Design, Execution, and Management of Medical Device Clinical Trials

SALAH M. ABDEL-ALEEM, PHD, is Senior Manager of Clinical Operations at Proteus Biomedical, Inc., a medical device and pharmaceutical company that develops therapies for cardiovascular and diabetic diseases. Dr. Abdel-aleem has over twenty years of clinical research experience in various academic and corporate settings.

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