R-TF-015-010 Annex E ISO 14155

Applicability and scope

This annex documents compliance with ISO 14155:2020 requirements for the DAO Derivación O 2022 clinical investigation. The investigation is a non-interventional prospective observational clinical investigation of a CE-marked medical device used within its intended purpose, conducted under Article 82 of Regulation (EU) 2017/745 (MDR) and the Spanish biomedical-research framework applicable at the time of conduct (Ley 14/2007 and Real Decreto 1090/2015). Under MDCG 2020-6 Appendix III the evidence is ranked 2–4 for the device-versus-reference-standard diagnostic-accuracy analysis; per MDCG 2020-1 §4.4 it contributes Pillar 3 Clinical Performance evidence. Where an ISO 14155 deliverable is marked "Maintained at site" or "Maintained by sponsor", the record is held by the relevant custodian under the sponsor's records-retention procedure and is available to the notified body and to competent authorities on formal request.

ISO 14155:2020 compliance checklist

Document	Purpose	Status	Justification and evidence location
Investigator's Brochure	Provides clinical and non-clinical data on the investigational device relevant to its study in human subjects.	TRUE	The device IFU at v1.1.0.0, together with the Device Description and Specifications record held within the technical file, collectively served as the Investigator's Brochure equivalent for the purpose of informing the investigators about the clinical and non-clinical profile of the device. The IFU and the Device Description and Specifications record are provided alongside the Clinical Investigation Plan.
Clinical Investigation Plan (CIP)	Describes the rationale, objectives, design, methodology, monitoring and conduct of the clinical investigation.	TRUE	R-TF-015-004 Clinical Investigation Plan.
Investigational Device Dossier (IDD)	Comprehensive technical and clinical data on the investigational device, including design, manufacturing and performance information.	TRUE	The Device Description and Specifications record and the design-history and verification-and-validation records within the technical file (under the per-version technical-file folder) collectively constitute the IDD for this non-interventional observational clinical investigation of a CE-marked device used within its intended purpose.
Subject Information Sheet and Informed Consent Form (ICF)	Ensures that potential study subjects are adequately informed about the investigation and provide voluntary consent.	TRUE	Patient Information Sheet and Informed Consent provided as Annex III to the CIP.
Ethics Committee approval	Official approval from the ethics committee to conduct the clinical investigation.	TRUE	CEIm of Euskadi, favourable opinion on 2022-11-23, reference PS2022074, together with the subsequent approval of the substantial modification; both retained in the Trial Master File.
Regulatory Authority authorisation	Authorisation or notification from the relevant regulatory bodies to proceed with the clinical investigation.	FALSE	Non-interventional observational clinical investigation of a CE-marked medical device used within its intended purpose; under the Spanish biomedical-research framework applicable at the time of conduct this category is subject to CEIm favourable opinion (obtained) but does not trigger a pre-market clinical-investigation authorisation under MDR Article 62. ISO 14155 and MDR Annex XV compliance were nonetheless considered in the design and conduct of the investigation.
Case Report Forms (CRFs)	Documents designed to record all protocol-required information to be reported to the sponsor on each subject.	TRUE	CRF version 1.0 and accompanying data dictionary held by the sponsor within the Trial Master File; source-data verification is performed against the site records under the Monitoring Plan.
Statistical Analysis Plan (SAP)	Pre-specifies primary, secondary and exploratory analyses, statistical methods, handling of missing data and operating thresholds.	TRUE	Statistical methods are pre-specified in CIP §Statistical Analysis. The operating-threshold deviation and the ITT-vs-analytical-sample treatment are declared in CIR §Protocol Deviations.
Protocol deviations log	Records all deviations from the CIP with rationale and regulatory handling.	TRUE	CIR §Protocol Deviations lists five declared deviations for this investigation. Supporting records are held by the sponsor under the records-retention procedure.
Adverse-event reporting procedure	Procedure for detection, classification, documentation and reporting of AEs, AEPs, SAEs and SUAEPs.	TRUE	Procedure described in CIP §Adverse events, adverse product reactions and product deficiencies. Passive AE surveillance by the Principal Investigators at each site; no AEs were reported during the investigation (see CIR §Adverse Events and Adverse Reactions to the Product).
