University of Virginia
Standard Operating Procedures for the
Human Research Protection Program
Table of Contents
1 Human Research Protection Program 9
1.1 Mission 9
1.2 Organizational Authority 10
1.3 Definitions 10
1.4 Ethical Principles 13
1.5 Regulatory Compliance 13
1.6 International Council on Harmonization-Good Clinical Practice (ICH-GCP) 14
1.7 Federalwide Assurance (FWA) 14
1.8 Research Under the Auspices of the Organization 15
1.9 Written policies and procedures 16
1.10 University of Virginia HRPP Structure 16
1.10.1 Institutional Official 17
1.10.2 Director of the HRPP 18
1.10.3 HRPP Staff 19
1.10.4 Institutional Review Board (IRB) 19
1.10.5 General Counsel’s Office 20
1.10.6 Department Chairs and/or Organizational Leaders and their Designees 20
1.10.7 The Investigator 20
1.10.8 Other Related Units 21
1.10.8.1 Sponsored Programs Administration 21
1.10.8.2. University of Virginia Investigational Drug Service (UVA IDS) 21
1.10.8.3 University of Virginia Cancer Center Protocol Review Committee (PRC) 22
1.10.8.4 University of Virginia Neonatal ICU Protocol Review Committee 22
1.10.9 Relationship Among Components 23
1.10.10 Study-Specific Coordination 23
1.11 Multi-Site Research Projects and IRB Authorization/Reliance Agreements 24
1.11.1 UVA engaged in only a part of a Multi-Site Research Project 25
1.11.2 Each research site obtains IRB Approval from their IRB 25
1.11.3 UVA Relies on a non- UVA IRB as the IRB of Record 25
1.11.4 UVA IRB serves as IRB of Record for non-UVA Sites 26
1.11.5 UVA PI serves as Overall PI or UVA serves as the Data Coordinating Center 26
2 Quality Assurance 27
2.1 External Monitoring, Audit, and Inspection Reports 28
2.2 Investigator Compliance Reviews 28
2.3 IRB Compliance Reviews 29
2.4 HRPP Quality Assessment and Improvement 30
3 Education & Training 32
3.1 Training / Ongoing Education of IRB Chair, Members, and Staff 32
3.2 Training / Ongoing Education of Investigators and Research Team 33
3.2.1 Initial Education 33
3.2.2 Continuing Education and Recertification 34
4 Institutional Review Board 35
4.1 IRB Authority 35
4.2 Roles and Responsibilities 36
4.2.1 Chair of the IRB 36
4.2.2 Vice Chair of the IRB 36
4.2.3 IRB Members 37
4.2.4 Alternate members 37
4.2.5 Subcommittees of the IRB 38
4.3 IRB Membership 38
4.4 Composition of the IRB 38
4.4.1 Appointment of Members to the IRB 39
4.4.2 IRB Registration Updates 40
4.5 Use of Consultants 40
4.6 Liability Coverage for IRB Members 41
4.7 Reporting and Investigation of Allegations of Undue Influence 41
5 Human Subject Research Determination 42
6 Exempt Studies 43
6.1 Limitations on Exemptions 43
6.2 Categories of Exempt Research 43
6.3 FDA Exemptions 45
6.4 Procedures for Exemption Determination 45
7 IRB Review Process 47
7.1 Definitions 47
7.2 Expedited Review 48
7.2.1 Categories of Research Eligible for Expedited Review 48
7.2.2 Expedited Review Procedures 51
7.2.3 Informing the IRB 52
7.3 Convened IRB Meetings 52
7.3.1 IRB Meeting Schedule 52
7.3.2 Pre Review 52
7.3.3 Primary and Secondary Reviewers 52
7.3.4 Materials received by the IRB 53
7.3.5 Quorum 54
7.3.6 Meeting Procedures 55
7.3.7 Guests 55
7.4 Criteria for IRB Approval of Research 56
7.4.1 Risk/Benefit Assessment 57
7.4.1.1 Scientific or Scholarly Review 57
7.4.2 Equitable Selection of Subjects 58
7.4.2.1 Recruitment of Subjects 58
7.4.3 Informed Consent 59
7.4.4 Data and Safety Monitoring 59
7.4.5 Privacy and Confidentiality 60
7.4.5.1 Definitions 60
7.4.5.2 Privacy 61
7.4.5.3 Confidentiality 61
7.4.6 Vulnerable Populations 62
7.5 Additional Considerations 62
7.5.1 Determination of Risk 62
7.5.2 Period of Approval 63
7.5.3 Review More Often Than Annually 63
7.5.4 Independent Verification That No Material Changes Have Occurred 64
7.5.5 Consent Monitoring 65
7.5.6 Investigator Qualifications 66
7.5.7 Investigator Conflicts of Interest (COI) 66
