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Francesco S Mennini,1,2 Raffaella Viti,1 Andrea Marcellusi,1–3 Paolo Sciattella,1 Ombretta Viapiana,4 Maurizio Rossini4 1Economic Evaluation and HTA (EEHTA), CEIS, Faculty of Economics, University of Rome “Tor Vergata”, Rome, Italy; 2Institute of Leadership and Management in Health, Kingston University, London, UK; 3Consiglio Nazionale delle Ricerche (CNR), Istituto di Richerche sulla Popolazione e le Politiche Sociali (IRPPS), Rome, Italy; 4Rheumatology Unit, Department of Medicine, University of Verona, Verona, 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. Keywords: spondyloarthritis, cost of illness, direct cost, claims database, Italy

Francesco Saverio Mennini,1,2 Andrea Marcellusi,1,3 Massimo Andreoni,4 Antonio Gasbarrini,5 Salvatore Salomone,6 Antonio Craxì71Centre for Economic and International Studies (CEIS) – Economic Evaluation and HTA (EEHTA) Faculty of Economics, University of Rome Tor Vergata, Rome, Italy; 2Institute of Leadership and Management in Health, Kingston University, London, UK; 3Department of Demography, University of Rome La Sapienza, Rome, Italy; 4Department of Public Health and Cell Biology, School of Medicine, University of Rome Tor Vergata, Rome, Italy; 5Gastroenterology Division, Catholic University of the Sacred Heart of Rome, School of Medicine, Rome, Italy; 6Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, University of Catania, Catania, Italy; 7Gastroenterology Division, University of Palermo, Palermo, ItalyBackground: At present, there are no specific nationwide epidemiological studies representing the whole Italian population. This study is aimed at describing the epidemiological and economic burden that HCV will generate in the next few years in Italy. Furthermore, the impact that future anti-HCV treatments may have on the burden of disease was considered. This analysis was developed for the period 2012–2030 from the perspective of the Italian National Health Service (NHS). Methods: A published system dynamic model was adapted for Italy in order to quantify the HCV-infected population in terms of disease progression and the associated costs from 1950 to 2030. The model structure was based on transition probabilities reflecting the natural history of the disease. In order to estimate the efficacy of current anti-HCV treatment strategies for genotypes 1 and 4, the sustained virological response (SVR) rate in registration clinical trials for both boceprevir and telaprevir was estimated. It was assumed that the efficacy for patients treated with peginterferon + ribavirin was equal to the placebo arm of a randomized clinical trial (RCT) relating to boceprevir and telaprevir. For genotypes 2/3 patients it was assumed that treatment efficacy with dual therapy was equal to a SVR rate from the literature. According to the aim of this study, only direct health care costs (hospital admissions, drugs, treatment, and care of patients) incurred by the Italian NHS have been included in the model. Costs have been extrapolated using the published scientific literature available in Italy and actualized with the 2012 ISTAT (Istituto Nazionale di Statistica) Price Index system for monetary revaluation. Three different scenarios were assumed in order to evaluate the impact of future anti-HCV treatments on the burden of disease.Results: Overall, in Italy, 1.2 million infected subjects were estimated in 2012. Of these, about 211,000 patients were diagnosed, while only about 11,800 subjects were actually being treated with anti-HCV drugs. A reduction of health care costs is associated with a prevalence decrease. Indeed, once the spending peak is reached during this decade (about €527 million), the model predicts a cost reduction in the following 18 years. In 2030, based on the more effective treatments currently available, the direct health care cost associated with the management of HCV patients may reach €346 million (−34.3% compared to 2012). The first scenario (new treatment in 2015 with SVR =90% and same number of treated patients) was associated with a significant reduction in HCV-induced clinical consequences (prevalence =−3%) and a decrease in direct health care expenses, corresponding to €11.1 million. The second scenario (increase in treated patients to 12,790) produced an incremental cost reduction of €7.3 million, reaching a net decrease equal to €18.4 million. In the third scenario (treated patients =16,770), a higher net direct health care cost decrease versus the base-case (€44.0 million) was estimated.Conclusion: Our model showed that the introduction of new treatments that are more effective could result in a quasi-eradication of HCV, with a very strong reduction in prevalence.Keywords: chronic hepatitis, cost of illness, forecast, new HCV treatment

