IRBMED Standard Operating Procedures

This section describes the mission of the Medical School Institutional Review Board (IRBMED), the purpose of the IRBMED, the authority under which it operates, and the scope of research conducted at the University.

1. Mission Statement and Organizational Summary
   
2. Scope of Human Research at the University
   
3. Authority under which the hrpp and IRBMED operates
   1. The Public Health Service Act and its amendments
   2. FDA regulations for human subjects protections found in 21 CFR 50…
   3. Rules for research involving recombinant DNA or research otherwise regulated by the National Institutes of Health (NIH)…
   4. Research regulated by the Department of Education (34 CFR 97, 98, 99)
   5. Privacy regulations issued under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 (45 CFR 160 and 164)
   6. Principles stated in International Conference of Harmonization (ICH) Efficacy Guidelines
   7. Additional Governing Laws, Regulations and Other Standards
4. Limitation on Institutional Authority
   
5. Ethical Principles
   
6. Protection from Undue Influence

This section describes the organization of the University of Michigan Medical School Institutional Review Board (IRBMED) and the roles and responsibilities of the various units that guide and support the program.

1. KEY ORGANIZATIONAL REPRESENTATIVES
2. Organizational Entities that Support IRBMED
   1. University of Michigan Office of Research
   2. The Academic Units
   3. Other University of Michigan Institutional Review Boards
   4. Other Research Review and Support Units
   5. Independence of Research Review Units and Response to Undue Influence
   6. Resources

This section describes the process by which the University’s Human Research Protection Program (HRPP) policies, including the IRBMED policies, are developed, approved, and implemented, and articulates minimum requirements for
IRBMED SOPs and Policies.

