Eosinophilic esophagitis in adults and adolescents: epidemiology, diagnostic challenges, and management strategies for a type 2 inflammatory disease.

Background: Eosinophilic esophagitis (EoE) is recognized as a chronic type 2 inflammatory disease characterized by the eosinophilic infiltration of the esophageal tissue, posing a significant disease burden and highlighting the necessity for novel management strategies to address unmet clinical needs. Objectives: To critically evaluate the existing literature on the epidemiology and management of EoE, identify evidence gaps, and assess the efficacy of current and emerging treatment modalities. Design: An extensive literature review was conducted, focusing on the epidemiological trends, diagnostic challenges, and therapeutic interventions for EoE. This was complemented by a survey among physicians and consultations with a scientific expert panel, including a patient's association (ESEO Italia), to enrich the study findings. Data sources and methods: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, scrutinizing epidemiological studies and management research to compile comprehensive insights into the disease's landscape. The physician survey and expert panel discussions aimed to bridge identified evidence gaps. Results: The review included 59 epidemiological and 51 management studies, uncovering variable incidence and prevalence rates of EoE globally, with an estimated diagnosed prevalence of 41 per 100,000 in Italy. Diagnostic challenges were identified, including nonspecific symptoms and the lack of definitive biomarkers, which complicate the use of endoscopy. Treatment options such as elimination diets, proton-pump inhibitors, and swallowed corticosteroids were found to have varying success rates, while Dupilumab, an emerging therapy targeting interleukin (IL)-4 and IL-13, shows promise. Conclusion: Despite advancements in understanding and managing EoE, significant unmet clinical needs remain, particularly in biomarker identification, therapy personalization, and cost-effectiveness evaluation. A comprehensive, multidimensional approach to patient management is required, emphasizing the importance of early symptom recognition, accurate diagnosis, and tailored treatment strategies. Dupilumab offers potential as a novel treatment, underscoring the need for future research to explore the economic and social dimensions of EoE care pathways.

Understanding and improving care for eosinophilic esophagitis: bridging gaps in diagnosis and treatment Eosinophilic esophagitis (EoE) is a chronic inflammatory condition affecting the esophagus. We reviewed studies on how common EoE is and how it's managed. In Italy, about 41 out of 100,000 people may have it. Diagnosis can be tricky due to vague symptoms, and current treatments vary in effectiveness. We found a need for better ways to diagnose and treat EoE, including exploring new therapies. A promising development is a biologic called Dupilumab. Future research should also consider the costs and social aspects of caring for people with EoE.

A budget impact model and a cost-utility analysis of reducer device (Neovasc) in patients with refractory angina.

Background: Refractory angina (RA) is a chronic condition characterized by the presence of debilitating angina symptoms due to established reversible ischemia in the presence of obstructive coronary artery disease (CAD). Treatments for this condition have undergone major developments in recent decades; however, the treatment for RA remains a challenge for medicine. In this sense, the Coronary Sinus Reducer System (CSRS) stands as the last line of therapy for ineligible patients for revascularization with reversible ischemia. The purpose of this report is to evaluate the potential burden on the National Health Service (NHS) and measure the health effects in terms of both quantity (life years) and quality-of-life aspects related to the reducer. Methods: Two different economic evaluation models were developed as part of the analysis. The budget impact was developed to estimate the potential burden on the NHS from incremental uptake of the use of the reducer in the target population. The utility cost analysis compares and evaluates the quality of life and health resource use and costs between the two alternatives, based on the research of Gallone et al. A deterministic and probabilistic sensitivity analysis was carried out to characterize the uncertainty around the parameters of the model. Results: In the budget impact analysis (BIA), the reducer is shown to be more expensive in the first 2 years of the model, due to the gradual uptake in the market and the cost of the device. Starting from the third year, assuming maintenance of effectiveness, there are savings in terms of resource absorption in direct healthcare costs arising from hospitalizations, emergency department accesses, coronarography, and visits avoided. Conclusion: The BIA and cost-effectiveness model show that the reducer device, despite an increase in resources absorbed in the first years of implementation and use, has the potential to result in increased quality of life in patients with RA. These costs are largely offset in the short term by the improved clinical outcomes achievable leading to savings from the third year onward in the BIA and a dominance ratio in the cost-utility analysis.

