R-TF-015-004 Clinical investigation plan LEGIT_MC_EVCDAO_2019
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 | Clinical validation study of a Computer-aided diagnosis (CADx) system with artificial intelligence algorithms for early non-invasive detection of in vivo cutaneous melanoma. |
| Device under investigation | Legit.Health |
| Protocol version | Version 3.0 |
| Date | 2021-10-28 |
| Protocol code | LEGIT_MC_EVCDAO_2019 |
| Sponsor | AI Labs Group S.L. |
| Coordinating Investigator | Dr. Jesús Gardeazabal García and Dr. Rosa Mª Izu Belloso |
| Principal Investigator(s) | Dr. Jesús Gardeazabal García and Dr. Rosa Mª Izu Belloso |
| Investigational site(s) | Hospital Universitario Cruces and Hospital Universitario Basurto |
| Ethics Committee | Comité de Ética de la Investigación con Medicamentos de Euskadi |
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
- Annexes
- Record signature meaning
Compliance statement
- Harmonized standard UNE-EN ISO 14155:2021.
- Regulation (EU) 2017/745 on medical devices (MDR).
- Harmonized standard UNE-EN ISO 13485:2016s.
- Regulation (EU) 2016/679 (GDPR).
- Spanish Organic Law 3/2018 on the Protection of Personal Data and guarantee of digital rights`.
- Spanish Organic Law 1090/2015 on regulating clinical trials with medicines, the Ethics Committees for Research with Medicines and the Spanish Registry of Clinical Studies.
Abbreviations and definitions
- CAD: Computer-Aided Diagnosis
- CIP: Clinical Investigation Plan
- CUS: Clinical Utility Questionnaire
- SUS: System Usability Scale
- GCP: Standards of Good Clinical Practice
- ICH: International Conference of Harmonization
- PI: Principal Investigator
- DLQI: Dermatology Quality of Life Index
- ICH: International Conference of Harmonization
- AUC: Area Under the ROC Curve
CIP or protocol specifications
Principal Investigator
- Dr. Jesús Gardeazabal García (Cruces University Hospital).
- Dr. Rosa Mª Izu Belloso (Basurto University Hospital).
Coordinating investigator
- Dr. Jesús Gardeazabal García (Cruces University Hospital).
- Dr. Rosa Mª Izu Belloso (Basurto University Hospital).
Collaborating Investigator(s)
- Hospital Universitario de Cruces
- Dr. Juan Antonio Ratón Nieto
- Hospital Universitario de Basurto
- Dr. Ana Sánchez Diez
- AI Labs Group S.L.
- Mr. Alfonso Medela
- Mr. Taig Mac Carthy
- Mrs. Andy Aguilar
- Mrs. Mireya Fernández
Investigational sites
- Hospital Universitario de Cruces
- Hospital Universitario de Basurto
Funding
This research was carried out without any funding or sponsorship.
Product Identification and Description
| Information | |
|---|---|
| Device name | Legit.Health Plus (hereinafter, the device) |
| Model and type | NA |
| Version | 1.0.0.0 |
| 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 |
| Class | Class IIb |
| Classification rule | Rule 11 |
| Novel product (True/False) | FALSE |
| Novel related clinical procedure (True/False) | FALSE |
| SRN | ES-MF-000025345 |
Justification of the design
Background and rationale
The incidence of cutaneous melanoma (CM), the deadliest form of skin cancer, has been rising significantly, with a sharp increase in both new cases and mortality rates over the past decades. Melanoma metastasizes quickly to distant organs and becomes resistant to conventional therapies, making treatment difficult. However, when diagnosed early, it can be effectively treated through simple surgical excision. The main challenge in early detection lies in differentiating melanoma from benign pigmented skin lesions, as they often share visual similarities, especially during an initial visual examination. Limited access to dermatologists and a lack of public awareness further complicate timely diagnoses, often leading to delayed detection when tumors are already advanced.
