Introduction

The Italian Medicines Agency (AIFA) plays a pivotal role in the evaluation, authorization, and regulation of drugs in Italy, especially in a time marked by an aging population, the advancement of personalized medicine, and the introduction of innovative yet high-cost drugs. To tackle these challenges and ensure citizens' access to effective therapies without straining the National Health Service (NHS) financially, innovative tools such as Monitoring Registries have been introduced. Monitoring Registries were initiated by AIFA in 2005 and serve a dual purpose [1, 2]. First, they promote prescribing appropriateness by tracking the real-world usage of drugs. Second, they serve as a regulatory mechanism, particularly for economically conditional reimbursement agreements known as Managed Entry Agreements (MEA). These MEAs facilitate access to high-cost innovative medications. AIFA's Monitoring Registries are comprehensive databases that collect data on drug use, adverse reactions, effectiveness, and other pertinent information regarding patients receiving specific drugs [3,4,5,6]. These registries offer several advantages:

  1. 1.

    Monitoring Drug Effectiveness: These registries enable AIFA to assess the long-term outcomes of treatments and gauge the real-world effectiveness of drugs in the Italian population.

  2. 2.

    Identifying Adverse Reactions: They help in the identification and analysis of adverse drug reactions, contributing to patient safety.

  3. 3.

    Detecting Inappropriate Drug Usage: By analyzing registry data, AIFA can spot patterns of inappropriate drug use and take corrective actions to improve therapy management and minimize waste.

  4. 4.

    Conducting Comparative Evaluations: The registries facilitate comparisons of the effectiveness and safety of different drugs for the same conditions, aiding in the selection of the most efficient treatments.

  5. 5.

    Supporting Clinical Research: Data from these registries can also be used for clinical and epidemiological research, providing new avenues for studying and deepening knowledge about drugs and treated conditions.

The presence of well-organized and up-to-date Monitoring Registries in Italy is regarded as a model of excellence in drug governance compared to other European countries [7]. These registries enable AIFA to efficiently manage negotiated risk-sharing agreements between the agency and pharmaceutical companies, including different MEA models such as outcome-based risk-sharing agreements and purely financial agreements. The AIFA Monitoring Registers platform serves as a critical tool for healthcare professionals. Prescribing clinicians use it to create personalized patient records, prescribe medications subject to AIFA monitoring, and complete the "end-of-treatment form" (ETF) upon treatment completion. Hospital pharmacists also use the platform to record medication dispensation. However, one challenge is that the AIFA web platform lacks automated pre-reimbursement controls. Consequently, treatments completed without the ETF being filled out by the prescribing clinician remain in the system without potential reimbursement evaluation. The objective of this work was to identify and intercept these completed treatments lacking the ETF, potentially resulting in a significant number of unassessed but reimbursable treatments. This initiative aimed to recover resources that could be reallocated to improve healthcare governance effectively and efficiently [8,9,10]. In summary, AIFA's Monitoring Registries and MEAs represent an Italian excellence in healthcare governance, allowing for rigorous contracting with pharmaceutical companies while ensuring citizens receive the best treatments within a sustainable National Health System. This comprehensive approach contributes to the safety, effectiveness, and financial sustainability of pharmacological therapies in Italy.

Methods

The study, conducted throughout the year 2022, encompassed 11 health districts within the Campanian healthcare company (Asl Napoli 3 SUD), serving a population of approximately 1,000,000 residents. The primary objective was to identify all completed treatments lacking the "end-of-treatment form" (ETF) completed by prescribing clinicians on the AIFA platform (Italian Medicines Agency). Two distinct types of analyses were employed: worklist interception and "Patient Search" interception.

  1. 1.

    Worklist interception: This method involved accessing the worklist menu, which provides access to all drug prescriptions for which patients have not yet visited their District Pharmacy for dispensation. Treatments listed in the worklist with prescription dates older than 4 months were considered as potential reimbursable treatments. The rationale behind patients not picking up prescribed medication was often related to therapeutic failure or exacerbation of the disease, especially in oncological cases.

  2. 2.

