R-TF-015-004 Clinical Investigation Plan

Scope

The purpose of this Clinical Investigation Plan (CIP) is to set out the rationale, objectives, design, methodology, conduct, implementation, record-keeping and the method of analysis for the clinical investigation.

CIP Identification

	CIP
Title of the clinical investigation	Pilot study for the clinical validation of an artificial intelligence algorithm for the automatic calculation of EASI to assess the severity of atopic dermatitis
Device under investigation	Legit.Health Plus
Protocol version	Version 4.0
Date	11/03/2026
Protocol code	Legit_aEASI_HVN v_4_0
Sponsor	AI LABS GROUP, S.L (Legit.Health)
Coordinating Investigator	Dra. Clara Ureña Paniego
Principal Investigator(s)	Dra. Clara Ureña Paniego
Collaborating Investigator(s)	Dra. Trinidad Montero Vílchez, Alfonso Medela, Andy Aguilar, Taig Mac Carthy, Dr. Jordi Barrachina
Investigational site(s)	Hospital Universitario Virgen de las Nieves
Ethics Committee	Comité Ético de Investigación de Granada

Table of contents

• Scope
• CIP Identification
• Compliance statement
• Abbreviations and Definitions
• CIP or protocol specifications
  • Principal Investigator
  • Coordinating Investigator(s)
  • Collaborating Investigator(s)
  • Investigational sites
  • Funding
• Product Identification and Description
  • Device accountability
• Justification of the design
  • Background and rationale
  • Evaluation of preclinical and clinical data
• Hypothesis
• Objectives
  • Primary objetive(s)
  • Secondary objective(s)
• Summary of the study
• Design and Methods
  • Type of clinical research
  • Population
  • Duration
  • Acceptance criteria
  • Inclusion and exclusion criteria
  • Variables
  • Condition of interest
  • Quality control
  • Limitations of clinical research
• Ethical considerations
  • Data confidentiality
  • Information to subjects and informed consent
  • Bias minimization measures
  • Calendar
  • Monitoring plan
  • Subject follow-up procedures
  • Completition of the investigation
  • Statistical analysis
  • Procedures
  • Data management
• CIP Modification
• CIP Deviations
• Start, follow-up and end reports
• Statements of compliance
• Informed Consent process
• Adverse events, adverse product reactions and product deficiencies
  • Adverse Events (AE) and Adverse Event to Product (AEP)
  • Product deficencies
  • Serious Adverse Events, serios adverse events to product and serious and unexpected adverse event to the product
  • Non-reportable Adverse Events
  • Notification Process
  • Foreseeable adverse events and adverse events to product
  • Emergency contact
  • Data Monitoring Committee (DMC)
• Vulnerable population (if applicable)
• Suspension or early termination of clinical research
• Publication policy
• Bibliography

Compliance statement

The clinical investigation will be conducted according to the Clinical Investigation Plan (CIP) and other applicable guidances and regulations. This includes compliance with:

• The ethical principles originating from the World Medical Association's Declaration of Helsinki
• Harmonized standard UNE-EN ISO 14155:2020
• Regulation (EU) 2017/745 on medical devices (MDR), including the applicable General Safety and Performance Requirements (GSPR) as outlined in Annex I, and the requirements of Annex XV (Chapter I and Chapter II, Section 3)
• Harmonized standard UNE-EN ISO 13485:2016
• MDCG 2024-3 for its structural and content expectations, MDCG 2021-8 concerning application requirements, and MDCG 2020-10/1 Rev 1 for safety reporting timelines and definitions
• Regulation (EU) 2016/679 (GDPR)
• Spanish Organic Law 3/2018 on the Protection of Personal Data and guarantee of digital rights.

All data processing within the device is carried out in accordance with the highest standards of data protection and privacy. Patient information is managed in an encrypted manner to ensure confidentiality and security.

The research team assumes the role of Data Controller, responsible for the collection and management of study data. Legit.Health acts as the Data Processor and is not involved in the processing of patient data.

The storage and transfer of data comply with European data protection regulations. At the conclusion of the study, all information stored in the device will be permanently and securely deleted.

The device employs robust technical and organizational security measures to safeguard personal data against unauthorized access, alteration, loss, or processing.

