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Facilitating the conduct of multinational clinical studies of orphan devices and/or of highly innovative (“breakthrough”) devices
Funding Program
Horizon Europe: Cluster 1 - Health
Call number
HORIZON-HLTH-2025-03-IND-03-two-stage
deadlines
Opening
22.05.2025
Deadline
16.09.2025 17:00
Deadline - 2nd stage
Opening
23.05.2025
Funding rate
100%
Call budget
€ 40,000,000.00
Estimated EU contribution per project
between € 6,000,000.00 and € 8,000,000.00
Link to the call
Link to the submission
Call content
short description
This topic aims at supporting activities that are enabling or contributing to one or several expected impacts of destination “Maintaining an innovative, sustainable, and competitive EU health industry”.
Call objectives
The focus of this topic is on multinational clinical studies of orphan devices and/or of highly innovative (“breakthrough”) devices, including digital and Artificial Intelligence (AI) based tools and techniques.
The emphasis within rare disease research and innovation has predominantly centred on pharmaceuticals, leaving a noticeable gap in the support for developing orphan devices. Orphan devices are specifically intended for use in rare diseases or conditions or in specific indications for rare cohorts of patients with an otherwise non-rare disease or condition. As, by their nature, orphan devices are intended for use in a small number of individuals each year, often infants and children, generating clinical data within an appropriate period of time and conducting clinical investigations is especially challenging due to low patient recruitment volumes.
Besides orphan devices, also highly innovative (“breakthrough”) devices are in the scope of this topic if they are expected to provide major clinical benefits for the treatment, diagnosis or prevention of a life threatening, seriously debilitating or serious and chronic disease or condition, regardless of whether they target small patient populations. Highly innovative (“breakthrough”) devices aim to address unmet medical needs. ‘Unmet medical needs’ should be understood as a condition for which there exists no satisfactory method of diagnosis, prevention or treatment in the EU or, even if such a method exists, in relation to which the device concerned will be of major advantage to those affected. Those may include devices using digital tools and AI based technologies.
Developers of such devices often face challenges to generate clinical data in the pre-market phase in a timely manner.
Time and cost of clinical data collection can adversely affect public health by significantly delaying the availability of devices needed to treat or diagnose rare diseases or conditions or that may improve patient care or public health. Many devices are used off-label to respond to this unmet need. Nonetheless, a high level of clinical evidence based on thorough clinical data is needed to ensure patient safety.
Clinical development strategies for implementing multinational clinical studies have the potential to offer improved efficiency and to reach larger patient samples. Challenges may arise from the potential uncertainty regarding how regional disparities in regulatory, clinical, business, ethical and cultural practices may affect study design, conduct, data interpretation and various other outcomes.
This topic targets those challenges by supporting multinational studies aiming to gather pre- or post-market clinical data to demonstrate the device’s safety and performance (including determination of any undesirable side-effects and their acceptability when weighed against the expected clinical benefits).
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Expected effects and impacts
The proposals should demonstrate that they address all the following activities for a device that is an orphan device or a highly innovative “breakthrough” device (or both), at any point of the pre-or post-market stage, including the development stage, with the overall purpose to generate data in support of CE marking under the Regulations on medical devices (MDR) or in vitro diagnostic medical devices (IVDR):
- Design and conduct multinational clinical studies in a minimum of two different countries in the EU or Associated Countries, with a focus on orphan devices and/or highly innovative (“breakthrough”) devices, with a view to demonstrate the safety and clinical performance of the device(s) subject to the study.
- Present a sound clinical study feasibility plan, including an appropriate patient selection and realistic recruitment plans at different sites, justified by scientific publications or preliminary results. Proposals should adopt a gender-sensitive and intersectional approach, considering individual characteristics such as gender, sex, race, ethnicity, disability and age. Additionally, socioeconomic, lifestyle and behavioural factors should be taken into account. For this, the topic requires the effective contribution of social sciences and humanities (SSH) disciplines and the involvement of SSH experts, institutions as well as the inclusion of relevant SSH expertise, in order to produce meaningful and significant effects enhancing the societal impact of the related research activities.
- Demonstrate potential clinical benefit for patients and healthcare providers, including quality of life and consideration of patient-reported outcomes when relevant.
- Involve patients, patient organisations, carers and healthcare professionals in the design of the clinical studies.
- Identify, collect and record relevant good practices and experiences related to the design, conduct, sample handling, data analysis and results reporting of multinational clinical studies. In addition, provide appropriate recommendations and lessons learned.
- For multinational clinical studies, authorisation for the study approval by more than one national competent authority may be necessary. Develop a regulatory strategy and interaction plan for generating appropriate evidence as well as engaging with regulators and other relevant bodies (e.g., European Medicines Agency (EMA), EMA expert panels, national regulators, Health Technology Assessment bodies, etc.) in a timely manner. Consider also the potential for future regulatory impact of the results.
Proposals may include multiple devices, but the minimum expected is one device.
