Post-market Clinical Follow-up (PMCF) GAP Analysis for

Legacy Devices Class III between

the Medical Device Directive (MDD 93/42/EEC) and

the Medical Device Regulation (MDR 2017/745)

Marina Makeenko

and Thierry Chevallier

2,3,4

Biotechni SAS, 178 Avenue du Serpolet, La Ciotat, France

Department of Biostatistics, Epidemiology, Public Health and Innovation in Methodology (BESPIM),

CHU Nîmes, Place du Pr. Robert Debré, 30029 Nîmes, France

UMR 1302, Institute Desbrest of Epidemiology and Public Health, INSERM, Univ. Montpellier, Montpellier, France

Tech4Health-FCRIN, France

Keywords: Medical Device, Post-market Clinical Follow-up, PMCF, GAP Analysis, Legacy Devices.

Abstract: The passage from the MDD 93/42/CEE to the MDR 2017/745 remains a big challenge for the manufactures.

The interpretation of the regulatory requirements stays unclear and can differ from one source to another,

especially when it comes to the clinical evaluation. Will the data collected under the MDD 93/42/CEE be

sufficient to prove the safety and security of the device? Under the directive each country was establishing its

own requirements for the conduct of the studies. The MDR has standardized these rules, so that all the clinical

data collections follow the same pathway. We will examine the PMCF of the class III devices already CE

marked under the directive (legacy devices) to find out if the new requirements will be asked to be in

compliance with the MDR. A Gap analysis between the MDD and MDR will help us in our research. A matrix

in the form of a questionnaire will be established to help us verify compliance of the PMCF under the MDR.

1 INTRODUCTION

The Medical Devices Regulation 2017/745 (MDR)

came in force on the 26th of May 2021 bringing

significant regulatory changes.

The new MDR requirements reinforced clinical

data, technical documentation, and labelling.

However, the most significant change concerned the

clinical part, as the manufacturers have to obtain a

bigger clinical data to prove safety and performance

of their products.

As the representative of the medium size

company, manufacturing implantable medical

devices class III we are at the heart of regulatory

constraints, which are becoming more and more

imposing. Our products already have a long

marketing history; therefore, they enter in the

category of legacy device.

“Legacy devices are all devices previously CE

marked under the European Medical Devices

Directive 93/42/EEC” (MDCG 2020-6).

We will analyse the requirements for the PMCF

report under MDR 2017/745 to build the gap analysis

between MDD and MDR, paying special attention to

the interpretation of the meaning « sufficient clinical

data », since this essential requirement of the MDR is

not clearly explained.

We will rely our researches on the MDR, Medical

Device Coordination Group (MDCG) and MEDDEV

guidelines. A literature review will be done using

scientific publications, notify body and consultancy

agencies articles.

We will apply our research on the example of a

Biotechni S.A.S., a family-owned company created in

1984 in Marseille and currently employing 48

members. Biotechni designs, producers and

commercialises a range of implants for hip, shoulder

and spine (classes I, IIa, IIb and III). All the products

produced by Biotechni are marketed since at list 10

years and are covered by a valid certificate issued in

accordance with Directive 93/42/EEC, valid until

May 2024.

To illustrate our gap analysis, we will use an

example of a femoral stem, used in association with a

femoral head and acetabular cup for a hip joint

replacement.

Makeenko, M. and Chevallier, T.

Post-market Clinical Follow-up (PMCF) GAP Analysis for Legacy Devices Class III between the Medical Device Directive (MDD 93/42/EEC) and the Medical Device Regulation (MDR

2017/745).

DOI: 10.5220/0010889400003123

In Proceedings of the 15th International Joint Conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2022) - Volume 1: BIODEVICES, pages 273-280

ISBN: 978-989-758-552-4; ISSN: 2184-4305

273

Below is the brief description of the device in

question.

Table 1: Filler-3ND femoral stem brief description.

MANUFACTURER BIOTECHNI S.A.S

PRODUCT RANGE FILLER-3ND® 135°

Titanium cementless femoral

hip stems (11 sizes)

PICTURE

CLASS III

INTENDED PURPOSE For use in total and partial

hip arthroplasty

Date of 1st CE marking 25/03/2004

TOTAL SALES 18 000

2 CLINICAL REQUIREMENTS

FOR LEGACY DEVICE

“Past performance is no guarantee of future results.

Study Proves Past Results Doesn’t Predict Future

Results…”

The founding fathers of the new MDR were

obviously very inspired by those quotes while

building the new regulations.

