The impact of direct acting antivirals on hepatitis C virus disease burden and associated costs in four european countries.

BACKGROUND AND AIMS: We assessed the clinical and economic impact of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) in England, Italy, Romania and Spain. METHODS: An HCV progression Markov model was developed considering DAA eligibility and population data during the years 2015-2019. The period of time to recover the investment in DAAs was calculated as the cost saved by avoiding estimated clinical events for 1000 standardized treated patients. A delayed treatment scenario because of coronavirus disease (COVID-19) was also developed. RESULTS: The estimated number of avoided hepatocellular carcinoma, decompensated cirrhosis and liver transplantations over a 20-year time horizon was: 1,057 in England; 1,221 in Italy; 1,211 in Romania; and 1,103 in Spain for patients treated during 2015-2016 and 640 in England; 626 in Italy; 739 in Romania; and 643 in Spain for patients treated during 2017-2019. The cost-savings ranged from € 45 to € 275 million. The investment needed to expand access to DAAs in 2015-2019 is estimated to be recovered in 6.5 years in England; 5.4 years in Italy; 6.7 years in Romania; and 4.5 years in Spain. A delay in treatment because of COVID-19 will increase liver mortality in all countries. CONCLUSION: Direct-acting antivirals have significant clinical benefits and can bring substantial cost-savings over the next 20 years, reaching a Break-even point in a short period of time. When pursuing an exit strategy from strict lockdown measures for COVID-19, providing DAAs should remain high on the list of priorities in order to maintain HCV elimination efforts.

Optimization of hepatitis C virus screening strategies by birth cohort in Italy.

BACKGROUND AND AIMS: Cost-effective screening strategies are needed to make hepatitis C virus (HCV) elimination a reality. We determined if birth cohort screening is cost-effective in Italy. METHODS: A model was developed to quantify screening and healthcare costs associated with HCV. The model-estimated prevalence of undiagnosed HCV was used to calculate the antibody screens needed annually, with a €25 000 cost-effectiveness threshold. Outcomes were assessed under the status quo and a scenario that met the World Health Organization's targets for elimination of HCV. The elimination scenario was assessed under five screening strategies. RESULTS: A graduated birth cohort screening strategy (graduated screening 1: 1968-1987 birth cohorts, then expanding to 1948-1967 cohorts) was the least costly. This strategy would gain approximately 144 000 quality-adjusted life years (QALYs) by 2031 and result in an 89.3% reduction in HCV cases, compared to an 89.6%, 89.0%, 89.7% and 88.7% reduction for inversed graduated screening, 1948-77 birth cohort, 1958-77 birth cohort and universal screening, respectively. Graduated screening 1 yielded the lowest incremental cost-effectiveness ratio (ICER) of €3552 per QALY gained. CONCLUSIONS: In Italy, a graduated screening scenario is the most cost-effective strategy. Other countries could consider a similar birth cohort approach when developing HCV screening strategies.

Predictive factors of overall functioning improvement in patients with chronic schizophrenia and schizoaffective disorder treated with paliperidone palmitate and aripiprazole monohydrate.

BACKGROUND: Long-acting injectable (LAI) antipsychotics can improve medication adherence and reduce hospitalisation rates compared with oral treatments. Paliperidone palmitate (PAL) and aripiprazole monohydrate (ARI) LAI treatments were associated with improvements in global functioning in patients with schizophrenia. OBJECTIVE: The objective of this study was to assess the predictive factors of better overall functioning in patients with chronic schizophrenia and schizoaffective disorder treated with PAL and ARI. METHOD: Enrolled were 143 (97 males, 46 females, mean age 38.24 years, SD = 12.65) patients with a diagnosis of schizophrenia or schizoaffective disorder, whom we allocated in two groups (PAL and ARI treatments). We assessed global functioning, amount of oral medications, adherence to oral treatment, and number of hospitalisations before LAI introduction and at assessment time point. RESULTS: Longer treatment time with LAIs (p < .001), lower number of oral drugs (p < .001), and hospitalisations (p = .002) before LAI introduction, and shorter duration of illness (p = .038) predicted better Global Assessment of Functioning scores in the whole sample (R2  = 0.337). CONCLUSION: Early administration and longer duration of ARI or PAL treatments could play a significant role in improving global functioning of patients with schizophrenia and schizoaffective disorder. Better improvement in functioning could be achieved with ARI in young individuals with recent illness onset and PAL in patients at risk for recurrent hospitalisations.

