Operations Manual - Contents Page

The HRPP Operations Manual (OM) is designed to illuminate the system and its overarching governing rules and to serve as a reference for investigators, IRBs, administrators, and others.

Part 1: Introduction, Purpose and Ethical Principles

Describes the scope of human research conducted at the University of Michigan, the mission and purpose of the University’s Human Research Protection Program (HRPP), and the authority and ethical principles under which the HRPP operates.

1. Mission and Purpose of the HRPP
2. Scope of Human Research at the University
   1. Types of Human Research Conducted
   2. Categories of Participants
3. Authority Under Which the HRPP Operates
   1. Institutional Authority
   2. Limitations on Institutional Authority
4. Ethical Principles
5. Protection from Undue Influence

Part 2: Organization of the HRPP

Describes the organization of the University of Michigan’s Human Research Protection Program (HRPP) and the roles and responsibilities of the various units that guide and support the program.  This section also describes the general allocation of resources to the various units involved in the HRPP.

1. Key Organizational Representatives
2. Organizational Entities that Support the HRPP
   1. The U-M Office of Research (UMOR)
      1. Policy Implementation, Communication, and Education
      2. Recordkeeping and Reporting
      3. Monitoring and Oversight
      4. Organization
         1. Leadership of the Human Research Protections Program (HRPP)
         2. Office of Research and Sponsored Programs (ORSP)
         3. Office of Research Compliance Review (ORCR)
         4. IRB Council
         5. eResearch
         6. Research Associate Deans (RADs)
   2. The Academic Units
   3. The Institutional Review Boards (IRBs)
      1. Authority of the University of Michigan IRBs
      2. Primary Responsibility to Human Subjects
      3. Standard Operating Policies, Procedures and Guidance
   4. Other Research Review Units
      1. UMHS Clinical Engineering
      2. Rogel Cancer Center
         1. Clinical Trials Office (CTO)
         2. Protocol Review Committee
         3. Tissue Procurement Service
      3. Conflict of Interest Committees
      4. Michigan Institute for Clinical and Health Research (MICHR)
      5. Institutional Biosafety Committee
      6. Investigational Drug Service
      7. Radiation Safety Service
      8. Research Centers
      9. Additional Units Supporting the HRPP
   5. Independence of Research Review Units and Response to Undue Influence
   6. Resources

Part 3: HRPP Policy

Describes the process by which HRPP policies are developed, approved and implemented, and articulates minimum requirements for IRB standard operating policies and procedures.

1. Introduction
2. HRPP Operations Manual
3. IRB Standard Operating Policies and Procedures
   1. IRB Authority and Guiding Principles
   2. IRB Organization and Personnel
      1. IRB Composition
      2. Use of Consultants
      3. Alternate IRB Members
      4. Educational and Training Activities
      5. Compensation and Liability Coverage
      6. IRB Member Evaluation
      7. IRB Member and Consultant Conflicts of Interest
   3. IRB Review Policies and Procedures
      1. IRB Jurisdiction and Authority
      2. Institutional Approval/Disapproval of IRB Decisions
      3. Submission of IRB Applications and Reports
      4. General Review and Approval Procedures
         1. Determining whether and under what authority the research is regulated
         2. Reviewing IRB applications
         3. Determining frequency of review
         4. Monitoring and verification
         5. Reporting changes in research to the IRB
         6. Preventing lapses in IRB approval
      5. Expedited Review
         1. Applicability criteria and categories
         2. Minor changes
         3. Expedited reviewers
         4. Expedited determinations
         5. Requirements for Continuing Review
         6. Limitations of use
      6. Criteria for IRB Approval
         1. Scientific merit and feasibility
         2. Minimizing risk
         3. Risk-benefit analysis
         4. Equitable subject selection
         5. Informed consent and parental permission
            1. General requirements
            2. Short form consent process
            3. Informed consent waivers, alterations, exceptions, and substitutions
            4. Studies subject to FDA regulations
            5. Studies subject to both HHS and FDA regulations
            6. Studies subject to HIPAA regulations
         6. Data monitoring
         7. Privacy and confidentiality protection
         8. Vulnerable subjects
         9. Test article accountability procedures
         10. Resources
      7. IRBs Reviewing and Monitoring FDA-Regulated Research
   4. IRB Administrative Functions
      1. IRB Meetings
      2. Notification of Decisions
      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

Part 4: Activities Subject to the HRPP

The conduct of human 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 the University’s HRPP or when the requirements of the HRPP are triggered, four questions must be answered: (i) is it human research under the Common Rule; (ii) is it human research under FDA regulations; (iii) is the University of Michigan engaged in the research; and (iv) when does the research begin and end. 