Abbreviations and Definitions

• AE: Adverse Event
• AEMPS: Spanish Agency of Medicines and Medical Devices
• AEP: Adverse Reaction to Product
• AUC: Area Under the ROC Curve
• CAD: Computer-Aided Diagnosis
• CMD: Data Monitoring Committee
• CIP: Clinical Investigation Plan
• CUS: Clinical Utility Questionnaire
• DLQI: Dermatology Quality of Life Index
• GCP: Standards of Good Clinical Practice
• ICH: International Conference of Harmonization
• IFU: Instructions For Use
• IRB: Institutional Review Board
• N/A: Not Applicable
• NCA: National Competent Authority
• PI: Principal Investigator
• PPV: Positive Predictive Value
• NPV: Negative Predictive Value
• SAE: Serious Adverse Events
• SAEP: Serious Adverse Event to Product
• SUAEP: Serious and Unexpected Adverse Event to the Product
• SUS: System Usability Scale

CIP or protocol specifications

Principal Investigator

Dra. Clara Ureña Paniego Servicio de Dermatología Hospital Universitario Virgen de las Nieves Av. de las Fuerzas Armadas, 2, Beiro, 18014 Granada

Coordinating Investigator(s)

Dra. Clara Ureña Paniego Servicio de Dermatología Hospital Universitario Virgen de las Nieves

Collaborating Investigator(s)

• Dra. Trinidad Montero Vílchez (Servicio de Dermatología del Hospital Virgen de las Nieves de Granada)
• Alfonso Medela (AI LABS GROUP, S.L.)
• Andy Aguilar (AI LABS GROUP, S.L.)
• Taig Mac Carthy (AI LABS GROUP, S.L.)
• Dr. Jordi Barrachina (AI LABS GROUP, S.L.)

Investigational sites

Hospital Universitario Virgen de las Nieves Av. de las Fuerzas Armadas, 2, Beiro, 18014 Granada

Funding

Sponsor: AI LABS GROUP, S.L. No external funding sources are anticipated.

Product Identification and Description

	Information
Device name	Legit.Health Plus (hereinafter, the device)
Model and type	NA
Version	1.1.0.0
Basic UDI-DI	8437025550LegitCADx6X
Certificate number (if available)	MDR 792790
EMDN code(s)	Z12040192 (General medicine diagnosis and monitoring instruments - Medical device software)
GMDN code	65975
EU MDR 2017/745	Class IIb
EU MDR Classification rule	Rule 11
Novel product (True/False)	TRUE
Novel related clinical procedure (True/False)	TRUE
SRN	ES-MF-000025345

Device accountability

Given that the investigational device is a Software as a Medical Device (SaMD), product accountability is managed through strict access control to the platform. Access to the software is granted exclusively to authorized investigators and registered patients during the clinical investigation through secure credentials (username and password). The sponsor will maintain a log of all active accounts and usage metrics associated with the clinical investigation. Upon completion, early termination, or temporary halt of the study, or if a user withdraws consent, their access credentials will be immediately revoked to prevent further use. Malfunctioning software versions or "expired" access rights are similarly managed by restricting access and disabling accounts, ensuring no unauthorized or obsolete product use occurs.

Justification of the design

Background and rationale

The skin is the largest organ of the human body, acting as a defensive barrier against external stressors and maintaining cutaneous homeostasis. Like any other organ, the skin suffers from diseases, one of the most common being Atopic Dermatitis (AD). This is a chronic inflammatory disease caused by both environmental and genetic factors. It is characterized by recurrent eczematous lesions associated with pruritus. AD affects up to 20% of children and 10% of adults, with a higher prevalence in industrialized countries.

To evaluate the severity of AD, multiple tools have been developed. Among them is the SCORing Atopic Dermatitis (SCORAD) and the Eczema Area and Severity Index (EASI). The EASI divides the body into four regions, assigning a score for the affected area and the severity of the signs (erythema, edema/papulation, excoriation, and lichenification).

It is important to note that EASI is the recommended instrument for measuring the severity and signs of AD according to the Harmonizing Outcome Measures in Eczema (HOME) initiative.

However, the manual method currently used has severe limitations, particularly the inherent difficulty for a human to quantify parameters objectively, stably, and precisely (e.g., counting lesions or quantifying the surface area of a lesion). This human limitation also reflects on the effort and time required to estimate the degree of affection. The time consumption is especially concerning given the shortage of medical professionals, particularly in dermatology.

