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.

L’intelligenza artificiale (IA) sta trasformando il sistema sanitario a una velocità senza precedenti, toccando la cura dei pazienti, l’organizzazione dei servizi e la gestione autonoma della salute da parte dei cittadini. Il JAMA Summit sull’IA ha delineato la complessità dell’ecosistema che si sta configurando, le criticità dei processi di valutazione e regolazione e la necessità di costruire infrastrutture di governance capaci di coinvolgere tutti gli attori. A queste sfide si aggiunge la questione della sostenibilità ambientale dello sviluppo tecnologico, segnalata tanto dalla ricerca scientifica quanto dall’enciclica papale “Magnifica humanitas”. La risposta a queste sfide richiede non solo nuovi strumenti tecnici e normativi, ma un ripensamento del modello di governance dell’IA che tuteli i diritti dei cittadini e valorizzi i principi dell’equità e della solidarietà.

'Ri-Medi' is a pilot project implementation of a medication review and deprescribing (MRDP) service in the primary care setting, involving two health districts of the Local Health Authority Roma 1 (Rome, Italy). General practitioners (GPs) are supported in this activity by a multidisciplinary team consisting of epidemiologists, pharmacists, statisticians, pharmacologists, geriatricians, internists, and healthcare managers. Together with GPs, the team chooses specific therapeutic focuses for which updated evidence-based information and indications on the target population are provided. The focus is on the elderly population in hyper-polypharmacy (10+ drugs). For the pilot phase, the therapeutic focus was on potentially inappropriate statin use in primary prevention in patients aged 80+ years. For each GP, the number of patients at risk was estimated. In addition, a survey among a sample of voluntary GPs was launched to investigate their interest in participating in this activity, to collect potential critical issues and impressions, and to identify areas of interest for future MRDP campaigns of interest.

INTRODUCTION:This study evaluated the safety of influenza vaccines in a large and representative population during the 2021/2022 campaign in Italy using a Self-Controlled Case Series (SCCS) design using regional health data registries. METHODS:This multiregional study used healthcare data to assess pre-specified potential adverse outcomes after flu vaccination during the 2021/2022 season. Participants were individuals aged 6 months or older, vaccinated or not, admitted to emergency care or hospital for at least one of the incident outcomes of interest. Risk periods were specifically defined for each outcome and compared to reference periods. The Self-Controlled Case Series design modified for event-dependent exposures was used, estimating relative incidences and excess cases by age, sex, dose, and adjusting for calendar time. RESULTS:No increased risks were observed for most of the study outcomes. An increased risk of thrombocytopenia (RI = 1.90; 95% CI: 1.00-3.61) and optic nerve neuritis (RI = 5.22; 95% CI: 1.31-20.79) was detected within 42 days after vaccination in individuals under 60 years. Sensitivity and ancillary analyses supported these findings. CONCLUSIONS:These findings confirm the overall safety of influenza vaccines during the 2021/2022 campaign, with no evidence of increased risk for most of the pre-specified adverse outcomes. The increased risks observed for thrombocytopenia and optic neuritis need further research.

The CAR-T therapies are characterized by high clinical, organizational, and economic complexity, requiring the adoption of dedicated governance models capable of ensuring equitable access, appropriateness, and sustainability. In this context, the Lazio Region has developed a regional network for the management of CAR-T therapies based on a multidisciplinary steering committee, a network of hospital centers, an informative platform, and a system for planning needs and assessing appropriateness. The system is based on the Real-World Data and a Horizon Scanning approach for the continuous updating of therapeutic indications. This experience represents an example of sustainable and replicable governance for the management of advanced therapies at the regional level.

Artificial intelligence (AI) is transforming healthcare at an unprecedented pace, affecting patient care, service organization, and citizens' autonomous health management. JAMA summit on AI outlined the complexity of the emerging ecosystem, the critical issues in evaluation and regulatory processes, and the need to build governance infrastructures capable of involving all stakeholders equitably. Added to these challenges is the environmental sustainability of technological development, highlighted by both scientific research and the papal encyclical "Magnifica humanitas". Addressing these challenges requires not only new technical and regulatory tools, but a rethinking of the AI governance model that protects citizens' rights and upholds the principles of equity and solidarity.

