CLINICAL EVALUATION REPORT AS PER MEDDEV 2.7/1 REV. 4 A detailed analysis by Asha Meria Johnson, Jr. Consultant @ I 3 Consulting.

1. CLINICAL
EVALUATION
AS PER MEDDEV 2.7/1 REV. 4 June 2016
by Asha Meria Johnson, Jr. Consultant
[Medical Device Regulations] at I 3 Consulting
E-mail: aj@i3cglobal.com
WHAT IS CLINICAL EVALUATION?
According to MEDDEV 2.7/1 REV. 4, CLINICAL EVALUATION is, “
A sound on-going procedure to collect, appraise and analyse
clinical data pertaining to a medical device and to evaluate
whether there is sufficient clinical evidence to confirm compli-
ance with essential requirements for safety and performance
when using the device according to the manufacturer’s Instruc-
tions for Use.”
Note: In exceptional cases where IFUs are not required, the col-
lection, analysis and assessment are conducted taking into ac-
count generally recognized modalities of use.

2. E.U. directives outlined requirements under which Medical Devic-
es could be marketed in all E.U. member states only after attain-
ing a CE mark in any one member country.
CLINICAL EVALUATION is an important step towards the path to
initial CE certification and must be actively updated thereafter.
The requirements of CLINICAL EVALUATION apply to all classes
of medical devices [I, IIa, IIb & III].
CLINICAL EVALUATION is necessary and important as it ensures
that the evaluation of safety and performance of the device is
based on the clinical evidence throughout the lifetime that the
device is on the market.

3. CLINICAL EVALUATION is performed in 5 discrete stages, based on a compre-
hensive analysis of available pre– and post-market clinical data relevant to the
intended purpose of the device in question including clinical performance and
clinical safety data.
¨ Stage 0: Scoping & the Clinical Evaluation Plan
¨ Stage 1: Identification of pertinent data
¨ Stage 2: Appraisal of individual data set in terms of scientific validity,
relevance & weighting
¨ Stage 3: Analysis of the data by confirming:
· the compliance with Essential Requirements (ER1, ER3, ER6)
performance & safety of the device, including its benefit/risk
profile
· contents of information from manufacturer’s data [IFU, Label,
promotional materials etc.]
· residual risks and uncertainties that requires to be addressed in
PMS
¨ Stage 4 : Finalized Clinical Evaluation Report

4. WHO SHOULD PERFORM CLINICAL EVALUATION?
Þ Should be conducted by a suitably qualified individual or team
Þ Manufacturer should justify the selection of the Clinical Evaluator
Þ Clinical Evaluators should possess knowledge of the following:
· Research methodology
· Information management
· Regulatory requirements
· Medical writing
· Device technology
· Clinical Expertise
· Relevant degree of 5yrs. of documented professional ex-
perience or 10 yrs. of documented professional experi-
ence

5. STAGE 0: SCOPING & THE CLINICAL EVALUATION PLAN
The Scope of Clinical Evaluation should be:
· Based on Essential Requirements
· Basis of future steps
· Identification, Appraisal & Analysis of both favourable and unfa-
vourable data
The Clinical Evaluation Plan should cover different aspects as shown:
ASPECTS BEFORE CE AFTER CE
Device description X X
Safety concerns, safety concerns, claims made by the manu-
facturer
X X
Information needed for equivalence X
Risk management documents X X
Current knowledge & State of the Art X X
Data Source & Type X X
Changes in design, materials and manufacture, information
materials
X

6. STAGE 0: SCOPING & THE CLINICAL EVALUATION PLAN
The Clinical Evaluation Plan should cover different aspects as shown:
ASPECTS BEFORE CE AFTER CE
Specific new clinical concerns X
PMS aspects such as:
· New clinical data of device and
equivalent devices
· New knowledge about potential
hazards, risks, performance,
benefits & claims, treatment
standards
X
PMS planning needs X

