This document presents the TAXINOMISIS First Subject Approvals Package which provides detailed information on the procedures that will be implemented for patient recruitment to the prospective clinical study protocol.

Since the initiation of the project on January first clinical partners communicated in order to define optimal protocol for clinical study that is part of Taxinomisis project and deliverable D5.1. At the end of January, during the kick off meeting the inputs for the study protocol were discussed among Consortium. The main goal of the study is to validate and adjust a stratification tool that will be defined from longitudinal studies in WP3. Data extracted from huge registries will be used to stratify patients with carotid disease in order to define those who are at increased risk of stroke when preventive surgery is beneficial. During the kick of meeting, all partners discussed the optimal manner to conduct clinical trial and which are the most important data to be delivered from this trial. Non clinical partners proposed parameters of interest for stroke in patients with carotid disease that should be validated in clinical trial.

During the kick off meeting, UBEO and Igor Koncar were elected to coordinate the study with the purpose to lead the clinical study from development of protocol to study conduction. After the kick off meeting clinical partners leaded by UBEO exchanged and discussed three consecutive versions of the clinical trial protocol that were additionally discussed in teleconferences with clinical and nonclinical partners. Study protocol accurately describes inclusion and exclusion criteria, primary and secondary endpoints and methods of patients’ examination and follow up visits. All these parameters were thoroughly discussed among clinical partners and evaluated by the teams of each clinical partner.

Patients with inclusion criteria will be examined (blood tests, ultrasonography and MRI of carotid bifurcation and MRI of the brain, carotid plaque sample analysis) while entering the clinical study and will be followed for three years with the same annual examinations. During that time primary and secondary endpoints will be followed and compared with those expected from developed stratification tool delivered from longitudinal data of huge registries that are already available in non-clinical partners. The study protocol was discussed with ESCVS representatives that will assess this trial from legal and ethical point of view.

Finally, the clinical trial protocol was accepted by all the clinical partners, approved by the Ethical board of University of Belgrade and the Clinical trial was submitted in registry for Clinical trials. The first patient of this clinical trial was recruited in UBEO on 30th of March 2018

In the following time, the clinical study will be approved by all the local Ethical committees of the clinical partners and patients’ recruitment will start in all participating centers.  The study protocol defined the recruitment committee that will schedule a conference call during M4 and discuss further recruitment goals of all individual partners in the following 14 months.

This document is the TAXINOMISIS midterm recruitment report for the project’s prospective observational clinical study. The report provides an overview of the research participants recruited so far, by each clinical centre, any problems encountered during the process and a detailed description of measures planned to be implemented to compensate any delays in the study’s subject enrolment goals.

Since the initiation of the project in January 2018, the clinical partners have defined the optimal protocol for the clinical study, part of the Deliverable D.5.1.  Dr. Igor Koncar was chosen as study coordinator with the purpose to lead the clinical study, from the development of the protocol to the conduction of the study. The clinical study protocol accurately describes the inclusion and exclusion criteria, the primary and secondary endpoints and the methods of patients’ examination and follow-ups. The clinical study protocol has been discussed with the ESCVS partner that oversees this trial from the legal and ethical point of view. The protocol has been accepted by all clinical partners, approved by the Ethical board of the University of Belgrade and the Clinical trial has been registered in an international registry for clinical trials under the reference number NCT03495830 (www.clinicaltrials.gov). The first patient of the clinical trial was recruited in UBEO on the 30^th of March 2018. The procedures for patient recruitment have been initiated in all participating clinical centres, after receiving the appropriate Ethical Approvals by the competent Ethics committees, except for the partner UMC UTRECHT as the decision of the corresponding Ethics committee is still pending, due to additional mandatory procedures and documents required. In addition, the protocol has defined a committee responsible to address problems and discuss further recruitment goals, for all clinical partners, in the following months of the recruitment period. Each collaborating clinical centre has projected a number of recruited patients and estimated a monthly rate of enrolment until M18, when recruitment is estimated to be finalized. Collectively, by December 31^st 2018, 88 patients have been recruited in UBEO, TUM-Med, N.K.U.A. and FCRB. As far as the quality of imaging data is concerned, a representative image (non-identifiable data), for each image modality used in each centre, has been approved by the study coordinator. Although, delays have been encountered mainly due to time-consuming procedures to acquire ethical approvals and due to different equipment specifications needed for image acquisition, the overall recruitment rate is considered acceptable and estimated to increase with the full engagement of the rest of the clinical partners to the recruitment process within the next months. Finally, the project coordinator (UOI) has developed the electronic Case Report Form (eCRF) platform which is necessary for data collection and management using the infrastructure services (IaaS) of a cloud provider engaged as a third-party processor under a contract compliant with Article 28 of the EU’s General Data Protection Regulation (GDPR). More specifically, the Greek Research and Technology Network (GRNET) has been added in the consortium as a third party providing in-kind contribution free-of-charge to the coordinator UOI (art. 12 of the Grant Agreement).

