime costs, and quality-adjusted life-years associated with PR and two BOC-based therapies-response-guided therapy (BOC/RGT) and fixed-duration therapy for 48 weeks (BOC/PR48). We estimated treatment-related inputs (efficacy, adverse events, and discontinuations) from clinical trials and obtained disease progression rates, costs, and quality-of-life data from published studies. We estimated the incremental cost-effectiveness ratio (ICER) for BOC-based regimens as studied in RESPOND-2, as well as by patient's prior response to treatment and the IL-28B genotype. RESULTS: BOC-based regimens were projected to reduce the lifetime incidence of liver-related complications by 43% to 53% in comparison with treatment with PR. The ICER of BOC/RGT in comparison with that of PR was $30,200, and the ICER of BOC/PR48 in comparison with that of BOC/RGT was $91,500. At a willingness-to-pay threshold of $50,000, the probabilities of BOC/RGT and BOC/PR48 being the preferred option were 0.74 and 0.25, respectively. CONCLUSIONS: In patients previously treated for chronic HCV genotype-1 infection, BOC was projected to increase quality-adjusted life-years and reduce the lifetime incidence of liver complications. In addition, BOC-based therapies were projected to be cost-effective in comparison with PR alone at commonly used willingness-to-pay thresholds.

Boceprevir for previously untreated patients with chronic hepatitis C Genotype 1 infection: a US-based cost-effectiveness modeling study.

BACKGROUND: SPRINT-2 demonstrated that boceprevir (BOC), an oral hepatitis C virus (HCV) nonstructural 3 (NS3) protease inhibitor, added to peginterferon alfa-2b (P) and ribavirin (R) significantly increased sustained virologic response rates over PR alone in previously untreated adult patients with chronic HCV genotype 1. We estimated the long-term impact of triple therapy vs. dual therapy on the clinical burden of HCV and performed a cost-effectiveness evaluation. METHODS: A Markov model was used to estimate the incidence of liver complications, discounted costs (2010 US$), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) of three treatment strategies for treatment-naïve patients with chronic HCV genotype 1. The model simulates the treatment regimens studied in SPRINT-2 in which PR was administered for 4 weeks followed by: 1) placebo plus PR for 44 weeks (PR48); 2) BOC plus PR using response guided therapy (BOC/RGT); and 3) BOC plus PR for 44 weeks (BOC/PR48) and makes projections within and beyond the trial. HCV-related state-transition probabilities, costs, and utilities were obtained from previously published studies. All costs and QALYs were discounted at 3%. RESULTS: The model projected approximately 38% and 43% relative reductions in the lifetime incidence of liver complications in the BOC/RGT and BOC/PR48 regimens compared with PR48, respectively. Treatment with BOC/RGT is associated with an incremental cost of $10,348 and an increase of 0.62 QALYs compared to treatment with PR48. Treatment with BOC/PR48 is associated with an incremental cost of $35,727 and an increase of 0.65 QALYs compared to treatment with PR48. The ICERs were $16,792/QALY and $55,162/QALY for the boceprevir-based treatment groups compared with PR48, respectively. The ICER for BOC/PR48 compared with BOC/RGT was $807,804. CONCLUSION: The boceprevir-based regimens used in the SPRINT-2 trial were projected to substantially reduce the lifetime incidence of liver complications and increase the QALYs in treatment-naive patients with hepatitis C genotype 1. It was also demonstrated that boceprevir-based regimens offer patients the possibility of experiencing great clinical benefit with a shorter duration of therapy. Both boceprevir-based treatment strategies were projected to be cost-effective at a reasonable threshold in the US when compared to treatment with PR48.

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.

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.

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.

Human papillomavirus vaccine introduction in low-income and middle-income countries: guidance on the use of cost-effectiveness models.

BACKGROUND: The World Health Organization (WHO) recommends that the cost effectiveness of introducing human papillomavirus (HPV) vaccination is considered before such a strategy is implemented. However, developing countries often lack the technical capacity to perform and interpret results of economic appraisals of vaccines. To provide information about the feasibility of using such models in a developing country setting, we evaluated models of HPV vaccination in terms of their capacity, requirements, limitations and comparability. METHODS: A literature review identified six HPV vaccination models suitable for low-income and middle-income country use and representative of the literature in terms of provenance and model structure. Each model was adapted by its developers using standardised data sets representative of two hypothetical developing countries (a low-income country with no screening and a middle-income country with limited screening). Model predictions before and after vaccination of adolescent girls were compared in terms of HPV prevalence and cervical cancer incidence, as was the incremental cost-effectiveness ratio of vaccination under different scenarios. RESULTS: None of the models perfectly reproduced the standardised data set provided to the model developers. However, they agreed that large decreases in type 16/18 HPV prevalence and cervical cancer incidence are likely to occur following vaccination. Apart from the Thai model (in which vaccine and non-vaccine HPV types were combined), vaccine-type HPV prevalence dropped by 75% to 100%, and vaccine-type cervical cancer incidence dropped by 80% to 100% across the models (averaging over age groups). The most influential factors affecting cost effectiveness were the discount rate, duration of vaccine protection, vaccine price and HPV prevalence. Demographic change, access to treatment and data resolution were found to be key issues to consider for models in developing countries. CONCLUSIONS: The results indicated the usefulness of considering results from several models and sets of modelling assumptions in decision making. Modelling groups were prepared to share their models and expertise to work with stakeholders in developing countries. Please see related article: http://www.biomedcentral.com/1741-7007/9/55.

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.

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.