1. Determining What Is and What Is Not Human Research
2. Determining Whether Research Involves Human Subjects
3. Determining Whether the University Is Responsible for IRB Oversight of Human Research
4. Determining When Research Begins and Ends
5. Authority to Make Regulated/Not Regulated Determinations and Notification of Decisions
   1. Authority to Make Human Research/Not Human Research Determinations
   2. Illustrations
   3. Student Practicum and Internships
   4. Notification of Decisions
6. Policy on Exempt Research
   1. Introduction
   2. Categories of Eligibility for Exempt Determination
      1. Federal Exemption Categories
      2. U-M Exemption Categories
   3. Authority to Grant Exempt Status
   4. Notification and Documentation of Exempt Status

Part 5: IRB Jurisdiction and Cooperative Research

Describes the scope of jurisdiction of the various University IRBs and policies on cooperative research and deferred review.

1. Introduction
2. Which U-M IRB
   1. IRBMED
   2. IRB-Health Sciences and Behavioral Sciences
   3. IRB-Flint
   4. General Exceptions
3. Cooperative Research
   1. Engagement in Human Research
   2. Default Position on Outside Entities Engaged in University Research
   3. Researcher and IRB Responsibilities with Regard to Performance Sites not Engaged in Research
   4. Special University IRB Responsibilities for Multi-Site Research in Which the University is Involved
      1. Generally
      2. U-M as a Lead or Operations Coordinating Center
4. Coordinated or Joint Review
   1. IRB of Record
      1. Statement of Principles
      2. Procedures for a U-M IRB to Become IRB-of-Record for Another Institution
      3. Procedures for Ceding Authority to Another IRB
   2. Responsibilities of the HRPP and Local IRB in Multi-Site Research
5. Unaffiliated Investigators
6. Research Involving Community Members in the Research Process

Part 6: Roles and Responsibilities of Investigators and Research Staff

Describes the roles and responsibilities of investigators and research staff engaged in University research.

1. Eligibility to Perform Research at the University of Michigan
   1. Principal Investigator
   2. Co-Investigator
   3. Subinvestigator
   4. Faculty Advisor
   5. Other Key Personnel
   6. Students/Trainees
2. Roles and Responsibilities of Investigators and Research Staff
   1. Principal Investigator
      1. Delegation of responsibilities
      2. Oversight of research team
      3. Knowledge of human research protection standards
      4. Evaluation of the adequacy of resources
      5. Training requirements
   2. Researchers
      1. Minimizing risks to subjects and protecting subject rights and welfare
      2. Obtaining and documenting informed consent
         1. Required general and basic elements of informed consent
         2. Additional elements
         3. Broad consent
         4. Other requirements
         5. Short form consent process
         6. Retention of signed consent
      3. Compliance with IRB and other requirements
      4. Conflict of Interest disclosures
      5. ClinicalTrials.gov registration
   3. Studies Regulated by the FDA
   4. Other

Part 7: Participant Protection

Describes some of the ways research participants are protected under the HRPP.

1. HRPP Protection Extends to All Subjects
2. Data and Safety Monitoring Plans and Boards
3. Payment to Research Subjects
4. Vulnerable Subjects
   1. Research Involving Pregnant Women, Fetuses, and Neonates
      1. Research involving pregnant women or fetuses
      2. Research involving neonates
      3. Research involving, after delivery, the placenta, the dead fetus, or fetal material
      4. Research not otherwise approvable
   2. Research Involving Prisoners
      1. Who is a prisoner?
      2. IRB composition
      3. Additional conditions on research involving prisoners
      4. Permitted categories of research
   3. Research Involving Children
      1. Research involving no more than minimal risk
      2. Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual subjects
      3. Research involving greater than minimal risk and with no prospect of direct benefit to individual subjects
   4. Research Involving Adults with Cognitive Impairment or Otherwise Impaired Decision-Making Capacity
      1. Research involving no more than minimal risk
      2. Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual subjects
      3. Research presenting a greater than minimal risk without the prospect of direct benefit to the indidual subjects
5. Compensation for Injuries
6. Advertising Materials

Part 8: Studies Regulated by the FDA and Use of Investigational Articles

Describes when or under what circumstances an Investigational New Drug application or Investigational Device Exemption is needed; and describes IRB responsibilities with respect to protocols involving investigational test articles.

