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Introduction: In 2021, the European Medicines Agency supported the "Covid Vaccine Monitor (CVM)," an active surveillance project spanning 13 European countries aimed at monitoring the safety of COVID-19 vaccines in general and special populations (i.e., pregnant/breastfeeding women, children/adolescents, immunocompromised people, and people with a history of allergies or previous SARS-CoV-2 infection). Italy participated in this project as a large multidisciplinary network called the "ilmiovaccinoCOVID19 collaborating group." Methods: The study aimed to describe the experience of the Italian network "ilmiovaccinoCOVID19 collaborating group" in the CVM context from June 2021 to February 2023. Comprising about 30 partners, the network aimed to facilitate vaccinee recruitment. Participants completed baseline and follow-up questionnaires within 48 h from vaccination over a 6-month period. Analyses focused on those who completed both the baseline and the first follow-up questionnaire (Q1), exploring temporal trends, vaccination campaign correlation, and loss to follow-up. Characteristics of recruited vaccinees and vaccineereported adverse drug reactions (ADRs) were compared with passive surveillance data in Italy. Results: From June 2021 to November 2022, 22,384,663 first doses and 38,207,452 booster doses of COVID-19 vaccines were administered in Italy. Simultaneously, the study enrolled 1,229 and 2,707 participants for the first and booster doses, respectively. Of these, 829 and 1,879 vaccinees, respectively, completed both baseline and at least Q1 and were included in the analyses, with a significant proportion of them (57.8%/34.3%) belonging to special cohorts. Most vaccinees included in the analyses were women. Comirnaty® (69%) and Spikevax® (29%) were the most frequently administered vaccines. ADR rates following Comirnaty® and Spikevax® were higher after the second dose, particularly following Spikevax®. Serious ADRs were infrequent. Differences were observed in ADR characteristics between CVM and Italian passive surveillance. Conclusion: This study confirmed the favorable safety profile of COVID-19 vaccines, with findings consistent with pivotal clinical trials of COVID-19 vaccines, although different proportions of serious ADRs compared to spontaneous reporting were observed. Continuous evaluation through cohort event monitoring studies provides real-time insights crucial for regulatory responses. Strengthening infrastructure and implementing early monitoring strategies are essential to enhance vaccine safety assessment and prepare for future pandemics. [ABSTRACT FROM AUTHOR]

Therapeutic use of an unauthorised drug (or of an authorised drug for an unauthorised indication) for patients with a life-threating disease is permitted outside a clinical trial as an Expanded Access Programme (EAP).The regulations regarding EAPs is not the same all over the world. For example, the recommendation of the European Medicines Agency (EMA) in EU countries also includes within EAPs patients who have been treated in a clinical trial and who wish to continue the treatment. Nevertheless, the patients treated in a clinical trial could have the option of continuing treatment for an extended period in an Open-label Extension study, aimed to generate long-term data on efficacy, safety, tolerability and administration.The aims of this paper - based on the difficulties and incoherence encountered by an Italian Ethic Committee (EC) during the authorisation process of EAPs - are: understanding the origin of this misclassification by analysing differences and similarities among USA, European and Italian regulations concerning EAPs; and showing difficulties in classifying international study protocols as a consequence of the lack of harmonisation of definitions.We performed a critical review of the current USA, European and Italian regulations and we analysed some practical cases by retrieving protocols from Clinicaltrials.gov and the Italian Clinical Trials Registry (OsSC) containing in the title the keywords 'Expanded Access Programme', "'Expanded Access', 'Open-label Extension study' or 'Early Access'.We observed that the Food and Drug Administration ( FDA) definition of EAP is very clear while the EMA definition is similar to that of an Open-label Extension study. This lack of a clear definition generates misclassification and it is possible to find an EAP with an efficacy or safety endpoint; or an EAP managed as a clinical trial; or an EAP classified in Clinical Trials Registries as a phase II, III or IV clinical trial.The internationalisation of the studies requires a harmonisation on a global level of legislation and definitions to eliminate misclassification of protocols. For this reason, the authors suggest that: a) the EMA definition should be harmonised with the FDA definition of EAPs, b) European regulation, even if optional, should be adopted in a compulsory way by national regulations. Moreover, separate registries for both EAPs and clinical trials should be organised. [ABSTRACT FROM AUTHOR]