This document presents the TAXINOMISIS Clinical study progression and status on posting the results of the clinical study. Data collected in the clinical study since patient recruitment and during follow up.

After the finalization of the clinical study protocol and Ethical approval in all clinical partners (D5.1) patient recruitment has been started. The main goal of recruitment was to collect data on 300 patients with carotid stenosis of 50% and more in the moment of recruitment and during follow up of 36 months.  The main goal of the study is to validate and adjust a stratification tool that will be defined from longitudinal studies in WP3. Data extracted from huge registries will be used to stratify patients with carotid disease in order to define those who are at increased risk of stroke when preventive surgery is beneficial. During the kick of meeting, all partners discussed the optimal manner to conduct clinical trial and which are the most important data to be delivered from this trial. Non clinical partners proposed parameters of interest for stroke in patients with carotid disease that should be validated in clinical trial.

During the kick off meeting, UBEO and Igor Koncar were elected to coordinate the study with the purpose to lead the clinical study from development of protocol to study conduction, data collection and analysis. Study protocol accurately describes inclusion and exclusion criteria, primary and secondary endpoints and methods of patients’ examination and follow up visits. All these parameters were thoroughly discussed among clinical partners and evaluated by the teams of each clinical partner. Finally, the clinical trial protocol was accepted by all the clinical partners, approved by the Ethical board of University of Belgrade and the Clinical trial was submitted in registry for Clinical trials (www.clinicaltrials.gov under the number NCT03495830/). The first patient of this clinical trial was recruited in UBEO on 30th of March 2018. Ethical approval in UMC has been accepted with delay () which caused delay in recruitment in this clinical partner. During the period M6-M20 305 patients were recruited based on the study protocol and inclusion and exclusion criteria. Due to delayed recruitment and lower recruitment rate in UMC and in USMI the number of recruited patients was achievedby increased recruitment in other partners (UBEO and NKUA). In addition majority of patients recruited in USMI was indicated for interevetion which prevented follow up of the carotid plaque. This was resolved by additional recruitment in USMI of 31 patients.

Patients included in the clinical study were prospectively follow by clinical, ultrasound and MRI examination during the period M20-M48. COVID-19 pandemic period started at M26 when work of most of the hospitals in the world was interrupted with COVID patients. In hospitals of all clinical partners clinical departments were occupied with COVID patients and countries of clinical partners suspended clinical examination of non-urgent patients as well as patients included in the clinical trials. This force major influenced further conduction of the task 5.3 and project extension has beenapproved. After six months of suspension partners initiated follow up examinations in their centers depending on epidemiological situations and decisions and instruction of official bodies of the hospitals, cities and countries. Due to variation of measures between the countries and even cities and hospitals patient follow was different among partners and it was dependent on COVID waves and their peaks. This variation influenced time laps between the follow up examinations as well.

