The document discusses proposed regulations for clinical evaluations and investigations of medical devices in the EU. It notes concerns about how notified bodies have assessed clinical data and challenges manufacturers to provide sufficient clinical evidence. New rules would require clinical investigations for implantable devices and class III devices, with equivalence not sufficient justification to avoid investigations. Notified bodies would be expected to thoroughly review clinical data and ensure studies are completed before certification. Clinical investigations in the EU would involve a single application process and oversight by member states.

1. Clinical Evaluation - The Impact of
The New Regulatory Framework
Rob Higgins
.

2. Problems With Notified Body
Assessments
Improvements have been seen as to how NBs have
handled this activity. However
• Still some concerns as to how Notified Bodies
have addressed this element
• Manufacturers have limited understanding
• Notified Bodies appear reluctant to challenge in
this area
2

3. Examples of Issues
Notified Bodies issuing certification even though
• data was based on unsubstantiated
‘equivalency’
• studies not complete
• No check on MS no objections or ethics committee
approvals for EU Investigations
3

4. Examples of Issues (Cont)
 Users supplied with non CE marked products to
‘evaluate’ - No Notified Body challenge
 Notified Bodies not reporting to ‘MEDDEV’
requirements
 Notified Bodies not taking into account the effect
of design changes to product during investigations
4

5. CE MARKING
what essential
requirements?
what information?
in vitro / animal data?
clinical data
5

6. STAGES EVALUATION
identify clinical data from
- literature
- clinical experience
- investigation
appraisal of data sets
- suitability
- contribution safety, performance
generate new or
additional data
no
is clinical evidence sufficient
to demonstrate conformity
with relevant ERs
analysis relevant data
- strength of evidence
- conclusions about performance, safety
yes
produce clinical
evaluation report
6

7. SOURCES OF DATA
•
•
•
literature searching
- protocol
- rationale
- sources, extent searches
- selection criteria
- inclusions, exclusions
clinical experience
- pms reports, adverse events, FCAs
clinical investigation
- plan (objectives, numbers, duration, end points)
- compliance
- regulatory authority/REC letters
- modifications
- final report
7

8. How is a Clinical Evaluation Performed
• Identification of pertinent standards and clinical
data.
• Appraisal of each individual data set in terms of
its relevance, applicability, quality and clinical
significance.
• Analysis of the the individual data sets whereby
conclusions are reached about the performance,
safety and presentational aspects of the device.
8

9. Who Should perform the Clinical Evaluation ?
Suitably Qualified and have Knowledge of
• the device technology and its application
• research methodology
• diagnosis and management of the conditions
intended to be treated or diagnosed by the device
9

10. CLINICAL EVALUATION REPORT
•
•
•
•
•
•
•
•
general details
description device, intended purpose
intended indications, claims
context evaluation (old, new technology)
choice clinical data
summary clinical data and appraisal
data analysis (performance, safety, ifu)
conclusions
10

11. CLINICAL EVALUATION REPORT
(Cont)
The clinical evaluation report should be
signed and dated by the evaluator(s) and
accompanied by the manufacturer’s
justification of the choice of evaluator
11

12. Notified Body Assessment of
Clinical Evaluation
• As part of a QS conformity assessment procedure
- Assessment of the manufacturer’s procedure for clinical
evaluation
- As part of the representative sampling of devices to
verify the clinical evaluation data for Class IIa and IIb
devices
•
As part of a design dossier or type examination dossier
assessment to assess and verify the validity of the
clinical evaluation report
12

13. LITERATURE REVIEW
Is data sufficient and of appropriate
quality to demonstrate safety, performance
and risk benefit analysis of……..
DEVICE IN QUESTION?
13

14. EQUIVALENCE
• clinical
same clinical condition, purpose
same site, similar population
• technical
similar specifications, properties, deployment
critical performance, principles operation
• biological
same materials, same tissues
14

15. Use of existing clinical data
• “Basically
equivalent to
proven designs!”
Regulatory
“Novel features,
extra benefits!”
Manufacturers can’t have it
both ways!
Marketing
15

16. INDICATION FOR CLINICAL INVESTIGATION
•
•
•
•
•
•
new device
new function
new feature
modification
new material
cannot mimic clinical situation
16

17. MHRA NB EXPECTATIONS
•
Follow MEDDEV 2.7.1 to include NB reporting
requirements
•
Ensure equivalency if Manufacturers have followed
literature route based on similar products
•
Review MS letters of No Objection, especially
Comments, for trials performed in EU
•
Thoroughly investigate cases where data indicates that
studies are not complete prior to certification
• Raise major non–conformities in cases where Users are
supplied with non CE marked products to ‘evaluate’
17

18. Proposed Regulations :
Clinical Evaluation
• Confirmation that a clinical evaluation must be performed
• For Implantable devices and devices falling within Class III
clinical investigations shall be performed. Demonstration of
equivalence shall generally not be considered as sufficient
justification for not carrying out a CI.
• If safety and performance requirements are not based on
clinical data then an adequate justification must be made
18

19. Clinical Investigatons
• Contact person must be established in the Union
• Must obtain a single identification number
• On receipt of application MS has 6 days in which to decide
whether the application is valid
• 35 day period in which a decision must be made
• Use of an electronic system
19

20. Clinical Investigatons (cont)
• 30 day deadline for approval of changes
• If the sponsor temporarily halts a clinical
investigation on safety grounds then they shall
inform MSs within 15 days
• Prescribes the information required to be in
Application
20

21. Clinical Investigations of Devices
Bearing the CE Marking
Post Market Clinical Follow Up Investigations must
be notified to MSs at least 30 days prior to
commencement
21

22. Clinical Investigations Conducted
in More Than One Member State
• Single application via electronic system
• Applicant shall propose one MS as the co-ordinator
22

23. Reviews for Class III Devices
Proposed Regulations
• Summary of the preliminary conformity assessment
to be reviewed by the MDCG
Parliamentary Committee
• ‘Special’ Notified Bodies to be designated by EMA
• Also data to be independently reviewed
23

24. Key Issues
• For Implantable devices and devices falling within Class III
clinical investigations shall be performed. Demonstration of
equivalence shall generally not be considered as sufficient
justification for not carrying out a CI
• 35 day period in which a decision must be made
• Post Market Clinical Follow Up Investigations must be
notified to MSs at least 30 days prior to commencement
• Clinical Investigations conducted in more than one Member
State
24