Literature Review

BioReg Services specializes in systematic literature reviews in compliance with the MDR Regulation (EU) 2017/745, IVDR Regulation (EU) 2017/746 and MEDDEV 2.7/1 rev.4 (2016) guidance.
Our team can design a comprehensive literature search protocol with complete documentation of the literature screening and data extraction process. We can obtain clinical evidence for the literature review for your new medical device or update the literature review of a CE-marked or legacy device to create an MDR-compliant document.
The literature review is part of the Clinical Evaluation Report and should be based on a search protocol that documents the search planning before execution.

For the literature search methods and strategy review, MEDDEV 2.7/1 revision 4, section A5 and MDCG 2020-13, Section D. The literature data should be retrieved from at least two databases. For e.g., you can use PubMed & Cochrane Library database. The literature search should clearly distinguish between two types of data: the device under Evaluation (or its equivalent device) and the State-of-Art (SoA). The literature search should be documented in sufficient detail so that the methods can be appraised critically, the results verified, and the search reproduced if required.
See our 3-part series blog about the Medical Device Literature Review Part 1, Part 2 and Part 3.
For more information, please contact the BioReg team.

Frequently Asked Questions

Question: What should be included in the Literature Search protocol?

Answer: The literature search protocol should provide a brief summary of the literature search strategy applied, commenting on:
• Adequacy of search terms: for example, it should be sufficiently broad to establish benchmarks, determine the general state of the art, determine potential risk, adverse events, undesirable side-effects, etc.
• Databases used
• Acceptability of inclusion and exclusion criteria.
• Both favorable and unfavorable data are included.
• Strategies for avoiding data duplication.
• Any deviations from the manufacturer’s literature search protocol.

Question: Since accessories are also referred to as devices (Article 1:4), we believe we need to perform a literature analysis for each accessory in our product. Is our approach correct?

Answer: We understand your logic; however, if you follow it to its full potential, you will have to do GSPR, PMS, PMCF, Risk, clinical evaluation, etc., for each accessory of the product, which was not, in our opinion, the legislator’s intention.   Each accessory contributes to the final product’s overall clinical evaluation, benefit-risk ratio, etc.; we can identify and describe such contributions. However, it is usually sufficient to perform the literature analysis for the final product only. I think that your approach may apply to a greater extent to the products contained in the “Procedure pack” (MDR 2(10) or “System” (MDR 2(11)). Similarly, for devices incorporating a medicinal product (Rule 14), you need to justify (clinical benefit, etc.) the addition of medicinal substance(s).

Question: What are the clinical evaluation requirements for orphan devices?

Answer: As per  MDCG 2024-10 Clinical evaluation of orphan medical devices, the clinical evaluation requirements for the orphan devices are the same as for the other medical devices (as per MDR, Article 61 and Annex XIV). The clinical evaluation includes the following stages:

• establish and update a clinical evaluation plan;
• identify relevant clinical data and any limitations in clinical data;
• appraise all relevant clinical data;
• analyze all relevant clinical data;
• generate new or additional clinical data needed to address outstanding issues;
• document this evaluation in a clinical evaluation report; and
• update the clinical evaluation through PMCF activities.

Question: Do implantable and/or class III orphan devices (OD) require clinical investigation, or maybe a literature route could be used?

Answer: These group devices would require clinical investigations unless they are exempt under MDR (Article 61). Due to the complexity of OD clinical trials, new guidance advises involving clinical experts for the appropriate clinical design. In addition, engagement with patients, patient associations, parents, and/or caregivers of the target population may also be helpful in confirming whether the study includes patient-relevant clinical outcomes.

In Appendix A.2 of MDCG 2024-10 Clinical evaluation of orphan medical devices, you can find additional considerations for clinical investigation design (for all medical device classes), including:

• Defining the study population
• Selecting appropriate objectives and endpoints
• Choice of study design
• Choice of comparator
• Study monitoring

The company should also assess the possibility of using clinical data extrapolated from the device’s use in other, non-orphan populations (see Appendix A.3 of the guidance on extrapolation).