Health and Economic Outcomes of Pembrolizumab in the Treatment of Metastatic Non-small Cell Lung Cancer (mNSCLC) and Melanoma in Italy.

BACKGROUND AND OBJECTIVE: In Italy, the management of metastatic non-small cell lung cancer and melanoma leads to significant healthcare challenges, necessitating cost-effective treatment strategies and offering valuable insights for healthcare policymakers and stakeholders. This study was designed to assess the costs, quality-adjusted life-years (QALYs) and disability-adjusted life-years (DALYs) associated with the health and economic outcomes of (1) pembrolizumab-combined chemotherapy administered as a first-line treatment for metastatic non-squamous and squamous non-small cell lung cancer (NSCLC) where the tumour presents with a programmed death-ligand 1 expression level < 50% and of (2) adjuvant pembrolizumab treatment for stage III melanoma. METHODS: Three cost-effectiveness models developed by MSD were investigated for each treatment indication. A unique model was built to assess the overall effect of pembrolizumab versus chemotherapy or watchful waiting in patients with lung cancer or melanoma, respectively. Theoretical cohorts of patients with metastatic squamous and non-squamous NSCLC were followed over time using a partitioned survival model with weekly cycles. A weekly cycle Markov model was employed for melanoma. The analysis was conducted from the Italian National Health Service perspective, considering a time horizon of 40 years (lifetime). A single closed cohort of treatable patients was followed over time for each indication (4000, 7000 and 900 for NSCLC squamous, non-squamous and melanoma, respectively). The costs evaluated included those for adverse drug events, non-drug disease management, subsequent treatment and terminal care. Drug acquisition and administration costs were excluded. RESULTS: For each treatment indication assessed, pembrolizumab produced downstream direct cost offsets (- €122,498,568, - €133,369,076 and - €32,993,242 for NSCLC squamous, non-squamous and melanoma indications, respectively), increased quality of life (+2088, +5317 and +2307 QALYs for NSCLC squamous, non-squamous and melanoma indications, respectively) and reduced disability (- 2658, - 7202 and - 3029 DALYs for NSCLC squamous, non-squamous and melanoma indications, respectively). Across indications, the total cost offsets of pembrolizumab were - €288,860,885, with 9712 QALYs gained and 12,889 DALYs avoided. CONCLUSIONS: The analysis demonstrated that, compared with chemotherapy, pembrolizumab is more cost effective in Italy as a first-line treatment in patients with metastatic squamous or non-squamous NSCLC and, if compared with watchful waiting, as adjuvant treatment in patients with stage III melanoma. The present analysis suggested that pembrolizumab use could lead to important health benefits for patients while offsetting a portion of cancer care costs.

Screening strategy to advance HCV elimination in Italy: a cost-consequence analysis.

BACKGROUND AND AIMS: Italy has the greatest burden of hepatitis C virus (HCV) infection in Western Europe. The screening strategy represents a crucial prevention tool to achieve HCV elimination in Italy. We evaluated the cost-consequences of different screening strategies for the diagnosis of HCV active infection in the birth cohort 1948-1968 to achieve the HCV elimination goal. METHODS: We designed a probabilistic model to estimate the clinical, and economic outcomes of different screening coverage uptakes, considering the direct costs of HCV management according to each liver fibrosis stage, in the Italian context. A decision probabilistic tree simulates 4 years of HCV testing of the 1948-1968 general population birth cohort, (15,485,565 individuals to be tested) considering different coverage rates. A No-screening scenario was compared with two alternative screening scenarios that represented different coverage rates each year: (1) Incremental approach (coverage rates equal to 5%, 10%, 30%, and 50% at years 1, 2, 3, and 4, respectively) and (2) Fast approach (50% coverage rate at years 1, 2, 3 and 4). Overall 106,200 cases were previously estimated to have an HCV active infection. A liver disease progression Markov model was considered for an additional 6 years (horizon-time 10 years). RESULTS: The highest increased number of deaths and clinical events are reported for the No-screening scenario (21,719 cumulative deaths at the end of ten years; 10,148 cases with HCC and/or 7618 cases with Decompensated Cirrhosis). Following the Fast-screening scenario, the reductions in clinical outcomes and deaths were higher compared with No-screening and Incremental-screening. At ten years time horizon, less than 5696 liver deaths (PSA CI95%: - 3873 to 7519), 3,549 HCC (PSA CI95%: - 2413 to 4684) and less than 3005 liver decompensations (PSA CI 95%: - 2104 to 3907) were estimated compared with the Incremental-scenario. The overall costs of the Fast-screening, including the costs of the DAA and liver disease management of the infected patients for 10 years, are estimated to be € 43,107,543 more than no-investment in screening and € 62,289,549 less compared with the overall costs estimated by the Incremental-scenario. CONCLUSION: It is necessary to guarantee dedicated funds and efficiency of the system for the cost-efficacious screening of the 1948-1968 birth cohort in Italy. A delay in HCV diagnosis and treatment in the general population, yet not addressed for the HCV free-of-charge screening, will have important clinical and economic consequences in Italy.

