Global and Regional Health Technology Assessment

Cost-effectiveness of brentuximab vedotin plus chemotherapy as frontline treatment of stage IV Hodgkin lymphoma in Italy

Chiara Bini — 2024-12-10

Objectives: Advanced Hodgkin’s lymphoma (HL) is a rare severe neoplasm, significantly limiting the ability of patients to do daily activities among other impacts of the cancer. Many adult patients present with advanced stage disease (stages III/IV). This analysis investigates the cost-effectiveness of brentuximab vedotin (BV) in combination with doxorubicin, vinblastine, and dacarbarzine (AVD) versus ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) for the frontline treatment of stage IV HL in Italy based on data from the ECHELON-1 clinical trial.

Methods: The analysis was conducted from the perspective of the National Health Service using a Markov model with three mutually exclusive health states and a lifetime time horizon. Transition probabilities were taken from the six-year follow-up data of ECHELON-1. Costs were obtained mainly from published literature and national tariffs. For all drugs, ex-factory prices net of the mandatory reductions required by law were considered. Scenarios on possible confidential drug discounts were also explored.

Results: BV in combination with AVD was associated with an increase of € 44,551 in total costs of 1.03 life-years (LYs) and 0.85 quality-adjusted life-years (QALYs) as compared with ABVD in the base-case scenario. The incremental cost-effectiveness ratio and the incremental cost-utility ratio were estimated equal to € 43,179/LYs and € 52,257/QALYs, respectively, when based on ex-factory prices. BV in combination with AVD was shown to be a cost-effective option in 24 out of 36 scenarios examining possible confidential discounts (ranging from 0% to 60%) for high-cost drugs included in the analysis based on a € 41,411/QALYs threshold for severe diseases.

Conclusions: Based on data from 6 years of follow-up from the ECHELON-1 trial, BV in combination with AVD has the potential to be a cost-effective option versus ABVD for the frontline treatment of stage IV HL in Italy.

A 1-year per-patient cost of therapy administration analysis of mosunetuzumab and tisagenlecleucel in relapsed or refractory follicular lymphoma patients receiving two or more lines of systemic therapy

Marco Bellone — 2024-12-09

Objective: A per-patient cost of therapy administration model was developed to estimate the cost of mosunetuzumab vs. tisagenlecleucel in patients with relapsing or refractory follicular lymphoma (R/R FL) receiving two or more lines of systemic therapy (3L+) from both the Italian hospital and societal perspectives.

Methods: A per-patient total cost of therapy administration model was developed to compare the resource consumption of two treatments – mosunetuzumab and tisagenlecleucel. The model considered direct costs such as healthcare labor costs for drug preparation and administration, non-drug consumable costs, and drug purchase. Indirect costs such as patient and caregiver’s loss of productivity, transportation, and relocation were also considered. The unit costs and resource use data were retrieved from literature and standard Italian tariffs. To appraise the impact of patients’ residency on access-to-care and out-of-pocket expenses, three scenario analyses were conducted.

Results: Over 1 year, mosunetuzumab costs approximately one-fourth of tisagenlecleucel per patient. The base-case scenario showed a hospital cost reduction of €158,870 per patient with mosunetuzumab, increasing to €161,974 when including societal costs. Scenario analyses for the societal perspective estimated cost differences of −€161,170, −€166,507, and −€166,811 for scenarios A, B, and C, respectively. Sensitivity analysis indicated that tisagenlecleucel’s price had the greatest impact on cost differences, followed by mosunetuzumab’s price.

Conclusions: This analysis identifies mosunetuzumab as an accessible therapeutic option for 3L+ R/R FL patients in Italy. Future research should collect real-time data and evaluate long-term outcomes.

Economic impact of dapagliflozin in the management of chronic kidney disease in Italy: results from a micro-simulation model

Roberto Ravasio — 2024-12-02

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).

Policy predictive model for better management of chronic obstructive pulmonary disease: economic-organisational implications in the Italian healthcare system

Debora Antonini — 2024-11-20

Background: Chronic obstructive pulmonary disease (COPD) represents a significant public health problem in Italy, with a high prevalence and a substantial economic burden on the National Health Service (NHS). Effective management of the disease is crucial for reducing exacerbations and improving patients’ quality of life.

Methods: This study employs a dynamic predictive model to assess the economic impact of implementing three specific health policies aimed at improving COPD management over a five-year horizon. The analysis is conducted from the perspective of the NHS, focusing on the direct costs associated with disease management.

Results: The implementation of the proposed policies demonstrated potential significant savings in direct healthcare costs. The first policy, focused on increasing therapeutic adherence, generated an estimated savings of 202 million €. The second, concerning the wider use of triple therapies, led to savings of about 142 million €. Finally, the third policy, aimed at reducing the delay in prescribing appropriate therapies, contributed to an additional saving of over 175 million € in the time horizon considered in the analysis. Overall, these results suggest a substantial improvement opportunity in COPD management, with significant economic benefits for the Italian NHS.

Conclusion: The study confirms the importance of targeted policies in the management of COPD, highlighting how strategic interventions can lead to significant resource savings while simultaneously improving patient care. These results provide a solid foundation for further research and serve as a useful guide for decision-makers in planning effective intervention strategies, aimed at optimizing resources and enhancing disease management in the Italian healthcare context.

