Identification of Pregnancy Adverse Drug Reactions in Pharmacovigilance Reporting Systems: A Novel Algorithm Developed in EudraVigilance.

Introduction: There is a need to strengthen the evidence base regarding medication use during pregnancy and to facilitate the early detection of safety signals. EudraVigilance (EV) serves as the primary system for managing and analysing information concerning suspected adverse drug reactions (ADRs) within the European Economic Area. Despite its various functionalities, the current format for electronic submissions of safety reports lacks a specific data element indicating medicine exposure during pregnancy.

Lessons Learned on Observed-to-Expected Analysis Using Spontaneous Reports During Mass Vaccination.

During the COVID-19 vaccination campaign, observed-to-expected analysis was used by the European Medicines Agency to contextualise data from spontaneous reports to generate real-time evidence on emerging safety concerns that may impact the benefit-risk profile of COVID-19 vaccines. Observed-to-expected analysis compares the number of cases spontaneously reported for an event of interest after vaccination ('observed') to the 'expected' number of cases anticipated to occur in the same number of individuals had they not been vaccinated. Observed-to-expected analysis is a robust methodology that relies on several assumptions that have been described in regulatory guidelines and scientific literature.

The Role of the European Medicines Agency in the Safety Monitoring of COVID-19 Vaccines and Future Directions in Enhancing Vaccine Safety Globally.

The European Union (EU) regulatory network was at the forefront of the safety monitoring of COVID-19 vaccines during the pandemic. An unprecedented number of case reports of suspected adverse reactions after vaccination called for huge efforts for the assessment of this safety information, to ensure that any possible risks were detected and managed as early as possible, while ruling out coincidental but temporally related adverse health outcomes. We describe the role of the European Medicines Agency alongside the EU regulatory network in the safety monitoring of the COVID-19 vaccines, and provide an insight into challenges, particularities and outcomes of the scientific assessment and regulatory decisions in the complex, dynamic international environment of the pandemic.

Safety Monitoring of COVID-19 Vaccines: Perspective from the European Medicines Agency.

Prior to deployment of coronavirus disease 2019 (COVID-19) vaccines in the European Union in 2021, a high vaccine uptake leading to an unprecedented volume of safety data from spontaneous reports and real-world evidence, was anticipated. The European Medicines Agency (EMA) implemented specific activities to ensure enhanced monitoring of emerging vaccine safety information, including intensive monitoring of reports of adverse events of special interest and the use of observed-to-expected analyses. The EMA also commissioned several independent observational studies using a large network of electronic healthcare databases and primary data collection via mobile and web-based applications.

Assuring Access to Safe Medicines in Pregnancy and Breastfeeding.

Scientists and regulators in Europe and the United States continue to seek methods and strategies to improve knowledge on rational use of medicines for pregnant and breastfeeding populations, an important subset of women's health. Regulatory agencies have made strides toward improvement, but much more is needed. Recognizing the importance of international collaboration, we have begun to consider how to address these important public health issues more globally.

An algorithm to detect unexpected increases in frequency of reports of adverse events in EudraVigilance.

Purpose: The European Medicines Agency developed an algorithm to detect unexpected increases in frequency of reports, to enhance the ability to detect adverse events that manifest as increases in frequency, in particular quality defects, medication errors, and cases of abuse or misuse.

Methods: An algorithm based on a negative binomial time-series regression model run on 6 sequential observations prior to the monitored period was developed to forecast monthly counts of reports. A heuristic model to capture increases in counts when the previous 4 observations were null supplemented the regression.

Enhanced Paediatric Pharmacovigilance at the European Medicines Agency: A Novel Query Applied to Adverse Drug Reaction Reports.

Background: Databases of suspected adverse drug reactions (ADRs) are a cornerstone of pharmacovigilance. With increasing numbers of reports, additional statistical approaches are needed to better use the data.

Aim: The present study was aimed at elucidating the European Medicines Agency's (EMA) use of a novel 'paediatric' query to analyse the data in its ADR database 'EudraVigilance'.

Usage of unpublished paediatric data.

The European Paediatric Regulation (EC No 1901/2006) has three main objectives: increasing the number of appropriate medicines for children, increasing information on these medicines and stimulating high-quality ethical research with children. To contribute to the information, pharmaceutical companies were required under article 45 of the Regulation to submit existing paediatric studies to regulatory authorities for review and update of the product information. Nearly, 19 000 study reports have been identified for a thousand active substances.

Comparison between paediatric and adult suspected adverse drug reactions reported to the European medicines agency: implications for pharmacovigilance.

Background: Databases systematically collecting reports of suspected adverse drug reactions (ADRs) are a cornerstone of pharmacovigilance in that they provide on-going large-scale surveillance in the 'real-world' setting. Several studies have provided data on ADRs in children reported to national databases. EudraVigilance (EV) is the European Medicines Agency's (EMA) web-based system for reporting and evaluating suspected ADRs.