Cost-effectiveness of HPV vaccination in 195 countries: A meta-regression analysis.

Cost-effectiveness analysis (CEA) is a well-known, but resource intensive, method for comparing the costs and health outcomes of health interventions. To build on available evidence, researchers are developing methods to transfer CEA across settings; previous methods do not use all available results nor quantify differences across settings. We conducted a meta-regression analysis of published CEAs of human papillomavirus (HPV) vaccination to quantify the effects of factors at the country, intervention, and method-level, and predict incremental cost-effectiveness ratios (ICERs) for HPV vaccination in 195 countries. We used 613 ICERs reported in 75 studies from the Tufts University's Cost-Effectiveness Analysis (CEA) Registry and the Global Health CEA Registry, and extracted an additional 1,215 one-way sensitivity analyses. A five-stage, mixed-effects meta-regression framework was used to predict country-specific ICERs. The probability that HPV vaccination is cost-saving in each country was predicted using a logistic regression model. Covariates for both models included methods and intervention characteristics, and each country's cervical cancer burden and gross domestic product per capita. ICERs are positively related to vaccine cost, and negatively related to cervical cancer burden. The mean predicted ICER for HPV vaccination is 2017 US$4,217 per DALY averted (95% uncertainty interval (UI): US$773-13,448) globally, and below US$800 per DALY averted in 64 countries. Predicted ICERs are lowest in Sub-Saharan Africa and South Asia, with a population-weighted mean ICER across 46 countries of US$706 per DALY averted (95% UI: $130-2,245), and across five countries of US$489 per DALY averted (95% UI: $90-1,557), respectively. Meta-regression analyses can be conducted on CEA, where one-way sensitivity analyses are used to quantify the effects of factors at the intervention and method-level. Building on all published results, our predictions support introducing and expanding HPV vaccination, especially in countries that are eligible for subsidized vaccines from GAVI, the Vaccine Alliance, and Pan American Health Organization.

Mathematical Modeling of Endemic Cholera Transmission.

Mathematical modeling can be used to project the impact of mass vaccination on cholera transmission. Here, we discuss 2 examples for which indirect protection from mass vaccination needs to be considered. In the first, we show that nonvaccinees can be protected by mass vaccination campaigns. This additional benefit of indirect protection improves the cost-effectiveness of mass vaccination. In the second, we model the use of mass vaccination to eliminate cholera. In this case, a high population level of immunity, including contributions from infection and vaccination, is required to reach the "herd immunity" threshold needed to stop transmission and achieve elimination.

Incentives can spur COVID-19 vaccination uptake.

Recent evidence suggests that vaccination hesitancy is too high in many countries to sustainably contain COVID-19. Using a factorial survey experiment administered to 20,500 online respondents in Germany, we assess the effectiveness of three strategies to increase vaccine uptake, namely, providing freedoms, financial remuneration, and vaccination at local doctors. Our results suggest that all three strategies can increase vaccination uptake on the order of two to three percentage points (PP) overall and five PP among the undecided. The combined effects could be as high as 13 PP for this group. The returns from different strategies vary across age groups, however, with older cohorts more responsive to local access and younger cohorts most responsive to enhanced freedoms for vaccinated citizens.

The urgency of resuming disrupted dog rabies vaccination campaigns: a modeling and cost-effectiveness analysis.

Dog vaccination is a cost-effective approach to preventing human rabies deaths. In Haiti, the last nation-wide dog vaccination campaign occurred in 2018. We estimated the number of human lives that could be saved by resuming dog vaccination in 2021 compared to 2022 and compared the cost-effectiveness of these two scenarios. We modified a previously published rabies transmission and economic model to estimate trends in dog and human rabies cases in Haiti from 2005 to 2025, with varying assumptions about when dog vaccinations resume. We compared model outputs to surveillance data on human rabies deaths from 2005 to 2020 and animal rabies cases from 2018 to 2020. Model predictions and surveillance data both suggest a 5- to 8-fold increase in animal rabies cases occurred in Haiti's capital city between Fall 2019 and Fall 2020. Restarting dog vaccination in Haiti in 2021 compared to 2022 could save 285 human lives and prevent 6541 human rabies exposures over a five-year period. It may also decrease program costs due to reduced need for human post-exposure prophylaxis. These results show that interruptions in dog vaccination campaigns before elimination is achieved can lead to significant human rabies epidemics if not promptly resumed.

Economic evaluation for mass vaccination against COVID-19.

