The inclusion of a medicinal product in a Monitoring Register takes place after obtaining the marketing authorisation, or after the authorisation of an extension of its therapeutic indications. In some particular cases, the Registers also monitor the medicines reimbursed by the NHS pursuant to Law 648/96, i.e. before they are placed on the market.

Law No. 135 of 7 August 2012 recognised the Monitoring Registers as an integral part of the Information System of the NHS (art.15, paragraph 10), while further subsequent regulations (Law 125/2015; Law 232/2016; Law 205/2017) have assigned to the Registers functions of evaluating the effectiveness of the medicinal product for the purpose of renegotiation, and of controlling expenditure for innovative medicines and for avoidable costs in health care.

The AIFA Registers attribute a very important role to the Regions in the management of the support infrastructure, allowing intervention also in the authorisation system of the prescribing centers. In fact, the Health Directors (Direttori Sanitari) are authorised and, in turn, authorise medical users and pharmacists to use the platform.

The management of the register platform is organised through a network that includes approximately 3,500 health structures, 52 regional managers, 963 Health Directors, 32,857 doctors and 2,318 pharmacists. This network allows the Regions to regulate the organisation of pharmaceutical assistance on the territory. Currently, 49 pharmaceutical companies have at least one monitoring register managed by the AIFA platform. Companies interact with individual pharmacies through a profile defined on the platform, providing for the fulfillment of the conditional reimbursement agreements (Managed Entry Agreements, MEA), stipulated in the negotiation.

AIFA has provided an advanced application of the different MEA models. According to an international taxonomy, these can be divided into two main categories: 1) Performance-Based Risk sharing schemes, outcome-based risk sharing agreements and 2) Financial based schemes, purely financial agreements. The first category includes the Payment by result (PbR), Risk sharing (RS) and Success fee (SF) agreements, while the second includes Cost sharing (CS) and Capping agreements. Cost sharing, generally adopted when there are more reliable data on the efficacy and safety of the medicine, provides a discount on the price of the first cycles of therapy for all patients eligible for treatment, as identified by the Summary of Product Characteristics. The risk sharing model, on the contrary, provides for a discount applicable only to patients who do not respond to treatment. The Payment by Result extends the RS modalities with the full reimbursement by the pharmaceutical company for all patients who do not respond to treatment (payback by pharmaceutical companies of 100% of therapeutic failures). This modality is usually used in the event that the benefit/risk ratio of the medicinal products presents a greater degree of uncertainty and requires a definition of the non-response based on the evidence available from the pivotal clinical trials. The Success fee provides that the NHS initially obtains the medicine from the owner company free of charge and, only after evaluating the response to treatment and in the event of therapeutic success, will remunerate the corresponding dispensed packs. Finally, the Capping agreement provides that the pharmaceutical company is responsible for dispensing the medicinal product after the quantities established by the negotiation agreement are exceeded.

Another important element in the enhancement of the Monitoring Registers is the need to ensure rapid access to potentially priority medicines for health protection. This need must necessarily be balanced by reimbursement strategies that allow the NHS not to waste the limited economic resources available, especially in the case of high-cost medicines. The role of the Registers becomes all the more priority in the regulatory context the more the object of the assessment concerns a recently authorised medicinal product, whose benefit/risk ratio, although positive, is not fully defined or can significantly change depending on the way it is used. of use. On the other hand, in the case of authorization of an extension of the therapeutic indication of a medicinal product already placed on the market, the Registers make it possible to ensure that the use of the medicine complies strictly with the new indication. In fact, most of the medicines included in the AIFA Registers come from a centralized authorisation (often accelerated and/or conditioned) and mainly relate to biological and/or high-cost medicines for the NHS. The establishment and implementation of a Register provide, first and foremost, the identification of specific indicators of predictability of the response to treatment and allow an efficient delimitation of patient subpopulations who can obtain the maximum benefit from the medicinal product. The selection of the indicator and its measurement with respect to the outcome of the treatment is a process carried out within AIFA Advisory Committees (CTS and CPR), together with the assessments of the economic implications related to the authorisation of the medicinal product.