Cost per response for abatacept versus adalimumab in rheumatoid arthritis by ACPA subgroups in Germany, Italy, Spain, US and Canada.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder leading to disability and reduced quality of life. Effective treatment with biologic DMARDs poses a significant economic burden. The Abatacept versus Adalimumab Comparison in Biologic-Naïve RA Subjects with Background Methotrexate (AMPLE) trial was a head-to-head, randomized study comparing abatacept in serum anti-citrullinated protein antibody (ACPA)-positive patients, with increasing efficacy across ACPA quartile levels. The aim of this study was to evaluate the cost per response accrued using abatacept versus adalimumab in ACPA-positive and ACPA-negative patients with RA from the health care perspective in Germany, Italy, Spain, the US and Canada. A cost-consequence analysis (CCA) was designed to compare the monthly costs per responding patient/patient in remission. Efficacy, safety and resource use inputs were based on the AMPLE trial. A one-way deterministic sensitivity analysis (OWSA) was also performed to assess the impact of model inputs on the results for total incremental costs. Cost per response in ACPA-positive patients favoured abatacept compared with adalimumab (ACR20, ACR90 and HAQ-DI). Subgroup analysis favoured abatacept with increasing stringency of response criteria and serum ACPA levels. Cost per remission (DAS28-CRP) favoured abatacept in ACPA-negative patients, while cost per CDAI and SDAI favoured abatacept in ACPA-positive patients. Abatacept was consistently favoured in ACPA-Q4 patients across all outcomes and countries. Cost savings were greater with abatacept when more stringent response criteria were applied and also with increasing ACPA levels, which could lead to a lower overall health care budget impact with abatacept compared with adalimumab.

Economic effects of treatment of chronic kidney disease with low-protein diet.

OBJECTIVE: The most recent literature has shown extensively that a low-protein diet in patients with chronic kidney disease (CKD) delays the natural progression of end-stage renal disease and the necessary treatment of chronic dialysis. The aim of this study was to estimate the cost-effectiveness of a very low-protein diet compared with a moderate low-protein diet. DESIGN: Markov model. SETTING: The study was conducted from the perspective of the Italian National Health Service. SUBJECTS: Patients with CKD stages 4 and 5. Seven hundred and two patients were considered, and half were treated with a very low-protein diet and the other half with a moderate low-protein diet. INTERVENTION: The Markov model estimates the costs and the quality-adjusted life years (QALYs) associated with a very low-protein diet versus a moderate low-protein diet for patients with CKD Stages 4 and 5. The transition probability was estimated on data from 7 studies, which determined the efficacy of very low-protein diets in delaying the need to start maintenance dialysis. Utilities and cost were estimated from literature review and projected for the lifespan considered in the model. The annual cost of dialysis per patient was approximately €34,072. The cost of a very low-protein diet was €1,440 per patient per year in the Lazio region (conservative assumptions). Probabilistic and deterministic sensitivity analyses were performed. MAIN OUTCOME MEASURE: QALY, cost of treatment, incremental cost-effectiveness ratio. RESULTS: The model estimates that a very low-protein diet should be more effective. Dietary treatment improved 0.09 QALYs after 2 years, 0.16 after 3 years, 0.36 after 5 years, and up to 0.93 incremental QALYs after the first 10 years. After 2 years, the model estimated increment cost in favor of the most restrictive dietary treatment of €826, €2,146, €5,203, and €10,375 for 2, 3, 5, and 10 years of follow-up respectively. CONCLUSIONS: The results of these simulations indicate that the treatment of CKD patients with a very low-protein diet is cost-effective relative to a moderate low-protein diet in an Italian setting. Further studies should test this model in other countries with different dialysis costs and dietary support.

