Overview of the new Guidance documents from MDCG on Clinical Investigations and Evaluations

May 5, 2020
in
 - written by 
Erika
Pinto
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The EU Medical Device Coordination Group (MDCG) has provided a series of guidance documents for manufacturers to use on their path to MDR compliance.  As of April 2020, the Medical Device Regulation (MDR)  has officially been extended by one year to May 2021. The EU commission has released four new guidance documents on Clinical Investigations and Evaluations.  The following documents will help manufacturers to conduct relevant clinical activities in an organized manner. 

The guidance documents released as of April 2020: 

  1. Guidance on PMCF Evaluation Report Template
  2. Guidance on PMCF Plan Template
  3. Guidance on Sufficient Clinical Evidence for Legacy Devices
  4. Guidance on Clinical Evaluation – Equivalence

This blog will provide an overview of the guidance documents and summarize each document so that manufacturers can take action accordingly. 

PMCF Evaluation Report Template

The template will help manufacturers compile their Post-Market Clinical Follow-up (PMCF) evaluation report according to the requirements of the MDR. This will allow manufacturers to present their PMCF data in an organised manner eventually making it easier for notified bodies and competent authorities to find information.

Under the MDR, PMCF is to be considered as a ‘continuous process to update the Clinical Evaluation’ which is then addressed in the PMS plan. 
The conclusions from the PMCF evaluation report will be used to update the Clinical Evaluation, the risk management documentation, the PMS plan and SSCP (if applicable)

Section Information to be addedAManufacturer & Contact DetailsBMedical Device description & specificationCActivities undertaken related to PMCF: resultsDEvaluation of clinical data relating to equivalent or similar devicesEImpact of results on the technical documentationFReference to specifications, harmonized standards or guidance documents appliedGConclusions

Section C is where you report all the activities mentioned in section C of the PMCF Plan and discuss the analysis of findings. Each activity performed a subsection is to be created with descriptions on type of activities and quality of data collected.

Section G is where you conclude the findings and relate them to the PMCF Plan. The conclusions stated here will be included in the Clinical Evaluation and risk management. The conclusions drawn can provide input to your next PMCF Plan

Download the official guidance document here

PMCF Plan Template

The aim of this document is to help manufacturers to 'compile a PMCF Plan'. To present the relevant post market clinical data in a harmonized way. It will eventually allow Notified Bodies and Competent Authorities to easily find relevant information. 

A PMCF plan shall specify the methods and procedures set up by the manufacturer, to proactively collect and evaluate clinical data from the use in or on humans of a CE marked medical device, placed on the market or put into service within its intended purpose, as referred to in the relevant conformity assessment procedure.

The aim of the PMCF plan is to indicate:

  •  How the manufacturer will confirm  the safety and performance of the device throughout the device life cycle
  • Detail the how the manufacturer will identify previously unknown side-effects and monitor the identified side-effects and contraindications;
  •  identifying and analysing emergent risks on the basis of factual evidence;
  •  ensuring the continued acceptability of the benefit-risk ratio, referred to in Section 1 and 9 of Annex I in the MDR;
  •  identifying possible systematic misuse or off-label use of the device, with a view to verifying that the intended purpose is correct.

The PMCF Plan template has been broken down into sections and each section requires different information as shown below.

SectionInformation to be addedAManufacturer contact detailsBMedical Device description & specificationCActivities related to PMCF: general & specific methods and procedures DReference to the relevant parts of the technical documentationEEvaluation of clinical data relating to equivalent or similar devices FReference to specifications, harmonized standards or guidance documents appliedGEstimated date of the PMCF evaluation report

Section C is where you need to detail the activities you intend to conduct. Examples are given in relation to conducting device registries, PMCF studies, Real-world evidence & Surveys. Each activity should be a subsection eg. C1, C2 and should include: 

  • Number of activity
  • Description of activity
  • Aim of the activity
  • Rationale and known limitations of the activity 
  • Timelines of the activity

Section E is where you indicate the information on equivalent/similar devices. For each device the following should be provided: 

  • Product name of equivalent/similar device
  • Intended purpose
  • Intended users
  • Intended patient population
  • Medical Conduction
  • Indication
  • Reference to clinical data evaluation in the CER (date, version & location in text)

Download the official guidance document here

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How do the two documents work together?

The PMCF Plan will dictate what activities you will conduct to collect PMCF data. The PMCF Evaluation Report will document the results of the analysed PMCF data. The Clinical Evaluation Report will include the conclusions from the PMCF evaluation report. The PMCF Plan is to be be addressed in the PMS plan 

Sufficient Clinical Evidence for Legacy Devices 

The aim of the document is to provide practical guidance on several scientific and clinical aspects that are relevant for conducting a clinical evaluation for Legacy Devices. There is guidance on each stage of the clinical evaluation process of the MDR Annex XIV Part A Section 1.

