University of Southern California Human Research Protection Program (HRPP) Policies and Procedures, Study notes of Immunology

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University of Southern California Human Research Protection Program (HRPP) Policies and Procedures Office for the Protection of Research Subjects (OPRS) USC Institutional Review Boards (IRB) July 2021 Updated 8/20/2021 USC HRPP Policies and Procedures – 07/2021 Page 1 University of Southern California Human Research Protection Program (HRPP) Policies and Procedures Office for the Protection of Research Subjects (OPRS) USC Institutional Review Boards (IRB) July 2021 Updated 8/20/2021 USC HRPP Policies and Procedures – 07/2021 Page 1 USC HRPP Policies and Procedures – 07/2021 Page 4 3.1 IRB RELIANCE AGREEMENTS ............................................................................................................................... 52 USC As Reviewing IRB ................................................................................................................................... 53 Relying IRB .................................................................................................................................................... 54 USC Investigator Relying on An External IRB ................................................................................................ 55 IRB Reliance Agreement With USC ................................................................................................................ 57 Engagement in Research ............................................................................................................................... 60 Engaged Research ......................................................................................................................................... 61 NOT Engaged Research ................................................................................................................................. 62 IRB Approval of USC Research at a Non-USC Site .......................................................................................... 67 3.2 TRANSFER OF IRB OVERSIGHT AND RESPONSE TO DISASTER ...................................................................................... 68 Disaster Response ......................................................................................................................................... 68 CHAPTER CONTENTS .............................................................................................................................................. 70 CHAPTER 4 CONFLICTS OF INTEREST ...................................................................................................................... 71 4.1 CONFLICTS OF INTEREST .............................................................................................................................. 71 Individual Conflict of Interest ........................................................................................................................ 71 Institutional Conflict of Interest .................................................................................................................... 72 4.2 USC CONFLICT OF INTEREST IN RESEARCH COMMITTEE (CIRC) .................................................................................. 72 4.3 INVESTIGATOR AND / OR RESEARCH TEAM CONFLICT OF INTEREST DISCLOSURES ............................................................ 74 Disclosures in the IRB application (iStar)....................................................................................................... 74 Disclosures in USC’s diSClose system ............................................................................................................. 74 Disclosures for Research Funded by the Health and Human Services ........................................................... 74 Disclosures to Sponsors ................................................................................................................................. 75 4.4 INSTITUTIONAL CONFLICT OF INTEREST (ICOI) ........................................................................................................ 75 4.5 IRB MEMBERS AND IRB CONSULTANTS CONFLICT OF INTEREST.................................................................................. 76 CHAPTER CONTENTS .............................................................................................................................................. 78 CHAPTER 5 USC INSTITUTIONAL REVIEW BOARDS (IRBS) ...................................................................................... 79 5.1 DESCRIPTION OF USC IRBS ................................................................................................................................ 79 5.2 THE MEMBERSHIP OF THE IRB COMMITTEES .......................................................................................................... 80 Number, Qualifications and Diversity of Members ....................................................................................... 80 Alternate Members ....................................................................................................................................... 80 Ex-Officio Members ....................................................................................................................................... 81 5.3 IRB MEMBER REQUIREMENTS ............................................................................................................................ 81 Selection and Appointment ........................................................................................................................... 81 Length of Service ........................................................................................................................................... 81 Duties ............................................................................................................................................................ 82 Attendance Requirements ............................................................................................................................ 83 Honorarium to Non-Affiliate IRB Members ................................................................................................... 83 Training of the Chair, Vice Chairs and Members ........................................................................................... 83 Evaluation of IRB Members ........................................................................................................................... 84 5.4 IRB USE OF CONSULTANTS ................................................................................................................................. 85 5.5 IRB SUPPORT STAFF.......................................................................................................................................... 85 USC HRPP Policies and Procedures – 07/2021 Page 5 5.6 IRB CHAIRS AND VICE CHAIRS ............................................................................................................................. 87 Chairperson ................................................................................................................................................... 87 Vice Chairpersons ................................................................................................. 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Bookmark not defined. 5.7 IRB VOTING REQUIREMENTS .............................................................................................................................. 88 5.8 IRB RECORDS .................................................................................................................................................. 88 IRB Membership Roster ................................................................................................................................ 88 Written Procedures and Guidelines............................................................................................................... 88 Meeting Minutes........................................................................................................................................... 88 Records Retained in the IRB Files .................................................................................................................. 90 Record Retention Requirements ................................................................................................................... 91 Access to Files ............................................................................................................................................... 91 5.9 DEVELOPMENT, APPROVAL, AND MAINTENANCE OF IRB POLICIES AND PROCEDURES ..................................................... 91 Investigator Responsibilities with Respect to Policies ................................................................................... 92 IRB Staff Responsibilities with Respect to Policies ........................................................................................ 92 CHAPTER CONTENTS .............................................................................................................................................. 94 CHAPTER 6 TYPES OF IRB SUBMISSIONS ................................................................................................................ 95 6.1 HUMAN SUBJECTS RESEARCH: WHAT IS AND WHAT IS NOT ...................................................................................... 95 What is Human Subjects Research (HSR) ...................................................................................................... 95 Clinical Trial / Clinical Investigation Defined ................................................................................................. 97 What is Not Human Subjects Research ......................................................................................................... 98 Distinctions Between Biomedical and Social Behavioral Research ............................................................... 99 Primary Investigator and Self-experimentation .......................................................................................... 101 6.2 EXEMPT REVIEW............................................................................................................................................. 102 6.3 EXPEDITED REVIEW ......................................................................................................................................... 108 6.4 FULL BOARD REVIEW ....................................................................................................................................... 112 6.5 NOT HUMAN SUBJECTS RESEARCH SUBMISSIONS .................................................................................................. 113 6.6 CODED SPECIMENS / DATA SUBMISSIONS ............................................................................................................ 114 6.7 URGENT REVIEW SUBMISSIONS ......................................................................................................................... 115 6.8 HUMANITARIAN USE DEVICE............................................................................................................................. 115 6.9 INTERNATIONAL RESEARCH ............................................................................................................................... 116 6.10 CONTINUING REVIEW .................................................................................................................................... 117 6.11 AMENDMENTS ............................................................................................................................................. 118 Edit Study Personnel ................................................................................................................................... 118 6.12 REPORTABLE EVENTS ..................................................................................................................................... 119 Adverse Events ............................................................................................................................................ 119 Adverse Device Effects ................................................................................................................................ 119 Unanticipated Problems Involving Risk to Subjects or Others (UPX) ........................................................... 120 Noncompliance in Research ........................................................................................................................ 121 Protocol Deviations ..................................................................................................................................... 121 Participant Complaints................................................................................................................................ 121 6.13 CLINICAL TRIAL PROGRESS REPORTS ................................................................................................................. 122 Data Safety Monitoring Reports ................................................................................................................. 122 USC HRPP Policies and Procedures – 07/2021 Page 6 Investigational Device Exemption (IDE) Annual Report .............................................................................. 122 6.14 DIFFERENCE BETWEEN HUMAN SUBJECTS RESEARCH AND QUALITY IMPROVEMENT RESEARCH ..................................... 122 6.15 INSTITUTIONAL RESEARCH .............................................................................................................................. 123 6.16 ORAL HISTORY RESEARCH .............................................................................................................................. 124 6.17 PILOT STUDIES ............................................................................................................................................. 124 6.18 RESEARCH USING DECEPTION .......................................................................................................................... 125 Deception Qualifying for Exempt Review .................................................................................................... 125 CHAPTER CONTENTS ............................................................................................................................................ 126 CHAPTER 7 PROCESS OF IRB SUBMISSIONS ......................................................................................................... 127 7.1 IRB ONLINE APPLICATION (ISTAR) ..................................................................................................................... 127 7.2 CLINICALTRIALS.GOV ....................................................................................................................................... 128 Review of Scientific Merit ........................................................................................................................... 129 7.3 CRITERIA FOR IRB APPROVAL OF RESEARCH ......................................................................................................... 131 Review of Research Funds/Budget .............................................................................................................. 133 7.4 REVIEW OF EXEMPT RESEARCH .......................................................................................................................... 