PurposeKnowledge of the benefits and risks of new drugs is incomplete at the time of marketing approval. Registries offer the possibility for additional, post‐approval, data collection. For all new drugs, which were approved in the European Union between 2007 and 2010, we reviewed the frequency, the type, and the reason for requiring a registry.MethodsThe European Public Assessment Reports, published on the website of the European Medicine Agency, were reviewed for drugs approved by the Committee for Medicinal Products for Human Use. We searched for key characteristics of these drugs, including therapeutic area (ATC1 level), level of innovation (the score is an algorithm based on availability of treatment and therapeutic effect), and procedural characteristics. In addition, we identified if these registries were defined by disease (disease registry) or exposure to a single drug (drug registry).ResultsOut of 116 new drugs approved in the predefined period, for 43 (37%), 1 to 6 registry studies were identified, with a total of 73 registries. Of these 46 were disease registries and 27 (single) drug registries. For 9 drugs, the registry was a specific obligation imposed by the regulators. The level of innovation and the orphan status of the drugs were determinants positively predicting post‐approval registries (OR 10.3 [95% CI 1.0‐103.9] and OR 2.8 [95% CI 1.0‐7.5], respectively).ConclusionsThe majority of registries required by regulators are existing disease registries. Registries are an important and frequently used tool for post‐approval data collection for orphan and innovative drugs.

Introduction In rare diseases, registry-based studies can be used to provide natural history data pre-approval and complement drug efficacy and/or safety knowledge post-approval. Objective The objective of this study was to investigate the opinion of stakeholders about key aspects of rare disease registries that are used to support regulatory decision making and to compare the responses of employees from industry to other stakeholders. Methods A web-based survey was used to gauge the importance of (1) common data elements (including safety outcomes), (2) data quality and (3) governance aspects that are generic across different rare diseases. The survey included 47 questions. The data were collected in the period April-October 2019. Results Seventy-three respondents completed ≥ 80% of the survey. Most of the respondents were from the industry (n = 42, 57%). For safety data, 31 (42%) respondents were in favour of collecting all adverse events. For data quality, the respondents found a level of 30% reasonable for source data verification. For missing data, a level of 20% was considered acceptable. Compared to responders from industry, the other stakeholders found it less relevant to share data with industry and found it less acceptable if the registry is financed by industry. Conclusions This study showed that the opinion towards data and governance is well aligned across parties, and issues of data and governance on their own should not pose a barrier to collaboration. This finding is supportive of the European Medicines Agency's efforts to encourage stakeholders to work with existing registries when collecting data to support regulatory decision making.

Real-world data/evidence (RWD/RWE) may provide insightful information on medicines' clinical effects to guide regulatory decisions. While its contribution has been recognized for safety monitoring and disease epidemiology across medicines' life cycles, using RWD/RWE to demonstrate efficacy requires further evaluation. This study aimed to (i) characterize RWD/RWE presented by applicants to support claims on medicines' efficacy within initial marketing authorization applications (MAAs) and extension of indication applications (EoIs), and (ii) analyze the contribution of RWD/RWE to regulatory decisions on medicines' benefit-risk profile. RWD/RWE was included to support efficacy in 32 MAAs and 14 EoIs submitted 2018-2019. Of these, RWD/RWE was part of the preauthorization package of 16 MAAs and 10 EoIs, and was (i) considered supporting the regulatory decision in 10 applications (five MAAs, five EoIs), (ii) considered not supporting the regulatory decision in 11 (seven MAAs, four EoIs), and (iii) not addressed at all in the evaluation of 5 applications (four MAAs, one EoI). Common limitations of submitted RWD/RWE included missing data, lack of representativeness of populations, small sample size, absence of an adequate or prespecified analysis plan, and risk of several types of bias. The suitability of RWD/RWE in a given application still requires a case-by-case analysis considering its purpose of use, implying reflection on the data source, together with its assets and limitations, study objectives and designs, and the overall data package issued. Early interactions and continuous dialogues with regulators and relevant stakeholders is key to optimize fit-forpurpose RWE generation, enabling its broader use in medicines development.

