Introduction: Primary biliary cholangitis (PBC) is a rare, chronic, cholestatic, autoimmune, and disabling liver disease whose treatments are aimed at reducing its progression.The aim was to describe patients with PBC, their healthcare resource utilization (HCRU) and costs on the Italian National Health Service (SSN).Methods: From an Italian administrative healthcare database (~5.5 million inhabitants), called ReS Db, patients with PBC in 2021 (prevalent) were selected by specific codes and described by demographics, comorbidities, one-year HCRU, and health sector costs charged to the SSN. The 3-year treatment pattern was evaluated in a cohort of patients newly diagnosed in 2019 (incident).Results: In 2021, 1375 patients with PBC were identified (prevalence: 28.2/100,000; females: 74.2%; mean age: 64 ± 15 years). During one-year follow-up of the prevalent cohort: 73.1% received ursodeoxycholic acid (UDCA); 3.0% obeticholic acid (OCA), and 3.4% off-label drugs; 19.9% were hospitalized, mainly for cirrhosis-related conditions; 61.2% were examined by a specialist. The annual mean cost was €4422/patient; drugs for PBC, concomitant drugs, and hospitalizations accounted for 12.1%, 31.7%, and 43.6% of total cost, respectively. Among the 40 incident patients, 38 (95%) received UDCA as first-line therapy.Conclusion: The study described the real-world impact of PBC in Italy from the perspective of the SSN and highlightedthe burden and therapeutic needs of patients treated with UDCA.
Introduction: The clinical management of ostomy and urinary incontinence poses a substantial challenge forhealthcare systems and patients, as it necessitates the provision of specialized medical devices. In Italy, thesedevices are distributed through multiple distribution modalities.Methods: This study aims to update a previous Budget Impact analysis on home distribution, using real-worlddata collected via surveys and applying an ABC approach. Structured questionnaires were administered to theASL of four Italian regions, collecting data on staff involvement, operational times, and resource utilization. TheBIM analysis compared two scenarios: the current distribution scenario and a hypothetical scenario with incremental adoption of home delivery.Results: The estimated average annual personnel costs per patient were € 153 for direct distribution, € 107 forhome delivery, and € 80 for indirect distribution. The revised scenario resulted in an increased resource consumption of € 214,475,929 over three years. This increase was offset by significant cost reductions in direct(-€ 165,195,792) and indirect distribution (-€ 52,704,435), yielding a cumulative saving of € 3,424,299 over theanalysis period. Sensitivity analysis confirmed the robustness of the results with respect to the main parameters.Conclusion: The integration of real-world data significantly improves the accuracy and robustness of the BIManalysis. The results support home distribution as a cost-efficient choice for the Italian National Health Service(SSN). The evidence generated provides valuable insights for policymakers to optimize resource allocation anddistribution strategies for stoma and urinary incontinence devices.
Introduction: Type 2 diabetes mellitus (T2DM) is a common chronic disease with management, associated with cardiovascular and renal comorbidities. In January 2022, AIFA Note 100 extended prescribing authority for inno vative antidiabetic drugs (SGLT-2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors) to General Practitio ners, influencing treatment patterns and management of high-risk patients. Methods: A retrospective observational analysis used administrative data from two Local Health Authorities in Italy, comparing three cohorts: Pre-COVID (2018), COVID (2020-2021), and Post-Note 100 (February 1, 2022 to January 31, 2023). Adults (≥18 years) with at least one prescription of non-insulin glucose-lowering drugs (ATC A10B) were included. Profiles were described, focusing on acarbose, DPP-4 inhibitors, metformin, pioglitazone, SGLT-2 inhibitors, GLP-1 receptor agonists, and sulfonylureas. Clinical characteristics included comorbidities, heart failure, hypertension, and chronic kidney disease. Healthcare costs (pharmaceuticals, outpatient specialist care, and hospitalizations) were analyzed. Results: Over 140,000 subjects were included. In the Post–Note 100 phase, GLP-1 receptor agonists and SGLT-2 inhibitors increased among new users (GLP-1 receptor agonists: 1.2% to 9.3%; SGLT-2 inhibitors: 2.6% to 14.1%) and among prevalent users, with a reduction in sulfonylureas and a decline in metformin monotherapy. Among patients with ≥ 2 comorbidities, SGLT-2 inhibitors became the most prescribed class. Use rose in heart failure, while both GLP-1 receptor agonists and SGLT-2 inhibitors increased in chronic kidney disease. Conclusions: Expansion of prescribing eligibility introduced by AIFA Note 100 led to a shift toward innovative therapies, aligning prescribing with guidelines, particularly in comorbid patients. Real-world data highlight the impact and support the evaluation of long-term outcomes.