134 Amendments and Revisions to Exempt Research ........................................................................................ 134 7.5 REVIEW OF EXPEDITED RESEARCH ...................................................................................................................... 135 Expedited Reviewers ................................................................................................................................... 136 7.6 REVIEW OF FULL BOARD RESEARCH .................................................................................................................... 137 Full Board Reviewer Assignments ............................................................................................................... 138 Primary and Secondary Reviewer Responsibilities ...................................................................................... 139 Use of Consultant Reviewers ....................................................................................................................... 139 Meeting Materials – Full Board .................................................................................................................. 140 Projects Needing Verification from Sources Other than the Investigator ................................................... 140 7.7 SPONSORED RESEARCH AND ANCILLARY APPROVALS .............................................................................................. 141 Funded Research ......................................................................................................................................... 141 Ancillary Committee Reviews ...................................................................................................................... 143 7.8 IRB REVIEW AND DETERMINATIONS ................................................................................................................... 144 Full Board Review ....................................................................................................................................... 144 Expedited and Exempt Review .................................................................................................................... 146 Review of Response to Contingencies ......................................................................................................... 146 7.9 IRB CORRESPONDENCE AND INVESTIGATOR RESPONSE ........................................................................................... 147 IRB Correspondence .................................................................................................................................... 147 Investigator Response ................................................................................................................................. 149 7.10 IRB MEETING SCHEDULES .............................................................................................................................. 149 IRB Meeting Schedule for Biomedical Study Review ................................................................................... 149 IRB Meeting Schedule for Social Behavioral Study Review ......................................................................... 149 7.11 ADDITIONAL IRB SUBMISSIONS ....................................................................................................................... 150 CHAPTER CONTENTS ............................................................................................................................................ 151 CHAPTER 8 IRB CONSIDERATIONS AFTER INITIAL APPROVAL .............................................................................. 152 8.1 AMENDMENTS – CHANGES TO RESEARCH AFTER APPROVAL .................................................................................... 152 USC HRPP Policies and Procedures – 07/2021 Page 9 11.2 ROLE OF THE USC IRBS RELATED TO HIPAA ...................................................................................................... 230 CHAPTER CONTENTS ............................................................................................................................................ 231 CHAPTER 12 INVESTIGATOR’S ROLE AND RESPONSIBILITIES ............................................................................... 232 12.1 DEFINITION AND ROLE OF PRINCIPAL INVESTIGATOR (PI) ...................................................................................... 232 Who may be a Principal Investigator on an IRB Application ....................................................................... 232 IRB Review of Investigator Qualifications ................................................................................................... 234 Principal Investigator Responsibilities ........................................................................................................ 234 Investigator Responsibilities to IRB ............................................................................................................. 234 12.2 INVESTIGATOR-INITIATED RESEARCH AND SPONSOR-INVESTIGATORS ....................................................................... 237 12.3 EDUCATIONAL REQUIREMENTS ........................................................................................................................ 238 Human Subjects Protections Training ......................................................................................................... 238 Good Clinical Practice (GCP) Training .......................................................................................................... 238 Research HIPAA Course ............................................................................................................................... 239 Responsible Conduct of Research ................................................................................................................ 239 12.4 PROFESSIONAL QUALIFICATIONS OF PIS ............................................................................................................. 240 12.5 USC INVESTIGATORS CONDUCTING MULTI-SITE RESEARCH ................................................................................... 240 IRB Review of Resource Adequacy .............................................................................................................. 240 Site Permission in Multi-Site Research ........................................................................................................ 241 USC as Coordinating Center for Multi-Site Research ................................................................................... 243 12.6 INVESTIGATOR CONFLICT OF INTEREST ............................................................................................................... 244 12.7 FACULTY ADVISOR’S ASSURANCE FOR STUDENT INVESTIGATORS ............................................................................. 246 12.8 STUDENT INVESTIGATOR’S ASSURANCE ............................................................................................................. 247 12.9 FAILURE TO SUBMIT A PROJECT FOR IRB REVIEW ................................................................................................ 248 12.10 SCIENTIFIC / RESEARCH MISCONDUCT ............................................................................................................. 248 12.11 ADEQUATE FUNDS AND ANCILLARY APPROVALS ................................................................................................ 249 12.12 INTENT TO PUBLISH EXPECTATIONS ................................................................................................................. 250 12.13 MANDATORY REPORTING ............................................................................................................................. 251 Abuse Disclosure Notification in Consent Documents ................................................................................. 251 Reporting of Positive Results of Communicable Disease Testing ................................................................ 251 12.14 SUICIDAL IDEATION IN RESEARCH ................................................................................................................... 252 Participants and the Potential for Suicidal Risk .......................................................................................... 252 Adverse Event Reporting and suicidal ideation ........................................................................................... 256 12.15 INVESTIGATOR AND STAFF SAFETY .................................................................................................................. 257 CHAPTER CONTENTS ............................................................................................................................................ 258 CHAPTER 13 VULNERABLE SUBJECT POPULATIONS ............................................................................................. 259 13.1 PROTECTION OF CHILDREN INVOLVED AS SUBJECTS IN RESEARCH (45 CFR 46 SUBPART D) .......................................... 259 Permissible Research with Children ............................................................................................................ 260 Permitted Categories for Research with Children ....................................................................................... 261 Permission from Parents and Assent from Children .................................................................................... 263 Consent Guidelines for Children by Age Group............................................................................................ 263 Waiver of Parental Permission .................................................................................................................... 264 USC HRPP Policies and Procedures – 07/2021 Page 10 Waiver of Child Assent ................................................................................................................................ 265 Waiver or Alteration of Informed Consent in Studies Involving No More than Minimal Risk ..................... 266 Children under Guardian Care ..................................................................................................................... 267 Children under the Jurisdiction of Dependency Court / Court Appointee .................................................... 268 Informed Consent for Children Not in Parental Custody ............................................................................. 269 California Exceptions Permitting Certain Minors to Consent ...................................................................... 269 Managing Disclosure of Sensitive Information ........................................................................................... 271 Mandatory Reporting ................................................................................................................................. 271 Enrolling Children in Long-Term Studies ..................................................................................................... 272 Research Involving Children in Educational Settings ................................................................................... 272 FERPA Rules and Research with Education Records .................................................................................... 273 PPRA Role in Research Supported by Department of Education ................................................................. 274 Research Supported by the Department of Defense (DOD)......................................................................... 274 13.2 PREGNANT WOMEN, FETUSES AND NEONATES IN RESEARCH (45 CFR 46 SUBPART B) ............................................... 275 13.3 PRISONERS IN RESEARCH (45 CFR 46 SUBPART C) .............................................................................................. 275 Additional PI Responsibilities................................................................................................................ 276 Federal Regulations Permit 5 Categories of Research with Prisoners (45 CFR 46.306) ............................... 276 IRB Considerations for Prisoner Subjects (45 CFR 46.305) ........................................................................... 277 Subjects Who Later Become Incarcerated ................................................................................................... 280 Limits under California Penal Code ............................................................................................................. 280 13.4 COGNITIVELY IMPAIRED PERSONS .................................................................................................................... 281 IRB Criteria for Reviewing Research with Cognitively Impaired Persons..................................................... 282 Assessing Capacity to Consent .................................................................................................................... 283 Consenting Cognitively Impaired Subjects .................................................................................................. 283 Voluntariness, Consent, and Assent ............................................................................................................ 284 Surrogate Consent ...................................................................................................................................... 284 Cognitively Impaired in Non-Emergency Room Environments .................................................................... 284 Cognitively Impaired in Emergency Room Environments ............................................................................ 285 CHAPTER CONTENTS ............................................................................................................................................ 287 CHAPTER 14 RESEARCH WITH UNIQUE REGULATORY CONSIDERATIONS ............................................................ 288 14.1 CHART REVIEWS / CASE STUDIES ..................................................................................................................... 288 Chart Reviews ............................................................................................................................................. 288 Case Studies ................................................................................................................................................ 289 14.2 SPECIMENS (HUMAN BIOLOGICAL MATERIALS) ................................................................................................... 291 14.3 SECONDARY DATA ANALYSIS ........................................................................................................................... 293 Identifiable Information and Biospecimens for Secondary Research .......................................................... 293 Material Transfer Agreements (MTAs) ....................................................................................................... 294 14.4 REPOSITORIES: BANKING OF SPECIMENS / DATA ................................................................................................. 295 Establishing a Repository at USC................................................................................................................. 296 Distribution of Specimens/ Data from a USC Biorepository ........................................................................ 296 Storing Specimens / Data Outside of USC ................................................................................................... 