Given these challenges, early melanoma diagnosis and prevention have become critical. Recent technological advancements in image recognition and artificial intelligence (AI) have shown promise in improving diagnostic accuracy. Studies have demonstrated that AI algorithms can classify skin lesion images, including melanomas, with a competency level comparable to that of dermatologists. These AI-driven computer-aided diagnosis (CAD) systems present a valuable opportunity for improving early detection and survival rates by assisting healthcare professionals and potentially empowering non-experts to detect melanomas earlier.
This study aims to clinically validate an AI-based system for diagnosing cutaneous melanoma, leveraging artificial vision and machine learning to differentiate between melanomas and benign skin lesions. By developing and validating this technology, the study seeks to improve diagnostic precision and contribute to earlier interventions, potentially enhancing patient outcomes and survival rates.
Risks and benefits of the product in investigation and clinical research
Participants in this study did not undergo any procedures posing a risk to their safety. However, using the device could optimize patient diagnosis, save costs and time, and provide better treatment to patients.
Hypothesis
A CAD system powered by with machine vision allows early and non-invasive diagnosis of cutaneous melanoma in-vivo.
Objectives
Primary objective
To validate that the artificial intelligence algorithm developed by AI Labs Group S.L. for the identification of cutaneous melanoma in images of lesions taken with a dermatoscopic camera achieves the following values:
- AUC greater than 0.8.
- Sensitivity of 80% or higher.
- Specificity of 70% or higher.
Secondary objective(s)
- To compare the performance of the artificial intelligence algorithm developed by the manufacturer with the performance of healthcare professionals of different specializations:
- Dermatologists.
- Primary care physicians.
- Validate the usefulness and feasibility of the artificial intelligence algorithm developed by the manufacturer in adverse environments with severe technical limitations, such as lack of instrumentation or lack of internet connection.
Summary of the study
This is a prospective observational analytical and cross-sectional study of a clinical case series. It is designed in order to validate Legit.Health as a valid tool to detect cutaneos melanoma in images from lesions and early. This research pretends to include 200 patients, which are pretended to represent a diverse population of patients with risk of melanoma. In this case, the data collection will include photographies and clinical and demographic data. The study adhered to strict ethical guidelines, ensuring patient confidentiality and compliance with international standards. Patients were provided with detailed information and informed consent. The study's robust methodology aimed to assess the clinical utility and usability of the device.
Design and methods
Type of clinical research
This is an observational analytical and cross-sectional study for the performance of the device detecting melanoma in patients with high risk. In this study there is one group of patients and there will be no control group, since the study aims to assess the validity of the medical device for melanoma detection and whether it can detect it with the same effectiveness as an expert dermatologist, its detection capability is compared with that of the specialist.
Population
Adult patients (>18 years) with skin lesions of suspected malignancy seen at the Dermatology Department of the Hospital Universitario Cruces and Hospital Universitario Basurto.
Duration
This study is estimated to have a recruitment period of 10 months for the inclusion of the first 40 patients. The recruitment period is extended by 12 months for the inclusion of patients up to a total of 200, with a minimum of 40 melanomas.
The total duration of the study is estimated at 36 months, including the time required after the recruitment of the last subject for the closing and editing of the database, the analysis of the data and the preparation of the final report of the study.
Acceptance criteria
- AUC greater than 0.8.
- Sensitivity of at least 80% or higher.
- Specifity of at least 70% or higher.
Inclusion criteria
- Patients with skin lesions with suspected malignancy.
- Age over 18 years old.
- Patients who consent to participate in the study by signing the Informed Consent form.
Exclusion criteria
- Patients under 18 years of age.
Variables
Main variable
- The main variable aims to estimate the diagnostic efficacy of the CAD system with artificial vision, taking as the Gold Standard the diagnosis of an expert dermatologist with more than 10 years of experience in dermatology, as is the case of the two Principal Investigators of the study.
Secondary variables
- Diagnoses that doctors make based on images of patients' skin lesions.
- System Usability Scale score.
Condition of interest
Patients with skin lesions and risk of cutaneous melanoma.