Therefore, even if the device has been marketed

for decades with no significant change in design, it

doesn’t exempt the manufacturer from the

complimentary clinical studies.

2.1 Exemptions from the Clinical

Requirements for Legacy Device

According to MDR Article 61(4 and 6) clinical

investigations shall be performed for Class III and

implantable devices, except if they have been

previously marketed under Directive and their

clinical evaluation is based on sufficient clinical data.

Another exemption from clinical investigations is

given in MDR Annex XIV, Part A (3), where it is

stipulated, that a clinical evaluation may be based on

clinical data relating to a device for which

equivalence to the device in question can be

demonstrated by technical, biological and clinical

characteristics with the authorisation of the full access

to the technical documentation.

2.2 Sufficient Clinical Data

Different sources are attempting to explain the

meaning of the word « sufficient ».

The Article 61(1) of the MDR states that

: “The

level of clinical evidence shall be appropriate in view of the

characteristics of the device and its intended purpose.”

Section 4 of MDCG 2020-6 guidance states:

“Both

the Directives and the MDR require the quantity and quality

of clinical data to be sufficient to demonstrate safety,

performance and the acceptability of the benefit-risk

ratio…and require clinical evidence to be sound and the

conclusions derived from this evidence to be scientifically

valid.”

Section 5 of the guidance tries to explain what

does the word sufficient means by saying:

“sufficient

clinical evidence is understood as the present result of the

qualified assessment which has reached the conclusion that

the device is safe and achieves the intended benefits.”

Does it really help to understand what does

“sufficient” mean? We are not so sure…

The manufacturer should conduct an analysis to

determine if additional data or change in PMCF

design to support the clinical evidence are required to

meet additional MDR requirements. This could be

achieved through a gap analysis with respect to new

MDR requirements.

The gap analysis is the difference between what

we have with MDD and what we should have to

comply with MDR.

To prepare the GAP analysis of the PMCF report

in the most exhaustive way we decided to separate our

researches in 3 main pillars:

1. Acceptable quantity of clinical data

2. Acceptable quality of clinical data

3. Additional sources of clinical and not clinical

data

The acceptable quantity of clinical data is the

quantity of information we need to make the study

results reliable and representing of a real life.

The acceptable quality of clinical data will be

appraised by its methodological quality and its

relevance.

The additional sources of clinical and not clinical

data will be considered to implement the PMCF

results.

The goal is to establish a generic matrix that could

be used for each legacy medical device.

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2.3 Acceptable Quantity of Clinical

Data

2.3.1 Sample Size

The choice of the sample size is one of the primary

endpoints the sponsor has to determine for the clinical

study.

As we can’t include all the population of interest,

we should determine what is the minimum number of

patients that would reflect as much as possible the

total population of interest, and therefore make study

results statistically significant.

The MDR requires to document the choice of

sample size, and to provide a rationale explication of

the procedures and the methods used.

The sponsor should define what endpoints would

be statistically measured through the clinical study to

demonstrate the device general safety and

performance conformity assessment. To assess

quality and performance of an implantable medical

device the survival rate is usually measured.

2.3.2 Duration of Clinical Study

The duration of a clinical investigation is also crucial

and must be considered while planning the PMCF.

“The follow-up period during the clinical investigation

shall permit the demonstration of clinical performance,

effectiveness or safety over a period of time sufficient to

represent a realistic test of the investigational device and

allow any risks associated with adverse device effects to be

identified and assessed” (ISO 14155 : 2020).

“Although there is not enough information yet available

to calculate exactly how long a hip replacement will last,

using available arthroplasty registry data, we estimate that

about three-quarters of hip replacements last 15–20 years

and just over half of hip replacements last 25 years in

patients with osteoarthritis” (How long does a hip

replacement last? A systematic review and meta-analysis of

case series and national registry reports with more than 15

years of follow-up - Jonathan T Evans, Jonathan P Evans,

Robert W Walker, Ashley W Blom, Michael R

Whitehouse*, Adrian Sayers* - 2019).

Taking into consideration the average duration of

the hip joint life cycle and the common practice in

designing the hip replacement PMCF studies, we

estimated the minimum duration of the study at 10

years.

2.4 Acceptable Quality of Clinical Data

“Clinical investigation that are currently being conducted

with respect to Directive 93/42/EC and Directive

90/385/EC by the date of application of the MDR, can

continue to be conducted” (MDCG 2021-6).

