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Operations Manual - IRB Jurisdiction and Cooperative Research

Operations Manual - Part 5

[Operations Manual Table of Contents]

I. INTRODUCTION

The University of Michigan (U-M) has registered nine Institutional Review Boards (IRBs) under its Federalwide Assurance (FWA) with the U.S. Department of Health and Human Services (HHS). Two (collectively referred to as IRB-Health Sciences and Behavioral Sciences (IRB-HSBS)), are operated by the U-M Office of Research and review health, behavioral, and social science research outside the University of Michigan Health System (UMHS). One IRB (IRB-Flint) reviews research from the U-M Flint campus; another (IRB-Dearborn) reviews research from the U-M Dearborn campus. Five IRBs (collectively referred to as IRBMED) review UMHS research, research involving investigational drugs, biologics, or significant risk devices, and select aspects of research conducted by the Functional MRI (fMRI) Laboratory. This section of the Operations Manual (OM) describes the scope of jurisdiction of these various University IRBs and outlines University policies on cooperative research and authorization agreements.

II. WHICH UNIVERSITY OF MICHIGAN IRB

The guidance below describes in more detail default IRB jurisdiction and principles underlying common exceptions to those defaults. It also describes the procedures to follow in determining jurisdiction in unusual cases. Special circumstances, such as the need for additional expertise during IRB review or the involvement of UMHS patients or facilities, will warrant the transfer of oversight of a project from the IRB that would normally review and monitor it to another University IRB. For any transfer, the receiving IRB will be provided with all information associated with the review by the original IRB via eResearch. 

A. IRBMED

1. Primary Jurisdiction

  • All research proposed by faculty, staff, students or trainees affiliated with the Medical School or the UMHS
  • All research using the patients, medical records, or facilities of the University of Michigan Hospitals and Health Centers
  • All research where the results will be submitted to the U.S. Food and Drug Administration (FDA) as part of an application for a research or marketing permit. This includes research involving investigational drugs, biologics or significant risk devices.
  • All clinical investigations conducted by School of Dentistry
  • Any research involving invasive techniques, such as deep muscle biopsies by the School of Kinesiology
  • Research using the fMRI Laboratory

2. Exceptions

By agreement of the IRBs, some categories of exempt research are reviewed by IRB-HSBS.

B. IRB-Health Sciences and Behavioral Sciences

1. Primary Jurisdiction

All research conducted by the faculty, staff, students or other trainees with a primary appointment in U-M Ann Arbor schools, colleges, units or programs not subject to IRBMED jurisdiction. These include but are not limited to:

  • U-M Institutional Research
  • College of Architecture and Urban Planning
  • College of Engineering
  • College of Literature, Science, and the Arts
  • College of Pharmacy
  • Institute for Social Research (ISR)
  • Ford School of Public Policy
  • Law School
  • Mary A. Rackham Institute
  • Rackham Graduate School
  • Ross School of Business
  • School of Dentistry
  • School of Education
  • School of Information
  • School of Music, Theatre, and Dance
  • School of Natural Resources and Environment
  • School of Kinesiology
  • School of Nursing
  • School of Public Health
  • School of Social Work
  • Stamps School of Art and Design
  • University Health Services
  • University of Michigan Transportation Institute (UMTRI)

2. Exeptions

By agreement with IRBMED, qualifying principal investigators (PIs) with a primary appointment to IRB-HSBS may submit fMRI protocols to IRB-HSBS for review under the terms of the IRBMED-approved Master Protocol.

C. IRB-Dearborn

1. Primary Jurisdiction

All research conducted by faculty, staff, students or other trainees with a primary appointment at U-M Dearborn.

D. IRB-Flint

1. Primary Jurisdiction

All research conducted by faculty, staff, students or other trainees with a primary appointment at U-M Flint.

E. General Exceptions

  1. In any case where the IRB with primary jurisdiction does not have the appropriate expertise or is not appropriately constituted (e.g. prisoner representative) to review a research proposal, the project may be transferred to the IRB with appropriate expertise for review and approval. 
  2. In those instances in which conflicts of interest preclude a quorum for review, the project may be transferred to an alternate IRB with appropriate expertise for review and approval. The selection of an alternative IRB will be made by the chair of the referring IRB in consultation with the receiving IRB, if the chair does not have a disqualifying conflict. If the chair has a disqualifying conflict of interest, the Vice President for Research (VPR) or designee will make the selection.
  3. In those instances in which another IRB or a faculty member, staff member, student, or other trainee requests review by an alternate U-M IRB, the chair will review the reasons for such a request; and if appropriate, consult with the other IRBs; and decide which IRB shall review. The VPR may overrule a chair’s refusal to refer an application to another U-M IRB.
  4. In rare instances, in which the rules below do not clearly define which IRB to use and the chairs cannot agree on jurisdiction, the matter may be referred to the IRB Council for a determination.