    “Patient Search” interception: This approach utilized the “Patient Search” menu, where a dedicated filter related to the “Pathology” was applied. The search aimed to identify all patients treated for specific pathologies with treatments that had old, unclosed dates, indicating a lack of the ETF completed by the physician. This allowed for the identification of patients who had previously picked up medication from their District Pharmacy but had not received further prescriptions from their physicians.

Subsequently, all unclosed treatments identified through these interception methods underwent a detailed analysis to select those with the potential to generate reimbursements. This process involved:

  1. 1.

    Excluding treatments containing drugs not subject to Managed Entry Agreement (MEA) conditions.

  2. 2.

    Cross-referencing the prescription and dispensation dates with the MEA agreement's validity range, available on the AIFA website. This step ensured a focus on unfinished treatments that lacked the ETF and had the potential for reimbursement.

An informatic database was established in each of the 11 District Pharmacies, recording selected treatments, prescribing physician names, hospital facilities, and contact information, such as email or phone numbers. Prescribing clinicians were subsequently contacted via phone or email, requesting them to assess the treatment for possible closure and to complete the appropriate ETF. This step is essential for the AIFA platform to automatically consider the possibility of reimbursement in accordance with the negotiated MEA conditions associated with each specific drug. Furthermore, to assess the effectiveness of this study, the year 2022 was compared with the preceding 5-year period in terms of the number of reimbursements obtained. An economic assessment was also conducted to quantify the total amount of euros recovered as a result of this study.

Results

By consolidating all the data gathered for each Health District, the outcome, quantified in terms of the count of reimbursements secured and delineated by year, is depicted in Fig. 1.

Fig. 1
figure 1

Number of managed reimbursements in a territorial area

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The surge in reimbursements achieved in the year 2022 can be directly attributed to the diligent efforts of hospital pharmacists in identifying a significant number of treatments that had been left incomplete by the prescribing physicians within the AIFA Registry platform. This proactive approach resulted in 72 reimbursements in 2022, as opposed to 14 in 2021, 18 in 2020, 24 in 2019, 28 in 2018, and 32 in 2017. The declining trend in reimbursements acquired from 2017 to 2021 is a consequence of the gradual closure of negotiated Managed Entry Agreements (MEAs) over time. Furthermore, we found it highly valuable to conduct an economic analysis of the reimbursements obtained in the year 2022 in comparison to the preceding 5-year period. The economic data collected have been presented in Table 1.

Table 1 Yearly breakdown of the number of reimbursements and their economic valuation in euros
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The economic analysis of the obtained reimbursements provides valuable insights into the significance of the recovery and monitoring efforts. In 2022, the year during which this initiative was implemented, an astounding €579,443.4 was recuperated. This represents a substantial increase when compared to the previous 5-year period. The fluctuations in outcomes can be directly attributed to heightened vigilance in monitoring and the expedited submission of reimbursement requests to pharmaceutical companies. Our research underscores the immense potential for success when the AIFA registry is managed by proficient experts. The discernible result arising from the data analysis is the substantial number of reimbursements secured precisely in the year when proactive measures were taken to identify reimbursable treatments. Consequently, the euro value of the reimbursements obtained in 2022 significantly surpasses the figures from the previous 5 years. This achievement is unequivocally attributed to the interception efforts undertaken by the District Pharmacists of the Local Health Authority (ASL). For these reasons, there was an increase of more than 100% in reimbursements obtained in 2022 when compared to previous years (+ 125% in 2017, + 157% in 2018, and + 200% in 2019), especially when contrasted with the years 2020 and 2021, during which the Covid-19 pandemic disrupted healthcare activities (+ 300% in 2020 and + 414% in 2021). It is noteworthy that the economic value in euros exhibits a non-proportional growth, highlighting the consistent rise in the cost of treatment over the years. Even in 2018, there was a higher economic reimbursement than in 2017 despite a lower number of recovered reimbursements (28 compared to 32) [11, 12]. In 2022, we witness a truly remarkable economic recovery compared to the previous years: + 250% (2017), + 237% (2018), + 371% (2019), + 657% (2020), + 2,208% (2021). These figures underscore the critical importance of such activities, facilitated by AIFA's platform and negotiation agreements, in ensuring the sustainability of the healthcare system.