1. Rulemaking at the University of Michigan is divided three ways…
2. HRPP OPERATIONS MANUAL
3. IRB STANDARD OPERATING POLICIES AND PROCEDURES
   1. General Provisions
   2. Organization and Personnel (Chairs, Members and Staff)
      1. IRB Composition, Rosters, and Meeting Procedures
         1. IRB Chairs and Co-Chairs
         2. IRB Members
         3. IRB Staff
         4. IRB Meetings
         5. IRBMED Meeting Schedules and Format
            1. Meeting Cancellation
            2. Ad Hoc Meetings
            3. Alternate Board Meeting Format
         6. Agendas & Review Items
         7. Convened Meetings
         8. IRBMED Meeting Minutes
            1. Content Requirements
            2. Review and Ratification Process
      2. Use of IRB Consultants
      3. Alternate IRB Members
      4. IRB Educational and Training Activities
         1. Orientation of IRB Members
         2. Orientation of IRB Staff
         3. Orientation of IRBMED Chairs
         4. Continuing Education for IRB Members and Office Staff
         5. Researcher Education
      5. IRB Compensation and Liability Coverage
         1. Compensation of Chairs
         2. Compensation of Committee Members
         3. Periodic Review of Compensation
         4. Liability Coverage
      6. Evaluations of IRB Chairs, Members, Staff and Regular Consultants
         1. Chairs and Member Performance Review
         2. Removal of a Chair or Member from an IRB
         3. IRB Staff Performance Review
         4. Regular Consultant Performance Review
      7. Conflicts of Interest involving Chairs, Members, Consultants and Staff
         1. Financial Disclosures
         2. Conflicts of Interest with Research Involving Chairs and Members
         3. Conflicts of Interest with Research Involving IRB Staff
         4. Conflicts of Interest Involving Consultants
         5. Conflicts of Interest Involving Guests
         6. Conflicts of Interest Involving a Convened Board
         7. Conflicts of Interest Involving Single Member Review and Expedited Review
         8. Conflicts of Interest Involving the Institution
   3. IRB Review Policies and Procedures
      1. IRB Jurisdiction andAuthority
         1. Human Subjects Research Studies Reviewed by the IRB
         2. Authority of the IRB to Approve, Disapprove or Require Modification to a Study
         3. Authority of the IRB to Suspend, Terminate or Place Restrictions on a Study
         4. Not-Regulated projects, Research without U-M Engagement, and Exempt Research
            1. Not-Regulated
            2. Research without U-M engagement
            3. Exempt
         5. International Research
            1. Federally Supported
            2. Non-Federally Supported
            3. IRBMED Requirements
            4. IRBMED Review
            5. Monitoring
      2. Institutional Approval/Disapproval of IRB Decisions
      3. Submission of IRB Applications and Reports
      4. General IRB Review and Approval Procedures
         1. Determining Whether and Under What Authority the Research is Regulated
         2. Reviewing IRB Applications….per 45 CFR 46.111 and 21 CFR 56.111 and 21 CFR 50
            1. Information Required for IRB Review
            2. Review Process / Primary Reviewers
            3. Timeliness of Submissions and Reviews
            4. Notice and Appeal of IRB Determinations
         3. Frequency of Review
         4. Monitoring and Verification by IRB
         5. Reporting Changes in Research to IRBMED (Amendments)
         6. Preventing Lapses in IRB Approval
      5. Expedited Review
         1. Expedited Review of Minor Changes
         2. Expedited Reviewers
         3. Expedited Review Determinations
         4. Requirements for Continuing Review
         5. Limitations of Use of Expedited Review
      6. Criteria for IRBMED Approval [1] [2]
         1. Scientific Merit and Feasibility
         2. Minimizing Risk: 45 CFR 46.111(a)(1)
         3. Risk-Benefit Analysis
         4. Equitable Subject Selection: 45 CFR 46.111(a)(3)
         5. Informed Consent and Parental Permission
            1. General Requirements
            2. Short Form ICD
            3. Informed Consent Waivers, Alterations, Exceptions and Substitutions
            4. Research Subject to Both HHS and FDA Regulations
            5. Research Subject to HIPAA Regulations
         6. Data Monitoring
            1. Considerations for the Imposition of Special Monitoring Requirements
            2. Examples of Special Monitoring Requirements
         7. Privacy and Confidentiality Protection
         8. Vulnerable Subjects
         9. Test Article Accountability Procedures
         10. Resources
      7. IRBMED Review and Monitoring of FDA-Regulated Research
   4. IRB Administrative Functions
      1. IRBMED Meetings
         1. Quorum requirements
         2. Non-scientist and non-affiliated member requirements
         3. Convened board voting procedures
         4. Expedited review or subcommittee review
         5. Conditional approval or deferral
         6. Virtual meetings (refer to the section on Alternate Board Meeting Format)
      2. Notification of Decisions
         1. Written notification
         2. Statement of the reasons in cases of disapproval
         3. Notification of the IO or DIO and other institutional officials
      3. IRB Response to Noncompliance, ORIOs and Other Required Reporting
      4. IRB Records and Reports
   5. Quality Assurance and Quality Improvement
4. OTHER REVIEW UNIT STANDARD OPERATING POLICIES AND PROCEDURES

The conduct of human subjects research triggers a broad array of regulatory and institutional requirements, including advance approval from IRBs and other review units. To determine whether a particular activity is subject to U-M’sHRPP or when the requirements of the HRPP are triggered, four questions must be answered.  First, is it human subjects research under the Common Rule? Second, is it human subjects research under FDA regulations?  Third, is U-M engaged in the research?  And finally, when does the research begin and end? Analysis of these questions is described below and in the decision aids attached to the Appendix.

1. Determining What is and what is not human subjects Research
2. Determining Whether Research Involves Human Subjects
3. Determining Whether the University is Engaged in Human Subjects Research
4. Determining When Human Subjects Research Begins and Ends
5. Authority to Make Regulated/Not-Regulated Determinations (Per the Common Rule and FDA) and Notification of Decisions
   1. Authority to Make Regulated/Not-Regulated Determinations
   2. Illustrations
   3. Student Practicum and Internships
   4. Notification of Decisions
   5. Review of Emergency Use of Investigational Agents
   6. Review of Humanitarian Use Devices (HUD) Under a Humanitarian Device Exemption (HDE)
   7. Non-Research Use of Investigational Products Regulated by the FDA
6. Policy on Exempt Research
   1. Introduction
   2. Categories of Eligibility for Exempt Determination
   3. Authority to Grant Exempt Status
   4. Notification and Documentation of Exempt Status

This section describes the scope of jurisdiction of the various University IRBs as well as policies on cooperative research and reliance agreements for accepting and ceding of IRB oversight.