1. Introduction
2. Research Involving INDs or IDEs
   1. IND Requirements for Research Involving Investigational Drugs or Biologics
      1. Exemptions from IND requirements
      2. FDA guidance
   2. IDE Requirements for Research Involving Investigational Devices
      1. Level of FDA oversight
         1. Significant risk device studies
         2. Non-significant risk device studies
         3. Significant risk/non-significant risk determination
      2. Sponsor role
      3. IRB role
      4. FDA role
      5. Exemption from IDE requirements
3. Expanded Access to Investigational Drugs, Biologics, and Devices
   1. Expanded Access as Research and Clinical Treatment
   2. IRB's Role
   3. Clinician Responsibility
   4. Expanded Access to Investigational Drugs and Biologics for Treatment Use
      1. Open label protocols or open protocol INDs
      2. Group C treatment IND
      3. Parallel track policy
   5. Expanded Access to Investigational Devices
      1. Compassionate use
      2. Treatment use
      3. Continued access
4. Emergency Use of Investigational Articles
   1. IRB Review
   2. Single Use
   3. Informed Consent
   4. Additional Guidance
   5. Emergency Use of Investigational Drugs and Biologics
      1. Clinician responsibilities
      2. FDA guidance
   6. Emergency Use of Investigational Device
      1. Clinician responsibilities
      2. FDA guidance
5. Planned Emergency Research Using Investigational Articles
6. Humanitarian Use Devices (HUD) and Humanitarian Use Exemptions (HDE)
7. FDA Sponsors and Sponsor-Investigators
   1. University/University Employee as Sponsor
   2. Sponsor-Investigator Responsibilites
   3. Clinical Trials Registration
   4. Noncompliance
   5. Manufacturer of Investigational Articles
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
      1. Electronic records
      2. Record retention
   7. Required Reporting
   8. ICH-E6 and GCP
   9. FDA Inspections of FDA-Regulated Research and Related Activities

Part 9: Conflicts of Interest and Commitment

Describes how 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 eliminate or manage conflicts to avoid these negative repercussions.

1. Applicable Policies
2. Conflict of Interest of Investigators and Research Staff
   1. Identification of Significant Financial or Outside Management Interests in 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 Review and Management
   3. IRB Risk/Benefit Analysis
3. Conflict of Interest of IRB Members, Consultants and Staff
4. Institutional Conflicts of Interest

Part 10: Sponsored Research

Describes policies and procedures for the administration of sponsored project agreements for human subjects research.

1. Role of the Division of Research Development Administration
2. Agreements with Sponsors
   1. Assurance of Compliance with Human Research Protection Requirements
   2. Medical Care for Research-Related Injury
      1. Provisions in Sponsor Agreements
      2. Informed Consent Documents
      3. Billing Calendars
   3. Communication of Findings that May Affect the Safety of Research Participants, or Their Willingness to Participate, or Influence the Conduct of Research
      1. Content of Communication Plans
      2. Communicating with Research Participants and IRBs
   4. Dissemination of Findings from the Research
      1. Policy on Disseminating Research Findings
      2. Standard Practice Guide for Implementing Policy
      3. Review/Comment and Delay Provisions
      4. Single Site Study Provisions
      5. Multi-Center Study Provisions
      6. Compliance with Federal Disclosure Requirements
      7. Dissemination to Research Participants
3. Finder Fees and Bonus Payments
4. Additional Information

Part 11: Laws, Regulations, and Standards 

Describes selected laws and regulations impacting human research conducted at the University of Michigan.

