Quality-adjusted life years for HER2-positive, early-stage breast cancer using trastuzumab-containing regimens in the context of cost-effectiveness studies: a systematic review.

INTRODUCTION: This study aims to provide a comprehensive assessment of economic and health-related quality of life (HRQoL) outcomes for human epidermal growth factor receptor 2 (HER2)-positive, early-stage breast cancer patients treated with trastuzumab-containing regimens, by focusing on both Incremental Cost-Effectiveness Ratios (ICERs) and quality-adjusted life years (QALYs). METHODS: A systematic search was conducted across PubMed, Embase, and Scopus databases without language or publication year restrictions. Two independent reviewers screened eligible studies, extracted data, and assessed methodology and reporting quality using the Drummond checklist and Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022), respectively. Costs were converted to US dollars (US$) for 2023 for cross-study comparison. RESULTS: Twenty-two articles, primarily from high-income countries (HICs), were included, with ICERs ranging from US$13,176/QALY to US$254,510/QALY, falling within country-specific cost-effectiveness thresholds. A notable association was observed between higher QALYs and lower ICERs, indicating a favorable cost-effectiveness and health outcome relationship. EQ-5D was the most utilized instrument for assessing health state utility values, with diverse targeted populations. CONCLUSIONS: Studies reporting higher QALYs tend to have lower ICERs, indicating a positive relationship between cost-effectiveness and health outcomes. However, challenges such as methodological heterogeneity and transparency in utility valuation persist, underscoring the need for standardized guidelines and collaborative efforts among stakeholders. REGISTRATION: PROSPERO ID: CRD42021259826.

The clinical effectiveness of one-dose vaccination with an HPV vaccine: A meta-analysis of 902,368 vaccinated women.

BACKGROUND: The comprehensive effectiveness of the HPV vaccine has been widely acknowledged. However, challenges such as dosing adherence and limited budgets have led to delays in HPV vaccination implementation in many countries. A potential solution to these issues could lie in a one-dose vaccination with an HPV vaccine, as indicated by promising outcomes in multiple studies. METHODS: In this systematic review and meta-analysis, we examine the comparative effectiveness of the one-dose vaccination with an HPV vaccine against two- and three-dose regimens. Our investigation focuses on clinical efficacy, encompassing the prevention of HPV16, HPV18, and hrHPV infections, HSIL or ASC-H incidence, and CIN2/3 incidence. RESULTS: Our analysis suggests that a single-dose HPV vaccine may offer effectiveness on par with two- or three-dose schedules. This conclusion is drawn from its capacity to confer immunogenic protection for at least 8 years of follow-up, coupled with its ability to mitigate infections and pre-cancerous occurrences. CONCLUSION: While our findings underscore the potential of the one-dose vaccination with an HPV vaccine, further research and prolonged study durations are necessary to establish robust evidence supporting this recommendation. As such, continued investigation will be critical for informing vaccination strategies.

Economic and humanistic burden of HPV-related disease in Indonesia: A qualitative analysis.

The burden of human papillomavirus (HPV) and HPV-related cancers and genital warts is increasing in developing countries, including Indonesia. The objective of this study was to qualitatively explore the humanistic and economic burden of these HPV-related diseases in patients in Indonesia. In 2021, in-depth interviews and focus groups were conducted with patients (N = 18) with HPV-related diseases and healthcare professionals (HCPs; N = 10) specialised in treating these patients. Interviews explored the physical, mental, social, and economic burden of HPV-related diseases. Patients emphasised the psychological and social burden of HPV-related diseases, which negatively impacted their mental state and close relationships. Treatment for HPV-related diseases was also associated with a substantial cost, which health insurance only partially alleviated. HCPs understood the physical negative impact of HPV-related diseases, but some understated patients' social, psychological, and financial burden. This research underscores the substantial economic and humanistic burden of HPV-related diseases that could be prevented by vaccination. In addition, it highlights the need for novel interventions to reduce negative psychosocial consequences of HPV-related diseases in Indonesia. Increased HCP education of the broader humanistic impacts of HPV-related diseases may improve patient support and increase awareness for preventive strategy.

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.

The Cost Analysis of Human Papillomavirus Vaccination Program in Indonesia.