Introduction: Assess the implications of Ministerial Decree (MD) 77/2022 in Italy, which decentralizes healthcare through proximity-based models, from the perspective of key actors involved, and discuss its relevance to sustainability and value assessment. Methods: A cross-sectional survey was conducted with four stakeholder groups: pharmaceutical companies, scientific societies, Health Economics and Outcomes Research (HEOR) experts, and patient advocacy organizations (N = 162). Structured questionnaires examined awareness/knowledge, perceived implementation, perceived impact, operational feasibility, and policy alignment. Results: Over 60% of respondents recognized the strategic value of proximity care. Key barriers included administrative burden (47%), resource constraints (38%), and lack of Key Performance Indicator (KPI)-based frameworks (55%). Treatments in oncology, geriatrics, and metabolic diseases were considered most suitable for decentralized provision. Divergent perspectives emerged professional stakeholders emphasized methodological rigour and outcome monitoring, while patient organizations foregrounded equity of access, responsiveness, and patient-facing feasibility. Conclusion: MD 77/2022 opens a policy window to align decentralized care pathways with sustainability and value assessment. However, the survey did not collect empirical pricing, reimbursement, or cost-effectiveness data; therefore, any implications for pricing governance should be interpreted as conceptual and hypothesisgenerating rather than as demonstrated effects. Heterogeneous implementation and fragmented outcome measurement remain the primary barriers; a minimum viable KPI set and routine data infrastructure are prerequisites for translating perceived value into decision-relevant evidence.
Introduction:In January 2024, the Commissione Scientifica ed Economica (CSE) became the national body responsible for the integrated scientific and economic evaluation of medicines in Italy. This study provides the first systematic description of the CSE's activity during its initial operational year, focusing on procedural workload, timelines, and negotiation outcomes. Methods:All publicly available "Esiti CSE" documents published by the Italian Medicines Agency (AIFA) between April 2024 and April 2025 were manually extracted and validated. Each record included the negotiation typology (TN-1 to TN-8), outcome, and iter duration. Descriptive analyses summarised distributions, median and mean durations, deferral rates, and trends over time. Results:A total of 641 procedures (523 products, 446 INNs) generated 2,145 individual outcomes. Argomento rinviato (deferral) was the most frequent outcome (55.7% of all decisions; 51% of procedures). The average procedure involved 1.9 deferrals, and 83% experienced at least one. Mean overall duration was 269 days (median 196; IQR 133-350), with the longest timelines for TN-1 and TN-4 negotiations (298 and 322 days, respectively). Oncology (L01, L04) and metabolic agents (A10) showed the greatest variability, while antivirals (J05) recorded the longest average duration (549 days) but a lower incidence of deferral. Conclusions:The first year of CSE activity reveals a high workload, variable timelines, and frequent deferrals, reflecting the complexity of integrating scientific and economic assessment within a single body. The results provide an empirical baseline for future monitoring and underscore the need for refinement of governance arrangements and procedural transparency in AIFA's new framework.