296 14.5 NIH GENOMIC DATA SHARING POLICY (GDS) .................................................................................................... 297 USC HRPP Policies and Procedures – 07/2021 Page 11 14.6 GENETIC RESEARCH ....................................................................................................................................... 299 Secondary Subjects in Genetic Research ..................................................................................................... 300 Human Gene Transfer Research (“Gene Therapy”) ..................................................................................... 300 Federal Oversight: FDA, NIH, RAC ............................................................................................................... 300 14.7 PREGNANCY TESTING IN RESEARCH................................................................................................................... 301 14.8 RESEARCH INVOLVING HIV TESTING AND AIDS .................................................................................................. 302 California Law and HIV Research ................................................................................................................ 302 Policy on Informing Subjects about HIV Serostatus .................................................................................... 304 Counseling................................................................................................................................................... 304 Exceptions to Informing Subjects about HIV Serostatus.............................................................................. 304 14.9 SURVEY RESEARCH ........................................................................................................................................ 304 14.10 SOCIAL MEDIA IN RESEARCH ......................................................................................................................... 305 Social Media Emergence and Dominance ................................................................................................... 305 Social Media Differences from Traditional Research .................................................................................. 305 Protecting Social Media Data ..................................................................................................................... 305 Definitions ................................................................................................................................................... 306 Expectations ................................................................................................................................................ 306 What is in the Terms and Conditions? ......................................................................................................... 308 Informed Consent Considerations ............................................................................................................... 308 Obtaining Data from a Vendor/Social Media Platform .............................................................................. 309 Obtaining Data from Third parties .............................................................................................................. 309 Best practices for social media data ........................................................................................................... 309 Examples of Social Media Policies for Research Data Sets .......................................................................... 310 14.11 INTERNET RESEARCH.................................................................................................................................... 311 Primary Requirements for Internet Data Collection .................................................................................... 311 Protocol Design and Internet Research ....................................................................................................... 312 Minors in Internet Research ........................................................................................................................ 314 Online Surveys............................................................................................................................................. 314 14.12 CONSIDERATIONS FOR SEXUAL ORIENTATION AND GENDER IDENTITY .................................................................... 315 CHAPTER CONTENTS ............................................................................................................................................ 316 CHAPTER 15 STUDENT RESEARCH ........................................................................................................................ 317 15.1 INTRODUCTION TO STUDENT RESEARCH............................................................................................................. 317 15.2 CLASSROOM ASSIGNMENTS INVOLVING HUMAN SUBJECTS ................................................................................... 317 15.3 REQUIREMENTS OF FACULTY WHO SUPERVISE STUDENT RESEARCH......................................................................... 321 Faculty Responsibilities for the Protection of Human Subjects ................................................................... 321 15.4 WAIVER OF FACULTY STATUS TO SERVE AS ADVISOR FOR RESEARCH ....................................................................... 322 15.5 INTERNATIONAL RESEARCH CONDUCTED BY STUDENTS ......................................................................................... 323 IRB Considerations ...................................................................................................................................... 323 Faculty Advisor Responsibilities .................................................................................................................. 325 15.6 STUDENTS AS RESEARCH SUBJECTS ................................................................................................................... 325 15.7 STUDENT RESEARCHERS’ ABUSE REPORTING OBLIGATIONS.................................................................................... 326 Student Researchers’ Abuse Reporting Obligations .................................................................................... 326 USC HRPP Policies and Procedures – 07/2021 Page 14 Reinstatement of Suspended Research ....................................................................................................... 406 18.10 IRB REPORTING REQUIREMENTS TO FEDERAL AGENCIES, INSTITUTIONAL COMMITTEES OR OTHERS ............................. 406 Report Contents and Routing of Report ...................................................................................................... 407 Distribution of Report and Timeline ............................................................................................................ 408 Record Retention ........................................................................................................................................ 409 CHAPTER CONTENTS ............................................................................................................................................ 410 CHAPTER 19 DATA SAFETY MONITORING (DSM) ................................................................................................. 411 19.1 DATA SAFETY MONITORING (DSM) ................................................................................................................. 411 Appointment of a Research Monitor for Department of Defense (DOD) Sponsored Research ................... 412 19.2 DATA SAFETY MONITORING BOARD (DSMB) .................................................................................................... 413 Factors that Suggest a DSMB Is Needed ..................................................................................................... 413 FDA Guidance on Data and Safety Monitoring Boards, Committees, and Plans ......................................... 413 IRBs and DMCs ............................................................................................................................................ 414 DMC Charters .............................................................................................................................................. 415 Independence of the DMC ........................................................................................................................... 415 19.3 THE RELATIONSHIP BETWEEN DSMBS AND IRBS ................................................................................................ 415 CHAPTER CONTENTS ............................................................................................................................................ 417 CHAPTER 20 COMPLAINTS REGARDING HUMAN SUBJECTS RESEARCH ............................................................... 418 20.1 HANDLING COMPLAINTS REGARDING HUMAN SUBJECTS RESEARCH ........................................................................ 418 Participant Complaints................................................................................................................................ 418 Complaints Regarding Undue Influence ...................................................................................................... 419 Complaints Regarding the IRB or HRPP....................................................................................................... 420 CONTENTS ............................................................................................................................................................ 421 APPENDICES ......................................................................................................................................................... 422 A. Federalwide Assurances (FWAs) ........................................................................................................ 422 B. IRB Reliance Agreements ................................................................................................................... 422 C. Glossary of Medical Terms ................................................................................................................. 422 D. Basic Principles of Ethical Research .................................................................................................... 422 Preface Page 15 USC HRPP Policies and Procedures PREFACE Commitment of USC to Human Research Subject Protection At USC, protection of research subjects is a university-wide function that merits and receives the highest level of institutional support, commitment, visibility, and rigor. A vast and successful research enterprise is a catalyst for societal benefits and economic well-being. Thus, maintaining public trust in USC’s academic research is a critical goal. An excellent Human Research Protection Program (HRPP) is a vital part of retaining this trust and assuring that priority is given to the rights and welfare of those who participate in research. This document reflects the practices, expectations and standards to which this Institution adheres. Chapter 1: USC Human Research Protection Program Page 16 USC HRPP Policies and Procedures Chapter 1: USC Human Research Protection Program Chapter Contents 1.1 – Human Research Protection Program (HRPP) 1.2 – Human Research Protection Program Components 1.3 – How the Organization Works Together to Protect Subjects 1.4 – Research Involving the Community 1.5 – Flexibility Policy Chapter 1: USC Human Research Protection Program USC HRPP Policies and Procedures – 07/2021 Page 19 USC IRBs review, approve, and monitor all research involving human subjects under the jurisdiction of their FWAs. Each IRB office provides administrative support to the IRB committees, provides assistance to investigators who are preparing IRB applications, and maintains records of IRB reviews and approvals for investigators. The USC IRBs are responsible for review of all biomedical and social and behavioral research conducted on the USC University Park Campus and Health Science Campus. The Office of Compliance and/or the Office of General Counsel are available for assistance and legal counsel in applying laws to research involving human subjects. Note: the terms “subject” and “participant” are used interchangeably throughout the Policies & Procedures. Chapter 1: USC Human Research Protection Program USC HRPP Policies and Procedures – 07/2021 Page 20 Human Research Protection Program (HRPP) Organizational Chart 1.2 Human Research Protection Program Components Institutional Official/Human Subjects Research Vice President of Research University of Southern California 3720 South Flower Street, 3rd Floor Los Angeles, CA 90089-4019 TEL: (213) 740-6709 FAX: (213) 740-8919 Chapter 1: USC Human Research Protection Program USC HRPP Policies and Procedures – 07/2021 Page 21 Office for the Protection of Research Subjects Director Program Manager Program Administrator University of Southern California 3720 South Flower Street, 3rd Floor Los Angeles, CA 90089-1146 TEL: (213) 821-1154 E-mail: oprs@usc.edu Web: https://oprs.usc.edu/ Institutional Review Board Associate Directors Chairs Vice-Chairs IRB Analysts USC IRB 3720 South Flower Street, Third Floor Los Angeles, CA 90033-0702 TEL: (323) 442-0114 FAX: (213) 821-5276 E-mail: irb@usc.edu Office of Research Integrity Research Integrity Officer University of Southern California 3720 South Flower Street, 3rd Floor Los Angeles, CA 90089-1146 TEL: (213) 821-7291 Research Technology Group / iStar Director Chapter 1: USC Human Research Protection Program USC HRPP Policies and Procedures – 07/2021 Page 24 Research Coordinator Bulletin and Education Meetings Information specific for coordinators and research support staff is communicated through the research coordinator’s bulletin. Featured topics include educational sessions, coordinator events and networking opportunities, coordinator FAQs, national coordinator resources and articles of interest. OPRS and the IRB offer education luncheons that provide policy updates, presentations that highlight current topics of interest in research, and guidance on how to use the IRB application system (on an ad hoc basis). Program Communication IRB staff meets regularly to ensure that issues within that IRB can be addressed and that all staff are made aware of any new regulations or guidance that may be available. Staff problems or concerns are also addressed at this time or can be done on an individual basis. Issues that can benefit or educate others in the HRPP are forwarded to the OPRS for discussion and distribution to the entire HRPP team. The Director of the Office for the Protection of Research Subjects and Vice President of Research meet as needed. In these meetings, issues pertaining to the HRPP are addressed as are new suggestions or decisions, needing input at the provost level. Research Involving the Community USC promotes the involvement of community members, when appropriate, in the design and implementation of research and the dissemination of results. Community involvement builds public awareness and trust in research. Additionally, the more involved the community is, the more likely it is to benefit from research discoveries. Researchers have flexibility to develop their own approach to engagement, in keeping with the needs of a particular community. However, the approach must be rooted in ethical considerations – respect for persons, equitable selection of subjects, and beneficence – and should emphasize community outreach, consultation, involvement and collaboration. Several initiatives have been established by the Southern California Clinical Translation Science Institute (SC-CTSI) that provide guidance for conducting community-engaged Chapter 1: USC Human Research Protection Program USC HRPP Policies and Procedures – 07/2021 Page 25 research. An overview of SC-CTSI services and available toolkits may be found on their website at Community Engaged Research. In addition to CTSI resources, the Office for the Protection of Research Subjects (OPRS) website provides information for prospective research participants about types of research being offered at USC, questions to consider before participation, and contact information for reporting research complaints and concerns. Brochures are available in English and Spanish to inform individuals in the community about what to know before participating in a research study. For additional information, see references below. 