Development of predictive biomarkers of disease progression and treatment response by using AI methodologies for chronic non-communicable diseases

Clinicians and healthcare professionals use clinically validated predictive biomarkers for implementing more effective clinical research and personalised medicine with better health outcomes in chronic non-communicable diseases. Key stakeholders have access to trustworthy Artificial Intelligence (AI) tools to guide the development of multimodal predictive biomarkers of higher accuracy and clinical value when compared to the established practice. The citizens benefit of better health outcomes thanks to improved clinical guidelines and the implementation of effective biomarker-guided clinical research and personalised healthcare. Scope: Biomarkers [1] are invaluable tools for improving patient outcomes, guiding treatment decisions, accelerating personalised medicine, more effective clinical research and the development of better medicines. However, despite the scientific discoveries of many clinically relevant biomarkers, estimated on the scale of tens of thousands, only a few biomarkers have been implemented in clinical practice. The traditional ‘one biomarker’ paradigm is insufficient for addressing the unmet clinical needs of chronic, progressive and multifactorial diseases, due to the complexity of the clinical phenotypes characterised by broad inter-and intra-patient heterogeneity. The established biomarkers have limitations in their use as prognostic and predictive indicators, for the assessment of the disease progression and the choices of the optimal therapeutic interventions tailored to the patients’ characteristics. Therefore, the topic focuses on the clinical development of predictive biomarkers of disease progression and treatment response for chronic non-communicable diseases (excluding cancer) by using established AI methodologies able to combine data of clinically used and candidate biomarkers, with available data from relevant clinical studies, longitudinal and Real-World Data (RWD) [2] . This topic is expected to support collaborative projects paving the way for future innovations in personalised medicine and enabling more timely and effective therapeutic interventions. The proposals should address all the following research and innovation activities: Set-up a multidisciplinary collaboration to map and evaluate the available information and data on biomarkers currently used in the clinical setting, candidate biomarkers from past and ongoing clinical studies, which are scientifically proven as clinically relevant to the disease progression and treatment response for the chronic non-communicable diseases under study. This should include stratification by biological sex, and where feasible, integration of gender-related variables and sociodemographic determinants that may modulate disease trajectories or treatment efficacy. Adapt and apply of established AI methods rather than developing novel ones from scratch, to deliver novel predictive biomarkers of disease progression and treatment response, by integrating data of currently used and candidate biomarkers, with suitable data from available longitudinal and other relevant clinical studies, including RWD, as necessary. To guarantee a solid and fast optimisation and training of the AI tools, the applicants should provide information in their proposal that the appropriate high-quality clinical data are readily available, and when necessary generate small-scale new data for the AI optimisation needs. The biomarkers under study should be multimodal, covering for instance molecular, cellular, physiological, imaging, behavioural and digital markers, and/or their combinations. The applicants should justify why the development of the biomarkers proposed is imperative to tackle the unmet clinical needs of the chronic non-communicable diseases under study. Use AI and, where needed, other relevant data and knowledge integration methods, to describe the relationships among different biomarkers and support the robust prioritisation of predictive biomarkers tailored to the characteristics of the patients’ and their disease stage and treatment response. Proposals should have strong emphasis on the AI trustworthiness [3] and develop the adequate performance metrics to assess their accuracy, reliability, reproducibility, including the assessment of possible inherent