ThrombUS+ D10.3: OEI - Requirement No. 3

D10.3| OEI: Ethics Advisor Report #2 v1.0 | 18 Dec 2025 | Publishable Summary i D10.3. OEI - Requirement No. 3 C. Sardeli, Independent Ethics Advisor Publishable Summary Due Date: 31 December 2025 Delivery Date: 18 December 2025 Horizon Innovation Action | Agreement No. 101137227 HORIZON-HLTH-2023-TOOL-05-05 Co-funded by the European Union D10.3| OEI: Ethics Advisor Report #2 v1.0 | 18 Dec 2025 | Publishable Summary ii ThrombUS+ Consortium ATHENA Research and Innovation Center in Information, Communication and Knowledge Technologies, Greece Eleni Kaldoudi [email protected] KTU Kaunas University of Technology Lithuania Vaidotas Marozas [email protected] VERMON Vermon SA France Mathieu Legros [email protected] FRAUNHOFER Institute for Photonic Microsystems, Fraunhofer Germany Nicolas Lange [email protected] TELEMED Telemed Ultrasound Medical Systems Lithuania Dmitry Novikov [email protected] EchoNous EchoNous Inc USA Pavlos Moustakidis [email protected] MEDIS medis Medizinische Messtechnik GmbH Germany Susann Balling [email protected] ComfTech ComfTech SLR Italy Lara Alessia Moltani [email protected] TAU Faculty of Medicine and Health Technology Tampere University, Finland Antti Vehkaoja [email protected] LMSU Lithuanian University of Health Science Lithuania Andrius Macas [email protected] GNP Papageorgiou General Hospital Greece Maria Bigaki [email protected] CSS-IRCCS Home Relief of Suffering Hospital Italy Elvira Grandone e.grand[email protected] HSV Simon Veil Hospital France Maxime Gautier [email protected] VDE Association for Electrical, Electronic & Information Technologies, Germany Thorsten Prinz thorsten[email protected] MEDEA MEDEA SRL Italy Pietro Dionisio [email protected] PHAZE Clinical Research and Pharma Consulting SA Greece Spiros Anagnostopoulos [email protected] PBY PredictBy Research and Consulting SL Spain Frans Folkvord [email protected] SciGen SciGen Technologies SA Greece Katerina Pavlidi [email protected] Disclaimer This document contains description of the ThrombUS+ project work, findings, and products. The authors of this document have taken any available measure for its content to be accurate, consistent and lawful. However, neither the project consortium as a whole nor the individual partners that implicitly or explicitly participated in the creation and publication of this document hold any sort of responsibility that might occur as a result of using its content. Views and opinions expressed are those of the author(s) only and do not necessarily reflect those of the European Union or HADEA. Neither the European Union nor the granting authority HADEA can be held responsible for them. In case you believe that this document harms in any way intellectual property held by you as a person or as a representative of an entity, please do notify us immediately. ThrombUS+ is an Innovation Action Project co-funded by the European Union, under HORIZON-HLTH-2023-TOOL05-05 “Harnessing the potential of real-time data analysis and secure Point-of-Care computing for the benefit of person-centred health and care delivery”. D10.3| OEI: Ethics Advisor Report #2 v1.0 | 18 Dec 2025 | Publishable Summary iii Document Control Page Project Grant Agreement: 101137227 Acronym: ThrombUS+ Title: Wearable Continuous Point-of-Care Monitoring, Risk Estimation and Prevention for Deep Vein Thrombosis Type: Innovation Action Start: 1 January 2024 End: 30 June 2027 Programme: Horizon Europe Call Identifier: HORIZON-HLTH-2023-TOOL-05-05 Call Topic Harnessing the potential of real-time data analysis and secure Point-of-Care computing for the benefit of person-centred health and care delivery Website: http://thrombus.eu/ Deliverable # 53 No: D10.3 Deliverable Title: OEI - Requirement No. 3 Deliverable Type: ETHICS Classification: SEN Task: WP10 [M01-M42] Task Leader: ATHENA [E. Kaldoudi] Work Package: WP10 [M01-M42] Work Package Leader: ATHENA [E. Kaldoudi] Responsible Partner: ATHENA Authors: C. Sardeli, Independent Ethics Advisor Due Date: 31 December 2025 Delivery Date: 18 December 2025 D10.3| OEI: Ethics Advisor Report #2 v1.0 | 18 Dec 2025 | Publishable Summary iv Contents About ThrombUS+ ...................................................................................................................................................... 1 Deliverable D10.2 Description .................................................................................................................................... 1 Cite this Document as ................................................................................................................................................. 1 Terms and Definitions ................................................................................................................................................ 2 Report by the Independent Ethics Advisor.................................................................................................................. 3 1. Name and Contact Details .................................................................................................................................. 3 2. Overview of ethics issues raised by the project activities ................................................................................... 3 2.1. Project activities timing and progress ............................................................................................................... 