Therefore, the Clinical investigation protocols

that have been approved under Directive 90/385/EC

can be keep going, as long as the quantity and quality

of the data are sufficient. But what constitutes the

quality of the data?

The quality appraisal of the clinical data is

uncertain, as it has to take into consideration several

aspects.

MEDDEV 2.7/1 rev. 4. point 9. suggests to

evaluate two main sources: the methodological

quality of the data, and the relevance of the data.

2.4.1 Methodological Quality

Different methods are available to conduct a clinical

study.

In case of legacy device observational prospective

or retrospective studies are most commonly used.

We are encouraged to conduct the methodology

evaluation to assess whether there are any points that

can be improved.

We have grouped the information from Appendix

A6 General principles of clinical evaluation of

MEDDEV 2.7/1 rev. 4. to constitute the checklist of

the desired parameters for a high-level scientific

validity study to demonstrate adequate clinical

performance and clinical safety.

Below are the points that should be taken into

consideration while assessing the methodological

quality of the study:

- Sufficient information on elementary aspects

- Proper statistical methods

- Adequate controls

- Proper collection of mortality and serious

adverse events data

- Legal activities

- Schedule for PMCF activities

Let’s see in details those points.

- Sufficient Information on Elementary Aspects

The clinical data should necessarily contain the

following elementary aspects:

a) Methods used

b) Products used

c) Number of patients

d) Clinical outcomes

e) Undesirable side-effects

f) Confidence intervals/ calculation of statistical

significance

g) Reference to the harmonised standards or

guidances.

Post-market Clinical Follow-up (PMCF) GAP Analysis for Legacy Devices Class III between the Medical Device Directive (MDD

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- Adequate Controls

a) Objective control parameters

b) Assessed endpoints are not subject to natural

fluctuations

c) No other treatments, that can influence the

clinical outcome are taken

d) Any other influencing factors

- Proper Collection of Mortality and Serious

Adverse Events Data

The lost to follow-up should be avoided as much as

possible. Therefore, the Investigator should have a

contact person that will be contacted if a patient is lost

to follow-up. The emergency contact should be

provided while recruitment. It could be mentioned in

the PMCF protocol.

The Sponsor should be immediately informed

about all adverse events or any sort of failures.

- Legal Activities

MDR clinical investigation requirements are based on

existing ethical and legal regulations.

“Clinical

investigations should be in line with well-established

international guidance in this field, such as the international

standard ISO 14155:2011” (Point 64 of the preamble to

MDR).

Article 74 precises that rules provided in points

(b) to (k) and (m) of article 62(4), article 75, article

76, article 77, article 80(5) and (6) and the relevant

provisions of Annex XV shall apply to all PMCF

investigations. This must be understood, that both

PMCF investigations with invasive or burdensome

procedures as well as the investigations free of such

additional measures should comply with the same

requirements.

Within MDR it must be understood that in-label,

observational, non-interventional studies will

however stay in a general category of clinical

investigation. That means that all the requirements

and obligations set up for the PMCF investigation

within the framework of the MDR must be observed.

The fact that the studies stay in the scope of

intended purpose and without bringing any additional

risk to patients does not exempt them from general

obligations.

Below is the list of the essential requirements to

the clinical investigation according to the ISO14155:

2020, and the analysis of this new requirements

applied to the Filler-3ND observational retro-

prospective study, started under MDD.

As we can see the design study started under

MDD can be improved and adjusted to comply as

much as possible with the new requirements.

Table 2: List of essential requirements ISO14155:2020

applied to Filler-3ND PMCF report.

List of

requirements

ISO14155-2020

Filler-3ND

PMCF report

Comments

Investigation

brochure

No Can be added

Clinical

Investigation Plan

Yes (PMCF

protocol)

Principle

Investigators CV

No Can be added

List of

investigation sites

No Can be added

Ethics committee

approval

For certain

countries

Ask for a EC

approval if a

new country

included

Regulatory

authorities’

approval

Yes

Signed agreement

between

investigator and

sponsor

Yes

Financial

agreement between

investigator and

sponsor - Yes

Yes

Insurance No

As the study

started under

MDD no need

to include it a

posteriori

Investigation site

selection report

No Can be added

- Schedule for PMCF Activities

Annex XIV, part B, point 6.2 (h) recommends

“a

detailed and adequately justified time schedule for PMCF

activities (e.g., analysis of PMCF data and reporting) to be

undertaken by the manufacturer”

PMCF report should indicate the targeted study

duration for subjects already enrolled or/and to be

enrolled to achieve target sample size.

