Personalised approaches to reduce risks from Adverse Drug Reactions due to administration of multiple medications

Healthcare professionals can adopt adverse drug reactions prevention and reduction strategies to integrate genetic and other biomarker information into clinical decision-making to optimise the use of medication, especially in situations of comorbidities. Healthcare systems benefit from cost savings thanks to reduced hospital admissions and other costs associated with ADRs related to the intake of multiple medicines. Clinical and regulatory guidelines and policies for medication management in case of multiple medications can be revised supported by robust evidence. Educational programs for healthcare providers and patients benefit from improved awareness and management of polypharmacy and ADRs. Scope: While medicinal products contribute considerably to the health of EU citizens, they can also have adverse reactions. It is estimated that around 5% of all hospital deaths are due to an adverse drug reaction. On average, 16% of hospitalised older [2] patients experience significant ADRs, varying in severity and mostly preventable, with commonly prescribed drug classes (such as diuretics, anti-bacterials, antithrombotic agents, analgesics, antineoplastics, etc.) accounting for most ADRs [3] . Overall, ADRs increase morbidity, mortality, hospitalisations, and healthcare costs. ADRs from multiple medications contribute significantly to healthcare costs due to increased hospitalisations and treatments, making this an area of focus to achieve cost efficiency. Initial failure to recognise ADRs can generate inappropriate prescription cascades, in which the side effects of drugs are misdiagnosed as symptoms of new problems, resulting in further prescriptions and further side effects that tend to accumulate, confusing and complicating the diagnostic while aggravating the evolution. Therefore, there is a distinct need for research to help identify and prevent such prescription cascades, possibly by maximising the use of technology, as well as to improve multiple drug management in order to reduce patient harm. Furthermore, it is also possible that aside from the ADRs specific to individual drugs taken in combination, new ADRs can emerge as results from the drug combinations themselves. Research activities under this topic should make use of the constantly improving health technologies and data analytics that provide new opportunities to address these issues more effectively, by better integrating medication management into healthcare practices, including into Electronic Health Records (EHR) and decision support systems. Identifying and validating relevant biomarkers for better patient stratification can contribute to significantly decreasing the risk of adverse drug reactions. Biomarkers can also help to detect adverse drug reactions early before occurrence of clinical symptoms and enable early countermeasures. Generating knowledge on the interaction and complexity of biochemical pathways can improve the understanding of patients' response to ADRs and thus provide better tailored treatments and early responses to adverse reactions. For this purpose, any biomedical strategy that allows a better stratification of patients to identify drug response patterns in well-defined patient groups could be used, including in-vitro or in-silico models for adverse drug reactions, imaging biomarkers, drug-drug/drug-gene/drug-food interactions, therapeutic dose reduction and pharmaco-exposomics, nutrition and beverage interference, smoking, vaping, pollution etc. De-escalation studies in view of improving multiple drug management can be also considered. Proposals should be sufficiently robust to examine differences across various populations, and also consider sex difference in drug reactions. The further use of results generated by the projects funded under this topic should be ensured through data sharing with the relevant stakeholders and the European Medicines Agency (EMA), in view of possible adoption of deprescribing or adjusted-prescribing guidelines by relevant authorities at EU and national levels. Where applicable, applicants are strongly encouraged to follow all relevant guidelines in the relevant scientific fields, including but not limited to: Joint EMA/Heads of Medicines Agencies (HMA)/EC Workshop recommendations on pharmacogenomics in medicines regulation and on implementation into clinical practice [4] . Pharmaceutical development of medicines for use in the older population, Scientific guideline from the EMA [5] . Guidelines from the Clinical Pharmacogenetics Implementation Consortium (‘CPIC guidelines’) [6] . Proposals funded under this topic should address all the following aspects: Leverage the role of pharmacogenomics, pharmacokinetics and pharmacodynamics in predicting and preventing adverse drug reactions in situations of multiple medications (three or more drugs administered concomitantly), and propose personalised medicine approaches, such as targeted therapies and biomarker-driven treatment strategies, to reduce the rate of adverse drug reactions and limit multiple medications. Maximise the use of technology, such as electronic health records, artificial intelligence and clinical decision support systems, to support safe medication use and prevent adverse drug reactions. Address the ethical, regulatory, and implementation challenges associated with integrating personalised medicine into clinical practice to address adverse drug reactions due to the administration of multiple medications. Generate evidence on the clinical utility and cost-effectiveness of treatment guided by pharmacogenomics and other relevant biomarkers-based approach, for single