bias. Use of AI and dataset should comply with existing privacy-preserving legislation. Moreover, proposals should consider the development of user-friendly and fit-for-purpose visualisation and decision-support tools to guide clinicians in evaluating the clinical plausibility of the biomarkers under study across diverse patient groups. Establish a biomarker validation platform to assess the clinical utility of the predictive biomarkers identified. To this end, the applicants should implement clinical validation studies in independent disease cohorts, RWD and exploratory clinical studies, as appropriate, to demonstrate their clinical value as prognostic and predictive indicators for more effective clinical research and better patient health outcomes as compared to the established clinical practice of chronic non-communicable diseases. Prospective clinical studies are expected to be led by entities in the EU/EFTA and/or Associated Countries. Develop a comprehensive exploitation plan for the valorisation of the research outputs and a regulatory strategy to support the alignment to the regulatory requirements for the qualification of the biomarkers and/or AI tools and engage with the regulators in a timely manner. The applicants should prioritise the exploitation of their research results in the EU. Participation of small and medium-sized enterprises (SMEs) [4] is encouraged with the aim to strengthen the scientific and technological basis of SMEs and valorise their health innovations. Proposals should apply good practices for GDPR [5] compliant personal data protection. Proposals are encouraged, where relevant, to exploit the available data services, expertise and digital tools offered by the relevant European research infrastructures [6] and/or data infrastructures [7] in the area of health funded under the Digital Europe Programme. All proposals selected for funding under this topic will be strongly encouraged to participate in networking and joint activities (e.g. participation in joint workshops, development of best practices, or joint communication activities), which may also involve networking with projects funded under Horizon Europe, or other EU programmes (e.g. the Digital Europe Programme [8] ). The proposals should allocate a sufficient budget for networking and joint activities, without the prerequisite to detail such activities at the proposal stage. Applicants should provide details of their clinical studies [9] in the dedicated annex using the template provided in the submission system. As proposals under this topic are expected to include clinical studies, the use of the template is strongly encouraged. [1] See definition as in the Strategic Research and Innovation Agenda of the Innovative Health Initiative Joint Undertaking: http://www.ihi.europa.eu/sites/default/files/uploads/Documents/About/IHI_SRIA_ApprovedJan22.pdf [2] EMA definition: “Real-World Data are routinely collected data relating to patient health status or the delivery of healthcare from a variety of sources other than traditional clinical trials (e.g. claims databases, hospital data, electronic health records, registries, mhealth data, etc.)”. [3] See introduction to this Work Programme part as well as the Ethics Guidelines for Trustworthy AI, published by the European Commission’s High Level Expert Group on Artificial Intelligence https://digital-strategy.ec.europa.eu/en/library/ethics-guidelines-trustworthy-ai and the Ethics by Design and Ethics of Use Approaches for Artificial Intelligence https://ec.europa.eu/info/funding-tenders/opportunities/docs/2021-2027/horizon/guidance/ethics-by-design-and-ethics-of-use-approaches-for-artificial-intelligence_he_en.pdf [4] https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32003H0361 [5] General Data Protection Regulation: https://commission.europa.eu/law/law-topic/data-protection_en , https://gdpr-info.eu [6] The catalogue of European Strategy Forum on Research Infrastructures (ESFRI) research infrastructures portfolio can be browsed on the ESFRI website: https://ri-portfolio.esfri.eu [7] https://digital-strategy.ec.europa.eu/en/policies/artificial-intelligence-health [8] https://digital-strategy.ec.europa.eu/en/activities/digital-programme [9] Please note that the definition of clinical studies (see introduction to this Work Programme part) is broad and it is recommended that you review it thoroughly before submitting your application.

