Artificial Urinary Sphincters as a Treatment for Post-Prostatectomy Severe Urinary Incontinence in Italy: A Cost-Utility Analysis

Abstract Objective: This study aimed at evaluating the cost-utility of artificial urinary sphincter (AUS) in men affected by postprostatectomy severe urinary incontinence and identifying the most cost-effective alternative among the various devices analyzed in Italy. Methods: A 5-year cycles Markov model was developed to simulate the disease evolution. The analysis compared conservative therapy, ZSI 375®, single-cuff (SC) AMS 800TM, and double-cuff (DC) AMS 800TM. A Probabilistic Sensitivity Analysis (PSA) was performed. One thousand Monte Carlo simulations were conducted to generate the Cost-Effectiveness Acceptability Curve for each intervention strategy. A sensitivity analysis on the price of the device was conducted. Results: From the Italian National Health Service perspective, DC AMS 800TM was the most cost-effective alternative in comparison with conservative therapy, with an Incremental Cost-Effectiveness Ratio (ICER) value equal to € 12,893. From the NHS + patient perspective, both the AMS 800TM devices (SC and DC) were dominant in comparison with conservative therapy. From the societal perspective, ICER was dominant for all the alternatives considered in terms of cost-effectiveness. The PSA showed that DC AMS 800TM had a greater probability to be cost-effective with respect to the other strategies considered in the analysis. The sensitivity analysis on the price of the device showed that in all the cases analyzed the incremental cost per QALY gained would be below € 25,000. Conclusions: This cost-utility analysis confirms that AUSs are cost-effective options in the Italian context with respect to conservative therapy. Among AUSs, DC AMS 800TM has the greatest probability to be cost-effective

Human papillomavirus 9-valent vaccine for cancer prevention: a systematic review of the available evidence.

In 2014, the Food and Drug Administration approved a new human papillomavirus 9-valent vaccine (9vHPV), targeting nine HPV types: HPV types 6, 11, 16, and 18, which are also targeted by the quadrivalent HPV vaccine (qHPV), plus five additional high cancer risk HPV types (HPV types 31, 33, 45, 52, and 58). The aim of the current study was to systematically retrieve, qualitatively and quantitatively pool, as well as critically appraise all available evidence on 9vHPV from randomized controlled trials (RCTs). We conducted a systematic review of the literature on 9vHPV efficacy, immunogenicity and safety, as well as a systematic search of registered, completed, and ongoing RCTs. We retrieved and screened 227 records for eligibility. A total of 10 publications reported on RCTs' results on 9vHPV and were included in the review. Sixteen RCTs on 9vHPV have been registered on RCT registries. There is evidence that 9vHPV generated a response to HPV types 6, 11, 16 and 18 that was non-inferior to qHPV. Vaccine efficacy against five additional HPV type-related diseases was directly assessed on females aged 16-26 years (risk reduction against high-grade cervical, vulvar or vaginal disease = 96·7%, 95% CI 80·9%-99·8%). Bridging efficacy was demonstrated for males and females aged 9-15 years and males aged 16-26 years (the lower bound of the 95% CIs of both the geometric mean titer ratio and difference in seroconversion rates meeting the criteria for non-inferiority for all HPV types). Overall, 9vHPV has been proved to be safe and well tolerated. Other RCTs addressed: 9vHPV co-administration with other vaccines, 9vHPV administration in subjects that previously received qHPV and 9vHPV efficacy in regimens containing fewer than three doses. The inclusion of additional HPV types in 9vHPV offers great potential to expand protection against HPV infection. However, the impact of 9vHPV on reducing the global burden of HPV-related disease will greatly depend on vaccine uptake, coverage, availability, and affordability

Health and Economic Outcomes of Pembrolizumab in the Treatment of Metastatic Non-small Cell Lung Cancer (mNSCLC) and Melanoma in Italy.

