The European Medical Device Regulation (EU MDR, 2017/745) has been called many things since it was first drafted, some of which cannot be repeated here.
One thing it has probably never been called is wishy-washy.
However, we will not hesitate to call it exactly that when it comes to state-of-the-art and the definition of the state-of-the-art in relation to clinical evaluation.
Clinical evaluation is mandatory under the EU MDR for all medical device manufacturers, as described in Annex XIV, Part A.
Clinical evaluations are designed to evaluate whether a medical device’s benefit-risk profile is acceptable and if the device is safe and efficient when used as intended.
In this article, we will review the state-of-the-art in the context of clinical evaluations and literature reviews.
Note: for the purposes of this article, the terms literature search and literature review are used interchangeably.
What is state-of-the-art, and why is it important for my literature review?
If you want to evaluate the quality of the apples you’ve picked in the supermarket, you compare them to the other apples in the bunch.
Are your apples as fresh, red, and crisp as the others, or might they even be better?
The same principle applies to state-of-the-art.
How do you evaluate whether your device’s safety, performance, and benefit-risk profile are acceptable through clinical data?
You compare it to similar devices and alternative therapies on the market.
Although the EU MDR mentions state-of-the-art 12 times, it doesn’t actually define what it is.
To better understand the definition of state-of-the-art, we must look to the International Medical Device Regulators Forum (IMDRF) for a definition.
In their document, “Essential Principles of Safety and Performance of Medical Devices and IVD Medical Devices,” issued in October 2018, the IMDRF defines state-of-the-art as:
“State of the art: Developed stage of technical capability at a given time as regards products, processes and services, based on the relevant consolidated findings of science, technology and experience.”
The Medical Device Coordination Group (MDCG) further clarifies that “… the state of the art embodies what is currently and generally accepted as good practice in technology and medicine. The state of the art does not necessarily imply the most technologically advanced solution…” in MDCG 2021-5 Guidance on standardisation for medical devices.
Although the term remains ambiguous, we can deduce that state-of-the-art is generally what is considered good practice in the industry.
Applied to clinical evaluations, state-of-the-art refers to the standard of care.
What sort of clinical data should be included in a state-of-the-art literature search?
Every medical device under clinical evaluation should consider the state-of-the-art as part of the published clinical data pertaining to the device in question. The MDR requires literature reviews in the clinical evaluation to include some key sections.
Every clinical evaluation report must provide context for the medical condition and medical devices in question.
Within the state-of-the-art framework, that means performing clinical data literature searches to understand the underlying medical condition and its history.
Likewise, state-of-the-art requires identifying competitors and similar devices on the market (devices within the same generic device group) and alternative therapies.
For example, suppose you are writing a clinical evaluation report and doing literature reviews for an orbital implant made from 3D-printed titanium. In that case, your state-of-the-art literature search should first investigate orbital trauma and any medical conditions associated with the use of orbital implants.
Thereafter, you would look for the historical context of orbital implants and the use of titanium implants and 3D-printed implants.
Lastly, you would look for similar devices on the market (competitors).
You would also look for alternative therapies, such as 3D-printed implants in PEEK (polyether ether ketone) and traditional implants that are manipulated during implantation.
Once you have information on the history of the medical condition and device, competitor and similar devices, and alternative therapies, you can perform an appropriate and objective evaluation of the benefit-risk profile of your 3D-printed titanium implant.
State-of-the-art data can be provided in the form of systematic reviews, clinical investigations, guidance documents, adverse event reports, and more.
State-of-the-art challenges for medical device literature search
While state-of-the-art sections are tailored to each medical device, and available clinical data, the process of performing state-of-the-art searches and evaluations is pretty similar across devices.
Due to the similarity in process, there are some challenges related to state-of-the-art that we see frequently.
When identifying similar (not equivalent) devices under the MDR, there are a few things to consider.
Similar devices are, well, similar in characteristics and technology.
In their eagerness, some manufacturers include similar devices that do not share technological features or processing techniques with their devices.
For example, if you are performing a clinical evaluation for a remoldable wrist splint, a fixed cast is not a similar device.
It is an alternative therapy.
Nor is an ankle brace a similar device, as it has different indications than our splint.
A similar device would be another remoldable wrist splint, preferably made from the same material and remolded using the same process.
Similarly to the above, medical alternatives and alternative therapies can also be complicated to evaluate for some manufacturers.
What is the alternative therapy to a surgical table, for example?
There might not be a realistic one, as surgical tables are the exclusive standard of care at this point, but there are still alternatives.
The patient could stand or lie on the floor or sit in a chair.
Alternative therapies become tricky for lower-risk devices and therapies or common interventions, as only one solution is typically used.
However, for most Class IIa devices and up, there are several alternative therapies to consider, as we saw in our orbital implant above.
Literature review strategies for the best state-of-the-art results
Once you have the clinical data process down, state-of-the-art literature reviews can become a walk in the park.
But getting your strategy down can be tricky.
There are some tips that can get you ahead of the line, though.
Establish a clear process
It should be clear to the notified body (and your boss and whoever else will be reading your literature review) exactly where you will obtain your clinical data and how.
Your literature search protocol is your plan for the entire show, so establishing a clear process early on can really be of help later on.
Anyone should be able to replicate your literature review and get more or less the same results.
Obviously, sometimes the databases change something, and searches will not be exactly the same, but on your end, you should do everything you can to ensure it is as accurate as possible.
Make your inclusion/exclusion criteria iron-clad
Your inclusion and exclusion criteria determine the borders of your literature review and your final inclusion results.
Taking the extra time at the beginning of your clinical evaluation to establish clear criteria can come in handy when sitting with 1800+ literature review results.
Having clear inclusion and exclusion criteria will make sorting and organizing your literature a breeze.