BACKGROUND: Vaccine is supposed to be the most effective means to prevent COVID-19 as it may not only save lives but also reduce productivity loss due to resuming pre-pandemic activities. Providing the results of economic evaluation for mass vaccination is of paramount importance for all stakeholders worldwide. METHODS: We developed a Markov decision tree for the economic evaluation of mass vaccination against COVID-19. The effectiveness of reducing outcomes after the administration of three COVID-19 vaccines (BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and AZD1222 (Oxford-AstraZeneca)) were modelled with empirical parameters obtained from literatures. The direct cost of vaccine and COVID-19 related medical cost, the indirect cost of productivity loss due to vaccine jabs and hospitalization, and the productivity loss were accumulated given different vaccination scenarios. We reported the incremental cost-utility ratio and benefit/cost (B/C) ratio of three vaccines compared to no vaccination with a probabilistic approach. RESULTS: Moderna and Pfizer vaccines won the greatest effectiveness among the three vaccines under consideration. After taking both direct and indirect costs into account, all of the three vaccines dominated no vaccination strategy. The results of B/C ratio show that one dollar invested in vaccine would have USD $13, USD $23, and USD $28 in return for Moderna, Pfizer, and AstraZeneca, respectively when health and education loss are considered. The corresponding figures taking value of the statistical life into account were USD $176, USD $300, and USD $443. CONCLUSION: Mass vaccination against COVID-19 with three current available vaccines is cost-saving for gaining more lives and less cost incurred.

Mobile nudges and financial incentives to improve coverage of timely neonatal vaccination in rural areas (GEVaP trial): A 3-armed cluster randomized controlled trial in Northern Ghana.

BACKGROUND: Despite progress in vaccination coverage, timeliness of childhood vaccination remains a challenge in many settings. We aimed to assess if mobile phone-based reminders and incentives to health workers and caregivers could increase timely neonatal vaccination in a rural, low-resource setting. METHODS: We conducted an open-label cluster randomized controlled 1:1:1 trial with three arms in 15 communities in Northern Ghana. Communities were randomized to 1) a voice call reminder intervention; 2) a community health volunteer (CHV) intervention with incentivized rewards; 3) control. In the voice call reminder arm, a study staff member made voice calls to mothers shortly after birth to encourage vaccination and provide personalized information about available vaccination services. In the incentive arm, CHVs promoted infant vaccination and informed women with recent births about available vaccination opportunities. Both CHVs and women were provided small monetary incentives for on-time early infant vaccination in this arm, delivered using mobile phone-based banking applications. No study activities were conducted in control communities. A population-based survey compared vaccination coverage across arms in the pre-intervention and intervention periods. The primary endpoint was completion of at least one dose of Polio vaccine within 14 days of life and BCG vaccination within 28 days of life. RESULTS: Six-hundred ninety births were identified; 106, 88, and 88 from pre-intervention and 150, 135, and 123 in the intervention period, in the control, voice call reminder and CHV incentive arms, respectively. In adjusted intent-to-treat analysis, voice call reminders were associated with 10.5 percentage point (95% CI: 4.0, 17.1) higher coverage of on-time vaccination, while mobile phone-based incentives were associated with 49.5 percentage point (95% CI: 26.4, 72.5) higher coverage. CONCLUSION: Community-based interventions using mobile phone technologies can improve timely early vaccination coverage. A CHV approach with incentives to community workers and caregivers was a more effective strategy than voice call reminders. The impact of vaccination "nudges" via voice calls may be constrained in settings where network coverage and phone ownership are limited. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov; NCT03797950.

Health and economic impact of the pneumococcal conjugate vaccine in hindering antimicrobial resistance in China.

Antimicrobial resistance (AMR) poses a serious threat to global public health. However, vaccinations have been largely undervalued as a method to hinder AMR progression. This study examined the AMR impact of increasing pneumococcal conjugate vaccine (PCV) coverage in China. China has one of the world's highest rates of antibiotic use and low PCV coverage. We developed an agent-based DREAMR (Dynamic Representation of the Economics of AMR) model to examine the health and economic benefits of slowing AMR against commonly used antibiotics. We simulated PCV coverage, pneumococcal infections, antibiotic use, and AMR accumulation. Four antibiotics to treat pneumococcal diseases (penicillin, amoxicillin, third-generation cephalosporins, and meropenem) were modeled with antibiotic utilization, pharmacokinetics, and pharmacodynamics factored into predicting AMR accumulation. Three PCV coverage scenarios were simulated over 5 y: 1) status quo with no change in coverage, 2) scaled coverage increase to 99% in 5 y, and 3) accelerated coverage increase to 85% over 2 y followed by 3 y to reach 99% coverage. Compared to the status quo, we found that AMR against penicillin, amoxicillin, and third-generation cephalosporins was significantly reduced by 6.6%, 10.9%, and 9.8% in the scaled scenario and by 10.5%, 17.0%, and 15.4% in the accelerated scenario. Cumulative costs due to AMR, including direct and indirect costs to patients and caretakers, were reduced by $371 million in the scaled and $586 million in the accelerated scenarios compared to the status quo. AMR-reducing benefits of vaccines are essential to quantify in order to drive appropriate investment.

