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 a medical device for the automatic assessment of severity and remote monitoring of patients with acne |
| Device under investigation | Legit.Health Plus |
| Protocol version | Version 8.0 |
| Date | 06/10/2025 |
| Protocol code | Legit.Heath_acne |
| Sponsor | AI LABS GROUP, S.L (Legit.Health) |
| Coordinating Investigator | Dr. Jose Luis Lopez Estebaranz |
| Principal Investigator(s) | Dr. Jose Luis Lopez Estebaranz |
| Collaborating Investigator(s) | Dr. Javier Martin Alcalde, Dra. Keila Mitsunaga, Dra. Constanza Bahilo, Dra. Marta López Pando, Alfonso Medela, Taig Mac Carthy, Jordi Barrachina |
| Investigational site(s) | Clínica DermoMedic |
| Ethics Committee | La Princesa University Hospital |
Table of contents
- Scope
- CIP Identification
- Compliance statement
- Abbreviations and Definitions
- CIP or protocol specifications
- Product Identification and Description
- Justification of the design
- Hypothesis
- Objectives
- Summary of the study
- Design and Methods
- Ethical considerations
- 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 applicableGeneral Safety and Performance Requirements (GSPR)as outlined in Annex I, and the requirements ofAnnex XV(Chapter I and Chapter II, Section 3)- Harmonized standard
UNE-EN ISO 13485:2016 MDCG 2024-3for its structural and content expectations,MDCG 2021-8concerning application requirements, andMDCG 2020-10/1 Rev 1for safety reporting timelines and definitionsRegulation (EU) 2016/679(GDPR)- Spanish
Organic Law 3/2018on 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
Dr Jose Luis Lopez Estebaranz Clínica DermoMedic Jorge Juan Street, 36, 28001 Madrid
Coordinating Investigator(s)
Dr Jose Luis Lopez Estebaranz Clínica DermoMedic
Collaborating Investigator(s)
- Dr Javier Martin Alcalde (Clínica DermoMedic)
- Dr Keila Mitsunaga (Clínica DermoMedic)
- Dr Constanza Bahilo (Clínica DermoMedic)
- Dr Marta López Pando (Clínica DermoMedic)
- Alfonso Medela (AI LABS GROUP, S.L.)
- Taig Mac Carthy (AI LABS GROUP, S.L.)
- Dr Jordi Barrachina (AI LABS GROUP, S.L.)
Investigational sites
Clínica DermoMedic C. de Jorge Juan, 36, 28001 Madrid
Funding
This project has been funded by the Diputación Foral de Bizkaia within the 2i 2022 Program.
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
Acne is an inflammatory skin disease caused by sebaceous gland dysfunction. Hair follicles become clogged with dead skin cells, hair, sebum, and bacteria, leading to cutaneous symptoms such as comedones, papules, pustules, nodules, and even scars. Globally, it is the eighth most common skin disease, affecting an estimated 80% of adolescents.
The discomfort of the disease involves not only superficial signs but also negative psychological repercussions, such as negative effects on social life and self-esteem. Both adolescents and adults with acne exhibit higher rates of anxiety and depression. Acne is also known for its characteristic spontaneous flare-ups and resolutions, making it very difficult to evaluate.
To prevent and avoid the negative consequences of acne, a precise diagnosis must be made. However, measuring the severity of acne is currently a challenge, as there is no standardized method widely used in clinical practice. The two most popular systems are the Investigator Global Assessment (IGA) and the Global Acne Grading System (GAGS). However, manual evaluation can be labor-intensive, time-consuming, and subject to bias.
In the last decade, there has been growing interest in applying advanced computational techniques, such as image processing and deep learning, to the diagnosis and evaluation of dermatological pathologies. AI LABS GROUP S.L. has developed a novel measurement system, called ALADIN, which has been retrospectively validated and integrated into the Legit.Health medical device. The main objective of this study is to perform an exhaustive clinical validation of this innovative automatic acne severity measurement system based on artificial intelligence algorithms.
