The Fundamentals of Clinical Research

P. Michael Dubinsky has more than forty years of experience in the field of GxP quality and compliance in government and industry. He has worked with the FDA and as a regulatory consultant for private corporations. He was also an Instructor in the areas of clinical trial compliance, regulatory audits, and quality at the University of California Berkeley Extension Programs. Karen A. Henry has worked as a clinical research professional since 1990. She has expertise in regulatory medical writing, standards and processes, trial management and monitoring, biostatistics, and data management. She is also a Lead Instructor for the Certificate Program in Clinical Research Conduct Management at the University of California Berkeley Extension Programs.

Preface viii

About the Authors xi

About the Companion Website xii

Part I Good Clinical Practice History 1

1 History 3
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Part II Drug Development in the Regulatory Environment 11

2 Regulatory Environment 13
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3 GCP in Context 25
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4 The Intersection of GCP and Regulation 31
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5 Regulatory Affairs 39
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Part III Good Clinical Practice 47

6 GCP Definition and Principles 49
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7 Players Roles and Responsibilities Overview 59
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8 IRB/IEC Roles and Responsibilities 67
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9 Investigator and Sponsor Roles and Responsibilities 73
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10 The Research Volunteer 85
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11 Regulatory Authority – Roles and Responsibilities 93
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Part IV Individual Clinical Trial 101

12 Individual Clinical Trial Overview 103
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13 Risk Assessment and Quality Management 129
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14 Trial Management; Start-up, On-Study, and Close-Out 135
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15 Trial Resourcing and Outsourcing 173
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16 The Investigator’s Brochure 183
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17 The Investigational Product (Clinical Supplies) 201
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18 The Clinical Trial Protocol and Amendments 211
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19 Informed Consent and Other Human Subject Protection 239
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20 Data Collection and Data Management 265
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21 Safety Monitoring and Reporting 285
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22 Monitoring Overview 301
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23 Investigator/Institution Selection 323
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24 Investigator/Institution Initiation 343
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25 Investigator/Institution Interim Monitoring 363
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26 Investigator/Institution Close-out 381
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27 Study Design and Data Analysis 401
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28 The Clinical Study Report 415
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29 Essential Documents 435
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Part V Quality in Clinical Trials 451

30 Quality Systems in Clinical Research 453
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31 Quality Responsibilities 463
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32 Standard Operating Procedures 475
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33 Quality Assurance Components 489
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34 Regulatory Authority Inspections 497
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References for all Chapters 503

Index 509