Clinical documentation for medical devices Medical Devices Regulation (EU) 2017/745 We prepare EU MDR-compliant clinical documentation for medical device manufacturers for submission to notified bodies and national regulatory authorities. EU MDR-compliant clinical documentation (English, Czech): - Clinical evaluation (plan, report) - Post-Market Clinical Follow-Up, - - PMCF (plan, report, study design) - Post-Market Surveillance System (plan, report) - Clinical investigation design to complement existing evidence - Biological Evaluation - Literature review Consulting - Strategy how to generate clinical evidence - Design of PMCF studies and clinical investigations Additional support: - Clinical expert for multiple medical specialties - Risk management specialist - Technical documentation

1. CLINICAL DOCUMENTATION
FOR MEDICAL DEVICES
We prepare EU MDR-compliant clinical
documentation for medical device
manufacturers for submission to notified
bodies and national regulatory authorities.
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www.aretezoe.com
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Medical Devices Regulation (EU) 2017/745

2. What we offer
EU MDR-compliant clinical documentation (English, Czech)
• C linical ev aluation (plan, report)
• Post-Market C linical Follow-U p, PMC F (plan, report, study design)
• Post-Market S urv eillance S y stem (plan, report)
• C linical inv estigation design to complement existing ev idence
• Biological Ev aluation
• Literature rev iew
Consulting
• Strategy how to generate clinical evidence
• Design of PMCF studies and clinical investigations
Additional support:
• C linical expert for multiple medical specialties
• R isk management specialist
• Technical documentation
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3. Clinical Documentation
Clinical Evaluation Plan (CEP) and Report (CER)
Literature review, appraisal, summary, protocol
Biological Evaluation (ISO 10993)
Post-Market Clinical Follow-Up (PMCF) Plan and Report
Post-Market Surveillance (PMS) Plan and Report
Periodic Safety Update Report (PSUR)
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Medical Device Regulation (EU) 2017/745

