Key takeaways
Written by Maria Nyåkern, Ph.D., is an international expert and a Swedish representative on the ISO technical committee responsible for developing ISO 14155. This article reflects her interpretation of the published standard and her professional judgment on its practical implications. Readers are encouraged to consult the full text of ISO 14155:2026 and applicable regulatory guidance for their specific context.
ISO 14155:2026, the fourth edition of the international standard for Good Clinical Practice (GCP) in medical device investigations, is now published. It supersedes ISO 14155:2020 and sets the framework for how new clinical investigations should be conducted across the EU, US, and other major markets.
The 2026 edition builds on the 2020 revision, which explicitly introduced the thirteen GCP principles, reinforced alignment with ISO 14971 on risk management, and moved ISO 14155 closer to the requirements of EU MDR Annex XV. It now introduces several further changes of practical importance for clinical investigations of medical devices.
ISO 14155:2026 should be applied from the outset. Design the CIP, monitoring plan, and quality system procedures to the 2026 standard.
Alignment is expected when significant changes are introduced; major CIP amendments are a natural trigger to review and update documentation to the 2026 edition.
Elements such as the clarified risk management framework, the CEC and DMC decision documentation, and the updated deviation/amendment distinction can be integrated progressively and, in many cases, without waiting for a specific study trigger.
The most immediate practical priorities for most sponsors are:
This article will break down the key changes in the latest ISO 14155 standard based on the following key areas:
ISO 14155:2026 introduces a clearer distinction between three categories of risk in a clinical investigation, each with a different management approach:
This structured distinction was implicit in the 2020 edition. Making it explicit helps sponsors design proportionate risk management frameworks and write monitoring plans that are genuinely risk-based rather than generically described as such. The term benefit-risk analysis has also been updated to benefit-risk evaluation, to align with the EU MDR.
Read our Illustrated Guide to Risk Management for Medical Devices and ISO 14971, a practical overview of risk management principles and how ISO 14971 is applied in practice.
Two governance-related changes stand out.
First, the Clinical Events Committee (CEC) is formally introduced in Clause 6.12. Prior to starting a clinical investigation, the sponsor shall consider establishing a CEC, and if one is established, information about its role must be included in the Clinical Investigation Plan (CIP).
The CEC is an independent group of clinical experts responsible for consistent, unbiased adjudication of clinical events across sites:
This is distinct from the DMC, whose primary function is safety monitoring and interim analysis.
Second, the DMC requirements are clarified in Clause 6.11. The DMC charter must now explicitly document the conditions for suspending or stopping a clinical investigation.
Sponsors are also required to justify, in the CIP, any decision not to establish a DMC. Standardised coding of safety data is encouraged to support harmonisation and reliable analysis.
One important nuance: the standard uses ”shall consider” for both DMC and CEC. This is not a blanket requirement to establish both committees for every investigation. It is a requirement to make a documented, reasoned decision on whether each is appropriate, based on the risk profile of the specific investigation.
Annex K is new in the 2026 edition and provides informative guidance on clinical investigation design, with particular emphasis on estimands and intercurrent events.
An estimand is a precise definition of the treatment effect that a clinical investigation is designed to estimate:
The estimand framework, developed in the pharmaceutical field through ICH E9(R1), is now introduced into device good clinical practice for the first time.
Because Annex K is informative rather than normative, estimands are not a mandatory requirement for all investigations. However, they are now clearly within the scope of ISO 14155, and for complex investigations, particularly those involving software-based devices, adaptive designs, or outcomes that are sensitive to intercurrent events, the estimand approach provides a more rigorous and reproducible basis for study design and statistical analysis.
Annex ZA is also new. It provides a comparison table mapping ISO 14155:2026 to EU MDR Annex XV, facilitating demonstration of conformity under EU law. Annex ZA also specifies that where ISO 14155 is used to support compliance with MDR, the definitions in the EU Regulation 2017/745 take precedence over those in the standard, a practically important clarification for European clinical investigations.
