3 Steps to MDR/IVDR Compliant Systematic Literature Review

Clinical Evaluation Reports

A systematic literature review is a method to collect, identify, and synthesize literature as objectively as possible with minimal selection bias. This type of search can be used to evaluate the safety and performance profile of medical devices for clinical evaluation reports or in vitro diagnostic devices for performance evaluation reports. Specifically, in the European Medical Device Regulation (MDR), to plan, continuously conduct, and document a clinical evaluation the manufacturer shall “identify available clinical data relevant to the device and its intended purpose and any gaps in clinical evidence through a systematic scientific literature review” (MDR Annex XIV Part A(1)(b)). Similarly in the European In Vitro Diagnostic Medical Devices Regulation (IVDR), to demonstrate scientific validity and analytical and clinical performance, the manufacturer shall “identify through a systematic scientific literature review the available data relevant to the device and its intended purpose and identify any remaining unaddressed issues or gaps in the data” (IVDR Annex XIII Part A(1.2)). Further, both regulations require appraisal of “all relevant data by evaluating their suitability for establishing the safety and performance of the device” (MDR Annex XIV Part A(1)(c) and IVDR Annex XIII Part A(1.2)).

This blog describes the three main steps to perform a systematic literature review of published clinical data for clinical (medical device) or performance (in vitro diagnostic) evaluation.  In addition to published reports in the scientific literature, other sources of clinical data include clinical investigations of the subject device and clinically relevant information from post-market surveillance (MDR Annex XIV Part A and IVDR Annex XIII Part A for medical devices and IVDs, respectively).

1. Defining the search
   Identifying the parameters of the search before performing the search reduces selection bias and improves the quality of data retrieved. The search protocol includes the scope or objective of the search, a list of sources or databases, proposed search terms and limits, and criteria for inclusion and exclusion. One challenge of defining a search protocol is to be comprehensive enough to capture the available clinical data, but at the same time specific enough that time is not wasted sifting through irrelevant data.
2. Assessing results
   Once the search protocol has been established, the comprehensive search can be performed and documented. Search documentation needs to be accurate and sufficiently descriptive so that the approach can be reviewed critically and the results verified. The published data identified by the search are evaluated for the inclusion and exclusion criteria described in the protocol. Records should be kept of the disposition and rationale for each search result. Then the included data are assessed for relevance and quality through the appraisal and weighting process. There are many methods that can be used to appraise and weight clinical data. The International Medical Device Regulators Forum (IMDRF) Medical Device Clinical Evaluation (MDCE) WG/N56FINAL:2019 Guidance outlines the general principles of this process.

   The next part of the assessment is to determine the level of evidence of the data. Depending on the intended purpose of the device (e.g., intervention, diagnosis, prognosis), there could be different sources and impact of bias. There are many systems to rank the rigor and potential influence of unintentional bias related to the study design. The common ones are recommended by the Australian National Health and Medical Research Council (NHMRC), Oxford Centre for Evidence-Based Medicine, and Cochrane handbook.

3. Synthesizing data
   Once the relevant data have been identified and evaluated, the safety and performance outcomes are summarized in the clinical evaluation report (or performance evaluation report for IVDR). Data pertaining to use of the subject device will be compared with the relevant state of the art benchmark rates.

   The search protocol, search report and copies of relevant references all become part of a device’s technical documentation. Overall, the systematic literature review required for MDR CER and IVDR PER is an important process that can be challenging to execute correctly. MED Institute scientists have these capabilities and can help you with these efforts. MED offers a variety of scientific communication services and is a full-service CRO.

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