1. University of Michigan IRB Jurisdiction
   1. IRBMED
      1. Primary Jurisdiction
      2. Exceptions
   2. IRB–Health Sciences and Behavioral Science (IRB-HSBS)
      1. Primary Jurisdiction
      2. Exceptions
   3. General Exceptions
      1. Transfer to another IRB for lack of expertise
      2. Transfer when conflicts of interest preclude a quorum
      3. Transfer by request of a faculty member, staff member, student, or other trainee
      4. Referral to the Vice President for Research or designee for a determination of jurisdiction
2. Cooperative Research
   
3. Reliance Agreements
   
4. IRBMED Resources
   
5. Reviewing IRB Responsibilities
   
6. Relying IRB Responsibilities
   
7. Unaffiliated Investigators
   
8. Community-Based Participatory Research (CBPR)

Every person involved in human research plays a critical role in protecting the rights and welfare of research participants. This section describes the roles and responsibilities of investigators and research staff engaged in University research.

1. ELIGIBILITY TO PERFORM RESEARCH AT THE UNIVERSITY OF MICHIGAN
2. ROLES AND RESPONSIBILITIES OF INVESTIGATORS AND RESEARCH STAFF FOR THE PROTECTION OF HUMAN SUBJECTS
   1. Generally
   2. Key Responsibilities
      1. Minimizing Risks to Subjects and Protecting Subject Rights and Welfare
      2. Obtaining and Documenting Informed Consent
      3. Compliance with IRB and Other Requirements
      4. Conflict of Interest Disclosures
      5. ClinicalTrials.gov Registration
   3. Studies Regulated by The Food And Drug Administration
      1. Generally
      2. Exception from Informed Consent Research
      3. Principal Investigator Responsibilities
      4. Sponsor-Investigator
      5. Manufacturers
      6. Guidelines for Good Clinical Practice (GCP) of the International Conference of Harmonization (ICH)
3. EDUCATION

All non-exempt human research subject to the HRPP is reviewed and must be approved by the applicable Institutional Review Board (IRB) or other duly constituted committee approved by the University of Michigan Office of Research (UMOR), using criteria similar to those applied to federally-funded research and consistent with the principles outlined in the Belmont Report. This section describes some of the ways research participants are protected under the HRPP.

1. HRPP PROTECTION EXTENDS TO ALL SUBJECTS
2. Vulnerable Subjects
   1. Research Involving Pregnant Women, Fetuses, and Neonates
   2. Research Involving Prisoners
      6. IRB Composition
   3. Research Involving Children
   4. Research Involving Adults with Cognitive Impairment or Otherwise Impaired Decision-making Capacity
3. Data and Safety Monitoring Plans and Boards
4. Advertising Materials
5. Payment to Research Subjects
6. Compensation for Injuries

The US FDA enforces the Food, Drug and Cosmetic Act and other laws and regulations governing the use of drugs, biologics, and devices for treatment and in research studies. This section describes when or under what circumstances an Investigational New Drug (IND) application or Investigational Device Exemption (IDE) is needed, and describes IRB responsibilities with respect to protocols involving investigational test articles.

1. Introduction
2. Research Involving INDs or IDEs
   1. Investigational Drugs and Biologics
   2. Investigational Devices
      1. Generally
      2. Significant Risk (SR) / Non-Significant Risk (NSR) Determinations
      3. Device Studies Exempt from IDE Requirements
   3. Humanitarian Use Devices (HUD)
3. Expanded access
   1. Investigational Drugs and Biologics
      1. Treatment INDs
      2. Group C Treatment IND
      3. Open Label Protocols or Open Protocol INDs
      4. Parallel Track Studies
   2. Expanded Access to Investigational Devices
      1. Compassionate Use (Devices)
      2. Treatment IDE
      3. Access (Devices)
4. Emergency Use of investigational articles
5. Planned Emergency Research Using investigational articles
6. Humanitarian Use Devices
7. FDA Sponsors and sponsor-investigators
8. Investigator and IRB Responsibilities for FDA-Regulated Research
   1. Ensuring Review by Appropriate IRB
   2. Verification of IND or IDE Acquisition Prior To Release of Final IRB Approval
   3. Oversight of FDA-Regulated Research
   4. Investigational Article Accountability
   5. Charging for Investigational Articles
   6. Records and Documentation
   7. Required Reporting
   8. ICH-E6 and GCP
   9. FDA Inspection of FDA-Regulated Research and Related Articles
   10. Additional Exceptions
       1. Emergency Use Authorizations
       2. Other Exceptions

Conflicts of interest and commitment in research can adversely impact the integrity of research results and the confidence of prospective volunteers in the research enterprise. The University seeks to identify, disclose, and avoid or manage conflicts to avoid these negative repercussions.

