The introduction of the European MDR Regulation marked a turning point for medical device manufacturers, placing the generation and collection of clinical evidence and data at the core of the regulatory process. By 2024, the MDR is no longer considered a “new regulation” but rather an established system requiring precise methodological approaches and targeted strategies tailored to the characteristics of different devices. At the AboutMedicalDevices conference, Eliana Russo, Head of Regulatory Affairs of Regulatory Unit at PRINEOS S.r.l., detailed the methodologies for conducting clinical investigations for MDR, as well as the organizational phases and specific activities for each stage.
Clinical Data Collection: Legacy Devices and New Devices
The methodology for collecting clinical data varies depending on the type of device:
- Legacy Devices (Devices Already on the Market)
Manufacturers must verify whether the available data are sufficient to demonstrate the safety and performance of the device:
- Sufficient Data: These are analysed and used to prepare the required documentation, including:
- Clinical Evaluation Plan (CEP)
- Clinical Evaluation Report (CER)
- Risk Analysis (RA)
- Post-Market Surveillance (PMS)
- Post-Market Clinical Follow-up (PMCF)
- Insufficient Data: New clinical evidence must be collected through a pre-market clinical investigation.
The best strategy for legacy devices is to utilize historical data when available. However, the MDR limits the principle of equivalence, which can only be applied if clinical, technical, and biological aspects are demonstrated to be equivalent. If any of these aspects are not met, equivalence cannot be used. Furthermore, contractual limitations exist, as the regulation requires a Class III manufacturer to have a signed agreement with a competitor to use their data—a challenging requirement to implement.
- Non-Legacy Devices
For new devices, the manufacturer must determine whether the principle of equivalence can be applied by analysing clinical data from equivalent devices produced by other manufacturers:
- Applicable Principle of Equivalence: Equivalent data are integrated into the required documentation.
- Non-Applicable Principle of Equivalence: New clinical data must be generated through a pre-market clinical investigation.
- Innovative Devices
For entirely new devices with no pre-existing clinical data, the only option is to conduct a pre-market clinical investigation to collect the necessary evidence.
Clinical Investigation for MDR: A Structured Process
When available clinical data are insufficient, clinical investigations become critical to demonstrate the safety and performance of the device. This process must be organized into three main phases:
- Planning: Define the objectives, methodologies, and timelines of the investigation.
- Execution: Conduct the clinical investigation according to established rules, ensuring accurate data collection.
- Analysis: Process the results to produce clinical evidence supporting regulatory compliance.
For each step, manufacturers must address key questions and perform specific activities to ensure the validity and effectiveness of the investigation.
Planning a Clinical Investigation: Key Questions and Organizational Phases
- What therapeutic level do we aim to achieve?
- What is the primary response variable?
- How should it be measured?
- Secondary endpoints?
- Clinical relevance threshold?
- Control group?
- Which subjects? How many subjects?
- Interim analyses?
- How many and which centres?
- Enrolment rate?
- Study duration?
- Rationale and study objectives: Literature research and evaluation.
- KOL involvement: Scientific advice.
- Study type: Experimental design, endpoints.
- Target population: Interim analysis, sample size, type and number of centres.
- Study procedures and duration: Flowchart development.
- Analysis plan: Target population analysis.
- Ethical submission and approval.
Conducting the Clinical Investigation: Key Questions and Organizational Phases
- Kick-off meeting?
- Subject screening?
- Instructions for treatment/intervention?
- Monitoring plan?
- Data adequacy and accuracy?
- Medical monitoring?
- Clarification requests?
- Protocol deviations?
- Adherence to study timelines and intervention?
- AE/SAE reporting?
- Centre selection
- Subject identification.
- Informed consent.
- Treatment/intervention.
- Monitoring.
- Documentation and centre management.
- Follow-up.
- Data management: Data cleaning and coding.
- Medical review.
Analysing the Clinical Investigation: Key Questions and Organizational Phases
- CRF/e-CRF?
- Sufficient number of completed subjects?
- Consistent and coherent data?
- Timely database closure?
- Appropriate use of statistical methods?
- Clinical relevance of results?
- Confirmation of result interpretation accuracy?
- Factors influencing result interpretation?
- Final data verification.
- Data validation.
- Database lock.
- Statistical analysis.
- Clinical inference.
- Clinical Investigation Report (CIR).
- Publication.
Conclusions
The MDR requires manufacturers to adapt to a system where the collection and analysis of clinical data are essential for market approval of medical devices. The ability to rigorously and strategically structure the process is critical to ensuring regulatory compliance, accelerating device approval, and safeguarding patient safety.
Aglatech14 ContenTalkers
Laura Legnani – Marketing Services Manager
