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Purpose: The first paper to specify the core content of pharmacoepidemiology as a profession was published by an ISPE (International Society for Pharmacoepidemiology) workgroup in 2012 (Jones JK et al. PDS 2012; 21[7]:677–689). Due to the broader and evolving scope of pharmacoepidemiology, ISPE considers it important to proactively identify, update and expand the list of core competencies to inform curricula of education programs; thus, better positioning pharmacoepidemiologists across academic, government (including regulatory), and industry positions. The aim of this project was to update the list of core competencies in pharmacoepidemiology. Methods: To ensure applicability of findings to multiple areas, a working group was established consisting of ISPE members with positions in academia, industry, government, and other settings. All competencies outlined by Jones et al. were extracted from the initial manuscript and presented to the working group for review. Expert‐based judgments were collated and used to identify consensus. It was noted that some competencies could contribute to multiple groups and could be directly or indirectly related to a group. Results: Five core domains were proposed: (1) Epidemiology, (2) Clinical Pharmacology, (3) Regulatory Science, (4) Statistics and data science, and (5) Communication and other professional skills. In total, 55 individual competencies were proposed, of which 25 were new competencies. No competencies from the original work were dropped but aggregation or amendments were made where considered necessary. Conclusions: While many core competencies in pharmacoepidemiology have remained the same over the past 10 years, there have also been several updates to reflect new and emerging concepts in the field. [ABSTRACT FROM AUTHOR]

Background: Real‐world data (RWD) are increasingly used to generate real‐world evidence (RWE) of vaccine safety and effectiveness for regulatory purposes. Assessing feasibility of using RWD sources prior to implementing observational studies is recommended. As a use case, we described the process and findings of a feasibility assessment to identify reliable and relevant data sources for monitoring the safety and effectiveness of the AS04‐HPV‐16/18 human papillomavirus (HPV) vaccine in China. Methods: Iterative multi‐step process: (1) targeted literature review and data source mapping; (2) expert opinion from national RWD experts; (3) survey to evaluate the identified data source operational infrastructure; and (4) continuous appraisal of published studies using the identified data source. Results: The Yinzhou Regional Health Information Platform (YRHIP) was identified as a data source of main interest, based on its large population coverage, high cervical cancer screening rates, and availability of adult electronic immunization records. Field meetings with national RWD experts confirmed its suitability for post‐authorization vaccine studies. Survey results showed that exposure data and relevant safety and effectiveness endpoints were recorded and linkable at the individual level across the platform. Iterative appraisal of emerging evidence from the literature corroborated these findings. Conclusions: This feasibility assessment indicates that the YRHIP has the capacity to capture demographic, exposure, outcome and other data required to generate RWE on HPV vaccine safety and effectiveness in China. Studies using the YRHIP to monitor the AS04‐HPV‐16/18 vaccine in routine use building on this feasibility assessment are ongoing. [ABSTRACT FROM AUTHOR]

Purpose: Heterogeneous results from multi‐database studies have been observed, for example, in the context of generating background incidence rates (IRs) for adverse events of special interest for SARS‐CoV‐2 vaccines. In this study, we aimed to explore different between‐database sources of heterogeneity influencing the estimated background IR of venous thromboembolism (VTE). Methods: Through forest plots and random‐effects models, we performed a qualitative and quantitative assessment of heterogeneity of VTE background IR derived from 11 databases from 6 European countries, using age and gender stratified background IR for the years 2017–2019 estimated in two studies. Sensitivity analyses were performed to assess the impact of selection criteria on the variability of the reported IR. Results: A total of 54 257 284 subjects were included in this study. Age–gender pooled VTE IR varied from 5 to 421/100 000 person‐years and IR increased with increasing age for both genders. Wide confidence intervals (CIs) demonstrated considerable within‐data‐source heterogeneity. Selecting databases with similar characteristics had only a minor impact on the variability as shown in forest plots and the magnitude of the I2 statistic, which remained large. Solely including databases with primary care and hospital data resulted in a noticeable decrease in heterogeneity. Conclusions: Large variability in IR between data sources and within age group and gender strata warrants the need for stratification and limits the feasibility of a meaningful pooled estimate. A more detailed knowledge of the data characteristics, operationalisation of case definitions and cohort population might support an informed choice of the adequate databases to calculate reliable estimates. [ABSTRACT FROM AUTHOR]

