Literature Search for Clinical Evaluation Reports

An EU MDR (Medical Device Regulation 2017/745) compliant Clinical Evaluation Report (CER) assesses a medical device's risk-benefit profile through various clinical data sources: non-clinical testing, clinical studies, post-market clinical follow-up, post-market surveillance activities, grey literature, and published literature and clinical data, among others.

For lower-risk medical devices that have not undergone clinical trials, clinical data will be collected almost entirely from literature searching published data through systematic reviews.

This article defines and explains some of the most critical terms and concepts in the CER literature review and search strategy.

Note: For this article's purposes, the terms literature search and literature review will be used interchangeably.

MEDDEV 2.7.1 Rev. 4

MEDDEV 2.7.1 Rev. 4 was issued in June 2016 to "... promote a common approach to clinical evaluation for medical devices regulated by directives 90/385/EEC and 93/42/EEC."

Although published as a guide for clinical evaluations of medical devices under the previous medical device directives, it is still used as the industry standard for guidance on clinical evaluation reports and literature searches.

Any medical device manufacturer or medical writer planning to perform compliant clinical evaluation reports for medical devices under the EU MDR should be familiar with and comfortable with MEDDEV 2.7.1 Rev. 4. You can read a thorough review of the guidance here.

Literature Search: The Basics

Clinical data

Clinical data is any safety or performance data that generated from the clinical use of a device, as defined in MEDDEV 2.7.1 Rev. 4.

Clinical data can be sourced from:

• Clinical investigations of the device concerned
• Clinical investigations or other studies reported in the scientific literature of a similar device for that equivalence to the device in question can be demonstrated
• Published and/or unpublished studies (such as grey literature) on other clinical experiences of either the device in question or a similar device

State of the art

State-of-the-art establishes your medical device within current industry standards and knowledge. The benefit-risk profile of a medical device is not complete before it has been compared to other similar devices on the market - it is the only way to assess whether your device poses more or less risk than other devices and whether it is more or less efficient.

MEDDEV 2.7.1 Rev. defines state-of-the-art as "...applicable standards and guidance documents, information relating to the medical condition managed with the device and its natural course, benchmark devices, other devices and medical alternatives available to the target population."

State-of-the-art is always established through conducting a literature search.

Literature search protocol

Before starting your literature review, you must establish your literature-searching endpoints - what you are looking for and how you will find it. Your literature search protocol should include the complete plan for your literature search, including search strategy, search methods, search terms, data sources, inclusion and exclusion reasons for the published results, and any further research required to fulfill the search objectives.

Annex-5.3 of MEDDEV 2.7.1 Rev. 4 includes a list of what you should include in your protocol.

It is a good idea to perform an initial search before writing your protocol to get a lay of the land and understand which research databases are right for you and potential areas of future research.

Literature databases

You need to look in the right places to find the right information. The relevant databases for your device might differ depending on risk classification and market authorizations, among others.

PubMed, Embase, and the Cochrane Library are the most frequently used, but others can also be relevant. Livivo is a German database focused on European literature, while clinicaltrials.gov includes data on global clinical trials.

Your search strategy should establish which databases are relevant for your medical device and why.

Literature appraisal

An effective literature search can return hundreds, if not thousands, of results. An effective literature review appraises relevant articles and discards articles that are not.

Literature appraisal is a tricky part of literature searching, but it can be simplified by reviewing four factors:

Suitability

Does the publication study your device or a similar or equivalent device?

Applicability

Does the publication study other devices that use the same technology and have the same intended use or application?

Population

Is the population in the article appropriate for your device's use?

Quality

Does the article apply appropriate scientific methods? Is it published in a peer-reviewed journal? Is the study design appropriate?

Arguably, quality is the most important aspect of a study if the other points have been met. MEDDEV 2.7.1 Rev. 4 describes issues to look out for in Annex 6.

Once you have discarded the unwanted publications, your dataset (the included publications) should be weighted. Weighting assigns higher values to high-quality, relevant data and lower values to less relevant or lower-quality data.

As with all other parts of literature searches, your data appraisal should be documented and presented so a third party can review it easily.

Equivalent device

Equivalent devices can be used as proxies when assessing clinical data. To be used, an equivalent device should have the same technical, biological, and clinical characteristics as your device.

In general, establishing equivalence can be complicated as you need sufficient access to the equivalent device data to justify equivalency claims. This typically means having access to the complete technical file, which most companies are loath to grant to their competitors.

Similar device

On the other hand, similar devices are relatively easy to use to support clinical evidence. You need less data to establish a medical device similar to yours.

Similar devices should have the same intended use, the same technology, and the same or very similar application and clinical indications.

A comprehensive search and literature review is a key part of the clinical evaluation report. It is how you place your medical device in the current industry and demonstrate that it is safe and efficient when it performs as intended.