COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK OFFICE OF THE EXECUTIVE VICE PRESIDENT FOR RESEARCH CLINICAL RESEARCH HANDBOOK Version 11 November 2020 Copyright © 2020 by The Trustees of Columbia University in the City of New York All rights reserved Table of Contents I. INTRODUCTION…………………………………………………… 1 A. Purpose of Handbook…………………………………………….. 1 B. Resources………………………………………………………… 1 1. Office of the Executive Vice President for Research (EVPR)… 1 2. Handbooks…………………..……………………………….... 1 3. Rascal………………………………………………………….. 2 C. Annexes…….................................................................................... 3 D. Clinical Research…………………………………………………. 4 1. Definitions of Clinical Research and Clinical Trials………….. 4 2. Sponsored Research vs. Non-Sponsored Research…………… 5 3. Clinical Research Terminology………………………………. 5 E. Regulatory Framework and Good Clinical Practice……………… 7 1. Federal Agencies and Regulations……………………………. 7 2. Health Insurance Portability and Accountability Act (HIPAA) 9 3. Good Clinical Practice (GCP)………………………………… 9 4. Codes of Ethical Conduct…………………………………….. 10 5. University Codes of Conduct………………………………… 10 F. NewYork-Presbyterian Hospital (NYP)…………………………. 10 G. Roles and Responsibilities……………………………………….. 11 1. Principal Investigator (PI)…………………………………...... 11 2. Clinical Research Coordinator (CRC)………………………... 13 3. Departmental Administrator (DA)…………………………… 14 4. Sponsor……………………………………………………….. 15 II. THE ABCs OF FDA REGULATED RESEARCH…………........ 17 A. Introduction………………………………………………………. 17 B. Phases of Clinical Research……………………………………………. 18 1. Pre-Clinical Research……………………………………….............. 18 2. Clinical Research…………………………………………………… 18 C. Investigational New Drugs……………………………………………. 19 D. Investigational Devices……………………………………………….. 21 E. Sponsor-Investigator Research………………………………………... 23 1. IND/IDE Assistance Program……………………………………… 23 2. Clinical Trials Monitoring Assistance Program…………………… 25 F. Summaries of IND and IDE Processes.................................................. 26 1. IND Process…………………………………………...................... 26 2. IDE Process…………………………………………..................... 28 G. Special Situations for the Use of Investigational Medical Products: Expanded Access (Single Patient/Small Group (Compassionate), Treatment and Emergency Uses) and Humanitarian Use.................... 30 1. Expanded Access........................................................................... 31 2. Emergency Use.............................................................................. 41 ________________________________________________________________________ Updated November 2020 Table of Contents Page i 3. Humanitarian Use………………………………………………... 43 III. GETTING STARTED: TRAINING………………………………….. 45 A. Introduction………………………………………………………….. 45 B. Research Compliance Training Finder………………………………. 45 C. Mandatory Training………………………………………………….. 45 1. Human Subjects Protection ………………………………........... 45 2. GCP Training for NIH-Funded Clinical Trials.............................. 45 3. Financial Conflicts of Interest and Research for PHS Researchers 46 4. Privacy and Security Training……………………………………. 46 5. Clinical Research Training……………………………………….. 47 6. Genetic Research Training.............................................................. 47 7. FDA S-I Training…………………………………………………. 47 8. Environmental Health and Safety (EH&S)………………………. 47 9. Radiation Safety………………………………………………….. 48 10. Epic Research Module Training………………………………… 48 D. Additional Training Resources………………………………………. 49 1. Additional Courses……………………………………………….. 49 2. Optional GCP Training.................................................................... 49 3. Billing Compliance……………………………………………….. 49 E. Medical Surveillance…………………………………………………. 49 IV. PREPARING FOR A STUDY: PROJECT FEASIBILITY AND STUDY DOCUMENTS………………………………………………………….. 51 A. Introduction…………………………………………………………. 51 B. Feasibility Assessment………………………………………………. 51 1. Internal Assessment………………………………………………. 51 2. Pre Study Site Visit (PSSV)……………………………………… 52 3. Biostatistics Consulting Service………………………………….. 53 C. Finding Funding……………………………………………………… 53 D. Protocols……………………………………………………………… 54 E. Budgets………………………………………………………………. 55 F. Case Report Forms (CRFs)…………………………………………… 58 V. PREPARING FOR A STUDY: IRB APPROVAL…………………… 60 A. Introduction………………………………………………………….. 60 B. IRB Review………………………………………………………….. 61 C. Timing of IRB Review………………………………………………. 63 D. Steps in Obtaining IRB Approval at Columbia University……........... 64 1. Creation of Protocol……………………………………………… 64 2. Submission of Protocol…………………………………………... 65 3. HRPO Pre-Review………………………………………………. 65 4. Administrative Review Committee……….……………………... 