Therefore, there is a need for the automation of scoring systems like EASI to allow a quick and precise assessment of AD severity. Automating EASI would save time in the evaluation of each patient while providing a more precise measurement. This study aims to clinically validate a novel artificial intelligence tool based on the automation of the EASI scoring system for assessing the severity of affected areas in patients diagnosed with AD.

Evaluation of preclinical and clinical data

These evaluations can be consulted in the T-015-005 Investigator's brochure.

Hypothesis

The hypothesis guiding this study is that the automatic measurement system for atopic dermatitis using EASI, based on artificial intelligence algorithms and developed by AI LABS GROUP S.L., exhibits a performance similar to that of an expert dermatologist and is capable of measuring the severity of atopic dermatitis equally or better than an expert dermatologist using the "gold standard" EASI.

This hypothesis is based on the notion that artificial intelligence introduces several significant changes in the diagnostic and severity measurement process of atopic dermatitis and eczema:

1. It allows for the precise and effective identification and bounding of areas affected by atopic dermatitis.
2. It allows standardizing the measurement of affected areas independently of the observer.
3. It allows determining the extent of the area affected by atopic dermatitis.
4. It allows determining the severity of atopic dermatitis based on the intensity of a series of visible signs.

Objectives

Primary objetive(s)

The primary objective of this study is to validate an automatic measurement system of the Eczema Area and Severity Index (EASI) based on artificial intelligence to determine the severity of atopic dermatitis, demonstrating that it performs with a precision similar to or better than the consensus of experts using the "gold standard" EASI.

Secondary objective(s)

N/A - the study focuses purely on the primary endpoint of correlating the AI-generated aEASI with the expert consensus EASI.

Summary of the study

This is a retrospective observational study. It aims to include 100 adult patients (≥ 18 years) diagnosed with atopic dermatitis treated at the Dermatology Department of the Hospital Virgen de las Nieves in Granada. The data collection period is estimated at 1 month, with a total study duration of 3 months.

Design and Methods

Type of clinical research

Retrospective observational study with a transversal character.

Population

Adult patients (≥ 18 years) diagnosed with atopic dermatitis who have been treated at the Dermatology Service of the Hospital Universitario Virgen de las Nieves de Granada.

Duration

Recruitment period: 1 month of retrospective data collection. Total study duration: 3 months, including data base closure, analysis, and final report preparation.

Acceptance criteria

• High correlation between the severity assessed by the dermatologist using EASI and the severity determined by the aEASI algorithm.

Inclusion and exclusion criteria

Inclusion Criteria:

• Patients with atopic dermatitis or eczema.
• Patients aged 18 years or older.
• Patients who have available images of the area affected by atopic dermatitis or eczema.

Exclusion Criteria:

• Patients under 18 years of age.
• Patients whose images are of poor quality or do not allow a correct assessment of severity.
• Patients presenting another concomitant inflammatory pathology (psoriasis, hidradenitis suppurativa).

Variables

Primary Variable: The primary variable is the severity of atopic dermatitis determined by the EASI. This will be determined first by expert dermatologists in atopic dermatitis and secondly by the AI algorithm (aEASI). Both scores will be correlated to check the precision of the automatic EASI scoring system.

Secondary Variables:

• Demographic data: sex, age, age of disease onset, SCORAD, IGA.

Condition of interest

Atopic dermatitis severity assessment using EASI.

Quality control

The Principal Investigator is responsible for reviewing and approving the study protocol and ensuring data quality. Data will be entered into an electronic Database (spreadsheet format). Validation processes using computerized filters based on validation rules will be executed to identify missing or incongruent values.

Limitations of clinical research

The main limitation is the quantity and quality of the collected images. Variability in illumination, color, shape, size, and focus are determinant. High intra-patient variability combined with an insufficient number of images could lead to lower precision. Another potential limitation is the "Hawthorne effect", where observers might change their judgments knowing they are being evaluated.

Ethical considerations

This study adhered to international Good Clinical Practice (GCP) guidelines, the Declaration of Helsinki in its latest amendment, and applicable international and national regulations. As applicable, approval from the relevant Ethics Committee was obtained prior to the initiation of the study. When applicable, modifications to the protocol were reviewed and approved by the Principal Investigator (PI) and subsequently evaluated by the Ethics Committee before subjects were enrolled under a modified protocol.