Novel health economic evaluation of a vaccination strategy to prevent HPV-related diseases: the BEST study.

BACKGROUND: The development of human papillomavirus (HPV)-related diseases is not understood perfectly and uncertainties associated with commonly utilized probabilistic models must be considered. The study assessed the cost-effectiveness of a quadrivalent-based multicohort HPV vaccination strategy within a Bayesian framework. METHODS: A full Bayesian multicohort Markov model was used, in which all unknown quantities were associated with suitable probability distributions reflecting the state of currently available knowledge. These distributions were informed by observed data or expert opinion. The model cycle lasted 1 year, whereas the follow-up time horizon was 90 years. Precancerous cervical lesions, cervical cancers, and anogenital warts were considered as outcomes. RESULTS: The base case scenario (2 cohorts of girls aged 12 and 15 y) and other multicohort vaccination strategies (additional cohorts aged 18 and 25 y) were cost-effective, with a discounted cost per quality-adjusted life-year gained that corresponded to €12,013, €13,232, and €15,890 for vaccination programs based on 2, 3, and 4 cohorts, respectively. With multicohort vaccination strategies, the reduction in the number of HPV-related events occurred earlier (range, 3.8-6.4 y) when compared with a single cohort. The analysis of the expected value of information showed that the results of the model were subject to limited uncertainty (cost per patient = €12.6). CONCLUSIONS: This methodological approach is designed to incorporate the uncertainty associated with HPV vaccination. Modeling the cost-effectiveness of a multicohort vaccination program with Bayesian statistics confirmed the value for money of quadrivalent-based HPV vaccination. The expected value of information gave the most appropriate and feasible representation of the true value of this program.

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.

Healthcare Resource Utilization, Cardiovascular Event Rate and Use of Lipid-Lowering Therapies in Secondary Prevention of ASCVD in Hospitalized Patients in Italy.

INTRODUCTION: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality in Italy, accounting for 22% of total deaths. Lowering low-density lipoprotein cholesterol (LDL-C) levels reduces the risk of cardiovascular (CV) events; thus, lipid-lowering therapy (LLT) is the first-line treatment for patients with ASCVD and hypercholesterolaemia. However, many patients with ASCVD fail to reach LDL-C treatment thresholds, leaving them at greater risk of CV events. Inpatient care accounts for 51% of total expenditure on cardiovascular disease in the European Union, but healthcare resource utilization (HCRU) data for ASCVD in Italy is limited. METHODS: The study analysed healthcare claims data for 17,881 patients with acute coronary syndrome, ischemic stroke or peripheral artery disease from the Umbria 2 and Marche regions of Italy. LLT treatment patterns and CV event rates were collected and HCRU estimated in the year before and after the index event. RESULTS: High-intensity LLTs were prescribed to 44.3% of patients and 49.6% received moderate-/low-intensity LLTs during the 6 months after the index event. The first year CV event rate was 18.0/100 patient-years for patients receiving high-intensity LLTs and 17.2/100 patient-years for those on moderate-/low-intensity LLTs. Higher costs were associated with patients untreated with LLT 6 months post-index event (€8323) than patients prescribed high-intensity (€6278) or moderate-/low-intensity LLTs (€6270). Hospitalization accounted for most of the total costs. CONCLUSIONS: This study found that CV events in secondary prevention Italian patients are associated with substantial HCRU and costs. More intensive LDL-C lowering can prevent CV events, easing the financial burden on the healthcare system.

Challenges and solutions to embed cancer survivorship research and innovation within the EU Cancer Mission.