Limitations of clinical research
The main limitation of machine learning lies in the quantity and quality of the images collected. Variability in illumination, color, shape, size and focus are determinants, in addition to the number of images per lesion. This means that a large variability within the same lesion and an insufficient number of images to reflect that variability can result in lower than expected accuracy.
Detection of skin lesions beyond that of cutaneous melanoma implies the need for a larger number of samples to train the artificial intelligence algorithms. Due to the need for a balanced dataset, i.e., same number of melanoma and non-melanoma images, we consider it necessary to collect cases of nevus and/or other types of skin lesions if necessary. For this reason, we believe that the proposed n = 40 is low considering all the types of lesions we want to analyze, for which we would need a much larger n, of approximately 200 people, of which at least 40 suffer from cutaneous melanoma.
For this reason, a preliminary study will be carried out with 40 patients and after the analysis, the need to expand the study sample will be decided. This study is intended to be a pilot study to be carried out in one year.
After analyzing the data from the pilot study with the first 40 patients included in the study, the results obtained have indicated that despite the good diagnostic capacity of the DAO system, the results of discrimination between melanoma and other pathologies is not representative of daily clinical practice, since it only and exclusively includes cases with a high suspicion of malignancy. Therefore, it is proposed to continue with the study and extend the sample to a total of 200 patients. In this way, it will be possible to validate the system in real cases that the dermatologist receives on a daily basis and to determine its ability to discriminate beyond the extreme cases.
Ethical considerations
The conduct of the study will conform to international Good Clinical Practice standards, to the Declaration of Helsinki in its latest active amendment, and to international and national rules and regulations and will not be initiated until approval has been obtained from the Euskadi Ethics Committee. Any modification of this protocol will be reviewed and approved by the Principal Investigator and must be evaluated by the Ethics Committee for approval before including subjects in a modified protocol.
The study will be conducted according to 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 the Protection of Personal Data and guarantee of digital rights with regard to data processing in which no data that allows the personal identification of subjects will be included, the information being managed in an encrypted manner.
Patients will be informed orally and in writing about all the information related to the study and adapted to their level of understanding. A copy of the consent form and information sheet should be provided to the patient. The investigator should allow the patient the necessary time to ask questions about the details of the study.
Preparation of the informed consent form is the responsibility of the Principal Investigator. This form should include all the elements required by the International Conference of Harmonization (ICH), current regulatory guidelines, and comply with the Standards of Good Clinical Practice (GCP) and ethical principles that originate from the Declaration of Helsinki.
The investigator or the Principal Investigator's designee will keep the original signed informed consent form in a secure restricted access area under the custody of the Principal Investigator and will never leave the center and will give a copy of the original signed consent form to the patient.
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, each patient 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 center.
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 with regard to 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.
Bias minimization measures
In clinical research, minimizing bias is essential to ensure the validity and reliability of the study's results. In this study, patients will be randomly selected to participate in this. Thus, outcomes will not be influence by pre-existing characteristics of the participants. Furthermore, we will use standarized protocols, Using standardized procedures for conducting the study and measuring outcomes ensures that all participants are treated and evaluated in the same way, reducing variability due to differences in how the intervention is applied or how outcomes are assessed. Finally, Collecting data prospectively reduces the chance that participants or investigators will inaccurately recall past events, which is common in retrospective studies. Along with this, before the study begins we define primary and secondary outcomes, which prevents selective reporting of only favorable outcomes. This ensures that all relevant data, whether positive or negative, are considered.
Calendar
This study estimates a recruitment period of 6 months. The total duration of the study is estimated at 12 months, including the time required after recruitment of the last subject for closing and editing the database, data analysis, and preparation of the final study report. The total duration of the study for each participant will be 6 months from the date of inclusion.his study is estimated to have a recruitment period of 10 months for the inclusion of the first 40 patients. The recruitment period is extended by 12 months for the inclusion of patients up to a total of 200, with a minimum of 40 melanomas.
The total duration of the study is estimated at 36 months, including the time required after recruitment of the last subject for closing and editing the database, data analysis and preparation of the final study report.