1.4 Flexibility Policy Basis of Flexibility Policy The University of Southern California has chosen to limit the application of the federal regulations to federally funded or federally regulated research. For research projects outside the scope of the federal regulations subjects will nonetheless be afforded equivalent protections. This Flexibility Policy is limited to studies involving no greater than minimal risk as well as no federal funding and not FDA regulated. The full policy can be found at the following link: USC Flexibility Policy (12/17/2018). Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests and any disclosure of the human subjects’ responses outside the research would not reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects’ financial standing, employability, educational advancement, or reputation. This policy establishes flexibility in review, administration, and oversight of human subjects research. USC will also be encouraging and supporting additional opportunities for flexibility when encountered. Flex projects determined to be minimal-risk research do not require continuing review (unless specifically required by the IRB); and may still require a HIPAA waiver. Informed consent will not be required of minimal risk studies eligible for the flex policy. However, should the reviewer determine informed consent is necessary; the study should not be flexed. Chapter 1: USC Human Research Protection Program USC HRPP Policies and Procedures – 07/2021 Page 26 Implementation of Flexibility Policy All human subjects research projects conducted or supported at USC remain subject to USC IRB policies and review, whether they qualify for this policy or not. When questions of applicability arise, studies will be reviewed on a case by case basis. Inclusion/exclusion of any research project will be at the discretion of the USC Institutional Review Boards (IRBs). The IRB may make exceptions to this policy for funded research that is not federally funded. Studies reviewed under this policy remain subject to USC IRB policies and review. Should a study approved under the Flexibility Policy obtain federal funding or should the risk level change, it is the responsibility of the Principal Investigator to notify the IRB and submit an amendment for the change. Under no circumstances will FDA regulated research be reviewed under this policy. Minimal risk studies approved under the Flex Policy will require an amendment if there is a change in risk, funding, or scope. Research projects that meet the federal definition for human subject research and exceed minimal risk are subject to the criteria for approval articulated in the regulations at 45 CFR 46 and/or FDA regulations as applicable and do not qualify for review under the flexibility policy. A Flexibility Coalition was established by the University of Southern California to disseminate flexibility policies and encourage similar programs at academic Institutions across the United States. Chapter 2: Federal Regulations and State Laws USC HRPP Policies and Procedures – 07/2021 Page 29 • Subpart C, “Additional Protections Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects” became final on November 16, 1978. • Subpart D, “Additional Protections for Children Involved as Subjects in Research” became final on March 8,1983 and was revised for a technical amendment on June 18, 1991. The Common Rule “does not affect any state or local laws or regulations (including tribal law passed by the official governing body of an American Indian or Alaska Native tribe) that may otherwise be applicable and that provide additional protections for human subjects.” FDA (21 PARTS 50 AND 56) Food and Drug Administration (FDA) regulations on the protection of human subjects are codified at Title 21 Parts 50 and 56 of the Code of Federal Regulations. Part 50, which sets forth the requirements for informed consent. Subpart C provides special protections for prisoners. Subpart D provides Additional Safeguards for Children in Clinical Investigations. Part 56 sets forth the provisions for Institutional Review Boards. Additional FDA regulations that are relevant to IRB review of research are Parts 312 (Investigational New Drug Application), 600 (Biological products), 812 (Investigational Device Exemptions) and 860 (Medical Device Classification Procedures). For a comparison of FDA and HHS Human Subject Protection Regulations, click here. For additional information about FDA-regulated research, refer to Chapter 18 – FDA- Regulated Research. HIPAA (45 PARTS 160 AND 164) The HIPAA Privacy Rule is under the jurisdiction of the Office of Civil Rights which is responsible for interpreting, establishing guidelines, and any subsequent modifications of the rule. Information regarding the most recent version of the Privacy Rule - Health Information Technology for Economic and Clinical Health (HITECH Act), may be found at: http://www.hhs.gov/about/news/2013/01/17/new-rule-protects-patient-privacy- secures-health-information.html Chapter 2: Federal Regulations and State Laws USC HRPP Policies and Procedures – 07/2021 Page 30 2.2 Department of Defense (DOD) and Department of the Navy (DON) The Department of the Navy (DoN) supports research involving human subjects conducted by a non-DoD institution by way of contracts, grants, assistance agreements, cooperative agreements, cooperative research and development agreements and other partnering agreements. As of February 1st, 2016, DoN no longer required or issued the Navy Addendum to the FWA. DoN implements human research protection requirements through the Common Rule (32 CFR 219), Department of Defense Instructions (DoDI 3216.02) and directives, and DoN instructions (SECNAVINST 3900.39D). The DoD and DoN also have additional requirements for research involving human subjects, including the requirement for review by a Human Research Protection Official (HRPO). Resources and guidance may be found at the following website: https://www.health.mil/Military- Health-Topics/Privacy-and-Civil-Liberties/Protect-Humans-in-Research/HRPO-Review- of-Research-Protocols Researchers should be cognizant that DOD requirements may lead to additional costs related to the conduct of the study. Researchers are urged to anticipate any specific subject protection costs that might be directly associated with the DOD project. For example, if a project poses greater-than- minimal risk and therefore requires a Research Monitor, costs associated with the monitor might qualify as direct costs. For assistance in identifying such costs and dealing with the funding agency, please consult with the USC Office of Contracts & Grants for assistance. Note: If you are designing a project that will involve other entities as collaborators or sub-contractors, you are strongly encouraged to consult with the DOD or the sponsor to identify additional requirements. (Refer to Appendix E) Research Supported by the Department of Defense (DOD) When submitting a study to the USC IRB that is supported by or in collaboration with DOD, specific additional information must be included in the iStar application. In addition to IRB requirements, federal regulations, state laws and institutional policies, the DOD (including the Navy, Army, Air Force, and Personnel and Readiness) requires the Institution to: Chapter 2: Federal Regulations and State Laws USC HRPP Policies and Procedures – 07/2021 Page 31 • Conduct initial and continuing research ethics education for personnel who are engaged in human subject research (who review, approve, oversee, or manage research) • Document determination by a designated staff person (other than investigators) whether research meets criteria for exemption • Ensure new research and substantive scientific amendments to approved research shall undergo scientific review and that the review is considered by the IRB • Ensure additional protections for military research subjects to minimize undue influence • Explain to subjects any provisions for medical care for research-related injury • Report unanticipated problems, adverse events, research-related injury, and suspensions or terminations of research within 30 days from the determination that the event is reportable • Appoint a Research Monitor when necessary • Safeguard for research conducted with international populations • Protect pregnant women, prisoners, and children • Comply with DOD limitations and modifications to research with vulnerable subjects. Research supported by or in collaboration with the Department of Defense (DOD) is subject to additional regulations. The DOD has adopted 45 CFR 46, Subpart B with limitations and modifications subject to subparts adopted by DOD. • Fetal research must comply with the US Code Title 42, Chapter 6A, Subchapter III, Part H, 289g • Include women and minorities as subjects, if study is a clinical investigation including Armed Services personnel Chapter 2: Federal Regulations and State Laws USC HRPP Policies and Procedures – 07/2021 Page 34 and well-being of participants. The IRB must approve the research monitor by name and a written summary of the monitors’ duties, authorities, and responsibilities. When a research monitor is required, consult with the IRB Chair. Research Related Injury Compensation Every research protocol involving greater than minimal risk shall provide an arrangement for emergency treatment and necessary follow-up of any research-related injuries to subjects. IRBs will determine whether research involving minimal risk also might include a similar arrangement for research-related injury. Subjects should be informed about how the costs for research related injuries will be covered. Waiver of Informed Consent Prohibited If the research involves an intervention or interaction with subjects a waiver of consent or parental permission is prohibited unless a waiver is obtained from the Secretary of Defense. International Research If the research involves human subjects who are not US citizens or DOD personnel, it is conducted outside the United States, and its territories and possessions additional DOD requirements must be met. Military and Civilian Personnel in Research Civilian personnel may experience "paycheck" vulnerability when research is conducted in the workplace. In addition, research findings may have unintended consequences for military and civilian personnel, such as loss of job, career, or benefits. Those involved in the research enterprise must recognize that non-participation may have subtle consequences and make every effort to avoid even the appearance of undue influence or coercion. “Minors” in the Military Individuals may join the military with parental permission when they are less than the state-mandated age of majority (generally 18 years). However, military members who are considered minors under state law must have parental permission, in addition to their assent, to participate in research. Chapter 2: Federal Regulations and State Laws USC HRPP Policies and Procedures – 07/2021 Page 35 Research with Data, Documents, Records, and Specimens Access to data, documents, records, and specimens for research purposes requires IRB review. Examples include mishap reports, blood specimens, training records, medical records, performance evaluations, employee records, fitness results. Women in the Military Federal regulations encourage women of childbearing potential to participate in drug development trials but require additional safeguards. State Laws Military commands must comply with relevant state laws. Research with Investigational Agents (Drugs, Devices, and Biologics) In addition to complying with DOD/DON regulations for research on investigational drugs, devices, and biologics, investigators must also adhere to the Food and Drug Administration regulations (21 CFR Part 56 - IRBs and 21 CFR Part 50 - Informed Consent). The FDA and DOD regulations on basic requirements for IRBs and for informed consent generally are consistent. Prisoners in Research (DOD) Research supported by or in collaboration with the Department of Defense (DOD) is subject to additional regulations. The DOD has adopted 45 CFR 46, Subpart C with limitations and modifications: • For research intended to enroll prisoners, the DOD does not allow review by expedited mechanism. • If a PI attests that it is in the best interest of a subject who becomes a prisoner to continue participation in the research, the DOD allows the IRB Chair to make a preliminary determination until the convened IRB (and DOD Component, if applicable) can review the request. Otherwise, the IRB may require that all research interactions and interventions with the prisoner-subject (including obtaining identifiable private information) cease until the convened IRB with consultation from the prisoner representative, can review this request to ensure that the rights and well-being of the human subject, now a prisoner, are not in jeopardy. Chapter 2: Federal Regulations and State Laws USC HRPP Policies and Procedures – 07/2021 Page 36 If the prisoner-participant can continue to consent to participate and is capable of meeting the research protocol requirements, the terms of the prisoner-participant’s confinement does not inhibit the ethical conduct of the research, and there are no other significant issues preventing the research involving human participants from continuing as approved, the convened IRB may approve a change in the study to allow this prisoner-participant to continue. Research supported by or in collaboration with the Department of Defense (DOD) is subject to additional regulations. The DOD has adopted 45 CFR 46, Subpart D with the following modification: • The DOD does not apply Subpart D to active duty personnel under the age of 18 as it considers all active duty military to be adults with legal capacity to participate in DOD supported research. For additional information, refer to Appendix E– Requirements for Department of Defense (DOD) Supported Research. Research Supported by the Department of the Navy (DON) Studies that are supported by (or done in collaboration with) the Department of the Navy (DON) are subject to requirements in addition to those imposed by the Department of Defense as described below. Researcher Responsibilities PIs are responsible for submitting documentation to DON prior to starting an IRB- approved study and upon subsequent reviews by the IRB (amendments, continuing reviews). DON uses such documentation to conduct a “headquarters-level administrative review.” Investigators should always report any serious adverse events, noncompliance, unanticipated problems involving risks to subjects or others, and protocol deviations and actions taken regarding the reports to the DON. Two DON components have documentation requirements. See the following links for the