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.

Italian Guidelines for the Management of Sporadic Primary Hyperparathyroidism.

AIM: This guideline (GL) is aimed at providing a clinical practice reference for the management of sporadic primary hyperparathyroidism (PHPT) in adults. PHPT management in pregnancy was not considered. METHODS: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) and Società Italiana dell'Osteoporosi, del Metabolismo Minerale e delle Malattie dello Scheletro (SIOMMMS) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for the clinical practice recommendations. RESULTS: The present GL provides recommendations about the roles of pharmacological and surgical treatment for the clinical management of sporadic PHPT. Parathyroidectomy is recommended in comparison to surveillance or pharmacologic treatment in any adult (outside of pregnancy) or elderly subject diagnosed with sporadic PHPT who is symptomatic or meets any of the following criteria: • Serum calcium levels >1 mg/dL above the upper limit of normal range. • Urinary calcium levels >4 mg/kg/day. • Osteoporosis disclosed by DXA examination and/or any fragility fracture. • Renal function impairment (eGFR <60 mL/min). • Clinic or silent nephrolithiasis. • Age ≤50 years. Monitoring and treatment of any comorbidity or complication of PHPT at bone, kidney, or cardiovascular level are suggested for patients who do not meet the criteria for surgery or are not operated on for any reason. Sixteen indications for good clinical practice are provided in addition to the recommendations. CONCLUSION: The present GL is directed to endocrinologists and surgeons - working in hospitals, territorial services or private practice - and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.

A pharmacoeconomic analysis from Italian guidelines for the management of prolactinomas.

Background: Prolactinoma, the most common pituitary adenoma, is usually treated with dopamine agonist (DA) therapy like cabergoline. Surgery is second-line therapy, and radiotherapy is used if surgical treatment fails or in relapsing macroprolactinoma. Objective: This study aimed to provide economic evidence for the management of prolactinoma in Italy, using a cost-of-illness and cost-utility analysis that considered various treatment options, including cabergoline, bromocriptine, temozolomide, radiation therapy, and surgical strategies. Methods: The researchers conducted a systematic literature review for each research question on scientific databases and surveyed a panel of experts for each therapeutic procedure's specific drivers that contributed to its total cost. Results: The average cost of the first year of treatment was €2,558.91 and €3,287.40 for subjects with microprolactinoma and macroprolactinoma, respectively. Follow-up costs from the second to the fifth year after initial treatment were €798.13 and €1,084.59 per year in both groups. Cabergoline had an adequate cost-utility profile, with an incremental cost-effectiveness ratio (ICER) of €3,201.15 compared to bromocriptine, based on a willingness-to-pay of €40,000 per quality-adjusted life year (QALY) in the reference economy. Endoscopic surgery was more cost-effective than cabergoline, with an ICER of €44,846.64. Considering a willingness-to-pay of €40,000/QALY, the baseline findings show cabergoline to have high cost utility and endoscopic surgery just a tad above that. Conclusions: Due to the favorable cost-utility profile and safety of surgical treatment, pituitary surgery should be considered more frequently as the initial therapeutic approach. This management choice could lead to better outcomes and an appropriate allocation of healthcare resources.

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.

Italian Guidelines for the Management of Prolactinomas.

INTRODUCTION: This guideline (GL) is aimed at providing a reference for the management of prolactin (PRL)-secreting pituitary adenoma in adults. However, pregnancy is not considered. METHODS: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinologi (AME) has identified potentially relevant outcomes, which have then been rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" have been considered in the systematic review of evidence and only those classified as "critical" have been considered in the formulation of recommendations. RESULTS: The present GL provides recommendations regarding the role of pharmacological and neurosurgical treatment in the management of prolactinomas. We recommend cabergoline (Cab) vs. bromocriptine (Br) as the firstchoice pharmacological treatment to be employed at the minimal effective dose capable of achieving the regression of the clinical picture. We suggest that medication and surgery are offered as suitable alternative first-line treatments to patients with non-invasive PRL-secreting adenoma, regardless of size. We suggest Br as an alternative drug in patients who are intolerant to Cab and are not candidates for surgery. We recommend pituitary tumor resection in patients 1) without any significant neuro-ophthalmologic improvement within two weeks from the start of Cab, 2) who are resistant or do not tolerate Cab or other dopamine-agonist drugs (DA), 3) who escape from previous efficacy of DA, and 4) who are unwilling to undergo a chronic DA treatment. We recommend that patients with progressive disease notwithstanding previous tumor resection and ongoing DA should be managed by a multidisciplinary team with specific expertise in pituitary diseases using a multimodal approach that includes repeated surgery, radiotherapy, DA, and possibly, the use of temozolomide. CONCLUSION: The present GL is directed to endocrinologists, neurosurgeons, and gynecologists working in hospitals, in territorial services or private practice, and to general practitioners and patients.

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.

Italian Guidelines for the Management of Non-Functioning Benign and Locally Symptomatic Thyroid Nodules.