3 2.2. Deviations from the ethics issues identified in the Ethics Summary Report ...................................................... 4 2.3. Ethics issues considered no longer applicable ................................................................................................... 4 3. Ethics Analysis .................................................................................................................................................... 4 3.1. Overview of the management of project’s activities in relation to ethics ......................................................... 4 3.2. Activities of the Ethics Advisor ........................................................................................................................... 5 3.3. Documents available to the Ethics Advisor ....................................................................................................... 5 3.4. Overview of evidence of ethics compliance ....................................................................................................... 5 3.4.1. Clinical Study B1 ....................................................................................................................................... 6 3.4.2. Clinical Study B2 ....................................................................................................................................... 6 3.4.3. Clinical Study B3 ....................................................................................................................................... 7 3.4.4. Clinical Study B4 ....................................................................................................................................... 7 3.4.5. Other ........................................................................................................................................................ 7 3.4.5.1. Pilot experimental study of the ThrombUS+ compression ultrasound module .............................. 8 3.4.5.2. System usability study to assess the DICOM anonymization software ........................................... 8 3.4.5.3. Short public survey .......................................................................................................................... 8 3.5. Ethics requirements included in GA and how the Consortium addressed them ................................................ 8 4. Recommendations to the Consortium ................................................................................................................ 9 5. Recommendations to the Commission/Executive Agency/Funding Body ........................................................... 9 Dx.x| Short Title v1.0 | 18 Dec 2025 | Publishable Summary About ThrombUS+ Deep vein thrombosis (DVT) is the formation of a blood clot within the deep veins, most commonly those of the lower limbs, causing obstruction of blood flow. In 50% of people with DVT, the clot eventually breaks off and travels to the lung to cause pulmonary embolism. Clinical assessment of DVT is notoriously unreliable because up to 2/3 of DVT episodes are clinically silent and patients are symptom free even when pulmonary embolism has developed. Early diagnosis of DVT is crucial and despite the progress made in ultrasound imaging and plethysmography techniques, there is a need for new methods to enable continuous monitoring DVT diagnosis at the point of care. ThrombUS+ brings together an interdisciplinary team of industrial, technology, regulatory, social science and clinical trial experts to develop a novel wearable diagnostic device for point-of-care, operator free, continuous monitoring in patients with high DVT risk. The device will combine autonomous, AI driven DVT detection based on a novel wearable ultrasound hardware, impedance plethysmography and light reflection rheography for immediate detection of blood clot formation in the lower limb. Activity and other physiological measurements will be used to provide a continuous assessment of DVT risk and support DVT prevention via serious gaming. The aggregated data will drive an intelligence decision support unit that will provide accurate monitoring and alerts. Extended reality will be used to guide experts to design exercises and patients to use the device optimally. ThrombUS+ is intended for use by postoperative patients in the ward, during long surgical operations, cancer patients or otherwise bedridden patients at home or in care units, and women during pregnancy and postpartum. ThrombUS+ will use big data sets for AI training collected in the project via 3 large scale clinical studies and will validate the outcome in the clinical setting via 1 early feasibility study and 1 multi-centre clinical trial. Deliverable D10.2 Description According to the opinions of the ethics experts that evaluated the submitted proposal prior to its funding, the proposal raised several ethics issues. Among others, that the clinical trial C1 requires a continuous DVT monitoring of high-risk patients (postoperative and mostly bedridden), using the ThrombUS+ wearable device, from 12 hours after surgery and for 3 days. This raised questions about the vulnerability of the participants and their autonomy, especially because the applicants missed to indicate participation of vulnerable individuals in Part A Ethics Issues Table. Furthermore, partner PBY was presented