What clinical evaluation is, and why it never finishes
Clinical evaluation demonstrates with clinical data that a medical device is safe, performs as intended and has a positive benefit–risk profile. It runs across the device's whole life rather than ending in a finished document: its plan and report are kept current as each lifecycle stage generates evidence and as post-market reports feed back into it.
What clinical evaluation is and what it produces
The MDR defines clinical evaluation as a systematic and planned process to continuously generate, collect, analyse and assess the clinical data pertaining to a device in order to verify its safety and performance, including clinical benefits, when it is used as intended by the manufacturer. Clinical evaluation needs a clinical evaluation plan and a clinical evaluation report. The plan is the starting point of the process, and the process results in the report. Together with the state of the art, those two documents are the main parts of the clinical evaluation process.
The purpose of clinical evaluation is to meet the MDR requirement to demonstrate with clinical data a device's safety, clinical performance and benefit–risk ratio. Only then can the device obtain the CE marking, and it keeps the marking only by keeping the evaluation current, through regular renewals and updates whose frequency depends on the device class.
Clinical evidence is the backbone of medical device regulation, and it demonstrates three things: that the device is safe, that it performs as intended, and that its benefit–risk profile is positive. If any one of them cannot be justified, the device cannot obtain the CE marking.
Under the MDR, every medical device requires a clinical evaluation. The evaluation identifies the pertinent data on the device and on similar devices through a systematic literature review and by gathering the manufacturer's data, defines the state of the art of the medical field, and appraises, analyses and summarises the clinical data in a clinical evaluation report. It also detects and highlights gaps between the existing data and the data that current regulations require.
A new device, a new model or a new iteration of an existing device has to undergo clinical evaluation to get the CE marking, and the path to that marking is not straightforward.
Clinical evaluation as a continuous process
Clinical evaluation is not a single document but a continuous process, an evidence strategy that runs across the entire evidence lifecycle. The MDR recast it as a continuous evaluation process, in which a clinical evaluation report is produced at regular intervals or when new information requires one, all underpinned by a clinical evaluation plan. The report's revision cycle is usually aligned with the device classification: every five years for class I devices, annually for class III or implantable devices, and every two years for other devices.
Under the MDR and IVDR, clinical evaluation has four functions across the device's life. It supports development by defining what evidence is needed and planning the data collection early; it demonstrates safety and performance for conformity assessment and CE marking; it monitors real-world performance through post-market surveillance and post-market clinical follow-up; and it maintains the evidence base through regular updates and periodic assessment. In this continuous cycle, post-market findings feed back into the evaluation and update its evidence base.
A manufacturer that writes the clinical evaluation plan and the clinical evaluation report, then treats the evidence as complete and collects no more clinical evidence for the device, receives a non-conformity from the notified body and cannot justify the device's safety and performance. So at every stage of the device's development, the plan, the report and the procedures that implement the process have to be in place.
In 2014, every medical device marketed in the European Union, Switzerland, Norway, Liechtenstein and Iceland required a clinical evaluation report in its technical file, whatever its classification. The report was required to obtain the CE mark, which indicates that the device is approved for marketing, and it had to be reviewed at least every five years as part of the mark's renewal. Although the report is technically a series of related documents, it is best described as the process that generates them. Best practice is for the reviews of clinical evidence to be systematic and transparent, conducted in a scientific and replicable manner, and to follow a well-defined standard operating procedure.
Clinical evidence across the device lifecycle
Clinical evidence is gathered at every one of the five stages of a device's lifecycle. Planning defines the intended use and identifies the initial evidence needs, and its key document is the device description, which carries the intended use. Design and development generates the preclinical evidence and, where one is needed, plans the clinical investigation that will demonstrate safety and performance; the state of the art, the clinical evaluation plan and the clinical evaluation report are produced here. Production manufactures under the quality management system, so that quality control makes each unit identical to the last. Post-production monitors real-world performance through post-market surveillance and post-market clinical follow-up. Obsolescence manages the end of the device's life and the final strategy reporting.
Four processes run continuously and in parallel across the whole lifecycle. Design control and development runs from beginning to end so that every requirement is verified and validated. Risk management is a living process from concept through post-market. Clinical evaluation, or performance evaluation for an in vitro diagnostic, runs from start to finish to keep the clinical data acceptable and the device demonstrably safe and performing. Post-market surveillance has its plan drawn up, and at each step the plan and the report confirm the device's safety.
Post-market reports in the evaluation
The post-market clinical follow-up evaluation report and the periodic safety update report both go into the clinical evaluation report. The findings of the follow-up activities are reported in the post-market clinical follow-up evaluation report, which should be part of the clinical evaluation report and of the technical documentation.