The clinical investigation of a medical device is any systematic investigation involving one or more human subjects, undertaken to assess the safety or performance of a device. It should be noted that this definition includes the use of both non-CE marked and CE marked devices.
- clinical investigations conducted to demonstrate conformity of devices (for medical devices that do not bear the CE marking) – Article 62 of the MDR;
- clinical investigations regarding devices bearing the CE marking (investigation in the context of post-market clinical follow-up (PMCF investigation)) – Article 74 of the MDR;
- clinical investigations not performed pursuant to any of the purposes listed in Article 62(1) of the MDR (other clinical investigations) – Article 82 of the MDR;
- clinical investigations of medical devices without an intended medical purpose (Annex XVI to the MDR).
Further information on clinical research can be found on the European Commission’s webpage on Guidance – MDCG endorsed documents and other guidance under Clinical investigation and evaluation.
The European Commission also published a Q&A document regarding clinical investigations – Regulation (EU) 2017/745 – Questions & Answers regarding clinical investigations.
The sponsor of a clinical investigation must submit an application/notification to the EU Member State(s) in which the clinical investigation is to be conducted, accompanied by the documentation referred to in Chapter II of Annex XV to the MDR. The application/notification must be submitted by means of the electronic system referred to in Article 73 of the MDR. Below is described the procedure for notifying a clinical investigation to the Public Agency of the Republic of Slovenia for Medicinal Products and Medical Devices (JAZMP), which will be used until the Clinical investigations module is made available in the European Database on Medical Devices (EUDAMED).
Further instructions on the application of some of the provisions of the MDR at a time when EUDAMED is not yet available are provided in the guidance MDCG 2021-1 Rev.1. Until EUDAMED becomes fully functional, the EU-wide unique single identification number for the clinical investigation, which is used for all relevant communication related to that clinical investigation, is the CIV-ID. The CIV-ID is the identification number currently used for the EUDAMED 2 system and supports Council Directive 93/42/EEC on medical devices (MDD) and Council Directive 90/385/EEC on active implantable medical devices (AIMDD).
At the time when EUDAMED is not yet available, applications for clinical investigations in electronic form are submitted by sending them electronically to the authority’s information system or to the unified information system for accepting applications, service and notification, which JAZMP does not currently have, therefore it is necessary to deliver the personally signed application in person at the JAZMP main office or to send it physically by post, in accordance with the second paragraph of Article 63 of the General Administrative Procedure Act (GAP).
The MDR lays down rules regarding the content of the application, the assessments conducted by EU Member States and ethics committees, and the conduct and reporting obligations of sponsors. Clinical investigations of medical devices may start upon the obtainment of a favourable opinion from the national competent authority for medical devices (the JAZMP) and from the national ethics committee (the Medical Ethics Committee of the Republic of Slovenia – KME RS). For further information on the KME RS, please visit this website.
The principles of clinical investigations of medical devices are set out in the international standard EN ISO 14155:2020 Clinical investigation of medical devices for human subjects – Good clinical practice (ISO 14155:2020), which addresses good clinical practice for the design, conduct, recording and reporting of clinical investigations carried out in human subjects to assess the safety and performance of medical devices.
CLINICAL INVESTIGATION TYPES
ARTICLE 62 OF THE MDR – CLINICAL INVESTIGATIONS CONDUCTED TO DEMONSTRATE THE CONFORMITY OF DEVICES
- to establish and verify that, under normal conditions of use, a device is designed, manufactured and packaged in such a way that it is suitable for one or more of the specific purposes, and achieves the performance intended as specified by its manufacturer;
- to establish and verify the clinical benefits of a device;
- to establish and verify the clinical safety of the device and to determine any undesirable side-effects, under normal conditions of use of the device, and assess whether they constitute acceptable risks when weighed against the benefits to be achieved by the device.
Where a clinical investigation is to be conducted to assess, outside the scope of its intended purpose, a device which already bears the CE marking, such investigation shall be considered in the same way as a clinical investigation of a medical device not bearing the CE marking.
Prior to carrying out a clinical investigation in the Republic of Slovenia, sponsors of clinical investigations conducted for the above-mentioned purposes and for devices of all risk classes (Class I to Class III), must submit an application to the JAZMP. The requirements and relevant documentation for carrying out clinical investigations are detailed in Articles 62 to 81 of the MDR and in Annex XV thereto.
ARTICLE 74 OF THE MDR – CLINICAL INVESTIGATIONS REGARDING DEVICES BEARING THE CE MARKING
Where a device bearing the CE marking is used in a clinical investigation within the scope of its intended purpose, the sponsor must assess whether this investigation will also lead to submitting subjects to additional procedures that are considered invasive or burdensome. In this case, the sponsor must notify the JAZMP at least 30 days before the start of the investigation and include the documentation referred to in Article 74 of the MDR as part of the notification.
For these investigations, which are also carried out in accordance with Article 74 of the MDR, the consent of the KME RS must be obtained prior to starting the investigation.
ARTICLE 82 OF THE MDR – REQUIREMENTS REGARDING OTHER CLINICAL INVESTIGATIONS
When a clinical investigation is not conducted for any of the purposes listed in Article 62(1) of the MDR, the relevant provisions of Article 62 of the MDR must nevertheless be complied with, including the provisions with regard to the protection of the rights, safety, dignity and well-being of the subjects and the scientific and ethical integrity of the clinical investigation.
EUROPEAN LEGISLATION, GUIDANCE AND STANDARDS – CLINICAL INVESTIGATIONS UNDER THE MDR
- Uredba o medicinskih pripomočkih (EU) 2017/745 (MDR)
- MDCG 2020-5 Guidance on clinical evaluation – Equivalence
- MDCG 2020-6 Guidance on sufficient clinical evidence for legacy devices
- MDCG 2020-7 Guidance on post-market clinical follow up (PMCF) plan template
- MDCG 2020-8 Guidance on post-market clinical follow up (PMCF) evaluation report template
- MDCG 2020-10/1 Guidance on safety reporting in clinical investigations in Appendix: Clinical investigation summary safety report form
- MDCG 2020-13 Guidance on clinical evaluation assessment report
- MDCG 2019-9 Summary of safety and clinical performance
- MDCG 2021-6 Regulation (EU) 2017/745 – Questions and Answers regarding clinical investigation
- MDCG 2021-8 Clinical investigation application / notification documents
- MDCG 2021-1 Rev. 1 Guidance on harmonised administrative practices and alternative technical solutions until EUDAMED is fully functional
- MDCG 2021-28 Substantial modification of clinical investigation under Medical Device Regulation