4. The importance of CER
Report is the result of clinical evaluation (process)
Essential part of submission, standalone document
Common source of non-compliance
Clinical data:
• Scientific literature
• Clinical experience (including PMCF)
• Clinical investigations
Process for regular updates to the document
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5. Strategy, plan
Strategy for how to
generate clinical evidence
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6. Strategy for how to generate clinical evidence
• Review of manufacturer’s existing documentation
• Review of clinical investigations and PMCF studies
• Review of biological compatibility documentation
• Review of results of bench tests
• Selection of equivalent devices
• Identification of gaps in clinical evidence
• Literature search strategy
• Strategy for obtaining additional clinical evidence, e.g., via PMCF
• The need to perform additional clinical investigation
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7. Scope of clinical evaluation
• Objective and type of clinical evaluation
• Components of clinical evaluation
• Product identification, description,
• Purpose of use
• Indications, contraindications, warnings, precautions
• Target population, disease
• Estimate of treated patients
• Recalls, FSCAs, adverse incidents, complaints
• Accessories
• Equivalent and similar medical devices
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8. Clinical Evaluation Plan
• Purpose of use, target population
• Indications, contraindications
• Intended clinical benefit
• General Safety and Performance Requirements
• Type of clinical evaluation
• Methods used for examining clinical safety
• Other aspects that require specific attention
• Changes introduced by manufacturer
• Post-market surveillance, vigilance, PMCF
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9. Questions the Clinical Evaluation
should address
• Concerns mentioned in previous Clinical Evaluation Report
• Clinical risks mentioned in the Risk Management File
• Signals from literature
• Signals from vigilance, PMCF, PMS
• Feedback from the field (distribution, users)
• Gaps in clinical evidence
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10. Initial
documentation
Materials required to prepare
clinical documentation
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11. Manufacturer’s documentation
• Manufacturer’s ad mi ni strati ve d etai l s
• Contact p erson, Person R esp onsi b l e for R egul atory Comp l i ance (PR R C)
• Instructi ons for use, l ab el i ng, op erati onal manual
• Issued Certi fi cates, Decl arati on of Conformi ty
• R i sk management fi l e
• R esul ts of cl i ni cal i nvesti gati on i f avai l ab l e
• Previ ous cl i ni cal eval uati on p l an/rep ort, PMCF p l an/rep ort, PMS p l an/rep ort
• Bi ol ogi cal eval uati on
• S al es for the rep orti ng p eri od , esti mate of treated p ati ents
• Li st of countri es where the d evi ce i s marketed
• Ad verse i nci d ents, comp l ai nts, FS CAs, recal l s
• Li st of ap p l i cab l e harmoni zed norms
• Eq ui val ent d evi ces: IFU , certi fi cates, other d ocumentati on
• G S PR checkl i st
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12. Harmonized norms
• National laws and regulations
• Applicable ISO standards
• EU legislation (MDD, MDR, REACH…)
• MDCG and MedDEV Guidelines
Comment: The reviewers can apply MDCG
guidelines that were not yet published after
the completion of the clinical evaluation.
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13. General Safety and Performance
Requirements (GSPR checklist)
• General requirements
• Requirements regarding design and manufacture
• Requirements regarding the information supplied
with the device
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14. Biological evaluation
• ISO 10993-1
• Nature and duration of contact with human body / tissues
• Chemical, physical characteristics and analyses
• Biological effects
• Tests for biological evaluation
• Justification why testing is not required
• Update of biological evaluation based on CER
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15. Clinical background
Current treatment options
State of the Art
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16. Clinical background
• Description of disease/state for which the
device is used
• Sources: Contemporary monographs
• Regular update of sections
• Methodology used to find information and
update the section
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17. State of the Art
• Reviews of technologies used for a specific
purpose, their advantages and disadvantages
• Methodology for initial search and process for
update of the section
• Type of publications: systematic review, meta-
analysis, review, clinical practice guidelines
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18. Alternative treatment options
• Treatment options used to treat a specific condition /disease based
on treatment standards, clinical guidelines, disease monographs
• What is the role of the device under evaluation in the context of
treatment (gold standard, second line treatment, specific
scenarios)
• Methodology for initial information search and a process for update
of the section
• Publication type: clinical guidelines and recommendations,
systematic reviews with or without meta-analysis
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19. Demonstration
of Equivalence
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20. Selection of equivalent products
• Meets the equivalence criteria in technical, biological
and clinical characteristics, as defined in MDCG-5
• Equivalent device has MDR certification
• Sufficient information available
• Device complies with the same harmonized norms
• The ability to use clinical data from literature depends
on the selection of equivalent product(s)
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21. Equivalence: Technical characteristics
• Device is of similar design
• Used under similar conditions of use
• Similar specifications and characteristics, including
• Similar specifications and properties including physiochemical
properties such as intensity of energy, tensile strength,
viscosity, surface characteristics, wavelength and software
algorithms
• Uses similar deployment methods where relevant
• Has similar principles of operation and critical performance
requirements
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22. Equivalence: Biological characteristics
• Uses the same materials or substances in contact
with the same human tissues or body fluids
• Similar kind and duration of contact with the same
human tissues or body fluids
• Similar release characteristics of substances
including degradation products and leachables
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23. Equivalence: Clinical characteristics
• Same clinical condition or purpose, including similar
severity and stage of disease
• Same site in the body
• Similar population, including as regards age, anatomy and
physiology
• Same kind of user
• Similar relevant critical performance in view of the
expected clinical effect for a specific intended purpose
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24. Literature
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25. Literature search: Scope
• Safety
• Efficacy
• State of the Art
• Clinical background
• Alternative treatment options
• Specific concerns
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26. Literature search: Inclusion criteria
Appropriate medical device
• Device under investigation
• Equivalent device
• Similar, generic device where equivalence can be demonstrated
Appropriate purpose of use
Appropriate patient population
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27. Types of
publication
Umbrella review
Meta-analysis, network meta-analysis
Systematic review of Randomized
Controlled Trials
Systematic review of Observational Studies
Randomized Control Trial
Other types of interventional studies
Cohort studies
Case-control studies
Observational studies
Case series, case reports
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28. Pyramida důkazu
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Expert opinions, background information
Randomized controlled studies
Cohort studies
Case-controlled studies
Case series, case reports
Systematic
reviews (SR)
Meta-analyses (MA)
Umbrella reviews (UR)
Volume of information
Prioritization by type of publication
• Limit the number of publications by type
of publication
• Prioritize high-quality evidence
• Find studies included in systematic
reviews and meta-analyses
• De-duplication of records: note studies
included in SR/MAs

