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A Summary of the European Commission’s
EVALUATION OF CLINICAL DATA
For a current copy of the guidance document you can
visit the EC’s website.
As part of the conformity assessment procedures required by 90/385/EEC (AIMD)
[1] and 93/42/EEC (MDD) it is the manufacturer’s responsibility to review and
analyze clinical data. Clinical data is often required to demonstrate safety and
effectiveness (performance) of a medical device.
The European Commission’s EVALUATION OF CLINICAL DATA: A GUIDE FOR MANUFACTURERS
AND NOTIFIED BODIES provides a roadmap on assessing clinical data.
What is considered “Clinical Data”?
Clinical data can be either the results of a clinical investigation or it can be
via literature, or a combination of the two.
In the circumstances where a combination of clinical investigation and
literature is used, an overall assessment should be made, paying special
attention and relating the information back to any market experience (if
available). The standard indicates that the manufacturer should relate the data
as it pertains to the device – and specifically to the hazards identified.
Technical File: Statement Affixed to the CE marking
The manufacturer’s technical file should have a statement on the clinical data.
It is important to note in the technical file whether the data used was
collected from:
Clinical Investigation
Literature
Or both
The technical file should include the complete set of clinical data.
RISK ANALYSIS AND CLINICAL ANALYSIS
Identifying foreseeable hazards associated with use of the device the
manufacturer can decide on how best to deal with the risk while weighing it on
the intended benefit. In circumstances where the clinical data is not sufficient
to address the identified clinical hazards, a clinical investigation will be
required.
There should be both technical and clinical parts to your risk analysis paying
special attention to distinguishing between: The specific use of device
(Intended Use), The technical solutions adopted (risks versus benefits of
different technologies) and the comparison amongst your device and the
historical methods/equipment (highlighting aspects specific to the design and
use of your device).
LITERATURE ROUTE
Having the option of using Literature as a means for clinical data requires that
the manufacturer assess the level of relevance to the device. It can be
difficult sometimes to separate the benefit of going via the Literature route
(obviously a lot cheaper and expedited) and whether or not the data adequately
addresses the safety and efficacy of the device. An organization however can
mitigate the effects of any bias (sometimes subconsciously generated) by
carefully selecting the person who will review the data.
Reviewing Literature
The reviewer should be selected carefully to ensure that:
a) He/she is impartial (demonstrates objectivity)
b) Qualified in the relevant field (i.e. Orthopaedic Surgeon, etc)
c) Up to date with the latest in the development of the particular field
What you need to do if you are thinking on submitting clinical data via the
Literature Route?
Protocol
Just as in the case of a clinical investigation Literature reviews should begin
with a protocol. The protocol should have a clearly defined objected while
specifying how the systematic review for literature will proceed.
The protocol should have the following:
1) Identification of Literature
2) Selection of Literature
3) Collation of Literature
4) And review of relevant studies
Identification of Literature
In most circumstances you should base your literature on recognized scientific
publications, giving rationale on why this data was picked from the specific
literature. In order to avoid being bias the identification of literature should
also include reasons why other publications/data was excluded. To ensure that
your organization has adequately gone through all relevant information, you
should indicate the extent to which sources of information were searched.
Your protocol should state how the literature will be searched and will include
the criteria on which the selection is based. Including justification on how
other sources of data become excluded in the effort.
Relevance of Data
The manufacturer must demonstrate how the literature relates to the device. This
demonstrated equivalency should touch on the clinical, technological and
biological (biocompatibility, material content, etc) aspects of the review.
Assessing Data
While excluding data originating from unsubstantiated opinions, isolated cases
or nonscientific information data is best obtained when deriving from
scientific/clinical trials. Clinical Trials data is best if the conditions of
the trial were controlled.
Critical Evaluation of the Literature (Literature Route)
As indicated above the critical evaluation should be done by an individual best
suited for the task.