- Conclusion About Study Design

We analysed point by point all the aspects, that

constitute the methodological quality of a study.

But as mentioned earlier, the quality of the study is

based on 2 pillars: the methodology and the relevance

of the data. In the next chapter we will analyse the

second pillar of the quality assessment, what

constitutes the data relevance of the study.

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2.4.2 Relevance of the Data

Article 61 of the MDR specifies the general

requirements regarding clinical investigations to

demonstrate conformity of devices.

According to article 62 of the MDR the clinical study

should demonstrate, that the following points have

been achieved:

1. Device achieves the performance intended as

specified by its manufacturer

2. Establish and verify the clinical benefits of a

device as specified by its manufacturer

3. Establish and verify clinical safety, detect any

undesirable side effects

4. Evaluate the benefit / risk ratio

All that information claimed by the manufacturer

should be confirmed by clinical data.

- Conformity with the IFU Allegations

Annex I, CHAPTER III points 23.4 of the MDR

precises the information that the manufacturer should

supply in the instructions for use.

The assessor will examine whether there is sufficient

clinical evidence to demonstrate that the device

performs as intended in the IFU.

- Benefits Claimed in Marketing Material

The information given about a medical device in the

marketing material must be consistent with the

manufacturer's intended purpose and the scope of use

of the medical device. Moreover, the allegations

claimed by the manufacturer in the advertising

information must be supported by clinical evidence.

- Target Groups

The target population should be identified in the

PMCF through the inclusion and exclusion criteria.

The inclusion/exclusion criteria must be strictly

respected as it can compromise the clinical results.

Generally, the population included in the study

should be homogenous which benefits from the same

level of infrastructures. Investigation site selection

report can be helpful to involve the centers of the

same level. The investigators should have the same

knowledge as well. Training records, providing

evidence, that the investigators have been trained are

very helpful.

3 ADDITIONAL SOURCES OF

CLINICAL AND

NON CLINICAL DATA

Annex XIV, part B, point 6.2 (a) of MDR precises

what are the available sources of the PMCF data

collection:

“the general methods and procedures of the

PMCF to be applied, such as gathering of clinical

experience gained, feedback from users, screening of

scientific literature and of other sources of clinical data”

Therefore, feedback from users and screening of

scientific literature can be put in place to implement

the PMCF.

In fact, user surveys are listed in the MDR as a

valid method of post-market clinical data collection.

3.1 Market Experience Feedback

PMCF surveys should not be ignored, as they

represent many advantages.

With the PMCF surveys the clinical data can be

significantly implemented.

The PMCF survey should have a clear objective

and not have conflicting purposes that could confuse

the PMCF results. PMCF surveys should be in line

with the PMCF clinical data collection and reply to

the same objectives, as precised in the Annex XIV,

part B, point 6.1.

The regular collection of the feedback from users

may help to identify any unknown side-effects,

emergent risks, misuse or off-label use of the device.

3.2 Alternate Therapies/State of the

Art/Current Knowledge

A critical review of the literature while assessing the

state of the art, alternative examination and treatment

methods should be considered when implementing

the PMCF.

The literature search should demonstrate if the

device in question is a well-established practice with

numerous articles validating both design, longevity

and security.

If the device is identified as belonging to the group

of « well-established technologies » a lower level of

clinical evidence may be justified to be sufficient for

the confirmation of conformity with relevant GSPRs.

3.3 Benefit-Risk Analysis

The aim of the PMCF plan is ensuring the continued

acceptability of the benefit-risk ratio, referred to in

Section 1 and 9 of Annex I in the MDR.

Post-market Clinical Follow-up (PMCF) GAP Analysis for Legacy Devices Class III between the Medical Device Directive (MDD

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The benefit-risk analysis should be documented in

the clinical evaluation report using all the available

sources of clinical and non-clinical data, obtained

through the PMCF activities.

Aspects that influence the acceptability of benefits

and risks can be found in Appendix A7.2 and in

Appendix A7.4 of MEDDEV 2.7/1 rev. 4.

The information gathered through the PMCF

activities should be sufficient to confirm the

acceptable benefit-risk ratio.

3.4 Gap Analysis Matrix

The main goal of this thesis was to establish a check

list, that will help to conduct a gap analysis of a

PMCF report. We grouped all the collected

information in a table-matrix.