OBJECTIVES: This study aimed to analyze and describe the cost of HPV vaccination program in Indonesia. METHODS: This study identified the cost-related HPV vaccination program implemented in Makassar, Manado, and Surabaya cities, Indonesia, according to the previous activities performed. Cost information was collected and analyzed in each specific activity for each cost components, using the HPV vaccination module of the World Health Organization Cervical Cancer Prevention and Control Costing tool. RESULTS: According to the Cervical Cancer Prevention and Control Costing tool, the recurrent costs, both financial and economic costs, dominated the HPV vaccination program costs in Surabaya (US dollars [USD] 264 618; USD 268 724), Makassar (USD 166 852; USD 293 300), and Manado (USD 270 815; USD 270 946), with a total cost of USD 702 285 for financial cost and USD 832 970 for economic cost. Vaccine procurement drives the recurrent cost. CONCLUSIONS: The implementation of demonstration program in Surabaya, Makassar, and Manado cities was considerably succeed. Any prediction related to the cost of implementation of HPV vaccination in Indonesia can be calculated and used to advocate regional or national government.

Economic Evaluations of HPV Vaccination in Targeted Regions of Low- and Middle-Income Countries: A Systematic Review of Modelling Studies.

Background: In countries with limited resources, a targeted HPV vaccination strategy by focusing in selected regions is preferable to be implemented than a nationwide vaccination strategy. Objective: This study aimed to review articles on economic evaluations of HPV vaccination in countries over the world that applied targeted vaccination strategies. Methods: Approximately 1769 articles were obtained from two databases (1242 and 527 articles from PubMed and ProQuest, respectively). The inclusion criteria in this systematic review were studies about full economic evaluations of HPV vaccination in targeted area or sub-national level and written in English. Full-text screening was applied to evaluate the eligibility. Final articles obtained were referred to the Consolidated Health Economic Evaluation Reporting Standard (CHEERS) checklist. Finally, we included only 4 articles that met all inclusion and exclusion criteria. Results: Included studies in this review focused in different targeted regions, such as Punjab State in India, Vientiane in Lao PDR, Southern Vietnam in Vietnam, and Brazilian Amazon in Brazil. From 24 criteria in the CHEERS checklist, all included studies could meet 21 criteria (87.5%). All included studies in this review applied modeling approaches, which can estimate the number of cases and treatment costs averted. Applying various settings, the results of this study showed that HPV vaccination could potentially reduce the number of cervical cancer cases by 20-72%. Taking cervical cancer screening into account, this study showed that targeted HPV vaccination was cost-effective or even cost-saving. Conclusion: Implementation of HPV vaccination in sub-national level as the initial step before nationwide vaccination is more favorable to be implemented in countries with limited budget.

Cost-Effectiveness Analysis of BCG Vaccination against Tuberculosis in Indonesia: A Model-Based Study.

Bacillus Calmette-Guerin (BCG), the only available vaccine for tuberculosis (TB), has been applied for decades. The Indonesian government recently introduced a national TB disease control programme that includes several action plans, notably enhanced vaccination coverage, which can be strengthened through underpinning its favourable cost-effectiveness. We designed a Markov model to assess the cost-effectiveness of Indonesia's current BCG vaccination programme. Incremental cost-effectiveness ratios (ICERs) were evaluated from the perspectives of both society and healthcare. The robustness of the analysis was confirmed through univariate and probabilistic sensitivity analysis (PSA). Using epidemiological data compiled for Indonesia, BCG vaccination at a price US$14 was estimated to be a cost-effective strategy in controlling TB disease. From societal and healthcare perspectives, ICERs were US$104 and US$112 per quality-adjusted life years (QALYs), respectively. The results were robust for variations of most variables in the univariate analysis. Notably, the vaccine's effectiveness regarding disease protection, vaccination costs, and case detection rates were key drivers for cost-effectiveness. The PSA results indicated that vaccination was cost-effective even at US$175 threshold in 95% of cases, approximating the monthly GDP per capita. Our findings suggest that this strategy was highly cost-effective and merits prioritization and extension within the national TB programme. Our results may be relevant for other high endemic low- and middle-income countries.

Cervical cancer prevention in Indonesia: An updated clinical impact, cost-effectiveness and budget impact analysis.

INTRODUCTION: The clinical and economic impact of cervical cancer consistently become a serious burden for all countries, including Indonesia. The implementation of HPV vaccination policy for a big country such as Indonesia requires a strong commitment from several decision-makers. The aim of this study was to provide a comprehensive description on cost-effectiveness and the budget-impact of HPV vaccination policy in Indonesia. METHOD: A cohort Markov model was used to evaluate the cost and the clinical impact of HPV vaccination for 10 years old girls in Indonesia. The researchers consider two doses of all three available HPV vaccines adjusted with the HPV infection profilewith 95% vaccination coverage to estimate the national cervical cancer incidence and mortality. The Budget impact analysis explores three different scenarios covering (1) Two districts per year expansion, (2) oneprovince per year expansion and (3) achieving the National Immunization Program in 2024. RESULTS: Upon fully vaccinating almost 2.3 million 10-year-old girls, 34,723; 43,414; and 51,522 cervical cancer cases were prevented by Quadrivalent, Bivalent and Nonavalent vaccines, consecutively. Furthermore, the highest (591 cases) and lowest (399 cases) mortality were prevented by Nonavalent and Quadrivalent vaccines, respectively. Most of the vaccines were considerably cost-effective and only the Bivalent vaccine with the GAVI/UNICEF price which will be considered a cost-saving strategy.To provide national coverage of HPV vaccination in Indonesia, the government has to provide an annual budget of about US$49 million and US$22 million using the government contract price and GAVI/UNICEF price, respectively. CONCLUSION: HPV vaccination shows a cost-effective strategy and the budget required to provide this policy is considerably affordable for Indonesia.