Introduction: Follicular Lymphoma (FL) is the second most common lymphoid malignancy, with 20% of patients progressing within 24 months of first-line therapy. Chimeric antigen receptor T-cell (CAR-T) therapies have improved outcomes in relapsed or refractory FL, yet their use requires significant resources and complex care pathways. Although outpatient CAR-T programs have shown promising safety and feasibility, limited evidence exists on their organizational, economic, and ethical implications in the Italian healthcare setting. This study compares the current CAR-T pathway for FL patients with a virtual optimized scenario incorporating outpatient management in selected phases. Methods: A multidimensional framework was applied to assess differences between standard in-hospital care (Standard Pathway) across three Italian public hospitals (Genoa, Rome, Perugia) and a partially outpatient model (Efficient Pathway). Literature review and expert consultations validated existing practices and informed optimization criteria. Structured surveys provided quantitative and qualitative inputs. Economic modelling estimated three-year full costs using patient-level data, while organizational and ethical aspects were evaluated through Likert scales. Results: Efficient Pathway shifted bridging therapy, post-infusion monitoring, and follow-up to outpatient settings, reducing total costs from € 611,070 (As-Is) to € 497,421 (To-Be). Organizational benefits included increased bed capacity (average score: 4.9/6) and consumable utilization (average score: 4.3/6), while ethical gains were observed in treatment accessibility (average score: 4.3/6). Conclusions: Introducing outpatient management into CAR-T phases may provide economic, organizational, and ethical advantages when supported by clear eligibility criteria and structured monitoring. As CAR-T indications expand, pathway redesign will be essential to ensure equitable access and sustain healthcare system resources.
Introduction: Timely access to new medicines is a key dimension of health system performance. In Italy, pricing and reimbursement decisions are taken by the Italian Medicines Agency (AIFA). In 2024, a reform established the Scientific and Economic Commission (CSE), integrating the former Technical-Scientific Committee and Pricing and Reimbursement Committee into a single decision-making body. This study evaluates whether the introduction of the CSE is associated with changes in the duration of the price and reimbursement process. Methods: An observational pre-post study was conducted using publicly available AIFA regulatory data. New chemical entities and orphan medicines under negotiation type 1 reimbursed between January 2022 and January 2026 were included. Time intervals were reconstructed from official AIFA committee agendas and compared between pre-reform (CTS/CPR) and post-reform (CSE) periods. Differences were assessed using the Wilcoxon rank-sum test. Results: The sample included 71 medicines (30 pre-reform; 41 post-reform). The median duration of the evaluation and negotiation phase decreased from 195 to 119 days after the introduction of the CSE (p < 0.004). Overall time to publication also decreased but not significantly. Administrative timelines remained stable. Conclusions: The CSE was associated with a significant reduction in evaluation-negotiation timelines, suggesting improved efficiency in the phase targeted by the reform. However, no significant reduction was observed in overall timelines, indicating persistent delays in downstream administrative phases.
Introduction: In Italy, drug prices and reimbursement are managed by the Italian Medicines Agency (AIFA), but regions actually enable patient access to medicines. Our aim is to provide evidence on (i) the current management of regional pharmaceutical policies, the use of resources and time to policy completion (TPC-procurement awarding), (ii) the potential impact on resources used and TPC of an earlier-enhanced access of regions to AIFA’s data. Methods: Four regions (Veneto, Emilia-Romagna, Campania, Puglia) were selected on a purposive basis. Data on policies and resources used were retrieved from a literature review and interviews with regional officers. TPC was tracked for medicines approved for reimbursement in Italy from January 2023 to June 2024. The potential impact of an earlier-enhanced access to AIFA’s data was detected through perceptual questionnaires self-compiled by regional officers. Results: To manage regional access, the regions employ a staff of 21 Full-Time-Equivalent (FTE) persons on average, ranging from 11 to 29. The mean TPC ranges from 135 to 361. The average score of perceived impact of an earlier-enhanced AIFA’s data equals 3.3 within a range of 1-4 for both FTE and TPC. An earlier access to public information (e.g., innovativeness appraisal) is perceived as impactful on TPC. Availability of data that are currently not shared with regions may have a greater potential impact on FTE. Conclusions: A great consensus emerged on the importance of timely access to revised P&R data. Systematic early disclosure by AIFA could help to improve efficiency in resource utilization and to expedite patient access to innovative medicines.