documentation requirements of each (note that the requirements differ): • Office of Naval Research (ONR) Chapter 2: Federal Regulations and State Laws USC HRPP Policies and Procedures – 07/2021 Page 39 • The research design must be compatible with both the operation of prison facilities and protection of human subjects. The researcher must observe the rules of the institution or office in which the research is conducted. • Any researcher who is a non-employee of the Bureau must sign a statement in which the researcher agrees to adhere to the provisions of 28 CFR 512. • All research proposals will be reviewed by the Bureau Research Review Board. Pilot Projects are not Considered Research Implementation of Bureau programmatic or operational initiatives made through pilot projects is not considered to be research. Research Design The project must have an adequate research design and contribute to the advancement of knowledge about corrections. Subject Selection and Incentives The selection of participants within any one organization must be equitable. Incentives may not be offered to help persuade inmate participants to participate. However, soft drinks and snacks to be consumed at the test setting may be offered. Reasonable accommodations such as nominal monetary recompense for time and effort may be offered to non-confined research participants who are both no longer in Bureau of Prisons custody and are participating in authorized research being conducted by Bureau employees or contractors. Confidentiality A non-employee of the Bureau may receive records in a form not individually identifiable when advance adequate written assurance that the record will be used solely as a statistical research or reporting record is provided to the agency. Except as noted in the consent statement to the participant, the researcher must not provide research information that identifies a participant to any person without that participant’s prior written consent to release the information. For example, research information identifiable to a particular individual cannot be admitted as evidence or used for any purpose in any action, suit, or other judicial, administrative, or legislative proceeding without the written consent of the individual to whom the data pertain. Chapter 2: Federal Regulations and State Laws USC HRPP Policies and Procedures – 07/2021 Page 40 Except for computerized data records maintained at an official Department of Justice site, records that contain non-disclosable information directly traceable to a specific person may not be stored in, or introduced into, an electronic retrieval system. If the researcher is conducting a study of special interest to the Office of Research and Evaluation (ORE) but the study is not a joint project involving ORE, the researcher may be asked to provide ORE with the computerized research data, not identifiable to individual participants, accompanied by detailed documentation. These arrangements must be negotiated prior to the beginning of the data collection phase of the project. Disclosure and Informed Consent Required elements of disclosure include: • Identification of the researchers • Anticipated uses of the results of the research • A statement that participation is completely voluntary and that the participant may withdraw consent and end participation in the project at any time without penalty or prejudice (the inmate will be returned to regular assignment or activity by staff as soon as practicable) • A statement regarding the confidentiality of the research information and exceptions to any guarantees of confidentiality required by federal or state law. For example, a researcher may not guarantee confidentiality when the participant indicates intent to commit future criminal conduct or harm himself or herself or someone else, or, if the participant is an inmate, indicates intent to leave the facility without authorization • A statement that participation in the research project will have no effect on the inmate participant's release date or parole eligibility Research Proposal Requirements When submitting a research proposal, the applicant shall provide the following information: • A summary statement, which includes: o Names and current affiliations of the researchers o Title of the study o Purpose of the study o Location of the study Chapter 2: Federal Regulations and State Laws USC HRPP Policies and Procedures – 07/2021 Page 41 o Methods to be employed o Anticipated results o Duration of the study o Number of participants (staff or inmates) required and amount of time required from each o Indication of risk or discomfort involved as a result of participation • A comprehensive statement, which includes: o Review of related literature o Detailed description of the research method o Significance of anticipated results and their contribution to the advancement of knowledge o Specific resources required from the Bureau of Prisons o Description of all possible risks, discomforts, and benefits to individual participants or a class of participants, and a discussion of the likelihood that the risks and discomforts will actually occur o Description of steps taken to minimize any risks • Description of physical or administrative procedures to be followed to: o Ensure the security of any individually identifiable data that are being collected for the study o Destroy research records or remove individual identifiers from those records when the research has been completed • Description of any anticipated effects of the research study on organizational programs and operations • Relevant research materials such as vitae, endorsements, sample consent statements, questionnaires, and interview schedules • A statement regarding assurances and certification required by 28 CFR 46, if applicable. Investigator Requirements and Responsibilities • The researcher must have academic preparation or experience in the area of study of the proposed research. • The researcher must assume responsibility for actions of any person engaged to participate in the research project as an associate, assistant, or subcontractor to the researcher. • At least once a year, the researcher shall provide the chief, Office of Research and Evaluation, with a report on the progress of the research. Chapter 2: Federal Regulations and State Laws USC HRPP Policies and Procedures – 07/2021 Page 44 Personally Identifiable Information Researchers are required to follow DOE requirements for the protection of personally identifiable information Reporting Requirements Researchers must promptly (within 48 hours) report the following to the human subject research program manager: • Any significant adverse events, unanticipated risks, and complaints about the research, with a description of any corrective actions taken or to be taken • Any suspension or termination of IRB approval of research • Any significant non-compliance with HRPP procedures or other requirements • Any compromise of personally identifiable information must be reported immediately (as soon as the breach is discovered). 2.5 Department of Education (ED) When research is supported by the Department of Education, USC fulfills its obligations with regard to the assurances and certification required by 34 CFR Sections 97 Subpart D (equivalent to 45 CFR Section 46 Subpart D), 24 CFR Section 356.3 and 34 CFR Section 99. The specific requirements for research supported by the Department of Education are listed below. Access to Instructional Materials Used in Human Subjects Research • All instructional material – including teachers' manuals, films, tapes, or other supplementary instructional material – which will be used in connection with any research or experimentation program or project must be available for inspection by the parents or guardians of the children engaged in such research. • Research or experimentation program or project means any program or project in any research that is designed to explore or develop new or unproven teaching methods or techniques. • Children are persons enrolled in research not above the elementary or secondary education level, who have not reached the age or majority as determined under state law. Chapter 2: Federal Regulations and State Laws USC HRPP Policies and Procedures – 07/2021 Page 45 2.6 State Laws that Apply to Human Subjects Research In addition to federal regulations 45 CFR 46 and Food and Drug Administration (FDA) regulations 21 CFR 50, 56, researchers are also expected to follow state and local laws. In California, there are additional state laws applicable to human subjects research. It is the responsibility of the Institution and researchers to know and follow these laws. Visit the Official California Legislative Information website to access California Codes. Investigators and IRB personnel with questions regarding how state or federal regulations apply to a specific research project should contact the Chair of the IRB and/or the Office of Compliance. Additional options include seeking guidance or interpretation from the USC Office of General Counsel. Final interpretation and expectations with respect to California law reside with the Office of Compliance, and Office of General Counsel at USC. The California Protection of Human Subjects in Medical Experimentation Act (Section 24170-24179.5) requires all medical experimentation to be “undertaken with due respect for human life and the right of individuals to determine what is done to their own bodies”. All participants in medical experiments must be provided a written “experimental subject’s bill of rights” in addition to informed consent. Refer to Chapter 9.2 – California Experimental Subject’s Bill of Rights for additional information. A “medical experiment” is defined (section 24174 California Health and Safety Code) as follows: • The severance or penetration or damaging of tissues of a human subject or the use of a drug or device, as defined in Section 109920 or 109925, electromagnetic radiation, heat or cold, or a biological substance or organism, in or upon a human subject in the practice or research of medicine in a manner not reasonably related to maintaining or improving the health of the subject or otherwise directly benefiting the subject • The investigational use of a drug or device as provided in Sections 111590 and 111595 • Withholding medical treatment from a human subject for any purpose other than maintenance or improvement of the health of the subject Chapter 2: Federal Regulations and State Laws USC HRPP Policies and Procedures – 07/2021 Page 46 2.7 Federalwide Assurance (FWA) The following describes the University of Southern California (USC) Federalwide Assurances of compliance maintained with the Office for Human Research Protections (OHRP)/Department of Health and Human Services (DHHS). The University is required to enter into this agreement because it receives federal funding for research involving human subjects. A Federalwide Assurance (FWA) is a binding written agreement between USC and OHRP. It states that the University will comply with federal regulations 45 Code of Federal Regulations Part 46, or simply 45 CFR 46 for all federally funded human subjects research. (See Appendix A). USC complies with requirements stipulated by other federal agencies when they serve as sponsors or have oversight of research conducted at USC. Refer to: https://oprs.usc.edu/policies-and-procedures/federal-agencies/ The USC IRBs are registered in the OHRP/FDA IRB database. Specific FWA Requirements FWA requirements must be met before OHRP/FWA is issued. These requirements pertain to the Institution, the intuitional official, and the IRBs: • The FWA applies to all federally funded research in which USC is engaged. Refer to Chapter 3.1 – Engagement in Research • The FWA requires compliance with the Federal Policy for Protection of Human Subjects (45 CFR 46) • The USC IRBs have written procedures for reporting unanticipated problems involving risks to subjects or others, serious or continuing noncompliance with federal regulations or IRB requirements and suspension or termination of IRB approval. USC must also ensure that a qualified person or persons determine research is exempt from IRB review. Finally, the USC IRBs have clear written procedures for conducting IRB initial and continuing review; approving research; Chapter 2: Federal Regulations and State Laws USC HRPP Policies and Procedures – 07/2021 Page 49 • individuals performing a service typically performed for non-research purposes, • fee for service activities/functions • an honest broker who provides IRB approved data or specimens to a research study, • pharmacy employees dispensing study drugs, • hospital employees who routinely collect and provide specimens • radiology clinic employees performing radiological imaging (x-rays, CT scans, MRI’s, ultrasounds, PET Scans, etc.), • laboratory employees providing routine laboratory analyses of blood samples for investigators as a commercial service, • transcription service employees providing transcriptions as a commercial service, • individuals not administering any study intervention being tested or evaluated under the protocol *The IRB will remove those listed who do not meet submission requirements. IRB Committee Responsibilities The IRB Committee is to review all human subjects research activities and document findings regarding ethical considerations, scientific merit, adherence to federal regulations and IRB policies and procedures. The IRB Committee must review and monitor ongoing human subjects research for adherence to the Federal regulations and IRB policies and procedures. IRB Staff Responsibilities In addition to routine IRB staff duties, the OPRS/ IRB staff will participate in ongoing auditing (refer to Section 17.3 – Audits and Assessment) and monitoring activities to assure adherence to the federal regulations. The IRB staff will participate in the revisions of the IRB policies and procedures as applicable. Chapter 2: Federal Regulations and State Laws USC HRPP Policies and Procedures – 07/2021 Page 50 IRB Administration Responsibilities All information provided under Federalwide Assurances must be updated at least every five years, even if no changes have occurred, in order to maintain an active Assurance approved by OHRP. Amendments to the Assurance are to be reported promptly to OHRP. This includes changes to IRB Chair/Vice Chair, or a legally recognized entity of USC. USC will maintain policies and procedures reflecting the current practices of the IRB in conducting reviews and approvals under its Assurance. These policies and procedures will be maintained and kept current by the USC OPRS. They will be reviewed and revised as needed at least every three years. Changes in policy are to be finalized by the Director of OPRS. The IRB’s budget will be reviewed annually, by the Director of OPRS, and the Vice President of Research and modified, as necessary, to accommodate the volume and type of research reviewed, education, space, facilities, and staff. Chapter 3: Reliance Agreements and Engagement in Research Page 51 USC HRPP Policies and Procedures Chapter 3: Reliance Agreements and Engagement in Research Chapter Contents 3.1 – IRB Reliance Agreements 3.2 – Transfer of IRB Oversight and Response to Disaster Chapter 3: Reliance Agreements and Engagement in Research USC HRPP Policies and Procedures – 07/2021 Page 54 relating to the research and ensure plans are incorporated into IRB review as applicable • Notify PI, Sponsor, and federal agencies, as appropriate of IRB decisions and action, and ensure appropriate communication plan for dissemination between sites • Maintain appropriate IRB records and documents relating to the IRB review, and make records