7.5.8 Institutional Conflicts of Interest 66
7.5.9 Significant New Findings 66
7.5.10 Advertisements and Recruitment Materials 67
7.5.11 Payments to Research Subjects 68
7.5.12 Non-Monetary Gifts and Incentives 69
7.5.13 State and Local Laws 69
7.6 Possible IRB Actions 69
7.7 Continuing Review 71
7.7.1 Continuing Review Process 71
7.7.2 Approval Considerations 72
7.7.3 Convened Board Review 72
7.7.4 Expedited Review 73
7.7.5 Possible IRB Actions after Continuing Review 73
7.7.6 Lapses in Continuing Review 74
7.8 Modification of an Approved Protocol 75
7.8.1 Procedures 75
7.8.2 Convened Board Review of Modifications 76
7.8.3 Expedited review of Modifications 76
7.8.4 Possible IRB Actions after Modification Review 77
7.8.5 Protocol/Research Plan Exceptions 77
7.9 Closing a Research Study 78
7.10 Failure to Respond 79
7.11 Appeal of IRB Decisions 79
7.12 Research Previously Approved By Another IRB 80
8 Study Suspension, Termination and Investigator Hold 81
8.1 Suspension/Termination 81
8.2 Investigator Hold 82
8.2.1 Procedures 82
8.3 Protection of Currently Enrolled Participants 83
9 Research overseen by a non- UVA IRB of Record 84
9.1 UVA Investigator Responsibilities 84
9.2 UVA IRB Responsibilities 84
9.3 Responsibilities after the study is open to enrollment at UVA 84
10 Documentation and Records 87
10.1 IRB Records 87
10.2 IRB Study Files 87
10.3 The IRB Minutes 88
10.4 IRB Membership Roster 90
10.5 Documentation of Exemptions 91
10.6 Documentation of Expedited Reviews 91
10.7 Access to IRB Records 91
10.8 Record Retention 92
11 Obtaining Informed Consent from Research Subjects 93
11.1 Definitions 93
11.2 Basic Requirements 94
11.3 Informed Consent Process 95
11.4 Determining a potential adult subject’s ability to consent to research 96
11.5 Basic Elements of Informed Consent 97
11.6 Documentation of Informed Consent 99
11.7 Special Consent Circumstances 100
11.7.1 Enrollment of persons with limited English-language proficiency 100
11.7.2 Braille consent 101
11.7.3 Consenting in American Sign Language (ASL) 101
11.7.4 Oral Consent 101
11.8 Subject Withdrawal or Termination 102
11.9 Waiver of Informed Consent 103
11.10 Waiver of Documentation of Informed Consent 104
11.11 Waiver of Informed Consent for Planned Emergency Research 104
11.11.1 Definitions 105
11.11.2 Procedures 105
11.11.2.1 FDA-regulated Planned Emergency Research 107
11.11.2.2 Planned Emergency Research Not Subject to FDA Regulations 108
12 Vulnerable Subjects in Research 108
12.1 Definitions 108
12.2 Involvement of Vulnerable Populations 110
12.3 Responsibilities 111
12.4 Procedures 111
12.5 Research Involving Pregnant Women, Human Fetuses and Neonates 112
12.5.1 Research Involving Pregnant Women or Fetuses 112
12.5.1.1 Research Not Conducted or Supported by DHHS 112
12.5.1.2 Research Conducted or Supported by DHHS 113
12.5.2 Research involving Neonates of Uncertain Viability or Nonviable Neonates 114
12.5.2.1 Research Not Conducted or Supported by DHHS 114
12.5.2.2 Research Conducted or Supported by DHHS 115
12.5.3 Viable Neonates 117
12.5.4 Research Involving, After Delivery, the Placenta, the Dead Fetus or Fetal Material 117
12.5.5 Research Not Otherwise Approvable 117
12.5.5.1 Research Not Conducted or Supported by DHHS 117
12.5.5.2 Research Conducted or Supported by DHHS 118
12.6 Research Involving Prisoners 118
12.6.1 Applicability 118
12.6.2 Minimal Risk 118
12.6.3 Composition of the IRB 118
12.6.4 Review of Research Involving Prisoners 119
12.6.5 Incarceration of Enrolled Subjects 120
12.6.6 Additional Duties of the IRB 120
12.6.7 Certification to DHHS 122
12.6.8 Waiver for Epidemiology Research 122
12.7 Research Involving Children 123
12.7.1 Allowable Categories 123
12.7.2 Parental Permission and Assent 125
12.7.2.1 Parental Permission 125
12.7.2.2 Assent from Children 126
12.7.2.3 Children Who are Wards 127