(1) Background: In 2022, monkeypox (Mpox) was declared a public health emergency. The European Medicines Agency has authorized the use of Imvanex/Jynneos, a smallpox vaccine, for coverage against pox. Healthcare workers (HCWs) are all considered by the European Centre for Disease Prevention and Control to be at risk, but in Italy, vaccination was offered only to laboratory personnel. The present study aims to investigate smallpox vaccination coverage (VC) that provides protection against Mpox among HCWs in an Italian university hospital and to assess HCWs' attitudes towards the possibility of getting vaccinated against Mpox. (2) Methods: We conducted a cross-sectional survey. 336 HCWs from selected wards were asked to fill out a self-declaration to collect their sex, profession, ward, vaccination status, and attitude toward Mpox vaccination. (3) Results: 60.71% of HCWs involved provided the requested data; 38.7% of them were previously vaccinated against smallpox, which corresponds to 23.5% of the total HCWs in the wards considered. Considering those born before 1979 as vaccinated, VC increases from 23.5% to 41.7%; the percentage of HCWs who adhered to vaccination is 23%; laboratory technicians showed a lower willingness to be vaccinated. The ward with the highest willingness to vaccinate is proctological surgery. (4) Conclusions: Based on our experience, a variability in smallpox VC and in willingness to vaccination has emerged both among different job titles and age categories and across the wards analyzed. Additionally, our survey reveals that vaccination attitudes are higher among HCWs from wards that currently do not have free access to such vaccinations. [ABSTRACT FROM AUTHOR]

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are effective and safe lipid-lowering treatments (LLT). The primary endpoint of the study was to assess the prevalence of patients eligible for treatment with PCSK9 inhibitors in a real-life clinical setting in Italy before and after the recent enlargement of reimbursement criteria. For this study, we consecutively considered the clinical record forms of 6231 outpatients consecutively admitted at the Lipid Clinic of the University Hospital of Bologna (Italy). Patients were stratified according to whether they were allowed or not allowed to access to treatment with PCSK9 inhibitors based on national prescription criteria and reimbursement rules issued by the Italian Medicines Agency (AIFA). According to the indications of the European Medicines Agency (EMA), 986 patients were candidates to treatment with PCSK9 inhibitors. However, following the prescription criteria issued by AIFA, only 180 patients were allowed to access to PCSK9 inhibitors before reimbursement criteria enlargement while 322 (+14.4%) with the current ones. Based on our observations, low-cost tailored therapeutic interventions for individual patients can significantly reduce the number of patients potentially needing treatment with PCSK9 inhibitors among those who are not allowed to access to the treatment. The application of enlarged reimbursement criteria for PCSK9 inhibitors could mildly improve possibility to adequately manage high-risk hypercholesterolemic subjects in the setting of an outpatient lipid clinic. [ABSTRACT FROM AUTHOR]

Background: Age-related macular degeneration (AMD) is a common and chronic eye condition characterized by the presence of progressive degenerative abnormalities in the central retina (macula). Notably, neovascular, or wet, AMD (nAMD) occurs when new, abnormal blood vessels grow under the macula causing scarring of the macula itself and resulting in a loss of central vision, visual distortion, and an impaired capacity of perceiving colour contrast and intensity. Brolucizumab, a new generation anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibody, was approved by the European Medicines Agency for the treatment of nAMD. The aim of this analysis is to evaluate the cost-effectiveness profile of brolucizumab, compared to the main therapeutic alternative available (aflibercept), for the treatment of nAMD.Methods: The simulation of costs and outcomes was carried out using a Markov model over a time horizon of 15 years. In base-case, treatment effectiveness inputs for brolucizumab and aflibercept were extracted from the HAWK and HARRIER studies and from a network meta-analysis. The Italian National Healthcare Service (NHS) perspective was considered, therefore only healthcare direct costs (treatment acquisition, administration, adverse events, disease monitoring) were analysed. In the alternative scenarios, the societal perspective and a prolonged time horizon were considered. Model robustness was tested through sensitivity analyses.Results: In the base-case analysis, brolucizumab was dominant over aflibercept (+ 0.11 years QALY gained and -€15,679 costs). Both one-way deterministic and probabilistic sensitivity analyses confirmed the robustness and reliability of base-case results. The results of the probabilistic sensitivity analysis showed that when the willingness to pay is equal to €50,000 per QALY gained, brolucizumab would be dominant in 84% of simulations and in the remaining simulations brolucizumab would be cost-effective compared to aflibercept. Results of the alternative scenarios and sensitivity analyses confirmed the results of base-case.Conclusion: The cost-utility analysis shows that brolucizumab is dominant over aflibercept. Treatment with brolucizumab reduces the economic impact of nAMD and determined a slight increase of quality-adjusted survival. This analysis gives a high level of confidence that the treatment with brolucizumab would reduce the burden of intravitreal injections, compared to aflibercept, a relevant therapeutic alternative in Italy. [ABSTRACT FROM AUTHOR]