65 5. Expedited Review……………………………………………… 67 6. Limited Review………………………………………………… 67 ________________________________________________________________________ Updated November 2020 Table of Contents Page ii 7. Full Board or Convened Review……………………………… 68 8. Post Review Status……………………………………………… 68 9. IRB Meeting Schedules……………………………………......... 69 10. Approval………………………………………………………… 69 11. Protocol Modifications………………………………………….. 70 12. Continuing Review and Annual Reports ………….……………. 71 13. Voluntary Study Closure……………….......…………………… 73 14. For Cause Study Suspension or Termination……………………. 74 15. External IRB Review……………………………………………. 74 16. Single IRBs……………………………………………………. 75 VI. PREPARING FOR A STUDY: REVIEW AND FINALIZATION OF PROPOSALS AND CONTRACTS……………………..................... 77 A. Introduction………………………………………………………. 77 B. Review Process…………………………………………………… 78 1. Non-Industry Sponsored Clinical Research…………………… 78 2. Industry Sponsored Clinical Research………………………… 79 C. Other Agreements………………………………………………… 81 1. Data Use Agreements…………………………………………. 81 2. Material Transfer Agreements………………………………… 81 D. Approval Process………………………………………………….. 82 1. PI Certification and Departmental and School Approvals…….. 82 2. Additional Approvals and Certifications………………………. 82 E. Submission/Execution…………………………………………….. 89 1. Non-Industry Sponsored Clinical Research…………………… 89 2. Industry Sponsored Clinical Research………………………… 89 VII. INITIATING A STUDY……………………………………………. 90 A. Introduction………………………………………………………. 90 B. Account Set Up and Modifications………….…………………… 90 1. Non-Industry Sponsored Clinical Research…………………… 91 2. Industry Sponsored Clinical Research………………………… 92 3. Pre-Award Spending and Advance Accounts…………………. 93 4. Project Information Notifications (PINs)……………………… 93 C. Billing …………………………………………………………… 93 1. Research Billing Review (RBR)……………………………… 93 2. Investigational Devices………………………………………. 94 3. Medical Equipment …………………………………………. 95 D. ClinicalTrials.gov…………………………………………………… 95 E. E-Verify………………………………………………………….. 99 F. Preparation for Initiation………………………………………...... 99 1. Investigator Meeting………………………………………....... 99 2. Study Documentation…………………………………………. 100 VIII. WORKING WITH STUDY SUBJECTS: RECRUITMENT AND ENROLLMENT……………………………………………………. 104 ________________________________________________________________________ Updated November 2020 Table of Contents Page iii A. Introduction……………………………………………………… 104 B. Finding Subjects………………………………………………… 104 C. Clinical Data Warehouse………………………………………... 105 D. Advertising……………………………………………………… 105 1. General……………………………………………………… 105 2. Non-English Speaking Subjects…………………………….. 106 E. RecruitMe..................................................................................... 106 F. Enrollment and Accrual………...........................………………. 107 1. Prescreening…………………………………………………. 107 2. Screening and Enrollment….........................….........……….. 107 3. Accrual………………………………………………………. 108 4. Documentation………………………………………………. 108 5. Registration of Subjects Epic…………………………… 109 IX. WORKING WITH STUDY SUBJECTS: INFORMED CONSENT… 110 A. Introduction……………………………………………………… 110 B. Elements of Informed Consent………………………………….. 110 1. Federal Regulations………………………………………….. 110 2. Informed Consent Forms……………………………………. 112 3. Exempt Research…………………………………………….. 113 C. Consent Process………………………………………………… 113 D. Documentation………………………………………………….. 114 E. Electronic Informed Consent........................................................ 115 F. Exceptions………………………………………………………. 116 1. Waiver of Consent…………………………………………… 116 2. Waiver of Written Documentation of Informed Consent…… 117 3. Emergency Waiver…………………………………………… 117 4. Surrogate Consent……………………………………………. 118 G. Special Situations……………………………………………….. 120 1. Non-English Speaking Subjects……………………………… 120 2. Vulnerable Populations……………………………………..... 125 3. Same Day Elective Surgery or Procedure…………………… 131 H. Other Consents…………………………………………………... 133 1. HIPAA……………………………………………………….. 133 2. Genetic Research…………………………………………….. 138 3. HIV Research………………………………………………… 140 I. Reconsenting Subjects…………………………………………... 140 X. WORKING WITH STUDY SUBJECTS: MANAGING THE STUDY 141 A. Introduction………………………………………………………. 141 B. Study Procedures…………………………………………………. 141 1. Types of Procedures………………………………………….. 141 2. Scheduling……………………………………………………. 141 3. Visit Tracking………………………………………………… 142 4. Visits…………………………………………………………. 142 ________________________________________________________________________ Updated November 2020 Table of Contents Page iv 5. Accessing Medical Records………………………………….. 143 6. Handling and Shipping Biological Samples…………………. 143 C. Investigational Products………………………………………… 144 1. Drugs………………………………………………………… 144 2. Devices………………………………………………………. 147 D. Subject Reimbursement/Compensation…………………………. 148 1.