Decision analysis is considered an essential tool that every responsible decision-maker should use to make rational, informed choices that are ideally optimal according to predefined and possibly shared criteria. In the management of public healthcare, decision analysis tends to propose more cost-effective choices for the benefit of the community, operating in a specific context of limited healthcare resources that do not allow satisfying all patient needs. The use of decision analysis in the public healthcare context inevitably refers to the bioethical value of health equity: the most cost-effective choice aims to satisfy the maximum number of patients with the scarce available resources, adopting a utilitarian interpretation of the equity criterion. Unfortunately, within the management of the public healthcare system, the use of decision analysis has faced challenges due to cultural, social, and organizational reasons. In Italy, the management of the National Healthcare System (SSN) and regions is structured into separate compartments (silos): pharmaceutical spending is managed separately from hospital and community care. Even today, managers of the pharmaceutical service must pursue the primary objective of keeping pharmaceutical spending within a predetermined maximum limit. During the early years of AIFA, this criterion hindered or at least discouraged the use of traditional pharmacoeconomic analyses in preparing Price and Reimbursement (P&R) dossiers for new drugs to be negotiated. The fundamental economic analysis required by AIFA was a simulated estimation of the budget impact of pharmaceutical spending in the first three years after the introduction of a new drug to the market. However, pharmacoeconomists from pharmaceutical companies progressively started submitting dossiers with BIA prepared according to international standards, which require evaluating the overall impact of the new drug not only on pharmaceutical spending but also on all types of healthcare costs (e.g., hospital costs, home care, etc.). Only in recent years, AIFA has explicitly valued cost-effectiveness analyses as a tool to support its decisions on drug prices and reimbursement. The recent AIFA Monitoring Report 2022, prepared by the Economic Evaluations Office (Table I), highlights that in recent years, there has been a progressive increase in the percentage of P&R dossiers including pharmacoeconomic analyses. In 2022, one hundred six dossiers, equivalent to 62% of the dossiers submitted to AIFA, were accompanied by a pharmacoeconomic study: 105/106 (99%) included Budget Impact Analysis (BIA), 73/106 (69%) also featured a Cost-Effectiveness (CEA) or Cost-Utility (CUA) analysis, and only 1/106 (1%) exclusively included a CEA. In summary, AIFA still considers BIA fundamental for negotiating the P&R of a drug intended for the Italian market. However, the percentage of dossiers including CEA studies is now significant and growing, particularly important for the negotiation of new drugs, especially orphan drugs. It should be emphasized that in the last two years, all dossiers for orphan drugs included a BIA and 86% also included a CEA. A similar trend, with slightly lower percentages, was observed for P&R dossiers of new chemical entities (Table 1). Analyzing the BIA and CEA studies presented to support the negotiation of recent innovative drugs, especially some orphan drugs, reveals that these analyses can justify very high reimbursement prices that these drugs have obtained. For instance, the purchase cost of a CAR-T therapy has reached several hundred thousand Euros in Italy. When successful, a single-dose CAR-T treatment for a young patient allows for a normal life expectancy and accumulates healthcare savings for each avoided year of illness. The importance of the pharmacoeconomic analyses in drug negotiation. A Farewell Editorial

Objectives No agent has yet been proven to be effective for the treatment of patients with severe COVID-19. Methods We conducted a pilot prospective open, single-arm multicentre study on off-label use of tocilizumab (TCZ) involving 63 hospitalised adult patients (56 males, age 62.6 +/- 12.5) with severe COVID-19. Clinical and laboratory parameters were prospectively collected at baseline, day 1, 2, 7 and 14. No moderate-to-severe adverse events attributable to TCZ were recorded. Results We observed a significant improvement in the levels of ferritin, C-reactive protein, D-dimer. The ratio of the partial pressure of oxygen (Pa0(2)) to the fraction of inspired oxygen (Fi0(2)) improved (mean +/- SD Pa0(2)/Fi0(2) at admission: 152 +/- 53; at day 7: 283.73 +/- 115.9, at day 14: 302.2 +/- 126, p<0.05). The overall mortality was 11%; D-dimer level at baseline, but not IL-6 levels were predictors of mortality. TCZ administration within 6 days from admission in the hospital was associated with an increased likelihood of survival (HR 2.2 95%CI 1.3-6.7, p<0.05). Conclusions In hospitalised adult patients with severe COVID-19, TCZ could be a safe option. An improvement in respiratory and laboratory parameters was observed. Future controlled trials in patients with severe illness are urgently needed to confirm the definite benefit with IL-6 target therapy.

