An Analysis of the Distribution of Direct Cost of Diabetes Care in Selected Districts in Italy.

INTRODUCTION: This study aims to define the distribution of direct healthcare costs for people with diabetes treated in two healthcare regions in Italy, based on number of comorbidities and treatment regimen. METHODS: This was a retrospective analysis using data from two local health authority administrative databases (Campania and Umbria) in Italy for the years 2014-2018. Data on hospital care, pharmaceutical and specialist outpatient and laboratory assistance were collected. All people with diabetes in 2014-2018 were identified on the basis of at least one prescription of hypoglycemic drugs (ATC A10), hospitalization with primary or secondary diagnosis of diabetes mellitus (ICD9CM 250.xx) or diabetes exemption code (code 013). Subjects were stratified into three groups according to their pharmaceutical prescriptions during the year: Type 1/type 2 diabetes (T1D/T2D) treated with multiple daily injections with insulin (MDI), type 2 diabetes on basal insulin only (T2D-Basal) and type 2 diabetes not on insulin therapy (T2D-Oral). RESULTS: We identified 304,779 people with diabetes during the period for which data was obtained. Analysis was undertaken on 288,097 subjects treated with glucose-lowering drugs (13% T1D/T2D-MDI, 13% T2D-Basal, 74% T2D-Oral). Average annual cost per patient for the year 2018 across the total cohort was similar for people with T1D/T2D-MDI and people with T2D-Basal (respectively €2580 and €2254) and significantly lower for T2D-Oral (€1145). Cost of hospitalization was the main driver (47% for T1D/T2D-MDI, 45% for T2D-Basal, 45% for T2D-Oral) followed by drugs/devices (35%, 39%, 43%) and outpatient services (18%, 16%, 12%). Average costs increased considerably with increasing comorbidities: from €459 with diabetes only to €7464 for a patient with four comorbidities. Similar trends were found across all subgroups analysis. CONCLUSION: Annual cost of treatment for people with diabetes is similar for those treated with MDI or with basal insulin only, with hospitalization being the main cost driver. This indicates that both patient groups should benefit from having access to scanning continuous glucose monitoring (CGM) technology which is known to be associated with significantly reduced hospitalization for acute diabetes events, compared to self-monitored blood glucose (SMBG) testing.

High costs, low quality of life, reduced survival, and room for improving treatment: an analysis of burden and unmet needs in glioma.

Gliomas are a group of heterogeneous tumors that account for substantial morbidity, mortality, and costs to patients and healthcare systems globally. Survival varies considerably by grade, histology, biomarkers, and genetic alterations such as IDH mutations and MGMT promoter methylation, and treatment, but is poor for some grades and histologies, with many patients with glioblastoma surviving less than a year from diagnosis. The present review provides an introduction to glioma, including its classification, epidemiology, economic and humanistic burden, as well as treatment options. Another focus is on treatment recommendations for IDH-mutant astrocytoma, IDH-mutant oligodendroglioma, and glioblastoma, which were synthesized from recent guidelines. While recommendations are nuanced and reflect the complexity of the disease, maximum safe resection is typically the first step in treatment, followed by radiotherapy and/or chemotherapy using temozolomide or procarbazine, lomustine, and vincristine. Immunotherapies and targeted therapies currently have only a limited role due to disappointing clinical trial results, including in recurrent glioblastoma, for which the nitrosourea lomustine remains the de facto standard of care. The lack of treatment options is compounded by frequently suboptimal clinical practice, in which patients do not receive adequate therapy after resection, including delayed, shortened, or discontinued radiotherapy and chemotherapy courses due to treatment side effects. These unmet needs will require significant efforts to address, including a continued search for novel treatment options, increased awareness of clinical guidelines, improved toxicity management for chemotherapy, and the generation of additional and more robust clinical and health economic evidence.

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.

From Prioritization to Universal Treatment: Successes and Challenges of Hepatitis C Virus Elimination in Italy.

Italy has had the highest prevalence of hepatitis C virus (HCV) infection and mortality from HCV-related liver cancer in Europe. Although direct-acting antivirals (DAA) were initially restricted to persons with advanced fibrosis, their use has since been extended to all infected individuals; more than 244 000 persons have been treated to date. HCV liver-related mortality is expected to decline by 75% by 2030, achieving the World Health Organization target for mortality. However, Italy risks failing to meet the overall goal of eliminating HCV infection by 2030. In this light, €71.5 million have been allocated for screening initially specific target populations (persons who inject drugs, prison inmates, and the 1969-1989 birth cohort). Herein, we outline the challenges and recommendations for how to move Italy toward HCV elimination, including expanding screening programs in other populations, increasing awareness through strategic communication, sustaining DAA access, and tailoring care models to meet the needs of key populations.

