The Document MDCG 2025–5 of the Medical Device Coordination Group provides comprehensive questions and answers on performance studies of in vitro diagnostic medical devices (IVDs) in accordance with EU Regulation 2017/746 (IVDR). It clarifies the definitions of performance studies, analytical and clinical studies, as well as the requirements for their conduct and reporting to the competent authorities. It explains which studies require an application or notification based on criteria such as invasive sample-taking, interventionality or the use of companion diagnostics. It also covers timing aspects, substantial modifications of performance studies and the use of CE-marked IVDs in performance studies to ensure the safety and performance of the devices. The document answers the following questions in particular:
What is a performance study according to the IVDR?
A performance study according to Article 2(42) IVDR is a study undertaken to establish or confirm the analytical or clinical performance of an in vitro diagnostic device (IVD). Unlike clinical or laboratory methods, which describe workflows or operating instructions, a performance study focuses on generating performance data for the device itself. Such studies may use fresh samples from human subjects, but may also use data from curated databases, registries, or previously collected patient data or materials.
What are analytical and clinical performance studies, and when are both required?
- Analytical performance studies assess the ability of an IVD to measure an analyte correctly (e.g. sensitivity, specificity, precision).
- Clinical performance studies demonstrate whether results correlate with a clinical condition (e.g. diagnostic sensitivity, predictive values).
Analytical studies are always required. Clinical performance data may also be obtained from literature or routine use – a study is necessary if this data is insufficient.
Which performance studies are regulated by the IVDR and which require submission to the competent authority?
All performance studies within the meaning of the IVDR are subject to general requirements (e.g. GSPR, data protection).
An application must be submitted for:
- surgically invsasive sample-taking only for the purpose of the performance studies,
- interventional clinical performance studies,
- additional risks for the subjects
- companion diagnostics involved but not only left-over samples are used.
Notification is sufficient in the following cases:
- companion diagnostics for which only left-over samples are used,
- PMPF studies with CE-IVDs and invasive procedures.
Studies without these characteristics do not need to be submitted, but remain subject to Article 57.
What is the meaning of “surgically invasive sample-taking done only for the purpose of the performance study” and “interventional clinical performance study”?
- Surgically invasive sample-taking means the use of invasive procedures only for the purpose of the study – in which case an application is required. Routine procedures used for study purposes are not considered to be ‘only for the purpose of the performance study’.
- Interventional studies influence patient management. There is a risk here of incorrect decisions being made due to unreliable test results.
What are „left-over samples“ and what submission requirements apply when they are used in performance studies?
Left-over samples are residual material from routine diagnostics without clinical need, possibly from biobanks.
Submission requirements:
- Companion diagnostics: Notification pursuant to Article 58(2)
- Non-companion diagnostics with additional risks: Application pursuant to Article 58(1)©
- PMPF with CE-IVDs and burdensome procedures: notification pursuant to Article 70(1).
What is meant by ‘burdensome’ procedures in PMPF studies, and when can such studies be started with CE-marked devices?
- Burdensome procedures are all procedures that may cause discomfort, risks or restrictions. The assessment must be made from the perspective of the person concerned.
- According to Article 71 (1) IVDR, a PMPF study involving burdensome procedures may be initiated after notification – approval is not generally required unless there are objections or negative ethical opinions.
So what do IVD manufacturers need to bear in mind with regard to performance studies?
Manufacturers are responsible for determining the intended purpose of their IVD. They must ensure that the product meets the general safety and performance requirements (GSPR) set out in Annex I of the IVDR – in particular for aspects not covered by the study. For the aspects examined in the study, appropriate precautions to protect patients, users and third parties must be taken and documented.
Compliance with the GSPR must be confirmed. The underlying evidence of GSPR compliance must be made available to the authorities upon request.
The performance study plan must describe the technical and functional characteristics of the IVD, including product specifications, the relationship to the intended clinical benefit, and whether a characteristic affects safety or performance.
In addition, clear, validated instructions for use, storage, maintenance and handling of the product must be provided. This information, including training requirements, must be written in a way that is understandable in the official language(s) of the Member State concerned. Particular attention must be paid to products for self-application or near-patient diagnostics.
If several IVDs are being investigated in a study, all relevant documents, such as the investigator’s brochure and the declaration of conformity, must cover all devices concerned in full.
What needs to be done now?
Only those who are familiar with and meet the requirements for analytical and clinical performance studies can bring IVDs to market safely, economically and in compliance with the law.
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