Cost-effectiveness of the national dog rabies prevention and control program in Mexico, 1990-2015.

BACKGROUND: Rabies is a viral zoonosis that imposes a substantial disease and economic burden in many developing countries. Dogs are the primary source of rabies transmission; eliminating dog rabies reduces the risk of exposure in humans significantly. Through mass annual dog rabies vaccination campaigns, the national program of rabies control in Mexico progressively reduced rabies cases in dogs and humans since 1990. In 2019, the World Health Organization validated Mexico for eliminating rabies as a public health problem. Using a governmental perspective, we retrospectively assessed the economic costs, effectiveness, and cost-effectiveness of the national program of rabies control in Mexico, 1990-2015. METHODOLOGY: Combining various data sources, including administrative records, national statistics, and scientific literature, we retrospectively compared the current scenario of annual dog vaccination campaigns and post-exposure prophylaxis (PEP) with a counterfactual scenario without an annual dog vaccination campaign but including PEP. The counterfactual scenario was estimated using a mathematical model of dog rabies transmission (RabiesEcon). We performed a thorough sensitivity analysis of the main results. PRINCIPAL FINDINGS: Results suggest that in 1990 through 2015, the national dog rabies vaccination program in Mexico prevented about 13,000 human rabies deaths, at an incremental cost (MXN 2015) of $4,700 million (USD 300 million). We estimated an average cost of $360,000 (USD 23,000) per human rabies death averted, $6,500 (USD 410) per additional year-of-life, and $3,000 (USD 190) per dog rabies death averted. Results were robust to several counterfactual scenarios, including high and low rabies transmission scenarios and various assumptions about potential costs without mass dog rabies vaccination campaigns. CONCLUSIONS: Annual dog rabies vaccination campaigns have eliminated the transmission of dog-to-dog rabies and dog-mediated human rabies deaths in Mexico. According to World Health Organization standards, our results show that the national program of rabies control in Mexico has been highly cost-effective.

Epidemiological impact and cost-effectiveness of universal meningitis b vaccination among college students prior to college entry.

OBJECTIVES: University students are at significantly higher risk of serogroup B meningococcal (MenB) infection, which can result in debilitating sequelae and excessive healthcare usage. This study aimed to elucidate the impact of universal pre-enrollment vaccination on MenB outbreak probability and the cost-effectiveness in outbreak-only scenarios. METHODS: We developed an infectious disease transmission model to determine the number of outbreaks averted under universal vaccination and a Markov model to simulate the costs accrued and QALYs lost associated with infection. The analysis was done on a hypothetical population of 40,000 college students over a four-year time frame. We used the outputs of these two models to calculate the incremental cost-effectiveness ratio (ICER) of universal MenB vaccination from a societal perspective. RESULTS: We find that the vaccination strategy was estimated to reduce MenB incidence by 63% and outbreak frequency rate by 90%. Under base case assumptions, the ICER of universal vaccination was $748,129 per QALY and in outbreak-only scenarios, it was cost-saving. CONCLUSIONS: Universal vaccination is not cost-effective at the current low MenB incidence levels and vaccine price in the U.S., but it is cost-saving if outbreak is imminent.

An economic case study of the control of dog-mediated rabies by an animal welfare organisation in Jaipur, India.

A global strategic plan for the elimination of dog-mediated human rabies deaths by 2030 was announced in 2018. The cost-effectiveness of annual mass dog vaccination programmes, as a control and elimination method, has been advocated on many occasions. Complementary methods, such as animal birth control (ABC) activities, have received less attention. This paper provides a case-study of a programme operated by Help in Suffering (HIS) in Jaipur, India from 1994/95 until 2016/17 comprising both ABC and additional vaccination-only activities. The availability of cost data alongside information on dog numbers, dog bites and human rabies cases provided an exceptionally detailed and unique retrospective dataset recording actual events and expenditures. Updated to 2016/17 prices, the total cost of the programme was 658,744 USD. Since 2007/2008, activity costs have been separated and returned costs of 10.78 USD per dog, both sterilised and vaccinated, and 1.86 USD per dog, vaccinated only. Over the course of the programme, the number of disability-adjusted life years (DALYs) due to premature death and the distress associated with dog bites was estimated to be 36,246 fewer than would have been expected if HIS had not been operating, based on a counterfactual scenario using pre-intervention values. Linking the DALY figure to the cost of the activities undertaken by HIS yields a cost of 26 USD per DALY averted. Discounted at 3%, the DALYs averted equate to 16,587 at a cost of 40 USD per DALY averted. Both cases make it a very cost-effective intervention, in relation to the threshold of investing one year's gross domestic product (GDP) per DALY averted (1981 USD in 2016/17). The monetary benefit from fewer dog bites and clinical human rabies cases requiring treatment amounted to 5.62 million USD after discounting, which, if attributed to Help in Suffering, yields a monetary benefit-cost ratio of 8.5. Thus, the potential monetary benefits greatly outweigh the programme costs, even without considering the DALYs averted. If a modest notional monetary value of one year's GDP is assigned to represent the human capital or production value of DALYs averted, the discounted societal economic benefit reaches 38.48 million USD and implies a benefit-cost ratio of 58.4. These economic analyses demonstrate that ABC activities in combination with additional vaccination efforts can be a cost-effective control measure for dog-mediated human rabies.