as “social sciences expert involved in health technology deployments” to advise on the clinical studies/trials protocols (Section 2 - Preparedness status - in 3 clinical studies and 2 clinical trials descriptions); however, this is a research and consulting firm specialising in data and behavioural science to advise organisations on decisionmaking processes. Its expertise is not particularly relevant to address issues of autonomy and vulnerability in patients participating in clinical trials. Due to the abovementioned, it was indicated that the project must appoint an Ethics Advisor with expertise in human-centred technology (AI-powered technology in particular), to help prioritise the well-being of the participants in the clinical trials and studies, to help the project adopt an ethics-by-design approach (rather than a conformity-by-design technical approach) for the development of ThrombUS – ThrombUS+. A report by the ethics advisor must be submitted to cover these issues every year starting at M12. D10.3 is the second yearly report compiled by the Independent Ethics Advisor appointed by the Consortium. Cite this Document as Sardeli C., ThrombUS+ Ethics Appraisal Report #2, Deliverable D10.3, ThrombUS+ Horizon Europe Innovation Action, EC Grant Agreement No. 101137227, 18 December 2025, https://doi.org/10.5281/zenodo.17963777, Publishable Summary. D10.3| OEI: Ethics Advisor Report #2 v1.0 | 18 Dec 2025 | Publishable Summary 2 Terms and Definitions Term Definition DVT Deep vein thrombosis EC European Commission ENTIS European Network of Teratology Information Specialists EU European Union GA Grant Agreement GDPR General Data Protection Regulation HADEA European Health and Digital Executive Agency hE Human Embryos hESC Human Embryonic Stem Cells IMI Innovative Medicines Initiative OEI Other Ethics Issues ORCID Open Researcher and Contributor Identification PGNA University General Hospital of Alexandroupoli, Associated Partner newly admitted to the Consortium D10.3| OEI: Ethics Advisor Report #2 v1.0 | 18 Dec 2025 | Publishable Summary 3 Report by the Independent Ethics Advisor Funding Programme Horizon Europe Call HORIZON-HLTH-2023-TOOL-05-05 Grant Agreement Number 101137227 Acronym ThrombUS+ Project Title Wearable Continuous Point-of-Care Monitoring, Risk Estimation and Prevention for Deep Vein Thrombosis Project start date-end date 1 January 2024 – 30 June 2027 Period covered M13 – M24 Jan 2025 to Dec 2025 1. Name and Contact Details Chrysanthi Sardeli, MD, PhD, Associate Professor LinkedIn: https://www.linkedin.com/in/dr-chrysanthi-sardeli-md-phd-a654524b/ GoogleScholar: https://scholar.google.com/citations?user=E9ZODW8AAAAJ&hl=en&oi=ao Scopus: https://www.scopus.com/authid/detail.uri?authorId=6506769092 2. Overview of ethics issues raised by the project activities 2.1. Project activities timing and progress Overall, project activities are progressing according to the GA and the approved workplan. There has been a delay in the recruitment in Study A, however this has been documented in the Interim Report #1 and mitigated. Study A has received all necessary ethics approvals and is now progressing steadily in five different sites (with the replacement of TAU by PGNA). The main ethics issues raised during this second project year are related to the Clinical Studies B. As already documented in the Interim Report #1, Clinical Study B2 was split into 3 different studies to allow for coherence in implementation. As a result, Studies B are as follows: Clinical Study B1: A multi-centre cohort study for ultrasound image set collection via ThrombUS+ prototype ultrasound components to create a training data set for research purposes (image processing and analysis, AI training). Clinical Study B2: A single-centre observational cohort study to collect lower limb activity measurements from healthy volunteers during physiotherapy exercises using commercial inertial measurement units D10.3| OEI: Ethics Advisor Report #2 v1.0 | 18 Dec 2025 | Publishable Summary 4 (IMUs) and camera sensors to create a training data set for research purposes (signal processing and analysis, AI training). Clinical Study B3: A single-centre observational cohort study to collect lower limb activity measurements from healthy volunteers during physiotherapy exercises using the inertial measurement unit (IMU) system developed in ThrombUS+ and commercial fixed position cameras with the aim to test and optimize IMU performance and fusion algorithms for human motion tracking. Clinical Study B4: Pilot phase clinical investigation to collect electrical impedance plethysmography data set from healthy volunteers and DVT patients using the ThrombUS+ prototype device developed during the project and a commercially available equivalent device as a reference. Studies B are planned as studies to collect signals and data to be used for training machine learning models and/or developing signal processing and analysis algorithms. The studies are planned to use experimental data collection components developed in the project and thus not yet certified for commercial use. An exception is Study B2, which uses solely commercial, certified activity sensors. Ethics related procedures have been respected, and the current status of attaining the necessary ethics approvals is as follows: all ongoing studies have been submitted for ethics assessment to relevant authorities and said authorisation has been attained for all participating sites. Planned pending studies have either been submitted for ethics assessment to relevant authorities or are in the process of submission for ethics assessment to relevant authorities prior to their initiation. 