Clinical Evaluation of Medical Devices: From Planning to Documentation!

Clinical evaluation is the key element in demonstrating the safety and performance of medical devices. Therefore, it is crucial for medical device manufacturers to have a deep understanding of the clinical evaluation process and allocate appropriate resources to ensure that their products meet the rigorous safety and performance standards. But what exactly are clinical evaluations? What purpose do they serve, and what legal requirements and regulatory hurdles are they subject to? The answers to these questions can be found in this second article of our series "Clinical Development of Medical Devices".

Clinical evaluations are the centerpiece of any Technical Documentation, as they comprehensively demonstrate safety and performance requirements. Recently, as we detailed in our previous article, the requirements have been tightened due to numerous scandals and warning letters. The aim is to make the safety and performance of medical devices more stringent and to monitor them more effectively. However, this advancement also means that medical device manufacturers need to invest more time, effort, and resources into planning, collecting, and evaluating clinical data.

For appropriate planning and comprehensive documentation of the clinical evaluation, a carefully developed Clinical Evaluation Plan (CEP) as well as a detailed Clinical Evaluation Report (CER) are of essential importance. These two documents are required for all device classifications (Class I to III), both for newly developed devices and for legacy devices already established on the market.

Why are clinical evaluations necessary?

As part of the conformity assessment of any medical device, compliance with relevant general safety and performance requirements is required. This includes the clinical evaluation as a central element (Article 5(3), MDR).

The purpose of the clinical evaluation is to confirm compliance with the relevant general safety and performance requirements when used as intended based on clinical data. This process also involves the evaluation of undesirable side-effects and of the acceptability of the benefit-risk ratio (Article 61, MDR).

The quantity and quality of clinical data must be sufficient, and the conclusions derived must be scientifically sound. The accurate and proper presentation, both in terms of content and form, is not trivial and can be developed using various guidelines. Experience and expert knowledge shorten the development time and increase the likelihood of a successful conformity assessment by a Notified Body.

What does the term "clinical data" mean?

Clinical data are information about the safety or performance of a product that is obtained during the application of the product. They can come from various sources, including:

• Clinical investigation(s) of the device concerned: These are systematic investigations involving trial subjects;
• Clinical investigation(s) or other studies reported in scientific literature, of a device for which equivalence to the device in question can be demonstrated: These are studies that examine a similar product and provide findings that can be applied to the product in question;
• Reports published in peer reviewed scientific literature on other clinical experience of either with the device in question or a device for which equivalence to the device in question can be demonstrated: These reports are based on clinical experience and are peer-reviewed to ensure the quality and accuracy of the information;
• Clinically relevant information coming from post-marketing surveillance, in particular post-market clinical follow-up: These are data collected after the product has entered the market to further monitor the safety and performance of the product.

Taken together, these various sources provide the data that can be used to evaluate the safety and performance of a product. Additionally, preclinical data can also be utilized, providing insights into safety aspects and potential performance of the product. The utilization and analysis of these data are crucial for obtaining the CE marking and monitoring of the respective medical device.

The respective clinical data for a medical device are collected, analyzed, evaluated, and documented during the clinical evaluation process in the CER, which plays an important role as part of the Technical Documentation in the certification of medical devices. The documentation undergoes a thorough review by the Notified Body to ensure that the clinical data support the safety and performance of the device in question.

The CEP describes the methodology and plan for collecting clinical data, while the CER is an assessment of the overall clinical evidence. Both documents build upon each other and contribute to the Notified Body´s informed decision on conformity with the MDR.

What information must a Clinical Evaluation Plan (CEP) provide?

The manufacturer has the following responsibilities related to the ongoing conduct and documentation of the clinical evaluation:

The CEP is a strategic document that defines the framework for conducting the clinical evaluation. It defines the methodology that will be used to collect and evaluate the clinical data. In this context, the manufacturer has the following responsibilities:

• Defining the scope and approach for the clinical evaluation: This includes determination of the general safety and performance requirements that must be supported with relevant clinical data;
• Creating a product description with clear information on the intended purpose and intended target groups, including clear indications and contraindications;
• Providing a detailed description of the intended clinical benefits, including specific parameters for clinical outcomes (clinical outcome parameters), both qualitative and quantitative - if possible;
• Specification of the regulatory methods used for assessing the clinical safety, taking into account the determination of residual risks and side effects;
• Defining benchmark parameters derived from the current state-of-the-art;
• Establishing how questions regarding the benefit-risk ratio will be addressed;
• Preparation of a clinical development plan.

Thus, the framework for the successive evaluation is established, which will be documented in the CER.

What information must a Clinical Evaluation Report (CER) provide?

The results of the clinical evaluation and the underlying clinical evidence on the safety and performance of the medical device are documented in a comprehensive evaluation report, which is used to support the conformity of the respective medical device. Both the clinical evidence and the non-clinical data generated by non-clinical test methods, along with other relevant documents, serve to demonstrate compliance of the product with the general safety and performance requirements.

What are the consequences if it turns out that there are not enough clinical data when preparing the Clinical Evaluation Report?

If it is found during the preparation of the CER that there are insufficient clinical data available, this can have various consequences:

• Adjustment of intended purpose: If insufficient clinical data are available to support the existing intended purpose of the medical device, it may be necessary to adjust the intended purpose. This could mean that the intended purpose needs to be restricted or that further clinical data needs to be collected to support the desired intended purpose;
• Adjustment of the literature search: If the existing literature is insufficient to meet the clinical data requirements, alternative literature search strategies may need to be employed. This could require an expanded search for case studies, reports on similar products, or similar medical indications;
• Filling the gaps through PMCF activities: PMCF (Post-Market Clinical Follow-Up) refers to the continuous monitoring of a medical device after it has been placed on the market to gather further clinical data and assess performance and safety of the device. If there is a lack of sufficient clinical data, PMCF activities can be planned and conducted to collect additional data and fill the existing gaps;
• Conduction of clinical investigations: If existing clinical data are insufficient, further clinical investigations may be necessary to generate additional data. Clinical investigations are controlled studies designed to answer specific questions about the safety and performance of a medical device. They require careful planning, execution, and reporting in accordance with regulatory requirements.

If it becomes apparent during the clinical evaluation that insufficient data are available, adequate measures should be taken to obtain the necessary information and fill the gaps.

TentaConsult - your reliable partner for the preparation of Clinical Evaluation Plans (CEPs) and Clinical Evaluation Reports (CERs)!

Creating a CEP and CER can undoubtedly be a challenging task. It is of utmost importance to invest in a thorough clinical evaluation process to ensure efficient market entry and maintain marketability after launch of the product.

As your competent partner and expert, we at TentaConsult Pharma & Med GmbH are at your side. Our goal is to support you in the preparation of the CEP and the CER and to accompany you throughout the entire clinical evaluation process. Our experienced team will work closely with you to create customized and accurate clinical evaluations that meet legal and regulatory requirements.

Feel free to contact us for more information and assistance! Our dedicated team looks forward to helping you create your CEP and CER and guiding you through every step of the clinical evaluation process.