The European Medical Device Regulation (MDR) outlines the requirements for the literature review needed for the clinical evaluation of medical devices.
You need a robust process for performing your literature review and finding clinical data to evaluate your device’s safety, benefit, and risk in an evidence-based manner.
Since the medical device literature reviews support your clinical evaluation report (CER) and post-market clinical follow-up (PMCF) report, it will be subject to scrutiny from competent authorities.
Therefore, it must live up to the MDR requirements for a comprehensive literature review of clinical data, such as published and gray literature on your medical device (and similar devices), and be clear, easily understandable, and reproducible.
This article will give you five practical tips on how to perform a literature review that will support your clinical evaluation report, find the correct relevant clinical data you need, live up to the rigorous requirements of the MDR, and, perhaps most importantly, be less of a headache for you and your team.
Note: while medical device literature reviews and searches are not technically the same, this article will use the two terms interchangeably.
Why are literature reviews so challenging?
At first look, the literature review might be relatively straightforward: you define a research question, come up with search terms, do your clinical literature searches, sort your literature, appraise your clinical data, and make conclusions based on your findings.
Successful literature reviews depend on a few things:
Framing of the research question
While seemingly an easy task, the research question frames and refines your full literature review. If you don’t get it right, arriving at the right results and relevant conclusions about your device’s benefit-risk profile in your literature review can be challenging.
Elaborating the right processes
The literature review is a small part of a device’s clinical evaluation.
Besides the initial literature reviews, your clinical evaluation includes continuous monitoring of your device’s market behavior and changes in the available clinical data, yearly updates to the clinical assessment, and rigorous documentation of all the involved processes.
For seasoned medical device manufacturers, the requirements can be difficult to live up to. The challenge can seem impossible for medical device manufacturers facing compliance with the EU MDR for the first time.
Understanding where and how to obtain the right and relevant results
Even when everything else goes right, you might not be getting the results you expected from your literature review.
This can be due to incorrect framing of the research question, not understanding exactly how your search terms interact with the database or even problems with choosing the suitable databases to search.
The last item is what we are focusing on today – how can you get the right results in your literature reviews that will support your clinical evaluation and demonstrate the acceptability of your benefit-risk profile?
1. Choose your databases wisely.
Not all databases are equal, and they will not necessarily yield the same results for your literature review. Therefore, it is not enough to search for just one.
For example, using the (unfiltered) search term “Silk fibroin” AND (dermal OR filler OR “dermal filler” OR “soft tissue augmentation”) will yield three results in PubMed, 16,700 results in GoogleScholar, and 181 results in LIVIVO.
Some of these differences are due to how the search engines work, while others are due to different publications available in each database.
It is important to understand how each database works and how to phrase your literature review terms to get valuable results in each database.
It is generally a perfect place to start as it contains a comprehensive catalog of peer-reviewed literature and connects to other relevant publications based on your literature search. However, It is not a complete search tool. For example, it might not fully cover European and Asian literature, and many articles are not open access.
It contains good coverage of medical devices and therapies used in Europe. However, the search is not as user-friendly as PubMed and can require a little getting used to. Furthermore, EMBASE is not free to search – it requires a subscription.
GoogleScholar is Google’s search engine for scholarly literature. It works much the same as Google; you can find articles, theses, books, abstracts, etc. GoogleScholar casts a very wide net, and it is essential to use the advanced search unless you’re searching for one article in particular. Many publications not available elsewhere can be accessed through GoogleScholar.
You should choose two of these databases, at least a third scientific database, and at least one clinical trial database.
A German database focuses on life science in general and includes publications on environmental and agricultural sciences. By de-selecting the option to have PubMed (The Medline database), you would find many European and Asian publications which are not available in PubMed, and most of the articles here are open access.
For clinical trials, Clinicaltrials.gov is the most popular database. The other valuable databases are
2. Be organized
Some literature reviews will give you a plethora of information, especially if you’re working with devices in larger fields, such as cardiovascular and orthopedic surgery. However, it is essential to be organized to look through all that information.
You must set up a straightforward process for how you will conduct your literature search before you start, i.e., you have to write a literature search protocol. You need to have each step in place before you do it – otherwise, it is easy to get lost when you’re halfway through or, even worse, when you’re almost done.