1. Applicable Policies
2. Conflicts of Interest of Investigators and Research Staff
   1. Identification and Disclosure of Outside Interests Related to Human Research
      1. Sponsored Project Proposals
      2. IRB Application
      3. Disclosures First Received by Schools and Colleges Pursuant to COI/COC Policies
      4. Sponsored Project and Technology Transfer Negotiations
   2. Conflict of Interest Review and Management
   3. IRB Risk/Benefit Analysis
3. Conflict of Interest of IRB Members, Consultants, And Staff
4. INSTITUTIONAL CONFLICTS OF INTEREST

This section describes policies and procedures for the administration of sponsored project agreements for human subjects research.

1. ROLE OF THE OFFICE OF RESEARCH AND SPONSORED PROJECTS
2. AGREEMENTS WITH SPONSORS
   1. Assurance of Compliance with Human Research Protection Requirements
   2. Medical Care for Research-Related Injury
   3. Communication of Findings That May Affect the Safety of Human Research Participants or Their Willingness to Participate or Influence the Conduct of the Research
   4. Dissemination of Findings from the Research
3. FINDERS FEES AND BONUS PAYMENTS
4. ADDITIONAL INFORMATION

The University of Michigan and its faculty, staff, and trainees are committed to complying with the laws and regulations that govern the conduct of human research and to upholding the highest ethical standards. This section describes selected laws and regulations impacting human research conducted at UM and the University’s implementation and educational activities to promote compliance with these regulations.

1. Federal Laws, Regulations, and Requirements Commonly Applicable to Research
   1. Federal Laws and Regulations Applicable to Research
   2. Federal Agencies and Additional Federal Requirements Applicable to Research
2. State Laws, Regulations, and Requirements Commonly Applicable to Research
   1. Informed Consent and Legally Authorized Representatives
      1. Who May Give Consent
   2. Confidentiality of and Access to Research Records and Other Information
   3. Mandatory Disclosure Requirements
   4. Additional Protections for Vulnerable Populations
      1. Research Involving Prisoners and Other Detained Persons
      2. Research Involving Pregnant Women, Fetuses, and Neonates
   5. Stem Cell Research
   6. Document Control and Record Retention and Destruction
   7. State Professional Licensing Laws and Institutional Credentialing Policies
3. International Research
   1. World Medical Association (WMA)
   2. International Conference on Harmonisation Good Clinical Practice (ICH-GCP)
   3. The General Data Protection Regulation (GDPR)
4. ACCESS TO LEGAL COUNSEL

This section describes the University’s and IRBMED’s quality assurance, quality improvement, and enforcement activities.

1. Quality assessment and Improvement
2. Reportable Events: Adverse Events, Unanticipated Problems, Non-Compliance, Suspensions and Terminations of IRB Approval
   1. Background
   2. Definitions
   3. Roles and Responsibilities for Required Reporting of Reportable Events
      1. Researchers
      2. The IRBs
      3. Institution
3. Compliance Oversight
   1. Response to Complaints or Allegations of Noncompliance
   2. Noncompliance Review Procedures
   3. How Compliance Concerns Are Brought Forward
   4. Receipt and Initial Handling of Allegations of Noncompliance
   5. Chair and Board Considerations and Determinations
   6. Actions of the HRPP Director as Delegated by the Institutional Official
   7. Response to Determinations of Noncompliance
   8. Institutional Notification and External Reporting Requirements
4. Questions and Contact Information
   1. IRBMED Director and Office
   2. Questions Concerning University Policies and Procedures

This section describes educational and training opportunities offered to IRBMED members, office staff, and researchers and study team members comprising the University research community.

1. EDUCATION IN GENERAL
   1. Required Training
2. TRACKING AND COMMUNICATING NEW DEVELOPMENTS
   
3. Educational Initiatives for the Research Community
   
4. IRBMED Staff Member Education