A table of content for the Critical Evaluation might look something like this:
-Medical Device Description
-Medical Device’s Intended Use (Functions)
-Analysis of Available Data (Favorable and Unfavorable)
-Equivalency (between Literature and Device; including equivalency between the
device and other devices on the market)
-Hazards Identified
-Description of Literature Review and Assessment
-Discussion on Efficacy of the studies in question
-Benefits of the Device (how it improves upon previous designs, methods, etc)
-Conclusions (demonstrating how objectives were met/not met)
-Signatures (Author, Review and Approved by, etc)
CLINICAL INVESTIGATIONS ROUTE
Identification of Relevant Documents
Clinical Investigations will be presented in the Technical File with the
following deliverables:
Protocol submitted to the Competent Authority (for which no grounds for
objection were raised)
Copy of “No Objection” letter from Competent Authority/Authorities
Copy of Ethics Committee Opinions and comments
If previously rejected a copy of the objection letter
Copy of singed and dated final report
Information to be checked
In all cases the notified body must check:
Copy of “No Objection” letter from Competent Authority/Authorities
Clinical Investigation Plan, which includes the following:
o number of patients entered
o objectives of investigation(s) (in particular which Essential Requirements are
being addressed
o duration of investigation(s) and patient follow up (short and long term)
o end points in terms of diagnostic tools and patient assessment
o inclusion and exclusion criteria
Deviations from the original Clinical Investigation Plan and Rationale for
digression
Final Report
One Final Report format might look something like this:
Title Of Investigation(S)
Identification Of The Medical Device(S), Including Names, Models As Relevant For
Complete Identification
-Name Of Sponsor
-Statement Indicating Whether The Investigation(S) Was Performed In Accordance
With CEN/ISO Standards
-Objectives
-Subjects
-Methodology
-Investigation(S) Initiation And Completion Dates, Including Date Of Early
Termination, If Applicable
-Results
-Conclusions
-Authors Of Report
-Date Of Report
THE ROLE OF THE NOTIFIED BODY
The Notified Body’s role differs depending on the conformity assessment route
taken.
As part of the design/type examination under Annexes II.4 or III, the Notified
Body assesses the clinical data assembled by the manufacturer and the
manufacturer’s evaluation and the validity of the conclusions drawn.
As part of quality system approval under Annex II.3, the Notified Body assesses
the manufacturer’s procedure for clinical data evaluation. This may include a
review of examples of such evaluations.
In reviewing the evaluation of clinical data submitted by the manufacturer, the
Notified Body decides whether or not the manufacturer has adequately:
described and verified the intended characteristics and performances related to
clinical aspects;
performed a risk analysis and estimated the undesirable side effects;
concluded on the basis of documented justification that the risks are acceptable
when weighed against the intended benefits.
The Notified Body’s a report which may be a separate report or part of the
overall report (for an ‘overall report’ the clinical part must be identified).
The contents should include the following:
Identification Of The Manufacturer;
Identification Of The Medical Device;
Basis Of Evaluation (Which Directive And Which Annex(es));
Submitted Documents;
Description Of The Device;
Assessment Of Clinical Safety And Performance;
Conclusion. The NB Should Justify And Document Each Step Of The Decision Making
Process Referred In 5.1.1. One Single “Unacceptable Risk/Benefit Ratio” Leads To
A Negative Conclusion The Names Of All NB Internal Assessors And External
Experts Involved In The Assessment Of The Manufacturers Documentation, Together
With Details Of The Aspects Assessed By Each
Date And Signature Of The Responsible Assessor(s)
In conclusion, the guidance document “EVALUATION OF CLINICAL DATA: A GUIDE FOR
MANUFACTURERS AND NOTIFIED BODIES” is an important document to help guide the
manufacturer (and Notified Body) on how to evaluate clinical data. This article
is presented as an introduction and many details are omitted. It is highly
recommended that you consult with the original guidance document in full.
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