Evaluation of the economic impact of the robotic approach in major and postero-superior segment liver resections: a multicenter retrospective analysis.

Background: Economic impact of robotic liver surgery (RLS) is still a debated issue due to the heterogeneity of liver resections considered and the lack of a rigorous methodology. Therefore, the aim of this study is to perform a time-driven activity-based costing (TD-ABC) comparing the costs of RLS, laparoscopic liver surgery (LLS) and open liver surgery (OLS) in the context of complex liver resections and to compare short term perioperative outcomes. Methods: The institutional databases of two Italian high volume hepatobiliary centres were retrospectively reviewed from February 2021 to April 2022. Patients submitted to major hepatectomies or postero-superior liver resections were selected and divided into three groups according to the approach scheduled (RLS, LLS and OLS) and compared. Major contributors of perioperative expenses were calculated using the TD-ABC model and accurately quantifying each unit resource consumed per patient and the time spent performing each activity. A primary intention-to-treat analysis (ITT-A) including conversions in the RLS and LLS groups was performed. Results: Forty-seven RLS, 101 LLS and 124 OLS were collected. LLS and RLS showed reduced blood loss, morbidity, mortality and hospital stay compared with open. A trend towards reduced conversion rate in RLS compared to LLS was registered. Total costs associated with RLS were estimated at €10,637 vs. €9,543 for LLS and vs. €13,960 for OLS. The higher intraoperative costs associated with RLS (+153.3% vs. OLS and +148.2% vs. LLS, P<0.001), primarily related to surgical equipment expenses, were slightly offset by the postoperative savings (-56.0% vs. OLS and -29.4% vs. LLS, P<0.001) resulting from significantly reduced hospital stays. Conclusions: RLS offers economic advantages over OLS, as initial higher costs are offset by better perioperative outcomes. The evolving robotic marketplace is expected to drive down RLS costs, promoting widespread adoption in minimally invasive procedures. Despite its higher costs than LLS, RLS's ability to enhance minimally invasive feasibility makes it a preferred choice for complex cases, reducing the need for conversions.

The economic and fiscal impact of incremental use of cell-based quadrivalent influenza vaccine for the prevention of seasonal influenza among healthcare workers in Italy.

BACKGROUND: Seasonal influenza has a significant impact on public health, generating substantial direct healthcare costs, production losses and fiscal effects. Understanding these consequences is crucial to effective decision-making and the development of preventive strategies. This study aimed to evaluate the economic and the fiscal impact of implementing an incremental strategy for seasonal influenza prevention using the cell-based quadrivalent influenza vaccine (QIVc) among healthcare workers (HCWs) in Italy. METHODS: To estimate the economic impact of implementing this strategy, we performed a cost analysis that considered direct healthcare costs, productivity losses and fiscal impact. The analysis considered a 3-year time horizon. A deterministic sensitivity analysis was also conducted. RESULTS: Assuming a vaccination coverage rate of 30% among HCWs, the analysis considered a total of 203 018 vaccinated subjects. On analysing the overall differential impact (including direct costs, indirect costs and fiscal impact), implementing QIVc vaccination as a preventative measure against influenza among HCWs in Italy would yield societal resource savings of €23 638.78 in the first year, €47 277.56 in the second year, and €70 916.35 in the third year, resulting in total resource savings of €141 832.69. CONCLUSIONS: The study demonstrated that implementing the incremental use of QIVc as part of a preventive strategy for seasonal influenza among HCWs in Italy could yield positive economic outcomes, especially in terms of indirect costs and fiscal impact. The resources saved could be utilized to fund further public health interventions. Policy-makers should consider these findings when making decisions regarding influenza prevention strategies targeting HCWs.