AIM: This guideline (GL) is aimed at providing a reference for the management of non-functioning, benign thyroid nodules causing local symptoms in adults outside of pregnancy. METHODS: This GL has been developed following the methods described in the Manual of the National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence and only those classified as "critical" were considered in the formulation of recommendations. RESULTS: The present GL contains recommendations about the respective roles of surgery and minimally invasive treatments for the management of benign symptomatic thyroid nodules. We suggest hemithyroidectomy plus isthmectomy as the first-choice surgical treatment, provided that clinically significant disease is not present in the contralateral thyroid lobe. Total thyroidectomy should be considered for patients with clinically significant disease in the contralateral thyroid lobe. We suggest considering thermo-ablation as an alternative option to surgery for patients with a symptomatic, solid, benign, single, or dominant thyroid nodule. These recommendations apply to outpatients, either in primary care or when referred to specialists. CONCLUSION: The present GL is directed to endocrinologists, surgeons, and interventional radiologists working in hospitals, in territorial services, or private practice, general practitioners, and patients. The available data suggest that the implementation of this GL recommendations will result in the progressive reduction of surgical procedures for benign thyroid nodular disease, with a decreased number of admissions to surgical departments for non-malignant conditions and more rapid access to patients with thyroid cancer. Importantly, a reduction of indirect costs due to long-term replacement therapy and the management of surgical complications may also be speculated.

Antibiotic-impregnated versus standard silicone catheter for external ventricular drainage in acute hydrocephalus associated to aneurysmal subarachnoid hemorrhage: a budget impact analysis from a single center Italian cohort.

BACKGROUND: Acute hydrocephalus is a frequent complication of aneurysmal subarachnoid hemorrhage, and it is generally treated by external ventricular drainage. In the last decades, antibiotic-impregnated ventricular catheters have been introduced in the neurosurgical practice in order to reduce secondary cerebrospinal fluid infections which increase morbidity, mortality, and health care costs. METHODS: Data of 100 patients treated at Fondazione Policlinico Universitario Agostino Gemelli IRCCS between January 2012 and December 2019 were retrospectively reviewed in order to determine the cost-effectiveness and budget impact of antibiotic impregnated versus non-impregnated catheters in the management of patients with aneurysmal subarachnoid hemorrhage related hydrocephalus. A budget impact model was built depending on the use of antibiotic impregnated versus non-impregnated catheters. The model was populated with data extrapolated from existing literature concerning the Italian healthcare setting and national tariffs. RESULTS: A 25% reduction in the number of cerebrospinal fluid infections was achieved by using antibiotic impregnated catheters, resulting in an overall saving equal to €5730.52/patient. Expanding results to a 100-patient sample, the possible savings would amount to €573,052.40 for the National Health Service. CONCLUSIONS: Antibiotic impregnated catheters use was associated to a reduction in cerebrospinal fluid infections rate as well as in costs related to hospital care when compared to nonimpregnated catheters. Thus these catheters represent, besides lifesaving, cost-saving devices that reduce the economic burden and ensure a safe clinical outcome in patients with aneurysmal subarachnoid hemorrhage related hydrocephalus. The present study provides concrete evidence of the benefit of Antibiotic impregnated catheters to decision-makers responsible of defining health policies.

Economic Aspects in the Management of Diabetic Macular Edema in Italy.

Background: Diabetic Macular Edema (DME) is the most common cause of vision loss in diabetic patients. Currently, the Vascular Endothelial Growth Factor inhibitors (anti-VEGFs) are used as the first line of DME treatment and corticosteroid implants are usually used as a second-line treatment. These implants are a safe and effective therapeutic option that can improve the quality of life of DME patients by reducing the intravitreal injections number. We determined the economic impact related to DME, also from the social perspective, and the consequences of the increased use of the dexamethasone implant. Methods: The analysis compares two scenarios: the first based on the current rate of recourse to the therapeutic alternatives available in the Italian healthcare setting (as is) and the second based on the assumption of an increased recourse to dexamethasone implants (to be). The results are expressed both in terms of the resource absorption associated with the two scenarios and in terms of the cost differential yielded by their comparison. Results: The increased use of the dexamethasone implant allows considerable savings in terms of healthcare professionals' time, follow-up and productivity lost by patients/caregivers. These savings would reduce healthcare costs for the management of DME patients in Italy by €2,058,238 in 5 years. Conclusions: To optimize the healthcare resources allocation, it is necessary to implement treatments that yield not only cost reductions but also a clinical benefit for patients. The dexamethasone implant use is an example of DME management that generates value for patients, health system and society.

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.

HPV Vaccination in Women Treated for Cervical Intraepithelial Neoplasia: A Budget Impact Analysis.