Participation of small and medium-sized enterprises (SMEs) is strongly encouraged.
For orphan devices or highly innovative devices relevant to rare disease patients, applicants should look for complementarities and potential synergies with actions implemented under ERDERA the co-funded European Partnership on Rare Diseases proposed under Horizon Europe, as well as synergies with actions implemented under the EU4Health programme.
The Joint Research Centre (JRC) may participate as a member of the consortium selected for funding. Proposals should consider the involvement of the European Commission's JRC regarding its experience in this field and with respect to the value it could bring in providing an effective interface between research activities and pre-normative science as well as strategies and frameworks that address regulatory requirements. In that respect, the JRC will consider collaborating with any successful proposal and this collaboration, when relevant, should be established after the proposal’s approval.
Applicants should provide details of their clinical studies 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.
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Expected results
Proposals under this topic should aim to deliver results that are directed, tailored towards and contributing to all the following expected outcomes:
- Healthcare providers increase their hands-on experience regarding the clinical use of orphan devices and/or of highly innovative (“breakthrough”) devices and get timely access to such devices with demonstrated clinical benefits;
- Developers and manufacturers collect and obtain scientific evidence on their proposed intervention/ approach with the device under investigation;
- Patients benefit from the development, studies and use of orphan devices and/or of highly innovative (“breakthrough”) devices;
- Companies in the EU and associated countries get a better market position in this field and improve their knowledge on how to conduct multinational clinical studies for these devices.
Eligibility Criteria
Regions / countries for funding
Moldova (Moldova), Albania (Shqipëria), Armenia (Հայաստան), Bosnia and Herzegovina (Bosna i Hercegovina / Босна и Херцеговина), Canada, Faeroes (Føroyar / Færøerne), Georgia (საქართველო), Iceland (Ísland), Israel (ישראל / إِسْرَائِيل), Kosovo (Kosova/Kosovë / Косово), Montenegro (Црна Гора), New Zealand (Aotearoa), North Macedonia (Северна Македонија), Norway (Norge), Serbia (Srbija/Сpбија), Tunisia (تونس /Tūnis), Türkiye, Ukraine (Україна), United Kingdom
eligible entities
EU Body, Education and training institution, Non-Profit Organisation (NPO) / Non-Governmental Organisation (NGO), Other, Private institution, incl. private company (private for profit), Public Body (national, regional and local; incl. EGTCs), Research Institution incl. University, Small and medium-sized enterprise (SME)
Mandatory partnership
Yes
Project Partnership
To be eligible for funding, applicants must be established in one of the following countries:
- the Member States of the European Union, including their outermost regions
- the Overseas Countries and Territories (OCTs) linked to the Member States
- countries associated to Horizon Europe - see list of particpating countries
Only legal entities forming a consortium are eligible to participate in actions provided that the consortium includes, as beneficiaries, three legal entities independent from each other and each established in a different country as follows:
- at least one independent legal entity established in a Member State; and
- at least two other independent legal entities, each established in different Member States or Associated Countries.
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.
Any legal entity, regardless of its place of establishment, including legal entities from non-associated third countries or international organisations (including international European research organisations) is eligible to participate (whether it is eligible for funding or not), provided that the conditions laid down in the Horizon Europe Regulation have been met, along with any other conditions laid down in the specific call topic.
A ‘legal entity’ means any natural or legal person created and recognised as such under national law, EU law or international law, which has legal personality and which may, acting in its own name, exercise rights and be subject to obligations, or an entity without legal personality.
other eligibility criteria
Specific cases:
- Affiliated entities (i.e. entities with a legal or capital link to a beneficiary which participate in the action with similar rights and obligations to the beneficiaries, but which do not sign the grant agreement and therefore do not become beneficiaries themselves) are allowed, if they are eligible for participation and funding.
- Associated partners (i.e. entities which participate in the action without signing the grant agreement, and without the right to charge costs or claim contributions) are allowed, subject to any conditions regarding associated partners set out in the specific call conditions.
- Entities which do not have legal personality under their national law may exceptionally participate, provided that their representatives have the capacity to undertake legal obligations on their behalf, and offer guarantees to protect the EU’s financial interests equivalent to those offered by legal persons.
- Legal entities created under EU law (EU bodies) including decentralised agencies may be part of the consortium, unless provided for otherwise in their basic act.
- International European research organisations are eligible to receive funding. International organisations with headquarters in a Member State or Associated Country are eligible to receive funding for ‘Training and mobility’ actions or when provided for in the specific call/topic conditions. Other international organisations are not eligible to receive funding, unless provided for in the specific call/topic conditions, or if their participation is considered essential for implementing the action by the granting authority.