available to relying institutions, upon request • Notify the relying institutions of any of the following, as relevant:  Serious and/or continuing noncompliance, suspensions, and/or  terminations  Audits, including findings and corrective actions  Reporting to a federal agency  Communication with regulatory agencies • Provide relevant minutes of IRB meetings to the relying institution/organization upon request. Relying IRB A Relying IRB defers to a review and approval of human research provided by an IRB that is unaffiliated with the institution. The responsibilities of the Relying IRB and the Reviewing IRB must be documented in an agreement. The agreement will include the applicable essential requirements set forth by AAHRPP Standard I-9. The Relying IRB reviews and approves local ancillary services and is responsible for local institution-specific compliance issues. Responsibilities of the Relying IRB • Ensure research personnel are appropriately qualified and meet relying institution standards for eligibility to conduct research, including but not limited to human subjects protection training and collection and maintenance of conflict of interest disclosure forms • Provide local context information to the reviewing IRB and ensure required information is incorporated into IRB-approved documents Chapter 3: Reliance Agreements and Engagement in Research USC HRPP Policies and Procedures – 07/2021 Page 55 • Provide local ancillary approvals to the reviewing IRB • Ensure research personnel are notified of their responsibilities when conducting research pursuant to a reliance agreement • Ensure compliance with the reviewing IRB determinations and requirements, applicable federal regulations, and all applicable state and local laws and institutional requirements • Ensure appropriate monitoring of research and perform reviewing IRB-directed audits upon request • Establish a process for reviewing conflicts of interest and creating management plans when appropriate • Document and notify the reviewing IRB of any of the following which relates to research:  PI and personnel changes  Changes that require ICF and HIPAA revision  Serious and/or continuing noncompliance  Restriction/suspension of research activities  Audits, including findings and corrective actions  Communication with regulatory agencies  Legal claims  Research misconduct • Receive notifications of issues from the reviewing IRB and take additional local action, if applicable USC Investigator Relying on An External IRB A USC investigator who is engaged in research and relying on an independent or external IRB must submit a Ceded Review application in iStar (iStar item 1.1). Refer to Chapter 4.2 Engagement in Research. The submission must include all required ancillary committee reviews (e.g. Radiation Safety, Biosafety) that apply. Chapter 3: Reliance Agreements and Engagement in Research USC HRPP Policies and Procedures – 07/2021 Page 56 The Ceded Review application must include all study documents approved by the reviewing IRB of record. The USC IRB will review the Ceded Review submission to verify that all requirements have been met. Required documentation may vary based upon the sponsor and/or agreement platforms such as SMART IRB. The investigator cannot conduct study activities until a Reliance Agreement or IRB Authorization Agreement (IAA) is fully executed. An acknowledgment letter will be issued by the USC IRB indicating that the study has been cleared to begin at USC. USC investigators must submit reportable events and participant complaints to the reviewing IRB as agreed upon, and to the USC IRB as described in Section 8.8 Reportable Events and Chapter 8.9 Participant Complaints. An amendment must be submitted to the USC IRB if any of the following changes occur: • Addition of investigators • New conflict of interest for investigators • Addition of special populations (adults who are not competent to consent or minors) • Addition of LAC+USC Medical Center as a study location • Changes in HIPAA authorization forms or waivers • Changes in funding or addition of research procedures that require review by other USC committees (Clinical Trials Office, Department of Contracts & Grants, Biosafety, and Radiation Safety Committee) When Relying on An External IRB That Is Not AAHRPP Accredited USC will consider the qualifications of an external IRB that is not AAHRPP accredited if such an arrangement is beneficial to USC, its investigators, and/or its research participants. The Principal Investigator must submit a Ceded Review application in iStar (iStar item 1.1) As per OHRP Guidance, an IRB Authorization Agreement will establish and clearly delineate roles and responsibilities of each party. The reviewing IRB will be required to meet the following criteria based on the nature of the study. For minimal risk research, USC IRB may:  Obtain an assurance from the non-accredited IRB that it will Chapter 3: Reliance Agreements and Engagement in Research USC HRPP Policies and Procedures – 07/2021 Page 59 USC IRB will act as the single IRB (sIRB) for full board multi-site studies of no more than 5 participating sites (including USC) due to limited resources. Maximum number of participating sites for expedited and exempt studies will be determined by the IRB on a case by case basis. In accordance with OHRP Guidance, an agreement must state the responsibilities of both parties. The agreement will include the applicable essential requirements set forth by AAHRPP Standard I-9. Cooperative (Multi-site) Research Beginning January 2020 USC participation in any cooperative multi-site research must rely upon approval by a single IRB for that portion of the research that is conducted in the United States. The following is regulation 45 CFR 46.114(b): (a) Cooperative research projects are those projects covered by this policy that involve more than one institution. In the conduct of cooperative research projects, each institution is responsible for safeguarding the rights and welfare of human subjects and for complying with this policy. (b) (1) Any institution located in the United States that is engaged in cooperative research must rely upon approval by a single IRB for that portion of the research that is conducted in the United States. The reviewing IRB will be identified by the Federal department or agency supporting or conducting the research or proposed by the lead institution subject to the acceptance of the Federal department or agency supporting the research. (2) The following research is not subject to this provision: (i) Cooperative research for which more than single IRB review is required by law (including tribal law passed by the official governing body of an American Indian or Alaska Native tribe); or (ii) Research for which any Federal department or agency supporting or conducting the research determines and documents that the use of a single IRB is not appropriate for the particular context. (c) For research not subject to paragraph (b) of this section. An institution participating in a cooperative project may enter into a joint review arrangement, rely on the review of another IRB, or make similar arrangements for avoiding duplication of effort. Chapter 3: Reliance Agreements and Engagement in Research USC HRPP Policies and Procedures – 07/2021 Page 60 National Cancer Institute (NCI) Central IRB (CIRB) USC is participating in the National Cancer Institute (NCI) Central IRB (CIRB). CIRB is the IRB of Record responsible for review of the study as well as review of local context issues for participating sites. Local policy, conflict of interest, HIPAA authorization, and ancillary committee approvals are still the responsibility of the relying IRB (USC). For research reviewed by NCI, the Clinical Investigator Support Office at USC Comprehensive Cancer Center (CISO) typically provides review of scientific merit, resources and financial aspects of the study. SMART IRB USC is a signatory to the SMART IRB Master Reliance Agreement that is supported by NIH funding and recommended by NIH policy for single IRB review. The agreement is designed to harmonize and streamline the IRB review process for multisite studies, while ensuring a high level of protection for research participants. When possible, USC will use the SMART IRB agreement as the basis for reliance when serving as the sIRB or being a relying IRB of a SMART IRB study. Engagement in Research The USC IRBs define engagement in research according to OHRP’s 2008 guidance on the engagement of Institutions in research and OHRP’s 2011 Correspondence on “Non- engaged Scenarios”. An Institution becomes “engaged” in human subjects research when its employees or agents (all individuals performing institutionally-designated activities or exercising institutionally-delegated authority or responsibility, including faculty and students): (i) Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or (ii) Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens. Chapter 3: Reliance Agreements and Engagement in Research USC HRPP Policies and Procedures – 07/2021 Page 61 An Institution is automatically considered to be “engaged” in human subjects research whenever it receives a direct HHS award to support such research. In such cases the awardee’s Institution bears ultimate responsibility for protecting human subjects under the award. IMPORTANT NOTE: The USC IRBs require review by a USC IRB and by the IRB(s) at other location(s) (if the other Institution is “Engaged in the Research”) regardless of funding unless an IRB Authorization Agreement (IAA) is required or obtained. (See Cooperative (Multi-Site) Research. Engaged Research In general, Institutions are considered engaged in an HHS-conducted or -supported non- exempt human subjects research project (and, therefore, would need to hold or obtain OHRP-approved FWAs and certify IRB review and approval to HHS) when the involvement of their employees or agents in that project includes any of the following: • Institutions that receive an award through a grant, contract, or cooperative agreement directly from HHS for the non-exempt human subjects research (awardee Institutions), even where all activities involving human subjects are carried out by employees or agents of another Institution • Institutions whose employees or agents intervene for research purposes with any human subjects of the research by performing invasive or noninvasive procedures. Examples of invasive or noninvasive procedures include drawing blood; collecting buccal mucosa cells using a cotton swab; administering individual or group counseling or psychotherapy; administering drugs or other treatments; surgically implanting medical devices; utilizing physical sensors; and utilizing other measurement procedures • Institutions whose employees or agents intervene for research purposes with any human subject of the research by manipulating the environment. Examples of manipulating the environment include controlling environmental light, sound, or temperature; presenting sensory stimuli; and orchestrating environmental events or social interactions. • Institutions whose employees or agents interact for research purposes with any human subject of the research. Examples of interacting include engaging in protocol dictated communication or interpersonal contact; asking someone to Chapter 3: Reliance Agreements and Engagement in Research USC HRPP Policies and Procedures – 07/2021 Page 64 If such an Institution does not have an FWA, its employees or agents may be covered by the FWA of another Institution that is engaged in the research through completion of an Individual Investigator Agreement and/or IRB Authorization Agreement 3. Institutions (including private practices) not initially selected as a research site whose employees or agents administer the study interventions being tested or evaluated under the protocol limited to a one-time or short-term basis (an oncologist at the Institution administers chemotherapy to a research subject as part of a clinical trial because the subject unexpectedly goes out of town, or is unexpectedly hospitalized), provided that all of the following conditions also are met: a. an investigator from an Institution engaged in the research determines that it would be in the subject’s best interest to receive the study interventions being tested or evaluated under the protocol b. the Institution’s employees or agents do not enroll subjects or obtain the informed consent of any subject for participation in the research c. investigators from the Institution engaged in the research retain responsibility for: i. overseeing protocol-related activities ii. ensuring the study interventions are administered in accordance with the IRB-approved protocol and iii. ensuring appropriate arrangements are made for reporting protocol-related data to investigators at the engaged Institution, including the reporting of safety monitoring data and adverse events as required under the IRB-approved protocol and iv. an IRB designated on the engaged Institution’s FWA is informed that study interventions being tested or evaluated under the protocol have been administered at an Institution not selected as a research site 4. Institutions whose employees or agents: a. inform prospective subjects about the availability of the research b. provide prospective subjects with information about the research (which may include a copy of the relevant informed consent document and other IRB approved materials) but do not obtain subjects’ consent for the research or act as representatives of the investigators Chapter 3: Reliance Agreements and Engagement in Research USC HRPP Policies and Procedures – 07/2021 Page 65 c. provide prospective subjects with information about contacting investigators for information or enrollment and/or d. seek or obtain the prospective subjects’ permission for investigators to contact them 5. Institutions (schools, nursing homes, businesses) that permit use of their facilities for intervention or interaction with subjects by investigators from another Institution. Example would be a school that permits investigators from another Institution to conduct or distribute a research survey in the classroom. 6. Institutions whose employees or agents release to investigators identifiable private information or identifiable biological specimens pertaining to the subjects of the research. Note that in some cases the Institution releasing identifiable private information or identifiable biological specimens may have institutional requirements that would need to be satisfied before the information or specimens may be released, and/or may need to comply with other applicable regulations or laws. In addition, if the identifiable private information or identifiable biological specimens to be released were collected for another research study covered by 45 CFR part 46, then the Institution releasing such information or specimens should: a. ensure that the release would not violate the informed consent provided by the subjects to whom the information or biological specimens pertain (under 45 CFR 46.116), or b. if informed consent was waived by the IRB, ensure that the release would be consistent with the IRB’s determinations that permitted a waiver of informed consent under 45 CFR 46.116 (c) or (d) Note that, in general, the Institutions whose employees or agents obtain the identifiable private information or identifiable biological specimens from the releasing Institution would be engaged in human subjects research. 