Clinical trials of medical devices

Clinical trials of medical devices confirm that the products are designed and manufactured in accordance with legal requirements. Under the MDR (Medical Device Regulation), clinical trials are mandatory in Europe for high risk and innovative devices.

Ensuring compliance with safety and performance requirements is the primary responsibility of medical device manufacturers, as confirmed by the conformity assessment. Its purpose is to verify whether the operation of a medical device meets the design assumptions, does not pose a threat to the life and health of users, and the benefits of its use outweigh any potential risks. Possible adverse effects are also identified.

The clinical evaluation can be based on current scientific literature, evaluation of results from available clinical investigations, or independent research. For Class III medical devices and implants, clinical trials are generally required. Clinical trials of medical devices confirm that the products are designed and manufactured in accordance with legal requirements.

The participants in a clinical studies of a medical device include:

• Sponsor: responsible for initiating, managing, and financing the clinical trial.
• Participants: individuals taking part in the trial.
• Investigator: responsible for conducting the trial, possessing the necessary scientific knowledge and patient care experience.
• Qualified personnel.

Before initiating a trial, documentation must be prepared, and positive opinions from ethical committees and the President of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products (URPL) must be obtained. The trial is conducted according to an established protocol, with ongoing monitoring and documentation to ensure credible data and adequate participant protection.

Design of a Clinical Trial

Clinical trials of medical devices aim to confirm or refute manufacturers’ statements regarding the safety and efficacy of the device. These trials must be designed and conducted to yield scientifically valid, reliable, and credible data. The technical and functional properties of the device, as well as the expected results of its operation, must be considered in the trial design.

Feasibility

The trial should be conducted in a clinical environment reflecting normal usage conditions, with participants from the target group. Therefore, finding an appropriate research center is crucial.

We offer support in assessing the feasibility of a trial and selecting a research center. As part of this service, we assess the availability of the desired patient base, the characteristics of the center, its facilities, personnel, and the availability of experts. We also consider past collaboration regarding timeliness, reliable documentation, and compliance with legal and ethical principles. This allows us to determine whether a study in a particular center makes sense and can reduce the duration and costs of the study significantly.

Informed Consent of Participants

Clinical trials of medical devices must be designed to minimize participants’ exposure to pain, discomfort, or anxiety and ensure their safety, dignity, and well-being. The risk should be predictable and minimized. The risk threshold, along with the degree of burden, should be detailed in the study plan and continuously monitored during the trial.

Participants must have access to medical care during the trial and have the right to withdraw from the study at any time without consequences. The well-being of the participant is always prioritized over the interests of science or society. Therefore, participant involvement requires informed consent.

Before providing informed consent, participants should receive information about:

• Conditions of the study, its duration, and the participant’s role.
• Expected benefits and risks of the study, as well as potential adverse effects.
• Participant rights during the study.
• Alternative treatment methods if the participant decides to withdraw from the study.
• Compensation measures for potential health damage resulting from participation.
• How to access the study results.
• This information should be presented clearly, comprehensively, and understandably to the participant during a discussion with a qualified member of the research team. It is crucial to ensure that the participant understands the information before providing it in writing, allowing adequate time for decision-making. Coercion or promises of financial benefits for participation are unacceptable.

If a participant is unable to provide independent consent, and there are grounds for their inclusion in the study, consent is provided by their legal representative. Additional requirements apply to the participation of minors, pregnant or breastfeeding women in studies.

Informed consent is prepared in writing, dated, and signed by the person conducting the discussion.

Submission of the application for clinical trial of a medical device

The application for permission to conduct a clinical trial of a medical device should be preceded by obtaining a positive opinion from the ethical committee. The application includes the investigator’s brochure, the clinical trial plan, and a statement from the person responsible for production that the device complies with the requirements. Additionally, evidence of participant insurance coverage, documents for obtaining informed consent, and principles of confidentiality and personal data protection are presented.

Application Form

Mandatory information to be included in the application:

• Contact details of the study sponsor and the manufacturer of the medical device.
• Information about the tested device.
• Summary of the clinical trial plan.
• Confirmation that the investigator and the center can conduct the study.
• Anticipated start date and planned duration of the study.
• The application form template can be found on the website of the relevant ethical committee.

Investigator’s Brochure

The investigator’s brochure is a document containing detailed information about the tested device, both clinically and non-clinically, known before the start of the study:

• Description of the device, its classification, and intended use.
• Manufacturer’s instructions for installation, use, maintenance, cleaning, and storage.
• Information about the labeling and labels attached to the device.
• Preclinical assessment based on previous studies and experimental data.
• Existing clinical data from scientific literature, studies of equivalent products on the market, and their use, safety, and corrective actions taken.
• Summary of the risk-benefit analysis, expected adverse effects, and contraindications.
• Safety and performance requirements of the device.
• Detailed description of clinical procedures and diagnostic tests, including deviations from normal clinical practice.
• Clinical Trial Plan.

