Clinical evaluation of Medical Devices
An introduction to the clinical evaluation of medical devices, a regulatory requirement that manufacturers must consider in order to obtain – and maintain – the CE marking of their devices.
This article takes into account the Regulation (EU) 2017/745 on medical devices and the Meddev 2.7/1 Rev. 4 guidance which – although thought for Directive 93/42/EEC – still represents the state of the art, pending its next revision.
The requirements are set out in Article 61 of the Regulation supplemented by its Annex XIV for clinical evaluation and post-market clinical follow-up. The standard ISO 13485:2016 mentions it in § 7.3.7 (design validation).
What is a clinical evaluation ?
Clinical evaluation is evaluating your clinical data (i.e. obtained after actual use of the device or equivalent), in order to prove compliance with the general requirements of the Regulation (the former essential requirements of the Directive). This evidence complements pre-clinical evaluation data obtained through laboratory tests and other verification and validation results.
This is a continuous process initiated for device certification and then constantly updated with the post-marketing surveillance.
To carry out a clinical evaluation, you will need to:
- Identify useful clinical data for your conformity demonstrations,
- Evaluate the relevance of this data, and
- Demonstrate compliance with regulatory requirements, based on your data.
Various types of clinical evaluations are possible
There are several routes to obtain your valuable clinical data:
- Analyzing data from the literature,
- Compile data specific to your device,
- Use data from an equivalent device,
- Proceed with a clinical investigation involving your device, to obtain new data.
The use of a equivalence is the simplest solution – it is even the principle of the FDA 510k – but it is reserved for non-innovative devices.
The clinical investigation is the most difficult route because it is long, risky and expensive (hundreds of k€). It is nevertheless mandatory for all class III and Implantable Medical Device (IMD) devices, except in special cases (including: MD already EC according to the Directive; change to an EC device; certain implantable MDs such as clips or orthodontic appliances; and if equivalence with another device can be demonstrated on the basis of the full technical file of the equivalent MD).
Planning the clinical evaluation
First stage: make a clinical evaluation plan.
This plan contains:
- A description of the scope of the evaluation taking into account:
- The characteristics of the device
- the performance and security requirements you will need to validate
- the intended use (which you will have already covered in the Usability Engineering)
- the medical and technical context, including alternatives to the MD being evaluated
- The types of evaluation selected,
- The stages of the evaluation and associated responsibilities,
- The list of documents already available (essentially: the result of the state of the art initiated in design and the technical documentation including the risk management standard and benefit/risk ratio evaluation)
- The list of evaluators,
- For class III and some IIb: a decision as to whether to consult a European expert group in advance of the clinical evaluation,
- And for post-marketing evaluations: the outcome of your post-marketing surveillance or even vigilance activities.
Note that this information can be split between the plan and the evaluation report as you see fit.
Is it necessary to use independent evaluators?
The profile of the evaluators (who will approve your report) is very constrained: their knowledge and skills regarding the device and the context will have to be demonstrated, a declaration of interest is also expected. Beware that some Notified Bodies may require one of the evaluators to be a doctor.
The decision to use an independent evaluator (external to your company) should be based on:
- The dangerousness of the device,
- How innovative it is, and.
- The context, which can rapidly evolve to the point of challenging the conclusions of an evaluation.
The use of an independent evaluator will be (for example):
- Systematic for a dangerous and innovative MD,
- Desirable for an MD that is under control but whose context is changing significantly, for example in the case of recent materiovigilances in the field,
- Dispensable for a device class I in a stable context.
Conducting an clinical evaluation by equivalence
Equivalence should compare the technical, biological and clinical aspects of the devices.
The differences have to be justified, from a security and performance perspective.
Finally – and this is a big feature of the regulation – access to the data of the equivalent device (to its technical documentation) must be proven. For class III and IMD this will necessarily involve a contract between the manufacturers, most often competitors.
Search the clinical literature
You are still allowed to use literature data, it will need to be updated as part of your post-marketing clinical follow-up activities anyway.
A literature search should be planned, specifying:
- The questions that will guide your search (see PICO method),
- The databases consulted (Medline, Google scholar, Embase, Cochrane…),
- The key words searched,
- The booleans used (AND, OR, NOT),
- The inclusion and exclusion criteria for documents (see for example PRISMA methods).
Evaluation of the relevance of the data
Your data has been identified, now it is time to evaluate it: establish whether it is worthy of being used to demonstrate your MD’s conformity.
The assessment is based on the relevance of the data, estimated according to criteria of methodological, scientific and especially clinical relevance. Several scoring systems are used to calculate a relevance score.
Data are evaluated according to their contribution to demonstrating security and performance (it is recommended that these two aspects are scored separately).
This estimate allows you to weight the data that will contribute to the demonstration of conformity.
Meet general requirements
The relevant clinical data is identified and weighed, what remains is to close the loop: proving that each applicable general requirement is met given the data.
You need to consolidate the responses to the general requirements of the regulation already addressed in your technical documentation:
- Demonstrating performance (general requirement 1)
- Demonstrating security (requirements 1 and 2)
- Management of risks (requirement 3)
- Assessing the acceptability of adverse side effects (requirement 8)
- Relevance of information provided (requirement 4)
- Accountability of monitoring activities, for a post-CE marking evaluation (requirement 3)
- And finally: evaluation of the acceptability of the benefit/risk ratio (requirements 1,2,3 and 8)
The results of your evaluation are recorded in a clinical evaluation report, a key part of your technical documentation.
But the clinical evaluation is not over yet: you will certainly have points to clarify, uncertainties to resolve … and the context will constantly evolve: technologies, uses, alternatives, consensus: everything is moving and the conclusions of your evaluations may only be valid for a few months!
This is the whole point of the post-market clinical follow-up (PMCF), a component of your PMS, covered in a specific Qualitiso article.