Background: Dapagliflozin, approved in the treatment of patients with chronic kidney disease (CKD), has demonstrated attenuation of CKD progression and a reduced risk of cardio-renal outcomes and all-cause mortality (ACM) versus placebo, in addition to standard of care (SoC). The aim of this economic evaluation was to assess the potential medical care cost offsets associated with reduced rates of cardio-renal outcomes in Italy. Methods: A comparative micro-simulation model estimated the outcome-related costs of dapagliflozin plus SoC versus SoC alone over a 3-year horizon based on the DAPA-CKD trial. Incidence rates of end-stage kidney disease (ESKD), hospitalizations for heart failure (hHF), acute kidney injury (AKI) and ACM were estimated for a treated population of 90,564 patients. Associated direct medical costs for non-fatal events (ESKD, hHF and AKI) were calculated using available literature and national tariffs. The analysis was restricted to outcome-associated costs and did not consider the cost of drug treatments and disease management. Results: Patients treated with dapagliflozin plus SoC experienced fewer incident events of ESKD (6,540 vs 9,751), hHF (2,146 vs 4,242), AKI (3,772 vs. 5,271) and ACM (5,780 vs 8,037) per 90,564 treated patients versus those treated with SoC alone. Reductions (–35,6%) in clinical events (ESKD, hHF and AKI) were associated with a 34.4% reduction in total costs (€ 170 million) over 3 years. The clinical effect of dapagliflozin on ESKD management accounted for a € 134.5 million reduction in total costs. Conclusion: Based on the DAPA-CKD trial, dapagliflozin may prevent cardio-renal event incidence with a positive effect upon the Italian National Healthcare Service (NHS). Over three years, we estimated that dapagliflozin can reduce the Italian NHS expenditure associated with the management of ESKD, hHF and AKI events by 34.4% (€ 170 million).

Objective: The aim of this study was to evaluate the economic consequences of the introduction of roxadustat on the market as treatment for chronic kidney disease (CKD)-related anaemia in Italy. Method: A budget impact model was developed to assess the economic impact of the introduction of roxadustat for the management of patient with CKD-related anaemia. The analysis was conducted considering National Health Service (NHS) perspective and three years’ time horizon. Eligible population for the treatment with roxadustat was estimated through published literature and clinicians’ support. Direct healthcare costs included drug acquisition (list prices for base case) and administration costs, monitoring costs, cost per blood transfusion, costs related to the management of adverse events and dialysis costs. Results: The model estimated a three years expenditure associated with the management of patients with CKD-related incident anaemia in Italy of about € 260 and € 44.6 million for non-dialysis dependent (NDD) and dialysis-dependent (DD) patients respectively. The introduction of roxadustat on the market could generate a reduction in the expenditure related to the iron supplementation both for NDD and for DD patients (−€ 397,305 and −€ 50,135 over three years of the analysis, respectively) and a reduction in the pharmaceutical expenditure for NDD patients (−€ 2.3 million, −€ 7.5 million and −€ 13 million at first, second and third year of the analysis). Overall, the introduction of roxadustat could generate a saving for NHS approximately equal to € 2.3, € 7.5 and € 13 million at first, second and third year of the analysis. Conclusion: The introduction of roxadustat could generate a reduction in the expenditure for the management of patients with CKD anaemia. A scenario analysis which used tender prices for ESAs and hypothesis of confidential discount for roxadustat showed that the saving for NHS will be kept if roxadustat’s discount is greater than 60.3%.

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.

