A clinical investigation under Article 74 MDR refers to a post-market clinical investigation intended to further evaluate a product that already bears the CE marking within its intended purpose, where participants undergo additional procedures that go beyond those performed under normal conditions of use and are invasive or burdensome. Regulation (EU) 2017/745 does not subject such investigations to an authorisation procedure, but to a notification requirement: the sponsor informs the Member States concerned at least 30 days before the start of the investigation via the electronic system referred to in Article 73. The term therefore denotes a distinct, procedurally less stringent category between pre-market clinical investigation and observational data collection. In terms of content, it is typically an instrument of post-market clinical follow-up, whose objectives, methodology and reporting are described there.
Constituent elements and notification procedure
Article 74(1) MDR is based on three conditions that must be met cumulatively: the product bears the CE marking in accordance with Article 20(1), the investigation remains within the intended purpose, and participants are subjected to additional procedures that are invasive or burdensome. What matters is the delta compared with routine use, not the invasiveness of the product itself: an additional biopsy, additional imaging with contrast agent, an additional blood draw, or an additional study visit involving a burdensome examination triggers the notification requirement, whereas interventions inherent to the product are not taken into account.
Notification is submitted via the electronic system pursuant to Article 73 and includes the documentation according to Annex XV, Chapter II—essentially the same dossier as for an authorization application: clinical investigation plan, investigator’s brochure, evidence of the suitability of the investigation sites and investigators, insurance details, and the benefit-risk assessment. The 30-day period is a waiting period prior to commencement, not an authorization period; explicit regulatory approval is not required. The national implementation, particularly regarding the involvement of the ethics committee, is governed by the laws of the respective Member State.
Provisions applicable by analogy
Article 74(1) expressly declares Article 62(4)(b) to (k) and (m), Articles 75 to 77, Article 80(5), and the relevant provisions of Annex XV to be applicable. This means that the substantive protection standards of the pre-market investigation apply almost unchanged: informed consent, protection of particularly vulnerable groups, investigator qualification, data protection, and the prohibition of undue inducements. Under Article 75, the sponsor remains obliged to notify substantial modifications; Article 76 provides for corrective measures by the Member States; Article 77 governs completion, early termination and reporting obligations, including the clinical investigation report. By contrast, the authorisation requirement under Article 62(1), including the assessment procedure under Article 70, does not apply. If an investigation falls outside the intended purpose, Article 74(2) refers to the full application of Articles 62 to 81.
Distinction from pre-market investigations and from activities not subject to notification
The Article 74 investigation differs from the clinical investigation under Article 62 MDR in purpose and procedure: Article 62 serves to demonstrate conformity prior to CE marking and requires authorisation by the Member State, whereas Article 74 serves to confirm safety and performance within the approved scope of use and requires only notification. At the lower end, the term is distinguished from post-market clinical follow-up activities that do not require notification: analyses from registries, cohort analyses based on routine data, user surveys, follow-up without additional examinations, and literature and vigilance analyses do not fall under Article 74 because they do not impose additional invasive or burdensome procedures on participants. For purely data-based collections, data protection law and applicable national professional and research law remain decisive.
Relevance for clinical trials
For study planning, classification under Article 62, Article 74(1) or Article 74(2) is the first and most consequential decision, as it determines the timeline, the scope of the dossier and the reporting pathways. It must be documented with reasons, as authorities and notified bodies must be able to understand the allocation, and misclassification may be assessed as conducting an investigation without the required authorisation. In practice, this means comparing each study procedure with the standard of care and explicitly assessing the delta.
Operationally, the investigation follows the same quality requirements as a pre-market study: a clinical investigation plan and investigator’s brochure in accordance with Annex XV, monitoring, safety reporting under Article 80(5), data management, and a final report, the results of which feed into the post-market clinical follow-up report and the update of the clinical evaluation. Full-service CROs such as Mediconomics support sponsors and manufacturers in classifying the project, preparing the notification documentation under Annex XV, Chapter II, and the operational conduct of such post-market investigations.
Frequently Asked Questions (FAQ)
Does an Article 74 investigation require regulatory authorisation?
No. What is required is notification to the Member States concerned at least 30 days before the start via the electronic system under Article 73. National requirements, for example regarding the involvement of an ethics committee, may also apply.
When is an additional procedure considered burdensome?
The decisive factor is the comparison with normal use of the product. Invasive interventions, additional imaging involving radiation or contrast agent exposure, and extensive additional appointments are generally considered burdensome, whereas purely questionnaire-based data collection or registry analyses are not.
Does Article 74 also apply to legacy devices during the transition period?
The MDR procedural rules for clinical investigations have applied since the date of application regardless of which regulatory framework the product’s certificate was issued under; what matters is that the product bears a valid CE marking and the investigation is conducted within the intended purpose.
Regulatory References
- Regulation (EU) 2017/745, Article 74 – Clinical investigations relating to devices bearing the CE marking
- Regulation (EU) 2017/745, Articles 62, 73, 75, 76, 77 and Article 80(5)
- Regulation (EU) 2017/745, Annex XV, Chapter II – Documentation to be submitted with the application for authorisation of a clinical investigation
- MDCG 2021-6 rev.1 – Questions and Answers regarding clinical investigation
- ISO 14155 – Clinical investigation of medical devices for human subjects