You should always do a preliminary search to get an overview of what kind of information and publications are out there and test the waters of your considered search terms. Get a feel for the task, so to speak.
Once you determined what you are looking for and how to get there, write a plan for the search. Include search terms, inclusion/exclusion criteria, the databases you’ll search, and what tools you’ll use during your search.
You are essentially creating a recipe for your search you can follow when you actually start.
This recipe will also work as your literature search protocol and report afterward. Writing every step of the process out and documenting them as you go will help you tremendously deliver a well-documented, well-organized, and well-written report to the competent authority when you are done, instead of remembering what you did and writing it down once you are done.
3. Use digital tools to make your life easier.
Expanding on the previous step, generating bibliographies and search result files, and storing references, let alone organizing them, is a pain in the butt.
There is a lot of meticulous detail-work and moving parts to the literature search, and there is no need to complicate matters for yourself – use as many digital tools to make your life easier as possible.
Download your search results
The extensive literature databases all have the option to download your search results in CSV, text, and database-specific formats, such as PMID.
Downloading your search results during each search and importing them into, for example, Excel gives you a significant advantage when it is time to review your publications against your inclusion/exclusion criteria.
More importantly, it provides a complete record of all your literature searches and results where you can mark which articles were included and excluded.
Use a citation manager.
References are simple to generate and work with manually, but they are incredibly time-consuming. Reference managers such as Endnote, Mendeley, and Zotero will help you tremendously with reference management and compiling bibliographies.
Databases such as PubMed allow you to save citations directly to your citation manager, and you can import references to the citation manager from your computer by drag-and-drop.
Some citation managers, such as EndNote, are fee-based and can be expensive, while others, such as Mendeley and Zotero, are free.
Some companies require their reference libraries in a specific format which is worth considering before settling on one citation manager, especially if you are a medical writer or freelancer.
4. Use (Boolean) operators
Boolean operators are always highlighted when people advise on literature reviews, but they are so for a reason. The right boolean operator can make or break your literature search (and sanity).
Operators allow you to narrow your literature review to focus on only the articles relevant to you and save you hours. Likewise, your search can be widened if you are not getting enough results.
The most well-known operators are AND, OR, and NOT.
Using the AND operator helps you focus on results that are relevant to you. For example, if you are researching the use of silk fibroin as a dermal filler, you will get many irrelevant results by only searching for silk fibroin. However, searching for silk fibroin AND dermal filler, you will get results for silk only in the context of fillers.
Typically, AND combines literature searches for a material or product and a surgical discipline or medical field.
The operator OR is used when you want to widen your literature search to include various terms relevant to your research question.
In the previous example, we looked for silk fibroin in relation to dermal fillers. Dermal fillers, however, can also be described as soft tissue augmentation. In that case, your search can be widened by adding OR to the search term: silk fibroin AND dermal filler, OR soft tissue augmentation. It would give you the option to search for variations of terms in the exact search without having to do a new search for each term variation.
The NOT operator is self-explanatory: it helps you exclude results that are irrelevant to you.
For example, you want to look at silk fibroin as soft tissue augmentation, but not in the context of otolaryngology. Adding this exclusion to the search term will restrict your results to only include the results you are actively looking for: silk fibroin AND soft tissue augmentation, NOT otolaryngology.
Other operators that can help steer your search are truncations (*) and quotation marks (“). Unfortunately, these terms are not used in all literature databases, so you have to figure out if they work in your chosen database and how before you can use them appropriately.
5. Use filters
Most literature reviews have some search restrictions in place. It can be a time limit, i.e., only doing literature searches for the last five years. It can be a language (no use getting results in Japanese if you can’t understand them), a medical discipline, or the type of publication you are looking for.
Every database will have filters you can use to refine and narrow down your search – make sure to use them as much as possible. It is your most straightforward tool to obtain the results you need.
The literature review can be overwhelming if you are starting. However, regulatory staff and medical writers are typically exposed to tight deadlines and time constraints, so making your life as simple as you can is vital. We hope these tips help you do just that! Using these simple tips, you can quickly elevate the quality of your literature review protocol and report and ensure you deliver a good product.