016 Mdr D9c8dd9a

Clinical Evidence Requirements

MDR Annex XIV clinical evaluation and post-market clinical follow-up guidance.

Table of Contents

• Clinical Evidence Framework
• Clinical Evaluation Process
• Literature-Based Evidence
• Clinical Investigation Requirements
• Post-Market Clinical Follow-up

Clinical Evidence Framework

Evidence Hierarchy

Evidence Requirements by Class

Clinical Evidence Pathway

Determine evidence strategy:

1. Assess device classification and risk level
2. Evaluate claim significance (diagnostic, therapeutic)
3. Determine if equivalence can be demonstrated
4. Identify available literature and clinical data
5. Assess gaps requiring additional investigation
6. Develop PMCF plan for ongoing evidence
7. Validation: Evidence strategy approved by Notified Body

Clinical Evaluation Process

Clinical Evaluation Workflow

Execute clinical evaluation per Annex XIV Part A:

1. Identify relevant safety and performance data
2. Define scope and search strategy
3. Conduct systematic literature search
4. Appraise and analyze clinical data
5. Assess benefit-risk profile
6. Document conclusions in Clinical Evaluation Report (CER)
7. Plan post-market clinical follow-up
8. Validation: CER reviewed by qualified clinical evaluator

Clinical Evaluation Report Structure

CLINICAL EVALUATION REPORT (CER)
├── 1. Executive Summary
│   ├── Device description and intended purpose
│   ├── Conclusions on safety and performance
│   └── Benefit-risk conclusion
├── 2. Scope of Clinical Evaluation
│   ├── Device identification
│   ├── Clinical claims to be evaluated
│   └── Equivalence assessment (if applicable)
├── 3. Clinical Background
│   ├── Disease/condition overview
│   ├── Current treatment options
│   └── State of the art
├── 4. Clinical Data Sources
│   ├── Pre-clinical data (bench, animal)
│   ├── Clinical investigation data
│   ├── Literature search methodology
│   └── Post-market surveillance data
├── 5. Data Appraisal
│   ├── Study quality assessment
│   ├── Relevance to subject device
│   └── Data contribution to evaluation
├── 6. Data Analysis
│   ├── Safety analysis
│   ├── Performance analysis
│   └── Benefit-risk determination
├── 7. Conclusions
│   ├── Clinical evidence summary
│   ├── Residual risks
│   └── PMCF requirements
└── 8. PMCF Plan Summary
    ├── Data gaps identified
    ├── PMCF activities planned
    └── Update schedule

Qualified Clinical Evaluator

Requirements per Annex XIV:

• Medical degree or equivalent healthcare qualification
• 4+ years clinical experience in relevant field OR
• Research background in relevant domain
• Training in clinical evaluation methodology
• Understanding of MDR requirements

Literature-Based Evidence

Literature Search Strategy

Execute systematic literature review:

1. Define PICO question (Population, Intervention, Comparison, Outcome)
2. Develop search string with Boolean operators
3. Select databases (PubMed, Embase, Cochrane, etc.)
4. Set date range and language filters
5. Execute search and document results
6. Screen abstracts and full texts
7. Validation: Reproducible search, documented exclusion criteria

Database Selection

Data Appraisal Criteria

Evaluate each source:

Equivalence Assessment

Demonstrate equivalence per MDCG 2020-5:

Technical equivalence:

• Similar design
• Same materials
• Same specifications
• Same manufacturing process

Biological equivalence:

• Same tissue contact
• Same biocompatibility
• Same sterilization method

Clinical equivalence:

• Same intended purpose
• Same clinical condition
• Same patient population
• Same user (professional/lay)

Clinical Investigation Requirements

When Investigation is Required

Clinical investigation mandatory:

• Class III implantable devices (Article 61(4))
• Novel technology without equivalent
• Significant modification to existing device
• New clinical claims not supported by literature
• Addressing gaps identified in clinical evaluation

Clinical Investigation Workflow

Conduct clinical investigation:

1. Develop Clinical Investigation Plan (CIP)
2. Submit to Ethics Committee for approval
3. Notify Competent Authority (via EUDAMED)
4. Conduct investigation per GCP principles
5. Collect and analyze clinical data
6. Prepare Clinical Investigation Report
7. Submit serious adverse event reports (within 7-15 days)
8. Validation: All subjects completed, data lock achieved

Clinical Investigation Plan Elements

Ethics Committee Submission

Required documentation:

• Clinical Investigation Plan
• Investigator's Brochure
• Informed consent documents
• Case Report Forms
• Investigator CVs
• Insurance certificate
• Device documentation

Post-Market Clinical Follow-up

PMCF Plan Requirements

Develop PMCF Plan per Annex XIV Part B:

1. Identify residual risks from clinical evaluation
2. Define clinical questions to address
3. Select PMCF methods (survey, registry, study)
4. Specify endpoints and success criteria
5. Define timeline and milestones
6. Plan data collection and analysis
7. Schedule PMCF Evaluation Report updates
8. Validation: PMCF Plan approved by Notified Body

PMCF Methods

PMCF Evaluation Report

Update frequency:

PMCF Report Structure

PMCF EVALUATION REPORT
├── 1. Executive Summary
│   └── Key findings and conclusions
├── 2. Scope
│   ├── Device covered
│   └── Reporting period
├── 3. PMCF Activities
│   ├── Methods employed
│   └── Data sources
├── 4. Results
│   ├── Safety data
│   ├── Performance data
│   └── Clinical questions addressed
├── 5. Conclusions
│   ├── Benefit-risk confirmation
│   ├── Residual risks updated
│   └── Need for corrective action
└── 6. Next Steps
    ├── CER update requirements
    └── PMCF Plan modifications

Integration with CER

PMCF data feeds clinical evaluation:

1. PMCF data collected per plan
2. Data analyzed in PMCF Evaluation Report
3. CER updated with PMCF conclusions
4. Risk management file updated
5. IFU updated if needed
6. Validation: CER update cycle completed