Until M48 baseline, first (12 month) and second (24 month) follow up examinations were completed in UBEO, NKUA, FCRB, UMSI while follow up of patients in TUM and UMC are delayed since the COVID measures were extended in Netherlands and Germany especially during the second half of 2021. During the follow up period collection of data progress was assessed and image data quality was tested, by coordinator (UOI) for MRI carotid plaque and brain and BIOIRC for ultrasound carotid plaque, since these partners were using imaging for deliverables in WP3. Differences in image quality were recognized, discussed and corrected while protocols for MRI and ultrasound examinations were corrected in order to gain sufficient data to be used in WP3. Insertion of data in eCRF is cautiously monitored during the study and monthly follow up conference calls between clinical partners are used to report progress in follow up.

This document presents the TAXINOMISIS Clinical study progression and the status on posting the results of the clinical study. Data collected in the clinical study since patient recruitment and during follow-up visits until the end of the study are also presented.

After the finalization of the protocol of the clinical study, and after ethical approval from all clinical partners had been obtained (D5.1), patient recruitment started. The main goal of recruitment was to collect data of 300 patients with carotid stenosis of ≥50% at the moment of recruitment and to perform a follow-up of these patients ending at 36 months. The outmost aim of the study was to contribute to the development, validation and adjustment of a stratification tool under the framework of WP3. Data extracted from large registries have been used to stratify patients with carotid disease to define those who are at increased risk of stroke when preventive surgery might be beneficial. During the kick-off meeting, all partners discussed the optimal manner to conduct the clinical trial and tried to define the most important data to be delivered from this trial. Non-clinical partners proposed parameters of interest for increased risk of stroke in patients with carotid disease that should be validated in the clinical trial.

During the kick-off meeting, UBEO and Ass. Prof. Igor Koncar were elected to lead and coordinate the clinical study starting with the development of the protocol to the study conduction, data collection and analysis. The study protocol that was defined precisely described the inclusion and exclusion criteria, primary and secondary endpoints, and the methods of patients’ examination and follow-up visits. All these parameters were thoroughly discussed among clinical partners and evaluated by each clinical partner. The clinical trial protocol was reviewed by ESCVS (WP6), accepted by all the clinical partners, approved by the Ethical Board of University of Belgrade and the Clinical trial was submitted in the registry for Clinical trials (www.clinicaltrials.gov) under the number NCT03495830. The first patient of this clinical trial was recruited in UBEO on the 30^th of March 2018. All the clinical partners received their local ethical approvals on time, except for the ethical approval of UMC, which was accepted with a delay (M15), and that caused a delay in recruitment in UMC. During the period M6-M20, 305 patients were recruited based on the study protocol and inclusion and exclusion criteria. Due to delayed and/or lower recruitment rate in UMC and in USMI, the required number of patients was achieved by increasing recruitment in other partners (UBEO and NKUA). In addition, all patients recruited in USMI were assigned for intervention which prevented follow-up of the carotid plaque. This was resolved by additional recruitment of 31 patients in USMI that were followed for only 12-24 months consequently since they were recruited at a later phase.

Patients included in the clinical study were prospectively followed by clinical, ultrasound and MRI examinations from M20-M66. COVID-19 pandemic started at M26 when the work of most of the hospitals in the world was interrupted. In hospitals of all clinical partners, clinical departments were occupied with COVID-19 patients, and clinical examinations and hospital visits of non-urgent patients, including patients in clinical trials, were suspended in the countries of all clinical partners. This force majeure influenced further conduction of the Task 5.3 and project extension has been requested and approved by the European Commission. After six months of suspension, the clinical partners initiated follow-up examinations in their centers depending on epidemiological situations in their respective countries, and the decisions and instructions of official bodies of the hospitals, cities and countries. Due to variation of epidemiological measures between the countries, and even cities and hospitals in the same country, patient follow-up was different between partners, and it was dependent on COVID-19 epidemic waves and their peaks. This variation influenced the intervals between the follow-up examinations of patients included in clinical trials, especially for the patients of TUM and UMC as delay was caused by the COVID-19 measures that were prolonged in the Netherlands and Germany during the second half of 2021. COVID-19 pandemic also contributed to lower compliance of recruited patients to the study and increased lost to follow up.