This study was conducted in compliance with European Regulation 2016/679, of 27 April, concerning the protection of natural persons with regard to the processing of personal data and the free movement of such data (General Data Protection Regulation, GDPR), and Organic Law 3/2018, of 5 December, on the Protection of Personal Data and the guarantee of digital rights. In accordance with these regulations, no data enabling the personal identification of participants was collected, and all information was managed securely in an encrypted format.

Participants were informed both orally and in writing about all relevant aspects of the study, with the information being tailored to their level of understanding. They were provided with a copy of the informed consent form and the accompanying patient information sheet. Adequate time was given to patients to ask questions and fully comprehend the details of the study before providing their consent.

The PI was responsible for the preparation of the informed consent form, ensuring it included all elements required by the International Conference on Harmonisation (ICH), adhered to current regulatory guidelines, and complied with the ethical principles of GCP and the Declaration of Helsinki.

The original signed informed consent forms were securely stored in a restricted access area under the custody of the PI. These documents remained at the research site at all times. Participants were provided with a copy of their signed consent form for their records.

Data confidentiality

Current legislation will be complied with in terms of data confidentiality protection (European Regulation 2016/679, of 27 April, on the protection of natural persons with regard to the processing of personal data and the free movement of such data and Organic Law 3/2018, of 5 December, on Personal Data Protection and guarantee of digital rights). For this purpose, when applicable, each participant will receive an alphanumeric identification code in the study that will not include any data allowing personal identification (coded CRD). The Principal Investigator will have an independent list that will allow the connection of the identification codes of the patients participating in the study with their clinical and personal data. This document will be filed in a secure area with restricted access, under the custody of the Principal Investigator and will never leave the centre.

Once the paper CRDs are completed and closed by the Principal Investigator, the data will be transferred to a database.

As in the CRDs, the Database will comply with current legislation in terms of data confidentiality protection (European Regulation 2016/679, of 27 April, on the protection of natural persons about the processing of personal data and the free movement of such data and Organic Law 3/2018, of 5 December, on the Protection of Personal Data and guarantee of digital rights) in which no data allowing personal identification of patients will be included.

Information to subjects and informed consent

Due to the retrospective nature of the study and the use of anonymized data/images, obtaining informed consent from the patients is not required.

Bias minimization measures

To minimize the Hawthorne effect and ensure objective evaluation, the images will be evaluated independently.

Calendar

Data collection period of 1 month. Total study duration estimated at 3 months.

Monitoring plan

A clinical monitoring plan has been established to oversee the progress of the clinical investigation, ensuring that it is conducted, recorded, and reported in accordance with the protocol, Good Clinical Practice, and the applicable regulatory requirements. Monitoring will rely on the Principal Investigator and the sponsor's regular review of the data inputs and internal database coherence checks.

Subject follow-up procedures

Given the retrospective nature of the study, no active subject follow-up is required. In the event of early termination, temporary suspension, or completion of the clinical investigation, there will be no impact on the standard of care as patients are not actively participating in an intervention.

Completition of the investigation

The database will be considered closed after completing all data management processes and resolving discrepancies. Following this, the statistical analysis and final study report will be executed.

Statistical analysis

Variables will be characterized using frequency distributions for qualitative variables and measures of central tendency and variability for quantitative ones. A statistical correlation analysis will be performed between the severity assigned by the physician using EASI and the severity assigned by the automatic EASI calculation algorithm. This could be a Pearson or Spearman correlation analysis depending on the distribution of the sample. Analyses will be performed using Python. Values of p lower than 0.05 will be considered significant.

Procedures

The Principal Investigator or assigned collaborators will review the images of patients with atopic dermatitis and select those that meet the inclusion criteria. The data will be collected in a spreadsheet CRF.

The selected images will be sent to Legit.Health to design an annotation project. The research team members will review the images, bounding the affected area and assigning an EASI score. This score will be recorded in the CRF. Subsequently, the same process will be repeated using the Legit.Health platform for the automatic EASI calculation (aEASI). Both scores will be correlated.

After analyzing all images, the physicians will complete the aEASI tool utility questionnaire using the System Usability Scale (SUS).