Abstract Background Achieving good adherence to self-injected treatments for multiple sclerosis can be difficult. Injection devices may help to overcome some of the injection-related barriers to adherence that can be experienced by patients. We sought to assess short-term adherence to, and tolerability of, interferon (IFN) β-1a administered via electronic autoinjection device in patients with relapsing-remitting multiple sclerosis (RRMS). Methods BRIDGE (RebiSmart to self-inject Rebif serum-free formulation in a multidose cartridge) was a 12-week, multicentre, open-label, single-arm, observational, Phase IV study in which patients self-administered IFN β-1a (titrated to 44 μg), subcutaneously (sc), three times weekly, via electronic autoinjection device. Patients were assessed at baseline and 4-weekly intervals to Week 12 or early termination (ET) for: physical examinations; diary card completion (baseline, Weeks 4, 8 only); neurological examinations (baseline, Week 12/ET only); MS Treatment Concern Questionnaire (MSTCQ; Weeks 4, 8, 12 only); Convenience Questionnaire (Week 12 only); Hospital Anxiety and Depression Scale (HADS); and Paced Auditory Serial Addition Task (PASAT; baseline only). Adherence was defined as administration of ≥ 80% of scheduled injections, recorded by the autoinjection device. Results Overall, 88.2% (105/119; intent-to-treat population) of patients were adherent; 67.2% (80/119) administered all scheduled injections. Medical reasons accounted for 35.6% (31/87) of missed injections, forgetfulness for 20.6% (18/87). Adherence did not correlate with baseline Expanded Disability Status Scale (P = 0.821) or PASAT (P = 0.952) scores, or pre-study therapy (P = 0.303). No significant changes (baseline-Week 12) in mean HADS depression (P = 0.482) or anxiety (P = 0.156) scores were observed. 'Overall convenience' was the most important reported benefit of the autoinjection device. Device features associated with handling and ease of use were highly rated. Mean MSTCQ scores for 'flu-like' symptoms (P = 0.022) and global side effects (P = 0.002) significantly improved from Week 4-12. Mean MSTCQ scores for pain at injection site and injection pain increased from Week 4-12 (P < 0.001). Adverse events were mild/moderate. No new safety signals were identified. Conclusion Convenience and ease of use of the autoinjection device may improve adherence and, therefore, outcomes, in patients with RRMS receiving sc IFN β-1a. Trial registration EU Clinical Trials Register (EU-CTR; http://www.clinicaltrialsregister.eu): 2009-013333-24

OBJECTIVES: Cytomegalovirus (CMV) infection represents a serious post-transplantation complication, particularly among transplant recipients with resistant or refractory (R/R) infection. Despite the improvement made in CMV prevention and treatment, remains a need for new therapies that are better tolerated and safer for patients, especially for refractory or resistant (R/R) infections. This analysis investigates the cost-effectiveness of maribavir versus investigator-assigned therapy (IAT) for treatment of post-transplant R/R CMV in the Italian context. METHODS: The analysis was conducted from the National Health Service (NHS) perspective using a Markov model previously developed in Excel® to evaluate the cost-effectiveness of maribavir versus IAT for the treatment of post-transplant R/R CMV. Health event rates and transition probabilities were informed by data from observational studies and from SOLSTICE clinical trial, which compared maribavir to conventional antiviral treatments for transplant patients with R/R CMV infections. Utilities were from SOLSTICE and a utility vignette study. Costs inputs were derived from published literature and Italian national tariffs for outpatient and hospital services. Costs and outcomes were discounted by 3%. RESULTS: Maribavir compared to the IAT used for the treatment of post-transplant R/R CMV achieved an incremental cost of € 11,455 for an incremental quality adjusted life year (QALY) gain of 0.313. This resulted in an incremental cost-effectiveness ratio of € 36,626/QALY, for maribavir compared to IAT, which is below the generally accepted, national willingness-to-pay threshold for orphan drugs (€ 37,000/QALY). CONCLUSIONS: This analysis showed that maribavir, an orphan drug treatment, is cost-effective compared to the current antiviral treatments used for treatment of post-transplant R/R CMV.

Objective: This paper aims to investigate the duration of the pricing & reimbursement (P&R) procedures submitted in Italy by pharmaceutical marketing authorization holders (MAH) for drugs indicated for rare diseases. Methods: All the data used in this analysis were publicly available on different sources of the Italian Ministry of Health, the Italian Medicines Agency (AIFA) and other official websites. The information was systematically collected to investigate the timeline (days) needed to complete the P&R process. The process was divided into 6 simplified steps and the median and range of days needed for each phase were estimated based on data reported in official/published documents. The analysis was stratified considering every single step of the assessment phase and included segmentation of drugs into indications for rare diseases, Orphan designation, Innovation assessment and Managed entry agreements (MEAs). Results: Overall, 181 first indication procedures were submitted to AIFA in the period considered and, of these, 167 (92.3%) were completed and 129 procedures were considered for the final analysis and the median duration of the entire process (MAH submission to final Gazette publication) was 434 days (range 176.0-918.0). The duration of procedures for rare diseases (n = 53) was longer than those for non-rare-disease procedures (n = 76) (463.0 days vs 407.5 days respectively). Among rare disease procedures, orphan designation and MEAs represent predictors for time prolongation while innovation is associated with a shorter assessment time. Conclusion: The study describes the time spent in each phase of the assessment and the appraisal process and demonstrates that uncertainty represents the main driver for the increment in the overall time.

