R-TF-015-010 Annex E ISO 14155

ISO 14155:2020 Compliance Requirements

This section documents compliance with ISO 14155:2020 requirements for clinical investigations of medical devices. The table below provides a comprehensive checklist of documentation required under ISO 14155 and indicates which documents have been provided or prepared for this clinical investigation.

Document Title	Purpose	Included	Justification if not provided
Investigator's Brochure	Provides clinical and non-clinical data on the investigational device relevant to its study in human subjects.	TRUE	Investigators were provided with the device's Instructions For Use (IFU v1.1.0.0), which summarises the clinical and non-clinical data on the investigational device relevant to its use in the investigation and which serves the role of the Investigator's Brochure for this simulated-use multi-reader multi-case investigation. The IFU is held in the technical file and can be provided for audit on request.
Clinical Investigation Plan (CIP)	Describes the rationale, objectives, design, methodology, monitoring, and conduct of the clinical investigation.	TRUE
Subject Information Sheet and Informed Consent Form (ICF)	Ensures that potential study subjects are adequately informed about the investigation and provide voluntary consent.	FALSE	The requirement for a Subject Information Sheet and Informed Consent Form (ICF) is waived due to the non-interventional nature of the research and the use of anonymized data. The study involved the review and annotation of fully anonymized dermatological images sourced from public atlases and databases, with no patient recruitment, patient contact, or interventions taking place. Healthcare professionals participating in the study received oral information and signed participation contracts. As per Spanish legislation and GDPR requirements, no patient consent is required for the use of anonymized, non-identifiable images from public sources.
Ethics Committee Approval	Official approval from the ethics committee to conduct the clinical investigation.	FALSE	See the Ethics Committee Non-Applicability Determination section below for the sponsor's documented determination of non-applicability, including the applicable Spanish legal instruments.
Regulatory Authority Authorization	Authorization or notification from relevant regulatory bodies to proceed with the clinical investigation.	FALSE	This simulated-use multi-reader multi-case investigation does not require authorisation from or notification to a regulatory authority as a clinical investigation of a medical device. No patients are recruited or contacted; no therapeutic or diagnostic intervention is performed on any patient; the study uses only retrospective, fully anonymised images from public dermatology atlases. Under the Spanish framework (Ley 14/2007, de 3 de julio, de Investigación Biomédica; Real Decreto 957/2020, de 3 de noviembre; Ley Orgánica 3/2018, de 5 de diciembre, on data protection; Regulation (EU) 2016/679) and in alignment with ISO 14155:2020 and MDR Annex XV principles, such simulated-use investigations do not require regulatory authorisation.
Case Report Forms (CRFs)	Documents designed to record all protocol-required information to be reported to the sponsor on each trial subject.	TRUE	CRF v1.0 was implemented through a secure web-based system designed for the standardised annotation of study images; its data dictionary is maintained by the sponsor and is held in the technical file. Data generated through investigator annotations were systematically captured (with timestamps and platform access logs providing source-data-verification traceability) and are available for export in a de-identified tabular format. Full traceability from source data to exported records is maintained in accordance with Good Clinical Practice (GCP) and applicable regulatory requirements; see also the CIP Data Management section.
Monitoring Plan	Describes the strategy, methods, responsibilities, and requirements for monitoring the clinical investigation.	TRUE	Detailed in the CIP
Subject Recruitment Materials	Materials used to recruit subjects, ensuring they are ethically and appropriately informed.	FALSE	This study is exempt from the requirement to provide Subject Recruitment Materials because it involves the prospective observational review and annotation of fully anonymized dermatological images. No active recruitment, advertisement, or solicitation of potential subjects (image annotators) was conducted for the purposes of this study, as healthcare professionals were directly invited to participate. As there was no general subject recruitment campaign, recruitment materials were not necessary. Healthcare professionals instead received oral information about the study and signed participation contracts. This approach is in alignment with ISO 14155:2021 and relevant regulatory guidelines for observational studies.
Signed Agreements	Contracts between the sponsor, investigators, and institutions detailing roles and responsibilities.	TRUE	Accessible upon formal request addressed to the study sponsor.
Delegation of Duties Log	Documents identifying the study-related duties and responsibilities assigned to each team member.	TRUE	Detailed in the CIP
Training Records	Evidence of training provided to the investigation team on the CIP, investigational device, and GCP principles.	TRUE	Training sessions were conducted for all investigators and study staff involved in the clinical investigation. The content of the training included the study protocol, the correct use of the device, data entry procedures, and compliance with ISO 14155 and Good Clinical Practice (GCP) requirements. Attendance logs were maintained, and the training records are available in presentation format (slides) detailing the topics covered. These presentations, along with participant attendance records, are retained as part of the study's essential documents and can be provided for audit or inspection upon request.
Investigational Device Accountability Records	Tracks the receipt, use, and disposition of the investigational device to ensure traceability.	FALSE	Given the software-only nature of the investigational device, the research team was granted controlled access to the manufacturer's annotation platform through individualised login credentials (username and password). Platform access logs provide full traceability of all annotation activities. The corresponding email communications confirming access provision can be provided for audit on request.
Subject Identification Code List	Confidential list linking subjects' codes to their identities, maintained by the investigator.	FALSE	This prospective observational study did not involve patient recruitment or the use of identifiable patient images. The research used fully anonymized dermatological images sourced from public atlases and databases. No patient identification, linkage codes, or identification lists were necessary or created. The healthcare professionals participating as image annotators provided their informed consent through participation contracts, and no subject identification code lists were required.
Screening and Enrollment Logs	Documents tracking the screening and enrollment status of potential and actual study subjects.	FALSE	This prospective observational study did not require formal screening and enrollment logs for subjects. Instead of recruiting patients for the study, the research involved inviting healthcare professionals (dermatologists and primary care practitioners) to participate in annotating dermatological images. These healthcare professionals were directly invited and signed participation contracts, without formal screening procedures. Enrollment records of participating healthcare professionals are maintained and available upon request. Consequently, traditional subject screening and enrollment logs were not applicable to this study design.
Investigational Device Dossier (IDD)	Comprehensive technical and clinical data on the investigational device, including design, manufacturing, and performance information.	TRUE	The Investigational Device Dossier is provided by the complete technical file held by the manufacturer (R-TF-012 series, covering design, manufacturing, preclinical performance and risk-management summary); it is available for audit on request. Investigators were oriented to the device via the IFU (see Investigator's Brochure row above) and the training records retained for this investigation.
Insurance Statement	Proof of insurance coverage for participants in case of study-related injuries.	FALSE	Insurance coverage was not required for this prospective observational study. The research involved only the review and annotation of anonymized dermatological images on a secure web-based platform. No procedures, interventions, or direct patient contact occurred that would create risk of injury to any study participants. Healthcare professionals participated voluntarily with informed understanding of the study's observational and non-interventional nature through participation contracts. Therefore, liability insurance specific to study-related injuries was not applicable.
Financial Disclosure Records	Documentation of any financial interests of investigators that could affect the study's integrity.	TRUE	Financial disclosure forms were collected from all investigators and study personnel involved in the clinical investigation. These forms document any potential financial interests, conflicts of interest, or relationships that could affect the study's integrity or objectivity. The disclosures are maintained as essential study documents and are available upon formal request.
Audit Certificates	Reports from independent audits assessing compliance with the CIP and GCP.	FALSE	An external independent audit was not deemed necessary for this study. Instead, an internal audit and comprehensive monitoring program was conducted by the sponsor to assess compliance with the Clinical Investigation Plan (CIP) and Good Clinical Practice (GCP) requirements. This internal audit included regular monitoring visits every three months, Source Data Verification (SDV), platform access audit trails, and documentation review. Given the straightforward observational design, limited duration, focused team, and robust internal monitoring mechanisms in place, an external audit was not required. All audit findings and monitoring reports are maintained as part of the study's essential documents.
Final Clinical Investigation Report	A comprehensive report summarizing the clinical investigation's methodology and results.	TRUE