Device-deficiency reporting procedure	Procedure for identification, documentation and handling of device deficiencies observed during the investigation.	TRUE	Procedure described in CIP §Product deficiencies. No device deficiencies were observed (see CIR §Product Deficiencies).
Annual safety / progress report to the Ethics Committee	Annual report to the CEIm covering progress, safety events and any deviations.	TRUE	Annual progress reports were submitted to the CEIm of Euskadi under the ethics-committee communication plan; copies retained in the Trial Master File.
Monitoring Plan	Describes the strategy, methods, responsibilities and requirements for monitoring the clinical investigation.	TRUE	Described in CIP §Monitoring plan.
Monitoring visit reports	Records of each monitoring visit performed, with findings, actions and follow-up.	TRUE	Monitoring-visit reports maintained by the sponsor within the Trial Master File and available on formal request.
Subject recruitment materials	Materials used to recruit subjects, ensuring they are ethically and appropriately informed.	FALSE	The Patient Information Sheet and Informed Consent (Annex III to the CIP) serves the same informative purpose. No additional advertising or recruitment materials were used.
Signed agreements	Contracts between the sponsor, investigators and institutions detailing roles and responsibilities.	TRUE	Clinical Trial Agreements between the sponsor and each participating institution are retained by the sponsor.
Delegation of duties log	Documents identifying the study-related duties and responsibilities assigned to each team member.	TRUE	Described in CIP §Principal Investigators and §Technical Support (Manufacturer).
Training records	Evidence of training provided to the investigation team on the CIP, investigational device and GCP principles.	TRUE	A study-initiation visit was conducted to familiarise the investigators with the CIP and the device. Training materials prepared for the initiation visit are retained under the sponsor's training-record procedure.
Investigational device accountability records	Track the receipt, use and disposition of the investigational device to ensure traceability.	TRUE	The investigational device is a software medical device; authorised users were granted controlled access via individual authenticated accounts (username and password). Access and usage are logged under the manufacturer's information-security procedure; audit logs document all access, usage and modifications during the investigation and are retained under the sponsor's records-retention procedure.
Subject Identification Code List	Confidential list linking subjects' codes to their identities.	Maintained at site	Maintained at each participating primary care centre under the custody of the Principal Investigator, available to the sponsor, the notified body and the competent authority on formal request, with confidentiality preserved under Regulation (EU) 2016/679 and Ley Orgánica 3/2018.
Screening and enrolment logs	Track the screening and enrolment status of potential and actual subjects.	Maintained at site	Maintained at each participating primary care centre under the custody of the Principal Investigator, available to the sponsor, the notified body and the competent authority on formal request, with confidentiality preserved under Regulation (EU) 2016/679 and Ley Orgánica 3/2018.
Insurance statement	Proof of insurance coverage for participants in case of study-related injuries.	TRUE	The sponsor maintains civil-liability insurance coverage that extends to this non-interventional observational clinical investigation. The insurance documentation is retained within the Trial Master File and available on formal request.
Financial disclosure records	Documentation of any financial interests of investigators that could affect the investigation's integrity.	TRUE	Financial disclosures are collected from each investigator and retained by the sponsor.
Audit certificates	Reports from independent audits assessing compliance with the CIP and GCP.	TRUE	An independent audit was conducted by the research-coordinating office of Biocruces Bizkaia Health Research Institute to assess compliance with the CIP, study procedures and GCP principles. Audit findings and actions are retained under the sponsor's quality-assurance procedure.
Final Clinical Investigation Report	Comprehensive report summarising the clinical investigation's methodology and results.	TRUE	R-TF-015-006 Clinical Investigation Report.

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