We have reached a watershed moment in Europe in our efforts to ensure increased survival and better outcomes for cancer patients. The EU Cancer Mission and the European Beating Cancer Plan together provide an unrivalled opportunity to make significant inroads into a disease that kills over 1.7 million European citizens annually. Harnessing these twin pillars of cancer research and cancer control can be transformative for the European cancer community and in particular for the European cancer patient. However, from a research perspective, in order to fully realise these benefits, we need to ensure that all aspects of the cancer continuum are addressed. Previous research efforts have focussed more on the diagnosis and treatment of cancer, whereas cancer survivorship, to date, has been overlooked. Here, we aim to redress this balance, by identifying the key challenges in cancer survivorship research that need to be addressed and proposing a series of recommended solutions, which, if acted upon, would deliver significant benefits for the nearly 20 million cancer survivors in Europe. To achieve this, we propose the development of a clearly articulated and sustainably funded European Cancer Survivorship Research and Innovation Plan. Embedding this plan within the framework of the EU Cancer Mission would be transformative for cancer survivors and society.

Budget Impact Analysis of Dalbavancin in the Treatment of Acute Bacterial Skin and Skin Structure Infections in Three European Countries.

BACKGROUND AND OBJECTIVE: Acute bacterial skin and skin structure infections (ABSSSIs) have been defined by the US Food and Drug Administration (FDA) in 2013 to include a subset of complicated skin and skin structure infections commonly treated with parenteral antibiotic therapy. Inpatient treatment of ABSSSIs involves a significant economic burden on the healthcare system. This study aimed to evaluate the economic impact on the National Health System associated with the management of non-severe ABSSSIs treated in hospitals with innovative long-acting dalbavancin compared to standard antibiotic therapy in Italy, Spain, and Austria. METHODS: A budget impact analysis was developed to evaluate the direct costs associated with the management of ABSSSI from the national public health system perspective. The model considered the possibility of early discharge of patients directly from the Emergency Department (ED), after 1 night in the hospital, or after two or three nights in the hospital. A scenario with Standard of Care was compared with a dalbavancin scenario, where patients had the possibility of being discharged early. The epidemiological and cost parameters were extrapolated from national administrative databases and from a systematic literature review for each country. The analysis was conducted in a 3-year time horizon. A one-way deterministic sensitivity analysis was conducted to examine the robustness of the results. RESULTS: The model estimated an average annual number of patients with non-severe ABSSSI in Italy, Spain, and Austria equal to 5396, 7884, and 1788, respectively. A total annual expenditure of about €9.9 million, €13.5 million, and €3.4 million was estimated for treating the full set of ABSSSI patients in Italy, Spain, and Austria, respectively. Dalbavancin reduced the in-hospital length of stay in each country. In the first year of its introduction, dalbavancin significantly reduced the total economic burden in Italy and Spain (- €352,252 and - €233,991, respectively), while it increased the total economic burden in Austria (€80,769, 0.7% of the total expenditure for these patients); in the third year of its introduction, dalbavancin reduced the total economic burden in each Country (- €1.1 million, - €810,650, and - €70,269, respectively). CONCLUSIONS: The introduction of dalbavancin in a new patient pathway to treat non-severe ABSSSI could generate a significant reduction in hospitalized patients and the overall patient length of stay in hospital.

The burden of atopic dermatitis in adults in Italy.

BACKGROUND: Moderate-to-severe atopic dermatitis (AD) generates a considerable consumption of healthcare resources and significant economic consequences for the patients and their families, healthcare systems (NHS) and society. Several studies on the burden of AD in paediatric patients are available in literature, while data in adults is scant. The purpose of this study was to estimate the direct and indirect costs of moderate to severe AD in adult patients in Italy. METHODS: Patients with Eczema Area and Severity Index (EASI) Score >20 were included in a multicentre, observational study conducted in six outpatient dermatology clinics throughout the national territory. Data were retrospectively gathered through a case report form investigating healthcare resources consumption, out-of-pocket expenses and patients' and caregivers' productivity loss. Descriptive statistics was used to illustrate data. Univariate generalized linear model with gamma distribution and identity function link was used to describe association between costs and disease severity. RESULTS: A total of 50 patients with a diagnosis of moderate-to-severe DA (EASI Score ≥20), equal to 89% of the total, were included in the analysis. The total annual burden of the disease, direct and indirect costs, amounted to € 4284 per patient; 19.3% accounted for direct medical costs, 19.9% for direct non-medical and 60.8% for indirect costs due to productivity loss. CONCLUSIONS: Moderate-to-severe AD in adults represents an important cost for the society imposing a high financial burden for the NHS, but even more for patients and caregivers. Results from this study may support identification of potential factors impacting on the choice of new therapeutic options to improve the clinical and economic management of this devastating disease.