Introduction: The present work aims to discuss the current scenario of procedures and regulations regarding budget impact analysis/models (BIA/BIM) at regional level in Italy and to provide a standardized approach and detailed recommendations for developing these analyses. Method: A systematic review of the literature was conducted in order to collect existing guidelines or specific regional procedures for budget impact analysis in Italy. All the records were analysed in qualitative terms according to a pre-specified analytical framework, based on the ISPOR BIA guidelines. At the end of the analysis, a consensus questionnaire was developed to establish agreed approaches and to provide possible solutions to any critical issues. A list of 39 statements was developed. The survey was distributed to 69 experts who rated their level of agreement with each statement on a 5-point Likert scale. Consensus was predefined as more than 66% of the panel agreeing/disagreeing with any given statement. Results: Sisty-nine experts answered the questionnaire; a total of 30/39 statements achieved consensus. There was agreement on most of the statements. Time horizon to consider and costs were the issues on which no agreement was found. The results allowed the working group to define a list of good practices. Conclusion: While the structure and development of BIM are now well-known and well-applied at national level, there remains a great diversity of management of BIM tools at regional level. Consensus was reached among participating experts, as to the main characteristics, determinants and features of regional BIA/BIM in the perspective of the Italian payer.

L’incontinenza urinaria (IU) è un sintomo frequente a seguito di prostatectomia radicale per carcinoma della prostata, dal momento che interessa quote elevate di pazienti, che variano a seconda della definizione, delle tempistiche di valutazione, dell’approccio chirurgico e di chi effettua la rilevazione e che possono anche superare l’80% dei pazienti [1]. Nella maggior parte dei casi, il problema si risolve a distanza di un anno. Tuttavia, l’incontinenza permane anche dopo 12 mesi in una quota non trascurabile di pazienti, che varia a seconda delle statistiche e che si attesta intorno a percentuali pari al 10% [1]. L’IU, oltre a rappresentare un problema di tipo igienico e sociale, compromette fortemente la qualità della vita del soggetto che, dopo aver superato il trauma e la paura della patologia oncologica, vive sentimenti di perdita di autostima, associati ad alterazioni nelle relazioni familiari, sociali e nel rapporto col partner, che interessano anche la vita lavorativa [2,3]. Il tavolo tecnico sull’incontinenza – istituito presso il Ministero della Salute – ha definito un percorso basato su evidenze cliniche, che risponde alla necessità di prendersi cura del paziente con IU dopo chirurgia prostatica [4]. Tra le diverse criticità rilevate sul territorio nazionale, emerge il mancato accesso alla terapia chirurgica dell’IU, che non viene proposta perché non effettuata nel centro di cura oncologica, per la limitata proposta di soluzioni terapeutiche offerte al paziente dal chirurgo e per la limitata disponibilità di presidi chirurgici, anche in relazione ai costi. Nel caso dell’IU da sforzo da incompetenza sfinterica dopo prostatectomia radicale, l’opzione dello sfintere urinario artificiale (AUS) rimane il gold standard per l’IU moderata-grave (raccomandazione B ICI, livello di evidenza 2b EAU). Tale giudizio è confermato anche dalla Regione Veneto che, con il Decreto del Direttore generale dell’Area Sanità e Sociale n. 58 del 15.06.2016, ha emanato le “Linee di indirizzo regionali per l’utilizzo di sfinteri urinari artificiali, sling e neurostimolatori sacrali nell’incontinenza urinaria e fecale”, con cui si stabilisce che «Lo sfintere urinario artificiale deve essere offerto agli uomini con incontinenza da sforzo (SUI) post-prostatectomia da moderata a severa, a seguito di fallimento della terapia conservativa» [5]. Il paradosso dell’impianto di AUS è che, pur essendo una soluzione terapeutica eccellente e costo-efficace per i pazienti con incontinenza urinaria da moderata a grave, la maggioranza dei candidati non ne ha accesso. Come evidenziato dalla analisi delle Schede di Dimissione Ospedaliera (SDO) 2016 [6], in Italia vengono effettuati non più di 240 impianti all’anno a fronte di una stima media di circa 1.000 pazienti/anno che vivono con incontinenza non risolta con terapia conservativa. Tali numeri dimostrano un evidente sottoutilizzo della tecnologia di elezione per questi pazienti. Le barriere all’adozione della soluzione chirurgica sono diverse; tra di esse si annoverano la scarsità di informazione adeguata ai pazienti e la mancata allocazione di risorse – economiche e professionali – adeguate a garantire la procedura: spesso gli ospedali hanno pochissime unità/professionalità disponibili, con lunghe liste d’attesa, e un rimborso inadeguato a coprire i costi della procedura da parte del Servizio Sanitario Regionale/Nazionale (SSR/SSN) [7]. Questi fattori disincentivano il ricorso all’impianto dell’AUS anche laddove clinicamente appropriato, determinando un trattamento insufficiente e inadeguato della popolazione eleggibile. Alla luce dell’analisi HTA condotta, sarebbe auspicabile un intervento normativo che riconosca dignità e valore all’impianto dell’AUS post-prostatectomia radicale, laddove la terapia farmacologica si rivelasse insufficiente alla soluzione del problema. L’analisi ha dimostrato come incrementando il numero di soggetti trattati con AUS (+29 pazienti trattati con il gold standard AMS 800TM [8]) rispetto alla terapia conservativa si verifichi un importante incremento della qualità di vita dei pazienti (rapporto di costo-efficacia altamente positivo e in alcuni casi dominante) accompagnato da una consistente riduzione del costo legato alla terapia conservativa (pannoloni). Si tratterebbe di un numero limitato di procedure, che consentirebbe, però, di migliorare notevolmente la qualità della vita dei pazienti interessati da questa condizione.