1. Legal and Regulatory Bodies
   1. Federal Agencies: Federal Research Laws and Regulations
      1. The "Common Rule"
      2. Department of Health and Human Services
         1. Office of Human Research Protections
         2. Food and Drug Administration
         3. National Institutes of Health, Office of Biotechnology Activities
         4. Office of Research Integrity
         5. Office for Civil Rights
      3. Department of Defense (DoD)
      4. Department of Justice (DoJ)
         1. Research Conducted with the Bureau of Prisons
         2. ​Research Conduct with the National Institute of Justice
      5. ​Environmental Protection Agency (EPA)
      6. Department of Education (ED)
      7. Department of Energy (DOE)
   2. State Governments and Laws:  Other Contractual Requirements
   3. International Research
      1. World Medical Association (WMA)
      2. ICH-GCP
2. Laws, Regulations, and Standards Commonly Applicable to Research
   1. Informed Consent and Legally Authorized Representatives
      1. General Requirements for Informed Consent
      2. Who May Give Consent
         1. Children as subjects
            1. Federal law
            2. Michigan law
         2. Incompetent and incapacitated people
      3. Michigan Law Requiring Special Consent
         1. Breast Cancer Treatment
         2. Electroconvulsive Therapy
         3. Genetic Testing
         4. HIV/AIDS Testing
         5. Pregnancy Termination
         6. Surgery for Mental Health Patients
         7. Terminal Illness
   2. Confidentiality of and Access to Research Records and Other Information
      1. General Research Records
      2. Research Involving Use or Disclosure of Patient Health Information
         1. Information Pertaining to HIV/AIDS
         2. Mental Health Treatment
         3. Substance Abuse Treatment
      3. Research Involving Student Records
         1. Directory Information Exception
         2. Study Exception
      4. Mandatory Disclosure Requirements
         1. Michigan Freedom of Information Act
         2. Public Health Reporting: Disease Surveillance
         3. Mandatory Reporting of Abuse, Neglect, and Violence
            1. Child abuse and neglect
            2. Vulnerable adults
            3. The "Gun and Knife Law"
         4. Court Orders and Subpoenas
      5. Protecting Against Disclosure: Certificates of Confidentiality
   3. Research Involving Prisoners and Other Detained Persons
   4. Research Involving Pregnant Women, Fetuses and Neonates
   5. Stem Cell Research
   6. Document Control and Record Retention and Destruction
      1. Generally
      2. IRB Responsibilities
   7. State Professional Licensing Laws and Institutional Credentialing Policies
   8. Clinical Trials Disclosure Requirements
3. Access to Legal Counsel

Part 12: Quality Assurance and Research Compliance

Describes the University’s quality assurance, quality improvement and research compliance oversight.

1. Quality Assessment and Improvement
   1. Performance Measurement and Quality Assessment
   2. Quality Improvement
2. Reportable Events: Adverse Events, Unanticipated Problems, and Suspension or Termination of IRB Approval
   1. Background
   2. Definitions
      1. Adverse Events (AEs)
      2. Unanticipated Problems
      3. Unanticipated Adverse Device Effect (UADE)
      4. Suspension
      5. Termination
      6. Noncompliance
      7. Serious Noncompliance
      8. Continuing Noncompliance
      9. Allegation of Noncompliance
   3. Roles and Responsibilities for Required Reporting of Reportable Events
      1. Researchers
      2. The IRBs
      3. Reporting Process
   4. Compliance Oversight
      1. Response to Complaints or Allegations of Noncompliance
      2. Noncompliance Review Procedures
         1. Process Summary
         2. Rights of Faculty, Staff, or Others Accused of Noncompliance
         3. Assurance of Appropriate Confidentiality
         4. Policy Against Retaliation for Reporting
      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 Reporting Requirements

Part 13:  Education and Training 

Describes educational resources available at the University and outreach activities to research participants and their communities.

1. Education in General
   1. Required Education
   2. Supplemental Education
2. HRPP Leadership Tracking and Communicating New Developments
3. IRB Chairs, Members, and Staff Education
4. Researchers and Research Staff Education
   1. IRB Educational Activities
   2. MICHR Educational Activities
   3. Additional Educational Activities
5. Research Participants and Their Communities: Engagement, Education, and Outreach Activities
   1. General Research Communications
   2. Research-Specific Communications
   3. MICHR’s Community Engagement Program
   4. UMHealthResearch.org
   5. Additional Community Engagement Initiatives
6. Quality Assessment of Community Outreach Programs