Before a new medical device reaches patients, manufacturers must prove with real clinical data that it is safe and performs as intended. In Europe, that proof usually comes from a clinical investigation, and ISO 14155 is the standard that governs how it must be designed, conducted, and reported. For anyone working in MedTech regulatory affairs, clinical operations, or quality, this standard sets the baseline for what counts as credible clinical evidence.
What is ISO 14155?
ISO 14155, formally “Clinical investigation of medical devices for human subjects — Good clinical practice,” is the international standard governing how clinical investigations of medical devices are planned, conducted, recorded, and reported. It adapts Good Clinical Practice, originally developed for pharmaceutical trials, into requirements tailored to devices, covering ethics review, study conduct, data integrity, and the responsibilities of everyone involved.
The standard runs on four pillars that shape every clinical investigation:
- Ethical considerations by protecting the rights, safety, and well-being of participants
- Study design and conduct by ensuring scientific rigor and regulatory compliance
- Data integrity by guaranteeing that collected data is accurate, complete, and traceable
- Roles and responsibilities by clearly defining the duties of sponsors, investigators, and ethics committees
In the EU, clinical data generated in accordance with ISO 14155 support the conformity assessment required for CE marking under the EU Medical Device Regulation (MDR) 2017/745.
For Class III and implantable devices, clinical investigations are practically unavoidable; for other classes, they become necessary whenever existing clinical data cannot sufficiently demonstrate safety and performance.
Where does ISO 14155 come from?
ISO 14155's ethical foundation predates the standard itself. The Nuremberg Trials of 1946–1947 established voluntary informed consent as a non-negotiable requirement in human research, and the World Medical Association's Declaration of Helsinki, first adopted in 1964 and most recently revised in October 2024, remains the reference framework on which those principles are built.
Before ISO 14155 existed, European clinical investigations of medical devices followed EN 540, a standard focused mainly on confirming device performance and identifying side effects. ISO 14155, first published in 1996, replaced EN 540 by weaving GCP principles into a device-specific framework. It has since been revised in 2003, 2011, and most recently in 2020, the version in force today; the 2020 revision strengthened risk management, improved data integrity requirements, and tightened alignment with the EU MDR and the Declaration of Helsinki.
How does ISO 14155 relate to MDR and IVDR?
ISO 14155 governs clinical investigations for medical devices only; it explicitly excludes in vitro diagnostics. IVD performance studies instead follow ISO 20916 under IVDR. Both standards feed the same underlying MDR and IVDR conformity assessment routes, but a company running both device and IVD studies needs two separate compliance frameworks, not one shared checklist.
This distinction matters most for organizations that run both types of studies in parallel, since a monitoring plan or data management approach built for one standard will not automatically satisfy the other.
Who's involved: sponsor, CRO, and investigator
A clinical investigation under ISO 14155 runs on three defined roles. The sponsor, usually the device manufacturer, holds overall responsibility and liability, even when parts of the work are delegated to a Contract Research Organization under a written agreement. At each site, the principal investigator answers for day-to-day conduct and participant safety.
The sponsor may delegate operational duties to a CRO, but the ultimate responsibility for data quality and integrity always stays with the sponsor; any delegation must be documented in a written agreement. Larger, multicentre studies typically also have a coordinating investigator, who helps align the work across sites.
The three phases of a clinical investigation
Planning
ISO 14155 organizes a clinical investigation into three phases: planning, where the sponsor builds the Clinical Investigation Plan and completes a risk assessment; conduct, where the study runs under Ethics Committee approval with continuous safety monitoring; and close-out, where results are compiled into the Clinical Investigation Report.
During planning, the sponsor develops the Clinical Investigation Plan (CIP), the master document that describes the study's objectives, design, endpoints, and procedures, along with the Investigator's Brochure, which summarizes the safety and performance data that justify human exposure to the device. A thorough risk assessment must demonstrate that the anticipated benefits of the investigation outweigh its risks, both for the device itself and for how the investigation is conducted. This phase also includes selecting qualified investigation sites and drafting a risk-based monitoring plan.
Conduct
A study can only start once the Ethics Committee, and where applicable, the relevant regulatory authority, has given written approval. Sites must be properly initiated, staff trained, and monitoring performed according to plan. Throughout the investigation, every adverse event and device deficiency must be assessed and, depending on its severity, reported to the Ethics Committee, the sponsor, and regulatory authorities within defined timelines. Data is typically captured in an electronic data capturing (EDC) system, and every piece of data must remain attributable, legible, contemporaneous, original, and accurate, according to the well-known ALCOA principle.
Close-out
A study closes once the last subject's last visit has taken place and been documented. Close-out activities include finalizing case report forms, resolving outstanding queries, documenting the disposition of investigational devices, and notifying the Ethics Committee and regulatory authorities. The sponsor then prepares the Clinical Investigation Report, summarizing the methodology, results, and conclusions, which is submitted to the Ethics Committee and regulatory authorities and, per the Declaration of Helsinki, must also be disclosed in a publicly accessible database such as ClinicalTrials.gov or EUDAMED.
How ISO 14155 protects participants: informed consent and vulnerable populations
ISO 14155 requires voluntary, fully informed consent before any study procedure begins, and additional safeguards apply whenever a subject cannot consent on their own. Vulnerable populations, including minors, pregnant patients, and people with cognitive impairment, may only be enrolled when the study cannot reasonably be run in a non-vulnerable population and offers them a possible direct benefit.
Special procedures apply when a subject cannot consent themselves, for example in emergencies or when a legally designated representative is required. These protections sit alongside the general consent requirement, not instead of it.
Why ISO 14155 matters
ISO 14155 exists to uphold two obligations at once: protecting the people enrolled in a study and producing data reliable enough for regulators, notified bodies, and the FDA to trust. That dual mandate is what allows a clinical investigation to serve as credible evidence rather than a paperwork exercise.
By harmonizing requirements across regions, the standard reduces friction for manufacturers conducting multinational studies, while providing Ethics Committees, monitors, and auditors with a shared reference point for evaluating how a trial was actually conducted. For anyone involved in planning or running a clinical investigation, whether as sponsor, CRO, or investigator, a solid working knowledge of ISO 14155 turns a study from a compliance exercise into a source of credible, defensible clinical evidence.
Want your team to master ISO 14155 in depth?
This article only scratches the surface of what ISO 14155 requires in practice, from the exact content of the Clinical Investigation Plan and Investigator's Brochure to the documentation trail expected during monitoring, audits, and close-out.
If your organization wants your clinical, regulatory, or quality team to build that expertise in a structured way, Qserve develops custom e-learning courses on ISO 14155, complete with a certificate of completion upon passing.