Objective: The objective of this analysis was to evaluate the cost-effectiveness of imipenem/cilastatin/relebactam compared to colistin-imipenem in the treatment of hospitalized patients with Gram-negative bacterial infections caused by imipenem-resistant pathogens. The perspective was both that of the National Health Service (NHS) and the social one. Methodology: A mixed model was developed to simulate a cohort of patients capable of highlighting the impacts of the disease on the quality of life and the absorption of economic resources of the patients in analysis. Modelled patients were those with hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP), complicated intra-abdominal infection (cIAI) or complicated urinal tract infection (cUTI) caused by carbapenem-resistant Gram-negative (GN) pathogens. The model begins with a short-term decision tree describing possible treatment routes and outcomes for patients during the hospitalization period. Patients who are healed in the decision tree enter the long-term Markov model, designed to capture the follow-up costs and health-related quality of life (HRQL) of patients healed over their lifetime. Results: The analysis, conducted on a hypothetical cohort of 1,000 patients, highlights how the use of imipenem/cilastatin/relebactam is advantageous both in terms of diagnosis and treatment in the short term and in terms of cost-effectiveness. In fact, it is dominant compared to colistin-imipenem both in the NHS and in the social perspective since, compared to an average saving of € 2,800.15 and € 3,174.63 respectively, it would generate an increase of 4.76 years of life and of 4.12 QALYs per patient.

OBJECTIVE: The Short Bowel Syndrome (SBS) is the most common cause of chronic intestinal failure (CIF) due to benign disease. The prevalence in Europe was estimated about 1.4 cases per million and few information are available for Italy. Home parenteral nutrition (HPN) is the primary and lifesaving treatment for patients with CIF. The parenteral nutrition (PN) has a great impact on the quality of life (QoL) of patients and the role of the caregiver is crucial for the disease management. The aim of this study was to evaluate the economic burden of SBS in Italy and to assess the impact of the disease and the parenteral nutrition on the quality of life of patients. METHODS: The total burden of SBS in Italy was assessed both in terms of costs and QoL using different tools. A prevalence-based cost of illness (COI) model was developed to estimate direct costs (PN cost, central venous catheter insertion cost, monitoring cost, hospitalization cost) and indirect costs (absenteeism, presenteeism, unemployment, abandonment of work due to the disease and economic benefits granted by the National Social Security Institute) associated with patient with SBS in Italy. The total annual costs were calculated considering a micro-costing approach, thus associating the average costs per patient with the prevalence of the disease. A systematic literature review (SLR) was conducted to collect epidemiological and direct cost data related to the patients with SBS. Hospital costs were estimated using the national Hospital Information System. Indirect costs were estimated using a human capital approach; therefore, the productivity loss was estimated both for patients and caregivers. A survey was conducted to obtain data about productivity loss and quality of life of patients and caregivers. The questionnaires were completed by clinicians, who were asked to indirectly report the experience of patients with SBS in parenteral nutrition currently being treated at their referral center. In a subsequent phase, a focus group was conducted to collect further information on QoL for patients and caregivers based on the experience of the KOLs involved. The QoL was evaluated considering a Likert scale. RESULTS: The prevalence of patients with gastrointestinal disease in HPN was estimated equal to 9.4 and 2.3 patients per million inhabitants for adults (age >18) and pediatric (age 0-18 years) patients, respectively. Knowing that SBS is the main cause of CIF due to benign disease, constituting 75% among adults and 56% among children, the number of adults with SBS in HPN present in Italy were 420, while the number of children with SBS in HPN were 77. Regarding direct costs, the mean total annual cost associated with adult and pediatric patient with SBS in Italy was estimated equal to € 36,434 and € 46,682, respectively. Parenteral nutrition accounted for 91% of the mean total cost estimated for the adult and for 87% of the mean total cost estimated for pediatric patient. Concerning indirect costs, the mean total annual cost per adult patient was estimated equal to € 51,093 (81% related to the productivity loss because of the abandonment of work due to the disease), while the mean total cost per pediatric patient was estimated equal to € 3,201 (60% related to caregiver’s presenteeism and 40% attributable to caregiver’s absenteeism). Finally, the average total annual cost per adult SBS patient in Italy was estimated at € 87,527 (42% of direct costs and 58% of indirect costs), whereas for pediatric patients it was estimated at € 49,882 (94% of direct costs and 6% of indirect costs). Overall, the weighted average cost for an SBS patient in Italy was estimated at € 81,712 (47% of direct costs and 53% of indirect costs). The analysis conducted on the QoL of patients with SBS in PN has shown that QoL was perceived as low (mean value equal to 5). The greatest impact on QoL was due to the disease (mean value equal to 9), while PN appeared to have less impact (mean value equal to 6). CONCLUSIONS: The analysis provides an estimate of the total burden associated with patients with SBS in Italy both in terms of cost and QoL. The cost associated with parenteral nutrition and indirect costs represent the main drivers of the total cost estimated for a patient with SBS in Italy. Based on the experience of the KOL involved in this study it was also found that the disease has a great impact on the QoL of these patients.

