The European Rare Diseases Research Alliance (ERDERA) aims to improve the health and well-being of the 30 million people living with a rare disease in Europe, by making Europe a world leader in Rare Disease (RD) research and innovation, to support concrete health benefits to rare disease patients, through better prevention, diagnosis and treatment. This Partnership will deliver a RD ecosystem that builds on the successes of previous programmes by supporting robust patient need-led research, developing new diagnostic methods and pathways, spearheading the digital transformational change connecting the dots between care, patient data and research, while ensuring strong alignment of strategies in RD research across countries and regions. Structuring goal-oriented public-private collaborations targeted at interventions all along the R&D value chain will ensure that the journey from knowledge to patient impact is expedited, thereby optimising EU innovation potential in RD. To support its ambition and missions ERDERA has been designed as a comprehensive and integrated ecosystem of which structure can be compared to an institute encompassing three main parts: (i) funding, (ii) internal (in house) Clinical Research Network that implements research activities targeting clinical trial readiness of RDs and accelerating diagnosis and translation of research discovery into improved patient care, and (iii) related supporting services (Data, Expertise, Education and Training) as well as an acceleration hub that serve external and internal RD community, all supported by all-embracing coordination and strategy and foundational (inter)national alignment.

Rare diseases are defined as diseases that affect not more than 1 person per 2000 in the European population. While individual rare diseases affect only a small percentage of the population, they collectively affect up to 30 million people in the EU. To facilitate access to high quality cross-border healthcare and promote and foster cooperation on rare disease healthcare between member states, 24 European Reference Networks (ERN) are currently active. The aim of the ERICA consortium, in which all 24 ERNs take part, is to build on the strength of the individual ERNs and create a platform that integrates all ERN’s research and innovation capacity. Through knowledge sharing, engagement with stakeholders in the rare disease domain and assembly of transdisciplinary research groups working across the global health spectrum ERICA strives to reach the following goals: • new intra- and inter-ERN rare disease competitive networks; • effective data collection strategies; • better patient involvement; • enhanced quality and impact of clinical trials; • increased awareness of ERN’s innovation potential; Through integration of ERN research activities, outreach to European research infrastructures to synergistically increase impact and innovation ERICA will strengthen the research and innovation capacity of the ERNs. This will result in safe, accessible and efficient access of therapies for the benefit of patients suffering from rare diseases and conditions.

RealiseD implements a collaborative and compRehensive mEthodological and operational Approach to cLinical trIalS in rarE Diseases enabling timely drug development and approval centred on patients’ needs with high level of evidence reachable in a limited environment. The core of RealiseD operational approaches includes the systematic procedures for patients’ referral, the certification of clinical sites and filling the gaps for successful development of rare and ultra rare diseases[(U)RD]’ clinical trials using 4 (U)RD diseases from 4 European Research Networks (ERNs). RealiseD methodological teams will optimise innovative statistical and quantitative approaches for design and analysis of (U)RD-CTs developed in the past 10 years and refined in the last years to facilitate the regulatory pathway for innovative drug development. RealiseD is implemented in a public private partnership consortium including regulators and HTA bodies representatives to co-create operational and methodological approaches in an iterative procedure using a multistakeholders’ agreement process. RealiseD will increase the incentives and motivation for the pharmaceutical industry by reducing many uncertainties on the path of drug development in (U)RD that will follow widely accepted rules. To achieve these innovative approaches, RealiseD will capitalise on an international multistakeholders effort as the problem in (U)RD drug development cannot be solved in a restricted geographical area. With the development and deployment of playbooks arising from the co-created developments, RealiseD will ascertain visibility and readiness of the innovations. The overall ambition of RealiseD is to change the paradigm of CT design for U(RD) by enlarging the spectrum of methodological and operational approaches and to establish a sustainable, innovative, and optimised CT paradigm for U(RD) medicinal product development programs, while maximizing the acceptance by all stakeholders.

As recognized by the Council Recommendation 2009/C 151/02, rare diseases (RD) are a prime example of a research area that can strongly profit from coordination on a European and international scale. RD research should be improved to overcome fragmentation, leading to efficacious use of data and resources, faster scientific progress and competitiveness, and most importantly to decrease unnecessary hardship and prolonged suffering of RD patients. In the specific context of the massive generation, need for reuse and efficient interpretation of data, introduction of omics into care practice and the structuration of RD care centers in European Reference Networks, it appears crucial and timely to maximize the potential of already funded tools and programmes by supporting them further, scaling up, linking, and most importantly, adapting them to the needs of end-users through implementation tests in real settings. Such a concerted effort is necessary to develop a sustainable ecosystem allowing a virtuous circle between RD care, research and medical innovation. To achieve this goal, the European Joint Programme on RD (EJP RD) has two major objectives: (i) To improve the integration, the efficacy, the production and the social impact of research on RD through the development, demonstration and promotion of Europe/world-wide sharing of research and clinical data, materials, processes, knowledge and know-how; (ii) To implement and further develop an efficient model of financial support for all types of research on RD (fundamental, clinical, epidemiological, social, economic, health service) coupled with accelerated exploitation of research results for benefit of patients. To this end, the EJP RD actions will be organized within four major Pillars assisted by the central coordination: (P1): Funding of research; (P2): Coordinated access to data and services; (P3) Capacity building; (P4): Accelerated translation of research projects and improvement outcomes of clinical studies.

XpanDH is a CSA aimed at mobilizing and building capacity in individuals and organisations to create, adapt and explore purposeful use of interoperable digital health solutions based on a shared adoption of the European Electronic Health Records Exchange format (EEHRxF) across Europe. This pan-European effort will use a “network-of-networks” approach ensuring that digital health actors are motivated and supported by tailored guidance and real examples to help early adopters to advance to the concrete use of EEHRxF-embedded digital health solutions to add value to health and care and promote Personal and European Health Data Spaces. XpanDH pursues the main goal of maturing and accelerating a sustainable and scalable interoperability environment for digital health innovations based on the EEHRxF, around 5 Goals: 1) To develop robust technical specifications and resources for the EEHRxF building; 2) To establish the X-Bundle Readiness model; 3) To verify the usefulness of the X-Bundle in real-world with a set of early adopters grouped under selected adoption domains; 4) To mature a pan-European digital health ecosystem of solution providers and end-users, 5) To develop a framework for sustainable ecosystem. The consortium will thrive on past and ongoing eHealth interoperability projects and services, and particularly on the X-eHealth and DigitalHealthEurope projects recommendations, through digital health data activism and strong patient engagement. It brings together 26 Digital Health Actors under a co-creation and co-implementation concept, supported by a Policy Board (linking to Governments and the eHealth Network). To expand its impact, 10 XpandDH networks of hundreds of health stakeholders will be nurtured to form a vibrant pan-European (Digital) Health space converging on common, usable, and reliable tools for real interoperable services that adoption of the EEHRxF and enhance healthcare cooperation for better health towards a European Health Union.