A cost-effectiveness analysis of Navina Smart on adult patients affected by neurogenic bowel dysfunction

Matteo Ruggeri — 2024-11-18

Background and Objectives: The objective of this study is to evaluate the economic impact of the device Navina Smart on patients affected by neurogenic bowel dysfunction and dependent on transanal irrigation within the Italian context. This study employs the perspective of the Italian National Health Service.

Methods: The analysis was conducted through a Markov model, comparing two scenarios: standard bowel care vs. transanal irrigation. The model operates on a 30-year time period. The results were reported in terms of net monetary benefit.

Results: Transanal irrigation therapy was dominant in all scenarios with lower costs and higher effectiveness. The population was assumed to be composed of 1,000 subjects. Setting the willingness to pay at €35,000.00/QALYs (quality-adjusted life years), the analysis yielded a net monetary benefit of €81,087 and cost savings of €66,101 per patient over 30 years.

Conclusion: The results of this study substantiate that transanal irrigation therapy treatment employing the Navina Smart device can significantly benefit patients suffering from neurogenic bowel dysfunction by relieving their symptoms. In addition, this therapy offers important cost savings for the Italian National Health Service by reducing resource utilization.

Survival, treatment duration and costs of patients with prostate cancer treated with triptorelin in Italy: a study of administrative databases

Orazio Caffo — 2024-11-11

Background: Several data support the efficacy/effectiveness, safety and favorable impact on quality of life of triptorelin treatment in patients with prostate cancer. However, little evidence is available concerning triptorelin use in the long term.

Methods: We analyzed data on triptorelin treatment in patients with prostate cancer in an integrated Italian administrative database, covering around 6 million health-assisted subjects throughout the country. Patients with at least one prescription for triptorelin in the period 2010-2020 and with no evidence of metastasis were included and followed up until 2021. Overall survival (OS) and duration of treatment were analyzed using Kaplan-Meier curves, starting from the date of first prescription.

Results: The cohort included a total of 3,411 patients (mean age: 76.8 ± 8.7 years), of whom 1,326 (38.9%) were treated with triptorelin only and 2,085 (61.1%) with triptorelin combined with an anti-androgen. Overall, 847 (24.8%) patients with prostate cancer died and 1,037 (30.4%) had a treatment switch during the follow-up period, and both the median OS and median duration of treatment were not reached in both groups. The mean annual total cost per patient was estimated as 5,574 €, with almost half of the costs related to medication expenses (2,737 €).

Conclusions: We found a long survival and duration of triptorelin treatment in this population of Italian patients with prostate cancer. This study with a long follow-up period further highlights the usefulness of healthcare utilization databases to integrate results obtained from clinical studies with those from everyday clinical practice.

The economic and social burden of congenital thrombotic thrombocytopenic purpura (cTTP) in Italy

Filippo Rumi — 2024-10-28

Background: Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare genetic disorder characterized by an abnormal clotting process leading to serious health complications such as thrombocytopenia and hemolytic anemia. Despite its clinical significance, the estimated broader economic and social impacts in Italy on patients and society remain underexplored.

Methods: A detailed questionnaire, developed and validated by a panel of cTTP experts, was distributed to healthcare professionals and patient associations to gather comprehensive data on the economic and social burden of cTTP in Italy. The study was focused on direct and indirect costs associated with the disease management of 15 patients with cTTP, as well as out-of-pocket expenses incurred by patients.

Results: The analysis revealed that of the 15 patients diagnosed with cTTP in Italy, 60% were adults aged 40-55 years. Productivity loss and diminished quality of life dominated the economic burden of cTTP, accounting for 81.05% of total costs. Direct medical costs, while substantial, represented a smaller portion of the overall financial impact. Additionally, out-of-pocket expenses, though constituting the smallest fraction, underscored the financial contributions made by patients towards their own care management.

Conclusion: The findings underscore the need for a multidisciplinary and holistic approach to cTTP management that extends beyond the clinical treatment. Addressing the economic and social implications of the disease is crucial for improving patient well-being and ensuring the sustainability of healthcare systems. The study advocates for increased awareness, research, and access to care for cTTP patients, highlighting the importance of comprehensive support networks to mitigate the disease’s broader societal impacts, estimated to be around 2 million euro for 15 patients in 10 years.

Drug utilization and medication adherence for the treatment of psoriatic arthritis: an Italian study

Fiorenzo Santoleri — 2024-10-09

Introduction: This study aims to evaluate the persistence, treatment adherence and drug cost associated with biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in the management of psoriatic arthritis (PsA) in Italy, with a focus on biosimilar drugs.

Methods: This was a retrospective observational study involving eight hospital pharmacies, between January 2017 and December 2020, on naïve patients with at least one b/tsDMARD dispensation indicated for PsA. Patients were followed up for 12 months and persistence and adherence were evaluated by proportion of days covered (PDC). The originator and biosimilar for adalimumab and etanercept were compared. Furthermore, the real annual cost per patient based on adherence to therapy was calculated.

Results: Patients initiating b/tsDMARDs for PsA had a mean persistence of 263 days and 48.6% remained persistent for 1 year. Adherent patients (PDC ≥ 0.8) were 47.6% for the overall population. Similar persistence and adherence were observed between patients treated with the adalimumab originator and its biosimilar, while patients treated with the etanercept originator showed lower persistence and adherence compared to those treated with its biosimilar (mean persistence: 222 vs. 267 days, patient persistent at 1 year: 29.4% vs. 51.5%, mean PDC: 0.53 vs. 0.70, adherent patients: 23.5% vs. 51.5%). The average annual drug cost ranged from €8,724 (etanercept) to €14,783 (ustekinumab), with an annual saving of more than €2,500 by using biosimilars.