Discussion

The healthcare system faces the formidable challenge of optimizing public pharmaceutical expenditure while ensuring patient access to state-of-the-art treatments. In Italy, the AIFA Registry assumes a pivotal role in ascertaining patient eligibility for treatment, compiling epidemiological data, and evaluating the safety and effectiveness profiles of drugs. The primary objective of this registry is to promote the judicious utilization of medications in alignment with established guidelines and to furnish real-world data regarding drug efficacy. Established in 2005 and comprehensively revamped in 2013, the AIFA Registry is an integral component of the National Health Service's Information System. Through the data it amasses, this registry assesses pharmaceuticals' benefit-to-risk and cost-effectiveness ratios. Moreover, the AIFA Registry actively participates in a comprehensive European Health Technology Assessment (HTA) initiative that employs a multidisciplinary approach to scrutinize the impact of therapeutic innovations on clinical practice with the aim of curtailing public expenditure [13]. Nevertheless, the efficacious execution of Managed Entry Agreements (MEAs) hinges on vigilant monitoring and adherence to specific prerequisites and deadlines. This encompasses precise disease restaging, meticulous control of the number of therapy cycles, vigilant monitoring and reporting of therapy responses, swift communication of adverse events, and provision of accurate follow-up information. The outcomes of this study underscore the paramount importance of District Pharmacists' proactive involvement in securing the discounts stipulated by the Italian Medicines Agency within the framework of MEAs. Indeed, this study demonstrates the feasibility of effectively recouping numerous reimbursements that, in the absence of such intervention, would have remained pending on the AIFA platform due to the absence of completion of the end-of-treatment documentation by the prescribing physician. The approach devised for identifying incomplete treatment records has proven exceptionally efficacious, as evidenced by the remarkable results achieved. This approach facilitated the acquisition of an impressive 72 reimbursements, with a cumulative economic value of €579,443.4, in the span of just 1 year (2022). This substantial economic figure underscores the efficiency of the Italian healthcare system: AIFA's negotiations and discussions with pharmaceutical companies render therapies that have become increasingly expensive over the years sustainable. The Italian government's endeavors, facilitated by the implementation of technologies such as Monitoring Registries, ensure the judicious allocation of public resources, eliminating wastage and guaranteeing optimal public healthcare for citizens [2, 14, 15]. It is undeniable that the years of the Covid-19 pandemic imposed substantial challenges on the Italian healthcare system, placing immense demands on all healthcare professionals who had to prioritize pandemic-related care over routine clinical practices [16, 17]. Many treatments and therapies, especially in the cardiovascular and neurological domains, received heightened medical attention [18, 19]. Consequently, there was an anticipated decline in physicians' and pharmacists' adherence to AIFA compliance in 2020 and 2021. However, the management of AIFA Monitoring Registries has significantly improved to date, and it will be intriguing to reevaluate this analysis at the conclusion of 2023, including an assessment of the extent of economic recovery vis-à-vis "innovative" therapies characterized by exorbitant costs. Undoubtedly, based on the findings of this study, it is manifested that the active collaboration of all healthcare personnel in meticulously overseeing electronically tracked treatments, from the initiation of the prescription to the completion of the treatment record (ETF), holds paramount significance.

Conclusion

The Italian healthcare regulations concerning price negotiation and bargaining are considered exemplary within the European context. The incorporation of Monitoring Registries and Managed Entry Agreements (MEA) signifies an evolutionary step toward ensuring the sustainability of healthcare for central governments. Nevertheless, it is imperative to ensure the precise execution of all mandated procedures, involving both medical practitioners and pharmacists. This study underscores the potential for enhancing the reimbursement process by integrating experienced pharmacists into healthcare policies, working collaboratively with clinical professionals. As an exploratory study, the available literature on the integration of pharmacists into multidisciplinary clinical teams remains limited. Nevertheless, our findings propose that optimizing the management of MEA-related matters could constitute a viable real-world approach, leading to enhancements in reimbursement processes and potentially reducing costs associated with innovative pharmaceuticals.