Eligibility and submission conditions

"> General conditions 1. Admissibility Conditions, proposal page limit and layout Applicants submitting a proposal for a blind evaluation (see General Annex F) must not disclose their organisation names, acronyms, logos nor names of personnel in the proposal abstract and Part B of their first-stage application (see General Annex E). Admissibility conditions are described in Annex A and Annex E of the Horizon Europe Work Programme General Annexes. Proposal page limits and layout are described in Part B of the Application Form available in the Submission System. 2. Eligible Countries Eligible countries are described in Annex B of the Work Programme General Annexes. A number of non-EU/non-Associated Countries that are not automatically eligible for funding have made specific provisions for making funding available for their participants in Horizon Europe projects. See the information in the Horizon Europe Programme Guide . 3. Other Eligibility Conditions In recognition of the opening of the US National Institutes of Health’s programmes to European researchers, any legal entity established in the United States of America is eligible to receive Union funding. If projects use satellite-based earth observation, positioning, navigation and/or related timing data and services, beneficiaries must make use of Copernicus and/or Galileo/EGNOS (other data and services may additionally be used). Subject to restrictions for the protection of European communication networks. Other eligibility conditions are described in Annex B of the Work Programme General Annexes. 4. Financial and operational capacity and exclusion Financial and operational capacity and exclusion are described in Annex C of the Work Programme General Annexes. 5a. Evaluation and award: Award criteria, scoring and thresholds The first-stage proposals of this topic will be evaluated blindly. Award criteria, scoring and thresholds are described in Annex D of the Work Programme General Annexes. 5b. Evaluation and award: Submission and evaluation processes For the first stage, the thresholds for each criterion will be 4 (Excellence) and 4 (Impact). The overall threshold applying to the sum of the two individual scores will be set at a level that ensures the total requested budget of proposals admitted to stage 2 is as close as possible to four times the available budget, and not less than three and a half times the available budget. For the second stage, the thresholds for each criterion will be 4 (Excellence), 4 (Impact) and 4 (Implementation). The cumulative threshold will be 12. Submission and evaluation processes are described in Annex F of the Work Programme General Annexes and the Online Manual . 5c. Evaluation and award: Indicative timeline for evaluation and grant agreement Indicative timeline for evaluation and grant agreement are described in Annex F of the Work Programme General Annexes. 6. Legal and financial set-up of the grants The granting authority may, up to 4 years after the end of the action, object to a transfer of ownership or to the exclusive licensing of results, as set out in the specific provision of Annex 5. Legal and financial set-up of the grants are described in Annex G of the Work Programme General Annexes. Specific conditions Specific conditions are described in the specific topic of the Work Programme. Application and evaluation forms and additional documents: Application and evaluation form templates Standard application form (HE RIA IA Stage 1 BLIND) - the application form specific to this call is available in the Submission System Standard application form (HE RIA, IA) - the application form specific to this call is available in the Submission System Standard evaluation form (HE RIA, IA and CSA Stage 1 BLIND) - will be used with the necessary adaptations Standard evaluation form (HE RIA, IA) - will be used with the necessary adaptations Guidance HE Programme Guide Model Grant Agreement (MGA) HE MGA Call-specific instructions Information on clinical studies (HE) Additional documents HE Main Work Programme 2026-2027 – 1. General Introduction HE Main Work Programme 2026-2027 – 4. Health HE Main Work Programme 2026-2027 – 15. General Annexes HE Programme Guide HE Framework Programme 2021/695 HE Specific Programme Decision 2021/764 EU Financial Regulation 2024/2509 Decision authorising the use of lump sum contributions under the Horizon Europe Programme Rules for Legal Entity Validation, LEAR Appointment and Financial Capacity Assessment EU Grants AGA — Annotated Model Grant Agreement Funding & Tenders Portal Online Manual Funding & Tenders Portal Terms and Conditions Funding & Tenders Portal Privacy Statement

Programme context