Conclusion: Poor adherence to medications contributes to suboptimal clinical outcomes. The comparison between biosimilar and originator offers further evidence in support of the biosimilar to optimizing resources in healthcare.

Budget impact analysis on the Italian healthcare system of roxadustat for the treatment of anemia due to chronic kidney disease

Chiara Bini — 2024-09-10

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%.

Assessment of innovativeness, and price and reimbursement negotiation of medicines: recommendations of an expert panel

Claudio Jommi — 2024-07-15

This paper illustrates the recommendations of a Working Group (WG) on the assessment of drugs innovativeness and the negotiation of price and reimbursement. The WG included researchers, institutions, clinicians, patient representatives and pharmaceutical companies.

The first part of the contribution summarizes the literature on drug pricing models, which was considered in the WG, and, in particular, the pricing criteria, the evaluation and negotiation processes, the management of the uncertainty of the evidence, the use of cross-reference pricing and price negotiation for new indications of existing drugs.

The second part illustrates the results of the WG with a focus on innovativeness assessment, value framework and price negotiation. The main recommendations of the WG are: to define more specific criteria for the identification of comparators and endpoints for macro therapeutic areas/settings; to produce guidelines on the use of indirect comparisons and studies supporting this evidence; to consider the drug value as the main driver of price and reimbursement negotiation; to maintain flexibility in the negotiation process, but, at the same time, to give greater structure and predictability in the assessment of value for money, with a more qualified role of cost-effectiveness and a range of threshold values for the incremental cost-effectiveness ratio; to selectively reintroduce Managed Entry Agreements and the Indication-based pricing model; to implement an early dialogue between the Italian Medicine Agency and the pharmaceutical companies in order to optimize the negotiation process, and a structured involvement of scientific societies and patient representatives.

Exploring the administrative burden faced by hematologists: a comprehensive study in Italy

Davide Petruzzelli — 2024-07-03

Background: Administrative burdens have been identified as a major issue impacting patient care, professional practice, and the overall efficiency of healthcare systems. The aim of this study is to assess the administrative burden faced by Italian hematologists.

Methods: A cross-sectional survey that included both closed-ended quantitative questions and open-ended free text answer options was administered to 1,570 hematologists working with malignancies and members of Italian GIMEMA Foundation – Franco Mandelli ONLUS and the Italian Linfomi Foundation (FIL). The survey was conducted online from May 24 to June 30, 2023. Descriptive statistics were computed for the quantitative data to clearly summarize the responses and descriptive analysis of free text responses was carried out.

Results: Surveyed hematologists spend an average of 47.07% of their time on administrative tasks, with 63.22% (n = 110) of respondents reporting spending at least half of their time on these activities. More than half (57.47%, n = 100) reported that “Patient care” is the medical task most affected by a lack of time. Additionally, 55.17% (n = 96) reported experiencing burnout in the past 6 months, with filling out “Forms” being identified as the top contributing administrative task by 27.59% (n = 48) of respondents, followed by “Scheduling” (24.71%, n = 43) and “Managing IT system failures” (21.84%, n = 38). Nearly half of the surveyed hematologists (45.40%, n = = 79) identified patient care as the top priority requiring more time.

Conclusions: The study confirms that the administrative workload of hematologists has a significant impact on patient care, communication, and burnout risk, reducing the time available for patient care, leading to exhaustion and concern about clinical errors.

Cabozantinib use in second or subsequent line of treatment in renal cell carcinoma: an analysis of Italian administrative databases

Cristian Lolli — 2024-07-03

Background: Cabozantinib use in everyday clinical practice for advanced or metastatic renal cell carcinoma (RCC) is relatively recent, and real-world data on treatment persistence, adherence and sequencing are still limited.

Methods: We conducted an analysis based on an integrated administrative database, covering around 6.9 million health-assisted Italian individuals, to explore the use of cabozantinib for RCC. Patients with at least one prescription for cabozantinib during 2017-2020 were searched. These were characterized during all available period (i.e. from 2010 onwards) before the index date and were observed after inclusion.

Results: A total of 113 patients treated with cabozantinib in second or subsequent line were included, and their demographic, clinical and treatment characteristics were described. About half of these RCC patients were aged >65 years (47.8%). Sixty patients (53.1%) were highly adherent to cabozantinib therapy, and the median cabozantinib treatment duration of use was 8.7 months (95% confidence interval: 5.8-11.1). During the first year of follow-up, the average total cost per patient was €32,508.

Conclusions: We described second or subsequent line cabozantinib treatment for RCC in a real-world setting and the economic burden of disease in Italy, taking advantage of large, integrated administrative databases.

Gender differences and hypercholesterolemia: real-world evidence from the study WECARE (Women Effective CArdiovascular Risk Evaluation)

Valentina Perrone — 2024-06-11

Introduction: The therapeutic control of LDL-cholesterol is essential in cardiovascular prevention, as recommended by the recent guidelines.

Objective: To evaluate gender differences in terms of demographic and clinical characteristics, treatment pattern, treatment adherence and healthcare costs in patients on lipid-lowering therapy, stratified by cardiovascular risk in the Italian real clinical practice.