7. STAGE 1: IDENTIFICATION OF PERTINENT DATA
DATA GENERATED AND HELD BY THE MANUFACTUR-
ER
· All data generated and held by the manufacturer
need to identified
· Complete data (clinical & use data) need to dis-
closed to the evaluators (including Europe & other
countries)
· All data should be adequately summarized, ap-
praised, analysed & referenced in the Clinical Evalu-
ation Report
DATA RETRIEVED FROM LITERATURE
· All data should be thorough and objective
· Searches should be varied with different search
criteria
· There should be a search protocol, search report
to verify the adequacy of searches and that needs
to be appraised critically
· Search protocols, documented search results and
reports become part of the Clinical Evidence
All data from pre-market clinical investigations Clinical data relevant to the device under evaluation or equiv-
alent devices
Data from Risk Management Activities and PMS programs:
· PMCF studies
· PMS Reports
· Literature search and evaluation reports for PMS
· Incident reports
· Complaints
· Field safety corrective action reports
· Other user reports etc.
Current knowledge/State of the art
· Applicable standards and guidance documents
· Clinical data that describe the clinical background
· Clinical data relevant for identifying potential clinical
hazards
· Clinical data that can justify the validity of criteria
used for demonstration of equivalent devices
· Clinical data that can justify the surrogate endpoints
Relevant pre-clinical study reports

8. STAGE 2: APPRAISAL OF INDIVIDUAL DATA SET IN TERMS
OF SCIENTIFIC VALIDITY, RELEVANCE & WEIGHTING
GENERAL CONSIDERATIONS:
· Determine the value of the data identified in Stage 1
- identify the information contained in each document
- evaluate methodological quality of the data
- determine relevance of the data
- systematically weight the contribution of each clinical
data set
· Systematic appraisal

9. STAGE 2: APPRAISAL OF INDIVIDUAL DATA SET IN TERMS
OF SCIENTIFIC VALIDITY, RELEVANCE & WEIGHTING
1. THE APPRAISAL PLAN
Following procedure and criteria are to be used for
appraisal:
Þ determining the methodological quality and the scientific validity of
each data set
Þ determining the relevance to the clinical evaluation
Þ weighting the contribution of each data set to the overall clinical evalua-
tion
Þ should be thorough and objective
Þ the appraisal should reflect the nature, history and intended clinical use
of the device on the basis of current knowledge/state of the art
Þ qualitative & quantitative appraisal is acceptable
Þ should be documented in the Clinical Evaluation Report

10. STAGE 2: APPRAISAL OF INDIVIDUAL DATA SET IN TERMS
OF SCIENTIFIC VALIDITY, RELEVANCE & WEIGHTING
2. CONDUCT OF THE APPRAISAL
Þ Follow the appraisal plan and apply its criteria
Þ Base their appraisal on full text of publications, full da-
tasets
Þ Document the appraisal process in the CER

11. STAGE 2: APPRAISAL OF INDIVIDUAL DATA SET IN TERMS
OF SCIENTIFIC VALIDITY, RELEVANCE & WEIGHTING
2.1 Methodological Quality & Scientific Validity
The evaluators should examine the methods used to generate/
collect the data and evaluate the extent to which the observed effect
(performance or safety outcomes) can be considered to be due to
intervention with the device or due to:
¨ Confounding Influences
¨ Bias, random error, inadequate disclosure of information,
misinterpretation
¨ Study design [pre-market & post-market clinical investiga-
tions]- sample size & power calculation, end-points, applied
controls , randomization, inclusion/exclusion criteria. Prog-
nostic factors, blinding of patients, follow-up, reliability
methods, serious adverse event recording and reporting,
handling of medications & missing data

12. STAGE 2: APPRAISAL OF INDIVIDUAL DATA SET IN TERMS
OF SCIENTIFIC VALIDITY, RELEVANCE & WEIGHTING
2.1 Methodological Quality & Scientific Validity
The evaluators should examine the methods used to generate/ col-
lect the data and evaluate the extent to which the observed effect
(performance or safety outcomes) can be considered to be due to
intervention with the device or due to:
¨ IRB/EC Approvals, Regulatory Approvals
¨ Clinical Investigation Plan– plan amendments and rationale
for changes
¨ Case report form, monitoring & audit records
¨ Serious Adverse Event Report [SAE], Intermediate Report
¨ Clinical investigation outside EU– analysis if transferrable to
EU population