Introduction: Human immunoglobulins are the standard of care for patients with immunodeficiencies and represent a first-line treatment for chronic inflammatory demyelinating polyneuropathy (CIDP). This study aimed to evaluate costs associated with facilitated subcutaneous (fSCIG), conventional subcutaneous (cSCIG), and intravenous (IVIG) administration of immunoglobulin in patients with primary or secondary immunodeficiency (PID and SID, respectively) and in patients with CIDP in Italy. Methods: A cost-minimization analysis from a societal perspective was developed, considering a one-year follow-up. Direct costs included acquisition and administration costs, while indirect costs were evaluated considering productivity loss due to in-hospital IVIG using a Human Capital Approach. The posology considered for immunodeficiency disorders and CIDP was obtained from observational studies and clinical trials, respectively. Subcutaneous and intravenous administration costs were obtained from published literature. Scenario analyses were conducted to test the key assumptions of the model. Results: This study indicates a potential reduction of annual societal expenditure in Italy of approximately €2,145 and €1,605 with fSCIG treatment in PID patients compared to cSCIG and IVIG, respectively. In SID patients, fSCIG would result in a reduction of societal expenditure of approximately €2,145 and €2,071 compared to cSCIG and IVIG. For CIDP patients, fSCIG treatment would result in a reduction of societal expenditure of €8,060 and €15,873 compared to cSCIG and IVIG, respectively. Conclusion: The use of fSCIG for patients with PIDs, SIDs or CIDP could lead to a reduction in the direct and indirect costs associated with the treatment of patients.
Introduction: Until 2024, Pricing and Reimbursement (P&R) requests for medicinal products in Italy were assessed by two separate bodies within AIFA: at first by the Technical Scientific Committee (CTS), then by the Pricing and Reimbursement Committee (CPR), occasionally requiring CTS re-discussion after CPR review, potentially extending the time to reimbursement (TTR). In March 2024, the Scientific and Economic Commission (CSE) replaced CTS and CPR. This study investigates the impact of CTS re-discussions on TTR, identifying common features and negotiation outcomes. Methods: We analyzed P&R procedures completed from 2016 through a proprietary IQVIA database tracking therapies approved by the European Commission. Re-discussions were defined as procedures evaluated by CTS after CPR review. Analyses included univariate statistics to evaluate average TTR differences, logistic regressions to identify factors associated with re-discussion, and Fisher’s exact tests to examine re-discussion rates by negotiation outcomes. Results: Among 474 requests, 14.98% were re-discussed. Re-discussion was associated with a significantly longer TTR (+50.41%; p<0.001). Odds of re-discussion were higher for new active substances (OR=1.94), orphan drugs (OR=1.72), and evaluation during Covid-19 (OR=2.83). Lower odds were seen for biologics, hospital-use, and solid tumor indications. Only Managed Entry Agreements were significantly associated with re-discussion among negotiation outcomes. Average TTR dropped after CSE introduction in all the subgroups that led to a significant probability of re-discussion. Conclusions: Findings suggest that integrated CSE evaluation has the potential to reduce TTR, underscoring the efficiency of an integrated approach to technical-scientific and economic-financial evaluations.
