How revision 4 of the guidance changed the work
Revision 4 of MEDDEV 2.7/1, the European guidance on the clinical evaluation of medical devices, arrived in 2016 without a transition period. It confirmed clinical evaluation as a planned process, asked more of the report and its literature searches and made equivalence to another device harder to claim, and in a notified body's judgement in 2022 it left manufacturers who wrote their reports to it only a few additional requirements to meet under the Medical Device Regulation.
The guidance's legal standing
MEDDEV 2.7/1 is not legally binding: it reflects the current state-of-the-art method for conducting and assessing clinical evaluations, and a manufacturer is free to apply it or another comparable method when showing compliance with the applicable directives.
Why the guidance was revised
Revision 4 was developed as a result of several scandals in Europe. To unify notified bodies and member states, the European Commission put several recommendations and regulations into force. One of them, Commission Implementing Regulation (EU) No 920/2013, required a common method and view of designation so that the requirements would be interpreted uniformly, and that regulation and the joint assessments cut the number of notified bodies from 83 to fewer than 60. The main finding of those joint assessments, by the designating member states and the Joint Research Centre audit team, concerned the clinical evidence and the qualification of the people evaluating and assessing it. Because full implementation of the Medical Device Regulation (MDR) was expected to take several years, the member states and other stakeholders decided to clarify the directives' requirements in an update of the guidance on clinical evaluation.
What the revision added to clinical evaluation
Revision 4, introduced in 2016, confirmed clinical evaluation as a planned, continuous and iterative process across a device's life cycle, and gave guidance on identifying, appraising and analysing clinical data, demonstrating equivalence to other devices, conducting literature reviews and structuring the clinical evaluation report. One account dates its release to June 2016. Another dates it to July 2016. The revision is more detailed, giving further guidance in particular on writing and updating clinical evaluation reports, and it includes essential details on the type of clinical data that can be used and on the responsibilities of the notified bodies. Revision 4 made these changes to clinical evaluation:
- the introduction of the clinical evaluation plan
- an expanded current knowledge section and a determination of the state of the art in the report
- an objective literature review methodology
- more difficulty claiming equivalence to other devices
- an increased emphasis on clinical investigations
The introduction of the plan was a significant change in the process. Before revision 4, clinical evaluation had three stages, the identification, appraisal and analysis of clinical data, and reports were produced when required and summarised the clinical evidence available up to that point; revision 4 added a Stage 0 that defined the scope and planning of the evaluation.
For literature reviews, the revision provided more detailed methods.
What the revision asked of the report
The essential requirements the report answers to are unchanged: the report provides evidence on the device's safety and performance when it is used according to the manufacturer's instructions for use, lays out its benefits against its risks and explains the acceptability of any side effects. Revision 4 requires the report to be updated more frequently for high-risk devices. It requires stricter inclusion criteria to be applied to the clinical literature. It also mandates that the post-market surveillance, post-market clinical follow-up results and claims matrices, or drafted plans for them, be included in the report. Enforcement of these requirements for the report was becoming increasingly strict as the MDR's then deadline of May 2020 approached.
What the revision cost the writer
Revision 4 made writing the report more complex, demanded greater attention to detail and analysis, and emphasised the validity of the data presented. By 2022, the report was closely linked to a plan with much more extensive current knowledge and state-of-the-art sections, a more objective and analytical literature review, and more extensive risk assessment, post-market surveillance and post-market clinical follow-up sections, so reports took longer to write than under revision 3, sometimes twice as long. The whole clinical evaluation process, though, had become a much more planned, objective, robust and comprehensive assessment than it used to be.
The implementation timeline
Revision 4 was published without a transition period, which placed many burdens on the device industry. To address this, a notified-body representative agreed implementation timelines with the members of the notified-body associations Team NB and NB MED, which were communicated to industry immediately after the guidance took effect. They recommended that manufacturers take three steps, in this order:
- Prepare an impact assessment and implementation plan within six months of the guidance's publication.
- Start updating clinical evaluation reports to the new revision by the beginning of January 2017 at the latest, prioritising the updates by how well established each device is and by its risk level, and prepare new device submissions to the new revision from January 2017.
- Bring every clinical evaluation report in line with the new revision by 31 December 2018.
Where compliance with the applicable directives was at issue, notified bodies continued to apply case-specific deadlines, and earlier action could be needed to resolve the compliance issues.
Devices whose compliance cannot be shown
One notified-body representative's advice to industry and medical writers was to check all the available clinical data for every device, regardless of classification, and decide whether compliance with the requirements of the directives then in force and of the coming MDR could be shown. Where it could not, he advised, the manufacturer should immediately run a corrective and preventive action and, in the worst case, rationalise the device. Manufacturers, in his view, have to concentrate their efforts on the devices for which sufficient clinical data are available and compliance with the essential requirements then in force and the MDR's coming safety and performance requirements can be shown.
What the Medical Device Regulation added
With the increased scrutiny expected under the new regulations, revision 4, a guide for manufacturers and notified bodies, was published to prepare them for the key requirements of clinical evaluation. Compliance with it does not mean compliance with the new regulations, but it brings manufacturers closer to compliance.
Revision 4 was a stepping stone on the way to the MDR, since moving directly from revision 3 to the regulation would have been a huge leap. The pandemic delayed the transition to the MDR by a year, until May 2021, so manufacturers and notified bodies had five years from the introduction of revision 4 to adapt their practices. The MDR then made these changes to clinical evaluation:
- a more extensive risk assessment and benefit-risk analysis
- benefits identified and supported by data
- the importance of post-market clinical follow-up reaffirmed
Bringing together and analysing all the clinical data is what clinical evaluation is about, and since revision 4 it has become a much more extensive task that involves a benefit-risk analysis of the device. Where the focus had been very much on a device's risks, the MDR meant that the benefits of using it also have to be demonstrated and all claims substantiated. Although the report's table of contents in Appendix A9 of revision 4 was still followed in 2022, its section 4.6, on the analysis of clinical data, often had to be expanded and adapted to meet the MDR's requirements. Post-market clinical follow-up has always been required; revision 4 confirmed the requirement and the MDR reinforced it. Much more detail about post-market clinical follow-up studies was therefore expected in the report's post-market surveillance section, with references to the follow-up plan and report. In June 2022 a notified body judged that manufacturers who had been writing their reports in line with revision 4 faced only a few additional requirements to reach the MDR's.
Revision 4 under the Medical Device Regulation
In 2017 it was unclear whether a further revision would be prepared, because the European Commission intended a regulation clear and detailed enough to avoid additional guidance documents. One notified-body representative held, though, that regulations are never clear to the final user and lead to multiple interpretations, so guidance documents are always helpful, and that a revision referring to the MDR would be necessary once the regulation was officially published. The 2022 work programme of the Medical Device Coordination Group's clinical working group included no replacement for MEDDEV 2.7/1 revision 4; the Commission had indicated that it would not replace every guidance written for the directives and was trying to prioritise those necessary to implement the regulations. Because the MDR does not say how to perform a clinical evaluation or write the report, revision 4 was still very much in use in 2022.