本報告已在2011年08月03日停止出版。
Abstract
Clinical trials of medical devices are costly, time-consuming and can make or
break the fortunes of a company. In addition, European laws create a labyrinth
of regulations for clinical trials that needs to be navigated with skill,
dexterity and knowledge. Therefore this report will furnish the reader with
information on why, when and how to conduct a clinical trial, and guide you
through all stages of the trial: from its preparation to capitalising on the
results, highlighting the potential pitfalls along the way.
The strategies discussed in this report can be applied successfully to any
market in the world. However, the legislation that governs the conduct of
clinical trials varies globally and, therefore, this report cover those
countries which are governed by the European Commission Directives.
Although this report traces the development of a device from its design to
final marketing, it will only discuss these events in terms of how they affect
and can be affected by clinical trials, and the focus of the report will be on
constructing efficient and effective clinical trials for medical devices in
general, with some specific examples.
The report covers clinical evaluation, which can take two forms: a collation
of scientific literature or the results of clinical trials. A clinical trial,
more properly termed a clinical investigation when referring to a medical
device, can be described as: A systematic study of human subjects to verify
the safety and performance of a specific medical device under normal
conditions of use.
Clinical trials (investigations) therefore act as a method of predicting the
future and long-term behaviour, efficiency and safety of a device in
situations where there are historical data on the device that can act as a
valid predictor of its performance. This is a legal requirement to gain
marketing approval for a medical device in the countries covered in this
course and can also act as a marketing tool for a company to show objective
evidence of the advantage of its product over a competitive technology and
lever purchasing decisions.
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
- 6.2.2 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
