Clinical Evaluation - The Impact of

The New Regulatory Framework

Rob Higgins .

2

Problems With Notified Body

Assessments

• 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

Improvements have been seen as to how NBs have

handled this activity. However

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

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

5

CE MARKING

what essential

requirements?

what information?

in vitro / animal data?

clinical data

6

STAGES EVALUATION

identify clinical data from

- literature

- clinical experience

- investigation appraisal of data sets

- suitability

- contribution safety, performance

analysis relevant data

- strength of evidence

- conclusions about performance, safety

is clinical evidence sufficient

to demonstrate conformity

with relevant ERs yes produce clinical

evaluation report

generate new or

additional data

no

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

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.

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

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

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

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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

13

LITERATURE REVIEW

Is data sufficient and of appropriate

quality to demonstrate safety, performance

and risk benefit analysis of……..

DEVICE IN QUESTION?

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

15

Use of existing clinical data

• “Basically equivalent to proven designs!”

“Novel features, extra benefits!” Regulatory

Marketing Manufacturers can’t have it both ways!

16

INDICATION FOR CLINICAL INVESTIGATION

• new device

• new function

• new feature

• modification

• new material

• cannot mimic clinical situation

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’

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

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

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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

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

22

Clinical Investigations Conducted

in More Than One Member State

• Single application via electronic system

• Applicant shall propose one MS as the co-ordinator

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

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