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 xiPreface xvAcknowledgments xxi1 An Overview of Clinical Study Tasks and Activities 1Key Clinical Study Tasks and Activities 2Discussion of Key Tasks and Activities 3Management of Key Clinical Tasks and Activities 9Example of the Spread Sheet for Managing Clinical Study Activities 10The Clinical Research Team 102 Development of Clinical Protocols, Case Report Forms, Clinical Standard Operating Procedures, Informed Consent Form, Study Regulatory Binder, Study Research Agreement, and Other Clinical Materials 15Clinical Protocol 17Case Report Forms (CRFs) 28Example of the Case Report Form Template 32Informed Consent Form (ICF) 35Instructions for Use of Device 38Study Regulatory Binder 39Study Research Agreement 40Research Agreement Template 43Research Contract Challenges 50Clinical Forms and Certificates 51Clinical Standard Operating Procedures (SOPs) 543 Qualification/Selection of Study Investigators and Study Monitoring Visits 63Qualification and Selection of Investigators 64Monitoring Visits 67Monitoring Reports 73Interim Monitoring Visit Report Template 754 Adverse Events Definitions and Reporting Procedures 81Adverse Event Definitions 83Policies, Regulations, and Guidelines Regarding Adverse Event Reporting 84Adverse Event Reporting Pathway 84Terms for Causality Assessment 85GAPS/Challenges in Adverse Event Reporting 86Adverse Event Reporting Time Periods (21 CFR 803) 88Differences between the United States and Europe in Reporting Adverse Events 88Serious Adverse Event Narratives 89Classification of Adverse Events 90Special Requirement for Reporting Certain Adverse Events 92Case Example 92Mandatory Device Reporting for FDA-Approved Devices 925 Statistical Analysis Plan (SAP) and Biostatistics in Clinical Research 93Statistical Analysis Plan (SAP) 94Selection of Study Endpoints 97Biostatistics in Clinical Research 1016 Final Clinical Study Report 113Final Clinical Report’s Outline 114Discussion of Sections in the Final Clinical Report 1167 Medical Device Regulations Combination Product, Study Committees, and FDA-Sponsor Meetings 127Medical Device Regulations 129Combination Products 164Study Committees 168FDA-Sponsor Meetings 170Registration of Clinical Trials 174Implementation of the HIPAA Privacy Rule in Clinical Research 175Institutional Review Boards (IRB) 180FDA’s Oversight of Clinical Trials (Bioresearch Monitoring) 191Code of Federal Regulations of Medical Devices 1948 Design Issues in Medical Devices Studies 195Design of the Clinical Trial 196Assumptions and Parameters of Clinical Trial Design 196Clinical Trials’ Design Issues and Data Analysis Issues 202Use of Historic Controls as the Control Group in IDE Studies 206Summary of Recommendations When Using Historic Controls 2189 Investigator-Initiated Clinical Research 221Definition and Examples of Investigator-Initiated Clinical Research 222Development, Conduct, and Management of Investigator-Initiated Clinical Research 224Regulation of Investigator-Initiated Clinical Research 225Required Infrastructure for Investigator-Initiated Clinical Research 226Clinical Research Sponsored by NIH 22710 Ethical Conduct for Human Research 229The Nuremberg Code (1947) 230World Medical Association—Declaration of Helsinki (1964–Present) 231National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1974) 231The Belmont Report (1978) 232Special Ethical Concerns in Clinical Research on Use of Placebo 232Glossary of Clinical Trial and Statistical Terms 235References 249Index 255