It is very important for a medical device manufacturer to perform a thorough clinical evaluation and literature research so that they can document state of art, incorporate safety, increase efficiency, and provide the intended clinical benefit of their manufactured device.
Tips for Medical Device Manufacturers to Perform Clinical Evaluation & Literature Research
Tip 1: Utilizing Information Present in Guidelines While Literature Researching
a. Guidelines Present in MEDDEV 2.7/1 Revision 4
Annex 5 of MEDDEV 2.7/1 Revision 4 provides some of the most important guidelines to the medical device manufacturers regarding the objectives of the literature searches.
b. Guidelines Present in MDCG Documents
When it comes to guidance on clinical evaluation and literature research, guidelines provided by MDCG Document 2020-13 “Clinical Evaluation ASSESSMENT Report Template” is another important tool for medical device manufacturers.
This document primarily aims at Notified Bodies, which review the clinical evaluation. However, it also provides indirect guidance to medical device manufacturers. Section D of MDCG Document 2020-13 focuses on literature search and literature review.
c. Other Documents
Medical device manufacturers can also seek guidance from other documents such as IMDR MDCE WG/N57FINAL:2019 regarding clinical evaluation and literature review.
Tip 2: Documentation of Literature Research
A medical device manufacturer should take extra care while documenting his literature research, as his literature review must be fully complete.
a. Following the Literature Research Protocol
An expected result of incomplete documentation from the medical device manufacturer usually comes in the form of non-conformity, unnecessary queries, and deviations in the audit.
According to MDCG document 2020-13, Notified Bodies are required to review the literature search documentation. According to it, the following metadata i.e.:
- Search terms;
- Databases used in literature search;
- Criteria of exclusion and inclusion
- Exclusion of duplicates;
- Procedure and documentation for literature review and
- Search methods used in literature evaluation are included in the literature research protocol.
According to Section D OF MDCG 2020-13:
“The clinical evaluation should clearly describe the selection criteria with respect to the regulatory purpose to which it will apply. The CER should clearly differentiate between the two types of data (device under evaluation or an equivalent device, state of the art or alternative treatment option). If the data does not relate to either of the above, provide a rationale with respect to its inclusion.”
b. Providing Additional Documentation
Apart from following the literature research protocol, medical device manufacturers also need to provide additional information given in the below diagram:
Tip 3: Essentials of Literature Research
According to MEDDEV 2.7/1 Revision 4, the medical device manufacturers should perform their literature search according to its criteria. According to its criteria, there are at least two essential topics that every medical device manufacturer should cover i.e.,
- State-of-the-art: A manufacturer needs a state-of-the-art search to demonstrate state-of-the-art for his device and the evaluation of another device in comparison.
- Statement on manufacturer’s device or evaluated device: Statement on the device is needed to show
- Safety;
- Performance, and
- The clinical benefit of the medical device.
Neglecting any of these searches either in state-of-the-art or device evaluation will increase the chances of non-conformity in the audit.
MEDDEV 2.7/1 Revision 4 recommends the PICO method for evidence-based medicine in literature research. For example, this PICO method can help a manufacturer is looking for search criteria in the state-of-the-art.
Tip 4: Search in Relevant Databases
a. Selection of Database According to EU MDR.
EU MDR does not provide any specific advice regarding choosing the correct databases. But according to Article 2(48), it requires peer-reviewed publications for this purpose. It also mentions “Relevant Specialist Literature” and “Databases” for this purpose. However, authors of clinical research can decide to choose the databases as per their wish for their research.
b. Selection of Database According to MDCG 2020-13 Section D:
For reducing bias in the literature review, Section D of MDCG 2020-13 tells the manufacturers to look into multiple databases.
c. Database Selection According to MEDDEV 2.7/1 Revision 4:
MEDDEV 2.7/1 Revision 4’s Annex 4 provides medical device manufacturers with some specific databases for the sake of literature research. These databases include:
- PubMed/Medicine: Provides a good baseline for starting the research. It may not provide completer coverage for European journals.
- EMBASE/Excerpta Medica: Facilitates searches all across Europe by providing the name of the device and manufacturer. Give complete information regarding coverage of medical devices and therapies used in Europe.
- Cochrane CENTRAL trials register: Provides coverage same as that of EMBASE.
Tip 5: Using Boolean Operators to Narrow Down Literature Search
A medical device manufacturer can easily save himself from reading non-specific literature resources by using Boolean operators to narrow down his literature search. These Boolean operators can also be used to expand the search in case the manufacturer does not find enough literature sources.
The most well-known Boolean operators which the manufacturer can use for combining different search terms are AND, OR, and NOT.
While using Boolean operators, using quotation marks and brackets helps in improving the quality of search results.
Use of Quotation Marks
Using “” while searching the term will help the manufacturer in searching for the term in exact order.
Use of Round Brackets
Use of () can help in referring Boolean operators to terms or units.
| Term Used for Search | Number of Publications Found per Search |
| Ice Pack | 1091 |
| “Ice Pack” (term searched with quotation marks) | 250 |
| “Ice Pack” AND “pain reduction” OR “Edema Reduction” (term searched with a quotation mark and OR & AND Boolean operators). | 120 |
| “Ice Pack” AND (“pain reduction” OR “edema reduction”) (term searched with quotation marks, brackets, and OR & AND Boolean operators). | 5 |
From the table, it is evident that efficient use of quotation marks, brackets, and Boolean operators narrow down the overall searching radius of the terms. This helps a medical device manufacturer to spend less time while working on his literature review. However, he must know that each database uses different operators. Therefore, he should consult the relevant website to find out what operator does that website use.
Tip 6: Reading only what’s Important While Going through Search Results
For a medical device manufacturer conducting literature research, it is almost impossible to give a complete read to each publication. In his initial research, there isn’t any need of reading the documents completely. The manufacturer can determine which documents are important for his literature review by looking at their abstract. Those non-relevant publications that are neither related to clinical evaluation nor have any relevance with the device under evaluation can be excluded from reading.
Manufacturers who find the information given in the abstract as incomplete should read the full-text publication.
“Abstracts lack sufficient detail to allow issues to be evaluated thoroughly and independently but may be sufficient to allow a first evaluation of the relevance of a paper. Copies of the full-text papers and documents should be obtained for the appraisal stage.”
Section D, MDCG 2020-13
Conclusion
The manufacturer must use MEDDEV 2.7/1 Revision 4 as their primary guide for literature search. This document along with MDCG 2020-1 helps the manufacturers to put their emphasis on
- Literature research;
- Availability and provision of full-text publications for literature research, and
- Complete meta-information.
Manufacturers should also use tools such as Boolean operators to help them in their research. They can also exclude those publications that are irrelevant to their cause and can thus save their time.
Looking for someone to help you in your Literature Research?
If you are a medical device manufacturer who is looking forward to show compliance to literature research requirements of MEDDEV 2.7/1 and MDCG, you can seek professional consultancy of TSQ&E. TSQ&E is an ISO 13485 certified company that is providing help to medical device manufacturers in showing compliance to FDA, MDR, and other regulatory requirements and standards. To get our help in literature research, contact us on 0541 1797423 or send us an e-mail at info@tsquality.it.
