Clinical investigations of medical devices - if they are necessary in the context of clinical evaluations

Clinical evaluation is the systematic and planned analysis and assessment of clinical data to demonstrate the safety and performance of a device, in accordance with Annex I of Regulation (EU) 2017/745 (MDR)‍. Manufacturers define the scope of the required clinical evidence and conduct clinical evaluations in accordance with Article 61 and Annex XIV Part A.

The importance of clinical investigations and clinical evaluations for medical devices under the MDR)

Central elements of Regulation (EU) 2017/745 on medical devices, the so-called Medical Device Regulation (MDR), are clinical evaluations and clinical investigations, which are of crucial importance for the authorisation and monitoring of medical devices. These can be found in Chapter IV in Articles Art. 61, 62 ff, Art. 74 and Art. 82.

Manufacturers of class III and certain class IIb devices may consult a panel of experts to review their clinical development strategy. Their comments are documented in the clinical evaluation report.

Clinical evaluations are based on a critical assessment of relevant scientific literature, a critical assessment of all available clinical investigations and consideration of other treatment options.

Clinical investigations are required for many implantable devices (such as stents or endoprostheses) and class III devices (highest risk class), unless the device has been designed by modification of a device already placed on the market by the same manufacturer, is similar to a device already placed on the market and this is confirmed by the notified body or the clinical evaluation of the device placed on the market is sufficient to show that the modified device fulfils the safety and performance requirements. In the plan for clinical follow-up after placing on the market, the notified body shall ensure that studies can demonstrate safety and performance.

Manufacturers of similar devices may be able to avoid clinical investigations if they have access to the original manufacturer's technical documentation and the original clinical evaluation is MDR-compliant. Clinical investigations are not required for devices that were lawfully placed on the market under previous directives or certain devices such as sutures. Proof of compliance with safety and performance requirements may exceptionally be based on non-clinical test methods if this is adequately justified.

Clinical investigations according to MDR, Art. 62 ff

Clinical investigations in accordance with Art. 62 are also conducted as part of a clinical evaluation, to establish or verify

• its suitability for a specific purpose or its performance,
• the clinical benefit claimed by the manufacturer, or
• safety, including undesirable side effects or risk-benefit analysis.

"Other clinical investigations"

This is to be distinguished from"clinical investigations after placing on the market" in accordance with Art. 74 for medical devices that are already CE marked and where additional, stressful or invasive procedures are planned for the participants. Special regulations apply here to protect the safety and rights of the participants. If the test assesses the CE-marked product for a purpose other than that originally intended, all relevant articles from 62 to 81 of the Regulation must be complied with.

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Other "other clinical investigations" according to Art. 82 have largely comparable requirements to clinical investigations according to Art. 62 and are carried out in accordance with this, if not for one of the purposes mentioned in Art. 62 (1).

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In Germany, in addition to Regulation (EU) 2017/745 (MDR), "other clinical investigations" are defined in §3 (4) of the Medical Devices Implementation Act(MPDG) and §47. Accordingly, an "other clinical investigation" of a medical device is an investigation that:

(a) is not part of a planned process for the development or monitoring of the device by the current or future manufacturer,

(b) is not conducted to demonstrate that the device complies with the requirements of Regulation (EU) 2017/745

c) is intended to answer scientific or other questions, and

(d) takes place outside a clinical development plan in accordance with Part A of Annex XIV to Regulation (EU) 2017/745.

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An "other clinical investigation" pursuant to Art. 82 (1) of Regulation (EU) 2017/745 and Section 1 may only be conducted in accordance with Section 47 MPDG if the following conditions are met:

1. Risk-benefit ratio: foreseeable risks and burdens must be acceptable in comparison to the expected benefit for the participants.
2. Minimisation of pain and discomfort: as little pain, discomfort and risk as possible for the participants. These must be defined in the trial plan and constantly monitored.
3. Medical care: A qualified doctor or dentist must be responsible for the medical care of the participants.
4. No undue influence: No undue incentives, such as financial benefits.
5. Suitable trial site: The trial centre (trial site) and its premises must be suitable for the trial.
6. Favourable vote by the responsible ethics committee.
7. Notification to the competent higher federal authority.

These 7 points above do not apply if the medical device already has CE marking, the test is carried out within the scope of the intended purpose and the participants are not subjected to any additional stressful or invasive procedures. However, doctors are obliged to seek consultation with an ethics committee in accordance with professional law (see Section 15 of the Model Code of Conduct for Doctors of the German Medical Association). In addition, the ethical principles for medical research on humans laid down in the Declaration of Helsinki of the World Medical Association apply. Section 47 (3) of the MPDG merely cancels the requirements of the preceding paragraphs 1 and 2, but not legal requirements arising from other legal provisions. Whether procedures are considered invasive or burdensome must be adequately justified to the ethics committee.

All clinical, post-marketing clinical investigations and "other clinical" investigations must be planned and conducted in such a way that the rights, safety, dignity and well-being of the participants are always paramount. The data obtained must be scientifically sound and reliable. This requires sufficient experience and expertise. Every clinical investigation is scrutinised both scientifically and ethically. An investigator in a clinical investigation is a professionally recognised person who is qualified to do so through their scientific knowledge and experience in patient care.

The new EU Medical Device Regulation (MDR) places clinical investigations and assessments at the centre of demonstrating the safety and performance of medical devices.

Clinical evaluations based on scientific literature and studies are mandatory for all risk classes. For implantable and Class III devices, additional clinical investigations are required in most cases. The MDR defines clear requirements for planning, conducting and monitoring these trials to ensure the highest quality standards. Only by demonstrating clinical safety and performance through robust evidence can medical devices receive marketing authorisation. Compliance with the MDR requirements for clinical investigations and evaluations is therefore essential for manufacturers.

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(Status: spring 2023)