During the follow up period, the progress of data collection was assessed (by UOI) by monitoring the data uploaded on the electronic case report form (eCRF). The quality of image data was assessed by the coordinator (UOI) for MRI of carotid arteries and plaques, while BIOIRC assessed the quality of the carotid plaque ultrasound imaging. This was done in synchronization with WP3, because these partners were using imaging data for the deliverables of this WP. Differences in image quality were recognized, discussed, and corrected, while the protocols for MRI and ultrasound examinations were corrected in order to achieve sufficient data to be used in WP3. Insertion of data in eCRF has been cautiously monitored during the study. Monthly follow-up conference calls between clinical partners are used to report progress in the follow-up of patients. At the final phase of the clinical study a separate session with the clinical partners has been organized and the report from the eCRF prepared by UOI was discussed among clinical partners. All missing data were reported and clinical partners did final entries in the eCRF in order to achieve completeness of data.

All collected imaging data are analyzed and used in WP3. Duplex ultrasound data of the carotid bifurcation are descriptively assessed, and blood flow measurements are recorded. MRI carotid plaques are annotated in order to be used in WP3, however, plaques are additionally assessed for the purposes of the study data analysis.

At M66 follow up has been finished and data have been entered in the eCRF. Data have been used in WP3 for the development of the risk stratification tool and all data were analyzed for the purposes of the clinical study. Cardiovascular and cerebrovascular events were registered while reasons for lost to follow up and intervention during follow up were recorded. Baseline demographic and carotid data are reported as well as information about the plaque progression, cerebrovascular, cardiovascular and mortality events.   Brain MRI is separately analyzed, and brain lesions are described in terms of location, number, volume, and etiology. Analysis of MRI brain lesions is ongoing while initial results are reported in the present deliverable. All collected data are used in WP3, as well as for additional analysis in WP5.

This document presents the results of the TAXINOMISIS study, which includes data collected from patient recruitment through follow-up visits until the study's completion. After finalizing the clinical study protocol and obtaining ethical approval from all clinical partners (D5.1), patient recruitment commenced. The primary objective was to gather data from 300 patients with carotid stenosis of ≥50% at the time of recruitment and conduct a 36-month follow-up. The ultimate goal of the study was to contribute to the development, validation, and refinement of a stratification tool as part of WP3. Large registries were utilized to stratify patients with carotid disease and identify those at a higher risk of stroke where preventive surgery could be beneficial. During the kick-off meeting, all partners deliberated on the optimal way to conduct the clinical trial and identified the key data that should be generated from the study. Non-clinical partners proposed parameters of interest for assessing the increased risk of stroke in patients with carotid disease, which would undergo validation in the clinical trial.

UBEO and Ass. Prof. Igor Koncar were chosen during the kick-off meeting to oversee and coordinate the clinical study, starting from protocol development to study implementation, data collection, and analysis. The study protocol provided precise guidelines on inclusion and exclusion criteria, primary and secondary endpoints, as well as methods for patient examination and follow-up visits. These parameters were thoroughly discussed and evaluated by all clinical partners. The clinical trial protocol underwent a review by ESCVS (WP6), received acceptance from all clinical partners, and was approved by the Ethical Board of the University of Belgrade. Additionally, the clinical trial was registered on the Clinicaltrials.gov registry under the number NCT03495830. The first patient was recruited at UBEO on March 30, 2018. All clinical partners obtained their local ethical approvals on time, except for UMC, which experienced a delay (M15) in receiving ethical approval, resulting in a delay in recruitment at UMC. From month 6 to month 20, a total of 305 patients were recruited based on the study protocol and inclusion/exclusion criteria. To compensate for the delayed or lower recruitment rate at UMC and USMI, recruitment efforts were intensified at other partner institutions (UBEO and NKUA). Furthermore, In USMI, all recruited patients underwent intervention, which hindered the follow-up assessment of the carotid plaque. To resolve this issue, an additional recruitment of 31 patients in USMI was conducted at a later phase. These patients were followed up for a duration of 12-24 months.