We have illustrated this matrix with the example

of the Filler-3ND PMCF report.

Table 3: GAP analysis Matrix.

Product Name

Product Class

Q.N° Question Response

Gaps, if

any/recom-

mendation

Sample size

Q1 What is the target size of the sample?

Q2 Has the sample size calculation been justified?

Q3 Has the sample size justification been approved by the Notify Bod

Q4 Has the target sample size

een reached?

Duration of the study

Q5 Is the duration of the study enough to demonstrate its safety and performance?

Methodology

Elementary aspects

Q6 Does the PMCF disclose the methods used?

Q7 Does the PMCF disclose the

roducts used?

Q8 Does the PMCF disclose the number of patients included?

Q9 Does the PMCF disclose all the clinical outcomes?

Q10

Does the PMCF disclose data from others activities? (device registry, PMCF studies, real world

evidence, surveys about the use of device, etc…)

Q11 Have the undesirable side-effects been observed?

Q12 Have confidence intervals/ calculation of statistical significance been used?

Q13 Does the study PMCF reference to any harmonised standards, relevant guidance on PMCF

Adequate controls

Q14 Are the endpoin

s assessment objective? (ex., pain is subjective)

Q15

Are the endpoints or symptoms assessed are subject to natural fluctuations? (ex. when the natural

evolution of the pathology is not clearly predictable)?

Q16 Are any other treatments, that can influence the clinical outcome taken?

Q17

May clinical outcomes can be affected by variability of the patient population, of the disease, of user

skills, of infrastructure…?

Collection of mortality and serious adverse events data

Q18 Has the consent of the subjects for contacting reference persons been obtained?

Q19 Is any failure or adverse event immediately reported?

Legal activities

Q20 Does the study have Investigation brochure?

Q21 Does the study have Clinical Investigation Plan?

Q22 Does the study have Principle Investigators CV?

Q23 Does the study have List of investigation sites?

Q24 Does the study have Ethics Committee approval?

Q25 Does the study have Regulatory Authori

y approval?

Q26 Does the study have signed agreement between investigator and sponsor?

Q27 Does the study have financial agreement between investigator and sponsor?

Q28 Does the study have insurance?

Q29

Does the study have Investigation site selection report (verifies that the qualification of investigation

site members has

een approved)?

Q30 Does the study have CRF?

Q31 Does the study have Adverse events form?

Q32 Does the study have Device deficiency form?

Q33 Does the study have Training records (evidence, that the investigators have been trained)?

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Table 3: GAP analysis Matrix (cont.).

Product Name

Product Class

Q.N° Question Response

Gaps, if

any/recom-

mendation

PMCF Schedule

Q34 Is there a PMCF Follow-Up schedule for on-going subjects?

Q35 Is there a PMCF Follow-Up schedule for additional planned subjects?

Relevance of the data

Indication/intended use/intended purpose in IFU

Q36 Is the exact indication/intended use/intended purpose as described in the device's IFU captured?

List down the indications/intended use/intended purpose in the below rows as per the IFU.

Q37 Indication # 1

Q38 Indication # 2

Benefits claimed in marketing material

Q39 Are the claims as described in the marketing material captured? List down the claims in the below

rows as per marketing material.

Q40 Claim # 1

Q41 Claim # 2

Contraindications/ Warnings & Cautions / Risks in IFU

Q42 Are the exact contraindications as described in the device's IFU captured?

Q43 Are the exact Warnings & Cautions as described in the device's IFU captured?

Q44 Are the exact Risks as described in the device's IFU captured?

Q45 Are previously unknown side-effects identified?

Q46 Are emergent risks identified and analysed?

Q47 Do the clinical results meet the expected benefits?

Q48 Is the benefi

-risk ratio continuously acceptable?

Q49 Is the performance characteristics of the device demonstrated?

Target group(s)

Q50 Has the inclusion/ exclusion criteria been respected by the target population?

Q51 Are the infrastructures of the sample homogeneous?

Q52 Is the social and economic level of the sample homogeneous?

Q53 Is the morphology of the sample homogeneous?

Additional sources of clinical and not clinical data

Market Experience feedback

Q54 Has market experience data been collected (complaints, medical device reports, customer surveys,

etc)? List down the data, that has been collected from the market.

Q55 Market experience data # 1

Q56 Market experience data # 2

Q57 Are possible systematic misuse or off-label use of the device identified?

Q58 Are the usability forms filled in regularly?