Methods: An observational analysis was conducted on the administrative databases of healthcare institutions, covering about 6.1 million health-assisted subjects. After inclusion of all patients on lipid-lowering therapy between January 2017 and June 2020, the population was investigated in the period before the first prescription of a lipid-lowering drug and followed-up for at least 12 months. Clinical and demographic variables were compared after stratification by gender and by cardiovascular risk (very high/high/other risk). The main outcome measures were treatment adherence and direct healthcare costs during follow-up.

Results: Of the 684,829 patients with high/very high cardiovascular risk, 337,394 were men and 347,435 women, aged on average 69.3 years and 72.1 years, respectively (p < 0.001). Men were characterised by a worse comorbidity profile. Regardless of cardiovascular risk, female subjects were associated with larger utilisation of low-potency statins and lower adherence (p < 0.001). The annual healthcare costs per patient during follow-up were higher in men than in women (p < 0.001).

Conclusions: The results highlighted larger utilisation of low-potency statins, a lower adherence and a milder comorbidity profile in women, the latter feasibly explaining the reduced healthcare costs compared to men.

How effective are prescriptive governance tools? Results from the application of AIFA notes

Giaele Moretti — 2024-06-10

Introduction: Prescription appropriateness is crucial for healthcare, balancing scientific evidence, optimal benefit/risk ratios and cost-effectiveness in alignment with the National Health System (NHS) sustainability. In Italy, various governance tools, including Notes AIFA, regulate drug reimbursements. This research aims to evaluate the impact of the introduction of Notes AIFA in curbing consumption and expenditures and assessing their lasting effects. We evaluate the effect generated by the Notes in terms of prescriptive appropriateness by assessing their effect on reducing overprescribing phenomena for drugs covered by the Notes. Note 96, focused on the prevention and treatment of vitamin D deficiency in adults, is used as a case study to evaluate the short- and long-term effectiveness of these tools on prescribing behaviors.

Methods: Using a quasi-experimental approach, administrative data on pharmaceutical consumption in Tuscany over 60 months (22 pre- and 38 post-Note) were analyzed. Interrupted Time Series (ITS) analysis at regional, and local health authorities (LHAs), and primary care group practices (AFTs) was performed.

Results and conclusions: The ITS analysis showed an immediate reduction in consumption rates and spending post-Note 96. This real-world study highlights short-term effectiveness and suggests a positive long-term impact, despite recognizing a physiological increase in consumption at the regional level. The findings emphasize that ongoing continual monitoring of its effectiveness is imperative to promptly identify failures in implementation and mitigate the risk of consumption escalation, potentially reverting to pre-intervention levels.

Determining value in the treatment of activated PI3Kδ syndrome in Spain: a multicriteria decision analysis from the perspective of key stakeholders

Alicia Gil — 2024-05-22

Introduction: Activated phosphoinositide 3-kinase (PI3K)δ syndrome (APDS) is an ultra-rare inborn error of immunity (IEI) combining immunodeficiency and immune dysregulation. This study determined what represents value in APDS in Spain from a multidisciplinary perspective applying multicriteria decision analysis (MCDA) methodology.

Methods: A multidisciplinary committee of nine experts scored the evidence matrix. A specific framework for orphan drug evaluation in Spain and the weights assigned by a panel of 98 evaluators and decision-makers was used. Re-evaluation of scores was performed.

Results: APDS is considered a very severe disease with important unmet needs, including misdiagnosis and diagnostic delay. Current management is limited to treatment of symptoms with off-label use of therapies supported by limited evidence. Therapeutic benefit is partial, resulting in limited disease control. Haematopoietic stem cell transplantation (HSCT), the only potential curative alternative, is restricted to a reduced patient population and without evidence of long-term efficacy or safety. All options present a limited safety profile. Data on patients’ quality of life are lacking. APDS is associated with high pharmacological, medical and indirect costs.

Conclusions: APDS is considered a severe disease, with limited understanding by key stakeholders of how treatment success is assessed in clinical practice, the serious impact that has on patients and the associated high economic burden. This study brings to light how MCDA methodology could represent a useful tool to complement current clinical and decision-making methods used by APDS experts and evaluators.

The economic impact of 14 compassionate use programs for medicines in Italy, in the perspective of the National Health Service

Claudio Jommi — 2024-05-21

Background: Compassionate use programs (CUP) for medicines allow patients, not recruited in trials, accessing medicines before marketing approval. The evidence on the economic impact of CUP is limited to one paper that did not include the possible long-term economic impact of medicines used in CUP compared to alternative treatments, like avoided hospitalization costs. This paper aims at covering this information gap, updating and integrating the existing evidence, with a cost analysis in the perspective of the Italian National Health Service (SSN).

Methods: Data were retrieved from the Roche CUP Database, the peer-reviewed literature (e.g. published cost-effectiveness studies, if any), the gray literature (e.g. regional documents for the alternative treatment cost) and unpublished data (e.g. cost-effectiveness analysis provided for price and reimbursement negotiation for medicines in CUP).

Results: We retrieved data from 14 CUPs and 3,485 patients (70% affected by tumors) (Jan 2015-August 2022). The alternative treatment mean cost per patient ranged from € 11.1 k to € 18.8 k. The net economic benefit ranged from € 47 million to € 75 million (€ 13.5 k-€ 21.5 k per patient). Avoiding alternative treatments mostly contributes to the economic benefit. The long-term economic impact accounted for 20/30% of the net economic impact. The net economic benefit for cancer drugs ranged from € 12.6 million to € 40.0 million.

