Clinical research continues to be one of the most vital components of pharmaceutical, biostatistical, and medical studies. Design, Execution, and Management of Medical Device Clinical Trials provides a uniform methodology for conducting and managing clinical trials. Written in a style that is accessible to readers from diverse educational and professional backgrounds, this book provides an in-depth and broad overview for successfully performing clinical tasks and activities.
Throughout the book, practical examples compiled from both the author's and other researchers' previous clinical trial experiences are discussed in a sequential manner as they occur in the study, starting from the development of the clinical protocol and the selection of clinical sites and ending with the completion of the final clinical study report. Next, readers are guided through the development of important clinical documents, including informed consent forms, case report forms, and study logs. A careful review of the Food and Drug Administration (FDA) and International Conference on Harmonisation (ICH) regulations applicable to medical devices is also featured. Additional coverage includes:
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Qualification and selection of investigators
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Study monitoring visits
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Definitions and reporting procedures for adverse events
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The use of biostatistical methodology in clinical research, including the use of biostatistics for sample size determination and study endpoints
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The roles and responsibilities of all members of a clinical research team
The book concludes with an insightful discussion of special ethical conduct for human research and challenging issues to consider during the design of clinical studies. A glossary lists important clinical and statistical terms used in clinical research, and an extensive reference section provides additional resources for the most up-to-date literature on the topic.
Design, Execution, and Management of Medical Device Clinical Trials is an excellent book for clinical research or epidemiology courses at the upper-undergraduate and graduate levels. It is also an indispensable reference for clinical research associates, clinical managers, clinical scientists, biostatisticians, pharmacologists, and any professional working in the field of clinical research who would like to better understand clinical research practices.
Table of Contents
List of Abbreviations xi
Preface xv
Acknowledgments xxi
1 An Overview of Clinical Study Tasks and Activities 1
Key Clinical Study Tasks and Activities 2
Discussion of Key Tasks and Activities 3
Management of Key Clinical Tasks and Activities 9
Example of the Spread Sheet for Managing Clinical Study Activities 10
The Clinical Research Team 10
2 Development of Clinical Protocols, Case Report Forms, Clinical Standard Operating Procedures, Informed Consent Form, Study Regulatory Binder, Study Research Agreement, and Other Clinical Materials 15
Clinical Protocol 17
Case Report Forms (CRFs) 28
Example of the Case Report Form Template 32
Informed Consent Form (ICF) 35
Instructions for Use of Device 38
Study Regulatory Binder 39
Study Research Agreement 40
Research Agreement Template 43
Research Contract Challenges 50
Clinical Forms and Certificates 51
Clinical Standard Operating Procedures (SOPs) 54
3 Qualification/Selection of Study Investigators and Study Monitoring Visits 63
Qualification and Selection of Investigators 64
Monitoring Visits 67
Monitoring Reports 73
Interim Monitoring Visit Report Template 75
4 Adverse Events Definitions and Reporting Procedures 81
Adverse Event Definitions 83
Policies, Regulations, and Guidelines Regarding Adverse Event Reporting 84
Adverse Event Reporting Pathway 84
Terms for Causality Assessment 85
GAPS/Challenges in Adverse Event Reporting 86
Adverse Event Reporting Time Periods (21 CFR 803) 88
Differences between the United States and Europe in Reporting Adverse Events 88
Serious Adverse Event Narratives 89
Classification of Adverse Events 90
Special Requirement for Reporting Certain Adverse Events 92
Case Example 92
Mandatory Device Reporting for FDA-Approved Devices 92
5 Statistical Analysis Plan (SAP) and Biostatistics in Clinical Research 93
Statistical Analysis Plan (SAP) 94
Selection of Study Endpoints 97
Biostatistics in Clinical Research 101
6 Final Clinical Study Report 113
Final Clinical Report’s Outline 114
Discussion of Sections in the Final Clinical Report 116
7 Medical Device Regulations Combination Product, Study Committees, and FDA-Sponsor Meetings 127
Medical Device Regulations 129
Combination Products 164
Study Committees 168
FDA-Sponsor Meetings 170
Registration of Clinical Trials 174
Implementation of the HIPAA Privacy Rule in Clinical Research 175
Institutional Review Boards (IRB) 180
FDA’s Oversight of Clinical Trials (Bioresearch Monitoring) 191
Code of Federal Regulations of Medical Devices 194
8 Design Issues in Medical Devices Studies 195
Design of the Clinical Trial 196
Assumptions and Parameters of Clinical Trial Design 196
Clinical Trials’ Design Issues and Data Analysis Issues 202
Use of Historic Controls as the Control Group in IDE Studies 206
Summary of Recommendations When Using Historic Controls 218
9 Investigator-Initiated Clinical Research 221
Definition and Examples of Investigator-Initiated Clinical Research 222
Development, Conduct, and Management of Investigator-Initiated Clinical Research 224
Regulation of Investigator-Initiated Clinical Research 225
Required Infrastructure for Investigator-Initiated Clinical Research 226
Clinical Research Sponsored by NIH 227
10 Ethical Conduct for Human Research 229
The Nuremberg Code (1947) 230
World Medical Association - Declaration of Helsinki (1964–Present) 231
National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1974) 231
The Belmont Report (1978) 232
Special Ethical Concerns in Clinical Research on Use of Placebo 232
Glossary of Clinical Trial and Statistical Terms 235
References 249
Index 255