The IRB is also authorized, in its discretion, to invite individuals with special expertise to assist in the review of issues that require expertise beyond or in addition to that available on the IRB. These individuals will identify any conflicts of interest to the IRB and they may not vote with the IRB.

III. COOPERATIVE RESEARCH

Researchers at the University of Michigan frequently interact with entities or individuals outside the University. The types of relationships are too numerous to list, but they may include:

  • Purchasing goods or contracting for commercial services;
  • Establishing research collaborations by subcontract from or to the University;
  • Serving as the coordinating site for a multi-center clinical trial being conducted elsewhere or serving as a performance site in a multi-center clinical trial;
  • Conducting research at clinics, schools, etc., where the outside site provides only access or where the outside site has or will have name-linked research data;
  • Conducting research in another country, but not in partnership with an established entity in that country, and establishing relationships with individuals, such as volunteer research assistants, who will provide services.

The University’s (and its researchers’) regulatory obligations and alternatives for addressing them differ depending on the relationship with the entity or individual outside the University in the context of the research project. In analyzing the many types of relationships that exist between the University and its researchers, on one hand, and outside entities or individuals, on the other, a primary distinction can be made between those that are “engaged” in human research versus those that are not engaged. This distinction is important because each engaged institution is responsible for safeguarding the rights and welfare of human subjects and for complying with applicable laws and regulations (including the Common Rule, as appropriate) and with its own HRPP policies and procedures. 

The VPR has implemented the policies described below and in Part 3 of this OM to ensure that the University can fulfill its affirmative obligation to assure appropriate oversight of research in which the University is “engaged” and also, under certain circumstances, of other “engaged” entities associated with University research.

A. Engagement in Human Research

A performance site becomes “engaged” in human research when its employees or agents intervene or interact with living individuals for research purposes, including obtaining informed consent, or obtain individually identifiable private information for those purposes. A performance site is always deemed to be “engaged” in human research when it receives a direct grant or other award to support the research. A performance site is “not engaged” in human research if its employees or agents do not intervene or interact with living individuals for research purposes, or obtain individually identifiable private information for those purposes.

See Part 4 of this OM and the OHRP guidance on engagement of institutions for additional guidance.

B. Default Position on Outside Entities Engaged in University Research: Avoid Duplicate Review

The University’s default position on research performed at multiple locations is that each may review and approve its own participation in the research but, when possible, an IRB Authorization Agreement should be used to avoid duplicate review. When the overall PI of research conducted at multiple locations is affiliated with the University, or the University is otherwise involved as the primary or coordinating center, the PI must assure the University IRB reviewing the research that each performance location involved in the research has requested an Authorization Agreement or that the research has been properly approved at that location before the research is initiated there and must notify the University IRB if any lapse or other change in approval status occurs. The IRB may take any steps it deems appropriate to verify the information provided by the PI.

The circumstances under which the University will agree to serve as IRB-of-Record for other engaged sites or to cede review of University research to other IRBs are described below in section IV.

C. Researcher and IRB Responsibilities with Regard to Performance Sites not Engaged in Research

When a performance site is not engaged in research, it is the responsibility of the PI to assure that the site’s facilities and resources are appropriate for the nature of the activities that will be conducted there. It is also the responsibility of the PI to notify the IRB promptly if a change in research activities changes the performance site’s engagement in research.

IRBs may ask investigators to submit statements from entities providing research services or site access but not “engaged” in research to provide evidence of permission by those entities for their involvement. The investigator may begin research activities at each site as it is approved by the IRB. Performance sites may be added to a research study with the submission of an amendment and the appropriate documents to the IRB for review and approval prior to beginning research activities at the new performance sites.

D. Special University IRB Responsibilities for Multi-Site Research in Which the University is Involved

1. Generally

IRBs whose jurisdiction typically extends to research in which the University is one of multiple engaged sites must have a method to:

  • Determine when other IRBs are involved;
  • Define their respective responsibilities in connection with the research;
  • Communicate as appropriate with the other involved IRBs; and
  • Notify investigators of any special expectations with regard to the conduct of multi-site research.

This may be accomplished through any combination of standard operating procedures (SOPs), application forms, formal and informal guidance, inter-institutional agreements, and other communications. For example, the University IRB should determine prior to the initiation of research how it will solicit and review reports of unanticipated problems involving risks to subjects or others, regardless of location, when those risks may have an impact on any matter within that IRB’s jurisdiction.