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 acne severity measurement system, ALADIN, integrated into the medical device and developed by AI LABS GROUP S.L., performs similarly or better than specialists and allows for remote monitoring of patients with facial acne.
This hypothesis is based on the notion that artificial intelligence introduces several significant changes in the acne monitoring process:
- It allows an automatic count of acne lesions, the most reliable method according to the literature.
- It allows monitoring remotely, providing flexibility and the possibility of detecting flare-ups.
- It allows the professional and the patient to continuously check the status of the pathology.
Objectives
Primary objetive(s)
The primary objective of this study is to validate that the functionality of the ALADIN severity measurement system measures the severity of facial acne with a capacity similar or superior to that of the specialist using a photograph taken with a smartphone.
Secondary objective(s)
- Validate that the medical device is a valid tool for remote monitoring of patients with facial acne.
- Validate that patient satisfaction with the center increases due to the use of the platform.
- Validate that the satisfaction of healthcare professionals increases due to the platform.
Summary of the study
This is a prospective observational study with a longitudinal character. It will include 30 patients with facial acne treated at the DermoMedic clinic. The recruitment period is 6 months, and the total study duration is 9 months. Each patient will participate for 3 months from the date of inclusion.
Design and Methods
Type of clinical research
Prospective observational study with a longitudinal character.
Population
Patients with facial acne treated at the DermoMedic clinic.
Duration
Recruitment period: 6 months. Total study duration: 9 months. Participation duration of each patient: 3 months from the date of inclusion.
Acceptance criteria
- High correlation between ALADIN severity score and investigator's IGA score (ICC>75%).
Inclusion and exclusion criteria
Inclusion Criteria:
- Patients with facial acne.
- Patients aged 18 or older, or those aged 16 or older whose parents or legal guardians give consent to participate.
- Patients who have signed the study's informed consent.
- Patients with a smartphone (a phone with internet access and a built-in camera of any model and technical specifications).
Exclusion Criteria:
- Patients who, in the investigator's opinion, will not comply with the study procedures (e.g., missing follow-up visits, not following instructions, or lacking cognitive capacity to understand instructions).
Variables
Primary Variable: The primary variable aims to determine the severity of facial acne using the ALADIN functionality of the Legit.Health medical device. This severity will be correlated with the IGA assigned by the investigators.
Secondary Variables:
- Demographic data: sex, age, and skin phototype (I to VI).
- IGA score in face-to-face consultations.
- IGA score from images uploaded remotely by the patient.
- Number of remote consultations using Legit.Health.
- Duration of remote consultations using Legit.Health.
- Duration of face-to-face consultations.
- Degree of patient satisfaction (Patient Satisfaction Questionnaire).
- Degree of healthcare professional satisfaction (Clinical Utility Questionnaire).
- Impact measurement using the Cardiff Acne Disability Index (CADI).
- Treatment satisfaction measurement (numerical scale from 0 to 10).
Condition of interest
Facial acne severity assessment and remote monitoring.
Quality control
The Principal Investigator is responsible for reviewing and approving the study protocol and ensuring data quality. Data will be entered into a paper-based Case Report Form (CRF) and subsequently transferred to a Database using double data entry. Validation processes will be executed to identify missing or incongruent values.
Limitations of clinical research
The main limitation is the volume and quality of collected images (illumination, color, shape, size, and focus). High intra-patient variability combined with an insufficient number of images reflecting that variability could lead to lower precision. Additionally, the study is strictly limited to facial acne, ignoring other body areas like the back or chest. The ALADIN functionality focuses solely on lesion counting without distinguishing between different types of lesions.
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
The Principal Investigator or assigned collaborators will explain the study to the patient using the Patient Information Sheet. If the patient wishes to participate, they will sign the Informed Consent, and a study code will be assigned. For minors (aged 16 or 17), consent must be provided by their parents or legal guardians.
Bias minimization measures
N/A - the study involves a prospective real-world setting where patients take their own photos and the system objectively measures severity against physician gradings.
Calendar
Recruitment period of 6 months. Total study duration estimated at 9 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 CRF inputs and internal database coherence checks.