Data management

The data will be managed and tabulated with consistency rules and logical ranges to control inconsistencies during data tabulation. A validation process of the clinical data will be carried out by running computer filters based on validation rules, which will automatically identify missing values or inconsistencies of clinical data according to the protocol. Additionally, manual editing and validation will be performed using descriptive and exploratory statistical techniques to complement the detection of logical errors and inconsistent values.

The database will be considered closed upon completion of all data management processes and satisfactory resolution of discrepancies and errors in the data. Any changes in the database after its closure can only be made after written agreement between the Principal Investigator and the technical coordinators of the project.

AI Labs Group, S.L. (hereinafter, the manufacturer) is the owner of the device. During the period of validity of this study, the manufacturer will grant a license to use the device by the research team free of charge. The research team will be the administrator of the account. Both patients and members of the medical team will have login credentials. The manufacturer will not have access to the account or patient information.

According to the definitions and roles set out in Regulation (EU) 2016/679 (GDPR), the Data Controller is the research team and the manufacturer is the Data Processor.

The storage of data and photographs will be in line with the European Regulation 2016/679 (GDPR) and the Organic Law 3/2018 of 5 December on the Protection of Personal Data and guarantee of digital rights. At the end of the study, all information stored in the device will be totally and permanently deleted.

The device complies with current legislation on the protection and confidentiality of personal data European Regulation 2016/679 (GDPR). Appropriate technical and organizational security measures are adopted to ensure the security of personal data and prevent its alteration, loss, unauthorized processing or access, given the state of technology, the nature of the data and the risks to which they are exposed, whether from human action or the natural physical environment.

CIP Modification

As indicated in the UNE-EN ISO 14155:2021 standard, the Clinical Investigation Plan (CIP) may be modified as necessary during the clinical investigation. The changes made must be described, along with their justification, potential impact on clinical performance, efficacy, safety, or other evaluation criteria, and identification of other affected documents.

CIP modifications will be prepared by the sponsor and agreed upon and accepted between the sponsor and the principal investigator. The modifications will be recorded with a justification for each one in the form of an amendment or addendum.

The required regulatory authority (AEMPS) and the Ethics Committee or Institutional Review Board (IRB) will be notified, if necessary. Modifications to the clinical investigation may only be implemented once favourable feedback and the corresponding approval have been obtained.

In accordance with Article 75 of Regulation (EU) 2017/745, substantial modifications to the clinical investigation must be approved by both the Ethics Committee for investigation with medicines (CEIm) and the Competent Authority (AEMPS) prior to their implementation.

• In the case of substantial modifications to authorized clinical investigations, a request must be submitted to the AEMPS and the CEIm.
• For non-substantial modifications to authorized clinical investigations, until the corresponding module is available in the EUDAMED database, the updated documentation will be sent to the AEMPS for inclusion in their file.

CIP Deviations

As indicated in the UNE-EN ISO 14155:2021 standard, the investigator may not deviate from the Clinical Investigation Plan (CIP), except in emergencies (section 4.5.4.b of the standard). In such cases, the investigator may proceed without prior approval from the sponsor and the Ethics Committee to protect the rights, safety, and well-being of human subjects. The use of waivers from the Clinical Investigation Plan is strictly prohibited.

These deviations must be documented by the principal investigator and notified to the sponsor and the IRB as soon as possible, and always within a maximum of 15 days. Immediately after receiving the notification, the sponsor will record and analyze the deviations carried out and their potential impact. Depending on the findings, the sponsor will take the necessary corrective and/or preventive measures.

In other circumstances, when deviations affect the rights, safety, and well-being of the subject or the scientific integrity of the clinical investigation, deviation requests and reports must be provided to the IRB if required.

Start, follow-up and end reports

The start of the study will be notified to the ethics committee.

Upon obtaining the study conclusions, a final report (T-015-006 Clinical Investigation Report (CIR)) will be prepared and submitted to the ethics committee.

Statements of compliance

The present clinical investigation will be conducted following the ethical principles originating from the Declaration of Helsinki.

Additionally, the clinical investigation will comply with the harmonized standard UNE-EN ISO 14155:2021 and the European Regulation MDR 2017/745. The statement specifying compliance with the general safety and performance requirements in accordance with MDR can be found in the document Manufacturer's Declaration of Compliance with Requirements.