Critical analysis of the literature

Q59 Is a thorough literature search performed to identify state of the art therapy/management/diagnostic

options available?

Q60 Is a description of all the available therapeutic/management/diagnostic options, historical context

and developments included?

Q61 Is a thorough literature search performed to identify state of the art therapy/management/diagnostic

options available?

Benefit-risk Analysis

Q62 Are all the risks identified from different sources?

Q63 Are the risks acceptable according to current knowledge/ the state of the art in the medical fields

concerned and according to available medical alternatives?

Q64 Is justification available for acceptability of risk(s)?

Q65 Are there any new risk(s) identified?

Q66 If new risks are identified, is the available clinical data sufficient to verify that the device is in

conformity with all the essential requirements pertaining to clinical performance and clinical

safety?

Q67 Does the risk/benefit analysis summarized, considering the current knowledge/the state of the art?

Q68 Does the report explain why the benefit/risk profile and the undesirable side-effects are acceptable

in relation to current knowledge/the state of the art?

Post-market Clinical Follow-up (PMCF) GAP Analysis for Legacy Devices Class III between the Medical Device Directive (MDD

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Table 4: Non-compliances of the Filler-3ND PMCF report, detected by GAP analysis Matrix.

GAP Endpoint Level of

importance

Correction action

Collection of mortality and

serious adverse events data

Medium Include reference persons to contact in case of lost to follow-up

durin

the recruitment

al activities Mino

To add Investi

ation brochure

Mino

To add Principle Investigators CV

Mino

Ask for a EC approval if a new country include

Insurance Mino

Not possible to ad

Mediu

To add Investi

ation site selection re

ort

Medium To add training records (evidence, that the investigators have been

trained)

Indication/intended use in IFU Mediu

Precise « total or

artial re

lacement » in the CRF

Target groups Medium Include training records, providing evidence, that the investigators

have been traine

Market Experience feedbac

Mediu

Market feedback should be collected at list once a yea

4 CONCLUSION/DISCUSSIONS

MDD to MDR transition is a very challenging step,

and the key of success is the organization. The

establishment of the regulatory roadmap with

deadlines and budgeting is absolutely necessary.

GAP analysis for all the important endpoints could be

very helpful. In our thesis we assessed PMCF report,

but other topics could be reviewed:

- CE Marking Technical File or Design Dossier

- Current device class and product families

- Risk management file review

- Clinical Evaluation Report(s)…

Below is the table that resume all the identified non-

compliances, detected by the GAP Analysis of the

Filler-3ND femoral stem. We estimated the level of

each non-compliance and suggested possible

correction action.

We can see that the PMCF Gap Analysis results

are good and some non-compliances can easily be

corrected, except one, but it is a minor non-

compliance.

We are convinced that the sufficient clinical data

is the most important point of the new MDR. It is

necessary to collect the data systemically in the most

exhaustive way.

The key success in this process is the investigators

implication. Therefore, our goal is to instill in

investigators the importance of clinical follow-ups,

by bringing arguments and following them in each

step of data collection.

REFERENCES

Regulation (EU) 2017/745 of the European parliament and

of the council of 5 april 2017.

Directive 93/42/CEE du conseil du 14 juin 1993 relative

aux dispositifs médicaux.

ISO 14155 – Clinical investigation of medical devices for

human subjects – Good clinical practice.

Guideline for good clinical practice E6(R2), 23 July 2015.

MEDDEV 2.7/1 revision 4 - Clinical evaluation: a guide for

manufacturers and notified bodies under directives

93/42/EEC and 90/385/EEC.

MEDDEV 2.12/2 rev2 – Post market clinical follow-up

studies - a guide for manufacturers and notified bodies.

Guide methodologique HAS – Choix méthodologiques

pour le développement clinique des dispositifs

médicaux, 4 octobre 2013.

MDCG 2020-6 – Regulation (EU) 2017/745: Clinical

evidence needed for medical devices previously CE

marked under Directives 93/42/EEC or 90/385/EEC.

How PMCF surveys can help collect clinical evidence

remotely during the COVID-19 pandemic.

MHRA guidance for manufacturers, 2020.

How long does a hip replacement last? A systematic review

and meta-analysis of case series and national registry

reports with more than 15 years of follow-up - Jonathan

T Evans, Jonathan P Evans, Robert W Walker, Ashley

W Blom, Michael R Whitehouse*, Adrian Sayers* -

2019.

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