What is Medical Device Clinical Evaluation?

Clinical Evaluation & the EU MDR

Clinical Evaluation is a systematic and planned process to assess the safety and performance of a medical device. The objective of Clinical Evaluation is to demonstrate conformity with the relevant Annex I General Safety and Performance Requirements (GSPRs) and to prove that the device’s benefit-risk profile continues to be acceptable.

Through the constant production, appraisal and systematic analysis of clinical evidence, Clinical Evaluation seeks to answer the question “does this medical device work as intended, and is it safe?”

A Clinical Evaluation is fed by information from multiple sources and processes, incorporating evidence generated and held by the manufacturer as well as evidence produced independently and published in the literature. It can be thought of as a ‘bringing together’ of clinical data accumulated through literature reviews, Post-Market Surveillance (PMS), Post-Market Clinical Follow-up (PMCF) and Vigilance systems, as well as conclusions drawn from Risk Management and Quality Management Systems (QMS).

The EU MDR requires that Clinical Evaluation is a constant process that is conducted throughout the entire lifetime of every medical device. Clinical Evaluation of each medical device is summarised periodically in a Clinical Evaluation Report (CER), with the periodicity determined by the risk class of the device.

MDR Annex XIV Part A contains detailed requirements for Clinical Evaluation under the MDR.

How has Clinical Evaluation changed under the MDR?

In May 2021 the new Medical Device Regulation (EU) 2017/745 will be fully in force. The MDR replaced the Medical Device Directive MDD 93/42/EC and represents a significant overhaul of all aspects of medical device regulation. All medical devices and medical device manufacturers within the EU will need to comply with the new MDR regulations in order to trade and sell in the EU market.

As a consequence of the enhanced requirements imposed by the MDR, many existing medical device Clinical Evaluation processes may fail to meet the required standard, even if they successfully met expectations under the MDD.

Specific changes to Clinical Evaluation introduced by the MDR include:

• Replacing the MDD Essential Requirements with the MDR Annex I General Safety and Performance Requirements (GSPRs). The GSPRs are more extensive and specific than the Essential Requirements, and raise the required evidence burden for manufacturers.
• Thoroughly overhauling rules on equivalence, making it much more difficult for manufacturers to successfully claim equivalence under the MDR. In many cases, manufacturers who previously claimed equivalence will need to completely re-engineer the Clinical Evaluation for their devices.
• Assigning a new risk classification to some devices, increasing the complexity of Clinical Evaluation required for devices that have been allocated a higher risk category.
• Introducing new requirements for Post-Market Clinical Follow-up (PMCF), detailed in MDR Annex XIV Part B, that require manufacturers to establish more robust PMCF systems and include outputs of PMCF into the Clinical Evaluation for each device.
• Mandating a higher level of detail and structure in CERs that periodically summarise the Clinical Evaluation of each medical device.
• Requiring Clinical Evaluation to account for the full scope of a medical device’s lifecycle, from initial realisation and design, through construction and manufacturing to marketing post-market surveillance and senescence.

How is a medical device Clinical Evaluation performed?

Performing Clinical Evaluation under the MDR is a technical task that draws heavily upon an ability to work with clinical evidence.

Medical device manufacturers will need to demonstrate that authors of CERs relating to their products are appropriately qualified to perform the work and are able to demonstrate a commitment to objectivity when handling data. Because Clinical Evaluation requires that appropriate weight is given to both favourable and unfavourable evidence, it is often beneficial for manufacturers to consider working with external specialists.

Guidance on how to perform a medical device Clinical Evaluation can be found in MDR Annex XIV Part A. The Annex requires that manufacturers:

• establish and regularly update a Clinical Evaluation Plan (CEP)
• identify all available clinical data (favourable or unfavourable) relevant to the device according to a documented search protocol
• identify any gaps in clinical evidence through a literature review
• appraise all relevant clinical data by evaluating the quality and relevance of each data source to the clinical evaluation
• generate any necessary new or additional clinical data required in order to address any identified gaps
• analyse all relevant clinical data in order to reach conclusions about the safety and performance of the device

In addition to information in Annex XIV Part A, further guidance on performing a Clinical Evaluation can be obtained from MedDev 2.7/1 rev 4, one of a series of advisory documents published by the European Commission. It is important to be aware that MedDev 2.7/1 rev 4 (as of December 2020) has yet to be updated to reflect changes introduced by the MDR.

Medical device Clinical Evaluation is a complex process requiring a high degree of clinical and regulatory expertise. Mantra Systems offers the opportunity for you to benefit from the expertise of our team of specially-trained medical professionals, bringing their clinical knowledge and acumen to your MDR Clinical Evaluation.

