Could Decreased Reporting of Suspected Adverse Reactions Generate Future Safety Concerns?

Introduction

According to the WHO ¹ definition, pharmacovigilance (PV) is the science and set of activities related to the detection, collection, evaluation, understanding, and prevention of adverse drug reactions and related safety issues. PV is critical for monitoring the risk-benefit ratio of post-marketing drugs and related safety issues. Pharmacovigilance databases contain information on reports of suspected adverse drug reactions, are of great value for identifying potential drug safety signals, or for investigating specific drug-event associations.^2,3 An adverse drug reaction (ADR) is defined as a response to a drug product that is harmful and unintended. ADRs are a major cause of morbidity and mortality, and increase healthcare costs and expenditures. Pharmacovigilance systems allow the identification and prevention of risks associated with the use of a drug by detecting safety signals from data in Databases (Example Eudravigilance) and support decisions made by regulatory agencies in different countries. Spontaneous reporting of ADRs is the cheapest, simplest, and most widely used method of recognizing new drug safety problems, and its main limitation is underreporting. Probably, the COVID-19 global pandemic has highlighted even more the importance of pharmacovigilance and drug safety monitoring, such that the PV systems of all global regulatory agencies have been strengthened. In particular, pharmacovigilance (PV) had to find ways to keep up with a pandemic with few precedents in human history. In this regard, however, the global impact of Covid-19 has been devastating; the pandemic and its emergence have prompted the field of PV to innovate and develop new and more efficient ways to collect and use drug safety data. In addition, several pharmacological agents have been used to treat COVID-19 infection, with risk of pharmacodynamic and pharmacokinetic interactions. The objective of this study is to observe ADR reports recorded in the National Pharmacovigilance Network (NFP) from the pre-pandemic period to the present, with the aim of assessing the influence of the pandemic on the quantity and quality of spontaneous ADR reporting. This observation explores the frequency, preventability, and severity of ADRs collected over a 3-year period (2019-2020-2021) in the Italian national pharmacovigilance network, in the Campania region, and at the local health authority 3 SUD Napoli. The objective of the study was to assess the influence of the COVID-19 pandemic and the onset of mass vaccination on the incidence and quality of ADRs reports.^4,5

Material and Methods

The analysis of extracted reports stratified by SOC (systemic organic class) shows that in 2019 at Asl Napoli 3 SUD there were 354 reports of which 289 (81.64%) concerning antineoplastic chemotherapy drugs. The data show that in the pre-pandemic period the highest incidence of reports concerned oncological drugs, as expected considering the narrow therapeutic window (therapeutic interval) of these pharmacological agents. Following the pandemic at the beginning of 2020, the number of reports abruptly dropped to only 42 in the first 8 months of 2020 without the incidence of any therapeutic class in particular prevailing. In total, there is a drastic reduction in reports of 88.13% compared to the previous year. This reduction is in line with what happened in the Campania Region (72.56%) and in Italy (40.75%). In the first 8 months of 2021 we seem to have a full resumption of pharmacovigilance activities with 675 reports in the local health unit Naples 3 South. The analysis by therapeutic class shows, however, that these reports are due exclusively to the marketing of anti-covid vaccines (95.5% equal to 644 registrations). In practice, only 31 reports in the year 2021 did not concern anti-COVID-19 vaccines, fewer than in 2020. The chemotherapy class, in 2021 was the subject of only 4 reports compared to 289 in 2019. This analysis shows how the COVID-19 pandemic and the subsequent mass vaccination have influenced the trend of pharmacovigilance reports in Italy.

Figures 1 to 3: ADRs reported, period 2019 to 2021 local health authority 3 SUD Napoli.

Figure 1.

ADRs reported in 2019.

Figure 3.

ADRs reported in 2021.

Figure 2.

ADRs reported in 2020.

Conclusion

Analysis of the data confirms that pandemic COVID-19 decreased the incidence of reporting. This can be attributed to number causes. First, health care workers were involved in a health emergency with few precedents in human history, and they were probably able to devote less time to PV reporting activities. In addition, the beginning of vaccination against COVID-19, and in particular the availability of vaccines with new methods, such as those with mRNA, ⁶ has shifted the attention of reporters (doctors, nurses, citizens, etc. . .) on any ADRs caused by vaccination. In fact, from the data shown, there is a surge in the incidence of reports of COVID-19 vaccines. Finally, an anomalous data to be highlighted is that there has not been an increase in the number of reports of ADRs for antiviral drugs such as remdesivir, immunomodulators/anti-inflammatory drugs, anticoagulants such as heparin, pharmacological treatments that have been widely used in this 3-year period as they are used for the treatment of COVID-19 infection.