Background. In order to support the economic and financial sustainability of the Italian health system, there is a need to define technically and economically efficient strategies that assure the self-sufficient apheretic production of plasma.Material and methods. Process and product costs at the Casa del Donatore (CD) in Bologna were determined on the basis of costing models used at Verona's Inter-hospital Department of Transfusional Medicine (IDTM) by academics from the University of Turin and those used at the Marche Regional IDTM by academics from Marche Polytechnic University. During the first phase, data was collected concerning donors, biological screening tests, the number of units produced/discarded, the materials used (individual pharmacy codes and related final expenditure), human resources (number, professional status, time involved, the number of activities per day, percentage productivity), equipment, and general costs. During the second phase, direct costs were verified and the costs common to the units produced were attributed using the functional principle.Results: The overall cost of a litre of plasma collected by means of apherisis (about (sic) 280) was similar at the three centres, but there were differences in their cost structures that could be attributed to organisational choices, economic factors and/or structural variables. Plasmapheresis accounts for 24% of the plasma collected in Marche and the CD, but 17% of that collected in Verona, whereas the donation index is lower in the CD (1.8) than in the other two centres (2.2). The annual donor screening tests are substantially similar, but there are some differences in their timing (at the time of screening candidate donors or at the time of first donation). There are also some differences in the use of tests that are not required by law but are carried out in order to protect donors and recipients. The working times in three centres are similar, but personnel costs vary because of their different retribution policies.Discussion. Comparing the cost determinants at each centre made it possible to highlight changes that each can make in order to improve efficiency, and may lay the basis for doing the same in other organisational contexts.

Background & aimsA recent meta-analysis showed that supplementation of omega-3 fatty acids in parenteral nutrition (PN) regimens is associated with a statistically and clinically significant reduction in infection rate, and length of hospital stay (LOS) in medical and surgical patients admitted to the ICU and in surgical patients not admitted to the ICU. The objective of this present study was to evaluate the cost-effectiveness of the addition of omega-3 fatty acids to standard PN regimens in four European countries (Italy, France, Germany and the UK) from the healthcare provider perspective.MethodsUsing a discrete event simulation scheme, a patient-level simulation model was developed, based on outcomes from the Italian ICU patient population and published literature. Comparative efficacy data for PN regimens containing omega-3 fatty acids versus standard PN regimens was taken from the meta-analysis of published randomised clinical trials (n = 23 studies with a total of 1502 patients), and hospital LOS reduction was further processed in order to split the reduction in ICU stay from that in-ward stays for patients admitted to the ICU. Country-specific cost data was obtained for Italian, French, German and UK healthcare systems. Clinical outcomes included in the model were death rates, nosocomial infection rates, and ICU/hospital LOS. Probabilistic and deterministic sensitivity analyses were undertaken to test the reliability of results.ResultsPN regimens containing omega-3 fatty acids were more effective on average than standard PN both in ICU and in non-ICU patients in the four countries considered, reducing infection rates and overall LOS, and resulting in a lower total cost per patient. Overall costs for patients receiving PN regimens containing omega-3 fatty acids were between €14 144 to €19 825 per ICU patient and €5484 to €14 232 per non-ICU patient, translating into savings of between €3972 and €4897 per ICU patient and savings of between €561 and €1762 per non-ICU patient. Treatment costs were completely offset by the reduction in hospital stay costs and antibiotic costs. Sensitivity analyses confirmed the robustness of these findings.ConclusionsThese results suggest that the supplementation of PN regimens with omega-3 fatty acids would be cost effective in Italian, French, German and UK hospitals.

Intravenous (i.v.) glutamine supplementation of parenteral nutrition (PN) can improve clinical outcomes, reduce mortality and infection rates and shorten the length of hospital and/or intensive care unit (ICU) stays compared with standard PN. This study is a pharmacoeconomic analysis to determine whether i.v. glutamine supplementation of PN remains both a highly favourable and cost-effective option for Italian ICU patients. A previously published discrete event simulation model was updated by incorporating the most up-to-date and clinically relevant efficacy data (a clinically realistic subgroup analysis from a published meta-analysis), recent cost data from the Italian health-care system and the latest epidemiology data from a large Italian ICU database (covering 230 Italian ICUs and more than 77 000 patients). Sensitivity analyses were performed to test the robustness of the results. Parenteral glutamine supplementation can significantly improve ICU efficiency in Italy, as the additional cost of supplemented treatment is more than completely offset by cost savings in hospital care. Supplementation was more cost-effective (cost-effectiveness ratio (CER)=€35 165 per patient discharged alive) than standard, non-supplemented PN (CER=€40 156 per patient discharged alive), and it resulted in mean cost savings of €4991 per patient discharged alive or €1047 per patient admitted to the hospital. Sensitivity analyses confirmed the robustness of these results. Alanyl-glutamine supplementation of PN is a clinically and economically attractive strategy for ICU patients in Italy and may be applicable to selected ICU patient populations in other countries.