Impact of Chronic Coronary Artery Disease and Revascularization Strategy in Patients with Severe Aortic Stenosis Who Underwent Transcatheter Aortic Valve Implantation.

The prognostic impact of coronary artery disease (CAD) after transcatheter aortic valve implantation (TAVI) is controversial. The aim of this study is to investigate the impact of CAD and different revascularization strategies on clinical outcomes in patients who underwent TAVI with third generation devices. Patients enrolled in the national observational Observational Study of Effectiveness of SAVR-TAVI Procedures for Severe Aortic Stenosis Treatment II study were stratified according to the presence of CAD (CAD+, n = 1,130) versus no CAD (CAD-, n = 1,505), and compared using a propensity matched analysis. CAD+ group was further stratified according to the revascularization strategy: no revascularization (n = 331), revascularization performed >90 days before index-TAVI (n = 417) and coronary revascularization performed <90 days before index-TAVI or during TAVI (n = 382). In-hospital, 30-day and 1-year clinical outcomes were estimated. The mean age of the overall population was 81.8 years; 54.9% of patients were female. Propensity score matching yielded 813 pairs and their 30-day all-cause mortality was comparable (p = 0.480). Major periprocedural adverse events were also similar between the groups. At 1-year follow-up, the rate of major adverse cardiac and cerebrovascular events (MACCEs) and all-cause mortality were similar between the groups (p = 0.732 and p = 0.633, respectively). Conversely, patients with CAD experienced more often myocardial infarction and need for percutaneous coronary intervention at 1 year (p = 0.007 and p = 0.001, respectively). Neither CAD nor revascularization strategy were independent predictors of 1-year MACCE. About 40% of patients presenting with severe AS and who underwent TAVI had concomitant CAD. The presence of CAD had no impact on all-cause mortality and MACCE 1-year after TAVR. However, CAD carries a higher risk for acute myocardial infarction and need of percutaneous coronary intervention during follow-up.

Financial Burden of Transcatheter Aortic Valve Implantation.

Given the increasing population eligible for transcatheter aortic valve implantation (TAVI), resource utilization has become an important focus in this setting. We aimed to estimate the change in the financial burden of TAVI therapy over 2 different periods. A probabilistic Markov model was developed to estimate the cost consequences of increased center experience and the introduction of newer-generation TAVI devices compared with an earlier TAVI period in a cohort of 6,000 patients. The transition probabilities and hospitalization costs were retrieved from the OBSERVANT (Observational Study of Effectiveness of AVR-TAVI procedures for severe Aortic steNosis Treatment) and OBSERVANT II (Observational Study of Effectiveness of TAVI with new generation deVices for severe Aortic stenosis Treatment) studies, including 1,898 patients treated with old-generation devices and 1,417 patients treated with new-generation devices. The propensity score matching resulted in 853 pairs, with well-balanced baseline risk factors. The mean EuroSCORE II (6.6% vs 6.8%, p = 0.76) and the mean age (82.0 vs 82.1 y, p = 0.62) of the early TAVI period and new TAVI period were comparable. The new TAVI period was associated with a significant reduction in rehospitalizations (-30.5% reintervention, -25.2% rehospitalization for major events, and -30.8% rehospitalization for minor events) and a 20% reduction in 1-year mortality. These reductions resulted in significant cost savings over a 1-year period (-€4.1 million in terms of direct costs and -€19.7 million considering the additional cost of the devices). The main cost reduction was estimated for rehospitalization, accounting for 79% of the overall cost reduction (not considering the costs of the devices). In conclusion, the introduction of new-generation TAVI devices, along with increased center experience, led to significant cost savings at 1-year compared with an earlier TAVI period, mainly because of the reduction in rehospitalization costs.

HPV Vaccination during the COVID-19 Pandemic in Italy: Opportunity Loss or Incremental Cost.

