In 2019, Italy registered approximately 65,000 spontaneous reports of suspected adverse reactions (ADR), of which around 58,000 were from drugs and 7,000 from vaccines, showing an increasing trend compared to the previous year.
With the arrival of the COVID-19 pandemic, spontaneous reporting activity saw a significant decline, mainly attributed to the increased commitment of health professionals in assistance activities: in 2020, about 41,700 reports were entered into the RNF (National Network of Pharmacovigilance), a decrease of 36% compared to 2019. The decrease mainly concerned drug reports.
In 2021, during the COVID-19 vaccination campaign, vaccine reports increased exponentially, surpassing 136,500. In contrast, drug reports further decreased by 20% (about 29,000).
The situation in 2022 reflects the “tail-end” of the vaccination campaign; vaccine reports, although decreased more than four times compared to the previous year, remained high, exceeding 31,000. Drug reports, on the other hand, have not returned to pre-pandemic levels and are halved compared to 2019 (about 29,200).
The mass COVID-19 vaccination campaign has made non-healthcare professionals aware of the spontaneous reporting activity, contributing to the high number of reports. The excessive encouragement to report in an emergency situation probably reduced interest in the current normal situation.
Therefore, it is crucial that regional pharmacovigilance centers and health and hospital companies promptly take action to raise awareness among health professionals and citizens about the importance of spontaneous reporting.
This was discussed in the ISOP web workshop on May 17, 2023, during which about a dozen projects were presented to stimulate spontaneous reporting.
Interventions for healthcare professionals
Training health professionals is an indispensable tool to promote and improve reporting quality: it is among the essential tasks set out in AIFA (Italian Medicines Agency) operational procedure for regional pharmacovigilance centers.
Starting in 2016, the Sardinian pharmacovigilance Center organized 1-2 day courses for small groups of health professionals from ASLs (Local Health Authorities) and hospitals and for general practitioners. This activity resulted in an increase in both the number and quality of reports and expanded the number of reporters. Positive effects tend to persist over time, but to ensure continuous training and engage an increasing number of professionals, dedicated and expert personnel is required.
An alternative is distance learning, which reaches a much larger audience and offers constant and up-to-date information. In Abruzzo, establishing a permanent table on pharmacovigilance, assigning specific budget objectives to certain Operational Units, and identifying Department or Operational Unit representatives have enabled the inclusion of training activity in a broader governance context. The project produced very positive results: an increase in the number of reports, including severe ones, an improvement in quality, and the involvement of a larger number of reporters.
Use of Monitors
Employing dedicated figures (monitors) to assist the healthcare staff of the Operational Units in reporting can increase awareness and promote spontaneous reporting.
At the Catania pharmacovigilance Center, the support of two monitors in contexts with a low number of reports in previous years led to a progressive and consistent increase in the number of reports. This type of intervention requires the availability of financial and human resources.
A lack of time dedicated to completing and sending the form is a factor causing under-reporting. Using simplified methods, which involve recording a limited amount of information, can facilitate health professionals. At the Veneto Oncological Institute, the pharmacovigilance responsible pharmacist involved the nursing staff administering the therapies in the reporting activity, agreeing only to record some essential data in a dedicated file.
This strategy proved effective in highlighting a greater number of reports on oncological drugs, although it has two limitations: an additional effort is required for those who must subsequently enter the reports, and the reporters do not autonomously use official channels.
Integrating pharmacovigilance into a specific and coordinated prescription appropriateness path within the Rare Diseases Network of Friuli Venezia Giulia allowed involving medical staff in the reporting activity and maintaining the results obtained even after the project renewal.
Similarly, in Emilia-Romagna, integrating pharmacovigilance and clinical risk management activities through the creation of a single IT platform simplified the reporting of events associated with therapeutic errors and allowed capturing and collecting reports that would otherwise not have been detected and included in the National Pharmacovigilance Network.
Dedicated interventions for citizens/patients
Starting from the ‘90s, citizens/patients have been able to directly report adverse reactions using the designated form (either paper or online). A lack of awareness of this opportunity and difficulties in finding and completing the form can be significant obstacles to reporting.
Interacting with patients when delivering medicines is an opportunity both to inform them about correct use (thus reducing the risk of adverse reactions) and to detect any issues that arose during therapy. In a study coordinated by the Pharmacovigilance Center of the Veneto Region, which involved seven regions, pharmacists interviewed over 12,000 citizens, providing a reporting form to those who claimed to have had an adverse drug reaction. The study improved communication between pharmacists and citizens, raised awareness about pharmacovigilance, and increased the number of reports. However, some challenges emerged, including sustainability and maintaining a consistent number of reports over time. Subsequently, the project led to the creation of a network of more than 1,000 “accredited” pharmacies (VigiRete), integrating pharmacovigilance into the “service pharmacy” activities and involving the pharmacist directly in reporting activities. Even during this phase, there was an increase in reports, but the results were not consistent.