Patients participating in the clinical study were regularly monitored through clinical, ultrasound, and MRI examinations from M20-M66. However, the COVID-19 pandemic, which began at M26, resulted in the interruption of hospital operations worldwide. Clinical departments of all clinical partners were occupied with treating COVID-19 patients, leading to the suspension of clinical examinations and hospital visits for non-urgent cases, including patients participating in clinical trials. This unforeseen event had a significant impact on the continuation of Task 5.3, and as a result, a project extension was requested and approved by the European Commission.

Due to variations in epidemiological measures, including differences between countries, cities, and even hospitals within the same country, the timing and frequency of patient follow-up varied among partners. The intervals between follow-up examinations were influenced by the waves and peaks of the COVID-19 epidemic. This variability particularly affected the follow-up of patients from TUM and UMC, as the COVID-19 measures in the Netherlands and Germany were extended during the second half of 2021. COVID-19 pandemic also contributed to lower compliance of recruited patients to the study and increased lost to follow up. This was the reason for another extension of six months that was approved by the European Commission.

Throughout the follow-up period, the data collection progress was assessed by the University of Ioannina (UOI) through monitoring the data uploaded on the electronic case report form (eCRF). The quality of image data, specifically for MRI of carotid arteries and plaques, was evaluated by UOI, while the BIOIRC assessed the quality of ultrasound imaging. This assessment was conducted in coordination with WP3, as these partners utilized imaging data for the deliverables of that work package. Monthly follow-up conference calls among clinical partners served as a platform to report on the progress of patient follow-up. During the final phase of the clinical study, a dedicated session was organized for the clinical partners to discuss the report prepared by UOI based on the eCRF data. Any missing data were identified and reported, and the clinical partners made the necessary final entries in the eCRF to ensure the completeness of the data.

All imaging data collected, including duplex ultrasound data of the carotid bifurcation and MRI carotid plaques, are analyzed and utilized in WP3. The duplex ultrasound data of the carotid bifurcation is assessed using descriptive analysis, and blood flow measurements are recorded. As for the MRI carotid plaques, they are not only annotated for use in WP3 but also subject to additional assessment specifically for the purposes of data analysis in the study. Additionally, brain MRI data were separately analyzed, focusing on the description of brain lesions in terms of location, number, volume, and etiology. Cardiovascular and cerebrovascular events were documented, and reasons for lost to follow-up and interventions during follow-up were recorded. Baseline demographic and carotid data were reported, providing information on plaque progression, cerebrovascular events, cardiovascular and mortality events. Data collected throughout the study are reported in this document.

The deliverable D6.1 presents the regulatory strategy and roadmap of the TAXINOMISIS project. It deals with the current regulatory context for medical devices and describes the TAXINOMISIS main outcomes and approach to attract the regulatory bodies. The TAXINOMISIS consortium aims to ensure that the information and data to be conveyed and discussed with the regulatory experts and bodies are presented in the right way and form. In this direction, documents related to the TAXINOMISIS outcomes and risk stratification predictions will be prepared including all the evidences and results from the clinical study. The Regulatory Manager of the project is Prof. Dimitrios I. Fotiadis (UOI). A meeting with regulatory bodies will be planned, as described in the DoA, when the risk stratification tool and lab on a chip will reach the necessary maturity from a technical point of view.