In Italy, within the legal mandate to pursue national self-sufficiency of secondary blood products, the Regions are starting to organize trade to offset need/availability unbalances. Therefore the determination of the full cost to the Regions of plasma collection and handling is needed. Plasma is obtained from voluntary, non-remunerated donors either from full blood or from apheresis, and is collected either directly in facilities of the Regional Health Services, or indirectly through the net of donors’ associations before being delivered to the transformation industry for processing. Amount and costs of materials and activities needed for collecting, producing, validating, and distributing plasma were obtained from the transfusional medicine department of the Verona province, Veneto Region. Attributable overhead expenses are assumed at 15% of direct cost. When plasma is collected as part of the whole blood or from multicomponent apheresis, common costs are attributed basing on the commercial value of single components, taken as proxy of the willingness-to-pay for them. In an alternative scenario, only product-specific costs are attributed to plasma recovered from whole blood donations, for which the driving need is the supply of red blood cells. Total cost per liter of plasma sent for processing is estimated in 114 and 286 euros, respectively, for collection from whole blood and apheresis. Given the current mix of plasma origin, the weighed mean cost of plasma to the Regions before processing charges is estimated in 157 €. When plasma recovered from whole blood donations is considered by-product, its cost per liter sent to industry is estimated in 27 €, and the corresponding weighed mean cost in 92 €. The Italian donor-based system, in addition to its ethical and social values, supplies plasma at a lower or comparable cost than commercially available.

To re-evaluate the economic consequences of parenteral glutamine supplementation (PGS) in light of the recent metaanalysis confirming that PGS at a dose >0,20 g/kg body weight per day in intensive care unit (ICU) patients is associated with reduced mortality, infection rate (IR) and length of stay (LOS). A simulation model was updated with the new meta-analysis data and clinical inputs for the control group from Italian ICU population reported in “Progetto Margherita”. Costs are evaluated from the perspective of the Italian hospital and derive from official sources. Sensitivity analyses are undertaken to test results’ reliability PGS is predicted to reduce mortality rates (-29.0%), IR (-21.2%) and overall LOS (-1.07 days/patient), yielding a saving of € 1,047 per patient treated. Treatment costs are completely offset by the reduction in hospital stay costs and antibiotic costs. Probabilistic sensitivity analysis indicates PGS strategy as dominant in more than 90% of cases. Also with contemporary comparative efficacy data is PGS in ICU patients expected to be effective in improving outcomes and containing costs in Italian hospitals providing intensive care.

OBJECTIVE: To simulate haemophilia A (HA) real-life management and compare the cost of different treatment strategies, both with plasma-derived and recombinant factor VIII (pdFVIII and rFVIII, respectively), from the perspective of the Italian NHS.METHODS: A discrete event (micro-)simulation (DES) model was developed to reproduce every possible HA patient clinical pathway: on-demand (OD) treatment of bleeding, continuous or discontinuous prophylaxis (PRO) with FVIII, inhibitors-tolerance-induction treatment (ITI), surgery in case of severe disability. Patient characteristics, treatment indications and disease evolution were modeled basing on data available in clinical literature in order to represent the actual state of art of HA management. In addition to the baseline scenario, reproducing current HA management, alternative strategies were simulated to explore the impact on the cost borne by the Italian NHS for these patients. Only differential direct sanitary costs were considered in the simulation, with a 3.5% discount rate.RESULTS: Baseline scenario results show difference between patients treated with pdFVIII and those treated with rFVIII: mean lifetime HA patient management cost was estimated at € 1,332,373 with pdFVIII treatment, compared with € 2,013,222 for rFVIII. The saving is due mainly to the lower acquisition cost of pdFVIII. Total medical costs are strongly and positively correlated with HA severity: cost per patient increases from € 86,269 (mild HA) to € 1,509,231 (severe HA) for patients treated with pdFVIII and from € 147,900 to € 2,621,540 in patients treated with rFVIII. All analyses conducted in the study lead to the conclusion that the use of pdFVIII is much less expensive than rFVIII, but therapeutically equivalent.CONCLUSION: Management of HA patients is complex and difficult to optimize; although involving a limited number of patients, lifetime management costs for the Italian NHS are extremely high. The main advantage of this model lies in the capability of estimating the economic impact of different strategic choices and economic/regulatory constraints.

