Alzheimer’s disease (AD) and Parkinson’s disease (PD) are common neurodegenerative conditions, posing a major societal burden. There is a lack of treatments to slow disease progression, and therapeutic development has been impeded by a lack of biomarkers that can detect individuals early in the disease, measure treatment effects, and stratify patients. European cohorts recruited for research on aging and neurodegeneration provide a huge potential for biomarker discovery and validation by providing bio-samples along with deep clinical and imaging phenotypes. However, these cohorts are difficult to access. An overview of the availability of data and samples is lacking, and protocols and regulations for data and sample collection, storage, and sharing vary. The European Platform for Neurodegenerative Diseases (EPND) will tackle the above issues by developing a self-sustaining European-based platform to facilitate discovery and access of relevant bio-samples and data. EPND will be built on an existing informatics infrastructure, the AD Workbench, which EPND will adapt to support resource- and participant-level discovery, data harmonisation, central and federated data and sample storage, and data analysis. The sample and data discovery tools will be connected to a network of over 60 cohorts on AD, PD, and related disorders. Together, these cohorts will facilitate access to data and samples of over 120,000 research participants including CSF (n=30,000), plasma (n=120,000), stools (n=6,000), urine (n=27,000), saliva (n=17,000) and digital biomarkers (n=2,000). Prospective data collection will also occur during the project. This approach provides the community with a new and powerful environment for collaborative cross study analysis of harmonised biomarkers, datasets and samples. EPND will provide visibility into the quality and standardization of the data and samples available in the platform from the cohorts available and will also provide protocols for ongoing data and sample collection. This will guarantee quality of samples available, an important factor for validation and regulatory approval for biomarkers. EPND will be guided by ethical, legal and regulatory experts, patients, and other stakeholders to ensure responsible practices and processes underpin all discovery, sharing and access of data and samples, whilst simultaneously ensuring the platform is self-sustainable by the end of the project. Thereby, EPND will provide the community with a long-term, powerful environment to aid biomarker research for neurodegenerative disorders, enabling critical advances in the development of treatments for AD and PD.

Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition affecting over five million people in the European Union. The combination of core symptoms (deficits in social-communication and repetitive and restricted behaviours and interests) and common comorbidities (e.g. epilepsy and depression) significantly reduces the quality of life and life-span of affected individuals. Currently there are no effective drug treatments for the core symptoms. Key factors that have hampered progress include; 1) limited understanding of the underlying pathophysiolog(ies); 2) lack of successful translation from animal models to humans; 3) testing of drugs with specific actions in biologically heterogeneous populations; 4) limited expertise of many European ASD centres in running large-scale clinical trials; and 5) trial designs (e.g. placebo effects). Our vision, therefore, is to apply a precision medicine approach to ASD and improve patient outcomes by tailoring treatments to a patient’s biological profile. Our efforts will build on the achievements of 5 other IMI initiatives, 4 Horizon 2020 networks, and 6 SMEs for the first time to; 1) align global resources to validate and qualify stratification biomarkers from infancy to adulthood; 2) develop objective outcome measures that can be used in trials; 3) create a European-wide clinical trials network that reliably carries out studies able to support filings to the EMA/FDA; 4) carry out better targeted clinical trials linked to other international efforts – including quick wins or “fast fails” of ineffective agents; 5) translate molecular mechanisms and drug effects between preclinical models and particular subtypes of ASD. Together we will bring Europe to the forefront of clinical research in ASD. Also we will provide a sustainable legacy that is accessible by others across the world, attracts industry into ASD, and helps transform healthcare.

RealHOPE will create an understanding of the real-life handling of protein drugs in hospital pharmacy, clinics and in the hands of patients by applying smart tag technologies. Different parameters will be logged and combined with protein characterisation at different stages, as well as with information from EFPIA partners on their drugs in use. Statistical evaluation of the data will be used to identify patterns in handling that are linked to protein destabilisation occurrence and type of protein degradation. Focus interviews with personnel in hospital pharmacies, clinics and with patients/care givers will be used to understand current handling practice and what the desired handling instructions and limitations are. These insights will be used to design in-use mimicking stability protocols for the protein drugs in the project. Ultra-scaled-down devices for stability assessment will be designed to be used in early phase for efficient development cost effective and safe future protein therapies. Protocols and devices will be validated towards the collected handling data base. Interventions in hospital pharmacies using e.g. compounding robots will be investigated. Techniques to assess e.g. aggregate formation in the final drug preparation situation will be evaluated together with SMEs producing analytical tools and hospital pharmacists. The collected data and interviews will form the base of development of teaching materials directed towards different target groups: hospital pharmacists, nurses and patients/care givers. App developers will be active in this part to design attractive and efficient apps for teaching and collecting therapy performance data.

EU-PEARL has the ambition of transforming the current approach of conducting single-compound clinical trials into the use of cross-company Integrated Research Platforms (IRPs), taking into consideration both patients’ interests and the opportunities from novel molecules for addressing medical needs. Patient-centric data and knowledge sharing have the potential to accelerate the development of new treatments and reduce the operational costs of clinical trials. EU-PEARL will improve clinical effectiveness, patients’ satisfaction and societal access to timely and affordable medicines and it will shape the clinical trials of the future. This will change the industry paradigm from competition to cooperation in four disease areas and provide the framework for designing IRPs in other disease areas. The main objectives of EU-PEARL are: (1) To create a reusable, accessible and sustainable modular IRP for the design and execution of patient-centric, cross- company IRP in any disease area with unmet needs; (2) To set up the open, dynamic, patient inclusive IRP governance structure that will manage the appropriate regulatory, ethical, legal, statistical and data utilisation requirements of the IRP; (3) To disseminate and exploit the EU-PEARL paradigm through the provision of the necessary common tools, procedures, expertise and operational skills working to the highest scientific, regulatory and ethical standards and best practices, developed jointly by public and industry partners in a consensus-based approach; and (4) To create trial-ready IRP networks in the four disease areas of Major Depressive Disorder (MDD), Tuberculosis (TB), Non-Alcoholic Steatohepatitis (NASH) and Neurofibromatosis (NF).

Clinical trials increase in size, complexity and costs. This is fuelled with the need to demonstrate effects in more complex therapeutic areas, and to detect subgroups with different benefit and safety responses. Complexities, rigid clinical control, physical distance and (perceived) burden put patient engagement under pressure. (S)low recruitment and retention compromise efficiency, generalisability and validity of traditional, site-centred trials. Remote Decentralized Clinical Trials (RDCTs) and hybrid approaches address these challenges. RDCTs are an operational strategy for technology-enhanced clinical trials, which enable (semi-)continuous data collection and real-world evidence generation, increase patient recruitment and retention and decrease patient and investigator burden and costs. Trials brought to the home of patients. Paradigmatic changes in EU clinical trial design are required to fully benefit from the digital era. Yet, the feasibility of running RDCTs needs to be rigorously demonstrated together with guidance and support measures for their execution. Trials@Home brings together a very strong consortium and will reshape clinical trial design, conduct and operations, by analysing, developing and piloting standards, recommendations and tools to define and operationalize RDCTs. Trials@Home will design and run a pan-European RDCT pilot based on: a. best practices of trials with RDCT elements, b. assessment of latest technological tools, c. the regulatory and ethical framework and potential changes required to facilitate RDCTs and d. stakeholder perspectives on the change from classical RCTs to RDCTs with strong patient involvement. The results of these assessments and the pilot will drive the formulation and dissemination of recommendations and tools for the implementation of RDCTs in Europe with the ultimate goal to improve the speed, quality and efficiency of clinical trials, and improving patients’ access to innovative treatment strategies.