7. Institutions whose employees or agents: a. obtain coded private information or human biological specimens from another Institution involved in the research that retains a link to individually identifying information (such as name or social security number), and b. are unable to readily ascertain the identity of the subjects to whom the coded information or specimens pertain because, for example: Chapter 3: Reliance Agreements and Engagement in Research USC HRPP Policies and Procedures – 07/2021 Page 66 i. the Institution’s employees or agents and the holder of the key enter into an agreement prohibiting the release of the key to those employees or agents under any circumstances ii. the releasing Institution has IRB-approved written policies and operating procedures applicable to the research project that prohibit the release of the key to the Institution’s employees or agents under any circumstances, or iii. there are other legal requirements prohibiting the release of the key to the Institution’s employees or agents For purposes of this document, coded means that: o identifying information (such as name or social security number) that would enable the investigator to readily ascertain the identity of the individual to whom the private information or specimens pertain has been replaced with a number, letter, symbol, and/or combination thereof (the code), and o a key to decipher the code exists, enabling linkage of the identifying information to the private information or specimens Although this scenario resembles some of the language in OHRP’s Guidance on Research Involving Coded Private Information or Biological Specimens, it is important to note that OHRP’s Guidance on Research Involving Coded Private Information or Biological Specimens addresses when research involving coded private information or specimens is or is not research involving human subjects, as defined in 45 CFR 46.102(e)(1) (see http://www.hhs.gov/ohrp/policy/cdebiol.html). The Guidance on Engagement of Institutions in Human Subjects Research (2008) should only be applied to research projects that have been determined to involve human subjects and that are not exempt under HHS regulations at 45 CFR 46.104. 8. Institutions whose employees or agents access or utilize individually identifiable private information only while visiting an Institution that is engaged in the research, provided their research activities are overseen by the IRB of the Institution that is engaged in the research. 9. Institutions whose employees or agents access or review identifiable private information for purposes of study auditing (a government agency or private USC HRPP Policies and Procedures – 07/2021 Page 69 Chapter 4: Conflicts of Interest Page 70 USC HRPP Policies and Procedures Chapter 4: Conflicts of Interest Chapter Contents 4.1 – Conflicts of Interest 4.2 – USC Conflict of Interest in Research Committee (CIRC) 4.3 – Investigator and/or Research Team Conflict of Interest Disclosures 4.4 – Institutional Conflict of Interest (ICOI) 4.5 – IRB Members and IRB Consultants Conflict of Interest USC HRPP Policies and Procedures – 07/2021 Page 71 Chapter 4 Conflicts of Interest This chapter describes conflicts of interest disclosures and management in relation to research. The focus is on conflict of interest specific to investigators, research team, IRB members, consultants and USC as an Institution. USC Conflict of Interest policies reflect the U.S. Department of Health and Human Services (DHHS) and Public Health Service (PHS) regulations effective 8/24/12 and the USC Office of Compliance policies. 4.1 Conflicts of Interest Individual Conflict of Interest An individual conflict of interest can arise when financial or other personal considerations compromise, or have the appearance of compromising, an individual’s professional judgment in proposing, conducting, supervising, or reporting research. Conflicts can exist at the individual or institutional levels and involve financial and non- financial interests. Conflicts of Interest may include but are not limited to the following: • Equity (stocks or options, do not include mutual funds) • Recruitment incentives (bonus payments) (these are prohibited) • Consulting Fees • Speaking Fees • Travel Reimbursement • Gifts • Corporate Officer or Board of Directors Chapter 4: Conflicts of Interest USC HRPP Policies and Procedures – 07/2021 Page 74 4.3 Investigator and / or Research Team Conflict of Interest Disclosures Disclosures in the IRB application (iStar) Potential or actual conflicts of interest must be disclosed at the time of submission of the initial and continuing review application to the IRB and at any time when the investigator and/or research team member establish a new outside relationship or change an existing relationship that creates a potential conflict of interest. Also, informed consent documents must disclose conflicts of interest, as applicable. Conflicts of interest must be declared when the participating study investigators or other research personnel (or their immediate family/domestic partner) have an aggregated financial interest, and/or intellectual property interest in the sponsor or products used with the project, equal to or exceeding $5,000 per year. Additionally, investigators must inform the IRB of monies received below $5,000 for specific conditions defined in the iStar application. When these conditions are met, the potential conflict of interest is reviewed by the Office of Compliance. Disclosures in USC’s diSClose system All disclosure of potential or actual conflict of interests must be made online using the diSClose system. Additionally, the IRB application includes conflict of interest questions for initial and continuing review applications. Investigators must also report conflict of interests if these arise during a study by submitting an amendment. Informed consent documents must disclose conflicts of interest, as applicable. Disclosures for Research Funded by the Health and Human Services Researchers who are proposing or have received HHS (including NIH, CDC, HRSA, and AHRQ) support must also make an annual disclosure of all financial interests related to their institutional responsibilities to USC, regardless of whether any of these interests give rise to a conflict of interest related to their research. The annual disclosure must be completed before a proposal can be submitted to HHS, and any identified conflicts must Chapter 4: Conflicts of Interest USC HRPP Policies and Procedures – 07/2021 Page 75 be managed before an account can be established. In addition, all HHS investigators must complete training on conflicts of interest once every four years. Disclosures to Sponsors Investigators must adhere to sponsor-specific disclosure requirements, as applicable. 4.4 Institutional Conflict of Interest (ICOI) An institutional conflict of interest may occur when a financial interest of the University (investments held by the University in a company) has the potential to bias research conducted by its employees or students or creates an unacceptable risk to human subjects. All Institutional Conflict of Interests that do not present a Significant Institutional Conflict of Interest shall be managed by disclosing the University’s relationship with the outside entity in all relevant publications, proposals, consent documents and presentations. An Institutional Conflict of Interest is deemed “significant” when a research project includes human subjects and any of the following condition applies: • The University holds any private equity in the outside entity, or • The University has the potential to receive cash payments from existing licensing arrangements with the outside entity, or • The University maintains an ownership interest or an entitlement to equity in a publicly traded sponsor of human subjects research as a result of technology licensing activities. Significant Institutional Conflicts of Interest are presumed to be unacceptable, unless compelling circumstances are present that justify allowing the research to proceed at the University despite the presence of a significant conflict. The University conducts a fact- specific inquiry to determine whether the specific circumstances of a relationship are compelling or not. For more information, refer to the USC Office of Compliance website: Conflict of Interest in Research Chapter 4: Conflicts of Interest USC HRPP Policies and Procedures – 07/2021 Page 76 The Vice President of Research (VPR) will determine on a case by case basis the need for an independent IRB review of studies involving ICOI. Independent review by an outside bioethicist will provide evaluation to determine whether the ICOI meets the threshold necessary to seek review by an independent IRB. If the VPR determines that the ICOI does not meet such criteria – the study will be reviewed by the USC IRB. If the interest is determined to be an institutional conflict, it will be subsequently reviewed by the Conflict of Interest Review Committee with the inclusion of external members. 4.5 IRB Members and IRB Consultants Conflict of Interest IRB members are subject to the Conflict of Interest policy. The IRB prohibits the participation in IRB initial or continuing review of any project in which the member has a conflicting interest, except to provide information requested by the IRB. An IRB member is considered to have a Conflict of Interest if: • The IRB member or a Close Relation of the IRB member (spouse, mutual financial dependent, significant other, or person in an intimate relationship, child, parent, or sibling (including in-laws and step-relations), grandparent, grandchild, niece or nephew, aunt or uncle, or cousin) is involved in the conduct of the research • When the IRB member or Close Relation of the IRB member has a supervisory, managerial or ownership interest in the research sponsor, or licensee, or a company having an economic interest in the research • Equity interest held by an IRB member or Close Relation of an IRB member in a research sponsor, or licensee, or in any company having an economic interest in the research • Incentive payments, bonus payments or finder’s fees relating to the proposal paid to the IRB member or Close Relation • Consultation arrangements between the IRB member or Close Relation of an IRB member and an organization or individual having an economic interest in the USC HRPP Policies and Procedures – 07/2021 Page 79 Chapter 5 USC Institutional Review Boards (IRBs) This chapter describes the purpose, role, composition and general procedures of the USC Institutional Review Boards (IRBs). The USC IRBs are responsible for the review of all human subjects research conducted at USC. 5.1 Description of USC IRBs This chapter covers IRB membership, the roles and requirements of IRB members, Chairs, Vice-Chairs, and reviewers at the University of Southern California (USC). Additionally, this chapter explains the use of consultants, the role of IRB staff, voting requirements, and IRB record keeping. There are four Institutional Review Boards at the University of Southern California. The IRBs review and approve research in accordance with Department of Health and Human Services (DHHS) regulations in 45 CFR 46. For studies involving products regulated by the Food and Drug Administration (FDA), the University of Southern California IRBs review research and comply with the requirements set forth in 21 CFR 50 and 56, as well as 21 CFR 312 and 812. In addition, the IRBs comply with HIPAA and its regulations set forth in 45 CFR 160 and 164, California law as it pertains to human subjects research and other federal regulations as applicable. At USC the Vice President of Research is designated the Institutional Official. USC IRBs have been delegated the following authority by the Institutional Official in his delegation memo dated 11/23/2005: • USC IRBs have the authority to approve, disapprove, or suspend human subject research projects. No USC faculty, staff, or student may conduct human subjects research without obtaining approval the appropriate IRB. • USC IRBs have the authority to observe, or have a third party observe, the consent process and the conduct of the research. Chapter 5: USC Institutional Review Boards (IRBs) USC HRPP Policies and Procedures – 07/2021 Page 80 5.2 The Membership of the IRB Committees Number, Qualifications and Diversity of Members Each IRB has a minimum of five members with varying backgrounds to adequately review the research activities conducted by the Institution. Major clinical and selected basic science departments are represented to provide the experience and expertise sufficient for review of the research activities conducted at the Institution. The IRB member with appropriate scientific expertise for each protocol will be designated to review the application. The IRB includes at least one member whose primary concerns are in scientific areas and at least one member whose primary concerns are in non- scientific areas. Also, the IRB consists of at least one member not otherwise affiliated with the Institution and not part of the immediate family of a person who is affiliated with the Institution. To enable each IRB to ascertain the acceptability of proposed research in terms of institutional commitments, regulations, applicable law, and standards of professional conduct and practice, each IRB includes persons knowledgeable in these areas and may include representatives of administration. Each IRB is sufficiently qualified through the experience, expertise and diversity of its members – including consideration of race, gender, cultural backgrounds, and sensitivity to such issues as community attitudes – to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects. The IRBs may review research that involves subjects who are considered vulnerable. They include subjects vulnerable to coercion or undue influence such as children, prisoners, individuals with impaired decision-making capacity, or economically or educationally disadvantaged persons). Consideration shall be given to the inclusion of one or more IRB members or consultants who are knowledgeable about, and experienced in, working with these categories of subjects. Alternate Members When deemed necessary by the IRB Chair, and when requested by department Chairs or deans, alternates will be appointed for IRB members. Formally appointed alternate IRB members may represent IRB members, provided the alternate's qualifications are comparable to the primary member to be replaced. The IRB membership rosters identify the primary member(s) for whom each alternate member substitutes. Prior to the IRB meeting, materials required for review are made available electronically through iStar to all members. Chapter 5: USC Institutional Review Boards (IRBs) USC HRPP Policies and Procedures – 07/2021 Page 81 The IRB minutes document when an alternate member replaces a primary member. When an alternate member substitutes for a primary member, the alternate must receive and review the same material the primary member received or would have received. Members and their alternates may not both vote. Alternates are not counted as “members” in establishing the numerical quorum of the IRB, except when they substitute for members during the IRB meeting. Alternates are invited to attend all IRB meetings, whether they are eligible to participate as voting members or not, in order to assure familiarity with the IRB practices and continuing education. Ex-Officio Members The IRB may include ex-officio members depending on the relevance of their office and their expertise and experience. The positions they hold preclude full IRB membership and therefore ex-officio members are not voting members of the IRB. 5.3 IRB Member Requirements Selection and Appointment The formal appointments of IRB members are made by the Vice President of Research. Typically, individuals who are responsible for business development are