Clinical evaluations for medical devices are long and arduous tasks.
But what many medical device manufacturers fail to take into consideration is that clinical evaluations are living processes.
They ebb and flow. And just like bodies of water, they ebb and flow at specific points in time and space.
Initially, your medical device clinical evaluation and literature review might be flowing along speedily – you’re gathering clinical evidence, setting up your literature search protocol, getting all your ducks in line.
But then suddenly, things start to slow down.
You have to choose scientific and regulatory databases, you have to set up your inclusion and exclusion criteria, you’re choosing search terms, and you are looking through various models for assessing your clinical evidence.
And slowly your literature search and process grinds to a halt.
Or you’ve finished your literature review and sent it off to the notified body.
You’ve got a great feeling about it and all that’s left to do is wait for the notified body feedback.
So you wait.
And wait some more.
And you get your literature search feedback, and the good feeling slowly leaks away.
The NB is not happy with your literature search process – it’s not systematic enough.
They don’t understand your exclusion criteria or why you’ve only chosen to appraise clinical data for your own device, not for your similar devices.
And once again, your literature search is slowing you down.
As you can probably tell, we see these scenarios a lot.
The literature search is usually where medical device manufacturers have the most problems with their clinical evaluation report, whether in the initial phases or after they get their notified body feedback.
And most of our clients come to us with, if not the same then very similar, issues during their literature search process.
In today’s article, we’re looking to guide you through some of the most frequent problems we see with literature searches and help you get through the ebbs of your clinical evaluation smoothly.
For the purposes of this article, the terms literature search and literature review are used interchangeably.
The clinical evaluation literature review – a brief overview
Do I really need a literature search?
Every clinical evaluation must have a literature review. So says the EU Medical Device Regulation.
In any case, you can’t really do a clinical evaluation without a literature search unless you have a ton of clinical trials and articles on your medical devices.
That’s a perk reserved for the fewest of manufacturers.
What should my literature review do?
A literature search is where you find external clinical data on your medical devices.
Your internal clinical data, such as post-market surveillance data, will also be evaluated in the clinical evaluation, but it is not enough on its own.
Furthermore, your literature search establishes the current knowledge and standard of care through the state-of-the-art section, where you can compare your device to other devices on the market using the same technology.
Essentially, your literature search contextualizes your medical device in the current market and help you make the case that your device is equally safe and efficient as the other devices out there. Neat!
Common issues with the literature review and clinical data
While every literature review is different, there are some issues we see more often than others.
These problems arise during the initial draft of the literature review, during internal or external audits, and after notified body review.
And while these problems can stem from any number of causes, it is usually due to lack of experience of the clinical evaluation writer.
Clinical evaluations and literature reviews are HARD
Regulatory affairs specialists tend to, well, specialize in different regulatory aspects.
And most regulatory affairs specialists are specialized in market authorizations in their local and surrounding markets.
They are not typically specialized in quality management, post-market surveillance, or clinical evaluation writing.
So, when tasked with performing a clinical evaluation literature search, their otherwise vast experience falls short.
Reading the EU MDR might seem simple enough, but the fact is that it can be difficult to discern the meaning of the short sections included on clinical evaluations.
Even MEDDEV 2.7/1 Rev. 4 can be difficult to interpret.
The good news is that every one of these issues is fixable!
We got you!
Lack of a systematic process
The lack of a systematic literature search and review process is by far the most common problem with literature searches.
There is a science to systematic processes, including for clinical evaluation reports and medical device literature reviews.
And it is something the notified body always picks up on, so getting it nailed down pays off every time your clinical evaluation is due an update.
Essentially, a systematic process just means you’re doing the same thing every time for every search term and database and that you are showing your work.
For example, if you search every scientific database for articles on both manufacturer and device name, it’s a systematic process.
You might know, because you know all about the literature out there, that you won’t find anything if you search a certain manufacturer or device term.
But you still have to do it and record that there are no results, so the notified body – and everyone else reading your report – know that you did the search and found nothing.
Likewise, you have to appraise all your data the same way.
You can’t differentiate between data for your device and data for any similar devices you’ve identified in the protocol – both sets of clinical data should be appraised the same way.
Claiming equivalence in your literature reviews and clinical evaluation report
Now, don’t get me wrong, equivalency has its place.
But that place is not in any EU MDR clinical evaluation!
Let me elaborate.
Equivalency for 510(k) submissions is simple.
The requirements aren’t that difficult and equivalency devices can relatively quickly be established.
However, while the MDR does include equivalence in its foundation, it is practically almost impossible.
The requirements for claiming equivalence are just too steep.
Luckily, equivalence doesn’t make an EU clinical evaluation any easier.
Equivalence doesn’t reduce your workload
The workload for your literature review is the same, whether you claim equivalency or use similar devices.
Actually, claiming equivalency is a little more work because you need to demonstrate that the two devices are basically the same.
Equivalency is simply not worth it under the EU MDR.
The notified bodies review equivalency claims like there’s no tomorrow and it is extremely hard to get unscathed through it, unless you have 100% complete access to all (and we do mean ALL) the documentation for the other device.
We highly recommend skipping equivalence and using similar/comparator devices instead.
Not triple-checking your numbers
There is a lot to keep track of during a clinical evaluation literature search.
When you include your literature search results, a.k.a. how many articles were retrieved in each search, how many duplicates were there, how many articles were included for review, etc., make sure you double-check them.
And then check them again when you’re done.
And again when you’re doing your final literature review revisions.
For some reason, getting those numbers right the first time is almost impossible.
Heck, even getting them right the second time is hard!
You’d think basic counting would be simple for people who regularly handle huge datasets and very technical writing in their literature review, but it’s not.
And there’s no shame in making those calculations four times if that’s what it takes to get them right.
Cause your notified body WILL notice.