In our first blog post after the summer break, we're introducing the new MDCG documents that specifically address clinical trials of medical devices. In this post, we'll present both documents and discuss the points that may be relevant for sponsors and, consequently, manufacturers.
Abbreviations
CE Marking on a product to signify that it meets the legal requirements to be sold on the extended Single Market in the European Economic Area (EEA).
CIP Clinical investigation plan
DMIDS German Medical Device Information and Database System
EUDAMED European database on medical devices
GSLA Basic Safety and Performance Requirements
IVDR Regulation (EU) 2017/746 of the European Parliament and of the Council on in vitro diagnostic medical devices
MDCG Medical Device Coordination Group
MDR Medical Device Regulation; EU Regulation 2017/745
MPI Medical Device Information System
MS Member State
NCA National Competent Authority
PMCF Post-market clinical follow-up
REC Research ethics committee
Underlying regulations
EU Regulation 2017/745 (MDR)
MDCG 2021-6
MDCG 2021-8
1 Introduction
The Medical Device Coordination Group (MDCG) regularly and continuously publishes guidance documents on the MDR. This is done in accordance with Article 105 of the MDR and Article 99 of the IVDR. The documents are prepared in cooperation with interested parties represented in the various groups and are presented in the following format: "MDCG Year-Number-Revision".
The MDCG is composed of representatives from all Member States, and is chaired by a representative of the European Commission. These documents are not documents of the European Commission and cannot be considered the official position of the European Commission. All views expressed in this document are not legally binding, and only the Court of Justice of the European Union can provide a binding interpretation of EU law.
They merely represent a common understanding of how the MDR and the IVDR should be applied in practice to ensure effective and harmonized implementation of the legislation.
This article deals with the two newly published MDCG documents 2021-6 and 2021-8.
MDCG 2021-6, is aimed at sponsors of clinical investigations of medical devices conducted within the scope of Regulation (EU) 2017/745 (MDR). It addresses questions and answers and may be supplemented with further questions and answers in due course.
the document MDCG 2021-8 “Clinical investigation application/notification documents” addresses the documents to be submitted when applying for a clinical investigation.
2. New MDCG documents
2.1 MDCG 2021-6
This MDCG document, published last April, contains a total of 28 general questions and related answers:
Firstly, the differences between the MDR and the previous Directive 93/42/EEC are discussed:
What are the general differences and improvements related to clinical investigations under the new Regulation (EU) 2017/745 (MDR) as compared to the Directives 93/42/EEC and 90/385/EEC?
Basically, there are none, except that the MDR represents a different, more binding set of rules, which is intended to ensure a more uniform and predictable feasibility of clinical trials.
Besides the definition of the clinical trial taken from the MDR (question 2), the third question is again interesting:
What is the difference between the performance, clinical performance and clinical benefit?
According to the MDR, the performance (definition see Article 2(22) of the MDR) of a product is its ability to fulfill its intended purpose as specified by the manufacturer. In a broader sense, the clinical performance (definition see Article 2(52) of the MDR) of a medical device is its ability to fulfill its intended purpose and thereby, when used as intended, to provide a clinical benefit (definition see Article 2(53) of the MDR). Clinical benefit is the positive effect of a product on a person's health, expressed in the form of a meaningful, measurable, patient-relevant clinical outcome (including diagnosis-related outcomes) or a positive effect on patient management or public health.
Fig. 1 Definition of performance, clinical performance and clinical benefit.
Until now, a precise distinction has never been made between performance (for fulfilling the intended purpose) and clinical performance (performance to provide clinical benefit, i.e., the clinical aspects of the performance).
This is important, not only in relation to clinical trials when choosing primary and secondary endpoints, but also when defining the claims regarding clinical performance within the framework of clinical evaluation.
The ninth question covers the topic of “additional burdensome investigations” and defines these in accordance with Article 74.
"Additional procedures that constitute a burden can encompass a wide variety of interventions, including those that may cause pain, discomfort, anxiety, potential risks or complications/side effects, disruption of life and personal activities, or other unpleasant experiences. It is usually determined from the perspective of the person experiencing the burden.".
Other invasive procedures include penetration into the body interior through the body surface, including through the mucous membranes of body orifices, or penetration into a body cavity through a body orifice
This includes, for example, blood tests or biopsies that are additionally performed as part of the clinical trial and are not part of routine clinical practice.
However, there is still uncertainty here, and it is recommended to contact the ethics committee and the relevant authority within the framework of the respective clinical trial in order to make the right decision regarding the application in case of any disputed questions concerning the additional burden.
Many questions arise regarding the correct regulatory pathway that must be followed for a clinical investigation in the specific context of a medical device. This concerns Articles 62, 74, and 82 of the MDR. We are happy to provide individual consultations on this topic as part of our free initial consultation .
Questions 15 through 20 address changes to the clinical trial protocol (amendments), and questions 21 through 28 deal with deadlines and transition periods.
This MDCG document is certainly suitable as a general overview for briefly addressing fundamental questions. However, detailed instructions or explanations are not provided and must be clarified during a consultation regarding the specific case.
2.2 MDCG 2021-8
Except in the case of a PMCF clinical investigation not covered by Article 74 of the MDR, an application must be submitted via the electronic system referred to in Article 73 of the MDR, containing the documents referred to in Annex XV Chapter II of the MDR.
Since the European database for medical devices (EUDAMED) does not yet exist, the MDCG has now created a series of documents for the application/notification of clinical trials in order to support the procedures for clinical trials under the MDR.
Attention: In Germany, clinical trials are applied for via the medical device information system, now the German Medical Device Information and Database System ( DMIDS ), at BfArM (formerly DIMDI ), which already contains the templates listed in the MDCG document as queries.
These documents include:
- Clinical trial - Application/notification form under the MDR
- Addendum to the application/notification form for clinical trials for:
- Additional test product(s) (Section 3)
- Additional comparator(s) (Section 4)
- Additional testing facility(ies) (Section 5)
- Supporting documents for the clinical trial - Appendix of documents to be attached
- Checklist of general safety and performance requirements, standards, common specifications and scientific recommendations
Where possible, the application/notification form for the clinical trial contains the same data fields as the EUDAMED system, which is still under development.
The templates are listed in the MDCG document and can be accessed via the following links:
Clinical investigation – application form under Medical Device Regulation
Additional investigational device(s) (section 3)
Additional comparator device(s) (section 4)
Additional investigation site(s) (section 5)
Furthermore, this document also contains a link to a list of the required documents, which is based on ISO 14155:2020.
Finally, you receive a template for the checklist of basic safety and performance requirements (GSLA), standards, common specifications, etc., which is based on the MDR checklist:
Fig. 2 List of standards, CS and scientific references, except those examined as part of the clinical trial
Fig. 3 Matrix for fulfilling the GSLA
Apart from the two Word templates, this MDCG document provides no new information for clinical trials conducted in Germany, as everything can be entered and applied for via the DMIDS.
3. What we can do for you
We function as a scientific research organization (CRO), independent of manufacturers. As such, we support you throughout your entire clinical trial project – from the initial idea to the evaluation and the clinical trial report.
4. How we can help you
At medXteam we clarify whether and if so which clinical trial needs to be carried out under what conditions and according to what requirements during the pre-study phase: In 3 steps we determine the correct and cost-effective strategy in relation to the clinical trial required in your case Data collection.
Do you already have some initial questions?
You can get a free initial consultation here: free initial consultation