Cost-effectiveness for high dose quadrivalent versus the adjuvanted quadrivalent influenza vaccine in the Italian older adult population.

Objectives: To assess the cost-effectiveness of switching from adjuvanted quadrivalent vaccine (aQIV) to high-dose quadrivalent influenza vaccine (HD-QIV) in those aged ≥65 years from the Italian National Health Service perspective. Methods: We developed a decision tree model over a 1-year time-horizon to assess influenza-related costs and health outcomes. Two hospitalization approaches were considered: "hospitalization conditional on developing influenza" and "hospitalization possibly related to Influenza." The first approach considered only hospitalizations with influenza ICD-9-CM diagnosis codes. The second included hospitalizations for cardiorespiratory events possibly related to influenza to better capture the "hidden burden". Since comparative efficacy of high-dose quadrivalent influenza vaccine versus adjuvanted quadrivalent vaccine was lacking, we assumed relative efficacy versus a common comparator, standard-dose influenza quadrivalent vaccines (SD-QIV). We assumed the relative efficacy of HD-QIV vs. SD-QIV was 24.2 and 18.2% for the first and second hospitalization approaches, respectively, based on published information. Due to lack of comparative efficacy data for aQIV vs. SD-QIV, we assumed three different scenarios: 0, 6, and 12% relative efficacy in scenarios 1, 2, and 3, respectively. Results: For the first hospitalization approach, HD-QIV was a cost-effective alternative to aQIV in all scenarios at a willingness-to-pay threshold of €30,000 per Quality Adjusted Life Years. The incremental cost-effectiveness ratios across the scenarios were €7,301, €9,805, and €14,733, respectively, much lower than the willingness-to-pay per Quality Adjusted Life Years threshold. For the second hospitalization approach, HD-QIV was a dominant alternative to aQIV across all scenarios. The robustness of the results was confirmed in one-way and probabilistic sensitivity analyses. Conclusion: Switching to HD-QIV from aQIV for the older adult in Italy would improve health-related outcomes, and would be cost-effective or cost saving.

Analysis of heterogeneity of the different health technology assessment reports produced on the transcatheter aortic valve implantation in patients with severe aortic valve stenosis at low surgical risk.

Background: Symptomatic severe aortic stenosis is a congenital or acquired aortic valve disease that occurs when the aortic valve of the heart narrows. It represents the most common valvular disease in adults and generally has a degenerative nature. Transcatheter aortic valve implantation (TAVI), due to its non-invasive approach, has become the standard treatment in patients who are ineligible to surgery or at high surgical risk, and it is also increasingly being performed in patients at intermediate to low surgical risk. The aim is to analyze the heterogeneity and explore the limitations of current health technology assessments (HTAs) on TAVI. Methods: For the purpose of this analysis, a review of the literature based on manual research was performed. A population, intervention, comparators, and outcome (PICO) model was used to gather the HTA reports assessing TAVI in the treatment of patients affected by symptomatic severe aortic valve stenosis at low surgical risk. Furthermore, a manual search has been developed to also include assessments from the Haute Autorité de Santé. Results: At the end of the investigation, a certain degree of heterogeneity in the evidence factored and in the recommendations on the technology has emerged. Relative to the clinical domains, the main drivers for the disparity are found in the type of evidence considered and in the use or not of the grading of recommendations, assessment, development, and evaluation (GRADE) methodology to evaluate the quality of the clinical evidence included. Another element concerns the chosen device generation assessed within the evaluation. In order to perform the economic evaluation, a cost-utility analysis and a budget impact model were developed. Despite some elements of heterogeneity, the economic assessments demonstrate a favorable or dominant cost-effectiveness profile for TAVI compared with surgical aortic valve replacement (SAVR). Conclusion: Despite the presence of heterogeneity elements both in clinical and economic domains, HTA agencies reached the same recommendations on the use of TAVI. It emerged the need for a centralized vision on the "strong" domains, which means giving up freedom to local bodies to adapt to their context on the "soft" ones. This approach could have the potential to strengthen the role of HTA in Europe by ensuring faster decision-making and equity of access to health innovations and reduce the heterogeneity in the assessment methods.

