Progress in the life sciences and related technologies offer great potential for therapeutic benefits to patients in need. However, major adaptations to current paradigms of bringing medicines to patients are required in order to realize that potential and to address important challenges in the healthcare ecosystem. Against this background, several initiatives are exploring new pathways to market, collectively referred to as Medicines Adaptive Pathways to Patients (MAPPs). The ADAPT-SMART consortium is aligning a limited number of major stakeholders eager to progress towards MAPPs implementation. It will act as a neutral collaborative platform that will engage industry, SMEs, regulators, Health Technology Assessment bodies (HTAs), payers, governments, clinicians and patients. The ADAPT-SMART consortium will contribute to align understanding of the impact of MAPPs, to share learnings between all stakeholders, and to allow the field to actively work towards MAPPs implementation. The impact of the ADAPT-SMART CSA will be a result of the delivery of • actionable advice/recommendations to IMI on how to best leverage results from past/current projects; • concrete proposals for future (IMI) projects; • actionable advice/recommendations and information to other actors in the healthcare environment; • synthesis of learnings from pilot projects and case studies with relevance to MAPPs; • communication of CSA outcomes by way of publications and conference presentations. This CSA will increase the probability of successful implementation of MAPPs and accelerate access to crucial therapies, thus improving the position of both the patients in need of novel treatments and the research-based pharmaceutical industry.

The overall goal of the Big Data for Better Outcomes (BD4BO) programme is to facilitate the use of ‘big data’ to promote the development of value-based, outcomes-focused healthcare systems in Europe. To fully exploit the transformative potential of big data, consideration will need to be taken of the use of detailed personal and biological information across the spectrum of care delivery, starting from the development of innovative medicines and treatments, to market access and adoption, diffusion, and use in healthcare systems by providers and patients. This paradigm shift requires shared understanding and standards among healthcare stakeholders including patients, providers, payers, regulators, policy makers, pharmaceutical industry, and academia. OBJECTIVES The proposed Coordination and Support Action (CSA) will establish an enabling platform that brings together these stakeholder groups across the BD4BO programme to ensure quality and consistency of individual projects in line with the overarching programme objective. Our consortium therefore aims to promote the use of big Data for better Outcomes, policy Innovation and healthcare system Transformation (DO->IT). Accordingly, we will: • Define a programme strategy that ensures quality, consistency and sustainability of health outcomes related activities across individual BD4BO projects. • Integrate, synthesise, and manage knowledge from all BD4BO projects, making it easily accessible via a single knowledge exchange platform. • Act as pivotal point of collaboration, stakeholder engagement and communication for all BD4BO projects. • Provide transparency and enable the use of patient health data and human biological samples for research purposes by developing minimum data privacy standards for Informed Consent Forms (ICFs) and supporting materials for use by individual BD4BO disease-specific projects and more widely in the Research and Development (R&D) sector.

The objectives of SEARCH are truly ground-breaking, seeking to enable extensive data aggregation and analysis while safeguarding the integrity and privacy of original datasets through synthetically derived proxies. This initiative is designed to address biomedical challenges in Europe and offer translational solutions that will ultimately contribute to the advancement of personalised medicine. Unlike traditional data-sharing platforms that mainly focus on technical obstacles, SEARCH adopts an innovative approach by addressing legal, ownership, and subject privacy concerns. It specifically targets distributed institutional repositories that are hesitant to share multimodal clinical data, overcoming security concerns through a combination of clinical synthetic data proxies and a Federated Learning framework. Until synthetic data proxies gain wider acceptance, this combined strategy aimed at alleviating security concerns, facilitates the scalability required for AI analysis and promotes creative public-private data collaborations. SEARCH will offer advanced data federation capabilities, incorporating unique Synthetic Data Generation features to create various data types, including those not comprehensively addressed currently (e.g., wearable device data, image sequences, and genomic data). Through curated access to these novel digital tools, SEARCH will facilitate convenient access for the healthcare industry and research community to address bottlenecks and challenges in the development of novel tools for personalized prevention, diagnosis and treatment based on explainable AI. Moreover, SEARCH will provide agreed-upon gold standard synthetic datasets for evaluating the performance of biomedical AI solutions. SEARCH aims to consolidate European Innovation and Research endeavours by promoting public and private collaborations to unlock the potential for innovation in the digital healthcare sector.

Cancer remains the leading cause of disease-related death in children. For the ~25% of children who experience relapses of their malignant solid tumors, usually after very intensive first-line therapy, curative treatment options are scarce. Preclinical drug testing to identify promising treatment options that match the molecular make-up of the tumor is hampered by the facts that i) molecular genetic data on pediatric solid tumors from relapsed patients and thus our understanding of tumor evolution and therapy resistance are very limited to date and ii) for many of the high-risk entities no appropriate and molecularly well characterized patient-derived models and/or genetic mouse models are currently available. Thus, quality-assured upfront preclinical testing of novel molecularly targeted compounds in a (saturated) repertoire of well-characterized models will establish the basis to increase therapeutic successes of these drugs in children with solid malignancies. Since these tumors are overall genetically much less complex than their adult counterparts, it is anticipated that it will be easier to identify powerful predictive biomarkers to allow for accurate matching of targets and drugs. To address this high, as yet unmet clinical need, we have formed the ITCC-P4 consortium consisting of academic and commercial partners from 8 European countries and covering the full spectrum of qualifications needed for quality-assured preclinical drug development including expertise in patient derived models, histopathology, in vivo pharmacology, bioinformatics and data management, centralized testing capabilities, medical expertise regarding the entities in question, regulatory knowledge, and project management of large consortia. With this consortium in a public-private partnership with the participating pharma companies we strongly believe to be ideally positioned to greatly expedite the development of more precise and efficacious drugs for children with malignant solid tumors

Europe generates real world health data (RWD) that has the potential to inform the development and evaluation of medicines and medical devices. However, multiple barriers remain that limit the access, analysis, interpretation, and use of RWD, hampering its use. Additionally, the limited uptake of existing guidelines for the generation and use of real world evidence (RWE) adds complexity in the use of RWD to inform decision making. The GREG consortium will leverage the learnings of previous and ongoing key RWE initiatives to fill these gaps by generating, pilot-testing, and disseminating evidence-based guidance and tools for the use of RWE to inform the development and evaluation of medicines, medical devices, and combinations. To achieve these goals, we will work with key stakeholders to iteratively test and improve our guidance and tools, backed by case studies from previous successful and unsuccessful examples. We will engage with the most relevant European RWE initiatives and access the largest network of RWD partners in Europe, namely the European Health Data and Evidence Network (EHDEN) through our partner, the EHDEN Foundation. Additionally, we will provide multi-stakeholder gatherings (including patient and public representatives) to promote the dissemination, adoption, and implementation of RWE for decision-making in Europe. Our public and private partners will co-create use cases working closely with key regulatory and health technology experts in bespoke fora. These will be used initially to evaluate existing guidelines, and later to pilot-test the GREG guidance and tools. Our outputs will include training for all involved stakeholders on the use of our guidance and tools, and practical templates to facilitate regulatory and health technology/payer submissions. Together, these will accelerate access to better medicines and medical devices for European citizens.