The Guide to Human Research Activities 1 The Guide to Human Research Activities Dana-Farber/Harvard Cancer Center Contributors: Office for Human Research Studies Office of Data Quality Clinical Trials Research Informatics Office Research Pharmacy Research Nursing Biostatistics Core Biosafety Officers Office of Faculty Activities Version: March 2017 The Guide to Human Research Activities 2 CONTENTS I. PREFACE AND ACKNOWLEDGMENTS II. DESCRIPTION OF INSTITUTIONAL RELATIONSHIPS III. INTRODUCTION IV. SECTIONS 1: Clinical Trials and Sponsorship 2: Offices and Staffing Central to the Clinical Trials Process 2.1 Office for Human Research Studies (OHRS) 2.2 The Office of Data Quality (ODQ) 2.3 The Clinical Trials Research Informatics Office (CTRIO) 2.4 Dana-Farber Cancer Institute (DFCI) Clinical Trials Office (CTO) 2.5 Massachusetts General Hospital (MGH) Cancer Center Protocol Office (CCPO) 2.6 Beth Israel Deaconess Medical Center (BIDMC) Cancer Clinical Trials Office (CCTO) 2.7 Clinical Investigations Leadership Committee (CLC) 2.8 Clinical Trials Operations Committee (CLINOPS) 2.9 Institutional Review Board (IRB) 2.10 Scientific Review Committee (SRC) and Scientific Progress Review 3: The Study Team 3.1 Overall Principal Investigator (Overall PI) 3.2 Site Principal Investigator (Site PI) 3.3 Collaborating Investigators (Co-investigators) 3.4 Biostatistician 3.5 Research Nurse 3.6 Study Coordinator 3.7 ODQ Data Analyst 4: Investigator and Study Staff Complaints and Suggestions 5: DF/HCC Standard Operating Procedures (SOPs) 6: Research Listserv and DF/HCC Membership 6.1 Subscribe to the Research Listserv 6.2 DF/HCC Membership and DF/HCC Website Access 7: Required Human Subjects Training 7.1 The CITI Program 7.2 Courses Version: March 2017 The Guide to Human Research Activities 3 7.3 Certification 7.4 DF/HCC Training List 7.5 Continuing Human Subjects Protection Education 8: Federal Guidelines for Research Involving Human Subjects 9: Degree of Risk 9.1 Minimal Risk 9.2 Greater than Minimal Risk 10: Research Methods for Drug Studies 10.1 The Drug Development Process 10.2 Types of Trials 10.2.1 Pre-Clinical 10.2.2 Phase I 10.2.3 Phase II 10.2.4 Phase III 10.2.5 Phase IV 10.2.6 Multi-Modality Trials 11: Expanded Access to Investigational Treatment 11.1 Emergency Use 11.2 Treatment IND (Single Patient IND) 12: Tissue/Data Collection and Record Review 12.1 Banking Specimens and/or Data for Future Research 12.2 Access to Banked Tissue/Data by Other Investigators 12.3 Research Involving Previously Banked Tissue 12.4 Research Involving Record Reviews 13: Medical Devices 13.1 Definition 13.2 Ordering 13.3 Storage 13.4 Authorization 13.5 Dispensing 13.6 Destroying 14: Behavioral/Social Science Research 15: Vulnerable Populations 15.1 Inclusion of Children as Participants in Research 15.2 Pregnant Women and Fetuses in Research 15.3 Cognitively Impaired Persons Involved in Clinical research 15.4 Research Involving Prisoners Version: March 2017 The Guide to Human Research Activities 4 16: Recruiting Trials Participants 16.1 Private Medical Information 16.2 Referring Physicians 16.3 Advertisements 16.4 Recruitment Letters 16.5 Scripts 16.6 Unacceptable Language and Suggested Alternatives 17: Pre-screening Potential Trial Participants 17.1 Appropriate Information to Gather 17.2 Pre-screening Procedures 18: Protocol Design 18.1 The Protocol Document 18.2 Protocol Sections 19: Informed Consent 19.1 Informed Consent Document 19.2 Standardized Consent Form Template 19.3 Incentives and Remuneration for Study Subject Participation 19.4 Assent and Children in Research 19.5 IRB Waiver of Informed Consent 19.6 IRB Waiver of Documentation of Informed Consent 19.7 Guidelines for Obtaining Consent 19.8 DFCI IRB Policy and Guidance on the Consent Process 20: Protocol Submission, Review and Activation 20.1 The Review Process 20.2 Submitting a Trial for Review 20.3 Basic Elements of an IRB Submission 20.4 Other Documents that May Be Required 20.5 The Review Committees 20.6 Description of Protocol Reviewers 20.7 Review and Approval by Other DF/HCC Departments/Committees 20.8 Notification of Board Actions 20.9 Review Outcomes 20.10 Response to Committee Requests 20.11 Claim of Exemption 20.12 New Submission Flow Chart 20.13 Protocol Activation and Distribution 21: Continuing Review Version: March 2017 The Guide to Human Research Activities 5 22: Changes to Previously Approved Research (Amendments) 22.1 Overview 22.2 Types of Amendment Submissions 22.3 Amendment Submission Requirements 23: Reports of Non-Compliance (Deviations, Violations, Exceptions and Other Events) 23.1 Overview 23.2 Major Deviations / Violations / Exceptions 23.3 Minor Deviations / Violations 23.4 Other Events 24: Unanticipated Problems Involving Risks to Participants or Others 25: Adverse Event (AE) Reporting Policy 25.1 Definitions 25.2 Adverse Event Grading System 25.3 Attribution 25.4 DFCI IRB Requirements 25.5 AE Reporting Form 25.7 CTEP-AERS 25.8 AE Follow-up Reports 25.9 Gene Transfer Reporting