Between 2000 and 2021, the European Medicines Agency (EMA) assigned the orphan designation to over 1,900 medicines. Due to their small target populations, leading to challenges regarding clinical trial recruitment, study design and little knowledge on the natural history of the disease, the overall clinical evidence submitted at the time of marketing authorisation application for these medicines is often limited. Patient registries have been recognised as important sources of data on healthcare practices, drug utilisation and clinical outcomes. They may help address these challenges by providing information on epidemiology, standards of care and treatment patterns of rare diseases. In this review, we illustrate the utility of patient registries across the different stages of development of medicinal products, including orphans, to provide evidence in the context of clinical studies and to generate post-authorisation long term data on their effectiveness and safety profiles. We present important initiatives leveraging the role of registries for orphan medicinal products’ development and monitoring to ultimately improve patients’ lives.

Previously performed CTs in PUPs were divergent, which prevented a direct comparison of outcomes. However, this study demonstrated that data from CTs and carefully designed registries may complement each other in the establishing of sufficient safety information for single products to improve clinical insights and support regulatory decisions.

Enrollment of patients into postapproval registries is poor, although the results for imposed registries seem better. Currently, registries only have a limited impact on resolving gaps in the knowledge of a drug's benefits and risks at time of marketing authorization.

Introduction As patient registries are not subject to regulatory requirements on the collection of adverse events (AEs) related to medicinal products, they may not have foreseen the collection of such information on a routine basis or as part of specific data collection schemes. Objective The European Medicines Agency conducted a survey among registries to better understand their approach towards the collection, management and reporting of AEs related to medicines. Method An online survey composed of 15 questions was distributed in May 2020 to registries listed in the European Network of Centres in Pharmacoepidemiology and Pharmacovigilance (ENCePP) resources database for completion by August 2020. Aggregated results are presented in this paper. Results One third of the registries completed the survey (31/85; 36.5%). Most of the respondents routinely collect information on medicines (29/31; 93.5%), out of which 65.5% (19/29) also collect data on AEs and adverse drug reactions (ADRs). Frequencies and timelines for collecting and reporting AEs/ADRs vary widely across registries, as does their level of experience in providing data to third parties for regulatory purposes. Conclusions The low response rate may indicate little interest in this topic or that registries were not originally developed for routine data collection on AEs/ADRs and, ultimately, monitoring of the safety of medicines. Results indicate that clear guidance on the collection and use of real-world data in regulatory frameworks and strengthened collaboration between registry holders, academia, regulators and medicines developers are needed to achieve comprehensive and high levels of quality of safety data captured by registries to support regulatory decision making. These will hopefully be enabled by the European Medicines Regulatory Network strategy to 2025.

Real world data (RWD) usually refers to healthcare information that is routinely collected in electronic healthcare records (EHR), hospital and pharmacy records, patient and disease registries, and health insurance databases. The collection and analysis of this vast amount of data is an important complement to that obtained from conventional randomised controlled trials (RCT). RWD has been used for healthcare quality improvements, to conduct clinical trials, to support drug and device development, and to inform medical guidelines. The utility of RWD is facilitated by common data models, which standardise format and content, and allow data from different health systems to be analysed together. The European Society of Cardiology (ESC) supports the use of RWD in collaboration with national cardiac societies, regulatory authorities and industry to encourage continuous quality of care improvements at the hospital and country level, to conduct registry-based randomised clinical trials (R-RCT) and to facilitate safety surveillance of novel drugs and devices. The European Medicines Agency (EMA) is developing systems and processes to enable the use of RWD that can help in trial planning, defining clinical contexts, and enhancing outcome assessments. RWD can also contribute to the measurement of the impact of regulatory actions, such as contraindications or restriction of indications by looking at medicines use patterns over time across European Member States. A number of other initiatives from the European Commission and the EMA are underway to strengthen the EU's health security framework, and foster the collection and utilisation of RWD.