INTRODUCTION: Prostate cancer (PC) is a very common tumor among men: in Italy its prevalence in 2006 was 0.9%. Androgen deprivation therapy is a way to treat hormone-responsive PC by decreasing testosterone levels. GnRH-analogues, including GnRH-agonists and GnRH-antagonists, are effective for this purpose. AIM: This article presents a cost-effectiveness analysis based on a semi-Markov model comparing the GnRH-antagonist degarelix and GnRH-agonist leuprolide in the treatment of hormone-dependent advanced prostate cancer from the perspective of the Regional Health Service in Veneto Region (Italy).MATERIALS AND METHODS: Effectiveness data were retrieved by a 12-month phase III non-inferiority clinical trial, comparing degarelix and 7,5 mg leuprolide in 610 patients treated for hormone-dependent prostate cancer. Epidemiological data came from a national database and were referred to Veneto Region. The values of the healthcare resources were calculated using regional and national prices (€ 2012). The model considers 3 exhaustive and mutually exclusive health status: first-line treatment, further-lines treatment and death. It lasts 10 years, with 28 days per cycle. The entry in the model is hypothesized at the age of 70 (the age with most PCs in Veneto Region). Effectiveness endpoints were life years saved and quality-adjusted life years, using 3% social discount rate. The incremental cost per QALY was related to the range of acceptability proposed by the Associazione Italiana di Economia Sanitaria (€ 25,000-40,000). The budget impact was calculated on a 5-year time horizon. Univariate and probabilistic sensitivity analyses were performed on every hypothesis of the model.RESULTS: Degarelix resulted in minor costs if compared to 7.5 mg leuprolide (€ 20,511.64 vs 22,256.49). The cost-driver was chemotherapic care (32.45% degarelix vs 44.30% 7.5 mg leuprolide). Life years saved were the same for both the alternatives (5.58), while QALYs obtained were higher in degarelix vs. 7.5 mg leuprolide (4.41 vs. 4.10). QALY better data probably could results from greater delay to disease progression in castrate resistant phase with degarelix than comparator and also due to superior symptoms relief. Therefore degarelix is dominant compared to the agonist. The probability for degarelix to be cost-effective increases with the increasing of the threshold for incremental QALY, being 69.95%, 93.76%, 95.55%, and 97.42% for threshold values equal to € 0, € 25,000, € 40,000, and € 100,000, respectively. The use of degarelix in Veneto Region instead of 7.5 mg leuprolide would result, after a five-year period, in total savings for the Regional Health Service equal to € 4,783, considering the treatment of 259 patients.CONCLUSIONS: In the treatment of hormone-dependent advanced prostate cancer PC, degarelix is thought to be an economically rational investment of resources for the Regional Health Service of Veneto Region because it’s dominant, in term of cost-effectiveness, to the comparator (agonist) thanks to superior QALY and reduced costs.

Anemia is a frequent complication of chronic kidney disease (CKD) due to the inability of the kidneys to release sufficient erythropoietin to regulate the production of red blood cells. Administration of erythropoiesis-stimulating agents (ESAs) is highly effective in correcting anemia of CKD. The ESAs currently approved in Italy are epoetin alfa, epoetin beta, epoetin theta, darbepoetin alfa, CERA and biosimilars epoetin alfa and epoetin zeta. All the ESAs are effective in correcting renal anemia and increasing hemoglobin levels, but the choice of which to use should also take into account their pharmacokinetics and pharmacodynamics, their administration route, and economic issues. However, regarding the optimal use of ESAs an issue that remains controversial is the most appropriate dose conversion between epoetin alfa and darbepoetin alfa. In fact clinical experience demonstrates that the dose relationship between epoetin alfa and darbepoetin alfa is non proportional across the dosing spectrum. In this review is presented an update on the latest available evidence in the treatment of anemia in CKD patients, with particular reference to the definition of the correct conversion ratio EPO:DARB.

