We have analysed the spontaneous report situation in Italy during 2014. As with last year, the data will be published in detail by AIFA in the OSMED Report, which will be available from next September, but in this review, we can disclose the most relevant data. In 2014, aside from over 4,000 reports in the literature, 51,181 spontaneous reports were included in the national pharmacovigilance network, with an overall increase of 25% compared to 2013.
The number of reports per million inhabitants ranged from 1,652 in Lombardy, to 128 in Abruzzo. The national average was 858, and confirms Italy ranked amongst the top countries in Europe. This strongly increasing trend was confirmed by the reports, which have doubled over the last three years. This number is also associated with quality, which implies the information contained in the reports was complete. In a recent publication from the WHO UMC Centre, Italy, with at least 1,000 reports/year, emerged as the highest ranking country in the world for documenting reports.1
The doubling of vaccination reports was mainly linked to a surveillance project into the adverse events associated with the tetravalent measles-mumps-rubella and varicella (MPRV) vaccine, which was being conducted in Veneto. The results of this project are not available yet.
In 2014, almost half of the reports in Italy were supplied by hospital doctors (46%). The number of reports from pharmacists (18%) was significant, whilst the number of general practitioners joining the system remained low (7%) with very poor reports (0.7%) from citizens.
As already noted, the situation was influenced by the active pharmacovigilance projects being conducted in Lombardy and other Italian regions. Many of these interventions have been made in hospital contexts which explains the high number of reports from these sources. Even the reports from pharmacists are primarily from hospital pharmacists who were gathering alerts from Emergency Department reports. Few reports were from pharmacists on the ground.
Overall, the percentage of serious reports in Italy was 32%. This varied greatly from region to region (for example, 42% in Lombardy and 18% in Veneto), which mainly related to the various active pharmacovigilance projects.
Almost half of the reports (49%) reported a complete resolution of the adverse event. There were however 381 cases that had a fatal outcome, in line with the numbers seen in previous years. The cases with fatal outcomes were mainly related to anticoagulant drugs (warfarin or new anticoagulants) and antiplatelet agents, with bleeding reactions occurring in elderly patients.
There were however 58 fatalities related to influenza vaccination, 33 of which related to the specialty Fluad®. All of the reports concerning this had been entered in the last two months of the year. The case of fatal reactions to the flu vaccine received wide media coverage at the end of last year. It all started when three deaths that occurred between the 7th and 18th November were attributed to the adjuvanted flu vaccine Fluad®. The vaccine is given particularly to the elderly, who generally have comorbidities and are taking multiple therapies, and thus have an increased mortality. The reported events were mostly cardiovascular, and the causal link with vaccination was very weak. Despite this, AIFA decided to give notice of the suspension of batches related to these reports, and made the National Institute of Health (ISS) carry out the tests needed to assess the safety of the vaccine. The hype attached to this decision led to many other reports of fatal outcomes being submitted in the days following the first withdrawal, implicating other batches of the vaccine. The tests performed by the ISS and the case assessments conducted in collaboration with the EMA have finally ruled out any involvement of the vaccine in the cases reported, and by the end of the year, AIFA lifted the ban on using the batches involved. Unfortunately, this story has had a very negative impact: millions of people have given up on vaccination, resulting in a sharp increase in influenza cases (and an increase in mortality).
Table 1: Number of reports in Italy in 2014 compared to 2013
|Compared to 2013|
|Region||No. reports||Rate||% Vaccinations||Total||Medications||Vaccinations|
|Friuli Venezia Giulia||750||614||20%||21%||12%||78%|
|Pr Aut di Bolzano||110||216||35%||6%||15%||-9%|
|Pr Aut di Trento||570||1,075||86%||391%||12%||1035%|
- Drug Saf 2014;37:65-77. CDI