Introduction: The Role of Clinical Evidence in Medical Device Compliance

In the European Union, gathering clinical evidence for medical devices is essential to regulatory compliance, particularly under the Medical Device Regulation (MDR. Clinical evidence helps demonstrate that a device is safe, performs as intended, and provides measurable clinical benefits. This article delves into the core requirements, guidance documents, and processes involved in gathering clinical evidence for medical devices, helping manufacturers navigate compliance while ensuring patient safety and device efficacy.

Overview of EU Regulations: MDR Explained

The regulatory environment in the EU is structured primarily around one main regulation for medical devices:

• Medical Device Regulation (MDR): This covers the majority of general medical devices, establishing stringent requirements for safety, quality, and performance to protect patient health.

MDR  aims to protect patients and healthcare providers by ensuring that all medical devices, whether diagnostic or therapeutic, meet strict safety and performance criteria before entering the market.

Key Standards and Guidance Documents for Compliance

A robust set of standards and guidance documents supports MDR compliance, helping manufacturers align their processes with regulatory requirements:

• ISO 14155: This international standard lays out good clinical practices for medical device trials, similar to Good Clinical Practice (GCP) in pharmaceuticals. It is particularly relevant for high-risk devices and ensures that clinical investigations adhere to ethical and scientific standards.
• MEDDEV 2.7.1: Originally intended for older EU directives, this guidance document remains highly applicable to MDR requirements for conducting clinical evaluations.

These standards and guidance documents are critical in designing, implementing, and documenting clinical investigations that meet EU requirements.

The European Commission, in addition to ISO standards, provides Medical Device Coordination Group (MDCG) documents. These include guidelines for clinical evaluation and investigation, which aid manufacturers by clarifying EU requirements for demonstrating safety, performance, and clinical benefits.

Clinical Evaluation, Investigation, and Evidence Requirements

Understanding the distinctions among clinical evaluation, clinical investigation, and clinical evidence is crucial for compliance.

Clinical Evaluation

A clinical evaluation is a systematic, documented assessment that manufacturers conduct to verify a device’s safety and performance. Clinical evaluations use available clinical data to confirm that a device meets its intended purpose without compromising patient safety. Evaluations include:

• Reviewing literature relevant to the device.
• Analysing post-market surveillance data, especially if the device is already available in other markets.
• Assessing data from equivalent devices, if applicable, to support the claims of the device being evaluated.

Clinical Investigation

A clinical investigation is a study involving human participants to generate specific clinical data. It is generally required for higher-risk devices, such as Class III and implantable devices, where the available data does not sufficiently address safety and performance requirements. Investigations must comply with ISO 14155 standards to ensure ethical and reliable results. This standard details practices for study design, data integrity, and participant safety, which are essential for generating valid clinical data for high-risk devices.

Clinical Evidence

Clinical evidence is the cumulative data that supports a device’s intended use and claims. This evidence base encompasses all information collected through evaluations and investigations, including:

• Clinical outcomes data.
• Safety data demonstrating that the device does not pose unacceptable risks.
• Performance data proving that the device performs as claimed and delivers measurable clinical benefits.

Differentiating Clinical Investigations and Evaluations

While clinical evaluations and clinical investigations are closely related, they serve distinct purposes and differ in data sources and methods:

• Clinical Evaluation: Uses available data sources like literature, post-market data, and, in some cases, equivalent device data. Evaluations are essential for all devices, as they confirm that the device meets basic safety and performance criteria.
• Clinical Investigation: Generates new data from clinical studies involving human subjects. Investigations are often necessary for high-risk devices where pre-existing data is insufficient.

Manufacturers may use equivalent device data in some cases, provided the device under evaluation shares similar technical, biological, and clinical characteristics with the equivalent device. This approach can expedite compliance but must be supported by detailed documentation proving the relevance of the equivalent data.