drugs and for combinations of drugs. Develop and implement strategies, including regulatory science approaches, for efficient integration of project results into daily healthcare. Align with similar work in other EU-funded projects or partnerships, such as the co-funded European Partnership for Personalised Medicine [7] , the co-funded European Partnership on Transforming Health and Care System [8] etc. while avoiding any potential overlaps. The participation of start-ups, micro, small and medium-sized enterprises (SMEs) [9] is encouraged with the aim of strengthening their scientific and technological foundations, enhancing their innovation potential, and exploring possibilities for commercial exploitation. Applicants should provide details of their clinical studies [10] 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] https://www.ema.europa.eu/en/glossary-terms/medicinal-product [2] Old age is often defined as starting around 60 or 65 years of age. [3] Emma L. M. Jennings et al., In-hospital adverse drug reactions in older adults; prevalence, presentation and associated drugs - a systematic review and meta-analysis, Age and Ageing 2020; 49: 948-958 doi: 10.1093/ageing/afaa188 [4] https://www.ema.europa.eu/en/documents/report/report-joint-ec-hma-ema-multi-stakeholder-workshop-pharmacogenomics-24-september-2024_en.pdf [5] https://www.ema.europa.eu/en/pharmaceutical-development-medicines-use-older-population-scientific-guideline [6] https://cpicpgx.org/guidelines [7] https://cordis.europa.eu/project/id/101137129 , https://www.eppermed.eu [8] https://cordis.europa.eu/project/id/101095654 , https://www.thcspartnership.eu [9] https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32003H0361 [10] 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 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 Award criteria, scoring and thresholds are described in Annex D of the Work Programme General Annexes. 5b. Evaluation and award: Submission and evaluation processes 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) - the application form specific to this call is available in the Submission System 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: “healthcare systems provide equal access to innovative, sustainable and high-quality healthcare thanks to the development and uptake of safe, cost-effective and people-centred solutions. This is to be accompanied by management models focusing on population health, health systems resilience, and health equity and patient safety, and also improved evidence-informed health policies”. Health systems are affected by limitations in sustainability and resilience, and face inequalities in access to high-quality and acceptable healthcare services. Health systems need to become more effective, efficient, accessible, fiscally and environmentally sustainable, and resilient in order to cope with public health emergencies, support healthcare workforce, adapt to environmental challenges like climate change, and contribute to social justice and cohesion. The transformation and modernisation of health systems will remain an important challenge for many years to come, but it also holds a significant opportunity to generate evidence, leverage existing and emerging solutions, implement digital and data-driven innovation and develop more accessible, cost-effective, flexible and equitable health systems. Research and Innovation under this destination should aim to support the transformation of healthcare systems ensuring fair and inclusive access to high-quality, acceptable, sustainable healthcare for all. Funded activities will focus on developing innovative, practical, scalable and financially sound solutions, that improve governance, provide decision-makers with new evidence, tools, and technologies, and ensure long-term fiscal, environmental and climate sustainability. A patient-centred approach should be adopted, improving patients’ health outcomes, empowering patients, fostering active dialogue among stakeholders (e.g. citizens, patients, caregivers, healthcare providers), and encouraging social innovation. Research and Innovation actions should prioritise supporting healthcare professionals and providers, ensuring they have the resources and tools needed to meet the diverse needs and preferences of citizens. Research and Innovation should facilitate scalable and transferable solutions that can be applied across different healthcare systems and national, regional, and local contexts. This should include generating knowledge that supports the transfer of solutions between countries, including measures to address health inequalities. Research and Innovation activities under this destination will contribute to, among other things, the European Care Strategy [2] , the digital transformation of health and care in the EU [3] , the European Pillar of Social Rights [4] , [5] , the EU strategy on adaptation to climate [6] , the Pharmaceutical Strategy for Europe [7] , the European Health Data Space (EHDS) [8] , the Strategy for European Life Sciences [9] and the European Green Deal [10] . They align with the Commission's Political Guidelines for 2024-2029 [11] , which include efforts to complete the European Health Union by promoting access for all to high-quality and affordable healthcare, fostering a resilient and innovative health ecosystem, and strengthening the competitiveness of the European Union [12] . In this Work Programme part, the focus of this destination will be on public procurement of innovative solutions for integrated or personalised care, aiming to develop and test solutions that improve access to and provision of healthcare. It will also support personalised medicine approaches to reduce adverse drug