12.8 Adults with Impaired Decision Making Capacity 128
13 FDA-Regulated Research 129
13.1 Definitions 129
13.2 FDA Exemptions 130
13.3 Procedures 131
13.4 Investigator Responsibilities 131
13.5 Dietary Supplements 133
13.6 Clinical Investigations of Drugs and Devices 134
13.6.1 IND/IDE Requirements 134
13.6.1.1 IND Exemptions 134
13.6.1.2 IDE Exemptions 136
13.6.1.3 Significant and Non-Significant Risk Device Studies 137
13.7 Humanitarian Use Devices 138
13.7.1 Definitions 138
13.7.2 IRB Review Requirements 139
13.7.3 Procedures 139
13.7.4 Emergency Uses of HUDs 141
13.8 Expanded Access to Investigational Drugs, Biologics, and Devices 141
13.8.1 Expanded Access to Investigational Drugs and Biologics 142
13.8.2 Expanded Access to Investigational and Unapproved Medical Devices 143
13.9 Emergency Use 143
13.9.1 Emergency Exemption from Prospective IRB Approval 144
13.9.2 Emergency Exception from the Informed Consent Requirement 144
13.9.3 Waiver of Informed Consent for Planned Emergency Research 145
14 Reportable Events 146
14.1 Definitions 146
14.2 Procedures 147
14.2.1 Reporting 147
14.2.2 Submission of Reports 149
14.2.3 IRB Procedures for Handling Reportable Events 150
15 Unanticipated Problems Involving Risks to Subjects or Others 151
15.1 IRB Review 151
16 Non-compliance 153
16.1 Definitions 153
16.2 Reporting 153
16.3 Review of Allegations of Non-compliance 154
16.4 Review of Findings of Non-compliance 154
16.4.1 Non-compliance that is not serious or continuing: 154
16.4.2 Serious or Continuing Non-compliance 155
16.4.3 Final Review 155
17 Complaints 157
18 Reporting to Regulatory Agencies and Organizational Officials 158
18.1 Procedures 158
19 Investigator Responsibilities 160
19.1 Investigators 160
19.2 Responsibilities 160
19.3 Investigator Records 162
19.3.1 Study Records 163
19.3.2 Regulatory Records 163
19.3.3 Record Retention 163
19.4 Investigator Concerns 163
20 Sponsored Research 165
20.1 Definitions 165
20.2 Responsibility 165
21 Conflict of Interest in Research 167
21.1 Researcher Conflicts of Interest 167
21.1.1 Procedures 167
21.1.1.1 Disclosure of Researcher COI 167
21.1.1.2 Evaluation of COI 167
21.1.1.3 Management of COI 168
21.2 IRB Member Conflict of Interest 168
21.3 Institutional Conflict of Interest 169
21.4 Recruitment Incentives 169
22 Participant Outreach 170
22.1 Responsibility 170
22.2 Outreach Resources and Educational Materials 170
22.3 Evaluation 170
23 Health Insurance Portability and Accountability Act (HIPAA) 172
23.1 Definitions (per HIPAA Privacy Rule Booklet for Research) 172
23.2 The IRB’s Role under the Privacy Rule 174
23.3 Authorization 176
23.4 Waiver or Alteration of the Authorization Requirement 177
23.5 Activities Preparatory to Research 178
23.6 Research Using Decedent's Information 179
23.7 Future Uses: Databases and Repositories 179
23.8 Corollary and Sub-studies 180
23.9 De-identification of PHI under the Privacy Rule 181
23.10 Limited Data Sets and Data Use Agreements 182
23.11 Disclosing a Limited Data Set 183
23.12 Accounting of Disclosures 183
24. Information Security 185
25 Special Topics 186
25.1 Community Based Research 186
25.2 International (Transnational) Research 187
25.2.1.1 IRB Responsibilities 188
25.2.1.2 Investigator Responsibilities 188
25.2.1.3 Consent Documents 189
25.2.1.4 Monitoring of Approved International Research 189
25.3 Research Involving Data and/or Biological Specimens 190
25.3.1 Overview 190
25.3.2 Definitions 190
25.3.3 General Information 191
25.3.4 Activities That Are Not Human Subjects Research 192
25.3.5 Exempt Research 193
25.3.6 Secondary Uses of Previously Collected Data/Specimens 193
25.3.7. Repositories – Collection, Storage, and/or Distribution of Data/Specimens 195
25.3.8. Informed Consent Requirements 197
25.3.9. Research Subject to FDA Regulations 199
25.3.10. Applicable Regulations/Guidance 200