D6.2 is a continuation of the deliverable D6.1 which mainly described the current framework in regulatory issues related to the activities of the TAXINOMISIS project. D6.2 describes specific actions followed by the consortium within the period M55-M72 to prepare the next steps of the regulatory strategy and roadmap considering all the results produced by the project. The outmost aim of this deliverable is to ensure that the information and data to be conveyed and discussed with the regulatory experts and bodies (ESCVS, ESVS) are presented in the right way and form. This deliverable falls within the scope of Task 6.2 which requires the development of the regulatory strategy and roadmap, arrange agency meetings, prepare and compile the questions and briefing documents related to the TAXINOMISIS outcomes and risk stratification predictions including all the evidences and results from the clinical study.

More specifically, in October  5^th , 2023 (see Appendix I) a meeting with regulatory experts was planned, as described in the DoA (figure 18), to present the risk stratification tool and the lab on a chip and obtain feedback on the regulatory needs related to the two main outcomes of TAXINOMISIS.

Additionally, during the last plenary meeting in Belgrade (13-14 November, 2023), the final clinical and technical results of the project were presented and the consortium discussed and agreed on the regulatory steps that should be followed for the installation and use of the risk stratification tool in clinical centers after the end of the project. Additionally, after the completion of the plenary meeting on November 14^th, 2023 a meeting with policy makers was held in Belgrade and the TAXINOMISIS outcomes were presented to a committee from the Serbian Office for Information Technologies and e-Government. It was decided that the tool will be introduced in Serbian clinical sites. BioIRC undertook the regulatory pathway implementation, UBEO undertook the sites identification and the contacts with the government AI committee, while Prof. Fotiadis (UOI) will monitor the aforementioned activities as Project Coordinator and Regulatory Manager.

Finally, to address the requirement of Task 6.2 to ensure that information and data are conveyed and discussed in a proper manner with regulatory experts and bodies from key organizations such as ESCVS and ESVS, the TAXINOMISIS project was presented by clinical and technical representatives of the consortium in all the following events (more information is available on the project’s website: https://taxinomisis-project.eu/news/):

- ESVS 37th Annual Meeting in Belfast, Northern Ireland (ESVS 2023)

-70th Congress of the European Society of Cardiovascular and Endovascular Surgery (ESCVS 2022)

- 68th Congress of the European Society of Cardiovascular and Endovascular Surgery (ESCVS 2019)

- Meet the ESVS in Serbia! (2022)

- TAXINOMISIS workshop in ESVS 33rd Annual Meeting (2019)

In this deliverable, economic models for three main questions that TAXINOMISIS aims to address for asymptomatic patients are considered. These questions have been formulated to identify asymptomatic carotid stenosis patients for recommending the ultrasound (US) screening, then find the patients under higher risk for stroke and provide advice on the optimal time for next follow-up US or other screening image modalities (such as Computed Tomography Angiography – CTA, or Magnetic Resonance Angiography – MRA).

TAXINOMISIS aims to answer the following questions for asymptomatic patients:

1. Q1 - To identify asymptomatic carotid stenosis patients in order to recommend US screening.
2. Q2 - To identify asymptomatic patients with higher risk for stroke in order to target intervention such as Carotid Endarterectomy (CEA) / Carotid Artery Stenting (CAS) versus best medication therapy (BMT).
3. Q3 - To provide advice on the optimal time for the next follow-up screening for the BMT group.

Cost effectiveness analysis of treatment options for carotid artery stenosis including plaque progression, rupture and diagnostic cost for Doppler ultrasound, MRA, or CTA is presented in Section 1. All other costs such as Medical Management, Surgical Intervention, Hospitalization, Complications, Follow-Up and Rehabilitation were considered as Stroke costs. Diagnostic Costs such as US and MRI (Magnetic Resonance Imaging) / CT (Computer Tomography) have been analysed in the prolonged time period with cycles of 30 years for patients over 65 years.

The TAXINOMISIS platform with software and hardware components is described in Section 2. Software components consist of Risk Assessment (Predictors and Biomarkers), 3D Reconstruction and Plaque Characterization, Blood Flow Modelling, Plaque Rupture, Plaque Growth (Continuous and Agent Based), Risk Stratification Tool, as well as Clinical Data. The hardware component is the Lab-on-a-Chip device.