- Joint Research Centre (JRC)— Where provided for in the specific call conditions, applicants may include in their proposals the possible contribution of the JRC but the JRC will not participate in the preparation and submission of the proposal. Applicants will indicate the contribution that the JRC could bring to the project based on the scope of the topic text. After the evaluation process, the JRC and the consortium selected for funding may come to an agreement on the specific terms of the participation of the JRC. If an agreement is found, the JRC may accede to the grant agreement as beneficiary requesting zero funding or participate as an associated partner, and would accede to the consortium as a member.
- Associations and interest groupings — Entities composed of members (e.g. European research infrastructure consortia (ERICs)) may participate as ‘sole beneficiaries’ or ‘beneficiaries without legal personality’. However, if the action is in practice implemented by the individual members, those members should also participate (either as beneficiaries or as affiliated entities, otherwise their costs will NOT be eligible.
- EU restrictive measures — Entities subject to EU restrictive measures under Article 29 of the Treaty on the European Union (TEU) and Article 215 of the Treaty on the Functioning of the EU (TFEU) as well as Article 75 TFEU, are not eligible to participate in any capacity, including as beneficiaries, affiliated entities, associated partners, third parties giving in-kind contributions, subcontractors or recipients of financial support to third parties (if any).
- Legal entities established in Russia, Belarus, or in non-government controlled territories of Ukraine — Given the illegal invasion of Ukraine by Russia and the involvement of Belarus, there is currently no appropriate context allowing the implementation of the actions foreseen in this programme with legal entities established in Russia, Belarus, or in non-government controlled territories of Ukraine. Therefore, even where such entities are not subject to EU restrictive measures, such legal entities are not eligible to participate in any capacity. This includes participation as beneficiaries, affiliated entities, associated partners, third parties giving in-kind contributions, subcontractors or recipients of financial support to third parties (if any). Exceptions may be granted on a case-by-case basis for justified reasons.
With specific regard to measures addressed to Russia, following the adoption of the Council Regulation (EU) 2024/1745 of 24 June 2024 (amending Council Regulation (EU) No 833/2014 of 31 July 2014) concerning restrictive measures in view of Russia’s actions destabilising the situation in Ukraine, legal entities established outside Russia but whose proprietary rights are directly or indirectly owned for more than 50% by a legal person, entity or body established in Russia are also not eligible to participate in any capacity. - Measures for the protection of the Union budget against breaches of the principles of the rule of law in Hungary — Following the Council Implementing Decision (EU) 2022/2506, as of 16 December 2022, no legal commitments can be entered into with Hungarian public interest trusts established under the Hungarian Act IX of 2021 or any entity they maintain. Affected entities may continue to apply to calls for proposals and can participate without receiving EU funding, as associated partners, if allowed by the call conditions. However, as long as the Council measures are not lifted, such entities are not eligible to participate in any funded role (beneficiaries, affiliated entities, subcontractors, recipients of financial support to third parties, etc.).In case of multi-beneficiary grant calls, applicants will be invited to remove or replace that entity in any funded role and/or to change its status into associated partner. Tasks and budget may be redistributed accordingly.
Additional information
Topics
Relevance for EU Macro-Region
EUSDR - EU Strategy for the Danube Region, EUSBSR - EU Strategy for the Baltic Sea Region, EUSALP - EU Strategy for the Alpine Space, EUSAIR - EU Strategy for the Adriatic and Ionian Region
UN Sustainable Development Goals (UN-SDGs)
Additional Information
Applications must be submitted electronically via the Funders & Tenders Portal electronic submission system (accessible via the topic page in the Search Funding & Tenders section). Paper submissions are NOT possible.
Applications must be submitted using the forms provided inside the electronic submission system (not the templates available on the topic page, which are only for information). The structure and presentation must correspond to the instructions given in the forms.
Applications must be complete and contain all parts and mandatory annexes and supporting documents.
The application form will have two parts:
- Part A (to be filled in directly online) contains administrative information about the applicant organisations (future coordinator and beneficiaries and affiliated entities), the summarised budget for the proposal and call-specific questions;
- Part B (to be downloaded from the Portal submission system, completed and then assembled and re-uploaded as a PDF in the system) contains the technical description of the project.
Annexes and supporting documents will be directly available in the submission system and must be uploaded as PDF files (or other formats allowed by the system).
The page limit for the Part B for the first stage of the 2-stage call is 10 pages.
This topic is part of the blind evaluation pilot under which first stage proposals will be evaluated blindly. Applicants submitting a proposal under the blind evaluation pilot must not disclose their organisation names, acronyms, logos nor names of personnel in the proposal abstract and Part B of their first-stage application.
Eligible costs will take the form of a lump sum as defined in the Decision of 7 July 2021 authorising the use of lump sum contributions under the Horizon Europe Programme – the Framework Programme for Research and Innovation (2021-2027) – and in actions under the Research and Training Programme of the European Atomic Energy Community (2021-2025). It is mandatory to submit a detailed budget table using the template available in the Submission system.
Call documents
Horizon Europe Work Programme 2025 Cluster 1 - HealthHorizon Europe Work Programme 2025 Cluster 1 - Health(1200kB)
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