OBJECTIVES: Italy was the first European country to introduce universal vaccination of adolescents, for both males and females, against Human Papilloma Virus (HPV) starting in 2017 with the NIP 2017-2019's release. However, vaccine coverage rates (VCRs) among adolescents have shown a precarious take-off since the NIP's release, and this situation worsened due to the impact of the COVID-19 pandemic in 2020. The aim of this work is to estimate the epidemiological and economic impact of drops in VCRs due to the pandemic on those generations that missed the vaccination appointment and to discuss alternative scenarios in light of the national data. METHODS: Through an analysis of the official ministerial HPV vaccination reports, a model was developed to estimate the number of 12-year-old males and females who were not vaccinated against HPV during the period 2017-2021. Based on previously published models that estimate the incidence and the economic impact of HPV-related diseases in Italy, a new model was developed to estimate the impact of the aggregated HPV VCRs achieved in Italy between 2017 and 2021. RESULTS: Overall, in 2021, 723,375 girls and 1,011,906 boys born between 2005 and 2009 were not vaccinated against HPV in Italy (42% and 52% of these cohorts, respectively). As compared with the 95% target provided by the Italian NIP, between 505,000 and 634,000 girls will not be protected against a large number of HPV-related diseases. For boys, the number of the unvaccinated population compared to the applicable target is over 615,000 in the 'best case scenario' and over 749,000 in the 'worst case scenario'. Overall, between 1.1 and 1.3 million young adolescents born between 2005 and 2009 will not be protected against HPV-related diseases over their lifetime with expected lifetime costs of non-vaccination that will be over EUR 905 million. If the 95% optimal VCRs were achieved, the model estimates a cost reduction equal to EUR 529 million, the net of the costs incurred to implement the vaccination program. CONCLUSION: Suboptimal vaccination coverage represents a missed opportunity, not only because of the increased burden of HPV-related diseases, but also in terms of economic loss. Thus, reaching national HPV immunization goals is a public health priority.

One-Year Outcomes and Trends over Two Eras of Transcatheter Aortic Valve Implantation in Real-World Practice.

BACKGROUND: Data reflecting the benefit of procedural improvements in real-world transcatheter aortic valve implantation (TAVI) practice are sparse. AIMS: To compare outcomes and trends of two TAVI eras from real Italian practice. METHODS: A total of 1811 and 2939 TAVI patients enrolled in the national, prospective OBSERVANT and OBSERVANT II studies in 2010-2012 and 2016-2018, respectively, were compared in a cohort study. Outcomes were adjusted using inverse propensity of treatment weighting and propensity score matching. RESULTS: The median age (83.0 (79.0-86.0) vs. 83.0 (79.0-86.0)) and EuroSCORE II (5.2 (3.2-7.7) vs. 5.1 (3.1-8.1)) of OBSERVANT and OBSERVANT II patients were similar. At 1 year, patients of the OBSERVANT II study had a significantly lower risk of all-cause death (10.6% vs. 16.3%, Hazard Ratio (HR) 0.63 (95% Confidence Interval (CI) 0.52-0.76)) and rehospitalization for heart failure (HF) (14.3% vs. 19.5%, Sub-distribution HR 0.71 (95%CI 0.60-0.84)), whereas rates of stroke (3.1% vs. 3.6%) and permanent pacemaker implantation (PPI) (16.6% vs. 18.0%) were comparable between study groups. CONCLUSIONS: Age and risk profile among patients undergoing TAVI in Italy remained substantially unchanged between the 2010-2012 and 2016-2018 time periods. After adjustment, patients undergoing TAVI in the most recent era had lower risk of all-cause death and rehospitalization for HF at 1 year, whereas rates of stroke and PPI did not differ significantly.

The Impact of COVID-19 Vaccination on the Italian Healthcare System: A Scenario Analysis.

BACKGROUND AND OBJECTIVE: During 2020, the only instruments for fighting against the pandemic peaks were lockdowns, physical distancing, closure of schools and non-essential businesses, and travel restrictions. The new vaccination strategy adopted in Italy in 2021 represented a new perspective for policymakers. OBJECTIVE: The aim of this study was to estimate the effects of the national immunisation strategy for coronavirus disease 2019 (COVID-19) in Italy on the national healthcare system. METHODS: An epidemiological scenario analysis was developed in order to simulate the impact of the COVID-19 pandemic on the Italian national healthcare system in 2021. Hospitalisations, intensive care unit (ICU) admissions and death rates were modelled based on 2020 data. Costs were estimated using hospital admissions from the Policlinico of Tor Vergata Hospital in Rome. Two scenarios were tested, one with vaccination and the second without. RESULTS: The roll-out of vaccinations to protect against COVID-19 was estimated to prevent 52,115 deaths in 2021, 45.2% less than what was expected in the absence of immunisation. Based on the assumptions underlying the two epidemiological scenarios, our model predicted an overall reduction of 2.4 million hospital admissions and 259,000 ICU admissions (74.9% and 71.3% less, respectively, than the world without vaccinations between June and December 2021). Overall, in Italy, the model estimated over €3.0 billion costs of hospitalisations due to COVID-19 in 2020. In 2021, vaccines prevented around 36% of the overall costs. CONCLUSIONS: This is the first study highlighting the effect of vaccines on the Italian healthcare system in terms of avoided cases, hospitalisations and costs. Our results have the potential to inform policymakers and the general population on the benefits of vaccinations.