What data sources are used in medical device Clinical Evaluation?

A medical device Clinical Evaluation draws together information from a range of sources and processes. Individually, all these processes are essential in ensuring safety and performance of medical devices. Clinical Evaluation aims to make an holistic assessment of the overall picture produced by the results of each of the individual processes. The MDR encourages manufacturers to make these processes inter-dependent and the correct approach to Clinical Evaluation ensures that results are utilised in this way.

Some of the processes that contribute data to Clinical Evaluation include:

Quality Management System

The Quality Management System (QMS) is a formalised system that ensures and continually improves the quality of all business activities.

It is an over-arching framework that includes post-market surveillance activities focusing specifically on medical device safety and performance, and broader company quality control measures that govern the wider activities of the organisation.

Article 10 MDR requires that all manufacturers establish, document, implement, maintain, keep up to date and continually improve a QMS.

The QMS itself determines processes for performing a Clinical Evaluation, including roles and responsibilities for individuals and departments whose activities contribute to clinically evaluating medical devices.

Post-Market Surveillance

Post-Market Surveillance (PMS) is a structured system that monitors the safety and performance of a medical device following its release onto the market.

It involves the collection and detailed review of data relating to real-life clinical experience with the device. PMS is comprised of two elements:

• Post-Market Clinical Follow-up (PMCF) that proactively collects data on the device’s clinical performance
• Vigilance systems that collect information on complaints and serious incidents as they occur

Data from PMS is a crucial component of Clinical Evaluation for every medical device. PMS data is also used in numerous other regulatory activities, including to update the device’s benefit-risk analysis and to inform improvements to risk management processes.

Post-Market Clinical Follow-up

Post-Market Clinical Follow-up (PMCF) is a component of PMS and Clinical Evaluation that has attained greater importance under the MDR. PMCF is the continuous process of proactively collecting and evaluating clinical data on the safety and clinical performance of a medical device.

Effective PMCF systems generate Real World Evidence (RWE) that demonstrates the real-life performance of a medical device throughout its entire lifetime.

Because Clinical Evaluation under the MDR is a continuous process, PMCF systems need to be prospective and capable of delivering data on an ongoing basis. PMCF data must also genuinely reflect real use of the device. Standard clinical investigations will not be suitable because they are normally time-limited and recruit patients within comparatively narrow criteria.

An ideal structure for generating real world evidence for PMCF under the MDR is with PMCF studies and surveys. They offer a number of advantages over alternative methods and, properly implemented, will secure a system that will stand the test of time.

MedDev 2.12/2 rev 2 focuses on requirements for designing and conducting PMCF studies. Results of PMCF are compiled in a technical document known as a PMCF Report and a dedicated section of the CER.

Clinical evidence

Clinical evidence forms the basis of all Clinical Evaluation under the MDR. It includes data that has been published independently of the company in medical or scientific journals, as well as data produced internally by the manufacturer.

Before it is possible to assess conformity of a device with the MDR Annex I GSPRs, it is necessary to identify and appraise all relevant clinical evidence, whether favourable or unfavourable.

Performing a Literature Review of external data is essential when undertaking Clinical Evaluation under the MDR. Systematic literature searches call for a high level of clinical acumen and appraisal skills.

Vigilance

Vigilance systems collect data on any serious incidents, complaints, and adverse events relating to the use of a medical device. Vigilance systems also concern the monitoring of trends of frequency and severity of side-effects, as well as detailing processes for the handling of Field Safety Corrective Actions (FSCAs). A distinction must be made between serious incidents and expected side-effects that are clearly documented in product information and technical documentation.

Risk Management

Risk Management concerns processes for identifying, analysing, monitoring and controlling risk. The MDR accepts that risks cannot be entirely eliminated from the use of medical devices, and instead requires that manufacturers provide evidence that the benefit-risk profile of the device is objectively acceptable. ISO 14971:2019 outlines an internationally-recognised standard for medical device risk management, and unlike many ISO standards has been updated to reflect changes introduced by the MDR.

Demonstrating an acceptable benefit-risk profile is a major objective of medical device Clinical Evaluation.

What happens after a Clinical Evaluation has been performed?

Clinical Evaluation is a continuous process that is constantly fed by data from the sources identified above. Periodically, however, the results of Clinical Evaluation must be summarised in a technical document known as a Clinical Evaluation Report (CER).

The CER must be an extensive summary of the findings of Clinical Evaluation, written objectively and carefully structured. CER writing is a demanding, technical task that requires a high level of regulatory expertise and medical writing capability.

MedDev 2.7/1 rev 4 contains guidance on structuring a CER but has not yet been updated to reflect changes introduced by the MDR.