Introduction: The duration of pricing and reimbursement (P&R) negotiations is a key performance indicator for medicines agencies in universal health coverage systems. In early 2024, the Italian Medicines Agency (AIFA) underwent a major reform, including the merging of the previous Scientific-Technical Committee and Price and Reimbursement Committee into a single Scientific and Economic Committee. This study evaluates the reform’s impact on time to P&R determinations for new medicines in Italy. Methods: A time-to-event analysis was conducted on 139 new chemical entities authorized by the European Commission (EC) between February 2021 and December 2023. The primary outcome was the time from marketing authorization (MA) to publication of AIFA’s P&R determination. Kaplan-Meier curves and Cox proportional hazards models were used to compare reclassification hazards between pre- (before March 2024) and postreform groups of medicinal products, based on a fixed separation date, adjusting for antineoplastic therapeutic area and pharmaceutical company size. Four sensitivity analyses tested the robustness of the results. Results: The multivariate Cox model, adjusting for antineoplastics, products from major corporations, and orphan medicines, showed that the reform was associated with an 84% increase in reclassification hazards (HR = 1.84, 95% CI 1.20-2.82, p = 0.005). Sensitivity analyses corroborated these findings, showing even greater improvements when focusing on national evaluation timeframes (HR = 11.57 and HR = 3.91). Conclusion: The consolidation of separate committees into a unified structure, as a part of the 2024 AIFA reform, was accompanied by accelerated P&R negotiations for new medicines in Italy, demonstrating that structural optimization of health technology assessment processes may enhance system efficiency.
Introduction: Italy retains a unique wealth of information on drug usage, embodied in the OsMed Report, published since 2001 and based on data collected by the National Observatory on the Use of Medicines. The Report analyzes data on drug dispensing, pharmaceutical expenditure, and prescribing appropriateness; it monitors regional and temporal variations in drug use and identifies public health issues, promoting a more appropriate use of medicines. Methods: As part of the III Edition of the Forum on Regional Pharmaceutical Policies, titled "Ensuring equitable and consistent access to pharmaceutical care while safeguarding the sustainability of the National Health Service", a dedicated Working Group examined how Regions can apply the OsMed Report to share strategies to improve therapeutic appropriateness. Results: The discussion emphasized the need for more efficient management of health data and a greater interoperability between information systems to enhance institutional responsiveness. Additionally, the Group explored the development of indicators linking pharmaceutical consumption to clinical outcomes, which could support regional planning through predictive and up to date tools. Conclusion: The Working Group highlighted the strengths and weaknesses of the OsMed Report, proposing solutions to make it more accessible and useful at the regional level, to promote therapeutic adherence and to improve the transparency of drug access timelines.
Introduction: In January 2022, Italy fully implemented EU Regulation No. 536/2014, revolutionizing the national framework for clinical research on medicinal products. This marked a critical shift for non-profit sponsors, who are now required to align with high-quality standards and ICH-GCP guidelines. Understanding their level of compliance is essential to identify systemic barriers and areas needing support. Methods: In March 2024, a 50-item anonymous pilot survey was distributed via social media to assess the operational and regulatory compliance of non-profit sponsors managing clinical trials in Italy. The survey focused on three domains: data management, risk assessment, and monitoring practices. Responses were collected from 32 non-profit sponsors. Results: The findings revealed substantial compliance gaps. Approximately 91% (n = 29) of respondents reported they rarely or never prepare core GCP-required documents, including Data Management Plans and Statistical Analysis Plans. Only 25% (n = 8) routinely conduct risk assessments before protocol drafting. Monitoring visits, either remote or on-site, were performed by 63% (n = 20) of sponsors. Among those not conducting on-site monitoring (n = 14), the primary constraints reported were staff shortages (29%, n = 4) and financial limitations (57%, n = 8). Alarmingly, within this same subgroup, 29% (n = 4) believed that on-site monitoring was unnecessary, despite regulatory mandates. This attitude extended to remote monitoring activities as well. Conclusions: The survey highlights major challenges faced by non-profit sponsors in meeting regulatory expectations. Limited resources and a lack of trained personnel significantly impair compliance with GCP standards. To ensure research integrity and patient safety, targeted support strategies and policy interventions are urgently needed to empower non-profit research in adapting to the evolving regulatory landscape.