Conclusions: Despite research limitations, this paper provides additional evidence on the economic impact of CUP in Italy. This could represent the first step of a broader analysis of the economic impact of early access schemes for drugs.

Regional administrative data and their role in planning, programming and controlling at regional level

Irene Marzona — 2024-04-25

Regional administrative data may help public administrations in organizing their information, identifying problems, defining solutions and verifying results of the actions taken.

The objective of this work is to present the discussion output of the working group (GDL) “The use of regional pharmaceutical data to facilitate health planning and outcome monitoring” which was held during the Regional Pharmaceutical Policy Forum of 2023.

The GDL focused on identifying a model for planning, programming and monitoring health resources based on the data-driven approach and on the use of already existing regional administrative data, defining some gaps and developing proposals to implement this strategy. In particular, were highlighted the needs to adopt a broader perspective that considers healthcare costs as a whole (and not, specifically, oriented towards the governance of pharmaceutical assistance), to create ad-hoc training courses focused on the use of real-world data, and, similarly to some European Countries, to move towards an open access policy (accessible data) that can be useful to improve citizens’ health protection services, in compliance with the GDPR.

Heart failure and economic impact: an analysis in real clinical practice in Italy

Melania Dovizio — 2024-04-22

Introduction: Heart failure (HF) affects 1% of subjects aged 45-55 and over 10% of subjects aged ≥ 80 and in Italy represents the third leading cause of hospitalization.

Objective: To analyse the clinical and economic burden of HF in the Italian real clinical practice.

Methods: A retrospective analysis was conducted on the administrative databases of healthcare institutions for 4.2 million health-assisted residents. Between January 2012 and March 2021, patients with a hospital discharge diagnosis for HF were included. Among healthcare utilization and costs, treatments, hospitalizations, and specialist services were evaluated. The HF group was compared with a population without HF (no-HF) similar for age, sex distribution, and cardiovascular risk factors.

Results: The same number of patients with (N = 74,085) and without HF (N = 74,085) was included. A profile of cardiovascular comorbidities emerged in the HF group, mainly hypertension (88.6%), cardiovascular disease (61.3%) and diabetes (32.1%). Hospitalizations from any cause were 635.6 vs 429.8/1,000 person-year in the HF vs no-HF group. At one-year follow-up, all-cause mortality was 24.9% in HF patients and 8.4% in no-HF. Resource utilization/patient was respectively 26.8 ± 15.9 vs 17.1 ± 12.5 for medications, 0.8 ± 1.2 vs 0.3 ± 0.8 for hospitalizations, and 9.4 ± 12.6 vs 6.5 ± 9.8 for specialist services. This resource utilization resulted in significantly higher total healthcare costs in the HF group vs no-HF group (€ 5,910 vs € 3,574, p < 0.001), mainly related to hospitalizations (€ 3,702 vs € 1,958).

Conclusions: HF patients show a significantly higher clinical and economic burden than no-HF, with total healthcare costs being about 1.7 times the costs of the no-HF group.

Keywords: Cardiovascular comorbidities, Healthcare costs, Heart failure, Hospitalizations

The socioeconomic burden of adult attention-deficit/hyperactivity disorder in Spain

Maria Merino — 2024-04-05

Introduction: The symptoms of attention-deficit/hyperactivity disorder (ADHD) in adults highly interfere with function in multiple dimensions, increasing the economic burden associated with ADHD. The aim of this study was to explore the impact of ADHD in Spanish adults and estimate the associated economic burden within the healthcare, social, economic, and legal domains.

Methods: An economic model was developed from a social perspective using a bottom-up approach, based on the scientific literature and a multidisciplinary expert group.

Results: The cost incurred per diagnosed adult patient with ADHD included an annual cost of €15,652 and a one-time cost of €7,893 (3,035 M€ and 1,531 M€ for Spain, respectively). Regarding the annual cost, 50% was attributed to costs within the economic domain, of which 53% were work-absenteeism-related. Moreover, 28% was attributed to costs within the social domain, of which 74% were substance-abuse-related. Regarding the one-time cost, 52% was attributed to costs within the healthcare domain, of which approximately 50% were hospitalization-related costs. Moreover, 42% was attributed to costs within the legal domain, of which 62% were imprisonment-related costs.

Conclusions: This is the first report on the socioeconomic burden of ADHD in Spanish adults, shedding light on the large burden that adult ADHD poses on the healthcare system and society at large, as symptoms have been shown to impact almost every aspect of life. This is particularly important for undiagnosed/untreated patients with ADHD in Spain, as appropriate treatments have shown positive results in these areas and may reduce its associated socioeconomic burden.

Regional Formularies in Italy: current state and future perspectives

Alberto Bortolami — 2024-03-08

Regional Formularies (RF) are considered part of pharmaceutical policies implemented by regions to govern access of medicines to regional market. However, they have been actually challenged, because of their presumed impact on differences of patient’s access across the regions. The paper aimed at investigating the current status of RF and Regional Therapeutic Committees (CTR) and at suggesting/recommending possible reforms.

The current status was investigated through a questionnaire administered to the regional pharmaceutical departments. Recommendations were retrieved from a multi-stakeholder work group carried out on 30-31 March 2023, embedded into a Forum focused on the regional pharmaceutical policies.

Nineteen out of twenty-one regions responded to the survey: 12 use RF, mainly managed by the CTR; the RF frequency of update and the time needed for drugs listing greatly vary across regions; pharmacists, specialists and general practitioners are always represented in CTR, whereas other healthcare professionals and experts are more rarely involved; in 3 regions the CTR does not publish any RF update; the CTR mainly rely, to take decisions, on the dimension of the target population, the cost of therapy compared to alternative treatments and the impact on pharmaceutical expenditure.