PURPOSE:Individuals with gender dysphoria (GD) experience discomfort or distress related to gender incongruence. Management often requires pharmacological support for hormonal and psychological needs. This study aimed to identify a cohort of GD patients in the Lazio Region and analyze their medication use compared with the general population. METHODS:Using regional health information systems, we identified individuals with incident hospitalizations for GD between 2011 and 2021. We assessed medication use in the year following discharge and compared it with an age- and sex-matched population sample (1:10 ratio). We calculated the proportion of individuals with at least one dispensed prescription in selected therapeutic classes, with 95% confidence intervals. RESULTS:We identified 365 individuals with GD (median age 26 years), of whom 52.9% were assigned male at birth (AMAB) and 47.1% were assigned female at birth (AFAB). Within one year, 72.1% (67.5%-76.7%) of GD individuals received at least one medication, compared to 43.1% (41.5%-44.7%) in the general population. Medicine use was higher among AMAB (83.9%) than AFAB (58.7%). The most prescribed drug classes were anti-infectives (35%), sex hormones (35%), gastrointestinal/metabolic agents (28%), and nervous system drugs (18%). Patterns differed by sex assigned at birth: estrogens, anti-androgens, and vitamins were common in AMAB, while acid-related disorder drugs, psychotropics, and testosterone were more frequent in AFAB. CONCLUSIONS:GD patients showed higher medication use than the general population, with distinct patterns by sex assigned at birth. These findings highlight the importance of monitoring and evaluating long-term safety of pharmacological therapies.

The importance of assessing end-of-life (EoL) care has grown due to increased life expectancy and chronic disease prevalence. Despite awareness of holistic care, cancer patients often receive aggressive treatments that may reflect disparities influenced by socioeconomic factors. This study investigates EoL care among cancer patients in Italy, focusing on the impact of socioeconomic position (SEP). A retrospective observational study was conducted using Italian health databases, focusing on cancer patients aged 35 years and older who died between 2015 and 2019 in Lazio, Italy. SEP was assessed using educational attainment and a composite deprivation indicator at the census-section level. EoL care intensity was measured using hospitalization rates, emergency department visits, medication use, and place of death. Logistic regression models [OR (95% CI)] were used to explore socioeconomic associations with care intensity. The study included 84 936 subjects, predominantly aged over 75, with lung, colorectal, and breast cancers being the most common. During the last month of life, individuals with middle to higher educational levels (upper-middle, university degrees) had increased risks of hospitalization (OR 1.06; 95% CI: 1.02-1.10; OR 1.09; 95% CI: 1.03-1.15), anti-neoplastic therapies (OR 1.29; 95% CI: 1.21-1.38; OR 1.48; 95% CI: 1.36-1.61), and in-hospital death (OR 1.08; 95% CI: 1.03-1.12; OR 1.16; 95% CI: 1.10-1.23) and lower risks of ED admissions (OR 0.91; 95% CI: 0.87-0.94; OR 0.76; 95% CI: 0.71-0.80) and opioid therapy (OR 0.90; 95% CI: 0.86-0.94; OR 0.87; 95% CI: 0.82-0.92). Similar results were observed when using the area-based SEP indicator. Socioeconomic differences influence EoL care pathways for patients with cancer in Italy. These findings suggest complex interactions between socioeconomic factors and care preferences, highlighting the need for tailored and equitable EoL care strategies.

Exposure to antibiotics during pregnancy is frequent, despite the limited evidence derived from clinical trials. Drug utilization studies could improve knowledge on utilization of these medications during this critical period. In this context, the present study aimed to describe antibiotic exposure during pregnancy in Italy at both national and regional levels. This retrospective population-based study involved a cohort of women who gave birth from 2016 to 2018 and were residents of one of the following Italian regions: Lombardy, Veneto, Emilia-Romagna, Tuscany, Umbria, Lazio, Apulia or Sardinia. A series of sociodemographic and clinical characteristics were retrieved from regional healthcare databases. The prevalence of the use of antibiotics was estimated in nine trimesters, which were divided into three different periods: pre- pregnancy (-III, -II, -I) during pregnancy (I, II, III) and post-pregnancy (+ I, + II, + III). Analyses were stratified by region and by prenatal invasive diagnostic performed. A total of 449,012 women were included in the study, of whom more than 37

