R-TF-015-010 Annex E ISO 14155
Applicability and scope
This Annex E records compliance of the DAO_Derivación_PH_2022 clinical investigation with the documentation and conduct requirements of UNE-EN ISO 14155:2021, as applicable to a non-interventional observational clinical validation of a CE-marked medical device used within its intended purpose. The investigation is positioned as Pillar 3 real-patient prospective clinical-performance evidence at Rank 2–4 under MDCG 2020-6 Appendix III, under MDCG 2020-1 §4.4. Under Article 2(2) of the MDR and the provisions of ISO 14155:2021, the investigation is non-interventional and is conducted within the Spanish biomedical-research framework under a CEIm favourable opinion; it does not trigger a pre-market clinical-investigation authorisation under MDR Article 62.
UNE-EN ISO 14155:2021 compliance requirements
The table below records, for each essential clinical-investigation document identified in ISO 14155:2021 Annex E, whether the document was provided for this investigation and — where not provided as a standalone artefact — the regulatory-level justification and the custodian record.
| Document Title | Purpose | Included | Justification and record location |
|---|---|---|---|
| Investigator's Brochure | Provides clinical and non-clinical data on the investigational device relevant to its study in human subjects. | TRUE | The Instructions For Use (IFU v1.1.0.0) and the Device Description and Specifications record held within the technical file serve as the Investigator's Brochure for this investigation, in accordance with ISO 14155:2021 §7.2 and Annex B, and were provided to the investigators at the study-initiation visit. |
| Clinical Investigation Plan (CIP) | Describes the rationale, objectives, design, methodology, monitoring, and conduct of the clinical investigation. | TRUE | Provided as R-TF-015-004 for this investigation. |
| Statistical Analysis Plan | Pre-specifies the analysis population, primary and secondary tests, multiplicity strategy and handling of missing data. | FALSE | The statistical-analysis approach is documented in CIP §Statistical Analysis. Pre-specification gaps (per-endpoint analysis unit, ITT vs per-protocol population, missing-data rule, multiplicity strategy) are declared in CIR §Protocol Deviations and the investigation is positioned as supporting Pillar 3 evidence on three evaluable secondary acceptance criteria. Confirmatory analyses on the primary endpoint are deferred to the PMCF Plan (R-TF-007-002), which includes a full SAP. |
| 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 Form provided as Annexes III and IV to the CIP (R-TF-015-004). Signed originals are retained under the custody of the Principal Investigator at each study centre. |
| Ethics Committee Approval | Official approval from the ethics committee to conduct the clinical investigation. | TRUE | CEIm Puerta de Hierro favourable opinion, reference 47/395984.9/22, dated 2022-06-24. Provided as Annex II to the CIP (R-TF-015-004). |
| Regulatory Authority Authorization | Authorization or notification from relevant regulatory bodies to proceed with the clinical investigation. | FALSE | Non-interventional observational clinical validation of a CE-marked medical device used within its intended purpose; under the Spanish biomedical-research framework applicable at the time of conduct, subject to CEIm favourable opinion (obtained) but does not trigger a pre-market clinical-investigation authorisation under MDR Article 62. AEMPS notification position is pending confirmation and is tracked as a follow-up. |
| Case Report Forms (CRFs) | Documents designed to record all protocol-required information to be reported to the sponsor on each trial subject. | TRUE | Electronic CRFs were captured through the validated, access-controlled web-based platform provided by the manufacturer. CRF content is retained under the sponsor's records-retention procedure. |
| Monitoring Plan | Describes the strategy, methods, responsibilities, and requirements for monitoring the clinical investigation. | FALSE | No standalone Monitoring Plan was prepared as a discrete artefact; monitoring activities are described in CIP §Monitoring Plan and were conducted by the sponsor's monitor. A standalone Monitoring Plan is a CAPA deliverable for future real-patient Pillar 3 investigations. |
| Subject Recruitment Materials | Materials used to recruit subjects, ensuring they are ethically and appropriately informed. | FALSE | The Patient Information Sheet and Informed Consent Form served the subject-information function; no additional recruitment materials (posters, advertisements) were used. This is consistent with the consecutive-enrolment design from hospital and primary-care consultations. |
| Signed Agreements | Contracts between the sponsor, investigators, and institutions detailing roles and responsibilities. | TRUE | Signed research agreements between the sponsor institution, the manufacturer and the investigational sites are retained under the sponsor's records-retention procedure within the Trial Master File. |