Objective. To assess the cost-effectiveness and economic sustainability of treosulfan plus fludarabine compared with busulfan plus fludarabine as a conditioning treatment for malignant disease prior to allogeneic haematopoietic stem cell transplantation (alloHSCT) in adult patients in Italy. Method. The two theoretical cohorts of patients aged ≥ 60 years with acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) were pooled and followed over time using a partitioned survival model with cycles of 28 days. Patients can transition between a post-HSCT recovery/remission state (Event-Free Survival state, EFS state), a relapsed/progressed disease state, and a death state. A lifetime horizon for cost-effectiveness analysis and a 5-years’ time horizon for budget impact analysis were used. The perspective of the Italian National Health Service was adopted. Utility values were obtained from published sources. Costs included: drug acquisition, HSCT procedure, management and treatment of adverse reactions, graft-versus-host disease (GvHD) and health states, end of life treatment. Discounting of 3% per year was applied for both costs and outcomes according to Italian guidelines. Sensitivity was tested through both one-way and probabilistic analyses. Results. Cost-effectiveness analysis showed that treosulfan is both more effective and less expensive compared with busulfan (+1.11 life-years, +0.96 quality-adjusted life-years per patient and -€ 41,784 per patient). On the side of economic sustainability, the introduction of treosulfan in the market could generate a cumulative decrement of the expense incurred by NHS of about -€ 179,174 over five years. Conclusion. Treosulfan could represent a cost-effective and sustainable treatment alternative from the perspective of the NHS.

Objective: To estimate the economic impact of the introduction of a new care system based on apomorphine and Patient Support Program for motor fluctuations (“on-off” phenomena) in patients with Parkinson’s disease which are not sufficiently controlled by oral anti-Parkinson medication in Italy. Method: A Budget Impact model was developed to evaluate the new care system in patients with Parkinson’s disease over a 3-years’ time horizon. The comparator treatments included in the analysis were treatments based on apomorphine and levodopa + carbidopa. The analysis was conducted from a National Health Service (NHS) perspective. Costs included in the analysis were acquisition costs and device costs. A deterministic sensitivity analysis was carried out to evaluate the uncertainty of the parameters used. A break-even analysis was conducted to identify the minimum number of subjects that would need to be treated with the new care system to obtain a positive Budget Impact (World With – World Without = 0). Results: The analysis shows that the introduction of the new care system based on apomorphine could generate a cost saving incurred by the NHS of over € 5.7 million in 3 years. Break-even analysis shows that if it were possible to intercept with the new treatment at least 9 patients treated with apomorphine, there would not be an increase in costs for the NHS. Conclusion: The new care system would respond to the unmet needs of patients with Parkinson’s disease by generating a reduction in the expenditure incurred by NHS.