25.4 Certificate of Confidentiality (CoC) 200
25.4.1 Statutory Basis for Protection 201
25.4.2 Usage 201
25.4.3 Limitations 202
25.4.4 Application Procedures 202
25.5 Mandatory Reporting 203
25.6 University of Virginia Students and Employees as Subjects 204
25.7 Student Research 204
25.7.1 Human Subject Research and Course Projects 204
25.7.1.1 Responsibility of the Course Instructor 205
25.7.1.2 Individual Research Projects Conducted by Students 205
25.7.2 Independent Study, Theses and Dissertations 205
25.8 Oral History 206
25.9 Genetic Studies 207
25.10 Case Reports Requiring IRB Review 207
25.10.1 Definitions 208
25.11 Research supported by the Department of Defense (DoD) 208
25.9 Research Supported by the Department of Justice (DOJ) 215
7
University of Virginia HRPP SOP Draft Version
1 Human Research Protection Program
The University of Virginia fosters a research environment that promotes the respect for the rights and welfare of individuals recruited for, or participating in, research conducted by or under the auspices of the Organization. The review and conduct of research, actions by the Organization will be guided by the principles (i.e., respect for persons, beneficence, and justice) set forth in the Ethical Principles and Guidelines for the Protection of Human Subjects of Research (referred to as the Belmont Report). The actions of Organization will also conform to all applicable federal, state, and local laws and regulations. In order to fulfill this policy, the Organization has established a Human Research Protection Program (HRPP). The University of Virginia HRPP, in partnership with its research community, is responsible for ensuring the ethical and equitable treatment of all human subjects in research conducted under its auspices. The research may be externally funded, funded from internal sources, or conducted without direct funding.
1.1 Mission
The mission of the HRPP is to:
· Safeguard and promote the health and welfare of human research subjects by ensuring that their rights, safety and well-being are protected;
· Provide guidance and support to the research community in the conduct of research with human subjects;
· Assist the research community in ensuring compliance with relevant regulations;
· To provide timely and high quality education, review and monitoring of human research projects; and
· To facilitate excellence in human subjects research.
The HRPP includes mechanisms to:
· Monitor, evaluate and continually improve the protection of human research participants
· Dedicate resources sufficient to do so
· Exercise oversight of research protection
· Educate investigators and research staff about their ethical responsibility to protect research participants
· When appropriate, intervene in research and respond directly to concerns of research participants
1.2 Organizational Authority
University of Virginia Human Research Protection Program operates under the authority of the Organization policy “University of Virginia Human Research Protection Program (HRPP)” adopted on July 7, 2017. As stated in that policy, the operating procedures in this document “…serve as the governing procedures for the conduct and review of all human research conducted under the auspices of the University of Virginia.” The HRPP Policy and these operating procedures are made available to all University of Virginia investigators and research staff and are posted on the HRPP website (http://www.virginia.edu).
1.3 Definitions
Common Rule. The Common Rule refers to the “Federal Policy for the Protection of Human Subjects” adopted by a number of federal agencies. Although the Common Rule is codified by each agency separately, the text is identical to DHHS regulations in 45 CFR 46 Subpart A. For the purposes of this document, references to the Common Rule will cite the DHHS regulations.