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

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

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

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

Milestones to reach Hepatitis C Virus (HCV) elimination in Italy: From free-of-charge screening to regional roadmaps for an HCV-free nation.

Although Italy has been on track for Hepatitis C Virus (HCV) elimination since 2019, it fell off track due to the decrease in the number of treated patients. HCV elimination in Italy will be possible if immediate action is taken. A health policy was implemented beginning in 2021, consisting of screening among key populations and birth cohorts (1969-1989), estimated to have a high prevalence of undiagnosed individuals. The active screening requires regional governance that manages the processes' complexity integrating a well-organized network between territory assistance and hospital to achieve an effective HCV care cascade. This document aims to support the regional decision-making process by defining paths for screening and linkage-to-care. Implementing active screening strategies beyond a risk-based approach is required as a General Practitioners' task. Simplified paths must be drawn for the key populations screening. The infrastructure built for COVID-19 vaccination could be used also for HCV screening. According to a multidisciplinary care delivery, screening should be supplemented with rapid linkage-to-care and treatment of newly diagnosed patients. The realization of the proactive screening during the first two years is vital because it will define the tracks for the whole HCV cost-effective screening of 1948-1988 birth cohorts in Italy.

Socio-economic impact of epilepsy in Italy.

The World Health Assembly recognizes the growing economic and societal burden of neurological disorders, a leading cause of disability and the second cause of mortality in the world. In this context we analysed the socio-economic impact of epilepsy in Italy with a specific focus on hospitalizations and costs related to disability pensions (DPs) and ordinary disability allowances. In the case of epilepsy, between 2009 and 2015 we observed an alarming increasing trend for DPs (+26%), indicating that substantial expenses must be supported throughout the patients' lifetimes by both the social security system and the National Health Service (NHS) on top of the impact on caregivers. We also analysed the hospital expenditure on epilepsy through the information available in the Hospital Discharge Cards between 2015 and 2018. Almost all admissions (76% ordinary hospitalizations, 24% day hospitals) were acute (95%), followed by rehabilitation (4%) and long-term care (1%). The cost of acute and ordinary hospitalizations was by far the highest in 2018, the last year of analysis. This large expense due to hospitalizations could be reduced through the implementation of different organizational and management approaches. Our recommendation is that the policy maker should consider the best approach to ensure an early diagnosis for patients and provide early access to drugs and/or surgery. Finally, the adoption of new innovative treatments should improve effectiveness and, at the same time, reduce the expense of the NHS, of the social system as a whole, with a tangible improvement in patients' quality of life.

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

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

Direct and indirect costs of cluster headache: a prospective analysis in a tertiary level headache centre.