Evaluación económica de la inclusión en el calendario vacunal de 4CMenB (Bexsero(R)) en España / Economic evaluation of the introduction of 4CMenB (Bexsero(R)) in the national vaccine schedule in Spain

INTRODUCCIÓN: Bexsero® (4CMenB), vacuna contra el meningococo B, fue autorizada en Europa en 2013. En España, a pesar de que el meningococo B es la principal causa de enfermedad meningocócica invasiva (EMI), Bexsero® está recomendada y financiada para pacientes con alto riesgo de EMI pero no de forma sistemática en el calendario vacunal del SNS. OBJETIVO: Evaluar el coste-utilidad, el impacto epidemiológico y los costes totales de la introducción de 4CMenB para una política vacunal informada en España. MÉTODO: Se adaptó para España un análisis de coste-utilidad, árbol de decisión probabilístico. Una cohorte de recién nacidos en 2015 fue modelizada con dos posologías mediante dos estrategias: vacunación sistemática con 4CMenB o no vacunación. Los costes se midieron desde la perspectiva del pagador y los beneficios se calcularon en años de vida ajustados por calidad (AVAC). Se realizó un análisis de Monte Carlo y se consideraron 32 escenarios para valorar la robustez y la incertidumbre de los resultados. RESULTADOS: Con la pauta 3+1, la vacunación sistemática previno el 54% de los casos y de las muertes, y se estimó una razón de coste-utilidad incremental (RCUI) de 351.389 €/AVAC (intervalo de confianza del 95% [IC95%]: 265.193-538.428). La pauta 2+1 previno el 50% de los casos y de las muertes, con una RCUI de 278.556 €/AVAC (IC95%: 210.285-430.122). CONCLUSIONES: Dada la incidencia actual de enfermedad meningocócica invasiva en España y la información disponible sobre 4CMenB, nuestro modelo indica que la vacunación sistemática no es coste-efectiva con el actual precio. Solo con un precio de 1,45 € para la pauta 3+1 o de 3,37 € para la pauta 2+1 podría ser recomendada basándose en su eficiencia

INTRODUCTION: Bexsero® (4CMenB), meningococcal B vaccine, was licensed in Europe in 2013. In Spain, despite MenB being the most frequent cause of invasive meningococcal disease (IMD), Bexsero® is recommended and financed for patients at increased risk of IMD but is not financed by the NHS in the routine vaccination schedule. OBJECTIVE: to evaluate the cost-utility, epidemiological impact, and total costs of the introduction of 4CMenB into the vaccination schedule to help inform vaccine policy in Spain. METHOD: We adapted a cost-utility analysis, a probabilistic decision-tree, to Spain. A cohort of new-born infants in 2015 was modelled with two dosages, using two different strategies: routine vaccination schedule with 4CMenB and non-vaccination. Costs were measured from a payer perspective and benefits were calculated in quality-adjusted life years (QALYs). A Monte Carlo analysis and 32 scenarios were performed to assess the robustness and the uncertainty of our results. RESULTS: With the 3+1 dosage, routine vaccination prevented 54% of cases and deaths and an incremental cost-utility ratio (ICUR) of 351.389 €/QALY (95% confidence interval [95%CI]: 265,193-538,428) was estimated. The 2+1 dosage prevented 50% of cases and deaths, with an ICUR of 278.556 €/QALY (95%CI: 210,285-430,122). CONCLUSIONS: Given the current incidence of invasive meningococcal disease in Spain and the information available from 4CMenB, our model shows that routine vaccination is not cost-effective at the current price. Only with a vaccine price of 1.45 € for the 3+1 schedule or 3.37 € for the 2+1 schedule could it be recommended based on efficiency criteria