Introduction: Chronic spontaneous urticaria (CSU) is a debilitating dermatological disease. The study aimed to estimate the indirect costs and out-of-pocket expenses incurred by CSU patients in Italy. Methods: The economic model was based on data collected through a survey conducted among patients and caregivers with the support of the Association for the Research and Cure of Urticaria (ARCO). Disease severity was classified into three categories: mild, moderate and severe. Indirect costs were estimated using the human capital approach. Out-of-pocket expenses were estimated in terms of direct healthcare costs borne by the patient and direct non-healthcare costs. Results: Data were analyzed for 122 patients; 7% of these reported mild CSU, 16% moderate and 78% severe. The average age was 46.8 years, with an average age at diagnosis of 38.2 years. Overall, 50% of employed patients lost workdays due to CSU, and 63.3% reported reduced productivity at work; 45.1% of patients received caregiver support, with 37.9% of employed caregivers reporting workdays lost. The economic model estimated an average annual indirect cost per patient with CSU of €4,281, mainly due to presenteeism (59%). Indirect costs increase with the severity of the disease. Average annual out-of-pocket expenses was €502.7 per patient. Conclusions: The study conducted based on data directly reported by patients could contribute to a better understanding of CSU, thereby promoting a more efficient approach to the care and support of patients and their families.
The rapid evolution of artificial intelligence (AI) in the pharmaceutical and medical device (MD) sectors has prompted interest in its potential role in supporting health technology assessment (HTA). This editorial presents an innovative project aimed at facilitating and expanding HTA activities for high-risk MDs (Class IIb-III) in Italy, where structured HTA processes for MDs are inconsistently implemented. The project centers on a freely accessible AI-based web tool designed to generate preliminary mini-HTA reports. The tool operates through two steps: users provide essential device information via an online form, and ChatGPT produces a structured draft report, including PICO statements, coverage of the nine EUnetHTA domains, and a preliminary summary of relevant PubMed evidence. Although these AI-generated reports are imperfect and require expert verification and refinement, they offer substantial practical advantages by reducing the initial workload and enabling rapid production of a first draft-within minutes rather than hours. The project includes detailed operational instructions and real application examples, such as an artificial iris device, presented in supplementary appendices. Future developments include the release of an English-language version to support broader international use. While AI cannot replace expert judgment, the editorial highlights its value as an accelerative tool that can streamline early HTA steps and promote more systematic evaluation of MDs across Italian regions. Continued iterative use is expected to improve system performance and enhance integration into HTA workflows.
Multicriteria and economic evaluations: toward a proposal for a new framework for drug pricing in Italy Introduction: The drug pricing and reimbursement process in Italy lacks a structured and shared framework to translate therapeutic value into consistent economic criteria, especially in a regulatory context characterized by spending caps and increasing pressure on access to innovations. The present work proposes a valuation model capable of combining methodological rigor and operational flexibility. Methods: A qualitative analysis was conducted based on the activities of the multidisciplinary Working Group, which compared international models (e.g., cost-effectiveness vs. multicriteria) to outline a pragmatic framework, adaptable to the Italian context. The framework validation was done through SWOT-analysis. Results: The framework is characterized by a modular structure, integrating clinical, economic and organizational components. The cost-effectiveness model was indicated as preferred to ensure consistency and transparency, while multicriteria remains useful in complex cases. The framework adapts to special contexts (e.g., orphan drugs) by providing more flexibility in ICER thresholds and the use of price-volume trade-off logic. The SWOT-analysis revealed strengths in the clear and shared nature of the rules and in reducing the risk of discretion; weaknesses include difficulty in defining thresholds and interpreting exceptions. Opportunities are in stakeholder involvement and in the possibility of faster and more standardized reporting. Major threats are related to limitations in technical expertise and possible resistance to accepting rules in exceptional cases. Conclusions: The proposed model represents a step toward a structured assessment of the value of medicines in Italy. Its adoption may promote equity, efficiency and sustainability, although requiring systemic and regulatory investment to ensure its viability.