Direct distribution services
Another “point of contact” between pharmacists and citizens/patients is the Direct distribution services, a privileged observatory for new drugs or those indicated for rare diseases, for which safety data are still lacking. In the direct distribution service of the Papardo Hospital in Messina, the presence of a pharmacovigilance expert pharmacist has significantly increased the number of citizen reports and improved their quality.
Patient empowerment, or their involvement in the aware management of their illness and treatment path, is especially crucial in oncology. At the Oncology Reference Center in Aviano (Pordenone), a structured counseling service (Pharmacy Clinical Desk) was established, managed by an expert hospital pharmacist, aiming to promote knowledge of therapies, potential adverse reactions, and their management, thereby reducing the risks associated with polypharmacy or concurrent use of herbal products or natural supplements. Direct patient contact with the pharmacist allowed for the identification of a larger number of adverse reactions, especially severe ones, without using additional personnel or resources.
Patient associations can be valuable allies in raising awareness about the importance of pharmacovigilance and the methods of reporting adverse reactions, for example, by involving them in creating and disseminating informative materials (leaflets, videos). An experience of this type was promoted and carried out by the pharmaceutical company Roche. Unfortunately, for such projects, it’s not possible to measure the impact on the quantity and quality of reports.
Days dedicated to pharmacovigilance for citizens can be an opportunity to introduce this activity and distribute informational materials. For example, the Regional Pharmacovigilance Center of Sardinia organized a day in a city park; it will be interesting to see if this initiative will have a measurable effect on the number and quality of reports.
A vaccination surveillance project in pediatric age (VigiFarmacoVax), coordinated by the Pharmacovigilance Center of the Veneto Region and involving 11 regions, explored whether sending an automatic SMS to parents a few days after vaccine administration could stimulate the reporting of post-immunization adverse events (PIAE). The ability for parents to report by simply responding to the SMS in their own language, without the need to fill out a form, encouraged reporting: over a year, more than 21,000 PIAE were collected and validated by Local Pharmacovigilance Managers. Natural language processing software was able to correctly identify severe adverse events by spotting specific keywords in the SMS content. The main limitation of such technological solutions is the need to integrate with the vaccination Registry and the National Pharmacovigilance Network.
Patients can be directly involved in reporting, as occurred in a multi-regional active pharmacovigilance study on biological drugs used in dermatology, rheumatology, and gastroenterology, coordinated by the Magna Graecia University in Catanzaro (Calabria). Patients were interviewed by phone, during which potential adverse reactions were investigated. In addition to increasing the number of reports, the study allowed for estimating the incidence of adverse reactions – a goal not achievable with spontaneous reporting – and identifying drug interactions that can modify the risk and adherence to treatments with biological drugs. This type of study is organizationally complex, requires the collaboration of multiple regions, and needs additional resources.
Conclusions and recommendations for future projects
The workshop highlighted a wide variety of projects, spread across the entire national territory, carried out with different methodologies and aimed at healthcare professionals and/or citizens/patients; unfortunately, the vast amount of work done is hard to quantify and, therefore, little known and appreciated.
In projects involving patients/citizens, reporting adverse reactions is a significant opportunity for support, listening, and dialogue with the healthcare professional and can help prevent risks associated with therapy.
Identifying “preferential” observation points (direct distribution, clinical desk, drug infusion administration) and “facilitator” professionals (pharmacists, nurses) are project success factors.
Regarding healthcare professionals, there’s a lack of interventions aimed at general practitioners; for this reason, projects aimed at involving general medicine in reporting activities are desirable.
Among the objectives, it is not only necessary to increase the number but also the quality of collected reports, as well as increase the number of reporters. It’s essential for study protocols to identify quality parameters in advance to measure before and after interventions.
Professionals in training (specialists, fellows) represent a valuable resource for project sustainability; however, to ensure the long-term continuity of interventions and consolidate results, adequately trained personnel with a stable role within the organization are required.
Incorporating projects into care pathways would enhance the role of spontaneous reporting in the broader context of promoting prescription appropriateness and patient safety, monitoring intervention efficacy through quality indicators.
There’s a need to increase the use of digital technologies, overcoming difficulties related to system integration and experimenting with solutions that facilitate reporting, both by citizens and healthcare professionals.
Marina Ferri (Azienda Provinciale per i Servizi Sanitari – Provincia Autonoma di Trento), Luca Leonardi (Azienda Provinciale per i Servizi Sanitari – Provincia Autonoma di Trento), Francesca Lombardi (Master in Tecnologie Farmaceutiche e Discipline Regolatorie - Università di Pavia), Marco Tuccori (Azienda Ospedaliero Universitaria Pisana)