The working group recommended to overcome the RFs, if they are merely considered a list of available drugs at regional level, focusing CTR activities to ensure market access and to govern the prescribing behaviour, and strengthening/anticipating the flow of information from the Italian Medicines Agency (AIFA) to the regions, to enable a more efficient approach to local access to drugs.

Cost per Number Needed to Treat (NNT) for upadacitinib in the treatment of bio-exposed patients with moderately-severely active ulcerative rectocolitis

Flavio Caprioli — 2024-03-07

Background: Only limited information is available on cost efficacy of the advanced therapies for the treatment of ulcerative rectocolitis. We evaluated the efficacy and the treatment costs of these advanced therapies in the treatment of bio-exposed (primary failure to a biological agent) patients with moderately to severely active ulcerative rectocolitis.

Methods: Data from a previous network meta-analysis (NMA) in the treatment of bio-exposed patients with moderately to severely active ulcerative rectocolitis was used. The analysis involved three therapies approved in Italy for the treatment of moderately to severely active ulcerative rectocolitis: upadacitinib (UPA), ustekinumab (UST) and vedolizumab (VDZ). According to the NMA results, the analysis was conducted considering two different timepoints: induction and maintenance. The pharmacoeconomic comparison between advanced therapies was carried out to estimate the respective cost for the NNT (Number Needed to Treat) compared to placebo using the clinical response (CRes) for the induction and clinical remission (CRem) and endoscopic improvement (EI) for the maintenance. Only the ex-factory price of each advanced therapy was considered. The cost per NNT was adopted as a cost-effectiveness indicator.

Results: Independently of the timepoint considered (induction or maintenance) and the clinical (CRem and CRes) or endoscopic endpoint (EI) evaluated, UPA had always the lower cost per NNT than UST and VDZ. For example, considering the induction and the CRes, the cost per NNT for upadacitinib (45 mg) was € 7,862.07 compared to € 30,459.38 for ustekinumab (6 mg/kg) and to € 67,868.00 for vedolizumab.

Conclusion: Upadacitinib is a cost-effective therapeutic option compared to ustekinumab and vedolizumab in the treatment of bio-exposed patients with moderately to severely active ulcerative rectocolitis.

Cost per NNT for upadacitinib in the treatment of patients with moderate-severe atopic dermatitis in Italy

Andrea Chiricozzi — 2024-02-16

Background: Targeted systemic therapies, including abrocitinib, baricitinib, dupilumab, tralokinumab and upadacitinib, are new treatments for moderate to severe atopic dermatitis (AD). We evaluated the efficacy and the costs of these targeted systemic therapies in the treatment of adult patients with moderate to severe AD.

Methods: The clinical efficacy was assessed considering the results of a previous network meta-analysis (NMA). The analysis involved five therapies approved in Italy for the treatment of moderate to severe AD: abrocitinib (ABR), baricitinib (BAR), dupilumab (DUP), tralokinumab (TRA) and upadacitinib (UPA). According to the NMA, the cost of the treatment was based on the number of administrations dispensed at 16 weeks and the clinical efficacy was measured by the number needed to treat (NNT) compared to placebo using the improvement ≥ 75% (EASI-75) or ≥ 90 (EASI-90) from baseline of the eczema area and severity index (EASI). Only the ex-factory price of the targeted systemic therapies was considered. The cost per NNT was adopted as a cost-effectiveness indicator.

Results: At 16 weeks, the cost per NNT based on EASI-75 was lower for UPA 15 mg (€ 6,384.00) compared to BAR 4 mg (€ 11,619.73) and 2 mg (€ 14,524.66), ABR 100 mg (€ 16,265.22), DUP 300 mg (€ 16,115.04) and TRA 300 mg (€ 31,710.24). UPA 15 (€ 8,512.00) also showed the lower cost per NNT based on EASI-90 at 16 weeks compared to BAR 4 mg (€ 14,788.75) and 2 mg (€ 20,862.70), ABR 100 mg (€ 25,922.69), DUP 300 mg (€ 25,992.00) and TRA 300 mg (€ 41,067.36).

Conclusions: The findings show that upadacitinib is the most cost-effective option (cost per NNT) for the treatment of moderate to severe atopic dermatitis.

Clinical and economic burden of peristomal skin complications: Activity Based Costing analysis

Agostino Fortunato — 2024-01-23

Introduction: An ostomy is a procedure in which an opening is made in the abdominal wall to establish a communication between the intestinal or urinary system and the external environment. Peristomal skin complications pose a constant challenge for the majority of individuals with a stoma, as they represent the most common postoperative complication. The aim of this study was to develop an economic evaluation model for assessing the costs associated with peristomal skin complications.

Methods: In order to identify these costs, a survey was conducted in collaboration with the Coloplast Ostomy Forum group with the aim of mapping and documenting the timelines and all activities in the management of these complications. The data obtained from the survey were subsequently analyzed using the Activity Based Costing methodology.

Results: The results of this analysis clearly indicate that the expenditure for initial visits is higher compared to subsequent ones, and that severe peristomal skin complications impose a greater economic burden than less severe complications. Specifically, the average total cost for managing severe peristomal skin complications amounts to € 104.6.