Cost Estimate of Immune-Related Adverse Reactions Associated with Innovative Treatments of Metastatic Melanoma.

BACKGROUND AND OBJECTIVE: Immuno-oncology therapies represent a new treatment opportunity for patients affected by metastatic melanoma. The purpose of this study was to estimate the costs of immune-related adverse events (irAEs) associated with the new anti-PD1 immuno-oncology therapies, with the anti-CTLA-4 immuno-oncology therapy and with the combined therapy (CTLA4 + anti-PD1) in patients affected by metastatic melanoma. MATERIALS AND METHODS: A probabilistic cost-of-illness (COI) model was developed to estimate the management costs of grade ≥ 3 adverse events associated with the new anti-PD1 therapies (pembrolizumab and nivolumab), the anti-CTLA-4 therapy (ipilimumab) and the combined therapy CTLA4 + anti-PD1 (nivolumab + ipilimumab) for the treatment of patients with metastatic melanoma from the National Health Service (NHS) perspective in Italy. Identification of the epidemiological and cost parameters was carried out through a systematic literature review (SLR). Univariate and probabilistic sensitivity analyses were performed to account for uncertainty and variation in the model results. RESULTS: The model estimated a cost associated with the management of grade ≥ 3 immune-related adverse events in patients with metastatic melanoma equal to €176.2 (95% CI 63.5-335.0) for anti-CTLA-4 therapy, €48.6 (95% CI 40.1-58.5) for the new anti-PDI therapies and €276.8 (95% CI 240.4-316.2) for the combined therapy. Among the innovative therapies for the considered metastatic melanoma, the combined therapy was the most expensive innovative treatment in terms of event management of immune-related grade ≥ 3 adverse events. CONCLUSION: This study may represent a useful tool to understand the economic burden associated with the management of irAEs associated with patients affected by metastatic melanoma.

Economic evaluation of spondyloarthritis: economic impact of diagnostic delay in Italy.

BACKGROUND AND AIM: Spondyloarthritis (SpA) is a disease that normally affects the axial skeleton. It progressively leads to overall stiffness up to severe postural deformity of rachis and functional impotence. The objective of the study was to quantify, through an economic model, the impact of specialized testing and pharmacological treatments carried out by the National Health Service (NHS) in normal clinical practice, before the patient is diagnosed with SpA in Italy. In line with the analysis objective, the chosen perspective is that of the NHS. METHOD: The study was conducted by analyzing the Health Search Database - IMS Health Longitudinal Patient Database, from which newly diagnosed SpA patients were identified over the period 1 January 2007 to 31 December 2013. The use of specialist health care services and pharmacological treatments provided to the patients before the final SpA diagnosis were estimated. RESULTS: Through a retrospective analysis of the Health Search Database, 1,084 subjects (aged 25-45 years) were identified. These patients produced an expense of approximately €153,000 in the 3 years prior to a confirmed SpA diagnosis, in terms of specialist check-ups and drugs, presumably not appropriately used due to a lack of diagnosis. If we assume that the Health Search Database is a representative sample of the Italian population, it may be estimated that, in the 3 years prior to SpA diagnosis, over €5.4 million was largely unduly spent in Italy to examine and manage 38,232 newly diagnosed SpA patients, between 2010 and 2013. CONCLUSION: The costs due to the delay in SpA diagnosis were quantified for the first time in Italy. For this reason, this work represents a contribution for national and regional decision makers to understand the current clinical practice and the economic consequences of a diagnostic delay in the short and medium term.

Healthcare resource utilization among patients with relapsed multiple myeloma in the UK, France, and Italy.

