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This article reflects on the 2010 pharmacovigilance legislation of the European Union (EU). Its legislative aim of better patient and public health protection through new responsibilities for pharmaceutical companies and regulatory bodies is considered to have been achieved and is well supported by the good pharmacovigilance practices 'EU-GVP'. For future progress, we set out a vision for high-quality pharmacovigilance in a world of ongoing medical, technological and social changes. To deliver this vision, four principles are proposed to guide actions for further progressing the EU pharmacovigilance system: synergistic interactions with healthcare systems; trustworthy evidence for regulatory decisions; adaptive process efficiency; and readiness for emergency situations (the 'STAR principles'). Like a compass, these principles should guide actions for building capacity, technology and methods; improving regulatory processes; and expanding policies, frameworks and research agendas. Fit for the future, the EU system should achieve further improved outputs in terms of safe, effective and trusted use of medicines and positive health outcomes within patient-centred healthcare., (© 2024. The Author(s).)

Studies using real-world data (RWD) can complement evidence from clinical trials and fill evidence gaps during different stages of a medicine's lifecycle. This review presents the experience resulting from the European Medicines Agency (EMA) pilot to generate RWE to support evaluations by EU regulators and down-stream decision makers from September 2021 to February 2023. A total of 61 research topics were identified for RWE generation during this period, covering a wide range of research questions, primarily generating evidence on medicines safety (22, 36%), followed by questions on the design and feasibility of clinical trials (11, 18%), drug utilization (10, 16%), clinical management (10, 16%), and disease epidemiology. A significant number of questions were related to the pediatric population and/or rare diseases. A total of 27 regulatory-led RWD studies have been conducted. Most studies were descriptive and aimed at estimating incidence and prevalence rates of clinical outcomes including adverse events or to evaluate medicines utilization. The review highlights key learnings to guide further efforts to enable the use and establish the value of real-world evidence (RWE) for regulatory decisions. For instance, there is a need to access additional fit-for-purpose and representative data, and to explore further means to provide timely evidence that meets regulatory timelines. The need for early interactions and close collaboration with study requesters, e.g., from the Agency's scientific Committees, to better understand the research question is equally important. Finally, the review provides our perspective on the way forward to maximize the potential of regulatory-led RWE generation., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

This study measured the exposure to different categories of medicinal products discussed by the European Union (EU) Pharmacovigilance Risk Assessment Committee from September to November 2018 in four electronic primary care health databases: IQVIA Medical Research Data-UK, IQVIA Medical Research Data-France, IQVIA Medical Research Data-Germany, and Clinical Practice Research Datalink Aurum, in the entire lifespan of each database until August 31, 2018. The assessment of 83 centrally authorized products and 45 nationally authorized products showed that coverage was better for products marketed for longer duration and worse for orphan drugs. The ability to detect associations against hypothetical comparators was better for more common events and for larger effect sizes. Coverage of advanced therapies was worse for those typically administered in a specialized rather than primary care setting. This study shows that to enable better informed regulatory decisions there is a need to access complementary data sources, particularly capturing secondary care prescribing., (© 2020 European Medicines Agency. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)

The analysis of safety data from spontaneous reporting systems has a proven value for the detection and analysis of the risks of medicines following their placement on the market and use in medical practice. EudraVigilance is the pharmacovigilance database to manage the collection and analysis of suspected adverse reactions to medicines authorised in the European Economic Area. EudraVigilance first operated in December 2001, with access to the database being governed by the EudraVigilance access policy. We performed a literature search including data up to December 2016 to demonstrate how the data from EudraVigilance has been used in scientific publications. We describe the results, including by type of publication, research topics and drugs involved. In 50% of the publications, the data are used to describe safety issues, in 44% to analyse methodologies used in pharmacovigilance activities and in 6% to support clinical perspectives. We also outline a description of the use of the database by the European Union regulatory network. Driven by the full implementation of the 2010 pharmacovigilance legislation, EudraVigilance has undergone further enhancements together with a major revision of its access policy, taking into account the use of the new individual case safety report standard developed by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use and the International Organization for Standardization. The aim of the broadened access is to facilitate more effective safety monitoring of authorised medicines, to make more data available for research and to provide better access to information on suspected adverse reactions for healthcare professionals and patients. In November 2017, the new full functionalities of EudraVigilance were launched, including the extensive web access to data on suspected adverse drug reactions and the possibilities for academic research institutions to request a more extensive dataset for the purposes of health research. The main objective of this article is to describe the new access to the database together with the opportunities that this new access can bring for research. It is intended to promote an appropriate use of the data to support the safe and effective use of medicines.

Introduction: New pharmacovigilance legislation was adopted in the EU in 2010 and became operational in July 2012. The legislation placed an obligation on all national competent authorities (NCAs) and marketing authorisation holders (MAHs) to record and report cases of suspected adverse drug reactions (ADRs) received from patients., Objectives: This descriptive study aims to provide insight into patient reporting for the totality of the EU by querying the EudraVigilance (EV) database for the period of 3 years before the new pharmacovigilance legislation became operational and the 3 years after as well as comparing patient reports with those from healthcare professionals (HCPs) where feasible., Methods: We queried the EV database for the following characteristics of patient and HCP reports: demographics (patient sex and age), seriousness, reported ADR terms, reported indications, number of ADRs per report, time to report an ADR, and most reported substances. Wherever feasible, direct comparisons between patient reports and HCP reports were performed using relative risks., Results: The EV database contained a total of 53,130 patient reports in the 3 years preceding the legislation operation period and 113,371 in the 3 years after. Member states contributing the most patient reports to the EV database were the Netherlands, the UK, Germany, France and Italy. The results for indications and substances show that patients were more likely than HCPs to report for genitourinary, hormonal and reproductive indications. Patients reported more in general disorders and administration site conditions Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC), whereas HCPs reported more Preferred Terms (PTs) belonging in the Investigations SOC. However, 13 of the 20 reactions most frequently reported by patients were also among the top 20 reactions reported by HCPs., Conclusion: Patient reporting complemented reporting by HCPs. Patients were motivated to report ADRs, especially those that affected their quality of life. Sharing these results with NCAs and patient associations can inform training and awareness on patient reporting.