Conclusion: This kind of analysis could provide support to decision-makers in dealing with a more accurate estimate of costs related to healthcare processes, aiming to implement rates able to “cover” the overall cost of certain healthcare activities. Specifically, there is currently no specific rate aimed at defining the value associated with the care and management of this type of complication, so this study confirms that this is an economic challenge that the National Health Service must address.

Italian healthcare resource consumption for patients on hemodialysis treated for chronic kidney disease-associated pruritus (CKD-aP)

Silvia Calabria — 2024-01-15

Background: Chronic kidney disease-associated pruritus (CKD-aP) affects patients on hemodialysis. This study identified hemodialysis patients presumably affected or not affected by CKD-aP and integrated healthcare costs, from the perspective of the Italian administrative healthcare data.

Methods: Through cross-linkage of Italian administrative healthcare data collected between 2015 and 2017 (accrual period) in the database of Fondazione ReS (Ricerca e Salute), patients undergoing in-hospital/outpatient hemodialysis were selected. Cohorts with and without CKD-aP were created based on the presence/absence of CKD-aP-related treatment (according to common clinical practice and guidelines) supplies and assessed in terms of CKD-aP-related treatments and mean healthcare costs per capita paid by the Italian National Health Service (INHS).

Results: Of 1,239 people on hemodialysis for ≥2 years, CKD-aP affected 218 patients. Patients with CKD-aP were older and with more comorbidities. During the follow-up year, on average, the INHS spent €37,065 per case, €31,286 per control and € 35,988 per non-CKD-aP subject. High-efficiency dialytic therapies performed to people on hemodialysis with CKD-aP largely weighed on the overall mean annual cost.

Conclusions: This real-world study identified patients on chronic hemodialysis potentially treated for CKD-aP. Interestingly, high-efficiency dialysis seems the most frequent and expensive choice for the treatment of CKD-aP. The discovery of appropriate and effective treatments for this condition might offer cost offsets.

A pharmacoeconomic analysis from Italian guidelines for the management of prolactinomas

Michele Basile — 2024-01-09

Background: Prolactinoma, the most common pituitary adenoma, is usually treated with dopamine agonist (DA) therapy like cabergoline. Surgery is second-line therapy, and radiotherapy is used if surgical treatment fails or in relapsing macroprolactinoma.

Objective: This study aimed to provide economic evidence for the management of prolactinoma in Italy, using a cost-of-illness and cost-utility analysis that considered various treatment options, including cabergoline, bromocriptine, temozolomide, radiation therapy, and surgical strategies.

Methods: The researchers conducted a systematic literature review for each research question on scientific databases and surveyed a panel of experts for each therapeutic procedure’s specific drivers that contributed to its total cost.

Results: The average cost of the first year of treatment was €2,558.91 and €3,287.40 for subjects with microprolactinoma and macroprolactinoma, respectively. Follow-up costs from the second to the fifth year after initial treatment were €798.13 and €1,084.59 per year in both groups. Cabergoline had an adequate cost-utility profile, with an incremental cost-effectiveness ratio (ICER) of €3,201.15 compared to bromocriptine, based on a willingness-to-pay of €40,000 per quality-adjusted life year (QALY) in the reference economy. Endoscopic surgery was more cost-effective than cabergoline, with an ICER of €44,846.64. Considering a willingness-to-pay of €40,000/QALY, the baseline findings show cabergoline to have high cost utility and endoscopic surgery just a tad above that.

Conclusions: Due to the favorable cost-utility profile and safety of surgical treatment, pituitary surgery should be considered more frequently as the initial therapeutic approach. This management choice could lead to better outcomes and an appropriate allocation of healthcare resources.

Patient-reported outcomes in epilepsy: a case study exploring their usage and impact

Simona Lattanzi — 2024-05-03

Background: This study aimed to obtain insights from epilepsy specialists on the use of Patient-Reported Outcome (PRO) measures and how they can affect the management of people with epilepsy and healthcare resource utilization.

Methods: The heads of two referral units for people with epilepsy at one tertiary care hospital were invited to respond to a structured survey.

Results: Paper-based questionnaires and face-to-face interviews were the main modalities used to measure the quality of life of people with epilepsy. The Quality of Life in Epilepsy Inventory-31 (QOLIE-31), the Adverse Event Profile (adult centre), the Generalized Anxiety Disorder-7, Short-Form Health Survey 36, PSY-Flex, SAFA and Child Behavior Checklist (paediatric centre) were the most used scales. There was consensus about the favourable impact of PRO upon patient management, disease management and measurement of the success of a treatment. Both respondents considered the PRO as important as other main indicators like efficacy and tolerability of the treatment. Lack of time, personnel and economic resources was identified as a barrier on the use of PRO. The PRO could reduce the number of visits, exams and treatments, and increase the time spent on each patient and the number of neuropsychological, psychological and rehabilitation services. The standardized use of PRO was considered useful and the increase in human resources was considered a priority to achieve this goal.

Conclusions: Despite the heterogeneity in the actual collection of PRO, there was a uniform perception about their role to optimize the care of people with epilepsy.

Costs and benefits in patients with NYHA class III heart failure treated with CardioMEMS in Italy

Andrea Messori — 2024-05-02

Background: CardioMEMS is a device suitable for telemedicine that is currently being evaluated by the Regional Health Technology Assessment (HTA) Committee of Tuscany. Two detailed HTA reports are available in the specialized literature, the results of which need to be transferred to our regional setting. These decisions in Tuscany are made by the so-called Centro Operativo HTA.