2.2. Deviations from the ethics issues identified in the Ethics Summary Report No deviations from the ethics issues included in the Ethics Summary Report have been identified. Project activities in months M12-M24 have not raised any additional specific ethical concerns. The Consortium has been advised of their obligations to reapply for ethics approvals every time they complete the planning of a new clinical trial. They have also asked for and received advice on how to best recruit study participants in a manner that respects their rights and situation, as indicated during the Ethics Assessment process of the project prior to its obtaining funding. The Consortium has also been advised that adopting an ethics-by-design approach means that they should make a conscious effort to ensure that the final product does not record more information than absolutely necessary for the aims of the project and that all information pertaining to possible threats to personal rights and freedom of participants and future users (should the product be made commercially available) is readily available to them. 2.3. Ethics issues considered no longer applicable Not applicable. 3. Ethics Analysis 3.1. Overview of the management of project’s activities in relation to ethics The project management, on behalf of the Consortium, complied to the ethics requirements included in the GA by appointing an Independent Ethics Advisor, by providing them full access to the files of the project, by meeting regularly with the Independent Ethics Advisor and by actively seeking and receiving advice on how to best conduct their work. Collaboration involved all project aspects, focusing on the Clinical Studies planned to be dealt with during second year of the project work plan. This way the project management ensured that project activities run on time for this reporting period and are in accordance with the ethics requirements of the GA. D10.3| OEI: Ethics Advisor Report #2 v1.0 | 18 Dec 2025 | Publishable Summary 5 3.2. Activities of the Ethics Advisor The Independent Ethics Advisor accessed and reviewed all project documents and select relevant recordings of project meetings located in the project’s private shared workspace (Teams/SharePoint), participated in regular meetings with the management and select Consortium members, offered advice on the ethics issues identified in the Ethics Summary Report but also on possible ways for the Consortium to adopt an ethics-bydesign approach. The particular ethics issue with Studies B (specifically, Studies B1, B3, and B4) relates to the fact that these studies plan to use experimental, non-CE-marked components developed within the ThrombUS+ project. These components are used exclusively for research data collection purposes and are not intended for diagnostic or therapeutic use. The Ethics Advisor engaged in and contributed to the consortium discussions to address the above issue following regulations and best practices. Elaboration and deliberations resulted in the following course of action: For each ThrombUS+ developed component to be used in a clinical study: − A comprehensive risk assessment was carried out, with the involvement of technical partners, VDE and reviewed by the Ethics Advisor − All potential risks associated with the use of the experimental components were systematically identified and analysed − Appropriate risk mitigation measures were defined and implemented − Residual risks were assessed and documented − Technical safety testing was conducted by respective partners. All risk analysis activities, safety assessments, mitigation measures, and conclusions are fully documented in the study protocol. The overall residual risk is considered “acceptable”. Ethics approval for Studies B1, B3 and B4 is requested by the respective Ethics Committees of the participating partners under Article 82 of Regulation (EU) 2017/745 (Medical Devices Regulation), as these studies constitute scientific research. These studies: − do not aim to demonstrate clinical performance or conformity of a medical device − do not involve diagnostic or therapeutic use of the prototype system − do not influence clinical decision-making or patient management. The prototype components are used solely for data acquisition in a research context. Given the scientific research nature of the studies under Article 82 MDR and the documented minimal risk profile demonstrated through the risk analysis and safety assessments, no additional study-specific insurance is foreseen at this stage. All relevant documentation has nevertheless been provided to the competent Ethics Committees to allow them to assess independently whether additional insurance coverage is required, in accordance with national and institutional requirements. 3.3. Documents available to the Ethics Advisor Τhe Consortium has granted full access to the project’s private shared workspace (Teams/SharePoint) and made sure that all project materials are readily available for inspection by the independent Ethics Advisor. 3.4. Overview of evidence of ethics compliance Below is a list of ethics approvals pertaining to the studies considered in the 2nd year of the project.