The Informed Consent Form (ICF) requirements are strengthened in several respects. Participants must be provided with clear information regarding the use of biological samples and health-related data generated during the investigation. The requirement for lay language is reinforced. Consent documentation must be accessible to the participant, not only technically complete.
A new re-consent requirement is clarified: when a clinical investigation has been suspended and is subsequently resumed, subjects must be re-consented before continuing participation. This reflects the principle that subjects consent to a specific investigation as it was described to them. If a suspension is significant enough to require resumption procedures, it is also significant enough to warrant renewed consent.
A substantive clarification concerns the handling of eligibility criteria. In the 2020 edition, deviations from inclusion or exclusion criteria were managed through the deviation process. The 2026 edition clarifies that exemptions to eligibility criteria, individual decisions that a specific subject may participate despite not fully meeting a criterion, affect the study design and must be managed through formal Clinical Investigation Plan (CIP) amendments, not simply documented as deviations.
This is an important distinction. A CIP amendment requires Ethics Committee (EC) and Competent Authority (CA) review; a deviation does not. The practical implication is that sponsors should design eligibility criteria carefully to anticipate foreseeable clinical edge cases and should not expect that post-enrolment documentation of a deviation will be considered sufficient if eligibility was knowingly waived without an amendment.
Several further changes are worth noting.
The definitions of observational clinical investigation and non-interventional clinical investigation have been clarified, addressing ongoing regulatory discussions about the distinction between these investigation types and their different regulatory pathways.
Adverse event categorisation is updated, including a clarification that an adverse event associated with a device deficiency may trigger both Figure F.1 (AE classification) and Figure F.2 (device deficiency reporting).
An implant card requirement has been included in Clause 9.2.2 for implantable devices.
Calibration requirements for measurement equipment used in investigations are added to the CIP procedure section (Annex A.6.4).
The Investigator’s Brochure (IB) template in Annex B now includes precautions (B.5), information on device training (B.2), and in-silico test data (B.3)
For teams looking to go deeper into the practical implementation of the latest version of the standard, including how to apply these requirements in real investigations, further ISO 14155 training may be helpful.
Take a look at our online Clinical Investigation for Medical Devices and ISO 14155 course that focuses on good clinical practice (GCP) for the design, conduct, recording, and reporting of clinical investigations carried out on human subjects to assess the clinical performance or effectiveness and safety of medical devices.
The course covers an orientation of the clinical investigation process according to the EN ISO 14155:2026 standard and the standard’s relation to MDCG guidance documents. This practical course is suitable for anyone working in clinical research and medical device development, such as regulatory affairs associates, QA engineers, and clinical research specialists.
Maria Nyåkern, Ph.D., is a consultant, entrepreneur, and B2B service provider in the medical device industry; she is the founder of AKRN Scientific Consulting, a CRO specializing in medical devices and minimally invasive cardiovascular therapies.
Maria is also a valued and respected trainer on clinical evaluation and clinical investigations of medical devices according to the EU MDR 2017/745 and the ISO 14155:2020 standard. She has vast ‘ hands-on’ experience, having set up and managed dozens of clinical investigations, and tens of thousands of patients, for different medical devices and indications for many of the top ten medical device manufacturers in the industry.
Below are some of the most common questions we hear about ISO 14155:2026.
No, ISO 14155:2026 requires sponsors to consider establishing a Data Monitoring Committee (DMC) and to justify the decision in the Clinical Investigation Plan (CIP) if one is not established. The decision should be based on the risk profile of the investigation.
A Clinical Events Committee (CEC) is an independent group of clinical experts responsible for consistent and unbiased adjudication of clinical events across sites, including classification of adverse events and endpoint assessment.
ISO 14155:2026 clarifies that when a clinical investigation is suspended and later resumed, subjects must be re-consented before continuing participation.
Yes, ISO 14155:2026 clarifies that exemptions to eligibility criteria affect the study design and must be handled through a formal CIP amendment, rather than being documented only as deviations.
New investigations should follow ISO 14155:2026 from the outset. Ongoing investigations are typically aligned when significant changes are introduced, such as major amendments to the clinical investigation plan.
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