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.

ObjectiveElectronic healthcare databases (EHDs) are useful tools for drug development and safety evaluation but their heterogeneity of structure, validity and access across Europe complicates the conduct of multidatabase studies. In this paper, we provide insight into available EHDs to support regulatory decisions on medicines.MethodsEHDs were identified from publicly available information from the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance resources database, textbooks and web-based searches. Databases were selected using criteria related to accessibility, longitudinal dimension, recording of exposure and outcomes, and generalisability. Extracted information was verified with the database owners.ResultsA total of 34 EHDs were selected after applying key criteria relevant for regulatory purposes. The most represented regions were Northern, Central and Western Europe. The most frequent types of data source were electronic medical records (44.1%) and record linkage systems (29.4%). The median number of patients registered in the 34 data sources was 5 million (range 0.07–15 million) while the median time covered by a database was 18.5 years. Paediatric patients were included in 32 databases (94%). Completeness of information on drug exposure was variable. Published validation studies were found for only 17 databases (50%). Some level of access exists for 25 databases (73.5%), and 23 databases (67.6%) can be linked through a personal identification number to other databases with parent–child linkage possible in 7 (21%) databases. Eight databases (23.5%) were already transformed or were in the process of being transformed into a common data model that could facilitate multidatabase studies.ConclusionA Few European databases meet minimal regulatory requirements and are readily available to be used in a regulatory context. Accessibility and validity information of the included information needs to be improved. This study confirmed the fragmentation, heterogeneity and lack of transparency existing in many European EHDs.

IntroductionA review of European Union (EU)-funded initiatives linked to ‘Real World Evidence’ (RWE) was performed to determine whether their outputs could be used for the generation of real-world data able to support the European Medicines Agency (EMA)’s regulatory decision-making on medicines.MethodThe initiatives were identified from publicly available websites. Their topics were categorised into five areas: ‘Data source’, ‘Methodology’, ‘Governance model’, ‘Analytical model’ and ‘Infrastructure’. To assess their immediate relevance for medicines evaluation, their therapeutic areas were compared with the products recommended for EU approval in 2016 and those included in the EMA pharmaceutical business pipeline.ResultsOf 171 originally identified EU-funded initiatives, 65 were selected based on their primary and secondary objectives (35 ‘Data source’ initiatives, 15 ‘Methodology’, 10 ‘Governance model’, 17 ‘Analytical model’ and 25 ‘Infrastructure’). These 65 initiatives received over 734 million Euros of public funding. At the time of evaluation, the published outputs of the 40 completed initiatives did not always match their original objectives. Overall, public information was limited, data access was not explicit and their sustainability was unclear. The topics matched 8 of 14 therapeutic areas of the products recommended for approval in 2016 and 8 of 15 therapeutic areas in the 2017–2019 pharmaceutical business pipeline. Haematology, gastroenterology or cardiovascular systems were poorly represented.ConclusionsThis landscape of EU-funded initiatives linked to RWE which started before 31 December 2016 highlighted that the immediate utilisation of their outputs to support regulatory decision-making is limited, often due to insufficient available information and to discrepancies between outputs and objectives. Furthermore, the restricted sustainability of the initiatives impacts on their downstream utility. Multiple projects focussing on the same therapeutic areas increase the likelihood of duplication of both efforts and resources. These issues contribute to gaps in generating RWE for medicines and diminish returns on the public funds invested.

IntroductionPatient registries, ‘organised systems that use observational methods to collect uniform data on a population defined by a particular disease, condition, or exposure, and that is followed over time’, are potentially valuable sources of data for supporting regulatory decision-making, especially for products to treat rare diseases. Nevertheless, patient registries are greatly underused in regulatory assessments. Reasons include heterogeneity in registry design and in the data collected, even across registries for the same disease, as well as unreliable data quality and data sharing impediments. The Patient Registries Initiative was established by the European Medicines Agency in 2015 to support registries in collecting data suitable to contribute to regulatory assessments, especially post-authorisation safety and effectiveness studies.MethodsWe conducted a qualitative synthesis of the published observations and recommendations from an initiative-led multi-stakeholder consultation and four disease-specific patient registry workshops. We identified the primary factors facilitating the use of registry data in regulatory assessments. We generated proposals on operational measures needed from stakeholders including registry holders, patients, healthcare professionals, regulators, marketing authorisation applicants and holders, and health technology assessment bodies for implementing these.ResultsTen factors were identified as facilitating registry use for supporting regulatory assessments of medicinal products. Proposals on operational measures needed for implementation were categorised according to three themes: (1) nature of the data collected and registry quality assurance processes; (2) registry governance, informed consent, data protection and sharing; and (3) stakeholder communication and planning of benefit-risk assessments.ConclusionsThese are the first explicit proposals, from a regulatory perspective, on operational methods for increasing the use of patient registries in medicines regulation. They apply to registry holders, patients, regulators, marketing authorisation holders/applicants and healthcare stakeholders broadly, and their implementation would greatly facilitate the use of these valuable data sources in regulatory decision-making.Electronic supplementary materialThe online version of this article (10.1007/s40264-019-00848-9) contains supplementary material, which is available to authorized users.

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