Conducting Medical Device Clinical Trials in the EU

Table of Contents

CHAPTER 1 INTRODUCTION

• 1.1 The medical device directives
  • 1.1.1 Proposed changes specific to clinical trials
  • 1.1.2 European Directive 2001/20/EEC
• 1.2 Guidelines
  • 1.2.1 I SO 14155 parts 1 and 2
• 1.3 Trials of CE-marked devices

CHAPTER 2 APPROVAL ROUTES AND CONSIDERATIONS

• 2.1 Classification
• 2.2 Risk analysis
• 2.3 Routes to approval

CHAPTER 3 PLANNING

• 3.1 The budg et
  • 3.1.1 Direct costs
    • 3.1.1.1 Manufacturing costs
    • 3.1.1.2 Pre-investigation development costs
    • 3.1.1.3 Clinical trial budget
      • ...Personnel costs
      • ...Patient-related costs
      • ...Miscellaneous costs
  • 3.1.2 I ndirect costs
• 3.2 Selection of the clinical investigation team
  • 3.2.1 Legal roles
    • 3.2.1.1 The sponsor
    • 3.2.1.2 The monitor
    • 3.2.1.3 The investigator
  • 3.2.2 Other roles
• 3.3 Study design
• 3.4 Clinical investigational plan

CHAPTER 4 PREPARATION

• 4.1 Documentation
  • 4.1.1 The clinical trial agreement (CTA)
  • 4.1.2 Clinical trial master agreements
  • 4.1.3 Investigator' s Brochure (IB)
  • 4.1.4 Ethics committee approval
  • 4.1.5 Patients' Informed consent (PIC)
  • 4.1.6 Adverse event form
  • 4.1.7 Subject screening log
  • 4.1.8 Subject identification code list
  • 4.1.9 Subject enrolment log
  • 4.1.10 Initials/sig natures list
  • 4.1.11 Case report forms (CRFs)
  • 4.1.12 Clinical study report (CSR)
  • 4.1.13 Other documents
• 4.2 Labelling and instructions for use
• 4.3 Insurance
• 4.4 Site selection
  • ...PI qualifications
  • ...Potential subject population
  • ...Adequate staff & resources - provide CVs, business cards, org anizational chart
  • ...Availability of appropriate facilities & equipment
  • ...EC services & turn around
  • ...Good clinical practice knowledge & compliance document any formal GCP training
  • ...Responsiveness of site and rapidity of study initiation
  • 4.4.1 I taly
• 4.5 Monitor selection
• 4.6 Training

CHAPTER 5 IMPLEMENTATION

• 5.1 Resource allocation
• 5.2 Subject recruitment
  • 5.2.1 Screening
  • 5.2.2 Retention
• 5.3 Monitoring

CHAPTER 6 CLOSING

• 6.1 Notification
• 6.2 Collection and filing
  • 6.2.1 Data management
    • 6.2.1.1 Data protection
  • 6.2.2 Risk management file
• 6.3 Analysis
• 6.4 The clinical study report

CHAPTER 7 ISSUES

• 7.1 US and European comparisons
  • 7.1.1 Good clinical practice
  • 7.1.2 Adverse events
  • 7.1.3 Reporting and publishing
  • 7.1.4 Classification
• 7.2 Conformity assessment
  • 7.2.1 Classification
  • 7.2.2 Notified bodies
  • 7.2.3 Conformity assessment
• 7.3 Advanced therapies legislation
• 7.4 Clinical Evaluation Task Force
• 7.5 Data protection
• 7.6 Branding

