The Medical Device Coordination Group (MDCG), an advisory body of the European Commission, the regulating authority in the sphere of medical devices, has published questions & answers on clinical investigation.
Please note that the document does not represent the official position of the regulating authority and should be used only for general references.
According to the guidance, a clinical investigation stands for any systematic investigation involving one or more human subjects undertaken to assess the safety or performance of a device.
Regulatory Background
By virtue of the present Q&A document, the MDCG provides additional recommendations to be considered by medical device manufacturers and other parties involved regarding clinical investigations carried out in accordance with the provisions of the Medical Devices Regulation 2017/745(MDR), which replaces the appropriate Directive.
First, the MDCG describes the differences between the regulatory requirements set forth under the MDR and Directives 93/42/EEC and 90/385/EEC replaced by the aforementioned Regulation.
According to the document, the legal nature of Directives and Regulations differs substantially. The Directives describe the recommended approach; each country is entitled to determine the particular way this should be achieved. In contrast, compliance with the provisions of Regulations is mandatory for all Member States. Hence, the regulatory requirements related to clinical investigations set forth by the Medical Devices Regulation should be applied identically in all countries irrespectively of the national legislation.
Moreover, the regulatory requirements prescribed by the MDR are much more detailed than the ones introduced by the Directive due to the fact that they incorporate ancillary provisions previously described in additional guidelines and recommendations.
At the same time, the MDCG emphasizes that in certain cases, the provisions of the national legislation related to clinical investigations should be applied.
Key Concepts Related to Clinical Investigations
The present MDCG guidance further provides definitions of the most important concepts used in the context of clinical investigations. These concepts include the following:
1. Performance of a medical device – its ability to achieve its intended purpose as stated by the manufacturer.
2. Clinical performance of a medical device – the ability of the device to achieve its intended purpose, thereby leading to a clinical benefit.
3. Clinical benefit – the positive impact of a device on the health of an individual, expressed in terms of a meaningful, measurable, patient-relevant clinical outcome(s), including outcome(s) related to diagnosis, or a positive impact on patient management or public health.
Regulatory Approach to be Applied
As stated in the MDR, any and all clinical investigations should be performed strictly in accordance with the applicable regulatory requirements set forth by the aforementioned Regulation. Clinical investigations are intended to evaluate the performance of a medical device, safety-related aspects, and also clinical benefits associated thereto, including its potential side effects.
Another important concept related to clinical investigations is a pilot clinical investigation, which is a special type of early-stage clinical investigation. During a pilot clinical investigation, a limited number of participants should be involved. Upon completion of a pilot clinical, the information collected could be used to further improve a medical device. For instance, such information could constitute a basis for changes to be implemented. At the same time, the information derived from a pilot clinical investigation is usually insufficient for the purpose of a general conformity assessment. Usually, a pilot clinical investigation is intended to collect preliminary data related to the safety and performance of a medical device. The document also refers to the international standard ISO 14155:2020, which contains additional details on the matter.
Apart from a pilot study, the Medical Devices Regulation describes other types of clinical investigations. The particular approach to be applied with regard to the clinical investigation should depend on the clinical development plan and also on the way the results of such an investigation are intended to be used. In the case of a general clinical investigation carried out in order to collect additional data necessary for conformity assessment, the provisions of the Regulation 2017/745 should be applied. In other cases, provisions of the relevant national legislation could be applied as well.
Pathways for Clinical Investigations
The particular pathway to be applied by the medical device manufacturer will also depend on the intended purpose of a medical device subject to review, as well as on the purpose of the clinical investigation itself. The MDCG describes the following cases:
1. If the medical device in question has already passed the appropriate conformity assessment, its further assessment should be carried out in the courts of a post-market clinical follow-up (PMCF) investigation. The scope of such clinical investigation should cover basic use cases for a medical device. The party interested in clinical investigation (the sponsor) shall duly notify the regulating authority 30 days in advance. Should the sponsor have reasonable doubts regarding the regulatory status of certain procedures taking place in the course of the clinical investigation, it should request additional clarification in advance.
2. If the aforementioned provision is not applicable, the relevant regulatory requirements set forth by the national legislation should be applied. In such a case, registration in a publicly available database of clinical investigations could take place.
3. Should the safety and performance of a medical device be outside the scope of clinical investigation, such investigation would not be covered by the MDR. Hence, the relevant provisions of national legislation should be applied.
As mentioned, the sponsor of a clinical study should, first of all, determine whether the medical device in question would be used within its intended purpose, indicated in such documents as:
- The EU declaration of conformity;
- The labeling supplied by the manufacturer;
- The CE conformity certificate;
- The clinical evaluation report.
Once the intended purpose of a medical device has been clearly identified, the sponsor shall determine whether it meets the purpose for which the device would be used in the course of planned clinical investigation. Such a determination should be based on the clinical investigation plan, which covers such aspects as the target population, the indications/contradictions, anatomical location where the device will be used, the duration of use, the planned procedures, and the planned users.
The MDCG additionally mentions that an investigational medical device could be used solely for the primary intended purpose indicated by its manufacturer.
Additional Aspects to be Considered
The present Q&A document also highlights some other important aspects to be taken into consideration by the medical device manufacturers and other parties involved. For instance, the MDCG emphasizes that if some of the procedures to be performed in the course of a planned clinical investigation are invasive or burdensome, special regulatory requirements should be applied, including the obligation of the sponsor to notify the regulating authority in advance as described above.
In summary, the Q&A document issued by the MDCG covers the main issues regarding clinical investigations and also outlines the regulatory requirements applied thereto. The document describes the approach to be applied by the sponsor when determining the particular pathway depending on the intended purpose of a clinical study or a medical device itself.
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Sources:
https://ec.europa.eu/health/sites/health/files/md_sector/docs/mdcg_2021-6_en.pdf