Requirements 25.10 PI-initiated/IND Holder Reporting Requirements 25.11 PI-initiated/Sponsor Holds IND Reporting Requirements 25.12 Industry-sponsored (Investigational) Reporting Requirements 25.13 Industry-sponsored (Commercial) Reporting Requirements 26: Privacy and Confidentiality 26.1 Health Insurance Portability and Accountability Act of 1996 (HIPAA) 26.2 What Constitutes PHI? 26.3 Minimum Necessary Standard for Research Activities 26.4 De-identified Information for HIPAA Privacy Rule 26.5 The Limited Data Set Option 26.6 Data Use Agreement Requirements 26.7 Accounting for Disclosures 26.8 Research on Deceased Persons 26.9 Waiver of Authorization for Research 27: Department of Biostatistical Science 27.1 Biostatistical Support for the Protocol Development Process 27.2 Biostatistical Support for Forms Development 27.3 Biostatistical Support for Data Collection and Storage 27.4 Biostatistical Support during Protocol Activation 27.5 Role of Biostatistics in Monitoring Active Trials Version: March 2017 The Guide to Human Research Activities 6 27.6 Biostatistics Involvement in Protocol Addenda 27.7 Analyses/Reports on DF/HCC Trials 28: Office of Data Quality (ODQ) 28.1 Introduction and Purpose 28.2 Mission 28.3 Functions of the ODQ 28.4 Participant Enrollment in Clinical Trials 28.5 Randomization Process 28.6 Phase I Dose-escalation Trials 28.7 Single Patient IND 28.8 Non-protocol Standard Treatment Registration 28.9 DF/PCC Network Affiliate Registration 28.10 Industry-led and Cooperative-group Registration 28.11 Non-patient Volunteer Registration 28.12 Electronic Confirmation of Registration 28.13 After-hours Registration 28.14 Removing a Participant from a Research Study 28.15 Protocol Closure Notification 28.16 Protocol Completion/Termination Notification 28.17 Reports Available from the Clinical Trials Research Informatics Office 28.18 Protocol Accrual Monitoring 28.19 Case Report Form (CRF) Design 28.20 Documentation and Storage of Data 28.21 Accrual-monitoring Program 28.22 Internal Auditing 28.23 DF/HCC Data and Safety Monitoring Board (DSMB) 28.24 DF/HCC Data and Safety Monitoring Committee (DSMC) 29: Education 29.1 Programs for Clinical Investigators Study Team Members 29.2 Programs for Study Team Members 29.3 Professional Certification of Study Team Members 29.4 eLearning Center 29.5 In-Services 30: NCI Investigator Registration and Renewal 31: Protocol Registration Requirements 31.1 ClinicalTrials.gov 31.2 Clinical Trials Reporting Program (CTRP) 32: Principal Investigators (PIs) 32.1 General Responsibilities of the PI Version: March 2017 The Guide to Human Research Activities 7 32.2 Financial Disclosure by Clinical Investigators 32.3 Conflict of Interest Policy 33: Study Coordinators 33.1 Roles and Responsibilities 33.2 Protocol Management 33.3 Data Management 33.4 Drug Accountability 33.5 Regulatory Submissions 33.6 The Regulatory Binder 33.7 Research Sampling 33.8 Monitoring and Audit Preparation 33.9 Checklist for Monitoring and Auditing Visits 34: Investigator-held INDs 34.1 IND Overview 34.2 General Principles of the IND Submission 34.3 IND Content and Format 34.4 Submission of the IND Application to the FDA 34.5 IND Application Approval Process 34.6 IND Post-Approval 34.7 IND Protocol Amendments 34.8 IND Safety Reports for Investigator-held INDs 34.9 IND Annual Reports 34.10 Final Study Reports 34.11 Withdrawal of an IND Application 34.12 General Responsibilities of the Investigator-Sponsor 34.13 Selecting Participating Investigators and Monitors 34.14 Informing Participating Investigators of New Observations 34.15 Reviewing Ongoing Investigations 34.16 Record Keeping and Record Retention 34.17 Inspection of Records and Reports 34.18 Disposition of Unused Investigational Drug 34.19 General Responsibilities of Participating Investigators 34.20 Control of the Investigational Drug 34.21 Participating Investigator Record Keeping and Record Retention 34.22 Participating Investigator Reports 35: Conducting PI-initiated Multi-center Trials at DF/HCC 35.1 Purpose and Function of a Lead Site 35.2 Overall PI Responsibilities 35.3 Lead Site Responsibilities 35.4 Participating Site PI Responsibilities 35.5 Regulatory Binder Version: March 2017 The Guide to Human Research Activities 8 35.6 Staff Training 35.7 Central Participant Registration 35.8 Adverse Event Reporting 35.9 Data Collection 35.10 Quality Assurance 35.11 Site Communication 35.12 Drug Ordering 35.13 Inter-institutional Agreement/Contract 35.14 Multi-center Coordinating Committee 36: Gene Transfer Research (Recombinant DNA) 37: Evaluation of Outreach Activities and Catchment Area V. Appendix R.1 Code of Federal Regulations R.2 Good Clinical Practice Guidelines R.3 Medical Terminology, Dictionaries and Other Resources R.4 Ethics References R.5 External Web Sites R.6 DF/HCC Web Sites R.7 DF/HCC Participating Institutions R.8 Regulatory Documents for Sponsors R.9 DF/HCC SOPS for Human Subject Research R.10 Office for Human Research Studies Information Sheets R.