In addition, a Markov model is described with health states and transition probabilities from one state to another (Section 3). Three states were defined for cost-effectiveness model. These three states are: Stenosis, Stroke and Death. Also, decision tree which includes two options: with usage of TAXINOMISIS solutions (“WITH TAXINOMISIS”) and without usage of TAXINOMISIS solutions (“NO TAXINOMISIS”) is described. Also, net monetary benefits (NMB) and net health benefits (NHB) are described. Tornado diagrams as powerful tools in sensitivity analysis are explained.

The TAXINOMISIS Risk Assessment module as an answer to the first question (Q1) is described in Section 4. It is shown that it can significantly reduce cost of screening for the whole population which is directly proportional to the percentage of risk patients in global population. Thus, pure benefit is to avoid US/MRI screening cost for the whole population. TAXINOMISIS Q1 cost-effectiveness analysis gives more than 3 times reduced costs for using TAXINOMISIS platform than without using the platform to estimate which asymptomatic patient should undergo screening with US.

The second TAXINOMISIS question (Q2) is described in Section 5. It aims to identify asymptomatic patients at a higher risk for stroke. The cost-effectiveness analysis has shown that the TAXINOMISIS platform reduces costs almost two times for the Q2 in comparison with standard clinical procedure. The calculated costs are 27,400 EUR for 10.2 life years (LY) for standard medication therapy using TAXINOMISIS vs 43,200 EUR for 12.6 LY for medication therapy and surgery without using TAXINOMISIS.

The third TAXINOMISIS question (Q3) is described in Section 6. It is related to patients under BMT, where TAXINOMISIS aims to provide advice on the optimal timing for the next follow-up screening. It considers factors such as the aggregated cost of US/MRI/CT screening over a 10-year period and determining the most effective and economical follow-up strategy. Cost-effectiveness analysis has shown that Quality-Adjusted Life Year (QALY) is starting from 6.30 with using TAXINOMISIS (option “WITH TAXINOMISIS”) up to 6.91 QALY without using TAXINOMISIS (option “NO TAXINOMISIS”), with a cost of 62,148 EUR with using TAXINOMISIS (option “WITH TAXINOMISIS”) up to 105,318 EUR without using TAXINOMISIS (option “NO TAXINOMISIS”). Obviously, TAXINOMISIS platform with its predictive modules can reduce a number of US and MRI/CT examinations and ultimately reduce the required time and costs to reach for a clinical decision regarding a surgical intervention. Also, TAXINOMISIS Q2 cost-effectiveness analysis has shown that calculated costs are 27,400 EUR for life years 10.2 LY for BMT and TAXINOMISIS vs 43,200 EUR for life years 12.6 LY for BMT and CEA/CAS. That means TAXINOMISIS platform reduces almost two times the cost for the TAXINOMISIS Q2 in comparison with the standard clinical procedure.

Finally, the impact of TAXINOMISIS adoption for the healthcare system is described in Section 7. It is shown that current clinical practice based on the latest evidence and guidelines in the field of carotid artery disease from organizations such as the American Heart Association (AHA) and the European Society for Vascular Surgery (ESVS) can be changed with TAXINOMISIS platform significantly (option “WITH TAXINOMISIS”). The cost–effectiveness analysis for all three TAXINOMISIS questions collectively addresses the challenge of managing asymptomatic carotid stenosis with significantly reduced costs in comparison to standard clinical practice for two or three times.

TAXINOMISIS progress and outcomes will be disseminated in a way that will appropriately address the target audiences on all stages of the project and create a lasting impact in the European economy and the public audience. This deliverable deals with the TAXINOMISIS presentation material developed during the first six months of the project (January 1^st, 2018 – June 30^th, 2018). TAXINOMISIS logo, press release, brochure, flyer, poster, social media and website are presented which will be updated according to the needs of the project within its lifecycle. The presented activities fulfill the initial dissemination activities plan of the project as presented in the DoA.