Monitoring plan
The Legit.Health team will hold a meeting with the investigative team every 3 months to address any potential questions and ensure that data is being collected properly.
Completition of the investigation
After the final closure of the clinical investigation, a Clinical Investigation Report (CIR: T-015-006 Clinical Investigation Report) will be drafted, even in the event of early termination or suspension. The CIR will be provided to the Ethics Committee and the Spanish Agency for Medicines and Medical Devices (AEMPS). The results obtained (whether positive, inconclusive, or negative) will be included in the previously mentioned public access database.
Additionally, if deemed appropriate, the results may be published in scientific journals. The Ethics Committee that approved this clinical investigation will be acknowledged, and any funds received by the author for the study and its source of funding will be disclosed. The anonymity of participants in the clinical investigation will be maintained at all times.
Upon completion of the study, the results of the clinical utility and satisfaction surveys, as per the annexed models, may be presented at conferences and scientific meetings, subject to prior authorization by both parties. Press releases and other communications may also be issued to share the study's results. All publications and communications must be reviewed and approved by the parties involved.
Statistical analysis
Each variable will be characterized using frequency distributions for qualitative variables and central tendency statistics such as mean and median and variability statistics such as standard deviation (S.D.) or interquartile range for quantitative variables according to their distributional characteristics.
Between-group and within-group comparisons will be made using parametric tests whenever the distributional characteristics of the data allow it. For intergroup comparisons, one- and two-factor Analysis of Variance techniques will be used with post-hoc comparisons if significant overall differences are detected. To evaluate intra-group changes, Student's t-test for related samples or Analysis of Variance/ANOVA with repeated measures will be used if the theoretical assumptions of the model are supported by the data. Otherwise, more flexible models (GEE) that allow incorporating different autocorrelation structures of the data will be fitted.
Comparisons between groups with respect to qualitative variables will be carried out by means of contingency tables and Fisher's exact or Chi-square tests. The probability of type I error will not be adjusted for multiple comparisons. The level of statistical significance in the contrasts (alpha) will be 5 percent with bilateral contrasts.
Comparisons between two continuous variables will be made using Pearson's or Spearman's correlation, depending on the distributional characteristics. All the analyses described so far will be performed based on the needs of descriptive results of the sample. Interobserver concordance analyses will also be performed by estimating the kappa coefficient. A study of diagnostic tests will be performed being the main measures in the results: sensitivity, specificity, positive and negative predictive values (PPV and NPV) and likelihood ratios (LR+ and LR-). The diagnosis of the lesion will be made according to the clinical judgment of expert dermatologists, such as the Principal Investigators, (considered the Gold Standard).
Analyses will be performed using appropriate statistical software, SPSS version 23.0 and STATA 13.0. Values of p lower than 0.05 will be considered significant.
Data management
The management of the collection and processing of the study data will be carried out through the design of a Data Collection Notebook (CRD) in paper format, in which the researchers assigned to this task will enter the source data of each patient participating in the study.
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 the Protection of Personal Data and guarantee of digital rights). For this purpose, each patient 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 center.
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 with regard to 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.
The transfer of data from the paper CRD to the electronic Database will be carried out using the double data entry technique. This will be done by the researchers collaborating in the project. 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 data discrepancies and errors. Any changes to the databases after closure can only be made after written agreement between the promoter and the technical coordinators of the project.
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 will be 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 favorable feedback and the corresponding approval have been obtained.
- In the case of substantial modifications to authorized clinical investigations, a request must be submitted to the AEMPS.
- 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 emergency situations (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.
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 in accordance with 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.
This clinical investigation will not commence until approval/favorable 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.
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.
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.
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.
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.
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.
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. Likewise, the sponsor or principal investigator will notify the IRB. 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 center.
If the clinical investigation is resumed, the sponsor must inform the principal investigator, the IRB 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.
Annexes
Annex I. Protocol of the study
Annex II. Ethics committee approval
Ethics committee approval
Record signature meaning
- Author: JD-018 Jordi Barrachina
- Review: JD-003 Taig Mac Carthy
- Approval: JD-005 Alfonso Medela