The respiratory syncytial virus causes numerous respiratory infections in children, with particularly severe manifestations during the first months of life, especially in premature infants or those with pre-existing clinical conditions.In Italy, the introduction of nirsevimab, a monoclonal antibody that is more practical and potentially usable in a broader population compared to the previous palivizumab, has highlighted several critical issues in the management of the prevention system. Initially, the manufacturer proposed the drug under category C, making it fully paid by patients. Subsequently, the company began direct negotiations with regional authorities, which independently planned the administration of the drug at no cost to patients, adopting differing and inconsistent approaches to preventive immunoprophylaxis programmes.Difficulties worsened when a statement from the Italian Ministry of Health clarified that regions undergoing financial recovery plans could not guarantee the administration of nirsevimab, as the treatment was excluded from the essential levels of care. The public and media uproar surrounding this exclusion prompted institutions to find a rapid solution. A national agreement was reached, allocating funds for an immunization campaign covering approximately 75% of newborns, corresponding to the availability guaranteed by the manufacturer. Additionally, a solidarity distribution mechanism was introduced, allowing up to 20% of doses to be shared among regions to protect the most vulnerable individuals.Despite the campaign started with the onset of the epidemic season, challenges persist in organizing procurement processes and managing immunoprophylaxis operations, resulting in significant disparities in implementation across regions.The nirsevimab case underscores the urgency of a nationally coordinated and shared strategy among central institutions, regional authorities, and other stakeholders to ensure equity and effectiveness in prevention policies, especially in light of upcoming regional autonomies.

Secondary hyperparathyroidism (SHP) is a clinically significant complication commonly present in chronic renal disease, especially in patients on haemodialysis. Pharmacological therapy aims to reduce the level of parathyroid hormone (PTH). Among specific treatments, the long-acting calcimimetic etelcalcetide was authorised in Italy a few years ago based on clinical trial results. However, real-world evidence of its efficacy remains limited. This study, founded by the Italian Medicines Agency (Pharmacovigilance call 2012–14), aims to perform a comparative evaluation of SHP control with the use of the two calcimimetics etelcalcetide and cinacalcet in patients on chronic haemodialysis in a real-world setting. A cohort of new users of cinacalcet and etelcalcetide from the Lazio Regional Dialysis and Transplantation Registry, covering the years 2018–2020, was enrolled. Study endpoints were retrieved through an ad hoc survey in regional dialysis centres. Indicators of SHP control were serum levels of PTH, phosphorus and calcium, which were evaluated by comparing the proportions of patients at target and mean blood levels at baseline, 12 and 24 months of observation. Overall, 652 haemodialytic patients were enrolled, 59% males and a mean age of 64 years. The majority of patients (500) began treatment with etelcalcetide. In both treatment groups, serum PTH improved over time, as evidenced by an increased proportions of patients achieving the therapeutic target (etelcalcetide from 37.8 at baseline to 59.3% at 24 months; cinacalcet from 39.5 to 63.3%) and a significant decrease of PTH blood levels (etelcalcetide from 605.2 to 372.9 pg/mL; cinacalcet from 577.9 to 285.1 pg/mL). Serum phosphorus levels also showed improvements over time, with more patients reaching target levels (etelcalcetide from 23.0 to 36.0%; cinacalcet from 19.1 to 26.7%). however mean blood levels decreased in cinacalcet users only. Results for serum calcium levels were less promising, with no change over time in the proportion of cinacalcet users reaching target levels, while etelcalcetide users saw a decrease. Mean calcium levels remained stable across both treatment groups. The present study shows improvements in SHP control in both treatment groups with negligible differences between the two. Along with previous findings of a mortality reduction in patients treated with etelcalcetide with respect to cinacalcet, with a borderline statistical significance, this study confirms the efficacy and safety of etelcalcetide in SHP treatment in patients in haemodialysis.

BACKGROUND AND PURPOSE:The purpose was to describe the use patterns of pharmacological and non-pharmacological therapies and investigate potential determinants of riluzole use in patients newly diagnosed with amyotrophic lateral sclerosis (ALS) in three Italian regions. METHODS:Amyotrophic lateral sclerosis patients were selected from administrative healthcare databases of Latium, Tuscany and Umbria from 1 January 2014 to 31 December 2019 based on hospital- and disease-specific co-payment exemption data. The first trace of ALS was considered the index date. Incident ALS cases were those without a trace of ALS during the 3-year look back. Patients were described in terms of demographics, clinical characteristics and drug use at baseline, and were classified into four categories based on riluzole use in the 2 years before and 1 year after the index date: prevalent, incident, former users and non-users. Use of symptomatic pharmacological and non-pharmacological therapies was described across these categories during 12 months after the index date. Determinants of riluzole use were also investigated. RESULTS AND CONCLUSIONS:A total of 1636 ALS incident subjects were detected in the three regions, mainly aged 65-74 years. Patients were generally fragile with a high prevalence of comorbidities at baseline. Riluzole was used by 27.4% of the overall study cohort at baseline and steeply increased in the first year after the index date differently between regions (Latium 61.2%, Tuscany 85.0%, Umbria 76.5%), with about half of the subjects being incident users. In the 12 months after the index date, also symptomatic therapies increased, in riluzole users and non-users. Determinants analysis showed that higher patient severity and complexity were associated with a lower likelihood of being treated with riluzole.