29. Sources
• PubMed
• Prospero
• Cochrane Library
• EMBASE
• ClinicalTrials.gov
• WHO International CT Registry Platform (ICTRP)
• Medscape
• Clinical guidelines (professional societies)
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30. Literature
Appraisal
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31. Evidence appraisal
G l ob al Harmoni zati on Task Force’s (G HTF, now IMDR F) S tud y G roup 5 on Cl i ni cal
S afety/Performance, S G 5/N2R 8:2007 ap p end i x D d evi ces
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Suitability
criteria Description Grading system
Appropriate device Was the data generated from the device in
question?
D1
D2
D3
Actual device
Comparable device
Other device
Appropriate device
application
Was the device used for the same intended
use (e.g., methods of deployment,
application, etc.)?
A1
A2
A3
Same use
Minor deviation
Major deviation
Appropriate patient
group
Were the data generated from a patient
group that is representative of the
intended treatment population (e.g., age,
sex, etc.) and clinical condition (i.e.,
disease, including state and severity)?
P1
P2
P3
P4
Applicable
Limited
Different population
(n/a, bench-top or pre-clinical
studies)
Acceptable
report/data
collation
Do the reports or collations of data contain
sufficient information to be able to
undertake a rational and objective
assessment?
R1
R2
R3
High quality
Minor deficiencies
Insufficient information

32. Contribution of individual publications
G l ob al Harmoni zati on Task Force’s (G HTF, now IMDR F) S tud y G roup 5 on Cl i ni cal
S afety/Performance, S G 5/N2R 8:2007 ap p end i x D d evi ces
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Suitability criteria Description Grading
system
Data source type (T)
Was the design of the study appropriate? 1
2
Yes
No
Outcome measures (O)
Does the outcome measures reported reflect
the intended performance of the device?
1
2
Yes
No
Follow-up (F)
Is the duration of follow-up long enough to
assess whether duration of treatment effects
and identify complications?
1
2
Yes
No
Statistical significance (S)
Has a statistical analysis of the data been
provided and is it appropriate?
1
2
Yes
No
Clinical significance (C)
Was the magnitude of the treatment effects
observed clinically significant?
1
2
Yes
No

33. Literature search protocol
• Overview, scope
• Identification of data
• Databases, registries
• Search criteria
• Inclusion and exclusion criteria
• Search results (document reason for exclusion)
• Appraisal of results
• Summary
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34. Appraisal of clinical evidence
• Specific concerns that need to be addressed
• Materials generated by the manufacturer
• Information from PMCF, PMS and vigilance
• Demonstration of equivalence
• Appraisal of evidence from literature
• Summary of clinical data
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35. Post-Market Clinical
Follow-Up (PMCF)
Post Market
Surveillance (PMS)
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36. Post-Market Clinical Follow-Up (PMCF) Plan
• MDCG 2020-7
• What data needs to be gathered, what
questions need to be answered?
• The choice of activities depends on
information needs
• Methodology must be defined in advance
• Justify methods used
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37. PMCF activities
• Targeted literature search
• Prospective PMCF study
• Retrospective PMCF study
• Specialized registries
• Questionnaire for health professionals
• Questionnaire for health patients
• Review of case reports
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38. PMCF Report
• MDCG 2020-8
• Results of activities recorded in PMCF Plan
• Discusses clinical data relating to equivalent and
similar devices
• Includes impact of the results on technical
documentation
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39. Post-Market Surveillance Plan
• Serious adverse incidents
• Information from Periodic Safety Update Reports (PSURs)
• Information from Field Safety Corrective Actions (FSCAs)
• Non-serious adverse incidents, adverse effects
• Information from trend reports
• Information from scientific literature
• Information from databases and registries
• Feedback from users, complaints
• Publicly available information on equivalent and similar devices
• Information from Post-Market Clinical Follow-Up (PMCF)
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40. PMS Report (Class I)
PSUR (Class IIa, IIb, III)
• Update the benefit-risk determination
• Data gathered during activities described in PMS Plan
• The main findings of the PMCF
• Estimate of patient exposure
• Class I devices: PMS Report (Article 85)
• Class IIa devices: PSUR every 2 years (Article 86)
• Class III devices: PSUR every year (Article 86)
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41. Analysis of
clinical
evidence
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42. Analysis of clinical evidence
• Outputs from risk analysis
• Clinical benefits
• Safety requirements
• Efficacy requirements
• Benefit:risk profile
• Acceptability of adverse effects
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43. Materials for
users
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44. Instructions for Use, labeling
• Document format, mandatory information
• Consider customary practices
• Appropriate for the type of user
• Electronic format acceptable
• Regular update based on clinical evaluation
• Comparison of changes!
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45. Update of marketing materials
• Results from clinical evaluation must be reflected
in marketing materials
• Accuracy of wording in marketing materials
• Can include literature references, PMCF studies
• Information from clinical guidelines
• Mandatory: information on manufacturer, contact
for reporting adverse events and complaints
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46. CONTACT
Website: https://www.aretezoe.com/
Email: veronikav@arete-zoe.com
T (US): +1-631-791-8129
T (Czechia): +420-721-079-971
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