BACKGROUND: Cluster headache (CH) is the most frequent trigemino-autonomic cephalgia. CH can manifest as episodic (ECH) or chronic cluster headache (CCH) causing significant burden of disease and requiring attack therapy and prophylactic treatment. The few data available on the economic burden of CH come from retrospective studies based on questionnaires, population surveys and medical insurance claims database. Although all these studies showed an important economic burden, they provided different estimates depending on variability of CH awareness and management, healthcare systems, available therapies and use of treatments according to different guidelines. METHODS: This prospective study aimed to quantify the total direct and indirect cost of ECH and CCH over a cluster period, both for the patient and for the National Health System (NHS), using data from subjects who consecutively attended an Italian tertiary headache centre between January 1, 2018 and December 31, 2018. RESULTS: A total 108 patients (89 ECH, 19 CCH) were included. Mean attack frequency was 2.3 ± 1.4 per day. Mean total cost of a CH bout was €4398 per patient and total cost of CCH was 5.4 times higher than ECH (€13,350 vs. €2487, p <  0.001). Direct costs represented the 72.1% of total cost and were covered for the 94.8% by the NHS. The costs for any item of expense were higher for CCH than for ECH (p <  0.001). Mean indirect costs for a CH bout were €1226 per patient and were higher for CCH compared to ECH (€3.538 vs. €732), but the difference was not significant. Days with reduced productive capacity impacted for the 64.6% of the total indirect costs. The analysis of the impact CH on work showed that 27%% of patients felt that CH had limited their career, 40% had changed their work pattern, 20% had changed their place of employment and 10% had lost a job due to the disease. CONCLUSION: Our results provide a valuable estimate of the direct and indirect costs of ECH and CCH in the specific setting of a tertiary headache centre and confirm the high economic impact of CH on both the NHS and patients.

Economic evaluation of colorectal cancer screening programs: Affordability for the health service.

OBJECTIVES: To estimate the cost-effectiveness of the public colorectal cancer screening program in the Abruzzo region, Italy. METHODS: Cost-effectiveness was analysed using a two-armed Markov model comparing: (1) Abruzzo screening program based on biennial faecal immunochemical occult blood testing, with colonoscopy as second level test for individuals with positive results, with (2) Treatment of symptomatic patients according to the stage of the neoplasm. Transition probabilities were adjusted for accuracy of tests and incidence of colorectal cancer. Diagnosis-related groups' charges and field collected data were used to estimate costs. Costs and benefits were discounted by 3.5%. Monte Carlo simulation confirmed the robustness of the model results. RESULTS: Assuming a compliance rate of 64.7%, the incremental cost-effectiveness ratio for the current colorectal screening program was €433.06/quality adjusted life year gained, considerably lower than conventional thresholds (around €30,000). CONCLUSION: Early detection and intervention programs help to avoid a large number of highly debilitating and expensive cancer treatments. These results show that the screening program currently implemented in Abruzzo should be considered as a good investment in health.

Estimation of the number of HCV-positive patients 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.

Budget impact of bimonthly use of cetuximab in patients diagnosed with metastatic colorectal cancer.

Aim: Cetuximab is used for the treatment of RAS wild-type metastatic colorectal cancer patients. Standard administration schedule is once a week; however, the bioequivalence of an every-other-week (EOW) schedule was demonstrated. Methods: We compared a base case scenario of 100% weekly administration to an EOW at 50 or 100%. Medical examinations, patient management and loss of productivity were considered. Results: Base case was estimated at €100.6 million versus €92.8 million and €84.9 million of EOW 50 and 100%, which showed a cost reduction of 8 and 16%, respectively. Indirect costs accounted for 65% in both scenarios. Conclusion: The adoption of an EOW administration schedule of cetuximab reduced direct and indirect costs substantially.

Economic Consequences of Investing in Anti-HCV Antiviral Treatment from the Italian NHS Perspective: A Real-World-Based Analysis of PITER Data.

OBJECTIVE: We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy. METHODS: A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered. RESULTS: The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively. CONCLUSIONS: This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV.

[Burden of diverticular disease: an observational analysis based on Italian real-world data.] / Valutazione dell'impatto economico delle complicanze della malattia diverticolare con i dati "real life" della Regione Marche.