As appropiate, clinical investigation will not commence until approval/favourable opinion has been obtained from the Clinical Research Ethics Committee (CREC) and the required regulatory authority (Spanish Agency for Medicines and Medical Devices, AEMPS), and it must comply with any additional requirements imposed by the CREC and/or AEMPS.

The statement regarding the funding of the clinical investigation, along with the description of the agreement between the sponsor and the research centers and between the sponsor and the principal investigator, can be found in the Clinical Trial Agreement (CTA) and can be accessed upon request.

Informed Consent process

Due to the retrospective nature of the study using pre-existing, anonymized images and clinical data, informed consent from the subjects is not required, as per the ethical approval for this specific investigation design.

Adverse events, adverse product reactions and product deficiencies

Adverse Events (AE) and Adverse Event to Product (AEP)

An AE is any unintended medical event, unanticipated illness or injury, or unintended clinical signs (including abnormal laboratory findings) in subjects, users, or other persons, whether or not related to the investigational product and whether intended or unintended.

A AEP is an adverse event related to the use of an investigational medical device.

Given these definitions, potential AEPs or AEs are documented in the product's IFU.

Product deficencies

Possible inadequacies of a medical device may relate to its identity, quality, durability, reliability, safety, or performance.

Considering this definition, the following issues could arise:

• Malfunctions, such as application crashes or failure to process images.
• Use errors, such as capturing poor quality photographs or incorrect data entry.
• Inadequate information provided by the manufacturer, such as a complex IFU and/or labeling.

Product deficiencies in the investigation will be managed by the sponsor according to non-conforming product control procedures. When appropriate, corrective and/or preventive actions will be taken to protect the safety of subjects, users, and other individuals.

Serious Adverse Events, serios adverse events to product and serious and unexpected adverse event to the product

According to UNE-EN ISO 14155:2021:

• A Serious Adverse Product Reaction (SAEP) is a SAE that has produced any consequence characteristic of a serious adverse event.
• A Serious Adverse Event (SAE) is an AE that resulted in any of the following events: death, serious deterioration of the health status of the subject, users or other persons, or fetal distress, fetal death, congenital anomaly or birth defect.
• A Serious Unexpected Adverse Event to the Product (SUAEP) is a SAE that, due to its nature, incidence, intensity or consequences, has not been identified in the updated risk assessment.

Taking into account these definitions, there are no SAEP, SAEs or SUAEPs related to the use of the product.

Non-reportable Adverse Events

note

List non-reportable adverse events, if applicable, including justification.

There are no specific non-reportable adverse events defined for this study. Since this is a retrospective study involving only the analysis of previously collected images, subjects are not exposed to any procedures that could endanger their safety, and no adverse events related to the investigational product are expected.

Notification Process

Any SAEP, product deficiency or finding related to the above will be duly documented and reported in accordance with the provisions of document MDCG 2020-10/1 “Safety reporting in clinical investigations of medical devices under the Regulation (EU) 2017/745”

In the situations detailed in the previous paragraph, the principal investigator must notify the sponsor immediately (but no later than 3 days after becoming aware of the event). The sponsor will then use the form published as an annex to said document, MDCG 2020-10/2 “Guidance safety report form”.

This form must be completed or updated for each reportable event or for new findings or updates of events already reported. It will be transmitted to all National Competent Authorities (NCA) where the clinical investigation is being conducted. In this case, the AEMPS. Once EUDAMED is available and fully operational, the obligations and requirements related to the preparation of safety reports through EUDAMED will apply from six months after the date of publication of the notice in the Official Journal of the European Union.

The notification period of the sponsor to the NCA(s) will be immediately (but no later than 2 days after becoming aware of the event) for reportable events that involve an imminent risk of death, serious injury or serious illness and that require immediate corrective action, or new findings or updates of related events. For the rest of reportable events or new findings or updates, the notification period will be immediately (but no later than 7 days after becoming aware of the event).

Likewise, as indicated in the UNE-EN ISO 14155:2021 regulation, the IRB must be notified of the SAEs, if the IRB so requires.

Foreseeable adverse events and adverse events to product

The foreseeable adverse events and expected adverse reactions to the product, as well as their incidence, mitigation and treatment are documented in the T-013-002 Risk management record of the product under study.

