Β© Copyright 2012
Foreword
Acknowledgements
Feedback
Abbreviationsβ
Preface
Introduction
Chapter 1 Sponsor oversight
1.1 Sponsors
1.2 Clinical trial authorisations and research ethics committee opinion
1.3 Good Clinical Practice and conduct of clinical trials
1.4 Pharmacovigilance
1.5 Manufacture, assembly, importation and labelling of IMP
1.6 Trial/project management
1.7 Chapter legislative references
Chapter 2 Clinical trial authorisations
2.1 Legal definition of a clinical trial
2.2
2.3 Clinical trial authorisation applications β assessment and amendments
2.4 Risk-adapted approach to the management of clinical trials
2.5 Clinical trial authorisation applications requiring expert advice
2.6 Voluntary Harmonisation Procedure
2.7 Chapter legislative references
Chapter 3 Ethical review
3.1 Appointment of research ethics committees
3.2 Application to research ethics committees
3.3 Informed consent
3.4 Amendments
3.5 Safety reporting to the research ethics committee
3.6 Other required reports to the research ethics committee
3.7 Retention of documentation by the research ethics committee
3.8 GCP inspections and ethical review
3.9 Chapter legislative references
Chapter 4 Key trial documentation
4.1 Expectations and legislative requirements
4.2 Generation of key trial documentation
4.3 Updating and amending key trial documents
4.4 Version control
4.5 Cross-checking and quality control
4.6 Sponsor oversight of third-party key trial documents
4.7 Key trial document considerations
4.8 Chapter legislative references
Chapter 5 Pharmacovigilance for clinical trials
5.1 Relevant terminology
5.2 Introduction to safety reporting
5.3 Adverse events β recording and notification
5.4 Serious adverse events
5.5 Suspected unexpected serious adverse reactions
5.6 Assessments and information required for reporting purposes
5.7 Considerations for blinded trials
5.8 Ongoing safety evaluation
5.9 Data monitoring committees/data safety monitoring boards
5.10 Safety reporting requirements for nIMPs
5.11 Out-of-hours medical cover
5.12 Investigator-initiated trials
5.13 Specific safety requirements for trials of advanced therapy products
5.14 Pharmacovigilance data collection
5.15 Development safety update reports
5.16 Chapter legislative references
Chapter 6 Investigational medicinal products
6.1 Requirements for a manufacturing authorisation for investigational medicinal products
6.2 Exemptions from the need for an MIA(IMP)
6.3 Declaration, certification and release
6.4 Contracting-out activities
6.5 Active pharmaceutical ingredient
6.6 Blinding
6.7 Labelling
6.8 Manufacture or reconstitution
6.9 The use of commercial supply in clinical trials
6.10 Supplies for investigator-initiated trials
6.11 Product recall
6.12 Non-investigational medicinal products
6.13 Drug accountability
6.14 Storage and distribution of investigational medicinal product
6.15 Administration at home
6.16 Use of trial material after trial completion
6.17 Prescribing and dispensing
6.18 Documentation retention
6.19 Chapter legislative references
Chapter 7 Monitoring
7.1 Introduction to monitoring
7.2 Monitoring overview
7.3 Monitoring strategy
7.4 Monitoring personnel
7.5 Monitoring activities
7.6 Output from monitoring
7.7 Source data verification and case report form management
7.8 Chapter legislative references
Chapter 8 Data management
8.1 Overview of the data management process
8.2 Case report forms and data collection tools
8.3 Clinical database
8.4 Data capture
8.5 Data validation
8.6 Database/dataset lock
8.7 Chapter legislative references
Chapter 9 Statistics
9.1 Statistical processes, procedures and records
9.2 Statistics personnel
9.3 Trial and protocol design
9.4 Statistical input to case report form design and data management activities
9.5 Randomisation and blinding
9.6 Statistical analysis plan
9.7 Statistical programming and analysis
9.8 Chapter legislative references
Chapter 10 Trial master file and archiving
10.1 Requirement for a trial master file
10.2 Trial master file organisation
10.3 Content of the trial master file
10.4 Control of the trial master file
10.5 Electronic trial master file
10.6 MHRA GCP inspection of trial master files
10.7 Archiving
10.8 Chapter legislative references
Chapter 11 Investigator sites
11.1 Research site
11.2 Investigator site research team
11.3 Site set-up
11.4 During the study
11.5 Study documentation
11.6 Chapter legislative references
Chapter 12 Phase I clinical trials
12.1 Introduction to Phase I clinical trials
12.2 Voluntary MHRA Phase I Accreditation Scheme
12.3 Authorisation and ethical opinion for a Phase I clinical trial
12.4 Contracts, agreements and insurance
12.5 Risk assessment and contingency planning
12.6 Dose escalation in clinical trials
12.7 IMP management
12.8 Facilities and equipment
12.9 Planning and resources
12.10 Training
12.11 Emergency procedures
12.12 Subject identification and recruitment
12.13 Chapter legislative references
Chapter 13 Clinical trial samples β analysis and evaluation
13.1 Organisation of laboratory work
13.2 Sample transportation, receipt and storage
13.3 Processing samples from clinical trials
13.4 Laboratory facilities and equipment
13.5 Reporting and archiving of data
13.6 Maintaining quality within the laboratory
13.7 The trial subject
13.8 Chapter legislative references
Chapter 14 Quality systems
14.1 Quality system structure
14.2 Training
14.3 Quality control
14.4 Quality assurance
14.5 Computer system validation
14.6 Chapter legislative references
Annexes
Annex 1 Introduction to GCP inspections
A.1.1 Legal basis for inspections
A.1.2 MHRA GCP inspectors
A.1.3 Types of GCP inspections
A.1.4 Scope of GCP inspections
A.1.5 Inspection schedule
A.1.6 Phases of the inspection process
A.1.7 Responding to findings
A.1.8 Close-out of the inspection
A.1.9 Follow-up for serious inspection findings
A.1.10 Re-inspections
A.1.11 Tips for preparing for a competent authority inspection
Annex 2 Relevant legislation and guidance
A.2.1 European legislation
A.2.2 UK legislation
A.2.3 Guidance documents and other useful reference texts
Annex 3 Advanced therapy investigational medicinal product trials
A.3.1 Considerations for advanced therapy investigational medicinal product trials
A.3.2 Annex legislative references
Annex 4 Considerations for use of electronic systems in clinical trial management
A.4.1 What is an IRT system?
A.4.2 Setting up an IRT system
A.4.3 Use of an IRT system
A.4.4 Maintenance of an IRT system
A.4.5 What to do when the IRT system is unavailable
A.4.6 Close-down of an IRT system
A.4.7 Annex legislative references
Glossary
Index
Table Index
Figure Index