Topics under this destination are directed towards the Key Strategic Orientation 2 “ The Digital Transition ” and Key Strategic Orientation 3 “ A More Resilient, Competitive, Inclusive, and Democratic Europe ” of Horizon Europe’s strategic plan 2025-2027 [1] . Research and Innovation supported under this destination should contribute to the following expected impact, set out in the strategic plan impact summary for the Health Cluster: “ Health technologies, data, new tools, and digital solutions are applied effectively thanks to their inclusive, ethically sound, secure and sustainable delivery, integration and deployment in health policies and in health and care systems. ” The Health Cluster will continue to drive the development and adoption of innovative technologies and digital solutions to improve healthcare and health systems. This will ensure that the EU remains at the forefront of breakthrough health and medical technologies and can achieve open strategic autonomy in essential medical supplies and digital innovations. In line with the Commission's Political Guidelines for 2024-2029 [2] , this destination will support research and innovation in tools and technologies strengthening the competitiveness of European health industry and reinforcing EU autonomy. This effort will contribute to the completion of the European Health Union which aims to enhance the resilience of healthcare systems, facilitate access to innovative and affordable healthcare solutions, and ensure that all citizens have access to high-quality, equitable, inclusive and sustainable healthcare. The development and use of innovative tools and technologies for biomedical research are the basis for prevention, early diagnosis, efficacious therapy and patient monitoring, essential components of efficient healthcare. These include enabling technologies, not least innovative biotechnological approaches, and emerging technologies like synthetic biology, digital tools including those based on Machine-Learning/Artificial Intelligence (ML/AI) and other data-driven approaches which will enable the development of more personalised medicine. Hence the combination of innovative tools, high-quality health data (incl. Real-World Data - RWD [3] ), digital technologies, modelling and AI tools holds great potential not only for advancing biomedical Research and Innovation but for developing health technologies that improve healthcare. However, the implementation of these tools and technologies faces specific barriers such as scalability, regulatory frameworks and public acceptance and trust. To overcome these challenges cross-sectoral cooperation among stakeholders including researchers, regulatory bodies, policymakers, industry, healthcare providers and patients, is necessary. This collaboration will facilitate the design and development of innovative health products and services, tailored to specific population groups, ultimately improving patient outcomes and reducing health inequalities. By taking a comprehensive and inclusive approach, this destination will prioritise the development of novel tools and technologies that address key considerations such as the rights of the individual, safety, effectiveness, appropriateness, accessibility, comparative value-added and fiscal sustainability while also ensuring ethical, legal and regulatory compliance. In this Work Programme part, Destination “ Developing and using new tools, technologies and digital solutions for a healthy society ” is driven mainly by three key Commission policies, the “Biotechnology and Biomanufacturing Communication” [4] the “Artificial Intelligence Strategy” [5] and the “Strategy for European Life Sciences” [6] and focuses on developing and applying innovative technologies to improve human health and healthcare systems. The topics under this destination cover efforts to develop AI based predictive biomarkers for disease prognosis and treatment response, advancing bio-printing of living cells for regenerative medicine, and integrating New Approach Methodologies (NAMs) to advance biomedical research, as well as developing virtual human twins for integrated clinical decision support. To increase the impact of EU investments under Horizon Europe, the Commission encourages cooperation between EU-funded projects to enable cross-fertilisation and other synergies. For example, this cooperation could take the form of networking, to joint activities, such as the participation in joint workshops, exchange of knowledge, development and adoption of best practices, or joint communication activities. Opportunities for such activities and potential synergies exist between projects funded under the same topic but also between other projects funded under different topics, Clusters or Pillars of Horizon Europe. Specifically, this could involve projects related to European health research infrastructures (under Pillar I of Horizon Europe), the EIC [7] strategic challenges on health (under Pillar III of Horizon Europe) or with projects on themes that cut across the Clusters of Pillar II such as with Cluster “Digital, Industry and Space” on digitalisation of the health sector or key enabling technologies. Expected Impacts : Proposals for topics under this destination should set out a credible pathway towards the development and use of new tools, technologies and digital solutions for a healthy society, and more specifically to one or several of the following impacts: Europe’s scientific and technological expertise and know-how, its capabilities for innovation in new tools, technologies and digital solutions, and