An Updated Analysis of the Impact of HPV Vaccination Based on Long-term Effectiveness in the Netherlands.

INTRODUCTION: Vaccination against human papillomavirus (HPV) is considered the most effective strategy to protect women from cervical cancer. Three HPV vaccines are currently licensed in Europe and, although they are generally supported by favorable health economic outcomes, current models fall short in predicting vaccination benefits. Here, we aim to re-evaluate the health benefits of HPV vaccination, using updated long-term effectiveness data and emphasizing quality of life losses related to pre-cancer disease and treatment. METHODS: We used a static Markov model that compared "only screening" (includes unvaccinated girls) and "vaccination" (assumes 100% vaccination coverage with the bivalent HPV vaccine). A lifetime cohort of 100,000 uninfected 12-year-old girls was included, in which the number of cases with cervical intraepithelial neoplasia grade 2 or higher/3 (CIN2+, CIN3), cervical cancer, and cervical cancer deaths per scenario were determined. Furthermore, the reduction in major excisional procedures, the preterm deliveries averted, and the related gain in quality-adjusted life years (QALYs) due to vaccination were estimated. RESULTS: The bivalent vaccine showed larger reductions in CIN2+, CIN3, cervical cancer cases, cervical cancer deaths, and major excisional treatments, after including long-term efficacy and effectiveness data, compared to previous data. Moreover, we observed an increased amount of QALYs gained due to prevention of major excisional treatment and the negative side effects related to it. CONCLUSIONS: Updated health economic models for HPV vaccination, using updated and long-term effectiveness data and including prevention of treatment-related side effects, demonstrate a substantial additional positive effect on vaccination outcomes. Indeed, extrapolation of the bivalent HPV vaccine's updated long-term effectiveness data against HPV-related cervical diseases shows that the positive effects of vaccination may be more substantial than previously estimated. There is a graphical abstract available for this article.

Cervical cancer is one of the most common cancers among women, and the most effective strategy for its prevention is vaccination against HPV infection. Several studies have predicted the benefits of vaccination; however, most of them fall short due to a lack of long-term data and treatment impact. The aim of this study is to re-evaluate the benefits of vaccination with the bivalent vaccine in the Netherlands using updated longer-term data and benefits from preventing treatment.We used a cost-effectiveness model to compare two scenarios: only screening and vaccination plus screening. We included 100,000 12-year-old girls in the model and compared the following outcomes: number of individuals with benign cervical lesions, number of individuals with cervical cancer, number of deaths, reduction in treatment after vaccination, premature births avoided after vaccination, and quality of life gains.We found that the bivalent vaccine showed larger reductions in pre-cancerous lesions (CIN2+, CIN3), cervical cancer cases, cervical cancer deaths, and major excisional treatments, compared to the results of previously published cost-effectiveness analyses when new longer-term data were included. The prevention of treatment for the lesions represents a significant added value for vaccination.Our modeling study confirms the protective effect of the bivalent vaccine on cervical cancer. Moreover, it reflects a substantial additional value of vaccination compared to the benefits of vaccination that have been shown before.

Non-restrictive open vial policy combined with the home visit vaccinations for improving BCG coverage in a high-incidence outreach region: A model-based cost-effectiveness analysis for Indonesia.

Background: Bacillus Calmette-Guérin (BCG) vaccination is recommended at birth or in the first week of life to achieve the most beneficial effects in protecting against the most severe type of tuberculosis (TB) disease in children. However, delayed vaccination is commonly reported, especially in outreach or rural areas. We assessed the cost-effectiveness of combining non-restrictive open vial and home visit vaccination strategies in order to increase timely BCG vaccination in a high-incidence outreach setting. Methods: We applied a simplified Markov model for the Papua setting, which resembled a high-incidence outreach setting in Indonesia, to assess the cost-effectiveness of these strategies from a health care and a societal perspective. A moderate increase (75% wastage rate and 25% home vaccination) and a large increase (95% wastage rate and 75% home vaccination) scenario were assessed in the analysis. We calculated incremental cost-effectiveness ratios (ICER) based on the incremental costs and quality-adjusted life years (QALYs) gained by comparing the two strategies to the base case scenario (35% wastage rate and no home vaccination). Results: The costs per vaccinated child were US$10.25 in the base case scenario, increasing slightly in the moderate (US$10.54) and large increase scenarios (US$12.38). The moderate increase scenario was predicted to prevent 5783 TB-related deaths and 790 TB cases while the large increase scenario predicted the prevention of 9865 TB-related deaths and 1348 TB cases for the entire lifespan of our cohort. From a health care perspective, the ICERs were predicted to be US$288/QALY and US$487/QALY, respectively, for the moderate and large increase scenarios. Using Indonesia's gross domestic product (GDP) per person as a threshold, both strategies were considered to be cost-effective. Conclusions: We found that the allocation of resources for timely BCG vaccination based on combining home vaccination and a less restrictive open vial strategy could substantially reduce childhood TB cases and TB-related mortality. Although outreach activities are more expensive than vaccination at a health care facility only, these activities proved to be cost-effective. These strategies might also be beneficial in other high-incidence outreach settings.