CAR-T therapies are a form of innovative and personalised immunotherapy in the field of onco-haematology. Diffuse large B-cell lymphoma (DLBCL) is a very aggressive form of non-Hodgkin's lymphoma (NHL) for which CAR-T therapies are approved as 3rd-line and more recently (from 11/11/2023), as 2nd-line for patients who relapse within 12 months after 1st-line chemo-immunotherapy. This study was conducted to estimate the eligible DLBCL population for CAR-T therapies in 2024 in Lazio region. Starting with a cohort of DLBCL patients from a previous work, a series of proportions were first obtained applying the eligibility criteria for CAR-T, and then applied to the annual incident cases of NHL in Lazio region. From 1,353 NHL cases, 392 (29%) were considered DLBCL of which 82% (322) received first line chemo-immunotherapy. They were then divided into two groups: with relapse ≤12 months (Group 1) and with relapse >12 months (Group 2). Fifty percent of Group 1 (46 cases) and part of those not eligible to ASCT (35%=16 cases) constitute the eligible population for CAR-T therapy as 2nd-line. From the 29 cases of Group 2, were calculated the proportions of CAR-T eligible patients among those not eligible for ASCT (35%=5 cases) and those who did not respond to salvage chemotherapy (65%=4 cases) and with post-transplant relapse (39%=3 cases). A total of 74 DLBCL patients were found to be eligible for CAR-T therapies. This study demonstrates that the use of Real World Data is a valuable tool in defining the target population for new therapeutic indications.

Background: In the context of a comparative study of efficacy and safety of drugs used in rare neuromuscular and neurodegenerative diseases (CAESAR—call AIFA_FV_2012-13-14), we assessed the use patterns of drugs indicated for myasthenia gravis (MG). Methods: A retrospective cohort study was conducted based on administrative healthcare data. For a cohort of MG patients, prevalent and incident use of pyridostigmine (Py) and other indicated drugs in the first year after case identification was evaluated. Prevalent combined use of major therapies (azathioprine (Az), prednisone (Pr), vitamin D (Vd)) stratified by Py use was assessed, and a comparison between therapies at the time of MG identification and during the first year of follow-up was performed. Results: We included 2369 MG patients between 2013 and 2019. Among them, prevalent and incident Py users were 38.4% and 22.0%, respectively. In the first year of follow-up, the use of Pr was observed in 74.5% of Py prevalent users and in 82.0% of Py incident users, respectively; the use of Az was observed in 24.9% and 23.0%, respectively; and the use of Vd was observed in 53.3% and 48.2%, respectively. Among 910 Py prevalent users, 13.1% also used Az, Pr, and Vd, while 15.3% used none of these. Among 938 non-Py users, 2.7% used Az, Pr, and Vd, while 53.8% used none of these. During the first year, an increase in combined therapies was evident in incident Py users. Conclusions: Our results suggest that, for some MG patients, there may be a need for treatments that combine a rapid onset of benefit with long-term and consistent disease control. These issues may be addressed by the new treatments currently being developed. To date, more studies are needed to address the heterogeneity, quality, and generalizability of the existing data and to evaluate patterns of use, efficacy, and safety of new or emerging therapies for MG.

