Collaborative Real-World Evidence Among Regulators: Lessons and Perspectives.

The International Coalition of Medicines Regulatory Authorities (ICMRA), comprising 38 global medicines regulatory authorities, collaborates on shared challenges, notably during the COVID-19 pandemic. This article focuses on the ICMRA COVID-19 Real-World Evidence (RWE) and Observational Studies Working Group. The Working Group aimed to address challenges related to RWE and observational studies during the pandemic, resulting in impactful studies and ICMRA statements on international collaboration for RWE and COVID-19 vaccine safety.

Sharing Is Caring? International Society for Pharmacoepidemiology Review and Recommendations for Sharing Programming Code.

Purpose: There is increasing recognition of the importance of transparency and reproducibility in scientific research. This study aimed to quantify the extent to which programming code is publicly shared in pharmacoepidemiology, and to develop a set of recommendations on this topic.

Methods: We conducted a literature review identifying all studies published in Pharmacoepidemiology and Drug Safety (PDS) between 2017 and 2022.

The STAR Compass to Guide Future Pharmacovigilance Based on a 10-Year Review of the Strengthened EU System.

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.

Real-World Evidence to Support EU Regulatory Decision Making-Results From a Pilot of Regulatory Use Cases.

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 natural language processing approach towards harmonisation of European medicinal product information.

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.

HARmonized Protocol Template to Enhance Reproducibility of Hypothesis Evaluating Real-World Evidence Studies on Treatment Effects: A Good Practices Report of a Joint ISPE/ISPOR Task Force.

Objectives: Ambiguity in communication of key study parameters limits the utility of real-world evidence (RWE) studies in healthcare decision-making. Clear communication about data provenance, design, analysis, and implementation is needed. This would facilitate reproducibility, replication in independent data, and assessment of potential sources of bias.

HARmonized Protocol Template to Enhance Reproducibility of hypothesis evaluating real-world evidence studies on treatment effects: A good practices report of a joint ISPE/ISPOR task force.

Problem: Ambiguity in communication of key study parameters limits the utility of real-world evidence (RWE) studies in healthcare decision-making. Clear communication about data provenance, design, analysis, and implementation is needed. This would facilitate reproducibility, replication in independent data, and assessment of potential sources of bias.

The Impact of Mandatory Reporting of Non-Serious Safety Reports to EudraVigilance on the Detection of Adverse Reactions.

Introduction And Objective: European Union legislation has mandated the submission of European Economic Area non-serious reports to the EudraVigilance database since November 2017. As spontaneous reports of suspected adverse reactions to medicines represent a key source of safety signals, the European Medicines Agency has undertaken this work to assess the effects of this requirement on the characteristics of the reports submitted to EudraVigilance and on the detection of adverse drug reactions through routine analyses of the database.

Methods: Changes in the numbers of serious and non-serious reports transmitted to EudraVigilance were examined over the period during which the legislation was implemented.

Exploring the opportunities for alignment of regulatory postauthorization requirements and data required for performance-based managed entry agreements.

Performance-based managed entry agreements (PB-MEAs) might allow patient access to new medicines, but practical hurdles make competent authorities for pricing and reimbursement (CAPR) reluctant to implement PB-MEAs. We explored if the feasibility of PB-MEAs might improve by better aligning regulatory postauthorization requirements with the data generation of PB-MEAs and by active collaboration and data sharing. Reviewers from seven CAPRs provided structured assessments of the information available at the European Medicines Agency (EMA) Web site on regulatory postauthorization requirements for fifteen recently authorized products.

STaRT-RWE: structured template for planning and reporting on the implementation of real world evidence studies.

In alignment with the International Council of Harmonization’s strategic goals, a public-private consortium has developed a structured template for planning and reporting on the implementation of real world evidence (RWE) studies of the safety and effectiveness of treatments. The template serves as a guiding tool for designing and conducting reproducible RWE studies; set clear expectations for transparent communication of RWE methods; reduce misinterpretation of prose that lacks specificity; allow reviewers to quickly orient and find key information; and facilitate reproducibility, validity assessment, and evidence synthesis. The template is intended for use with studies of the effectiveness and safety of medical products and is compatible with multiple study designs, data sources, reporting guidelines, checklists, and bias assessment tools.

Does additional monitoring status increase the reporting of adverse drug reactions? An interrupted time series analysis of EudraVigilance data.

Purpose: To evaluate the impact of including a medicine in the list of medicinal products subject to additional monitoring (AM) on the reporting of adverse drug reactions (ADRs) in the european economic area (EEA).

Methods: Interrupted time series using the monthly number of EEA ADR reports in EudraVigilance during 12 months before and after the addition to AM list. The main outcome was the change (%) in reporting of ADRs with step change as the a priori impact model.

What are the patients' and health care professionals' understanding and behaviors towards adverse drug reaction reporting and additional monitoring?

Background: The additional monitoring (AM)/black triangle concept is aimed to enhance ADR reporting for certain types of medicinal products for which the safety profile is less well established.

Purpose: The objective of this survey was to assess (a) attitudes towards ADR reporting and reasons for not reporting an ADR and (b) awareness of AM among HCPs, patients or their careers in EU countries.

Methods: An online questionnaire which was available in all EU languages was completed by 2918 responders coming from all EEA countries.

Randomized Controlled Trials Versus Real World Evidence: Neither Magic Nor Myth.

Compared with drugs from the blockbuster era, recently authorized drugs and those expected in the future present a heterogenous mix of chemicals, biologicals, and cell and gene therapies, a sizable fraction being for rare diseases, and even individualized treatments or individualized combinations. The shift in the nature of products entails secular trends for the definitions of "drugs" and "target population" and for clinical use and evidence generation. We discuss that the lessons learned from evidence generation for 20th century medicines may have limited relevance for 21st century medicines.

Navigating stormy waters: 10 years of operation of the European Union Regulatory Network Incident Management Plan for Medicines for Human Use.

Purpose: The article provides an overview of the European Union Incident Management plan (EU-IMP) and reviews its first 10 years of operation. It outlines its scope, objectives, triggers, principles, and components.

Methods: Records were extracted from the European Pharmacovigilance Issues Tracking Tool and a separate tracking system for the period August 20, 2009 to August 19, 2019.