13. STAGE 2: APPRAISAL OF INDIVIDUAL DATA SET IN TERMS
OF SCIENTIFIC VALIDITY, RELEVANCE & WEIGHTING
2.1 Methodological Quality & Scientific Validity
The evaluators should examine the methods used to generate/ col-
lect the data and evaluate the extent to which the observed effect
(performance or safety outcomes) can be considered to be due to
intervention with the device or due to:
¨ Gap analysis
¨ Applicable Ethical and Regulatory standards: ISO 14155,
Declaration of Helsinki [DoH], GCP
¨ Vigilance Data device registry data, case series, patient dos-
siers, and other use data
¨ Statistical methods– suitability & exclusions
¨ Quality Assurance– compliance with all the relevant stand-
ards
¨ Report Quality- disclosure of methods & data, Validity of
conclusions drawn by authors

14. STAGE 2: APPRAISAL OF INDIVIDUAL DATA SET IN TERMS
OF SCIENTIFIC VALIDITY, RELEVANCE & WEIGHTING
2.2 Relevance & Weighing of the Clinical Data Set
The evaluation of the relevant data collected is done by
checking whether it is intended to directly demonstrate ade-
quate clinical performance and clinical safety of the device
(often referred to as pivotal data), or whether the data serves
an indirect supportive role.
¨ Pivotal Data
Data of device under investigation or of the equiva-
-lent device
¨ Other Data
Data for the purpose of identifying and defining cur-
-rent knowledge/state of the art, identifying hazards,
validity of equivalence criteria, validity of surrogate
end-points, input for planning of pivotal studies

15. STAGE 2: APPRAISAL OF INDIVIDUAL DATA SET IN TERMS
OF SCIENTIFIC VALIDITY, RELEVANCE & WEIGHTING
2.2 Relevance & Weighing of the Clinical Data Set
Aspects to consider when determining relevance for the De
vice under evaluation, Equivalent Device, Benchmark de
vice and Other devices:
¨ Extent to which the data generated are representa-
tive of the device under evaluation
¨ Aspects covered (performance data, safety data,
claims etc.)
¨ Intended purpose or the claims relevant to the device
¨ Model, Size or Setting of the device
¨ User group, patient demographics
¨ Medical indication, Severity of the medical condition
¨ Duration of use

16. STAGE 2: APPRAISAL OF INDIVIDUAL DATA SET IN TERMS
OF SCIENTIFIC VALIDITY, RELEVANCE & WEIGHTING
2.3 Weighting of the Clinical Data Set
Based on their scientific validity and relevance, the data
should be weighted according to their relative contributions.
No single well established method for weighting clinical da-
ta. Hence:
¨ the evaluators should identify appropriate criteria to
be applied for a specific evaluation;
¨ these pre-defined criteria should be followed strictly
by the evaluators.

17. STAGE 3: ANALYSIS OF THE CLINICAL DATA
3.1 General Considerations
Analysis of clinical data is performed to determine if the ap-
praised data sets available for a medical device collectively
demonstrate compliance with each of the Essential Require-
ments pertaining to the clinical performance and clinical
safety of the device, when the device is used according to its
intended purpose.
In order to demonstrate compliance, the evaluators should
a) use sound methods;
b) make a comprehensive analysis;
c) determine if additional clinical investigations or other
measures are necessary;
d) determine PMCF needs

18. STAGE 3: ANALYSIS OF THE CLINICAL DATA
3.2 Specific Considerations
a) Use of Sound Methods– Qualitative or Quantitative
b) Perform a Comprehensive Analysis
¨ determine compliance of Clinical performance and
safety with Essential Requirements
¨ adequacy of pre-clinical testing to verify safety risks
to patients and users associated with the intended
purpose benefits to patient
¨ confirmation of device performance as intended by
the manufacturer, usability, design, IFU
¨ gaps in the evidences need to be identified
¨ assess the consistency in documents

19. STAGE 3: ANALYSIS OF THE CLINICAL DATA
3.2 Specific Considerations
c) Determine if additional clinical investigations or other
measures are necessary-done to generate any missing data
and eliminate compliance issue
d) Determine PMCF needs– residual risks, any uncertainties,
unanswered questions, rare complications, uncertainties
regarding medium- and long-term performance, or safety
under widespread use.

20. STAGE 3: ANALYSIS OF THE CLINICAL DATA
3.3 Where demonstration of conformity with Essential
Requirements based on clinical data is not deemed
Appropriate– Adequate Justification has to be given,
· Based on output of Risk Management Process
· Based on device/body interaction, clinical per-
formances intended and claims of manufactur-
er
· Adequacy of demonstration of conformity with
Essential Requirements
A clinical evaluation is still required with above men-
tion information and evidence-based justification must
be presented in the Clinical Evaluation Report.