AIMS: To assess the real-world healthcare resource utilization (HRU) and costs associated with different treatment regimens used in the management of patients with relapsed multiple myeloma in the UK, France, and Italy. METHODS: Retrospective medical chart review of characteristics, time to progression, level of response, HRU during treatment, and adverse events (AEs). Data collection started on June 1, 2015 and was completed on July 15, 2015. In the 3 months before record abstraction, eligible patients had either disease progression after receiving one of their country's most commonly prescribed regimens or had received the best supportive care and died. Costs were calculated based on HRU and country-specific diagnosis-related group and/or unit reference costs, amongst other standard resources. RESULTS: Physicians provided data for 1,282 patients (387 in the UK, 502 in France, 393 in Italy) who met the inclusion criteria. Mean [median] total healthcare costs associated with a single line of treatment were €51,717 [35,951] in the UK, €37,009 [32,538] for France, and €34,496 [42,342] for Italy, driven largely by anti-myeloma medications costs (contributing 95.0%, 90.0%, and 94.2% of total cost, respectively). During active treatment, the highest costs were associated with lenalidomide- and pomalidomide-based regimens. Mean cost per month was lowest for patients achieving a very good partial response or better. Unscheduled events (i.e. not considered part of routine management, whether or not related to multiple myeloma, such as unscheduled hospitalization, AEs, fractures) accounted for 1-9% of total costs and were highest for bendamustine. LIMITATIONS: The use of retrospective data means that clinical practice (e.g. use of medical procedures, evaluation of treatment response) is not standardized across participating countries/centers, and some data (e.g. low-grade AEs) may be incomplete or differently adjudicated/reported. The centers involved may not be fully representative of national practice. CONCLUSIONS: Drug costs are the main contributor to total HRU costs associated with multiple myeloma. The duration of active treatment may influence the average total costs, as well as response, associated with a single line of therapy. Improved treatment outcomes, and reductions in unscheduled events and concomitant medication use may, therefore, reduce the overall HRU and related costs of care in multiple myeloma.

Model of Management (Mo.Ma) for the patient with schizophrenia: crisis control, maintenance, relapse prevention, and recovery with long-acting injectable antipsychotics (LAIs).

INTRODUCTION: Schizophrenia is a severe mental disease that affects approximately 1% of the population with a relevant chronic impact on social and occupational functioning and daily activities. People with schizophrenia are 2-2.5 times more likely to die early than the general population. Non-adherence to antipsychotic medications, both in chronic and first episode schizophrenia, is one of the most important risk factors for relapse and hospitalization, that consequently contributes to increased costs due to psychiatric hospitalization. Atypical long-acting injectable (LAI) antipsychotics can improve treatment adherence and decrease re-hospitalization rates in patients with schizophrenia since its onset. The primary goals in the management of schizophrenia are directed not only at symptom reduction in the short and long term, but also at maintaining physical and mental functioning, improving quality of life, and promoting patient recovery. AIM: To propose a scientific evidence-based integrated model that provides an algorithm for recovery of patients with schizophrenia and to investigate the effectiveness and safety of antipsychotics LAI in the treatment, maintenance, relapse prevention, and recovery of schizophrenia. METHODS: After an accurate literature review we identified, collected and analyzed the crucial points in taking care schizophrenia patients, through which we defined the steps described in the model of management and the choice of the better treatment option. Results. In the management model we propose, the choice of a second generation long acting antipsychotic, could allow from the earliest stages of illness better patient management, especially for young individuals with schizophrenia onset, a better recovery and significant reductions of relapse and health care costs. LAI formulations of antipsychotics are valuable, because they help patients to remain adherent to their medication through regular contact with healthcare professionals and to prevent covert non-adherence. CONCLUSIONS: The proposed schizophrenia model of management could allow better patient management and recovery, in which the treatment with LAI formulation is a safe and effective therapeutic option. This new therapeutic approach could change the cost structure of schizophrenia by decreasing costs with efficient economic resource allocation guaranteed from efficient diagnostic and therapeutic pathways.