Defining Clinical Benefit and Performance Claims

When submitting evidence for compliance, manufacturers must clarify and justify the clinical benefit and performance outcomes claimed for their devices:

• Performance Claims: Define the technical functions of the device, such as how efficiently or accurately it achieves its intended purpose.
• Clinical Benefit: Represents the positive impact of the device on patient outcomes, such as reducing the severity of symptoms or improving quality of life.

For example, in the case of a defibrillator, performance might be defined by the device’s ability to deliver a shock within a specific timeframe, while the clinical benefit would be its effectiveness in restoring normal heart rhythm and potentially saving lives.

Documenting and Submitting Clinical Data for CE Marking

Manufacturers must submit a range of documents to apply for CE marking, which certifies that the device complies with EU standards:

• Clinical Evaluation Report (CER): This report summarises the findings of the clinical evaluation, presenting the evidence that the device is safe and performs as intended.
• Risk Management File: This document, aligned with ISO 14971, outlines all identified device risks, their likelihood, and mitigation strategies. It should include clinical risks identified through evaluations or investigations.
• Post-Market Clinical Follow-Up (PMCF) Plan: A plan for ongoing monitoring once the device is in use, ensuring that it continues to perform safely and effectively.

The documentation required for CE marking can vary depending on the device’s risk class. High-risk devices typically require more rigorous documentation, including a CER that addresses all identified clinical risks and substantiates safety and performance claims.

Special Considerations for Software and AI in Medical Devices

Devices with embedded software or artificial intelligence (AI) require additional considerations under MDR. AI-driven functions—such as diagnostic software that interprets medical images—are classified as medical devices if they assist in patient diagnosis or treatment.

Manufacturers of AI-enabled devices must ensure that:

• Reliability and Repeatability: AI systems should provide consistent, reliable results in clinical settings.
• Data Quality: Evidence must demonstrate that the AI’s output is accurate, supporting the device’s intended purpose.

The European Commission’s guidelines for AI and software in medical devices provide additional compliance requirements, especially as AI in healthcare continues to evolve.

Best Practices for Clinical Data Collection and Submission

To navigate compliance efficiently, manufacturers should adopt a structured approach to gathering and presenting clinical data:

• Follow Relevant ISO Standards: Using ISO 14155 and 20916 standards as guidance ensures that data collection is both ethical and scientifically sound.
• Leverage MDCG Guidance: MDCG documents clarify expectations for clinical evaluation and evidence, ensuring that submissions meet notified body standards.
• Engage Notified Bodies Early: Discussing compliance and documentation requirements with notified bodies early in the process can prevent delays and minimise rework.

Clear, organised documentation and a proactive approach to clinical data collection streamline the compliance process, reducing regulatory hurdles and accelerating time to market.

Conclusion: Ensuring Compliance and Patient Safety in EU Markets

Gathering clinical evidence for medical devices involves understanding MDR requirements, following ISO standards, and structuring data to support regulatory submissions. By focusing on the quality of clinical evidence, manufacturers can ensure their devices meet EU standards, fostering trust with healthcare providers and contributing to patient safety across the EU.

Written by Educo Life Sciences Expert, Janette Benaddi

Janette Benaddi is a business mentor, international speaker/trainer and expert consultant to the medical device industry. Janette has over 25 years’ experience of managing pre and post market clinical studies in both devices and pharmaceuticals. Throughout her career Janette has worked with several multinational organizations in various clinical, regulatory and marketing roles. In addition, she set up a very successful medical device CRO company in the late nineties which she later successfully sold to another large multinational organization in 2013. She has extensive experience of conducting clinical studies with medical device products as well as regulatory expertise for CE marking of devices. Specifically, she has been involved in writing and reviewing hundreds of Clinical investigations/evaluations for the medical device industry, she has also provided training to Notified bodies on medical device studies as well as other medical companies. She is highly regarded as a medical device trainer with an exceptional ability to share her vast knowledge and expertise in an engaging manner.

This article was written using materials from the course, Gathering Clinical Evidence for Medical Devices.