Health economic evaluation of current vaccination strategies and new vaccines against tuberculosis: a systematic review.

Introduction: Bacillus Calmette-Guérin (BCG) is the only licensed vaccine for tuberculosis, but its effectiveness is limited and varies by age. New candidate vaccines are currently being investigated. In response to the declining incidence of TB, practices relating to BCG vaccination have changed in various countries in recent years. A valid cost-effectiveness study is therefore needed in order to assist decision-makers in the implementation of cost-effective strategies for BCG vaccination. Areas covered: Studies involving economic evaluations of BCG vaccination were reviewed in order to present current findings concerning a range of BCG vaccination strategies in a variety of regions, target populations, and vaccine types. The Quality of Health Economic Studies (QHES) instrument was used to assess the quality of the studies included in the analysis. Expert opinion: Most of the studies showed a favorable economic profile of BCG vaccination. Selective strategies seem the most cost-effective option for low-incidence areas. Varying results on revaccination strategies did not lead to any conclusive finding on the cost-effectiveness of the strategies. A novel vaccine - either a BCG replacement or booster vaccine that provides better protection, especially in adults - has the potential to enhance the cost-effectiveness of vaccinating against tuberculosis.

Prevention of Surgical Site Infections: A Systematic Review of Cost Analyses in the Use of Prophylactic Antibiotics.

Introduction: The preoperative phase is an important period in which to prevent surgical site infections (SSIs). Prophylactic antibiotic use helps to reduce SSI rates, leading to reductions in hospitalization time and cost. In clinical practice, besides effectiveness and safety, the selection of prophylactic antibiotic agents should also consider the evidence with regard to costs and microbiological results. This review assessed the current research related to the use of antibiotics for SSI prophylaxis from an economic perspective and the underlying epidemiology of microbiological findings. Methods: A literature search was carried out through PubMed and Embase databases from 1 January 2006 to 31 August 2017. The relevant studies which reported the use of prophylactic antibiotics, SSI rates, and costs were included for analysis. The causing pathogens for SSIs were categorized by sites of the surgery. The quality of reporting on each included study was assessed with the "Consensus on Health Economic Criteria" (CHEC). Results: We identified 20 eligible full-text studies that met our inclusion criteria, which were subsequently assessed, studies had in a reporting quality scored on the CHEC list averaging 13.03 (8-18.5). Of the included studies, 14 were trial-based studies, and the others were model-based studies. The SSI rates ranged from 0 to 71.1% with costs amounting to US$480-22,130. Twenty-four bacteria were identified as causative agents of SSIs. Gram negatives were the dominant causes of SSIs especially in general surgery, neurosurgery, cardiothoracic surgery, and obstetric cesarean sections. Conclusions: Varying results were reported in the studies reviewed. Yet, information from both trial-based and model-based costing studies could be considered in the clinical implementation of proper and efficient use of prophylactic antibiotics to prevent SSIs and antimicrobial resistance.

Cost Effectiveness of Human Papillomavirus Vaccination for Men Who have Sex with Men; Reviewing the Available Evidence.

BACKGROUND: Men who have sex with men require special attention for human papillomavirus vaccination given elevated infection risks and the development of, in particular, anal cancer. OBJECTIVE: Our purpose was to review the cost effectiveness of human papillomavirus vaccination for both currently vaccine-eligible and non-eligible individuals, particularly the men-who-have-sex-with-men population, and synthesize the available evidence. METHODS: We systematically searched for published articles in two main databases (PubMed and EMBASE). Screening and data extraction were performed by two independent reviewers. The risk of bias was assessed using a validated instrument (Bias in Economic Evaluation, ECOBIAS). Methodological aspects, study results, and sensitivity analyses were extracted and synthesized to generate a consistent overview of the cost effectiveness of human papillomavirus vaccination in the men-who-have-sex-with-men population. RESULTS: From 770 identified articles, four met the inclusion criteria. Across the studies, human papillomavirus vaccination showed incremental cost-effectiveness ratios ranging from dominant to US$96,146 and US$14,000 to US$18,200 for tertiary prevention and primary prevention, respectively. The incremental cost-effectiveness ratio seemed most sensitive to vaccine efficacy, vaccine costs, and the incidence of anal cancer in the selected target populations. CONCLUSION: This review presents the human papillomavirus vaccine, both as a primary and adjuvant (tertiary) vaccination, as a potentially cost-effective strategy for preventing mainly-but not limited to only-anal cancer in men-who-have-sex-with-men populations.