Budget impact of prophylactic treatment of rVIII-SingleChain in moderate and severe hemophilia A in Italy.

INTRODUCTION: rVIII-SingleChain, a recombinant factor VIII (rFVIII), has demonstrated safety and efficacy in patients with hemophilia A in clinical trials and real-world evidence. This analysis aimed to estimate the potential budget impact of increasing the usage of rVIII-SingleChain for the prophylactic treatment of hemophilia A over 3 years in Italy. METHODS: Patients with moderate and severe hemophilia A receiving prophylaxis were included in the analysis. Epidemiological data were obtained from published literature. Mean product consumption and mean annual bleeding rate for rVIII-SingleChain, rFVIIIFc, octocog alfa and BAY 81-8973 were based on pooled real-world data from Italy, Germany and US. A budget impact model has been developed in order to compare two scenarios: a base-case scenario where current rVIII-SingleChain shares are kept constant over 3 years and an alternative scenario where rVIII-SingleChain shares increase by taking from other rFVIII products. Analysis 1 was based on the current Italian list prices and Analysis 2 considered current regional acquisition prices for both scenarios. RESULTS: Annually, adult patients treated with rVIII-SingleChain prophylaxis are expected to consume 324,589 units per patient, resulting in annual costs of €240,196 per patient. In Analysis 1, comparing the base case (constant market share of 9% rVIII-SingleChain over time) with the alternative scenario (higher rVIII-SingleChain market share and increasing from 15% in the first year to 25% in the third year), the total expenditure for prophylaxis using rFVIII products is expected to decrease by €1.4 million in Year 1, by €3.1 million in Year 2 and by €5.4 million in Year 3. In Analysis 2 based on regional prices, the results remained consistent. DISCUSSION/CONCLUSION: This analysis suggests that increasing utilization of rVIII-SingleChain in hemophilia A patients may lead to cost savings as a result of reduced consumption with uncompromised efficacy in bleed protection.

Why was the study done? Hemophilia A is a rare inherited bleeding disorder. People with severe hemophilia are more likely to bleed compared to people without hemophilia and bleeds can occur spontaneously or in response to trauma. Patients are treated with medication to reduce the chance of bleeding. However, the cost of treating patients with hemophilia can be high and place demands on the healthcare system.What did we do and find?This study looked at the cost of treating people with hemophilia in Italy and used a type of economic analysis (called budget impact modelling) to estimate the effect of increasing the use of a particular medication (rVIII-SingleChain), compared to other medications that are available. Different variations of the model were tested to compare a range of scenarios.The results of this analysis suggested that increasing the use of rVIII-SingleChain may lead to cost-savings for the Italian healthcare system, compared to using the other currently available treatments. This analysis suggests that the use of rVIII-SingleChain enables people with hemophilia A to remain protected from bleeds, whilst using less product compared to other available medications.What is the influence of this study on the wider field?This type of analysis can be useful to healthcare systems, to guide the decision-making process regarding which medications to use or when making decisions related to healthcare policy.

The added value of applying a disinvestment approach to the process of health technology assessment in Italy.

OBJECTIVES: The objective of the present policy analysis was to understand how a disinvestment approach to the process of health technology assessment (HTA), applied to the field of medical devices, might help Italian policymakers to properly spend the resources in healthcare. METHODS: Previous international and national experiences in disinvestment for medical devices were reviewed. Precious insights for the rational expenditure of the resources were derived by assessing the evidence available. RESULTS: The disinvestment of ineffective or inappropriate technologies or interventions with an inadequate value-for-money ratio has become a growing priority for National Health Systems. Different international disinvestment experiences of medical devices were identified and described through a rapid review. Although most of them have a strong theoretical framework, their practical application remains difficult. In Italy, there are no examples of large and complex HTA-based disinvestment practices, but their importance is becoming increasingly acknowledged, especially given the need to prioritize the funds provided by Recovery and Resilience Plan. CONCLUSIONS: Anchoring decisions on health technologies without reassessing the current technological landscape through a robust HTA model might expose to the risk of not ensuring the best employment of the resources available. Thus, it is necessary to develop a strong HTA ecosystem in Italy through adequate consultation with stakeholders to enable a data-driven and evidence-based prioritization of resources toward choices characterized by high value for both patients and society as a whole.