Background and objective: In Italy, the management of metastatic non-small cell lung cancer and melanoma leads to significant healthcare challenges, necessitating cost-effective treatment strategies and offering valuable insights for healthcare policymakers and stakeholders. This study was designed to assess the costs, quality-adjusted life-years (QALYs) and disability-adjusted life-years (DALYs) associated with the health and economic outcomes of (1) pembrolizumab-combined chemotherapy administered as a first-line treatment for metastatic non-squamous and squamous non-small cell lung cancer (NSCLC) where the tumour presents with a programmed death-ligand 1 expression level < 50% and of (2) adjuvant pembrolizumab treatment for stage III melanoma. Methods: Three cost-effectiveness models developed by MSD were investigated for each treatment indication. A unique model was built to assess the overall effect of pembrolizumab versus chemotherapy or watchful waiting in patients with lung cancer or melanoma, respectively. Theoretical cohorts of patients with metastatic squamous and non-squamous NSCLC were followed over time using a partitioned survival model with weekly cycles. A weekly cycle Markov model was employed for melanoma. The analysis was conducted from the Italian National Health Service perspective, considering a time horizon of 40 years (lifetime). A single closed cohort of treatable patients was followed over time for each indication (4000, 7000 and 900 for NSCLC squamous, non-squamous and melanoma, respectively). The costs evaluated included those for adverse drug events, non-drug disease management, subsequent treatment and terminal care. Drug acquisition and administration costs were excluded. Results: For each treatment indication assessed, pembrolizumab produced downstream direct cost offsets (- €122,498,568, - €133,369,076 and - €32,993,242 for NSCLC squamous, non-squamous and melanoma indications, respectively), increased quality of life (+2088, +5317 and +2307 QALYs for NSCLC squamous, non-squamous and melanoma indications, respectively) and reduced disability (- 2658, - 7202 and - 3029 DALYs for NSCLC squamous, non-squamous and melanoma indications, respectively). Across indications, the total cost offsets of pembrolizumab were - €288,860,885, with 9712 QALYs gained and 12,889 DALYs avoided. Conclusions: The analysis demonstrated that, compared with chemotherapy, pembrolizumab is more cost effective in Italy as a first-line treatment in patients with metastatic squamous or non-squamous NSCLC and, if compared with watchful waiting, as adjuvant treatment in patients with stage III melanoma. The present analysis suggested that pembrolizumab use could lead to important health benefits for patients while offsetting a portion of cancer care costs

Screening strategy to advance HCV elimination in Italy: a cost-consequence analysis

Background and Aims: Italy has the greatest burden of hepatitis C virus (HCV) infection in Western Europe. The screening strategy represents a crucial prevention tool to achieve HCV elimination in Italy. We evaluated the cost-consequences of different screening strategies for the diagnosis of HCV active infection in the birth cohort 1948–1968 to achieve the HCV elimination goal. Methods: We designed a probabilistic model to estimate the clinical, and economic outcomes of different screening coverage uptakes, considering the direct costs of HCV management according to each liver fibrosis stage, in the Italian context. A decision probabilistic tree simulates 4 years of HCV testing of the 1948–1968 general population birth cohort, (15,485,565 individuals to be tested) considering different coverage rates. A No-screening scenario was compared with two alternative screening scenarios that represented different coverage rates each year: (1) Incremental approach (coverage rates equal to 5%, 10%, 30%, and 50% at years 1, 2, 3, and 4, respectively) and (2) Fast approach (50% coverage rate at years 1, 2, 3 and 4). Overall 106,200 cases were previously estimated to have an HCV active infection. A liver disease progression Markov model was considered for an additional 6 years (horizon-time 10 years). Results: The highest increased number of deaths and clinical events are reported for the No-screening scenario (21,719 cumulative deaths at the end of ten years; 10,148 cases with HCC and/or 7618 cases with Decompensated Cirrhosis). Following the Fast-screening scenario, the reductions in clinical outcomes and deaths were higher compared with No-screening and Incremental-screening. At ten years time horizon, less than 5696 liver deaths (PSA CI95%: – 3873 to 7519), 3,549 HCC (PSA CI95%: – 2413 to 4684) and less than 3005 liver decompensations (PSA CI 95%: – 2104 to 3907) were estimated compared with the Incremental-scenario. The overall costs of the Fast-screening, including the costs of the DAA and liver disease management of the infected patients for 10 years, are estimated to be € 43,107,543 more than no-investment in screening and € 62,289,549 less compared with the overall costs estimated by the Incremental-scenario. Conclusion: It is necessary to guarantee dedicated funds and efficiency of the system for the cost-efficacious screening of the 1948–1968 birth cohort in Italy. A delay in HCV diagnosis and treatment in the general population, yet not addressed for the HCV free-of-charge screening, will have important clinical and economic consequences in Italy. (ITER Collaboration Study Grp

The economic burden of HCV-induced diseases in Italy. A probabilistic cost of illness model

