# Facilitating the conduct of multinational clinical studies of orphan devices and/or of highly innovative (“breakthrough”) devices
EUACC page: https://www.euacc.ai/calls/HORIZON-HLTH-2025-03-IND-03-two-stage
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## Public content

**topic id:** HORIZON-HLTH-2025-03-IND-03-two-stage
**call id:** HORIZON-HLTH-2025-03-two-stage
**title:** Facilitating the conduct of multinational clinical studies of orphan devices and/or of highly innovative (“breakthrough”) devices
**programme:** Horizon Europe
**cluster:** HLTH
**status:** closed
**deadline date:** 2026-04-16T00:00:00+00:00
**deadline model:** two-stage
**start date:** 2025-05-22T00:00:00+00:00
**url:** https://ec.europa.eu/info/funding-tenders/opportunities/portal/screen/opportunities/topic-details/HORIZON-HLTH-2025-03-IND-03-two-stage
**description:** Expected Outcome:
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”. To that end, 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[1] 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.
 Scope:
The focus of this topic is on multinational clinical studies[2] of orphan devices[3] 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[4] 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[5]. 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).
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[6] 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[7], 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[8] the co-funded European Partnership on Rare Diseases proposed under Horizon Europe[9], 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[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] For the purpose of this topic, the reference to ‘devices’ includes both medical devices and in vitro diagnostic medical devices, unless otherwise specified.
[2] See definition of clinical studies in the introduction to this work programme part.
[3] A device should be regarded as an ‘orphan device’, if it meets the following criteria: i) the device is specifically intended to benefit patients in the treatment, diagnosis, or prevention of a disease or condition that presents in not more than 12.000 individuals in the European Union per year and ii) at least one of the following criteria are met:
- there is insufficiency of available alternative options for the treatment, diagnosis, or prevention of this disease/condition, or
- the device will offer an option that will provide an expected clinical benefit compared to available alternatives or state of the art for the treatment, diagnosis, or prevention of this disease/condition, taking into account both device and patient population-specific factors. MDCG 2024-10 Guidance on clinical evaluation of orphan medical devices: https://health.ec.europa.eu/document/download/daa1fc59-9d2c-4e82-878e-d6fdf12ecd1a_en?filename=mdcg_2024-10_en.pdf.
[4] See Appendix 8 to MEDDEV 2.7/1 revision 4 (https://ec.europa.eu/docsroom/documents/17522/attachments/1/translations) or the FDA’s Breakthrough Devices Program (https://www.fda.gov/medical-devices/how-study-and-market-your-device/breakthrough-devices-program).
[5] Based on Article 4(2) of Commission Regulation 507/2006 which defines the term ‘unmet medical needs’ in the field of medicinal products.
[6] ‘Clinical benefit’ is defined in the Medical Device Regulation (EU) 2017/745, Article 2(53) as follows: Clinical benefit means the positive impact of a device on the health of an individual, expressed in terms of a meaningful, measurable, patient-relevant clinical outcome(s), including outcome(s) related to diagnosis, or a positive impact on patient management or public health.
[7] EMA pilots scientific advice for certain high-risk medical devices - European Medicines Agency (EMA): https://www.ema.europa.eu/en/news/ema-pilots-scientific-advice-certain-high-risk-medical-devices
[8] ‘European Rare Diseases Research Alliance’, https://erdera.org, https://cordis.europa.eu/project/id/101156595
[9] https://ec.europa.eu/info/funding-tenders/opportunities/portal/screen/opportunities/topic-details/horizon-hlth-2023-disease-07-01
[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.
**conditions:** General conditions
1. Admissibility Conditions, Proposal page limit and layout
Applicants submitting a proposal under the blind evaluation pilot (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 Eligible 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.

The Joint Research Centre (JRC) may participate as member of the consortium selected for 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).

The following exceptions apply: subject to restrictions for the protection of European communication networks.

Other Eligible 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
This topic is part of the blind evaluation pilot under which first stage proposals will be evaluated blindly.

Evaluation and award: 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.

Evaluation and award: 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
Evaluation and award: 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
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) [[This decision is available on the Funding and Tenders Portal, in the reference documents section for Horizon Europe, under ‘Simplified costs decisions’ or through this link: https://ec.europa.eu/info/funding-tenders/opportunities/docs/2021-2027/horizon/guidance/ls-decision_he_en.pdf]].

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) - 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) - 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)
Lump Sum MGA
Call-specific instructions
Information on clinical studies (HE)
Detailed budget table (HE LS)
Guidance: "Lump sums - what do I need to know?"

Additional documents1
 HE Main Work Programme 2025 – 1. General Introduction
HE Main Work Programme 2025 – 4. Health
HE Main Work Programme 2025 – 14. 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
**action type:** HORIZON  Research and Innovation Actions
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    **110793:** 
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        **budget Year Map:** 
          **2025:** 40000000
        **deadline Dates:** 
          - 2025-09-16
          - 2026-04-16
        **deadline Model:** two-stage
        **expected Grants:** 5
        **max Contribution:** 8000000
        **min Contribution:** 6000000
        **planned Opening Date:** 2025-05-22
**keywords:** HORIZON-HLTH-2025-03-IND-03-two-stage, HORIZON-HLTH-2025-03-two-stage, Clinical research, Clinical trials, Other clinical medicine subjects, Public health, Rare diseases
**last synced at:** 2026-11-09T17:23:17.403+00:00

## Review record

No independent verification record is available.

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