21. STAGE 4: THE CLINICAL EVALUATION REPORT [CER]
¨ CLINICAL EVALUATION REPORT documents Clinical Evalua-
tion and its outputs.
¨ It Should contain sufficient information to be read and under-
stood by an independent party [E.g. : Regulatory body– Noti-
fied body]
¨ The contents should be cross-referenced to the relevant docu-
ments that support them
¨ CER should outline the different stages of the Clinical Evalua-
tion:
· Stage 0 : Scope of the Clinical Evaluation
1. Should explain the scope and context of the evaluation, including which prod-
ucts/ models/sizes/ settings are covered by the clinical evaluation report, the
technology on which the medical device is based, the conditions of use and the
intended purpose of the device;
2. documents any claims made about the device’s clinical performance or clinical
safety.

22. STAGE 4: THE CLINICAL EVALUATION REPORT [CER]
¨ CER should outline the different stages of the Clinical Evalua-
tion:
· Stage 1 : Identification of Pertinent Data
1. Should explain the literature search strategy;
2. Should present the nature and extent of the clinical data and relevant pre-
clinical data that have been identified.
· Stage 2 : Appraisal of Pertinent Data
1. Should explain the criteria used by the evaluators for appraising data sets;
2. Should summarise the pertinent data sets (methods, results, conclusions of the
authors);
3. Should evaluate their methodological quality, scientific validity, the relevance
for the evaluation,
4. The weighting should be attributed to the evidence, and any limitations;
5. Should present justifications for rejecting certain data or documents.

23. STAGE 4: THE CLINICAL EVALUATION REPORT [CER]
¨ CER should outline the different stages of the Clinical Evalua-
tion:
· Stage 3 : Analysis of Clinical Data
1. Should explain if and how the referenced information, such as confirmation of
compliance with clinical data requirement from applicable harmonised stand-
ards and the clinical data, constitute sufficient clinical evidence for demonstra-
tion of the clinical performance and clinical safety of the device under evalua-
tion;
2. Should explain whether there are adequate data for all aspects of the intended
purpose and for all products/ models/ sizes/ settings covered by the clinical
evaluation.
3. Should describe the benefits and risks of the device (their nature, probability,
extent, duration and frequency);
4. Should explain the acceptability of the benefit/risk profile according to current
knowledge/ the state of the art in the medical fields concerned, with reference
to applicable standards and guidance documents, available medical alterna-
tives, and the analysis and conclusions of the evaluators on fulfilment of all Es-
sential Requirements pertaining to clinical properties of the device (MDD ER1,
ER3, ER6; AIMDD ER1, ER2, ER5);
5. Should analyse if there is consistency between the clinical data, the information
materials supplied by the manufacturer, the risk management documentation
for the device under evaluation;

24. STAGE 4: THE CLINICAL EVALUATION REPORT [CER]
¨ CER should outline the different stages of the Clinical Evalua-
tion:
· Stage 3 : Analysis of Clinical Data
6. Should check whether there is consistency between these documents and the
current knowledge/ the state of the art;
7. Should identify any gaps and discrepancies;
8. Should identify residual risks and uncertainties or unanswered questions (such
as rare complications, uncertainties regarding medium- and long term perfor-
mance, safety under wide-spread use) that should be further evaluated during
PMS, including in PMCF studies.
¨ Evaluators should check the evaluation report and pro-
vide verification that it includes accurate information
and sign it. Their CV and Declaration of Interest should
be submitted by the manufacturer along with the CER
¨ CER should be dated and version controlled.

25. ROLE OF THE NOTIFIED BODY
The notified body plays the main role in the assessment and
verification of clinical evaluation reports and supporting docu-
mentation provided by medical device manufacturers to support
demonstration of conformity of a device with the Essential Re-
quirements of the relevant Directive.
The NB assessment by conformity assessment route includes:
· AUDIT
· DESIGN DOSSIER ASSESSMENT
The NB should write a Clinical Evaluation Assessment Report
[CEAR] based on the assessment of the submitted CER and sup-
porting documents by the manufacturer.
CLINICAL
EVALUATION
AS PER MEDDEV 2.7/1 REV. 4 June 2016
by Asha Meria Johnson, Jr. Consultant
[Medical Device Regulations] at I 3 Consulting
E-mail: aj@i3cglobal.com