not selected to serve as IRB members. Non-affiliate members not associated with the Institution are identified by interest and relevance and are recommended for appointment by members of the IRB, IRB staff, Departments or Schools. IRB committee membership lists can be found on the OPRS websites: Length of Service Appointments to the IRBs are for a period of 1 year. Expertise and diverse membership are expectations for both campus IRBs. Continued tenure on the IRB is at the discretion of the Director in consultation with the IRB Chairs. Evaluations of IRB composition and formal evaluation of individual members are conducted at the end of the fiscal year at the time of IRB budget review/approval. Appointment letters indicating satisfactory evaluation of returning members are sent to IRB members at the end of one fiscal year for the next fiscal year. The duties and responsibilities of IRB members are stated in appointment letters from the Chapter 5: USC Institutional Review Boards (IRBs) USC HRPP Policies and Procedures – 07/2021 Page 84 Evaluation of IRB Members The duties and responsibilities of IRB members will be stated in appointment letters from the Vice President of Research. At any time, at the discretion of the Vice President of Research a member may be removed and replaced with the need to ensure that the board includes the expertise and representation required. Expectations and subsequent evaluation of IRB members follow: • IRB members will be re-appointed annually if expectations are met. Expectations are outlined in the document: USC IRB Members Standards and Responsibilities. This document may be used as a self-evaluation tool and serves as a review guide for the annual formal evaluation processes of each IRB member. The re-appointment letter will acknowledge that the IRB member has been evaluated and satisfied the membership criteria. • If a board member is removed/replaced in order to ensure that the board maintains required expertise and representation, or if a member fails to meet the expectations outlined in USC IRB Members Standards and Responsibilities, correspondence will be sent informing them their service is no longer needed. IRB members are evaluated on an ongoing basis by the IRB Director, Chairs, and the Director of OPRS. However, formal evaluations occur annually with the IRB Director and/or Director of OPRS. Performance is assessed according to the criteria outlined in USC IRB Member Standards and Responsibilities. Member evaluation also includes determining whether a member should be designated to conduct IRB reviews using the expedited procedure. Written feedback is provided to all members about their performance annually Chairs are evaluated on an ongoing basis and undergo a formal evaluation annually by the Director of OPRS and IRB Director in coordination with the Vice President of Research. Performance is assessed according to the same standards as members along with review of their additional responsibilities. Chairs are assessed according to leadership ability, meeting management, engagement in the expedited review process, and effectiveness as representatives of the IRBs. Written feedback is provided to the Chairs annually. Chapter 5: USC Institutional Review Boards (IRBs) USC HRPP Policies and Procedures – 07/2021 Page 85 5.4 IRB Use of Consultants Each IRB may, at its discretion, invite individuals with competence in issues that require expertise beyond, or in addition to, that available on the IRB. The consultants will be provided with the same information that the primary and secondary reviewers receive. Consultants are not counted as “members” in establishing the quorum for each IRB and shall not vote with the IRB. An honorarium for consultants may be provided. The IRB member Conflict of Interest policy also applies to consultants. The IRB prohibits the participation in IRB review of any project in which the member has a conflicting interest, except to provide information requested by the IRB. Refer to Chapter 4.5 – IRB Members and IRB Consultants Conflict of Interest for more information. The consultant may appear in person or provide a written review to the IRB members. Consultant(s) may be asked to attend the meeting for further clarification, if deemed necessary by the IRB Chair or Vice Chair. Key information from the consultant will be included in the IRB meeting minutes and a copy of all documentation will be kept in the study file. 5.5 IRB Support Staff The IRB support staff assists the Chair and Vice Chairs in IRB activities. The support staff is responsible for submitting written correspondence to investigators regarding IRB actions. IRB staff shall document meeting minutes in accordance with federal regulations and guidance. Required documents are listed in Chapter 5.8 – IRB Records. IRB staff may be trained to perform exempt reviews and designated to conduct expedited reviews. IRB staff training may be provided. Staff member training includes taking the CITI education courses, reading the Human Subjects Newsletter/listserv, and learning federal, state, and local regulations, and institutional the policies and procedures. A Bachelor’s Degree or prior IRB experience is required. Annual reviews are conducted to evaluate IRB staff. The IRB staff will be evaluated annually, at the time of budget reviews, by the IRB Chair/Director. The following criteria will be measured: knowledge of the IRB process Chapter 5: USC Institutional Review Boards (IRBs) USC HRPP Policies and Procedures – 07/2021 Page 86 and regulations, continuing training, work attendance, and, overall ability to function as an asset to the IRB. If a staff member is found to be deficient in a particular area or areas, they will be further educated on the IRB process. The evaluation will be reflected in the annual salary determination. IRB Support Staff Duties: • Screen submissions before IRB review • Prepare IRB meeting agenda • Prepare meeting minutes (see “Meeting Minutes” in Chapter 5.8 – IRB Records) • Prepare correspondence • Facilitate review of IRB applications • Customer service • Database and information management • Mentor new IRB staff • Respond to subject concerns • Follow office procedures • Follow IRB policy and procedures and make suggestions/recommendations • Undertake and provide education and training • Intra-institutional relationships • Handle meeting logistics • Review and approve non-material contingencies such as those related to personnel changes (excluding change of PI), punctuation and wording or verification that something missing has been supplied • Preliminary review of initial/continuing review documents (confirm all required documents have been submitted by the investigator, confirm the consent document submitted by investigator matches the one on file, identify issues and concerns for IRB consideration) Chapter 5: USC Institutional Review Boards (IRBs) USC HRPP Policies and Procedures – 07/2021 Page 89 number of votes for each action during the meeting, and documentation of a non-scientist member for each vote. IRB minutes will document when an IRB member knowledgeable about or experienced in working with specific/vulnerable populations was assigned as a reviewer and/or was present for the vote. IRB minutes will document the uses of a consultant present at a convened meeting and include a brief description of the consultant’s expertise. When a convened IRB meeting includes non-members and or guests, the minutes will record the name(s) of all such attendees. Each IRB will keep a roster of all members and, for each action, record which members voted. This document will be kept separate from the distributed minutes. Additionally, IRB staff shall document all meeting minutes according to federal regulations and the requirements listed below. The IRB meeting minutes include: • Confirmation that quorum was maintained for each vote • Attendance for each action • Summary of discussion of controversial issues (if any) and their resolution • Record of IRB decisions (actions taken by the IRB) • Record of voting (including the number of members voting for, against, and abstaining) for each action • The basis for requiring changes in or disapproving research • Names of IRB member(s) recused and not present during the discussion or vote in any research protocol under review and of those who abstain due to conflicts of interest • Description of the materials reviewed for both new and continuing review proposals. Such materials might include the IRB application, clinical protocol, investigators brochure, informed consent form documents, continuing review form, primary reviewer’s evaluation (for continuing review) and any other materials submitted for review • All applicable waivers are discussed and documented (with justification) in the IRB minutes including, waiver or alteration of informed consent and written informed consent Chapter 5: USC Institutional Review Boards (IRBs) USC HRPP Policies and Procedures – 07/2021 Page 90 • Protocol specific determinations on studies involving vulnerable populations (45CFR46 Subparts B, C, D) are documented and justified according to the regulations • Approval period for initial and continuing reviews • Rationale for significant risk/non-significant risk device determinations • If an IRB member has a Conflict of Interest regarding a study being reviewed, they will recuse themselves from the review of the study. The name and reason for absence will be included in the minutes • When an alternate member replaced a primary member and reason for substitution. Minutes from each IRB meeting are distributed to all IRB members, to the Vice President of Research and relevant institutional administration for review according to the Federalwide Assurance. IRB members are required to review the minutes and note any corrections or additions at the first meeting following distribution of the minutes. Records Retained in the IRB Files IRB files contain the following documents and information for each study (45 CFR 46.115(b)): • iStar application • Draft/Approved consent documents • Clinical protocol, including amendments/revisions • Investigators brochure(s) • Scientific evaluations, if any, that accompany the proposals • Funding information • Recruitment materials • Staff and designated reviewer reviews • Amendments • Reportable events Chapter 5: USC Institutional Review Boards (IRBs) USC HRPP Policies and Procedures – 07/2021 Page 91 • Category of approval for exempt, expedited, Full Board (when necessary), and continuing review submissions • Progress reports submitted by investigators • All continuing review activities • Reports of injuries to subjects • Statements of significant new information/findings provided to subjects • Emergency use reports • IRB minutes • Correspondence between the IRBs and investigator Record Retention Requirements Documentation relating to IRB review is kept indefinitely, even when a project is cancelled without subject enrollment. However, research records are maintained for a minimum of three years after completion of the research or as determined by the University’s policy or sponsor requirements and records. Records containing protected health information are retained for at least six years after completion of the research. However, USC, like many institutions, retains IRB records indefinitely. Access to Files IRB records are accessible for inspection and copying by authorized representatives of federal agencies or departments at reasonable times and in a reasonable manner. 5.9 Development, Approval, and Maintenance of IRB Policies and Procedures The USC IRB Policies and Procedures are written and applied according to federal regulations, state laws, university policies, funding agencies and accrediting bodies. To assure continued compliance, the following will be conducted: Chapter 6: Types of IRB Submissions USC HRPP Policies and Procedures – 07/2021 Page 94 Chapter 6: Types of IRB Submissions Chapter Contents 6.1 – Human Subjects Research: What is and What is Not 6.2 – Exempt Review 6.3 – Expedited Review 6.4 – Full Board Review 6.5 – Not Human Subjects Research Submissions 6.6 – Coded Specimens / Data Submissions 6.7 – Just-in-Time (JIT) Submission 6.8 – Humanitarian Use Device 6.9 – International Research 6.10 – Continuing Review 6.11 – Amendments 6.12 – Reportable Events 6.13 – Clinical Trial Progress Reports 6.14 – Difference Between Human Subjects Research and Quality Assurance Research 6.15 – Institutional Research 6.16 – Oral History Research 6.17 – Pilot Studies 6.18 – Research Using Deception USC HRPP Policies and Procedures – 7/2021 Page 95 Chapter 6 Types of IRB Submissions All USC human subjects research projects must undergo review and approval by an IRB prior to initiating research activities. This chapter defines human subjects research, outlines what kind of studies require and do not require IRB approval and details the types of submissions and review. The USC IRBs review all human subjects research activities at USC to determine the appropriate category of review. 6.1 Human Subjects Research: What is and What is Not The initial determination of whether a study is or is not human subjects research is made by referring to the federal (45 CFR 46) definitions of human subjects and research. Any activity that meets OHRP definitions of both “research” and “human subjects” or the FDA definitions of both “clinical investigation” and “human subjects” is considered human subjects research. FDA and DOD have different definitions. What is Human Subjects Research (HSR) Human Subjects Definitions The following are definitions used by OHRP, FDA, and DOD: • OHRP (46.102(e)1-4) A human subject is a living individual about whom an investigator (whether professional or student) conducting research (i) Obtains information or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or (ii) Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens.” Chapter 6: Types of IRB Submissions USC HRPP Policies and Procedures – 07/2021 Page 96 “Identifiable biospecimens” and “identifiable private information”– is a biospecimen or private information for which the identity of the subject is or may readily be ascertained. Intervention includes both physical procedures by which Information or biospecimens are gathered (for example, venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes. Interaction includes communication or interpersonal contact between investigator and subject. Private information includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, information that has been provided for specific purposes by an individual and that the individual reasonably expects the information will not be made public e.g., a medical record). • FDA (21 part 50.3) An individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy human or a patient.” When an investigational device is used on a specimen, the specimen may be considered a “human subject” under FDA definitions. • Department of Defense (DOD) [32 CFR 219.102(f) reference (c)] “Research Involving a Human Being as an Experimental Subject” is: “An activity, for research purposes, where there is an intervention or interaction with a human being for the primary purpose of obtaining data regarding the effect of the intervention or interaction. Examples of interventions or interactions include, but are not limited to, a physical procedure, a drug, a manipulation of the subject or subject's environment, the withholding of an intervention that would have been undertaken if not for the research purpose.” (DODD 3216.02, E2.1.3) Defining Research • OHRP 46.102(l) Research means a systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge. Activities that meet this definition constitute research for purposes of