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

Obiettivo: Questo studio ha lo scopo di valutare il rapporto costo-efficacia di ceftolozano/tazobactam rispetto a meropenem per il trattamento di pazienti con polmonite acquisita in ospedale (HABP) o polmonite associata a ventilazione meccanica (VABP) sia secondo la prospettiva del Servizio Sanitario Nazionale (SSN), sia secondo la prospettiva sociale. Metodo: L’analisi è stata condotta mediante lo sviluppo di un albero decisionale e di un modello di Markov al fine di catturare rispettivamente gli effetti di breve e di lungo periodo. Una popolazione target ipotetica di 1.000 pazienti con vHABP/VABP è stata seguita per un orizzonte temporale lifetime (40 anni). In particolare, con riferimento all’albero decisionale di breve termine, sono stati sviluppati due diversi setting al fine di valutare il valore della terapia empirica rispetto all’avvio del trattamento dopo la conferma dell’antibiogramma. I pazienti trattati e guariti entrano nel modello di Markov di lungo termine seguendo la mortalità della popolazione generale. Risultati: L’analisi ha evidenziato come ceftozolano/tazobactam, in entrambi i setting di trattamento (empirico e confermato), possa risultare un’opzione costo-efficace rispetto a meropenem sia nella prospettiva del SSN sia nella prospettiva sociale (ICER per QALY rispettivamente pari a € 1.913 e pari a € 2.203 per il setting di trattamento empirico e rispettivamente pari a € 6.163 e pari a € 6.597 per il setting di trattamento confermato). Conclusioni: Alla luce dei risultati emersi dall’analisi, è possibile notare come l’introduzione di ceftolozano/tazobactam all’interno del contesto sanitario italiano possa rappresentare una soluzione terapeutica valida sia sotto il profilo economico sia sotto il profilo di efficacia.

Objective: The aim of this work was to evaluate the cost-effectiveness of evolocumab in addition to standard statin therapy with or without ezetimibe in the treatment of patients with clinically evident atherosclerotic cardiovascular disease (ASCVD) with levels of LDL-C above 100 mg/dL. Method: A theoretical cohort of patients was forecast by a Markov model that includes 11 health states for a lifetime horizon. In the base-case, the standard therapy was characterized by statins with or without ezetimibe. Two sub-populations have been considered, Recent MI (Myocardial Infarction in the last year) and Multiple events (population with multiple MI). The results were also presented for a subset of the Multiple events populations consisting of patients who have experienced a myocardial infarction (MI) in the last year. Results: For the Recent MI and Multiple events populations, ICER values of € 39,547 and € 35,744 respectively were estimated. The value of ICER was lower for the Multiple events with MI < 1 year population (€ 29,949). Considering statins with ezetimibe as standard therapy, ICER values were found to be equal to € 39,781, € 35,986 and € 30,190 respectively for the populations Recent MI, Multiple events and Multiple events with MI < 1 year. Conclusions: The estimated ICER values for the Recent MI, Multiple events and Multiple events populations with MI < 1 year were below the cost-effectiveness threshold of € 40,000, suggesting therefore how the treatment with evolocumab in addition to the standard therapy can be a cost-effective treatment both compared to standard therapy with statins and standard therapy with statins + ezetimibe.

Objective: To assess, from an epidemiological and economic point of view, the consequences of the reduction in the supply of antiretroviral drugs due to the COVID-19 pandemic. Method: The analysis was conducted by adapting a Markov model previously published in literature. The simulations were conducted considering the possibility of continuous treatment for patients already diagnosed (no therapeutic interruptions are expected) and an immediate start of patients with new diagnosis during 2021. This analysis was compared with a scenario involving a therapeutic interruption or diagnostic delay caused by COVID-19. Results: The analysis showed that the scenario characterized by a treatment delay, compared to the scenario of early resumption of therapy, could generate an increase in the number of patients with CD4 < 200 equal to 1,719 subjects (+16%) and a reduction in the number of patients with CD4 500 equal to 6,751 (−9%). A timely resumption of treatment for HIV+ patients could prevent 296, 454 and 687 deaths in the third, fifth and tenth years of analysis respectively with a potential cost reduction equal to 78,9 million at a 10 year time horizon. Conclusions: These findings show that it is essential, especially in a pandemic situation such as the present one, to introduce technological, digital and organizational solutions, aimed at promoting timely diagnosis and at accelerating the therapeutic switch for patients who are no longer targeted.

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. [ABSTRACT FROM AUTHOR]

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.