reactions due to the administration of multiple medication, and research to identify and address low-value care in health and care systems, improving healthcare outcomes, efficiency, and fiscal sustainability. To increase the impact of EU investments under Horizon Europe, the Commission encourages and supports cooperation among EU-funded projects to foster cross-fertilisation and synergies. This includes networking, joint activities such as workshops, knowledge exchange, best practices development, and joint communication activities. Synergies can be explored not only between projects funded under the same topic, but also between projects funded under other topics, Clusters or Pillars of Horizon Europe. For instance, collaborations may arise between projects related to European health research infrastructures (under Pillar I), the EIC [13] strategic challenges on health (under Pillar III), or across the Clusters of Pillar II such as Cluster “Culture, Creativity and Inclusive Society” focusing e.g. on the long-term sustainability of public health systems (e.g. economic and organisational models and measures for cost effectiveness and fiscal sustainability), or Cluster “Digital, Industry and Space” focusing on the digitalisation of the health sector, including the use of Artificial Intelligence (AI). The Commission aims to foster synergies between Horizon Europe and other EU programmes. To this end, applicants are encouraged to explore the funding opportunities available through the EU4Health Programme (2021-2027) [14] , the EU's public health programme, as a means of capitalising on potential collaborations and maximising impact. Expected impacts : Proposals for topics under this destination should set out a credible pathway to contributing to ensuring access to innovative, sustainable, inclusive and high-quality healthcare, and more specifically to one or several of the following impacts: Health and social care services and systems have improved governance mechanisms, making them more effective, efficient, accessible, resilient, trusted and sustainable, from fiscal, organisational and environmental perspectives. This includes shifting from hospital-centred to community-based, people-centred and integrated healthcare structures, embedding technological innovations and prioritising health promotion and disease prevention and management. Healthcare providers are trained and equipped with the skills and competences needed for future healthcare systems that are modernised, digitally transformed and equipped with safe innovative tools, technologies and digital solutions for healthcare. This will involve better patient management, improved patient engagement and health outcomes, reorganised workflows, and improved resource management. Citizens play a key role in managing their own healthcare, informal carers (including unpaid carers) are fully supported (e.g. by preventing overburdening and economic stress) and the specific needs of groups in a vulnerable situation are recognised and addressed. This includes improved access to healthcare services, financial risk protection, timely access to quality healthcare services including essential medicines and vaccines. Health policy and systems adopt a holistic approach -considering individuals, communities, organisations, society- in evaluating health outcomes, public health interventions, healthcare organisation, and decision-making. They benefit from evidence based, scalable and transferable healthcare solutions (e.g. between countries and healthcare settings) including for addressing health inequalities and ensuring environmental and climate sustainability in the health sector. The actions resulting from the topics under this destination will also create strong opportunities for synergies with actions stemming from the EU4Health programme, in particular contributing to the goals under the general objective “ protecting people in the Union from serious cross-border threats to health ” and specific objective 4 “ to strengthen health systems, their resilience and resource efficiency ”. 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 [15] 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] Communication from the European Commission on the European care strategy, COM(2022) 440, 7.9.2022 [3] Communication from the European Commission on enabling the digital transformation of health and care in the Digital Single Market; empowering citizens and building a healthier society, COM(2018) 233, 25.4.2018 [4] https://employment-social-affairs.ec.europa.eu/policies-and-activities/european-pillar-social-rights-building-fairer-and-more-inclusive-european-union_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://climate.ec.europa.eu/eu-action/adaptation-climate-change/eu-adaptation-strategy_e [7] https://health.ec.europa.eu/medicinal-products/pharmaceutical-strategy-europe_en [8] https://health.ec.europa.eu/ehealth-digital-health-and-care/european-health-data-space-regulation-ehds_en [9] 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 [10] https://commission.europa.eu/strategy-and-policy/priorities-2019-2024/european-green-deal_en [11] https://commission.europa.eu/about/commission-2024-2029_en [12] https://commission.europa.eu/topics/eu-competitiveness_en [13] https://eic.ec.europa.eu [14] https://commission.europa.eu/funding-tenders/find-funding/eu-funding-programmes/eu4health_en [15] 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

https://www.ema.europa.eu/en/documents/report/report-joint-ec-hma-ema-multi-stakeholder-workshop-pharmacogenomics-24-september-2024_en.pdf Annex A Horizon Europe Programme Guide Online Manual Standard application form (HE RIA, IA) 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