The Economic and Fiscal Impact of Influenza Vaccination for Health Care Workers in Italy.

Influenza has a significant impact on the health care system and also on production and economic systems. Vaccinated health care workers (HCWs) are more likely to have improved productivity compared to unvaccinated workers. The study aim was to estimate the economic and fiscal impact of an influenza vaccination program for HCWs in Italy. We performed a cost analysis aimed to estimate the indirect costs (productivity losses due to working days lost) and the increase in tax revenues derived from the increase in vaccination coverage among HCWs. Assuming an incremental increase in vaccination coverage of 10% per year over a period of 5 years, total savings could be obtained in terms of a reduction in productivity losses equal to -€4,475,497.16 and an increase in tax revenues of €327,158.84. This revenue could be used to finance other health interventions. Our results are fundamental in view of the sustainability of health systems and of a value-based allocation of health resources. Therefore, a complete social perspective, including the fiscal impact of flu vaccination, should be adopted to assess the economic value of influenza vaccines. Currently, health policies based on the whole value of flu vaccination are needed.

A Proposal for Value-Based Managed Entry Agreements in an Environment of Technological Change and Economic Challenge for Publicly Funded Healthcare Systems.

Managed entry agreements (MEA) represent one of the main topics of discussion between the European National Payers Authorities. Several initiatives on the subject have been organized over the past few years and the scientific literature is full of publications on the subject. There is currently little international sharing of information between payers, mainly as a result of the confidentiality issues. There are potential benefits from the mutual sharing of information, both about the existence of MEAs and on the outcomes and results. The importance of involving all the players in the decision-making process on market access for a medicinal product (MP) is that it may help to make new therapies available to patients in a shorter time. The aim of this project is to propose a new pathway of value-based MEA (VBMEA), based on the analysis of the current Italian pricing and reimbursement framework. This requires elaboration of a transparent appraisal and MEA details with at least a 24-month contract. The price of the MP is therefore valued based on the analysis of the VBMEA registries of the Italian Medicines Agency. Although the proposal focuses on the Italian context, a similar approach could also be adapted in other nations, considering the particularities of the single health technology assessment (HTA)/payer system.

Analysis of the multidisciplinary approach for the management of patients affected by chronic myeloid leukaemia.

Background: Chronic myelogenous leukaemia (CML) is a pathological clinical condition with a yearly incidence between 10 and 15 cases per million people, 14 in Italy. Its incidence increases with age, reaching 20-25 yearly cases per million individuals in people over 70 years. A growing importance has been given to the need of a multidisciplinary approach (MDA) for the management of patients with CML. Objective: To analyse the importance of MDA as compared with the current Italian standard of care for the management of CML patients based on the involvement of several health professional figures. Methods: A group of healthcare professionals from several healthcare structures were gathered in a first Advisory Board (AB) and divided into as many groups as the number of belonging health structures representative of the Italian provision of therapeutic approaches for CML. In a second AB, the results were validated by the same panel of experts. Results: The number of dedicated health professionals within the dedicated ward ranged from 1 to 13. Most structures rely on several professionals intervening only in case of necessity. Only one centre provides a booking service based on clinical needs to avoid waiting times. Most centres report there is basically no disagreement in the definition of the clinical pathway and there is a high adherence to national and international CML guidelines. Conclusions: The development of forms of interorganisational and interprofessional coordination to improve the diagnosis and the treatment of CML patients have been for long on the agenda of policy makers, managers and professionals for more than 20 years. This analysis represents a starting reference to consider for the evaluation of an MDA in the Italian context.