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. This preparedness was key for two high‐profile safety signals: thrombosis with thrombocytopenia syndrome (TTS), a new clinical entity associated with adenovirus‐vectored vaccines, and myocarditis/pericarditis with messenger RNA vaccines. With no existing case definition nor background rates, the signal of TTS posed particular challenges. Nevertheless, it was rapidly identified, evaluated, contextualized and the risk minimized thanks to close surveillance and an efficient use of available evidence, clinical expertise and flexible regulatory tools. The two signals illustrated the complementarity between spontaneous and real‐world data, the former enabling rapid risk identification and communication, the latter enabling further characterization. The COVID‐19 pandemic has tremendously enhanced the development of tools and methods to harness the unprecedented volume of safety data generated for the vaccines. Areas for further improvement include the need for better and harmonized data collection across Member States (e.g., stratified vaccine exposure) to support signal evaluation in all population groups, risk contextualization, and safety communication. [ABSTRACT FROM AUTHOR]

Information derived from routinely collected real‐world data has for a long time been used to support regulatory decision making on the safety of drugs and has more recently been used to support marketing authorization submissions to regulators. There is a lack of detailed information on the use and types of this real‐world evidence (RWE) as submitted to regulators. We used resources held by the European Medicines Agency (EMA) to describe the characteristics of RWE included in new marketing authorization applications (MAAs) and extensions of indication (EOIs) for already authorized products submitted to the EMA in 2018 and 2019. For MAAs, 63 of 158 products (39.9%) contained RWE with a total of 117 studies. For 31.7% of these products, the RWE submitted was derived from data collected before the planned authorization. The most common data sources were registries (60.3%) followed by hospital data (31.7%). RWE was mainly included to support safety (87.3%) and efficacy (49.2%) with cohort studies being the most frequently used study design (88.9%). For EOIs, 28 of 153 products (18.3%) contained RWE with a total of 36 studies. For 57.1% of these products, studies were conducted prior to the EOIs. RWE sources were mainly registries (35.6%) and hospital data (27.0%). RWE was typically used to support safety (82.1%) and efficacy (53.6%). Cohort studies were the most commonly used study design (87.6%). We conclude that there is widespread use of RWE to support evaluation of MAAs and EOIs submitted to the EMA and identify areas where further research is required. [ABSTRACT FROM AUTHOR]

Introduction: Information regarding availability of electronic healthcare databases in the Asia‐Pacific region is critical for planning vaccine safety assessments particularly, as COVID‐19 vaccines are introduced. This study aimed to identify data sources in the region, potentially suitable for vaccine safety surveillance. This manuscript is endorsed by the International Society for Pharmacoepidemiology (ISPE). Methods: Nineteen countries targeted for database reporting were identified using published country lists and review articles. Surveillance capacity was assessed using two surveys: a 9‐item introductory survey and a 51‐item full survey. Survey questions related to database characteristics, covariate and health outcome variables, vaccine exposure characteristics, access and governance, and dataset linkage capability. Other questions collated research/regulatory applications of the data and local publications detailing database use for research. Results: Eleven databases containing vaccine‐specific information were identified across 8 countries. Databases were largely national in coverage (8/11, 73%), encompassed all ages (9/11, 82%) with population size from 1.4 to 52 million persons. Vaccine exposure information varied particularly for standardized vaccine codes (5/11, 46%), brand (7/11, 64%) and manufacturer (5/11, 46%). Outcome data were integrated with vaccine data in 6 (55%) databases and available via linkage in 5 (46%) databases. Data approval processes varied, impacting on timeliness of data access. Conclusions: Variation in vaccine data availability, complexities in data access including, governance and data release approval procedures, together with requirement for data linkage for outcome information, all contribute to the challenges in building a distributed network for vaccine safety assessment in the Asia‐Pacific and globally. Common data models (CDMs) may help expedite vaccine safety research across the region. [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]

Purpose Investigational and marketed vaccines are increasingly evaluated, and manufacturers are required to put in place mechanisms to monitor long-term benefit-risk profiles. However, generating such evidence in real-world settings remains challenging, especially when rare adverse events are assessed. Planning of an appropriate study design is key to conducting a valid study. The aim of this paper is to illustrate how feasibility assessments support the generation of robust pharmacoepidemiological data. Methods Following an initiative launched by the International Society for Pharmacoepidemiology in May 2014, a working group including members of the private and public sectors, was formed to assess the value of conducting feasibility assessments as a necessary step before embarking on larger-scale post-licensure studies. Based on five real-life examples of feasibility assessments, lessons learned and recommendations were issued by the working group to support scientific reasoning and decision making when designing pharmacoepidemiologic vaccine studies. Results The working group developed a toolbox to provide a pragmatic approach to conducting feasibility assessments. The toolbox contains two main components: the scientific feasibility and the operational feasibility. Both components comprise a series of specific questions aimed at overcoming methodological and operational challenges. Conclusions A feasibility assessment should be formalized as a necessary step prior to the actual start of any pharmacoepidemiologic study. It should remain a technical evaluation and not a hypothesis testing. The feasibility assessment report may facilitate communication with regulatory agencies toward improving the quality of study protocols and supporting the endorsement of study objectives and methods addressing regulatory commitments. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]