Comparing 3 Approaches for Making Vaccine Adoption Decisions in Thailand.

BACKGROUND: The World Health Organization (WHO) has developed the Total System Effectiveness (TSE) framework to assist national policy-makers in prioritizing vaccines. The pilot was launched in Thailand to explore the potential use of TSE in a country with established governance structures and accountable decision-making processes for immunization policy. While the existing literature informs vaccine adoption decisions in GAVI-eligible countries, this study attempts to address a gap in the literature by examining the policy process of a non-GAVI eligible country. METHODS: A rotavirus vaccine (RVV) test case was used to compare the decision criteria made by the existing processes (Expanded Program on Immunization [EPI], and National List of Essential Medicines [NLEM]) for vaccine prioritization and the TSE-pilot model, using Thailand specific data. RESULTS: The existing decision-making processes in Thailand and TSE were found to offer similar recommendations on the selection of a RVV product. CONCLUSION: The authors believe that TSE can provide a well-reasoned and step by step approach for countries, especially low- and middle-income countries (LMICs), to develop a systematic and transparent decision-making process for immunization policy.

'It takes two to tango': Bridging the gap between country need and vaccine product innovation.

BACKGROUND: Despite a growing global commitment to universal health coverage, considerable vaccine coverage and uptake gaps persist in resource-constrained settings. One way of addressing the gaps is by ensuring product innovation is relevant and responsive to the needs of these contexts. Total Systems Effectiveness (TSE) framework has been developed to characterize preferred vaccine attributes from the perspective of country decision-makers to inform research and development (R&D) of products. A proof of concept pilot study took place in Thailand in 2018 to examine the feasibility and usefulness of the TSE approach using a rotavirus hypothetical test-case. METHODS: The excel-based model used multiple-criteria decision analysis (MCDA) to compare and evaluate five hypothetical rotavirus vaccine products. The model was populated with local data and products were ranked against decision criteria identified by Thai stakeholders. A one-way sensitivity analysis was performed to identify criteria that influenced vaccine ranking. Self-assessment forms were distributed to R&D stakeholders on the usability of the approach and were subsequently analysed. RESULTS: The model identified significant parameters that impacted on MCDA rankings. Self-assessment forms revealed that TSE was perceived as being able to encourage closer collaboration between country decision makers and vaccine developers. CONCLUSIONS: The pilot study demonstrates that it is feasible to use an MCDA approach to elicit stakeholder preferences and determine influential parameters to help identify the preferred product characteristics for R&D from the perspective of country decision-makers. It found that TSE can help steer manufacturers to develop products that are better aligned with country need. Findings will guide further development of the TSE concept.

Immunogenicity and safety of human papillomavirus (HPV) vaccination in Asian populations from six countries: a meta-analysis.

Cervical cancer is a serious public-health problem in Asian countries. Since human papillomavirus (HPV) infection is the main risk factor for cervical cancer, HPV vaccination is considered a promising strategy to prevent cervical cancer. However, comprehensive immunogenicity and safety information for Asian populations is lacking. We searched four electronic databases including PubMed, EMBASE, Cochrane Library, and clinicaltrials.gov. We reviewed selected manuscripts and extracted the pooled relative risk (RR) from immunogenicity and safety information on HPV vaccination among women in Asian countries. We identified two quadrivalent-vaccine studies and eight bivalent-vaccine studies conducted in Asian countries. Analysis across these studies suggested that the HPV vaccines significantly enhanced HPV16- and HPV18-specific antibody among both uninfected (RR 85.69; 95% confidence interval (CI) 31.51-233.04 and 62.77; 95% CI 37.4-105.51) and infected individuals (RR 8.60; 95% CI 6.95-10.64 and RR 8.13; 95% CI 5.96-11.11). Furthermore, HPV vaccination among Asian populations has a favorable safety profile, with only slightly higher risks of local (RR: 1.89; 95% CI 1.65-2.17) and systemic (RR: 1.33; 95% CI 1.18-1.50) adverse events in vaccinated individuals compared with controls. For Asian populations, HPV vaccines enhance the level of HPV16- and HPV18-specific antibodies for both uninfected and infected individuals. Also, the risk of adverse events related to vaccination are acceptable. More data are needed to establish vaccine efficacy with regard to prevention of HPV infection and further outcomes including cervical intraepithelial neoplasia (CIN) and cervical cancer.

A Model Based Cost-Effectiveness Analysis of Routine Genotyping for CYP2D6 among Older, Depressed Inpatients Starting Nortriptyline Pharmacotherapy.

