Literature and Data Appraisal in Clinical Evaluation Reports

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Substantiating the safety and performance of your medical device is the most important part of bringing a medical device to market. In the European Union (EU), the clinical evaluation report (CER) is a major component of this process. The identification of literature and other data relevant to your device is critical to the success of your report. Subsequently, the values and limitations of this data should be assessed by way of an appraisal. During the appraisal, the data is weighted based on their relative contributions to demonstrating the safety and performance of the device. There are many different ways to perform this appraisal, but some requirements need to be met for your CER to pass the scrutiny of a Notified Body. The article provides an overview of those requirements.

MEDDEV 2.7/1 Revision 4 advises that you perform the clinical evaluation in discrete parts labeled Stage 0 through Stage 4. Stage 0 requires that you define the scope and plan the clinical evaluation, while stage 1 calls for identifying the data that you will use in the evaluation. During Stage 1, you perform a literature search to identify clinical data relevant to the device under evaluation (subject device) and, if applicable, the equivalent device, as well as data on the current knowledge or state of the art.

The next step, Stage 2, is where the appraisal of the literature occurs. In this stage, you will determine the value of the literature you identified in Stage 0 and Stage 1 in regard to its contribution to the clinical safety and performance of the device. This is done by identifying what relevant information each document contains and evaluating the quality of the methodology of the research and the scientific validity of its data, as well as systematically weighting how the information held therein contributes to the clinical evaluation as a whole. The first step in this stage requires you to create an appraisal plan which is a systematic, unbiased outline that explains the process and criteria to be used for the appraisal. Your appraisal plan should be thorough and objective and define and assign weighting to both positive and negative components of each document. The criteria on which your appraisal is based should adequately reflect the nature, history, and intended clinical use of the devices and should be based on current knowledge while applying recognized scientific standards.

Once you have completed the appraisal plan, the appraisal can commence. Your appraisal should be based on full text literature and of other documents and not abstracts or summaries. MEDDEV 2.7/1 Rev. 4 divides the guidance of appraisal process into three which include:

1. How to evaluate methodological quality and scientific validity

Assess the methods used to gather and synthesize the data and determine to what extent the performance and safety outcomes are a result of confounding influences, bias, random error, inadequate disclosure of information, and/or misinterpretation. When assessing the methodological quality and scientific validity of the evidence, you can consider a range of factors. Some examples include:

  • Study design of pre-market and post-market clinical investigations: including but not limited to adequacy of endpoints, applied controls, adverse event reporting, medication handling, follow-up period, and procedures for retrieving complete information (e.g. procedures for when a subject leaves the study or when contact with patients are lost)

  • Additional aspects for appraisal of the quality of clinical investigations generated and held by the manufacturer including: the clinical investigational plan, amendments and rationale for these changes, and clinical investigation report; monitoring and audit case reports; ethics committee documents; and regulatory body approvals
  • Information derived from vigilance data, device registry data, case series, patient dossiers, and other use data
  • Data processing and statistics
  • Quality assurance
  • Report quality: including adequacy of disclosure of methods used adequacy of disclosure data

2. How to determine the relevance of your data sets for the clinical evaluation

Determine whether the data you are appraising is intended to be pivotal or supportive. If the data is pivotal it must be of a quality that demonstrates clinical performance and clinical safety of the subject device. Pivotal data must be derived from the subject or equivalent device and used for its intended purpose. You must also appraise and weight data that are not pivotal to ascertain how they affect the state of the art of the subsequent medical field, the identification of hazards, justification of the validity of equivalence criteria, and surrogate endpoints. The hazards you identify in this data can be used to identify unknown hazards associated with the device. A summary of the information obtained from data that is not pivotal should be included in the literature review of the clinical evaluation report.

3. How to weight the contribution of each data set

Weight your data according to their relative contributions in terms of their scientific validity and relevance. There is no single method for weighting clinical data so you should identify and pre-define the appropriate criteria for each evaluation and strictly follow these criteria. The highest rating should be assigned to clinical data when it is derived from a randomized controlled clinical investigation, using the subject device for its intended purposes with users who represent the target population. If you reject any evidence, including studies and reports that are generated and those that are held by the manufacturer, you should document the reason for rejection.

No matter what method you choose to use for the appraisal of literature and data identified for your CER, it is important that you follow some basic guidelines when carrying it out. This includes properly planning your appraisal and defining criteria; weighting the data based on its quality, scientific validity, relevance and contribution to demonstrating the safety and performance of the device. A proper appraisal helps to ensure the validity of the next stage in the CER process (Stage 4 – analyzing the clinical data to determine compliance with the MDR General Safety and Performance Requirements).

How Nerac Can Help?

Nerac’s Medical Device team has experience developing MDR 2017/745 compliant documents. Our analysts are experts in literature searches, appraisals, and Clinical Evaluation Reports. Contact Nerac today to discuss how we can help you with your clinical evaluation needs.

About the Analyst

Miriam Sharif-Murray, M.S., RAC

Miriam Sharif-Murray brings over 20 years of medical device/regulatory experience to Nerac clients. After completing her degrees, she worked as a chemist for chemical and medical device manufacturers where she further strengthened her scientific knowledge and built her expertise in the regulatory environment.

Academic Credentials

  • M.S., Biology, Tennessee State University
  • B.A., Biology, Fisk University

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