Chronic constipation is a common disorder, especially in women. Options available for different subgroups of constipation are limited and in most cases unsatisfactory. The most severe forms of chronic constipation often require the use of laxatives in high doses or the use of invasive therapies. The introduction of a new drug, such as prucalopride, active in promoting intestinal transit, can help to improve the therapy of patients with chronic idiopathic constipation who have not found relief from previous treatment with laxatives. In this review, after a brief discussion of pathophysiology and pharmacotherapy of chronic constipation, we evaluate the pharmacological profile, therapeutic and cost of prucalopride, recently authorized in the EU countries and also available in Italy for the treatment of chronic constipation in women who did not benefit from the use of laxatives.

Introduction: The supplementation of alanyl-glutamine dipeptide in critically ill patients necessitating total parenteral nutrition (TPN) improves clinical outcomes, reducing mortality, infection rate, and shortening intensive care unit (ICU) hospital lengths of stay (LOSs), as compared to standard TPN regimens. Methods: A Discrete Event Simulation model that incorporates outcomes rates from 200 Italian ICUs for over 60,000 patients, alanyl-glutamine dipeptide efficacy data synthesized by means of a Bayesian random effects meta-analysis, and national cost data has been developed to evaluate the alternatives from the cost perspective of the hospital. Simulated clinical outcomes are death and infection rates in ICU, death rate in general ward, and hospital LOSs. Sensitivity analyses are performed by varying all uncertain parameter values in a plausible range. Results: The internal validation process confirmed the accuracy of the model in replicating observed clinical data. Alanyl-glutamine dipeptide on average results more effective and less costly than standard TPN: reduced mortality rate (24.6% ± 1.6% vs. 34.5% ± 2.1%), infection rate (13.8% ± 2.9% vs. 18.8% ± 3.9%), and hospital LOS (24.9 ± 0.3 vs. 26.0 ± 0.3 days) come at a lower total cost per patient (23,409 ± 3,345 vs. 24,161 ± 3,523 Euro).Treatment cost is completely offset by savings on ICU and antibiotic costs. Sensitivity analyses confirmed the robustness of these results. Conclusions: Alanyl-glutamine dipeptide is expected to improve clinical outcomes and to do so with a concurrent saving for the Italian hospital.

Rheumatoid arthritis (RA) is a chronic, progressive and degenerative illness, which affects about 0.5% of the adult population with significant social costs. In Italy there are approximately 300,000 people with RA, with twice as many women than men. RA causes progressive deformity and disability and is associated with numerous co-morbid conditions that reduce the life expectancy of 5-10 years. The costs of RA have a serious impact on the entire community, especially in terms of disability, hospitalization and medical care. In Italy has been estimated that cost of illness could reach about 1,600 million euros, of which over two thirds are represented by indirect costs. The treatment of RA is evolving and the introduction of biological drugs has resulted in a significant progress in terms of therapeutic possibilities. Etanercept, the only soluble receptor of TNF-alfa currently approved appears to be cost-effective and it is recommended by major guidelines for the treatment of RA. http://dx.doi.org/10.7175/rhc.v3i3.201

A very recent Meta-Analysis shows that the addition of Omega-3 fatty acid in standard Total Parenteral Nutrition (TPN) is associated with reductions in infection rate, ICU, and overall lengths of stay (LOSs) for both Intensive Care Unit (ICU) and elective surgery patients. Aim of this study is the CE analysis of its use in these patient populations, as compared to standard lipid emulsions. Within a Discrete Event Simulation (DES) scheme, a patient-level simulation model was developed, with the inclusion of baseline outcomes rates from the Italian ICU patient population and from published literature; comparative efficacy data for standard and Omega-3 fatty acids-based regimens from the meta-analysis of published randomized clinical trials (conducted on 23 studies with a total of 1502 patients), and country-specific cost data. Clinical outcomes included in the model are death rates, nosocomial infection rates, and ICU/hospital LOSs. Costs are referred to Italian, French German and UK health care systems. Probabilistic and deterministic sensitivity analyses are undertaken to test results' reliability. Omega-3 fat emulsions emerged as more effective on average than standard TPN both in ICU and in non-ICU patients: in all the four national contexts here considered, reduced mortality rates, infection rates, and overall LOSs yield a lower total cost per patient. Treatment costs are completely offset by the reduction in hospital stay costs and antibiotic costs. Sensitivity analyses confirmed the robustness of these findings. These results indicate that the addition of Omega-3 to standard TPN is expected to improve clinical outcomes and concurrently give a saving for Italian, French, German and UK hospitals.