| Delegation of Duties Log | Documents identifying the study-related duties and responsibilities assigned to each team member. | FALSE | Delegated duties are enumerated in CIP §Research Team and §Collaborating Investigators; no standalone Delegation of Duties Log was maintained as a discrete artefact. A standalone log is a CAPA deliverable for future real-patient Pillar 3 investigations. |
| 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 investigational device. Training materials for the study-initiation visit are archived in the Trial Master File under the sponsor's training-record procedure and are available on audit request. |
| Investigational Device Accountability Records | Tracks the receipt, use, and disposition of the investigational device to ensure traceability. | TRUE | The investigational device is a software medical device delivered through a validated, access-controlled web-based platform. The research team was granted individual authenticated user accounts (username and password). Access provisioning and revocation events are recorded in the manufacturer's access-control log held within the Trial Master File. No physical-device accountability is applicable. |
| Subject Identification Code List | Confidential list linking subjects' codes to their identities, maintained by the investigator. | TRUE | Maintained confidentially at each study centre under the custody of the Principal Investigator, in accordance with the study confidentiality controls. |
| Screening and Enrollment Logs | Documents tracking the screening and enrollment status of potential and actual study subjects. | TRUE | Maintained confidentially at each study centre under the custody of the Principal Investigator, in accordance with the study confidentiality controls. |
| Investigational Device Dossier (IDD) | Comprehensive technical and clinical data on the investigational device, including design, manufacturing, and performance information. | TRUE | The MDR Annex II Technical File constituents (device description, R-TF-012 series design-and-development records, R-TF-013-002 risk management record, verification and validation records, cybersecurity documentation and IFU v1.1.0.0) serve as the Investigational Device Dossier and are retained by the manufacturer within the QMS. |
| Insurance Statement | Proof of insurance coverage for participants in case of study-related injuries. | FALSE | Under Article 2(2) of the MDR and the provisions of ISO 14155:2021, this clinical investigation is non-interventional and does not require specific insurance coverage for study participants. Supporting documentation (CIP and CEIm favourable opinion) is available on audit request. |
| Financial Disclosure Records | Documentation of any financial interests of investigators that could affect the study's integrity. | TRUE | Financial disclosures of investigators and manufacturer-affiliated personnel are retained within the Trial Master File. The manufacturer-affiliated co-authorship of publications cited in CIR §Clinical Relevance is disclosed per MEDDEV 2.7/1 Rev 4 §8 and ISO 14155:2021 §6.6. |
| Deviations Log | Log of protocol deviations, their categorisation (major/minor), dates, corrective actions and endpoint impact. | TRUE | Protocol deviations are enumerated in CIR §Protocol Deviations as a numbered list with category, rationale and mitigation; the deviations log is held within the Trial Master File under the sponsor's records-retention procedure. |
| Adverse-Event Reporting Procedure | Procedure for identification, reporting, review and archiving of AEs and AEPs. | TRUE | Defined in CIP §Adverse events, adverse product reactions and product deficiencies and in the sponsor's vigilance procedure. No AEs or AEPs were observed during this investigation; the AE/AEP register is held within the Trial Master File. |
| Device-Deficiency Reporting Procedure | Procedure for identification, reporting, review and archiving of product deficiencies. | TRUE | Defined in CIP §Product deficiencies and in the sponsor's non-conforming-product control procedure. No device deficiencies were observed during this investigation; the deficiency register is held within the Trial Master File. |
| Annual Safety / Progress Report to Ethics Committee | Yearly report to the Ethics Committee summarising conduct, enrolment, deviations and safety. | TRUE | Annual monitoring reports were submitted to CEIm Puerta de Hierro during the conduct of the investigation, as declared in CIP §Start, follow-up and end reports. Copies are retained within the Trial Master File. |
| Audit Certificates | Reports from independent audits assessing compliance with the CIP and GCP. | FALSE | No independent audit was conducted for this investigation. An audit is not required under ISO 14155:2021 for non-interventional observational investigations. |
| Final Clinical Investigation Report | A comprehensive report summarising the clinical investigation's methodology and results. | TRUE | Provided as R-TF-015-006 for this investigation. |
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