The health-economic studies of HPV vaccination in Southeast Asian countries: a systematic review.

INTRODUCTION: The cervical cancer-related burden is an important problem in Southeast Asian (SEA) countries. However, only 3 out of 11 countries implement the comprehensive prevention program. Areas covered: This is a retrospective review from all relevant studies until 2015 from two main databases, MEDLINE/Pubmed and Embase in order to provide an evidence on the health economics of HPV vaccination in the region. Expert commentary: The implementation of HPV vaccination will generate substantial health and economic benefit in SEA countries since the number of cervical cancer cases in this region are generally high. Therefore, a clear recommendation on how HPV vaccination should be implemented in a country, for example on how many doses will be used, how much cost is required or is it a school based- or clinical based-delivery, is critically required.

Cost-Utility Analysis of Human Papillomavirus Vaccination and Cervical Screening on Cervical Cancer Patient in Indonesia.

BACKGROUND: Although cervical cancer is a preventable disease, the clinical and economic burdens of cervical cancer are still substantial issues in Indonesia. OBJECTIVES: The main purpose of this study was to model the costs, clinical benefits, and cost-utility of both visual inspection with acetic acid (VIA) screening alone and human papillomavirus (HPV) vaccination in addition to VIA screening in Indonesia. METHODS: We developed a population-based Markov model, consisting of three health states (susceptible, cervical cancer, and death), to assess future costs, health effects, and the cost-utility of cervical cancer prevention strategies in Indonesia. We followed a cohort of 100,000 females 12 to 100 years old and compared VIA screening alone with the addition of HPV vaccination on top of the screening to "no intervention." RESULTS: The implementation of VIA screening alone and in combination with HPV vaccination would reduce the cervical cancer incidence by 7.9% and 58.5%, corresponding to 25 and 98 deaths avoided within the cohort of 100,000, respectively. We also estimated that HPV vaccination combined with VIA screening apparently yielded a lower incremental cost-effectiveness ratio at international dollar 1863/quality-adjusted life-year (QALY), compared with VIA screening alone (I$3126/QALY). Both strategies could however be definitely labeled as very cost-effective interventions, based on a threshold suggested by the World Health Organization. The incremental cost-effectiveness ratio was sensitive to the discount rate, cervical cancer treatment costs, and quality of life as part of the QALY. CONCLUSIONS: The addition of HPV vaccination on top of VIA screening could be a cost-effective strategy in Indonesia even if relatively conservative assumptions are applied. This population-based model can be considered as an essential tool to inform decision makers on designing optimal strategies for cervical cancer prevention in Indonesia.

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.

Assessment of the Broader Economic Consequences of HPV Prevention from a Government-Perspective: A Fiscal Analytic Approach.

BACKGROUND: Cervical cancer poses a substantial burden in terms of morbidity, mortality, and economic losses, especially in low/middle-income countries. HPV vaccination and/or cervical cancer screening among females may reduce the burden of HPV-related diseases, including cervical cancer. However, limited funds may impede the implementation of population-based programmes. Governmental investments in the prevention of infectious disease may have broader economic and fiscal benefits, which are not accounted in conventional economic analyses. This study estimates the broader economic and fiscal impacts of implementing HPV vaccination and/or cervical cancer screening in Indonesia from the perspective of the government. METHODS: A government-perspective quantitative analytic framework was applied to assess the Net Present Value (NPV) of investment on cervical cancer prevention strategies including HPV vaccination, cervical screening and its combination in Indonesia. All monetary values were presented in International Dollars (I$). RESULTS: Based on a cohort of 10,000,000 Indonesian 12-year-old females, it was estimated that HPV vaccination and/or cervical cancer screening result in a positive NPV for the Indonesian government. The combination of cervical screening and HPV vaccination generated a substantial reduction of cervical cancer incidence and HPV-related mortality of 87,862 and 19,359, respectively. It was estimated that HPV vaccination in combination with cervical screening is the most favorable option for cervical cancer prevention (NPV I$2.031.786.000), followed by HPV vaccination alone (NPV I$1.860.783.000) and cervical screening alone (NPV I$375.244.000). CONCLUSION: In addition to clinical benefits, investing in HPV vaccination and cervical screening may yield considerable fiscal benefits for the Indonesian governments due to lifelong benefits resulting from reduction of cervical cancer-related morbidity and mortality.

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.