OBJECTIVE: Genotyping for CYP2D6 has the potential to predict differences in metabolism of nortriptyline. This information could optimize pharmacotherapy. We determined the costs and effects of routine genotyping for old aged Dutch depressed inpatients. METHODS: With a decision-tree, we modelled the first 12 weeks of nortriptyline therapy. Direct costs of genotyping, hospitalization, therapeutic drug monitoring and drugs were included. Based on genotype, patients could be correctly, sub-, or supratherapeutically dosed. Improvement from sub- or supratherapeutically dosed patients to correctly dosed patients was simulated, assuming that genotyping would prevent under- or overdosing of patients. In the base case, this improvement was assumed to be 35%. A probabilistic sensitivity analysis (PSA) was performed to determine uncertainty around the incremental cost-effectiveness ratio (ICER). RESULTS: In the base case analysis, costs for genotyping were assumed €200 per test with a corresponding ICER at €1 333 000 per QALY. To reach a €50 000 per QALY cut-off, genotyping costs should be decreased towards €40 per test. At genotyping test costs < €35 per test, genotyping was dominant. At test costs of €17 per test there was a 95% probability that genotyping was cost-effective at €50 000 per QALY. CONCLUSIONS: CYP2D6 genotyping was not cost-effective at current genotyping costs at a €50 000 per QALY threshold, however at test costs below €40, genotyping could be costs-effective.

Threshold cost-effectiveness analysis for a therapeutic vaccine against HPV-16/18-positive cervical intraepithelial neoplasia in the Netherlands.

In this study, the potential price for a therapeutic vaccine against Human Papilloma Virus (HPV)-16 & 18 (pre)-malignant cervical lesions is examined. A decision tree model was built in the context of the new Dutch cervical cancer-screening program and includes a primary test for the presence of HPV. Based on data of cervical cancer screening and HPV prevalence in the Netherlands, cohorts were created with HPV-16 or 18 positive women with cervical intraepithelial neoplasia (CIN) 2 or 3 or cervical cancer stage 1A (FIGO 1A). In the base case, the vaccine price was based on equal numbers of effective treatments in the vaccine branch and the current treatments branch of the model, and parity in cost, i.e. total cost in both branches are the same. The vaccine price is calculated by subtracting the cost of the vaccine branch from cost in the standard treatment branch and divided by the total number of women in the cohort, thereby equalizing costs in both strategies. Scenario analyses were performed taking quality adjusted life years (QALYs) into account with €20,000/QALY, €50,000/QALY and €80,000/QALY as corresponding thresholds. Sensitivity analyses were specifically targeted at the characteristics of the type-specific HPV test in the screening practice and vaccine efficacy. A probabilistic sensitivity analysis (PSA) was performed to quantify the level of uncertainty of the results found in the base case. In the base case, break-even vaccine prices of €381, €568 and €1697 were found for CIN 2, CIN 3 and FIGO 1A, respectively. The PSA showed vaccine pricing below €310, €490 and €1660 will be cost saving with a likelihood of 95% for CIN 2, CIN 3 and FIGO 1A, respectively. The vaccine price proved to be very sensitive for inclusion of QALY gains, including the HPV-type specific test into the Dutch screening practice and vaccine efficacy.

Cost-minimization model of a multidisciplinary antibiotic stewardship team based on a successful implementation on a urology ward of an academic hospital.

BACKGROUND: In order to stimulate appropriate antimicrobial use and thereby lower the chances of resistance development, an Antibiotic Stewardship Team (A-Team) has been implemented at the University Medical Center Groningen, the Netherlands. Focus of the A-Team was a pro-active day 2 case-audit, which was financially evaluated here to calculate the return on investment from a hospital perspective. METHODS: Effects were evaluated by comparing audited patients with a historic cohort with the same diagnosis-related groups. Based upon this evaluation a cost-minimization model was created that can be used to predict the financial effects of a day 2 case-audit. Sensitivity analyses were performed to deal with uncertainties. Finally, the model was used to financially evaluate the A-Team. RESULTS: One whole year including 114 patients was evaluated. Implementation costs were calculated to be €17,732, which represent total costs spent to implement this A-Team. For this specific patient group admitted to a urology ward and consulted on day 2 by the A-Team, the model estimated total savings of €60,306 after one year for this single department, leading to a return on investment of 5.9. CONCLUSIONS: The implemented multi-disciplinary A-Team performing a day 2 case-audit in the hospital had a positive return on investment caused by a reduced length of stay due to a more appropriate antibiotic therapy. Based on the extensive data analysis, a model of this intervention could be constructed. This model could be used by other institutions, using their own data to estimate the effects of a day 2 case-audit in their hospital.

The cost-effectiveness of HPV vaccination in addition to screening: a Dutch perspective.

Addition of the HPV vaccine to available cytological screening has been proposed to increase HPV-related cancer prevention. A comprehensive review on this combined strategy implemented in the Netherlands is lacking. For this review, we therefore analyzed all relevant studies on cost-effectiveness of HPV vaccines in combination with cervical screening in the Netherlands. Most of the studies agree that vaccination in pre-sexual-activity periods of life is cost-effective. Based on published sensitivity analyses, the incremental cost-effectiveness ratio was found to be mainly driven by vaccine cost and discount rates. Fewer vaccine doses, inclusion of additional benefits of these vaccines to prevent HPV-related non-cervical cancers and vaccination of males to further reduce the burden of HPV-induced cancers are three relevant options suggested to be investigated in upcoming economic evaluations.