Human Papillomavirus (HPV) is the most common sexually transmitted infection. Its progression is related to the development of malignant lesions, particularly cervical intraepithelial neoplasias (CINs). CINs correlate with a higher risk of premature births, and their excisional and ablative treatment further increases this risk in pregnant women. These complications are also correlated with higher healthcare costs for their management. In Italy, more than 26,000 new cases of CINs are estimated to occur yearly and their economic burden is significant. Therefore, the management of these conditions is a public health priority. Since HPV vaccination is associated with a reduced risk of relapse in women surgically treated for HPV-related injuries, we estimated the economic impact of extending HPV vaccination to this target population. This strategy would result in a significant reduction in the general costs of managing these women, resulting in an overall saving for the Italian Health Service of €155,596.38 in 5 years. This lower cost is due not only to the reduced incidence of CINs following vaccination, but also to the lower occurrence of preterm births. Extending HPV vaccination to this target population as part of a care path to be offered to women treated for HPV injuries is therefore desirable.

Cognitive and Physical Activity-Related Aspects of Children Associated to the Performance of the Crunning Movement.

The aim of this investigation was to identify possible related factors associated to the performance of the crunning test in European children and adolescents. A total number of 559 children and adolescents (age range 6-14 years) of which 308 boys (55.1%) and 251 girls (44.9%), from seven European countries, were screened. A questionnaire concerning demographic and personal life-related factors and a cognitive assessment were performed. A regression analysis was conducted with the performance measures of the crunning movement. T-tests and ANCOVA were used to analyze sub-group differences. Boys have greater crunning performance values compared to girls (5.55 s vs. 7.06 s, p < 0.001) and older children perform better than younger ones (R2 -0.23; p < 0.001). Children with healthy and active habits (exercising or spending time with family members vs. reading or surfing the internet) performed better in the test. Children engaged in team sports had better crunning performances compared to those engaged in individual sports (6.01 s vs. 6.66 s, p = 0.0166). No significant association was found regarding cognitive-related aspects in either children engaged in team or individual sports and the crunning performance. Older and male children performed better in the crunning test than younger and female children. Physical activity-related aspects of children's life are associated with crunning movement performance. No association was found between higher cognitive performance and the crunning test results.

Cost-effectiveness analysis of genetic diagnostic strategies for Lynch syndrome in Italy.

Lynch syndrome (LS) is an autosomal dominant condition caused by pathogenic variants in mismatch repair (MMR) genes that predispose individuals to different malignancies, such as colorectal cancer (CRC) and endometrial cancer. Current guidelines recommended testing for LS in individuals with newly diagnosed CRC to reduce cancer morbidity and mortality in relatives. Economic evaluations in support of such approach, however, are not available in Italy. We developed a decision-analytic model to analyze the cost-effectiveness of LS screening from the perspective of the Italian National Health System. Three testing strategies: the sequencing of all MMR genes without prior tumor analysis (Strategy 1), a sequential IHC and MS-MLPA analysis (Strategy 2), and an age-targeted strategy with a revised Bethesda criteria assessment before IHC and methylation-specific MLPA for patients ≥ than 70 years old (Strategy 3) were analyzed and compared to the "no testing" strategy. Quality Adjusted Life Years (QALYs) in relatives after colonoscopy, aspirin prophylaxis and an intensive gynecological surveillance were estimated through a Markov model. Assuming a CRC incidence rate of 0.09% and a share of patients affected by LS equal to 2.81%, the number of detected pathogenic variants among CRC cases ranges, in a given year, between 910 and 1167 depending on the testing strategy employed. The testing strategies investigated, provided one-time to the entire eligible population (CRC patients), were associated with an overall cost ranging between €1,753,059.93-€10,388,000.00. The incremental cost-effectiveness ratios of the Markov model ranged from €941.24 /QALY to €1,681.93 /QALY, thus supporting that "universal testing" versus "no testing" is cost-effective, but not necessarily in comparison with age-targeted strategies. This is the first economic evaluation on different testing strategies for LS in Italy. The results might support the introduction of cost-effective recommendations for LS screening in Italy.

Effects of a Physical Activity Intervention on Physical Fitness of schoolchildren: The Enriched Sport Activity Program.

Background: Physical fitness in youth is a predictor of health in adulthood. The main objective of the present study was to understand if an enriched sport activity program could increase physical fitness in a population of schoolchildren. Methods: In a sample of 672 children aged 10.0 ± 1.90 years, different motor skills were tested by the 1 kg and 3 kg ball throw (BT), the standing broad jump (SBJ), the 30 m sprint (30mS), the leger shuttle run (LSR), the illinois agility test (IGT), and the quadruped test (QT). Within the controlled-trial, the intervention group (ESA) underwent an additional warm-up protocol, which included cognitive enhancing elements, for 14 weeks while the control group continued with ordinary exercise activity. Results: A significant increase was present regarding the 1 kg and 3 kg BT, the SBJ, the 30mS, and the IGT, while no significant difference was shown regarding the QT and the LSR in the ESA group between pre and post intervention. In the control group, no differences were present for any test except for the QT and the LSR post-test. Conclusion: A 14-week structured physical intervention had moderate effects regarding throwing, jumping, sprinting, and agility in a sample of schoolchildren.