Principles of good clinical practice

Good Clinical Practice guidelines provide an international quality standard for the regulation of clinical trials. They include standards on how clinical trials should be conducted, provide assurance of safety and efficacy of newly developed drugs and protect human rights. Principles of Good Clinical Practice describes the ethical principles and regulatory requirements that influence the current and future conduct of clinical research. As well as providing essential information on clinical trial design and pharmacovigilance, coverage also includes: informed consent; investigator and sponsor responsibilities; site monitoring; institutional review boards and independent ethics committees; clinical trial registration and reporting; quality assurance; future implications for good clinical practices. This text aims to be a one-stop source for guidance and checking the rules for proper conduct of clinical trials, as well as providing a historical perspective of the clinical research landscape. Principles of Good Clinical Practice will be a definitive text for Clinical Development personnel at pharmaceutical companies, Contract Research Organizations (CROs), PharmD and postgraduate pharmacy students, and medical, pharmacy and drug company libraries.

• Preface p. ix
• About the editors p. x
• Contributors p. xii
• Abbreviations p. xiv
• 1 Introduction to Good Clinical Practice p. 1 Sean W. Develin
• 2 Regulatory requirements p. 15 Catherine Burgess and Marie-Laure Papi and Kristel Van de Voorde and Guy Nys
• Introduction p. 15
• International Conference on Harmonisation requirements p. 15
• The United States (US) regulatory framework p. 17
• The European Union regulatory framework p. 27
• Summary p. 37
• 3 Informed consent p. 41 Steven P. Steinbrueck and Barbara S. Davis and Elizabeth E. Bodi
• Background p. 42
• Regulations and guidelines p. 44
• Introduction to form and process p. 44
• Liability, understanding, therapeutic misconception p. 51
• Developing a 'gold standard' p. 54
• Leadership p. 57
• Additional topics p. 57
• Summary p. 60
• 4 Investigator responsibilities p. 63 Jesse Goldman and Michael J. McGraw and Adam N. George
• Qualifications p. 64
• Assessment of the research p. 65
• Communication with the Institutional Review Board or Independent Ethics Committee p. 67
• Communication with sponsor p. 68
• Protecting safety, rights, and welfare of subjects p. 68
• Investigational product p. 71
• Safety reporting p. 73
• Assessment of causality p. 73
• Documentation and record retention p. 74
• Financial disclosure p. 75
• Inspections by health authorities p. 75
• Summary p. 75
• 5 Sponsor responsibilities p. 77 Donna W. Dorozinsky
• Quality p. 77
• Medical expertise p. 78
• Study design p. 79
• Data management p. 80
• Record keeping p. 81
• Safety reporting p. 83
• Investigator selection p. 86
• Investigational product p. 86
• Registration of clinical trials p. 88
• Reporting of clinical trial results p. 88
• Summary p. 89
• 6 Clinical trial design p. 91 Steven Gelone and Patrick Scoble
• Introduction p. 91
• What is clinical research? p. 91
• Historical perspective on clinical research p. 92
• Why is clinical research needed? p. 92
• The phases of drug development p. 93
• Where does clinical research begin? p. 95
• Critical concepts in clinical research p. 95
• Approaches to the design of clinical research studies p. 95
• Bias in clinical research p. 98
• Type I error, Type II error, and sample size p. 100
• Equivalency/non-inferiority versus superiority in clinical trials p. 102
• Clinical equipoise in controlled clinical trials p. 104
• Comparison of placebo versus the best-available control group in controlled clinical studies p. 105
• Challenges in conducting clinical research p. 105
• The interpretation and integration of clinical research into clinical practice p. 106
• 7 Site monitoring p. 109 Vickie T. Payne
• Selection and qualifications of the monitor p. 109
• The evaluation visit p. 110
• The initiation visit p. 112
• The monitoring visit p. 114
• The close-out visit p. 117
• Summary p. 119
• 8 Institutional Review Boards and Independent Ethics Committees p. 121 Michael R. Jacobs
• Composition, procedures, and function p. 122
• Protection of human subjects p. 125
• Review of the protocol, Investigator's Brochure, and informed consent p. 128
• Qualifications of the investigator and investigative team p. 138
• Risk-benefit analysis p. 139
• Continuing review p. 144
• Final thoughts p. 145
• 9 Pharmacovigilance p. 149 Stephen Klincewicz and Yuung Yuung Yap and Adrian Thomas
• Introduction p. 149
• Adverse events p. 150
• Reporting guidelines and timeline p. 153
• Signal detection p. 159
• Databases p. 161
• Conclusion p. 163
• 10 Clinical trial registration and reporting p. 167 Barbara Godlew and Shawn Pelletier and Maureen Strange
• Introduction and history p. 167
• Clinical trial registration p. 170
• Clinical trial results databases p. 175
• Legislation and regulatory requirements p. 177
• Clinical trial disclosure implications for future therapeutic development p. 178
• Summary p. 180
• 11 Quality assurance p. 183 Peter Smith
• Introduction p. 183
• Defining quality p. 184
• Auditing: purpose of auditing p. 185
• The audit plan p. 186
• Conduct of the audit p. 188
• Types of audit p. 188
• Summary p. 200
• 12 Future implications of Good Clinical Practice p. 203 Thomas Jacobsen
• Globalization of clinical research p. 203
• Genomics p. 205
• Gene transfer p. 207
• Stem cell research p. 208
• Nanotechnology p. 210
• Conclusion p. 212
• Appendix 1 The Nuremberg Code p. 215
• Appendix 2 World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects p. 217
• Appendix 3 The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research p. 223
• Glossary p. 235
• Index p. 245