CHAPTER 8 COUNTRY SPECIFICS

• 8.1 Austria
  • 8.1.1 Competent Authority
  • 8.1.2 Notified bodies
  • 8.1.3 Translation
  • 8.1.4 Notification requirements
  • 8.1.5 Insurance
  • 8.1.6 Other issues
• 8.2 Belg ium
  • 8.2.1 Competent Authority
  • 8.2.2 Notified bodies
  • 8.2.3 Translation
  • 8.2.4 Notification requirements
  • 8.2.5 Insurance
  • 8.2.6 Other issues
• 8.3 Denmark
  • 8.3.1 Competent Authority
  • 8.3.2 Notified bodies
  • 8.3.3 Translation
  • 8.3.4 Notification requirements
  • 8.3.5 Insurance
  • 8.3.6 Other issues
• 8.4 Finland
  • 8.4.1 Competent Authority
  • 8.4.2 Notified bodies
  • 8.4.3 Translation
  • 8.4.4 Notification requirements
  • 8.4.5 Insurance
  • 8.4.6 Other issues
• 8.5 France
  • 8.5.1 Competent Authority
  • 8.5.2 Notified bodies
  • 8.5.3 Translation
  • 8.5.4 Notification requirements
  • 8.5.5 Insurance
  • 8.5.6 Other issues
• 8.6 Germ any
  • 8.6.1 Competent Authority
  • 8.6.2 Notified bodies
  • 8.6.3 Translation
  • 8.6.4 Notification requirements
  • 8.6.5 Insurance
  • 8.6.6 Other issues
• 8.7 Ireland
  • 8.7.1 Competent Authority
  • 8.7.2 Notified bodies
  • 8.7.3 Translation
  • 8.7.4 Notification requirements
  • 8.7.5 Insurance
  • 8.7.6 Other issues
• 8.8 Italy
  • 8.8.1 Competent Authority
  • 8.8.2 Notified bodies
  • 8.8.3 Translation
  • 8.8.4 Notification requirements
  • 8.8.5 Insurance
  • 8.8.6 Other issues
• 8.9 The Netherlands
  • 8.9.1 Competent Authority
  • 8.9.2 Notified bodies
  • 8.9.3 Translation
  • 8.9.4 Notification requirements
  • 8.9.5 Insurance
  • 8.9.6 Other issues
• 8.10 Norway
  • 8.10.1 Competent Authority
  • 8.10.2 Notified bodies
  • 8.10.3 Translation
  • 8.10.4 Notification requirements
  • 8.10.5 Insurance
  • 8.10.6 Other issues
• 8.11 Spain
  • 8.11.1 Competent Authority
  • 8.11.2 Notified bodies
  • 8.11.3 Translation
  • 8.11.4 Notification requirements
  • 8.11.5 Insurance
  • 8.11.6 Other issues
• 8.12 Switzerland
  • 8.12.1 Competent Authority
  • 8.12.2 Notified bodies
  • 8.12.3 Translation
  • 8.12.4 Notification requirements
  • 8.12.5 Insurance
  • 8.12.6 Other issues
• 8.13 The UK
  • 8.13.1 Competent Authority
  • 8.13.2 Notified bodies
  • 8.13.3 Translation
  • 8.13.4 Notification requirements
  • 8.13.5 Insurance
  • 8.13.6 Other issues

CHAPTER 9 SECTOR INFORMATION

• 9.1 Class
  • 9.1.1 Class I
  • 9.1.2 Class IIa
  • 9.1.3 Class IIb
  • 9.1.4 Active Im lantable Medical Devices
• 9.2 Medical devices compared to pharm aceuticals
  • 9.2.1 Timelines
    • 9.2.1.1 Study size
    • 9.2.1.2 Approval process

CHAPTER 10 CASE STUDIES

• 10.1 Drug device combination product
• 10.2 Sample size
• 10.3 Site selection
• 10.4 Storage
• 10.5 Device accountability
• 10.6 Classification

APPENDIX

LIST OF TABLES

• Table 2.1 Risk matrix
• Table 2.2 Risk management
• Table 2.3 A hierarchy of evidence
• Table 3.1 Processes conducted in the planning phase
• Table 3.2 Processes and costing for an investigator with a 12 patient investigation
• Table 4.1 Processes conducted in the preparatory phase
• Table 5.1 Processes conducted in the im plementation phase
• Table 5.2 Documentation and location
• Table 5.3 Clinical investigation properties
• Table 5.4 The funnel effect in subject recruitment
• Table 6.1 Processes conducted in the closing phase
• Table 6.2 Documentation and location at closure of investigation
• Table 7.1 European and US GCP requirements
• Table 7.2 Comparative classification rules in the EU and the US
• Table 7.3 Examples of Medical Devices Classified Using Annex I X of the European Medical Device Directive (EC/93/42) and the US system
• Table 7.4 Impact of phonetic sounds
• Table 8.1 Documents/information for initial submission in Austria
• Table 8.2 Documents/information for initial submission in Belgium
• Table 8.3 Documents/information for initial submission in Finland
• Table 8.4 Documents/information for initial submission in Germany
• Table 8.5 Documents/information for initial submission in Ireland
• Table 8.6 Documents/information for initial submission in Italy
• Table 8.7 Documents/information for initial submission in The Netherlands
• Table 8.8 Documents/information for initial submission in Spain
• Table 8.9 Documents/information for initial submission in the UK
• Table 9.1 The medical device and pharm aceutical sectors
• Table 9.2 EC approval issues in European Countries for m edical devices
• Table 9.3 CA approval issues in European Countries for m edical devices
• Table 9.4 Regulatory and ethical review time in European countries for pharmaceuticals and medical devices

LIST OF FIGURES

• Figure 2.1 Classification process for multi-part wound drainage device
• Figure 2.2 Flow chart of procedures and guidance documents involved in initiating a clinical trial
• Figure 3.1 Requirements and processes leading to planning phase of a clinical investigation
• Figure 5.1 Example of a subject questionnaire for the clinical investigation of a continuous glucose sensor in the management of Type 1 diabetes in adults
• Figure 7.1 Adverse events reporting requirements in the US
• Figure 7.2 Adverse events reporting requirements in Europe
• Figure 7.3 Brand logo of NWTHA asthma audit
• Figure 9.1 Approval route for Class I devices
• Figure 9.2 Approval route for Class IIa devices
• Figure 9.3 Approval route for Class IIb devices
• Figure 9.4 Approval route for Class III devices
• Figure 9.5 The phases of a clinical investigation for a medical device