In order to provide responsible access to health data by reconciling benefits of data sharing with privacy rights and ethical and regulatory requirements, Findable, Accessible, Interoperable and Reusable (FAIR) metadata should be developed. According to the H2020 Program Guidelines on FAIR Data, data should be “as open as possible and as closed as necessary”, “open” in order to foster the reusability and to accelerate research, but at the same time they should be “closed” to safeguard the privacy of the subjects. Additional provisions on the protection of natural persons with regard to the processing of personal data have been endorsed by the European General Data Protection Regulation (GDPR), Reg (EU) 2016/679, that came into force in May 2018. This work aims to solve accessibility problems related to the protection of personal data in the digital era and to achieve a responsible access to and responsible use of health data. We strongly suggest associating each data set with FAIR metadata describing both the type of data collected and the accessibility conditions by considering data protection obligations and ethical and regulatory requirements. Finally, an existing FAIR infrastructure component has been used as an example to explain how FAIR metadata could facilitate data sharing while ensuring protection of individuals.

Although postmarketing studies conducted in population‐based databases often contain information on patients in the order of millions, they can still be underpowered if outcomes or exposure of interest is rare, or the interest is in subgroup effects. Combining several databases might provide the statistical power needed. A multi‐database study (MDS) uses at least two healthcare databases, which are not linked with each other at an individual person level, with analyses carried out in parallel across each database applying a common study protocol. Although many MDSs have been performed in Europe in the past 10 years, there is a lack of clarity on the peculiarities and implications of the existing strategies to conduct them. In this review, we identify four strategies to execute MDSs, classified according to specific choices in the execution: (A) local analyses, where data are extracted and analyzed locally, with programs developed by each site; (B) sharing of raw data, where raw data are locally extracted and transferred without analysis to a central partner, where all the data are pooled and analyzed; (C) use of a common data model with study‐specific data, where study‐specific data are locally extracted, loaded into a common data model, and processed locally with centrally developed programs; and (D) use of general common data model, where all local data are extracted and loaded into a common data model, prior to and independent of any study protocol, and protocols are incorporated in centrally developed programs that run locally. We illustrate differences between strategies and analyze potential implications.

In the European Union (EU) and United States (US), specific regulations have been released to provide incentives to develop and sell orphan medicinal products. We analysed the status of orphan drugs designated that not yet received a marketing authorisation or already marketed for patients affected by rare diseases in the EU and US up to December 2015. For each drug, the following data were extracted: designation date, active substance(s), orphan condition and indication, trade name, approved therapeutic indication, approved ages, genetic nature of disease and if affects children. In the EU, 1264 Orphan Drug Designations have been granted and 133 medicinal products were approved covering a total of 179 indications and 122 rare conditions. Among these, 79 were approved under Regulation (EC)141/2000 (65 still listed in the Orphan Medicinal Products Register and 14 lost the orphan designation but still authorised) and 23 were approved centrally by the European Agency before the Orphan Regulation entered into force. On the other hand, in the US 3082 designations and 415 orphan products, covering a total of 521 indications and 300 rare conditions, were granted. As a result, the mean of designations per year is 79 in the EU and 93.4 in the US, while the mean of approved indications per year is 8.5 in the EU and 15.8 in the US. No orphan product is marketed in the EU for bone and connective tissue, ophthalmic, poisoning/overdose, renal, urinary and reproductive rare diseases. Among the marketed medicinal products, only 46.6% in the EU and 35.2% in the US are approved for children. If all the existing market approvals were merged, 362 additional therapeutic indications in the EU and 72 in the US would be covered. Our data show that notwithstanding the incentives issued, the number of medicines for rare diseases is still limited, and this is more evident in certain therapeutic areas. However, by merging all the existing approvals, patients would benefit of substantial advantages in both geographic areas. Efforts and cooperation between EU and US seem the only way to speed up the development and marketing of drugs for rare diseases.

Background: The lack of harmonization of evaluation criteria by Ethics Committees in the European Union (EU) has led to inconsistent ethics reviews received by research sites participating in multicenter non-interventional studies. The European General Data Protection Regulation (GDPR) appears to be implemented at national level with a substantial degree of variance in interpretation. The European Reference Networks (ERNs) were struggling in setting an Informed Consent Form (ICF) for registries, allowing reuse of data for research purposes. The aim of this work is to develop an adaptable ICF for research purposes to be used in ERN registries.Methods: To work on this challenge, a team was established within the European Joint Programme on Rare Diseases (EJP RD) to develop a patients’ registry ICF template allowing easy adaptation to ERNs, country, and site-level specificities. ERN and patients’ representatives validated the choice of developing a GDPR-compliant template for research purposes. The feedback received from 34 Ethics Committees on the Clinical Patient Management System ICF, including the submission of patients’ data to the ERN registries and the EU consent regulatory framework were analyzed along with existing ontologies for data access and reuse. An adaptable ICF was developed following iterative cycles of consultation and review by clinicians, research experts, ethics and regulatory advisors, and patients’ representatives. The development of pediatric material for minor participants was also undertaken.Results and Conclusion: Research oriented ICF templates for adults and for parents/legal representatives of patients were released in 26 national languages. This adaptable ICF aims to foster, according to patients’ preferences, the reuse of registries data for research purposes in compliance with the applicable laws and standards. Pediatric material is being finalized to collect minors’ assent. ICF machine-readability is also progressing to enhance data discovery and facilitate its access and reuse conditions.

The reuse of paediatric individual patient data (IPD) from clinical trials (CTs) is essential to overcome specific ethical, regulatory, methodological, and economic issues that hinder the progress of paediatric research. Sharing data through repositories enables the aggregation and dissemination of clinical information, fosters collaboration between researchers, and promotes transparency. This work aims to identify and describe existing data-sharing repositories (DSRs) developed to store, share, and reuse paediatric IPD from CTs. A rapid review of platforms providing access to electronic DSRs was conducted. A two-stage process was used to characterize DSRs: a first step of identification, followed by a second step of analysis using a set of eight purpose-built indicators. From an initial set of forty-five publicly available DSRs, twenty-one DSRs were identified as meeting the eligibility criteria. Only two DSRs were found to be totally focused on the paediatric population. Despite an increased awareness of the importance of data sharing, the results of this study show that paediatrics remains an area in which targeted efforts are still needed. Promoting initiatives to raise awareness of these DSRs and creating ad hoc measures and common standards for the sharing of paediatric CT data could help to bridge this gap in paediatric research.