INTRODUCTION: Diverticular disease (DD) represent a wide variety of conditions associated with the presence of diverticula in the colon. The most serious form is an acute episode of diverticulitis which can lead to hospitalization and surgery with various types of consequences. The main aim of this study was to evaluate, from both cross-sectional and longitudinal perspective, the economic burden of diverticulitis in the real practice. METHOD: A deterministic linkage was performed at individual user level between the different administrative sources of the Marche Region through anonymised ID number for a period of analysis between 1 January 2008 and 31 December 2014. We enrolled all patients with at least one hospitalization for "diverticulitis of the colon without mention of haemorrhage" (ICD-9-CM code 562.11) or "diverticulitis of the colon with haemorrhage" (ICD-9-CM code 562.13) as primary or secondary diagnosis. Cost and outcome were analysed considering transversally (for contemporaneous) and longitudinal (for cohort) perspective. Hospital mortality at one year after discharge was evaluated by mortality rates and Kaplan-Meier curve considering the surgery performed (or not performed) during the index hospitalization. RESULTS: Considering the cross-sectional perspective, 427 patients per year were estimated (about 35 patients per 100,000 adult residents) with an average number of hospitalization equal to 1.14. The direct healthcare costs incurred by the Marche region for episodes of diverticulitis in 2008-2014 amounted to approximately € 11.4 million (€ 1.6 million a year), of which € 10.9 million (95.5%) for the hospitalizations, € 246,000 (2.1%) for pharmaceutical treatment and € 270,000 (2.4%) for specialist outpatient services. The cohort analysis estimates an intra-hospital mortality rate equal to 5.9 per 100 patients' year (5.5 for non-surgery patients and 8.9 for surgery patients - P<0.05). Kaplan-Meier curve demonstrate that there were no differences between intra-hospital mortality due to surgery during index hospitalization. CONCLUSIONS: Our study is the first analysis in Italy to use real-world data to measure the burden of DD with a cross-sectional and longitudinal perspective. This study could be useful for decision maker that could quantify the economic and epidemiological burden of DD in hospital.

Burden of Disease of Human Papillomavirus (HPV): Hospitalizations in the Marche and Veneto Regions. An observational study.

BACKGROUND AND OBJECTIVES: HPV (human papillomavirus) is the virus most often responsible for sexually transmitted infections. The burden of HPV-related diseases on hospital resources represents a major public health problem. The aim of this study was to assess the economic burden of HPV-related diseases (anal cancer, genital cancer, genital warts, oropharyngeal cancer) on hospital resources in two Italian regions. METHODS: A retrospective, non-randomized, observational study was developed in the Marche and Veneto Regions, based on patients receiving hospitalization between 2008 and 2011. All hospitalizations were identified through administrative archives, according to the International Classification of Diseases (ICD-9 CM) to which a defined tariff was assigned. RESULTS: We identified 5299 hospitalized patients in Veneto and 1735 in the Marche Region. The mean annual hospitalization rate was 49.44 per 100,000 individuals in Veneto and 48.41 in Marche. The total mean annual cost attributable to HPV-related diseases was €5.78 (SD 0.80) million in Veneto and €2.24 (SD 0.17) million in Marche. Costs associated with genital cancer amounted to €1.61 million in Veneto and €1.06 million in Marche (28% and 47% of the total mean annual cost, respectively). Oropharyngeal cancer accounted for 36% in Veneto (€2.08 million) and 28% in Marche (€632,645). Hospitalization costs related to anal cancer were €882,567 in Veneto and €377,719 in Marche; genital warts accounted for €1.19 million in Veneto and €171,406 in Marche. Finally, the mean cost per patient was €4364 in Veneto and €5176 in Marche. CONCLUSIONS: The present work estimated the cost of HPV-related diseases for hospitalized patients in two Italian regions. The considerable estimated annual economic burden is a powerful driver for the governance of the public health sector.

Cost-effectiveness analysis of the nine-valent HPV vaccine in Italy.