Objectives: The aim of this study was to estimate the total annual direct costs incurred by the National Health Service for the management and treatment of CSCC and advanced CSCC patients in Italy. Methods: An incidence-based cost of illness (COI) model was developed to estimate direct costs associated with the treatment and management of CSCC patients in Italy. The identified treatment pathway was validated with a team of clinical experts and was distinguished between resectable CSCC and locally advanced CSCC or metastatic CSCC. Treatments costs were obtained through the analysis of the National Hospital Discharge Database (HDD) for the years 2015-2018; monitoring and terminal care costs were obtained from national tariffs of outpatient care service and from the literature respectively. Results: Associating the estimated costs for each phase of the treatment pathway with the proportion of patients present in each phase, the COI model estimated an annual economic burden of about € 25.9 million for the management and treatment of patients with CSCC in Italy, € 2.7 million of which were associated to patients with advanced CSCC. The average cost per patient with advanced CSCC was higher compared to that of patient with resectable CSCC (€ 4,490 vs € 2,236 respectively). Conclusions: Our analysis showed that advanced CSCC patients are associated with a higher average cost than patients with resectable CSCC.

Seasonal influenza is caused by two subtypes of influenza A and two lineages of influenza B. Although trivalent influenza vaccines (TIVs) contain both circulating A strains, they contain only a single B-lineage strain. This can lead to mismatches between the vaccine and predominant circulating B lineages, a concern especially for at-risk populations. Quadrivalent influenza vaccines (QIVs) containing a strain from both B lineages have been developed to improve protection against influenza. Here, we used a cost-utility model to examine whether switching from TIV to QIV would be cost-effective for the at-risk population in Italy. Costs were estimated from the payer and societal perspectives. The discount rate for outcomes was 3.0%. Univariate and probabilistic sensitivity analyses were performed to examine the effects of variations in parameters. Switching from TIV to QIV in Italy was estimated to increase quality-adjusted life-years (QALYs) and produce cost savings, including €1.6 million for hospitalization and approximately €2 million in productivity. The incremental cost-effectiveness ratio was €23,426 per QALY from a payer perspective and €21,096 per QALY from a societal perspective. Switching to QIV was most cost-effective for individuals ≥ 65 years of age (€19,170 per QALY). Probabilistic sensitivity analysis showed that the switching from TIV to QIV would be cost-effective for > 91% of simulation at a maximum willingness-to-pay threshold of €40,000 per QALY gained. Although the model did not take herd protection into account, it predicted that the switch from TIV to QIV would be cost-effective for the at-risk population in Italy.

BACKGROUND:HCV is one of the main causes of cirrhosis, hepatocellular carcinoma (HCC) and liver transplantation. AIM:The aim of this study was to estimate the number of living individuals diagnosed with hepatitis C in Italy. This study also aimed to stratify these subjects as diagnosed and cured, diagnosed awaiting a cure, and undiagnosed (individuals who were not diagnosed, living or lived with hepatitis C). METHODS:To quantify the number of ill patients in Italy, an inquiry was conducted based on questionnaires submitted to three nationally representative regions, namely, Campania, Lazio and Piemonte, as representatives of the three main areas of Italy (North, Centre and South regions). The data were collected through a questionnaire to acquire demographic and clinical information on patients in the participating hospitals. The questionnaires contained 6 questions on sex, age, region of residence, disease condition, type of exemption and category. The questionnaires were administered individually to consecutive patients through face-to-face interviews conducted by specialised personnel in each centre. Data were collected between September 2017 and January 2018. RESULTS:In total, 2,860 questionnaires were analysed. They were completed by the patients (55% male), who had an average age of 61 years (64 years for women and 59 years for men). In total, 54% of the sample declared that they were still infected with HCV (1,548 patients out of 2,860 respondents), while the remaining subjects declared that they had been cured. The inquiry showed that 46.6% of the sample had at least a 016 exemption (chronic hepatitis), while more than 51% (1,469 interviewed patients out of 2,860 respondents) had a different type of exemption. Only 2% of the respondents declared that they had no exemption. Assuming that the analysed sample is representative of the actual HCV-positive population in Italy and considering the number of 016 exempt patients in the regional data, the model estimates that there are 443,491 cured and HCV-positive living patients and 240,043 ill patients who have yet to be treated. CONCLUSIONS:Although this study has limitations, it represents a considerable improvement over the previously available studies. This study can help decision-makers implement more effective strategic planning to eliminate hepatitis C.