The deliverable D7.2 describes the communication and dissemination activities of TAXINOMISIS within the first 18 months of the project (January 1^st, 2018 – June 30^th, 2019). It constitutes the first version of a series of three deliverables describing the communication and dissemination activities at different time frames of the project (M18, M36, and M60). Both the communication and dissemination strategies will be continually monitored within the duration of the project and will change in accordance with the needs of the dissemination and communication process aiming to create a lasting impact in the European society and economy.

The deliverable D7.3 describes the communication and dissemination activities of TAXINOMISIS within the last 18 months of the project (July 1^st, 2019 – December 31^th, 2020). It constitutes the second version of a series of three deliverables describing the communication and dissemination activities at different time points of the project (M18, M36, and M66). Both the communication and dissemination strategies will be continually monitored within the duration of the project aiming to create a lasting impact in the European society and economy. It should be emphasized that within the period January 1^st – December 31^st 2020 the dissemination and communication activities of TAXINOMISIS were continued despite the impact of the Covid-19 outbreak.

Deliverable D7.4 – Communication and dissemination activities v3 reports on the work performed in WP7 – Dissemination, exploitation and commercialization activities (Task 7.1. Evidence-based communication and dissemination) during the last 36 months of the project (from 1^st January 2021, to 31^st December 2023). This document represents the third version of deliverables detailing the communication and dissemination efforts at different milestones of the project (M18, M36 and M72). Both communication and dissemination strategies have been consistently monitored throughout the project duration, with the goal of creating a lasting impact on European society. The report outlines the dissemination objectives, strategy, criteria and channels, identified key target groups and provides a detailed description of the undertaken dissemination and communication activities.

The aim of D8.1: Project handbook, risk management and quality assurance plan is to provide TAXINOMISIS consortium with the overall description of the management structure, including the main activities to ensure the Consortium compliance with EU regulations and their contractual and legal requirements, to manage and control project objectives, resources, schedules and activities and ensure the integration of administrative related tasks. This report also presents the project periodic reports, including management report, report on the distribution of funds, financial and audit certificates, communication with the European Commission concerning administrative and managerial issues (i.e. financial issues, contract amendments, reporting).

Therefore, each partner can use the project handbook to retrieve information for the project management rules that the TAXINOMISIS consortium as a whole will follow to ensure a high project quality and effective cooperation. The proper implementation of these rules is a responsibility of the Project Coordinator.

This deliverable summarizes the data pertaining to gender equality for the entire consortium throughout the duration of the project and provides sex disaggregated data on workforce as well as wellbeing data of the people involved in the project throughout their involvement in the project. Gender equality monitoring occurred via questionnaires completed by a representative chosen at each partner site. To monitor the Consortium’s commitment to the gender actions, the Gender & Equal Opportunity Manager (Prof. C. Monaco) collected information, including but not limited to, sex-disaggregated data on workforce (permanent or newly appointed) and on invited speakers in workshops and conferences organised within TAXINOMISIS; impact of family friendly working conditions will also be considered. Six months before the end of the project, a survey was administered across partners to evaluate impact of the working environment and career as well as professional mobility in terms of work-life balance. Information collected was assembled and discussed in a deliverable, the “Report on Gender and Equal Opportunities”.

Our data shows that there was an overall representation of both genders throughout all levels of leadership in people involved in the TAXINOMISIS project. The participation of women in research was highly represented, and the Consortia achieved gender balance in decision making.

The findings presented in this document demonstrate a very positive result for recruitment of female staff members in key positions. The findings indicate that TAXINOMISIS gender equality data findings concur with the Horizon 2020 objectives of fostering gender balance in research teams, addressing the gaps in participation of women in its funded research projects and to ensure gender balance in decision making.