BACKGROUND: In Italy HPV vaccination with the quadrivalent vaccine (Gardasil®) is offered actively and free of charge to girls aged 12 since 2007. A nine-valent vaccine (Gardasil 9®) received the European market authorization in 2015 to protect, with only 2 doses, against around 90% of all HPV positive cancers, over 80% of high-grade precancerous lesions and 90% of genital warts caused by HPV types 6/11. METHODS: A dynamic transmission model simulating the natural history of HPV-infections was calibrated to the Italian setting and used to estimate costs and QALYs associated with vaccination strategies. The analyses compared two strategies with the nine-valent vaccine (cervical cancer screening and vaccination in girls only or vaccination in boys and girls) to four alternative strategies (cervical cancer screening and vaccination with quadrialent vaccine in girls only, in both boys and girls, with bivalent vaccine in girls and screening strategy only). The National Health Service perspective was considered. CONCLUSION: The switch to the nine-valent vaccine in Italy can further reduce the burden associated to cervical cancer and HPV-related diseases and is highly cost-effective. RESULTS: Compared to the current vaccination program with quadrivalent vaccine, the nine-valent vaccine in a programme including girls and boys shows further reductions of 17% in the incidence of cervical cancer, 35 and 14% in anal cancer for males and females, as well as over a million cases of genital warts avoided after 100 years. The new technology is associated with an ICER of 10,463€ per QALY gained in universal vaccination, decreasing to 4483€ when considering the vaccine switch for girls-only.

Primary Biliary Cholangitis: advances in management and treatment of the disease.

Primary Biliary Cholangitis, previously known as Primary Biliary Cirrhosis, is a rare disease, which mainly affects women in their fifth to seventh decades of life. It is a chronic autoimmune disease characterized by a progressive damage of interlobular bile ducts leading to ductopenia, chronic cholestasis and bile acids retention. Even if the disease usually presents a long asymptomatic phase and a slow progression, in many patients it may progress faster toward cirrhosis and its complications. The 10year mortality is greater than in diseases such as human immunodeficiency virus/Hepatitis C Virus coinfection and breast cancer. Ursodeoxycholic acid is the only treatment available today, but even if effective in counteracting the disease progression for the majority of patients, in approximately 40% is not able to decrease effectively the alkaline phosphatase, a surrogate marker of disease activity. Recently, obeticholic acid received the European Medicines Agency conditional approval, as add on treatment in patients non responders or intolerant to ursodeoxycholic acid. The present paper illustrates the opinion of a working group, composed by clinical pharmacologists, gastroenterologists/hepatologists with specific expertise on Primary Biliary Cholangitis and patient associations, on the state of the art and future perspectives of the disease management. The agreement on the document was reached through an Expert Meeting.

[The economic value of vaccinations: a systematic review of Italian economic evaluations and HTA reports]. / Le implicazioni economiche delle vaccinazioni: una revisione sistematica delle valutazioni economiche e di HTA condotte in Italia.

INTRODUCTION: Decision-making in healthcare should rely on evidence-based approaches able to make possible a transparent and robust assessment of all the aspects related to health technologies. One of the assessment elements is represented by the efficiency that is the specific objective of economic evaluations and also of Health Technology Assessment (HTA). The collection and synthesis of evidence is the first indispensable step in order to foster a proper convey of scientific knowledge to the decision-makers. This work, carried out within a broader project on the transfer of evidence from the scientific to the decision making world, is aimed to release an overview of economic evaluations and HTA on vaccines conducted in Italy. The project was carried out within the activities of the ISPOR Italy-Rome Chapter. METHODS: A systematic review of Italian economic evaluations and HTA performed on vaccines and published up to May 2015 was carried out. PubMed, Scopus and the NIHR HTA databases were queried and a hand-search was performed on key journals in the field (Global & Regional Health Technology Assessment; PharmacoEconomics Italian Research Articles; Giornale italiano di HTA; Politiche Sanitarie; HTA Focus - Pills of Clinical Governance; Pillole di Farmacoeconomia; Giornale Italiano di Farmacoeconomia e Farmacoutilizzazione; IJPH; Quaderni dell'IJPH). Studies were considered eligible if showing the results of a full economic evaluations and if performed in Italy. RESULTS: The literature search yielded 10 HTA reports and 33 economic evaluations. Among the latter, 20 (60,6%) were cost-effectiveness analyses. Ten studies (23,3%) assessed the vaccination against S. pneumoniae figuring out that it is cost-effectiveness and even costsaving in cases of newborns and subjects at risk. Nine studies (20,9%) addressed influenza vaccination and demonstrated its dominance on non-vaccination in the elderly. Eight studies (18,6%) evaluated the HPV vaccines concluding that they are cost-effective. Five studies (11,6%) devoted to anti-rotavirus vaccination showing its dominance on non-vaccination, in particular from the society perspective. Vaccination against pertussis, hepatitis B, chicken pox, measles, rubella, mumps were eventually shown cost-saving. The vaccine against Neisseria meningitidis was considered potentially cost-effective. CONCLUSION: The Italian scientific evidence on efficiency of vaccination is broad and allows concluding that vaccinations are value for money interventions.