Background: The use of quinolones has been associated with the development of serious and persistent adverse drug reaction (ADR) mainly affecting muscles, joints and the nervous system. This risk has led the European Medicines Agency (EMA) to endorse some restrictions on the use of this class of antibiotic. Therefore, we performed a study to primary estimate the reporting probability of musculoskeletal, neurological, and psychiatric ADRs among quinolone generations using national data. Methods: We retrieved Individual Case Safety Reports (ICSRs) with a quinolone as suspected drug among those reported through the Campania spontaneous reporting system from January 1st, 2001 to April 30th 2019. Moreover, we retrieved national aggregated safety data from the online public report system (RAM system) for the period from January 1st, 2002 to March 31st, 2019. Risk factors were classified as "age greater than 60 years," "therapeutic indication," "renal failure," "organ transplantation," "use of corticosteroid," and "history of side effects". Reporting odds ratio (ROR) was computed to evaluate the reporting probability of musculoskeletal, neurological, or psychiatric events among quinolones generations. Results: A total of 87 ICSRs with a quinolone as suspected drug that reported at least one musculoskeletal, neurological, and psychiatric adverse event were identified in the Campania spontaneous reporting system. Forty-nine (56.3%) ICSRs reported risk factors (total risk factors 59). The most reported risk factor was "age greater than 60 years" (69.5%), followed by "therapeutic indication" (16.9%), "renal failure" (5.1%), "organ transplantation" (3.4%), "use of corticosteroid" (3.4%), and "history of side effects" (1.7%). Second-generation quinolones were associated with a lower reporting probability of musculoskeletal (ROR 0.70; 95% CI 0.63–0.79), neurological (ROR 0.81; 95% CI 0.73–0.90), and psychiatric (ROR 0.55; 95% CI 0.44–0.63) ADRs compared to the third generation of quinolones. Conclusions: Our findings showed that third-generation quinolones were always associated with a higher reporting probability of musculoskeletal, neurological, and psychiatric ADRs compared to the second generation ones. Moreover, we described risk factors in more than half of our cases suggesting that the inappropriate use of quinolones is a phenomenon that may frequently predispose patients to the occurrence of these ADRs. [ABSTRACT FROM AUTHOR]

• Cough and cold medicines are frequently used in children to treat upper respiratory tract infections without solid proof of benefits. • Safety issues have been raised about the use of these drugs in young children. • In 2007 international warnings were issued advising against use of these drugs in young children. • Cough and cold medicines prescribing by primary care physicians has not really been influenced by international warnings in the Netherlands, where no additional national warnings were made and only partially in Italy. • A concerted action should be taken in Europe to advise strongly against the OTC use and prescription of cough and cold medicines in young children. The aim of the study was to assess the influence of national and international warnings on the prescription rates of cough and cold medicines (CCMs) in the youngest children (<2 years) in the Netherlands and Italy. Analysis of outpatient electronic medical records of children <2 years in Italy and the Netherlands was carried out. Age and country specific prescription prevalence rates were calculated for the period 2005-08. Comparisons of prescription rates in 2005 (pre) and 2008 (post) warnings were done by means of a chi-square test. The cohort consisted of 99 176 children <2 years of age. After international warnings, overall prescription rates for CCMs decreased slightly from 83 to 77/1000 person years ( P= 0.05) in Italy and increased in the Netherlands from 74 to 92/1000 children per year. Despite the international warnings, prescription rates for nasal sympathomimetics and opium alkaloids increased in the Netherlands ( P < 0.01). In Italy a significant decrease in the prescription rates of opium alkaloids and other cough suppressants ( P < 0.01) was observed, and also a significant reduction in use of combinations of nasal sympathomimetics. Despite the international safety warnings and negative benefit-risk profiles, prescription rates of cough and cold medicines remain substantial and were hardly affected by the warnings, especially in the Netherlands where no warning was issued. The hazards of use of these medicines in young children should be explicitly stipulated by the European Medicines Agency and all national agencies, in order to increase awareness amongst physicians and caretakers and reduce heterogeneity across the EU. [ABSTRACT FROM AUTHOR]