OBJECTIVES:To investigate the use of maintenance immunosuppressive treatments following liver transplantation and to compare their risk-benefit profiles in clinical practice. DESIGN:Retrospective multicentrer cohort study. SETTING:Four Italian regions (Lombardy, Veneto, Lazio, Sardinia). METHODS:Data were integrated from the national transplant information system and administrative claims data from four Italian regions. All adults who underwent incident liver transplantation between 2009 and 2019 were identified and categorised into two groups: cirrhosis or hepatocellular carcinoma (HCC). The trend of immunosuppressive treatment over years was analysed, and their effectiveness/safety profiles were compared using multivariate Cox models (HR; 95% CI). MAIN OUTCOME MEASURES:Mortality, transplant reject/graft failure, incidence of severe infections, cancer, diabetes, major adverse cardiovascular events and lipid-modifying agents use. RESULTS:The study comprised 750 subjects in the cirrhosis cohort and 1159 in the HCC cohort. Over the study years, there was a decline in the use of cyclosporine-CsA, while combination therapy involving tacrolimus with other drugs increased compared with monotherapy. Overall, tacrolimus monotherapy use was slightly over 40% in both groups, followed by tacrolimus+mycophenolate (39.5%-cirrhosis; 30.6%-HCC) and tacrolimus+molecular target of rapamycin inhibitors (mTORi) (8.5%-cirrhosis; 13.3%-HCC). No significant differences emerged in risk-benefit profile of different tacrolimus-based therapies, except for a higher risk of mortality in cirrhosis subjects under tacrolimus monotherapy compared with tacrolimus+mycophenolate (HR: 2.07; 1.17 to 3.65). CONCLUSIONS:The study highlights a shift over time in postliver transplant therapeutic patterns, favouring the use of tacrolimus in combination with mycophenolate or mTORi, rather than monotherapy. Moreover, a potential association between tacrolimus monotherapy and increased mortality in the cirrhosis cohort was identified. Further research is warranted to investigate these findings more deeply and to optimise treatment strategies for liver transplant recipients.

BACKGROUND:Monitoring biologic drug therapy during pregnancy in women with immune-mediated inflammatory diseases (IMIDs) is crucial to ensure treatments align with evidence-based practices. RESEARCH DESIGN AND METHODS:A retrospective cohort study based on healthcare claims data from eight Italian regions was conducted, analyzing deliveries between 2009 and 2021. The study included women receiving biologic drugs within nine months before their last menstruation. Exposures to biologics, conventional disease-modifying anti-rheumatic drugs (DMARDs) and symptom-relieving medications were assessed in the trimesters (T) before, during and after pregnancy. Factors influencing biologic treatment persistence during pregnancy were analyzed. RESULTS:A cohort of 1,763 deliveries was considered. Biologic drugs were prescribed for rheumatic (33.6%), dermatological (32.6%), and gastrointestinal diseases (28.4%). Biologic use declined during pregnancy (TI = 37.3%; TII = 17.6%; TIII = 11.3%), increasing again postpartum. During pregnancy, there was increased use of symptom-relieving medications for rheumatic diseases and DMARDs for gastrointestinal diseases. Factors associated with continued biologic treatment included being older than 35 years and the region of delivery. CONCLUSIONS:This study found a decrease in biologics drug use during pregnancy and highlights the necessity for personalized therapeutic approaches. Geographic variations in biologic drug use emphasize the need for educational initiatives about the risk-benefit profiles of these therapies during pregnancy.

La terapia immunosoppressiva post-trapianto di organo solido comprende l’assunzione di tacrolimus (Tac) o ciclosporina (CsA), con antimetaboliti (Antim) o inibitori del segnale di proliferazione (mTORi), con/senza prednisonici. È stata condotta una survey con l’obiettivo di indagare l’esperienza clinica riguardo l’uso, il profilo di efficacia e sicurezza e i determinanti di scelta delle terapie immunosoppressive di mantenimento. Il questionario è stato inviato a operatori di 45 centri trapianto italiani (rene - R, fegato - F, cuore - C, polmone - P). Sono state ottenute 71 risposte, provenienti da 15 regioni italiane. La terapia di prima scelta indicata è stata Tac + Antim, a eccezione del trapianto di fegato in cui è risultata Tac in monoterapia. Secondo il 44,1% dei rispondenti la terapia di prima scelta risulta cambiata negli ultimi 15 anni: la CsA è stata sostituita da Tac e vi è stato un maggiore ricorso a mTORi. Per quanto riguarda i determinanti della terapia indice, la scelta degli schemi da applicare dipende principalmente da linee guida internazionali, esperienza pregressa e protocolli interni alla struttura (rispettivamente 80,3%, 54,9%, 50,7%). Rispetto alla terapia standard, i criteri che guidano la prescrizione di terapie differenti riguardano principalmente la presenza di comorbilità (R: 81,3%; F: 88,2%; C: 73,3%; P: 85,7%) e la valutazione di specifici parametri clinici del ricevente. Inoltre, la maggior parte degli intervistati si ritiene favorevole a utilizzare, ove disponibile, le versioni generiche. Dalla survey emergono aspetti clinici non rilevabili dai flussi amministrativi sanitari correnti; le integrazioni di tali informazioni cliniche nei flussi correnti consentirebbero di fornire un quadro più ampio sui fattori che influenzano la scelta degli schemi terapeutici immunosoppressivi post-trapianto d’organo.