Subject follow-up procedures
In the event of early termination, temporary suspension, or completion of the clinical investigation, subjects will continue to receive the standard of care as determined by their treating physician. If a subject withdraws their consent, no further data will be collected, but previously collected data will be processed according to data protection regulations, and the patient's routine medical care will not be affected. For subjects lost to follow-up, the investigating site will make reasonable attempts to contact the subject (e.g., via phone or email) before officially recording them as lost. After the clinical investigation, subjects will return to their regular clinical care pathways without any alteration to their healthcare provision caused by the study.
Completition of the investigation
The database will be considered closed after completing all data management processes and resolving discrepancies. Any subsequent changes to the databases can only be made by written agreement between the Principal Investigator and the project technical coordinators.
Statistical analysis
Variables will be characterized using frequency distributions and measures of central tendency and variability. Parametric tests will be used for intergroup and intra-group comparisons where applicable (e.g., ANOVA, Student's t-test). For non-parametric data, exact tests (Fisher or Chi-square) will be used. Continuous variables will be compared using Pearson or Spearman correlations. Sensitivity, specificity, PPV, NPV, LR+, and LR- will be calculated comparing Legit.Health results to the paper questionnaire system used as the gold standard. Analyses will be performed using SPSS version 23.0 and STATA 13.0, with p < 0.05 considered significant.
Procedures
Selection and Recruitment Visit: The patient will receive information about the study and sign the informed consent. Demographic data will be collected, and patients will receive instructions for using the Legit.Health app and taking photos. A guided first photograph session will occur in the clinic, and the investigator will record their IGA score.
Procedures performed by the patient at home: Patients will take facial selfies at the beginning, middle, and end of the study using their smartphones. Legit.Health will be used to upload these photos, which involves a DIQA (Dermatology Image Quality Assessment) check to ensure image quality >= 60%. Patients will also autonomously complete the CADI questionnaire monthly. At the end of the study, patients will fill out the satisfaction questionnaire.
Follow-up Visits: Patients will attend 2 follow-up visits with the investigator. In each visit, a photo will be taken, and the IGA score will be recorded. At the final visit (month 3), the patient satisfaction questionnaire and the Clinical Utility Questionnaire (for the healthcare professional) will be completed.
Remote evaluation of photographs: At the end of the study, the principal investigators will analyze the photographs using the IGA measurement scale within a dedicated Legit.Health annotation platform to ensure blinding and rigorous evaluation.
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. Annual follow-up reports will be submitted thereafter.
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
The patient, or in their absence, the family member or legally authorized representative, must provide written consent before their inclusion in the clinical investigation. This will occur after they have understood, through a prior interview with the principal investigator or a member of the research team, the objectives of the investigation, its risks, inconveniences, and benefits, as well as the conditions under which it will be conducted, and after being informed of their right to withdraw from the investigation at any time without explanation and without incurring any responsibility or prejudice.
The principal investigator will discuss the study with the subject and provide the information objectively, without coercion or influence, and without offering any inappropriate or undue incentive. The principal investigator will use non-technical language in the subject's native language (or that of the spouse/closest relative or legally authorized representative) for better understanding and will allow sufficient time for reading and comprehending the information.
Each participant will document their informed consent by signing and dating the informed consent form. Each signed and dated consent will be kept by the principal investigator, and a copy of the informed consent will be provided to the subject.
If new important information arises that could affect the subject's willingness to continue participating in the clinical investigation, it will be provided in any case. If necessary, their continued informed consent will be confirmed in writing.
The patient information form (or family member or legally authorized representative), as well as the informed consent document, can be found in the Patient Information Sheet and Informed Consent Form (PIS/ICF).
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
List non-reportable adverse events, if applicable, including justification.
There are no specific non-reportable adverse events defined for this study, as the device intervention involves no physical risk to patients and acts as a clinical decision support tool. Moreover, potential adverse events like psychological discomfort or data breaches are theoretical and heavily mitigated.
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: Dr. Jose Luis Lopez Estebaranz
- 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)
Adolescents aged 16 to 17 may be included with informed consent from their parents or legal guardians.
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