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.

Optimizing diagnostic algorithms to advance Hepatitis C elimination in Italy: A cost effectiveness evaluation.

OBJECTIVES: Optimized diagnostic algorithms to detect active infections are crucial to achieving HCV elimination. We evaluated the cost effectiveness and sustainability of different algorithms for HCV active infection diagnosis, in a context of a high endemic country for HCV infection. METHODS: A Markov disease progression model, simulating six diagnostic algorithms in the birth cohort 1969-1989 over a 10-year horizon from a healthcare perspective was used. Conventionally diagnosis of active HCV infection is through detection of antibodies (HCV-Ab) detection followed by HCV-RNA or HCV core antigen (HCV-Ag) confirmatory testing either on a second sample or by same sample reflex testing. The undiagnosed and unconfirmed rates were evaluated by assays false negative estimates and each algorithm patients' drop-off. Age, liver disease stages distribution, liver disease stage costs, treatment effectiveness and costs were used to evaluate the quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratios (ICER). RESULTS: The reference option was Rapid HCV-Ab followed by second sample HCV-Ag testing which produced the lowest QALYs (866,835 QALYs). The highest gains in health (QALYs=974,458) was obtained by HCV-RNA reflex testing which produced a high cost-effective ICER (€891/QALY). Reflex testing (same sample-single visit) vs two patients' visits algorithms, yielded the highest QALYs and high cost-effective ICERs (€566 and €635/QALY for HCV-Ag and HCV-RNA, respectively), confirmed in 99.9% of the 5,000 probabilistic simulations. CONCLUSIONS: Our data confirm, by a cost effectiveness point of view, the EASL and WHO clinical practice guidelines recommending HCV reflex testing as most cost effective diagnostic option vs other diagnostic pathways.

An Analysis of the Social and Economic Costs of Breast Cancer in Italy.

BACKGROUND: Breast cancer is the most prevalent cancer affecting women and it represents an important economic burden. The aim of this study was to estimate the socio-economic burden of breast cancer (BC) in Italy both from the National Health Service (NHS) and the government perspectives (costs borne by the social security system). METHODS: The economic analysis was based on the costs incurred by the NHS from 2008 to 2016 (direct costs related to hospitalizations) and by the National Social Security Institute (INPS) from 2009 to 2015 (costs of social security benefits) for patients with breast cancer. The analysis was based on the Hospital Information System (HIS) and Disability Insurance Awards databases. For both databases, patients affected by a malignant neoplasm of the female breast, carcinoma in situ, or secondary malignant neoplasm of the breast were considered. RESULTS: Results show that more than 75,000 women were hospitalized for breast cancer every year, with an overall cost for hospitalization of about €300 million per year. From the Social Security analysis, a number of 29,000 beneficiaries each year was estimated. Considering per patient social costs, breast cancer at the primary stage cost €8828 per year, while secondary neoplasms cost €9780, with an average total economic burden of €257 million per year. CONCLUSIONS: This analysis focused on the economic impact of breast cancer in Italy, showing that an advanced stage of the disease was associated with a higher cost.

Drug Prices and Value of Oncology Drugs in Italy.

OBJECTIVE: The main objective of this study was to evaluate the potential role of efficacy data and other information available at the time of price and reimbursement (P&R) decision-making process within the definition of oncology treatment costs in Italy. METHODS: The study included all P&R dossiers submitted to the Italian Medicines Agency between July 2015 and December 2017. It prospectively collected the data of the P&R process starting from dossier submission up to the Italian Health Service reimbursement decision. The cost of treatment per patient was estimated using both the list price ("gross cost") and the confidential net price ("net cost") of drug packages and applied to the median duration of treatment. A 2-sample stage Heckman decomposition model was used to evaluate the potential role of efficacy data and other information available at the time of P&R decision making on the gross and net cost. RESULTS: A total of 37 oncology drugs related to 58 therapeutic indications were analyzed. The multivariate model showed that the variation of progression-free survival is the only variable predictor statistically associated with treatment cost, but this effect was observed only when confidential net prices were used (P=.026). CONCLUSIONS: Considering the perspective of a developed country having a public healthcare service with a central reimbursement negotiation is determined a relevant reduction in the treatment cost purchased by public payers. This is a useful approach to guarantee the affordability of innovative oncology drugs and to contain public expenditures on healthcare. Furthermore, the negotiation of confidential discounts and agreement clauses in managed entry agreements seemed to reward oncology drugs displaying an added therapeutic benefit.