Clinical trial of medical devices

CLINICAL AFFAIRS under MDR

Clinical trial of medical devices

If insufficient clinical data are available for the clinical evaluation of a medical device, own clinical data must be collected in the context of a clinical trial of the medical device in question.

DIN EN ISO 14155 “Clinical investigations of medical devices for human subjects – Good clinical practice” defines a clinical investigation as a “systematic test on one or more test subjects which is carried out to evaluate the clinical performance, medical efficacy or safety of a medical device”. Thus, the sole purpose of a clinical trial is to obtain proprietary clinical data regarding the safety and/or performance of a medical device.

Clinical trials

The term "clinical trial"

According to DIN EN ISO 14155, the terms “clinical trial”, and “clinical study” are synonymous with the term “clinical examination”. In practice, however, the term “clinical trials” is used for medicinal products, while the term “clinical tests” is used for medical devices.

Prior to the introduction of the term “other clinical trials” in the MDR (Article 82), the term “clinical trial” was also used for experimental trials and basic research to answer scientific and other defined medical questions, including medical devices. According to Article 82 of the MDR, these trials, i.e., all clinical trials of a medical device that are not planned and conducted as part of the clinical development plan, from the initial feasibility study to confirmatory clinical trials to post-market surveillance studies, are included under the term “other clinical trials.”

According to the Medizinprodukterecht-Durchführungsgesetz (MPDG), which replaced the Medizinproduktegesetz (MPG), it is an “other clinical trial” if the clinical trial:

Accordingly, manufacturers of medical devices should only distinguish between “clinical trials” and “other clinical trials” and use the term “clinical trials” only when investigation of medicinal products is meant.

Regulatory requirements for a clinical trial

According to the MDR, clinical trials should be conducted in accordance with well-established international guidelines, such as the international standard ISO 14155 “Clinical investigation of medical devices in humans – Good clinical practice”. The ethical orientation should be based on the principles of the latest version of the “Declaration of Helsinki” of the World Medical Association. This sets out basic ethical requirements in relation to the planning, conduct and assessment of risks and burdens on study participants of clinical trials, which may only be initiated if the expected benefits justify the risks.

The general requirements for clinical trials conducted to demonstrate compliance of devices are described in Article 62 of the MDR. In addition, the provisions of Articles 63 through 80, the acts adopted pursuant to Article 81, and Annex XV “Clinical Trials” count.

“Clinical trials” and “other clinical trials” require the approval of an ethics committee established under national law and are thus subject to authorization. The primary concern of clinical trials is the protection of the subjects participating in the trial. Risks associated with the medical device must be assessed prior to the planning and conduct of a clinical trial in accordance with DIN EN ISO 14971 (Annex H) “Medical devices – Application of risk management to medical devices”. Obtained clinical data must be scientifically sound, reliable and solid.

In addition to the MDR, the Ordinance on Clinical Testing of Medical Devices (MPKPV), the Medical Safety Plan Ordinance (MPSV), the Medical Devices Act (§ 20 – § 23 MPG) and the new Medical Devices Law Implementation Act (MPDG) form the regulatory requirements for clinical trials on a national level.

In addition, the following MEDDEV guidelines related to clinical trials should be considered:

Purpose of the Clinical Trial

Clinical investigations on medical devices serve one or more of the following purposes according to Article 62 of the MDR:

To establish and verify that a device is designed, manufactured and packaged to be suitable, under normal conditions of use, for one or more of the specific purposes listed in Article 2(1) and to perform as intended by its manufacturer
To establish and verify the clinical benefits of a device as specified by its manufacturer
To establish and verify the clinical safety of the device and to determine any undesirable side effects of the device that may occur under normal conditions of use and to assess whether these pose acceptable risks compared to the benefits provided by the device

When is a clinical trial generally always required?

Important role in the conduct of clinical trials

Key decision makers in clinical trials include the sponsor, investigator, and monitor.

The sponsor is a natural or legal person who assumes responsibility, organization and financing of a clinical trial. If problems occur during a clinical trial, the sponsor decides with the investigator on the necessary measures and informs the competent authority. Any necessary training of staff involved in the clinical trial is verified, organized and documented by the sponsor.

The investigator is a person responsible for conducting the human clinical trial at a trial site. This person must have sufficient qualifications and experience in patient care. For example, the investigator certifies that, to his knowledge, subjects have not previously expressed any objection to participation in the clinical trial. He or she ensures that the clinical trial is conducted in accordance with the clinical trial protocol.

All clinical trial data shall be recorded, processed, handled and stored by the sponsor or investigator in such a way that it can be correctly transmitted, interpreted and verified.

The monitor is a person independent of the investigational site who is responsible for monitoring and reporting on the progress of the human clinical trial of a medical device for quality assurance purposes. He ensures that the clinical trial is conducted in accordance with the clinical trial protocol, good clinical practice and regulations.

The following aspects, among others, are important for the conduct of the clinical trial:

Manufacturers must submit an online application to conduct clinical trials and await their approval. The application is submitted by the sponsor via the central medical device information system of the German Institute of Medical Documentation and Information (DIMDI). According § 20 Abs. 1 of the German Medical Devices Act (MPG), clinical trials are subject to approval by the competent higher federal authority (BoB), in Germany the Federal Institute for Drugs and Medical Devices (BfArM), and to the approving assessment by the competent Ethics Committee (EK). The BfArM and the Ethics Committee review the application. The clinical trial may only be started once the approval has been granted
Manufacturers are obliged to prepare a clinical investigation plan (CIP) in accordance with DIN EN ISO 14155:2020, which corresponds to the state of the art in science and technology (with justification, objectives, design and planned analyses, methodology, monitoring, execution and reporting of the clinical trial). Clinical trials must be conducted in accordance with this clinical investigation plan.
Manufacturers must prove that the medical devices meet the basic requirements according to § 7 MPG, which are not investigated in the context of the clinical trial and that with regard to these points all precautionary measures have been taken to protect the health and safety of the subjects, the users and third parties
There must be insurance coverage for the subjects
Manufacturers are obliged to register, evaluate and report adverse events (to the competent higher federal authority, in the case of medical devices: Federal Institute for Drugs and Medical Devices (BfARM))

Clinical Investigator's Brochure (IB)
Information and consent forms for test persons
Contact details of manufacturers and investigators
Inspector information
Monitoring-Plan
Description of the medical device, medical application/procedure
Preclinical evaluation including the underlying scientific evidence
Proof of biological safety testing
Risk analysis and risk assessment
Follow-up and medical care plan for subject risk analysis and risk assessment
Final clinical investigation report (Clinical Investigation Report) according to MDR Annex XV, Chapter III. The Clinical Investigation Report contains a critical evaluation of all data collected, including all negative results

The documents to be submitted for the clinical trial authorization application are detailed in Annex XV, Chapter II of the MDR.

In accordance with Article 70 of the MDR, the application for approval of a clinical trial will in future be made by the sponsor via the European database for medical devices “EUDAMED”. This electronic system, which operates at Union level, serves among other things to report and record all clinical trials in a publicly accessible database and to simplify the application procedure for clinical trials at international level. Currently, in accordance with § 33 of the Medical Devices Act, the Medical Devices Information System Team at BfArM provides the necessary data from the national medical devices information system for the European database. Via an XML upload, the data are transferred weekly from the national databases to EUDAMED. Due to the delayed introduction of EUDAMED (currently planned introduction 2022), only national authorities can and must currently use EUDAMED. Currently, the national registration obligations for clinical trials at DIMDI (German Institute of Medical Documentation and Information) apply.

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clinical data under MDR

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Clinical trial of medical devices