Budget impact of implementing platelet pathogen reduction into the Italian blood transfusion system.

BACKGROUND: Despite improvements in blood donor selection and screening procedures, transfusion recipients can still develop complications related to infections by known and emerging pathogens. Pathogen reduction technologies (PRT) have been developed to reduce such risks. The present study, developed whithin a wider health technology assessment (HTA) process, was undertaken to estimate the costs of the continuing increase in the use of platelet PRT in Italy. MATERIALS AND METHODS: A multidisciplinary team was established to perform the HTA and conduct a budget impact analysis. Quantitative data on platelet use were derived from the 2015 national blood transfusion report and from the Italian Platelets Transfusion Assessment Study (IPTAS). The current national fee of 60 Euro per platelet PRT procedure was used to quantify the costs to the Italian National Health Service (INHS). The analysis adopts a 3-year time-frame. In order to identify the impact on budget we compared a scenario representing an increased use of PRT platelets over time with a control scenario in which standard platelets are used. RESULTS: Progressive implementation of PRT for 20%, 40% and 66% of annual adult platelet doses could generate an increase in annual costs for the INHS amounting to approximately 7, 14 and 23 million Euros, respectively. Use of kits and devices suitable for the treatment of multiple adult platelet doses in one PRT procedure could lower costs. DISCUSSION: In order to fully evaluate the societal perspective of implementing platelet PRT, the increase in costs must be balanced against the expected benefits (prevention of transfusion-transmissible infections, white cell inactivation, extension of platelet storage, discontinuation of pathogen detection testing). Further studies based on actual numbers of platelet transfusion complications and their societal cost at a local level are needed to see the full cost to benefit ratio of platelet PRT implementation in Italy, and to promote equal treatment for all citizens.

The cost-effectiveness of an eradication programme in the end game: Evidence from guinea worm disease.

BACKGROUND: Of the three diseases targeted for eradication by WHO, two are so-called Neglected Tropical Diseases (NTDs)-guinea worm disease (GWD) and yaws. The Guinea Worm Eradication Programme (GWEP) is in its final stages, with only 25 reported in 2016. However, global eradication still requires certification by WHO of the absence of transmission in all countries. We analyze the cost-effectiveness of the GWEP in the end game, when the number of cases is lower and the cost per case is higher than at any other time. Ours is the first economic evaluation of the GWEP since a World Bank study in 1997. METHODS: Using data from the GWEP, we estimate the cost of the implementation, pre-certification and certification stages. We model cost-effectiveness in the period 1986-2030. We compare the GWEP to two alternative scenarios: doing nothing (no intervention since 1986) and control (only surveillance and outbreak response during 2016-2030). We report the cost per case averted, cost per disability adjusted life year (DALY) averted and cost per at-risk life year averted. We assess cost-effectiveness against a threshold of about one half GDP per capita (less than US$ 500 in low income countries). All costs are expressed in US$ of 2015. RESULTS: The GWEP cost an estimated US$ 11 (95% uncertainty interval, 4.70-12.49) per case averted in the period 1986-2030. The pre-certification and certification phases can cost as much as US$ 0.0041 and US$ 0.0015 per capita per year. The cost per DALY averted by the GWEP relative to doing nothing is estimated at US$ 222 (118-372) in 1986-2030. The GWEP is probably more cost-effective than control by the year 2030. The GWEP is certainly more cost-effective than control if willingness to pay for one year of life lived without the risk of GWD exceeds US$ 0.10. DISCUSSION: Even if economic costs are two times as high as the financial costs estimated for the period to 2020, the GWEP will still be cost-effective relative to doing nothing. Whether the GWEP turns out to be the most cost-effective alternative in the period beyond 2015 depends on the time horizon. When framed in terms of the number of years of life lived without the risk of GWD, a case can be made more easily for finishing the end game, including certification of the absence of transmission.