Ethics Committee Non-Applicability Determination

This clinical investigation is a simulated-use multi-reader multi-case (MRMC) study performed entirely on retrospective, fully anonymised dermatological images obtained from public dermatology atlases and other freely available public sources. The investigation does not involve the recruitment of patients, direct contact with patients, or the collection or processing of patient-identifiable data; no therapeutic or diagnostic intervention is performed on any patient as a consequence of the study. Healthcare professionals acting as readers participate in their professional capacity as expert evaluators of device performance; they are not enrolled as research subjects within the meaning of biomedical-research law.

Accordingly, the sponsor has determined, and documents herein, that this investigation does not fall within the material scope of:

• Ley 14/2007, de 3 de julio, de Investigación Biomédica, which governs biomedical research involving human subjects, human biological samples and personal health data in Spain.
• Real Decreto 957/2020, de 3 de noviembre, por el que se regulan los estudios observacionales con medicamentos de uso humano and, by analogy for medical-device performance studies, the Spanish framework transposing the requirements of Regulation (EU) 2017/745 Article 62 and Annex XV for clinical investigations of medical devices involving human subjects.

The sponsor further confirms that the study is conducted in accordance with the ethical principles of the Declaration of Helsinki to the extent applicable to retrospective studies of anonymised material; complies with Regulation (EU) 2016/679 (GDPR) and with Ley Orgánica 3/2018, de 5 de diciembre, de Protección de Datos Personales y garantía de los derechos digitales for the handling of any personal data collected from reader-participants; and is registered in the public trial registries identified in the corresponding Clinical Investigation Plan and Clinical Investigation Report.

This determination of non-applicability is signed off by the sponsor and retained in the technical file. Where a participating site or competent authority requires a formal ethics-committee opinion or waiver for local conduct, such opinion is obtained and attached separately; otherwise this determination applies.

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-018 Clinical Research Coordinator
• Approver: JD-022 Medical Manager