Medical Device Clinical Investigations under ISO 14155

As outlined in the MDR, the rules regarding clinical investigations should align with established international guidance, such as ISO 14155:2011. This alignment facilitates the acceptance of results of the clinical investigation conducted within the EU in other regions, and vice versa. It is important to note that the new edition of this standard was released in 2020 providing updated guidelines for the design and conduct of clinical investigations for medical devices, and ISO 14155:2020 is not recognized as a harmonized standard under the MDR. While both ISO 14155 and the MDR text outline procedural and documentation requirements for clinical investigations, they may sometimes present differing requirements. According to ISO 14155, it is essential to consider whether other standards or national requirements apply to the investigational devices or the clinical investigation. If differences in requirements exist, the most stringent apply. The MDCG 2024-3 document further explains that adherence to ISO 14155 is strongly recommended, as it serves as a valuable resource for sponsors planning and developing their clinical investigations, although it is not mandatory for investigations conducted under the MDR. For example, when preparing the Clinical Investigation Plan (CIP), sponsors are encouraged to review both the MDR and ISO 14155. If discrepancies arise between the MDR and the standard, the legal requirements of the MDR take precedence. 

Yes, ISO 14155:2020 extends its applicability to post-market clinical investigations, which are part of the post-market clinical follow-up (PMCF) required by the Medical Device Regulation MDR. While the principles of ISO 14155 can guide post-market studies, not all elements of the standard may be relevant, and the applicability of requirements should be evaluated based on the specific nature of the investigation.

For post-market interventional clinical Investigations, most principles of the standard generally apply, with certain exemptions. These exemptions may include aspects such as device accountability and specific labelling requirements for clinical investigations. Furthermore, if sufficient information about the medical device’s use within its approved indications is available, certain requirements, such as the preparation of the Investigational Brochure, may be waived. Reporting to regulatory authorities may also not be necessary unless required by national regulations.

For post-market non-Interventional clinical Investigations, similar exemptions may apply. Additionally, informed consent may no be applicable, although consent applying requirements for personal data protection remains mandatory.

In summary, ISO 14155 provides a flexible framework for conducting post-market clinical investigations, ensuring scientific and ethical rigor while allowing for necessary adjustments based on the investigation's nature and the existing product documentation.

ISO 14155:2020 does not exist in isolation; it is closely intertwined with ISO 14971, which outlines the risk management framework for medical devices. Together, they ensure that medical devices are both safe and effective, addressing not only the clinical investigation phase but also the entire product lifecycle. Moreover, a clinical investigation is a method of providing clinical data to allow conclusions on the acceptability of the benefit-risk ratio established by the device’s risk management process.

Annex H of ISO 14155 explicitly details how ISO 14971 should be applied to manage potential safety concerns during clinical investigations. From one side, during the planning phase of a clinical investigation, ISO 14155 requires that a thorough risk assessment be performed according to ISO 14971 and considered in clinical investigation activities. This involves identifying potential hazards associated with the investigational medical device, estimating and evaluating the associated risks, and implementing control measures to mitigate these risks and ensure patient safety. A summary of the benefit-risk analysis, including the identification of residual risks, is required to be included in the clinical documentation.

On the other hand, ISO 14155 emphasizes that risk management is an ongoing process throughout the clinical investigation, meaning that risk management principles from ISO 14971 must be integrated into the clinical investigation process. For both the investigational device including clinical procedure and clinical investigation process, the sponsor shall predefine or establish risk acceptability thresholds and trigger a risk assessment to determine whether actions are needed as soon as thresholds are reached or exceeded. This approach aids in identifying and mitigating risks early, thereby enhancing the overall safety profile of the medical device under investigation.

ISO 14155 mandates that all risk management activities be documented in the clinical investigation documentation, ensuring transparency and traceability of how risks were managed throughout the study. Any new risks identified during the investigation must be evaluated and managed according to ISO 14971 principles. Consequently, the risk management documentation must also be updated to reflect new findings from the clinical investigation.