Public health value of universal HPV vaccination.

BACKGROUND: The story of Human Papillomavirus vaccination demands reflection not only for its public health impact on the prophylactic management of HPV disease, but also for its relevant economic and social outcomes. Greater than ever data confirm the efficacy and support the urge for effective vaccination plans for both genders before sexual debut. METHODS: A review of previous experience in gender-restricted vaccination programs has demonstrated a lower effectiveness. Limiting vaccination to women might increase the psychological burden on women by confirming a perceived inequality between genders; and even if all women were immunized, the HPV chain of transmission would still be maintained through men. RESULTS: The cost-effectiveness of including boys into HPV vaccination programs should be re-assessed in view of the progressive drop of the economic burden of HPV-related diseases in men and women due to universal vaccination. The cost of the remarkable increase in anal and oropharyngeal HPV driven cancers in both sexes has been grossly underestimated or ignored. CONCLUSIONS: Steps must be taken by relevant bodies to achieve the target of universal vaccination. The analysis of HPV vaccination's clinical effectiveness vs. economic efficacy are supportive of the economic sustainability of vaccination programs both in women and men. In Europe, these achievements demand urgent attention to the social equity for both genders in healthcare. There is sufficient ethical, scientific, strategic and economic evidence to urge the European Community to develop and implement a coordinated and comprehensive strategy aimed at both genders and geographically balanced, to eradicate cervical cancer and other diseases caused by HPV in Europe. Policymakers must take into consideration effective vaccination programs in the prevention of cancers.

Cost-Effectiveness Analysis of Universal Human Papillomavirus Vaccination Using a Dynamic Bayesian Methodology: The BEST II Study.

BACKGROUND: Human papillomavirus (HPV) plays a role in the development of benign and malign neoplasms in both sexes. The Italian recommendations for HPV vaccines consider only females. The BEST II study (Bayesian modelling to assess the Effectiveness of a vaccination Strategy to prevent HPV-related diseases) evaluates 1) the cost-effectiveness of immunization strategies targeting universal vaccination compared with cervical cancer screening and female-only vaccination and 2) the economic impact of immunization on various HPV-induced diseases. OBJECTIVE: The objective of this study was to evaluate whether female-only vaccination or universal vaccination is the most cost-effective intervention against HPV. METHODS: We present a dynamic Bayesian Markov model to investigate transmission dynamics in cohorts of females and males in a follow-up period of 55 years. We assumed that quadrivalent vaccination (against HPV 16, 18, 6, and 11) is available for 12-year-old individuals. The model accounts for the progression of subjects across HPV-induced health states (cervical, vaginal, vulvar, anal, penile, and head/neck cancer as well as anogenital warts). The sexual mixing is modeled on the basis of age-, sex-, and sexual behavioral-specific matrices to obtain the dynamic force of infection. RESULTS: In comparison to cervical cancer screening, universal vaccination results in an incremental cost-effectiveness ratio of €1,500. When universal immunization is compared with female-only vaccination, it is cost-effective with an incremental cost-effectiveness ratio of €11,600. Probabilistic sensitivity analysis shows a relatively large amount of parameter uncertainty, which interestingly has, however, no substantial impact on the decision-making process. The intervention being assessed seems to be associated with an attractive cost-effectiveness profile. CONCLUSIONS: Universal HPV vaccination is found to be a cost-effective choice when compared with either cervical cancer screening or female-only vaccination within the Italian context.