The clinical trial plan justifies the study objectives, defines endpoints, inclusion and exclusion criteria for participants, sample size with scientific justification, and study assumptions. The plan describes the entire project, outlines the study methodology, documentation procedures, and monitoring, and specifies the results analysis method. The plan should include:

• Study identification – number, sponsor and investigator data, funding description, study summary.
• Device designation and description.
• Risks and benefits to be analyzed.
• Description of the study’s significance.
• Objectives and hypotheses.
• Study design with evidence of its reliability and significance.
• Monitoring plan.
• Data management.
• Information on changes in the plan.
• Procedures in case of deviations.
• Information on who is responsible for controlling access to the device, further handling of the device after the study, and return of unused, defective, or expired devices.
• Declaration of compliance with ethical principles and good clinical practice.
• Description of the process of obtaining informed consent.
• Reporting adverse events and defects.
• Criteria and procedures for observing participants after the study, including those who did not complete the study.
• Principles for preparing a report and publishing results.
• List of device properties covered by the study.

Once the ethics committee has provided its opinion, the sponsor submits an application for permission to conduct a clinical trial to the President of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products (URPL), along with confirmation of payment for the permit.

The President of the Office issues or refuses to issue a permit through an administrative decision.

Clinical trials monitoring

It is the sponsor’s responsibility to present the clinical trial plan, and it is the investigator’s responsibility to ensure that the trial is conducted according to the approved plan.

The sponsor-investigator agreement should guarantee the timely reporting of adverse events and incidents. The sponsor must also provide evidence that the study is conducted in accordance with good clinical practice and establish a procedure for extraordinary situations.

The sponsor appoints an independent monitor unrelated to the research center to verify compliance with the study plan and regulations, confirm data credibility and reliability, and ensure the protection of participants’ rights, safety, and well-being. The monitor may be a person with the necessary knowledge who is familiar with the study protocol and has reviewed the documentation and knows the applicable procedures.

We provide access to experts from various therapeutic fields with the competence and tools to monitor the progress of clinical trials of medical devices effectively and independently. An experienced monitor ensures the completion of the study on time and the reduction of unnecessary costs.

Managing Data from a Clinical Trial

Proper management of data collected during a study is crucial for its results. Maintaining coherence during the collection, integration, and verification of clinical trial data allows for efficient reporting, monitoring of the study’s progress, and interpretation of its results. Regulations also require that measures used for data management ensure protection against unauthorized access, disclosure, alteration, or accidental loss. The method of data collection and management should be established during the planning stage of the study.

We offer support in data management in both traditional and electronic forms. Electronic data management systems, besides the convenience and easier organization of entered data, provide quick access to data from other research centers. Our specialists have experience working on various platforms, significantly simplifying, and speeding up data entry.

Importantly, the sponsor is also obliged to register notifications regarding adverse events deemed decisive for the assessment of study results, serious adverse events, and defects in the device that could lead to adverse events. These circumstances should be reported through the electronic system.

Execution of a Clinical Trial

After the completion of a clinical trial, the sponsor informs the President of the Office within 15 days. Within a year of the trial’s completion, the sponsor submits a report to the President of the Office, including:

• Basic information about the study.
• Author’s data and the date of report preparation.
• Study summary.
• Description of the tested device and its intended use.
• Summary of the clinical trial plan.
• Detailed description of study results with statistical analysis.
• Discussion of serious adverse events, adverse device effects, or defects and corrective actions taken.

The report should have a specified structure and contain the required content. Proper documentation of clinical trials not only requires an understanding of medical terminology and concepts related to the research area but also knowledge of legal and normative requirements. The process of preparing documentation involves statistical data analysis, clinical assessment, and the preparation of documents in the appropriate form.

The report on the clinical trial of medical devices also includes a summary prepared in a way understandable to laypeople, especially potential users of the medical device. The report of the clinical trial is a part of the clinical evaluation process and included in the technical documentation of the medical device.

If the study has been suspended or terminated earlier, the President of the Office should also be informed. If safety reasons were the cause, notification should be made within 24 hours. A report on the interrupted study should be submitted within 3 months.

All documents are made publicly available.

Are clinical trials for medical devices mandatory in Europe?

Clinical trials in Europe according to MDR are mandatory for high risk and innovative medical devices. However even class I devices should have clinical evidence, that demonstrate the safety and effectiveness for claims on the labelling. It depends on the type of clinical evidence we have already got. Clinical data should provide sufficient clinical evidence necessary to demonstrate conformity with the relevant GSPR (General Safety and Performance Requirements.

How to conduct clinical trials for medical devices in Europe?

To conduct a clinical trial for medical devices in Europe Manufacturer or Sponsor should define the regulatory pathway for the device. The purpose of clinical investigation should be established. e.g. to establish performance, clinical benefits, clinical safety and any undesirable side-effects. National provisions should be additionally checked to start the clinical trial in specific EU country.