Establish or update a clinical evaluation plan

Manufactures are  required  to  document  a  clinical  evaluation  plan  to  meet  the requirements of MDR Annex XIV Section 1a. It is suggested to include:

  • Identification of the relevant GSPRs
  • Specification of the intended purpose, target groups, indications, contraindications
  • Detailed description of intended clinical benefits with relevant and specified clinical outcome parameters 
  • Specification  of  qualitative  and  quantitative  aspects  of  clinical  safety  and performance

Identify available clinical data

All clinical data from both the pre-market and post-market phases should be identified, which may include: 

Pre-market sourcesPost-market sourcesClinical investigation reports of the device concernedPMS clinical data, complaint and incident reportsClinical investigation reports or other studies reported in scientific literature
PMCF studies, including post-market clinical investigationsReports published in peer reviewed scientific literature on other clinical experience
Independent clinical studies conducted using the deviceOther pre-market data, e.g. case reports
Device registries
Data retrieved from the literature.

Furthermore, the MDR requires confirmation of conformity with the relevant GSPRs to be based on clinical data.

Appraisal of the clinical data 
To identify and assess the level of evidence bias or other impossible shortcomings, it is important to use data obtained from different sources. Clinical data appraisal should be conducted using verified/validated assessment tools.

Generation of new clinical data
If it is not adequately comprehensive to provide sufficient clinical evidence and the demonstration of equivalence is no longer possible, new data may need to be generated prior to CE-marking under the MDR.  However, there shall be sufficient clinical evidence to confirm safety, performance and the acceptability of the benefit-risk determination.

Analysis of the clinical data
The aim of the last stage is the determination if all clinical data are collected and appraised as described in the previous stages and demonstrate together conformity with relevant GSPR.

The demonstration should be based on:

  • The usage of reliable, justified and sound analytical methods
  • Results of performed comprehensive analysis
  • Identification of any missing data and/or gaps
  • Determination of PMCF needs
  • Determination of benefit-risk ratio

Download the official guidance document here

Clinical Evaluation - Equivalence

The goal of this guidance document is to detail the differences between the MEDDEV and the MDR when it comes to demonstrating equivalence. The idea here is to give companies the additional support and guidance needed to provide a more harmonized approach in the EU.

The MDR requires that technical, biological, and clinical characteristics are taken into account when demonstrating equivalence to another device. The characteristics are also described in the MEDDEV however there are some differences between them. 

Technical Characteristics 

  • MDR demonstrate that the device question and the device presumed to be equivalent are used under “similar conditions of use” where MEDDEV specifies under “same conditions”
  • MDR have added and specifically pointed out “software algorithms” to the specification and properties for a medical device where MEDDEV have not. 

Biological Characteristics 

  • The MDR has additional requirements for devices  that  are  composed  of substances  or  of  combinations  of  substances that  are  intended  to  be introduced into the human body, absorbed by or locally dispersed.

Clinical Characteristics 

  • MDR does oppose MEDDEV requiring that, for manufacturers to compare clinical characteristics, the device shall have the “same kind of user”, which means any healthcare professional or layperson who uses a device.
  • The MDR does not explicitly state that the medical device needs to be used for “the same medical indication, gender and duration” of use as the equivalent device as MEDDEV points out.

Demonstration of equivalence 
Both MDR and MEDDEV state that consideration must be given to the characteristics mentioned above and a gap analysis should be conducted  by  the  manufacturer  to  evaluate  any  clinically  significant difference

  • In addition, MDR requires that considerations of equivalence shall ”be based on proper scientific justification”.

Use of data from similar devices 
The document highlights that, in cases where equivalence cannot be demonstrated under the MDR, the data from similar devices may be useful for a variety of other purposes.

The MDR defines this similar device as “a set of devices having the same or similar intended purposes or a commonality of technology allowing them to be classified in a generic manner not reflecting specific characteristics”.

Clinical Data Identification
Clinical evaluation of the device under assessment shall be made according to the MDR which both includes favorable and unfavorable data. If the data meets the requirements of MDR, it progresses to data appraisal and analysis for evaluating the sufficient clinical evidence for the purpose of confirmation of conformity.

Equivalence Table

The guidance document provides a ‘Equivalence Table’ to clearly show equivalence and the supporting data. The table is divided into 3 sections to classify Technical, Biological & Clinical Characteristics. The document also highlights that manufacturers are to identify differences between the devices and not only focus on similarities. The examples provided are to be interpreted as examples and not to be considered as an exhaustive list. 

Scientific justifications shall be provided for the different characteristics when claiming no clinically significant difference in the safety and clinical performance of the device.

When more than one device is used for equivalence then a separate table is to be completed and the documents demonstrating the equivalence are to be added in the clinical evaluation report.

Download the official guidance document here

In conclusion, these guidance documents are useful tools for manufacturers on their path to MDR compliance. They indicate the need for structured, organized and compliant data collection and management. 

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