Aim: To validate, with local cost-effectiveness data, the decision on CardioMEMS that will be made in the Tuscany region.

Methods: Two detailed international HTA reports were rearranged and adapted to our regional setting to generate a simplified analysis that could form the basis of our decision. Two willingness-to-pay (WTP) thresholds of €20,000/quality-adjusted life year (QALY) and €50,000/QALY were considered.

Results: Based on epidemiological and regulatory information, the target population in Tuscany for this device is 166 cases. The value-based price of CardioMEMS is estimated to be €4,332 and €16,662 at WTP thresholds of 20,000/QALY and 50,000/QALY, respectively. Its current price in Italy is €12,000.

Conclusion: In our region, the introduction of CardioMEMS is likely to be gradual, around 50 patients/year (or €0.60 million/year at current price). This example highlights the need to adapt the information published in the international literature to the local context in which the approval decision is made. In this context, simplified analyses are easier to apply than complex Markov models.

Early access programs for medicines: a reform proposal for the Italian National Health Service

Patrizia Popoli — 2024-06-17

The present paper illustrates a reform proposal on early access for medicines. In this proposal early access stands for patient’s access, outside of clinical trials and covered by the Italian National Health Service (Servizio Sanitario Nazionale, SSN), to a new medicine or an indication of an already approved medicine before the approval o in between the approval and the decision on price and reimbursement status. The proposal emerged from a multi-stakeholder working group within the Sixth Edition of the “Seminari di Mogliano Veneto”. The reform proposal is aimed at converting the current early access programs (mainly, the programs introduced with Laws 648/96 and 326/03) into a single program inspired by the one introduced in France in 2021. The proposal provides indications on eligibility criteria for drugs and patients, application procedure, evaluation process, economic safeguard clauses, data collection, issues derived from the circumstance that the drug/indication included into the early access program is not reimbursed afterwards and the actions to implement this program.

The role and impact of health economics in the optimization of patient care in osteoarthritis: insights from a practical example

Mickaël Hiligsmann — 2024-04-03

Osteoarthritis (OA) is a degenerative joint disease with a substantial global burden, causing chronic pain and reduced quality of life. Managing OA efficiently while maximizing healthcare resources is crucial. Health economics and health technology assessment (HTA) are central tools providing a framework to evaluate the clinical, economic, and ethical aspects of healthcare technologies and interventions. This article presents some insights into the role of health economics and the HTA process in OA management. It also illustrates an example of cost-effectiveness analysis in a specific healthcare context, on the basis of a recent clinical trial involving hyaluronic acid treatment for knee OA. While HTA offers valuable insights, it faces challenges like data availability and resource constraints. Integrating health economics into decision-making can enhance patient care and allocate resources effectively in OA and other healthcare domains.

HTA regulation: how is Italy moving?

Francesca Patarnello — 2024-03-05

Within the European evolutionary framework concerning citizens’ health, the focus shifts to the new HTA regulation, set to alter processes and influence decision-making at the individual country level regarding reimbursement and pricing. The ambitious goal of achieving faster and more uniform access will significantly reshape the evaluative model stabilized over the years, characterized by the creation of different rules and processes among member states and diverse output timelines across the countries.

The imminent adoption of a more collaborative process necessitates member countries and companies to address several steps to ensure a smooth transition without penalizing the unique aspects of individual countries or impeding real access. Italy, actively participating in European preparatory activities with AIFA, faces challenges in adapting its formal process due to AIFA’s ongoing reform since November 2022, which is not yet materialized.

National-level companies heavily depend on leadership and involvement rules from their HTA agencies, with the risk that agencies with more established engagement models with external stakeholders may present themselves on January 12, 2025, the start date of the new process for oncological and ATMP drugs, better prepared and may excel in designing scoping meetings and in formulating PICO.

Therefore, the activation of a country culture of HTA and a robust and extended “readiness” phase involving all stakeholders are desirable, along with the establishment of collaboration networks with universities and scientific societies to make valuable knowledge and qualified resources more readily available, crucial element for the delicate transition from the old to the new evaluative system.

The future of drugs distribution in the National Health System

Massimo Medaglia — 2024-01-15

The distribution of drugs reimbursed by the NHS in Italy can be summarized in three forms: direct (DD), on behalf of (DPC) and affiliated. The following document presents the results of the discussion of a multidisciplinary experts’ panel, from different professional realities in the healthcare system, on alternative methods of drugs’ distribution. It was highlighted how regional autonomy has led to extremely innovative experiences but also to a lack of homogeneity regarding the access to pharmaceutical assistance across Italy. The main recommendations developed by the experts can be summarized as follows:

To ensure decisions regarding prescription and classification, with respect to the healthcare delivery settings, with the consequent distribution model and purchasing processes, is AIFA’s responsibility.
To evaluate the reclassification of drugs from class H to class A-PHT for drugs intended to be taken at patient’s home, in cases where close monitoring by specialistic structures is not necessary.
To limit the inclusion of a drug in PHT to conditions of differential diagnostic complexity, need for recurrent patient’s referral to the healthcare facility, presence of AIFA monitoring register, settings of drugs’ administration (home hospitalization and home care).
In the field of PHT drugs, AIFA should, with the support of a multidisciplinary technical table:

Update the list periodically.
Identify the drugs on the list for which DD is preferential, leaving the others in DPC.
Evaluate the conditions to transfer some drugs to distribution under an agreement.