OBJECTIVE: The hepatitis C virus (HCV) induces several pathological conditions worldwide, with a substantial medical and economic burden. The objective of this study was to estimate the average annual cost incurred by the National Health Service (NHS), as well as society, due to HCV in Italy. METHODS: A probabilistic incidence-based cost of illness model was developed to estimate an aggregate measure of the economic burden associated with HCV-induced diseases either in terms of direct or indirect costs. Indirect costs were calculated on the basis of lost productivity according to the human capital approach. A systematic literature review was carried out to identify epidemiological and economic data which were used to inform the model. Furthermore, a one-way probabilistic sensitivity analysis with 5,000 Monte Carlo simulations was performed, in order to test the robustness of the results and define the proper 95% Confidence Interval (CE). RESULTS: Overall, the total economic burden associated with HCV-induced diseases was estimated in €1.06 billion (95%CI: €0.61- €1.63). A percentage of 60.6% was associated with indirect costs (95% CI: €0.37-€0.99 billion) and 39.4% with direct costs (95% CI: €0.23-€0.65 billion). In chronic hepatitis C, cirrhosis, hepatocellular carcinoma (HCC), liver transplantation and HCV-induced deaths, an average annual economic burden amounting to €0.26 (95%CI: €0.14-€0.41), €0.56 (95%CI: €0.30-€0.89), €0.051 (95%CI: €0.0007- €0.25), €0.05 (95%CI: €0.03-€0.08) and €0.15 (95%CI: €0.07-€0.27) billion respectively, was estimated. CONCLUSIONS: Italy is one of the European countries with the highest number of people affected by chronic HCV infection, the leading cause of cirrhosis, HCC and liver-related death. HCV-induced diseases generate high costs to Italian NHS. These highly debilitating and lifethreatening complications generate a rather large amount of indirect costs for the Italian society as well

Economic Consequences of Anti-HCV Treatment of Patients Diagnosed Through Screening in Italy: A Prospective Modelling Analysis

Aim: To evaluate the cost-consequences of the investment for anti-hepatitis C virus (HCV) treatment by the Italian National Health System (NHS) for patients who will be newly diagnosed through active HCV screening, implemented in Italy from 2020. Methods: A previously published Markov model was used to estimate the disease complications avoided and the associated savings over 20 years to treat a standardised population of 10,000 HCV-infected patients diagnosed as a result of screening. Disease progression probabilities and fibrosis stage distribution were based on previously reported data in the literature. Real-life treatment effectiveness and medical expenses for disease management were estimated starting from a representative cohort of HCV-treated patients in Italy (Italian Platform for the Study of Viral Hepatitis Therapies). The breakeven point in time (BPT) was defined as the years required for the initial investment in treatment to be recovered in terms of cumulative costs saved. Results: Over a 20-year time horizon, the treatment of 10,000 standardized patients diagnosed through active HCV screening results in 7769 avoided events of progression, which are associated with €838.73 million net savings accrued by the Italian NHS. The initial investment in treatment is recouped in 4.3 years in the form of savings from disease complications avoided. Conclusion: Investment in treatment of newly diagnosed patients will bring a significant reduction in disease complications, which is associated with great economic benefits. This type of action can reduce the infection rate as well as the clinical and economic disease burden of HCV in Italy

Economic Consequences of Anti-HCV Treatment of Patients Diagnosed Through Screening in Italy: A Prospective Modelling Analysis

Aim To evaluate the cost-consequences of the investment for anti-hepatitis C virus (HCV) treatment by the Italian National Health System (NHS) for patients who will be newly diagnosed through active HCV screening, implemented in Italy from 2020. Methods A previously published Markov model was used to estimate the disease complications avoided and the associated savings over 20 years to treat a standardised population of 10,000 HCV-infected patients diagnosed as a result of screening. Disease progression probabilities and fibrosis stage distribution were based on previously reported data in the literature. Real-life treatment effectiveness and medical expenses for disease management were estimated starting from a representative cohort of HCV-treated patients in Italy (Italian Platform for the Study of Viral Hepatitis Therapies). The breakeven point in time (BPT) was defined as the years required for the initial investment in treatment to be recovered in terms of cumulative costs saved. Results Over a 20-year time horizon, the treatment of 10,000 standardized patients diagnosed through active HCV screening results in 7769 avoided events of progression, which are associated with euro838.73 million net savings accrued by the Italian NHS. The initial investment in treatment is recouped in 4.3 years in the form of savings from disease complications avoided. Conclusion Investment in treatment of newly diagnosed patients will bring a significant reduction in disease complications, which is associated with great economic benefits. This type of action can reduce the infection rate as well as the clinical and economic disease burden of HCV in Italy