The article presents a study concerning the 1394/2007/CE regulation which impose policies in the authorization and supervision of advanced therapy medicinal products (ATMPs) in Italy. It states that the market authorization of pharmaceutical products is handled by the European Commission (EC) after the drugs have been evaluated by the European Medicines Agency (EMEA). It describes the liabilities of drug manufacturers who violate the regulation.

Simple Summary: The purpose of this work was to investigate the relationship between animal welfare (AW) and antimicrobial use (AMU) in dairy farms due to limited knowledge in this sector. AW was assessed using a survey in 79 Italian farms housing over 15,000 cows. The average AW level was good. Nevertheless, a wide difference among farms emerged, both in terms of AW and AMU, which underlined the importance of creating a monitoring system to identify problem farms as well as virtuous farms (as positive examples). The use of antimicrobials deemed critical for human medicine by the European Medicines Agency was frequent, particularly in farms with good management. This could be due to a tendency to choose those perceived as the best antimicrobials. Nevertheless, it is possible to reduce the use of critical antimicrobials without affecting animal health and production. Farms with better management used more intramammary products for dry cows; thus, reducing AMU may require selective dry cow therapy in several herds. Two of the farms involved in the study did not use any antimicrobials, but their AW was poor, suggesting a management review including a possible reintroduction of AMU. Our study highlights the importance of implementing a tailored antimicrobials stewardship. Information regarding the relationship between animal welfare (AW) and antimicrobial use (AMU) in dairy cows is limited. The current study aimed to investigate this relationship on Italian farms and to identify potential targets of AMU reduction. The study was performed at 79 Italian dairy farms housing over 15,000 cows during 2019. AW was scored with an on-farm protocol assessing farm management and staff training, housing systems, and animal-based measures. AMU was estimated using a defined daily dose per kg of animal biomass (DDDAit/biomass) for Italy. The median AW score was 73% (range: 56.6–86.8%). The median AMU was 4.8 DDDAit/biomass (range: 0–11.8). No relationship between the total AMU and AW was found. Management and staff training were positively associated with the use of the European Medicines Agency's category B antimicrobials, which are critical for human medicine, and with intramammary products for dry cow therapy. In those farms, antimicrobial stewardship should aim to reduce the category B antimicrobials and selective dry cow therapy. Our results underline the importance of implementing both an integrated monitoring system (AW, AMU, etc.) and antimicrobial stewardship tailored to the specific needs of each dairy farm. [ABSTRACT FROM AUTHOR]

Data on antimicrobial use (AMU) in heavy pig production (>150 kg) are limited. The aim of this study was to investigate the AMU in this production. Data from 2015 were collected for 143 fattening farms. The AMU was estimated through a treatment index per 100 days (TI100) using the defined daily dose animal for Italy (DDDAit). When possible, a comparison with the European Medicines Agency's defined daily doses for animals (DDDvet) was performed. The median TI100 was 10.7 (range, 0.2–49.5). Group treatments represented 94.6% of overall consumption. The AMU calculated using DDDAit and DDDvet were strongly correlated (ρ = 0.976; p < 0.001). The AMU was negatively correlated with injectables use (ρ = −0.46, p < 0.001) and positively correlated with oral products (ρ = 0.21, p = 0.014), premixes (ρ = 0.26, p = 0.002), and mortality (ρ = 0.18; p = 0.027). Farm size was negatively correlated with AMU (ρ = −0.29, p < 0.001). Smaller farms were more frequently above the median TI100 (odds ratio = 2.3, 95% confidence interval = 1.2–4.7), suggesting that they may have lower biosecurity and management standards. The results of this study should provide useful insights for the development of an Italian monitoring system. [ABSTRACT FROM AUTHOR]