Product information (PI) is a vital part of any medicinal product approved for use within the European Union and consists of a summary of products characteristics (SmPC) for healthcare professionals and package leaflet (PL) for patients, together with the product packaging. In this study, based on the English corpus of the EMA product information documents for all centrally approved medicinal products within the EU, a BERT sentence embedding model was used together with clustering and dimensional reduction techniques to identify sentence similarity clusters that could be candidates for standardization. A total of 1258 medicinal products were included in the study. From these, a total of 783 K sentences were extracted from SmPC and PL documents which were aggregated into a total of 284 and 129 semantic similarity clusters, respectively. The spread distribution among clusters shows separation into different cluster types. Examples of clusters with low spread include those with identical word embeddings due to current standardization, such as section headings and standard phrases. Others show minor linguistic variations, while the group with the largest variability contains variable wording but with significant semantic overlap. The sentence clusters identified could serve as candidates for further standardization of the PI. Moving from free text human wording to auto-generated text elements based on multiple-choice input for appropriate parts of the package leaflet and summary of product characteristics, could reduce both time and complexity for applicants as well as regulators, and ultimately provide patients and prescribers with documents that are easier to understand and better adapted for search availabilities. [ABSTRACT FROM AUTHOR]

The understanding of the benefit risk profile, and relative effectiveness of a new medicinal product, are initially established in a circumscribed patient population through clinical trials. There may be uncertainties associated with the new medicinal product that cannot be, or do not need to be resolved before launch. Postlicensing or postlaunch evidence generation (PLEG) is a term for evidence generated after the licensure or launch of a medicinal product to address these remaining uncertainties. PLEG is thus part of the continuum of evidence development for a medicinal product, complementing earlier evidence, facilitating further elucidation of a product's benefit/risk profile, value proposition, and/or exploring broader aspects of disease management and provision of healthcare. PLEG plays a role in regulatory decision making, not only in the European Union but also in other jurisdictions including the USA and Japan. PLEG is also relevant for downstream decision‐making by health technology assessment bodies and payers. PLEG comprises studies of different designs, based on data collected in observational or experimental settings. Experience to date in the European Union has indicated a need for improvements in PLEG. Improvements in design and research efficiency of PLEG could be addressed through more systematic pursuance of Scientific Advice on PLEG with single or multiple decision makers. To date, limited information has been available on the rationale, process or timing for seeking PLEG advice from regulators or health technology assessment bodies. This article sets out to address these issues and to encourage further uptake of PLEG advice. [ABSTRACT FROM AUTHOR]

Pharmacovigilance and risk minimization must be planned during drug development and forms a critical part of the regulator's decision on whether a medicinal product can be authorized. Pharmacovigilance systems should ensure proactive monitoring of all authorized medicines throughout their lifecycle in clinical use. Signal detection and management are core activities in pharmacovigilance, rapidly delivering new information on the safety of medicines in real‐world use which helps to fill knowledge gaps. The first 6 years of the European Union (EU) signal management system resulted in 453 recommendations issued by the Pharmacovigilance Risk Assessment Committee (PRAC), of which more than half were for drug labeling changes. The EU pharmacovigilance network has demonstrated its ability to detect and evaluate new drug safety signals. This has resulted in new warnings to guide the safe and effective use of medicines in Europe. [ABSTRACT FROM AUTHOR]

This article provides an overview of the European Union pharmacovigilance system resulting from the rationalisation and strengthening delivered through the implementation of the revised pharmacovigilance legislation. It outlines the system aims, underlying principles, components and drivers for future change. At its core, the Pharmacovigilance Risk Assessment Committee is responsible for assessing all aspects of the risk management of medicinal products, thus ensuring that medicines approved for the European Union market are optimally used by maximising their benefits and minimising risks. The main objectives of the system are to promote and protect public health by supporting the availability of medicines including those that fulfil previously unmet medical needs, and reducing the burden of adverse drug reactions. These are achieved through a proactive, risk proportionate and patient-centred approach, with high levels of transparency and engagement of civil society. In the European Union, pharmacovigilance is now fully integrated into the life cycle of medicinal products, with the planning of pharmacovigilance activities commencing before a medicine is placed on the market, and companies encouraged to start planning very early in development for high-innovation products. After authorisation, information on the safety of medicines continues to be obtained through a variety of sources, including spontaneous reports of adverse drug reactions or monitoring real-world data. Finally, the measurement of the impact of pharmacovigilance activities, auditing and inspections, as well as capacity building ensure that the system undergoes continuous improvement and can always rely on the best methodologies to safeguard public health. [ABSTRACT FROM AUTHOR]

The authors comment on the changes brought by the new European Union (EU) pharmacovigilance legislation which would make pharmacovigilance as a foward-looking activity from mainly reactive to principally proactive. They set out the direction of travel for better public health promotion and protection in a complex and changing environment. They also offer views on some alternatives to traditional drug licensing models to improve efficacy and safety.