Emergency contact

The emergency contact person for reporting serious adverse events and serious adverse effects of the product:

• Name: Dra. Clara Ureña Paniego
• Professional role: Principal Investigator
• E-mail: N/A
• Telephone: N/A

Data Monitoring Committee (DMC)

Information on the DMC (Data Monitoring Committee), if established. This is an independent committee that the sponsor may establish to evaluate, at indicated intervals, the progress of the clinical investigation, the safety data or the critical clinical performance or efficacy endpoints and to recommend to the sponsor whether to continue, suspend, modify, or stop the clinical investigation.

Vulnerable population (if applicable)

N/A

Suspension or early termination of clinical research

As indicated in the UNE-EN ISO 14155:2021 regulation, the sponsor may suspend or terminate the clinical research early for significant and documented reasons. These are:

• If during the clinical research the suspicion of an unacceptable risk arises, including a serious threat to the health of the subjects. It must be suspended while the risk is determined.
• If an unacceptable risk that cannot be controlled is confirmed.
• Due to the impossibility of including a minimum number of subjects that allows the final assessment of the study within a reasonable period according to the characteristics of the study.
• When instructed by the IRB or the required regulatory authority (AEMPS).
• Due to non-compliance with the obligations assumed in the contract by any of the contracting parties.
• By mutual agreement between the parties, expressed in writing.
• By the will of one of the parties, expressed in writing at least one month in advance.

In the event of a suspension or early termination of the clinical research, the sponsor will inform the AEMPS. The sponsor must provide the resources to comply with the obligations of the CIP and with the existing agreements. The principal investigator must inform the subjects if so stipulated in the agreement between the sponsor and the research centre.

If the clinical investigation is resumed, the sponsor must inform the principal investigator and, where appropriate, the AEMPS. Approval from the IRB and, where appropriate, from the AEMPS will be required for such resumption. The principal investigator must inform the subjects.

In accordance with Article 77 of Regulation (EU) 2017/745, the sponsor must notify the Member States in which the clinical investigation is being conducted of the end of the clinical investigation, its temporary halt, or its early termination, within the deadlines specified by the regulation (within 15 days of the end, or within 24 hours in case of early termination or temporary halt for safety reasons). This notification must be accompanied by a justification in case of early termination or temporary halt.

Publication policy

Statement indicating the conditions and time periods in which the results of the clinical research will be offered for publication, including the role played by the sponsor and the criteria for authorship of the publication.

The description of the clinical research will be recorded in a publicly accessible database (e.g. ClinicalTrials.gov or EUDAMED once fully functional) before the recruitment of the first subject. Its content will be updated during the conduct of the clinical research.

In accordance with the legal requirements and ethical principles established in Section 1 of Chapter I of Annex XV of Regulation (EU) 2017/745, a Clinical Investigation Report (T-015-006 Clinical Investigation Report (CIR)) will be prepared within one year of the end of the clinical investigation or within three months of its early termination or temporary halt. The CIR will be provided to the IRB and the AEMPS.

The results of the clinical investigation will be published in the aforementioned public database. The summary of the clinical investigation report and its results (whether positive, negative, or inconclusive) will be made available to the public within 1 year from the end of the clinical investigation, or within 3 months in the event of early termination or temporary halt.

In addition, if deemed appropriate, the results obtained will be published in scientific journals. The CEIC that has approved this clinical research will be mentioned, and the funds obtained by the author for or for its conduct and the source of funding will be stated. The anonymity of the subjects participating in the clinical research will be maintained at all times.

After the completion of the study, the results of the clinical utility and satisfaction surveys carried out according to the model in Annex I may be communicated at congresses and scientific meetings with prior authorization from both parties. Communications and press releases may also be made to communicate the results of the study. All publications and communications must be accepted and approved by the parties involved.

Bibliography

References can be consulted in the original PDF protocol document.

Signature meaning

The signatures for the approval process of this document can be found in the verified commits at the repository for the QMS. As a reference, the team members who are expected to participate in this document and their roles in the approval process, as defined in Annex I Responsibility Matrix of the GP-001, are:

• Author: Team members involved
• Reviewer: JD-003 Design & Development Manager, JD-004 Quality Manager & PRRC
• Approver: JD-001 General Manager

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