its ability to take-up, scale-up and integrate innovation in healthcare is world-class. Citizens benefit from targeted and faster research resulting in safer, more sustainable, efficient, cost-effective, accessible and affordable tools, technologies and digital solutions for improved (personalised) disease prevention, diagnosis, treatment and monitoring for better patient outcome and wellbeing, in particular through increasingly shared health resources (interoperable data, infrastructure, expertise, citizen/patient driven co-creation) [8] . The EU gains high visibility and leadership in terms of health technology development, including through international cooperation. The burden of diseases in the EU and worldwide is reduced through the development and integration of innovative diagnostic and therapeutic approaches, personalised medicine approaches, digital and other people-centred solutions for healthcare. Both the productivity of health Research and Innovation, and the quality and outcome of healthcare is improved thanks to the use of health data and innovative analytical tools, such as AI supported decision-making, in a secure, ethical and inclusive manner, respecting individual integrity and underpinned with public acceptance and trust. Citizens trust and support the opportunities offered by innovative technologies for healthcare, based on expected health outcomes and potential risks involved. Legal entities established in China are not eligible to participate in both Research and Innovation Actions (RIAs) and Innovation Actions (IAs) falling under this destination. For additional information please see “Restrictions on the participation of legal entities established in China” found in the Annex B of the General Annexes of this Work Programme. The protection of European communication networks has been identified as an important security interest of the Union and its Member States. Entities that are assessed as high-risk suppliers [9] of mobile network communication equipment (and any entities they own or control) are not eligible to participate as beneficiaries, affiliated entities and associated partners to topics identified as “subject to restrictions for the protection of European communication networks”. Please refer to the Annex B of the General Annexes of this Work Programme for further details. [1] https://research-and-innovation.ec.europa.eu/funding/funding-opportunities/funding-programmes-and-open-calls/horizon-europe/strategic-plan_en [2] https://commission.europa.eu/about/commission-2024-2029_en [3] EMA definition: “Real-World Data are routinely collected data relating to patient health status or the delivery of healthcare from a variety of sources other than traditional clinical trials (e.g. claims databases, hospital data, electronic health records, registries, mhealth data, etc.)”. [4] Commission Communication on Building the future with nature: Boosting Biotechnology and Biomanufacturing in the EU; COM(2024) 137 final: https://research-and-innovation.ec.europa.eu/document/download/47554adc-dffc-411b-8cd6-b52417514cb3_en [5] Commission Communication on Artificial Intelligence for Europe; COM(2018) 237 final: https://digital-strategy.ec.europa.eu/en/policies/european-approach-artificial-intelligence ; https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=COM:2018:237:FIN [6] https://research-and-innovation.ec.europa.eu/strategy/strategy-research-and-innovation/jobs-and-economy/towards-strategy-european-life-sciences_en ; https://ec.europa.eu/commission/presscorner/detail/en/ip_25_1686 [7] https://eic.ec.europa.eu [8] Commission Communication on the digital transformation of health and care; COM(2018) 233 final [9] Entities assessed as “high-risk suppliers”, are currently set out in the second report on Member States’ progress in implementing the EU toolbox on 5G cybersecurity of 2023 (NIS Cooperation Group, Second report on Member States’ progress in implementing the EU Toolbox on 5G Cybersecurity, June 2023) and the related Communication on the implementation of the 5G cybersecurity toolbox of 2023 (Communication from the Commission: Implementation of the 5G cybersecurity Toolbox, Brussels, 15.6.2023 C(2023) 4049 final).

Hivatkozott dokumentumok

http://www.ihi.europa.eu/sites/default/files/uploads/Documents/About/IHI_SRIA_ApprovedJan22.pdf https://ec.europa.eu/info/funding-tenders/opportunities/docs/2021-2027/horizon/guidance/ethics-by-design-and-ethics-of-use-approaches-for-artificial-intelligence_he_en.pdf Annex A Horizon Europe Programme Guide Online Manual Standard application form (HE RIA IA Stage 1 BLIND) Standard application form (HE RIA, IA) Standard evaluation form (HE RIA, IA and CSA Stage 1 BLIND) Standard evaluation form (HE RIA, IA) HE MGA Information on clinical studies (HE) HE Main Work Programme 2026-2027 – 1. General Introduction HE Main Work Programme 2026-2027 – 4. Health Decision authorising the use of lump sum contributions under the Horizon Europe Programme Rules for Legal Entity Validation, LEAR Appointment and Financial Capacity Assessment EU Grants AGA — Annotated Model Grant Agreement Funding & Tenders Portal Terms and Conditions