2. University of Michigan as a Lead or Operations Coordinating Center

In general, the Lead Site (also referred to as the Lead Coordinating Center (LCC) or Clinical Coordinating Center (CCC)) has the ultimate responsibility for providing administrative oversight, management of data, and the provision of organizational support in the conduct of a multi-site research project. If a U-M faculty is designated as the Lead Site PI for the conduct of a multi-site research project, the IRB will require additional information to ensure there is appropriate regulatory oversight and management and may suggest the submission of a separate Coordinating Center application in eResearch. Information reviewed by the IRB will include, but is not limited to, the following:

(a) Regulatory Documentation

The Lead Site PI must submit a plan to the IRB for managing the regulatory documentation (e.g. informed consent, protocol amendments, site IRB approvals, etc.) from each of the participating sites. The Lead Site PI must also require each participating site to maintain and manage its own regulatory documentation according to their institutional policies and procedures. The Lead Site PI is also responsible for creating a manual (or other relevant documentation), for example, a Manual of Operations binder, which contains all the information required by each individual site to complete the study. This manual will be shared with each site.

(b) Participating Site Communication Plan

The Lead Site PI must describe the plan for documented communications between the participating sites and the LCC/CCC. Communications may include information on changes to the regulatory documentation (research protocol, informed consent, etc.), interim analysis on the progress of the research project, or safety reporting.

(c) Reporting of Serious Adverse Events and Unanticipated Problems

The Lead Site PI is responsible for the development, collection, and maintenance of a plan to review, in a timely fashion, all serious adverse events and unanticipated problems. The Lead Site is responsible for meeting the reporting timelines to the IRB as described in the research protocol, as well as, monitoring the participating sites reporting obligations to their own IRB and the U-M Lead Site.

(d) Data Collection and Analysis (Data Coordinating Center (DCC))

The Lead Site PI is responsible for either the development of case report forms (CRFs), or other data collection instruments, or delegating the task to another site (DCC). The Lead Site PI is also responsible for managing retention of documents according to institutional or sponsor policies and procedures. If the Lead Site PI also has the responsibility of data coordination, then he/she should submit a separate application in eResearch for the functionality of the DCC and provide the IRB with a plan for the review of the study data and the submission of any required interim analysis results sent to participating sites.

(e) Participating Site Training

The Lead Site PI should confirm that all participating sites have received appropriate human subjects research training for the conduct of the project and understand the regulatory reporting requirements. In general, the Lead Site PI should ensure that the participating sites are familiar with the research project design and procedures, reporting of serious adverse events (SAEs) and unanticipated problem(s), administration and documentation of study drug or device dispensation, compliance monitoring, and record retention.

(f) Additional Responsibilities

The Lead Site PI should also determine the plan for delegation of authority within the study team and the participating site(s), for ongoing project management as necessary. The Lead Site PI is responsible for ensuring appropriate IRB approval is obtained by sites prior to initiation of the project at that site.

IV. COORDINATED OR JOINT REVIEW

For federally funded research, an institution with an FWA that is participating in a cooperative project may enter into a joint review arrangement, rely upon the review of another qualified IRB, or make similar arrangements for avoiding duplication of effort. The University permits similar arrangements for non-federally-funded research. In either case, the VPR or designee must approve the arrangement for either individual studies or categorically (e.g., Master Agreements with commercial IRBs). Any coordinated or joint review effort requires a written agreement among the involved institutions, regardless of whether they maintain FWAs.

Note: See FDA Policy on "Non-Local IRB Review" for additional guidance on cooperative research and reliance on non-local IRBs for approval of FDA-regulated research.

A. IRB-of-Record

An IRB is considered the IRB-of-Record when it assumes IRB responsibilities for another institution. In appropriate circumstances, the University will consider becoming the IRB-of-Record for the engagement in research by an outside entity or ceding authority for review and oversight of University research, in whole or in part, to an outside IRB. Such a review-sharing arrangement requires a formal agreement between the institutions approved by the Institutional Official(s) (IOs) or their designee(s).

The VPR has delegated authority for approving IRB authorization agreements to the HRPP Director.

IRBs have a central role in determining whether proposed arrangements preserve and promote protections for human participants in research for which they have responsibility, and, thus, are acceptable. Conflict of Interest Committee review is also triggered via the eResearch application process.

1. Statement of Principles

Under certain circumstances the University will agree to become the IRB-of-Record for research conducted at another entity or allow another institution's IRB to serve as IRB-of-Record for University research. The University will not normally provide IRB-of-Record services for research in which the University is not engaged or in which its investigators are not otherwise involved. Nor will the University provide IRB-of-Record services for research over which the University does not feel it can appropriately address the local context or otherwise exercise adequate oversight.

2. Procedures for a University IRB to Become IRB-of-Record for Another Institution

Requests for U-M IRB-of-Record services may arise by request from an outside entity to the Office of Research and Sponsored Projects (ORSP), to one of the IRBs, or to the U-M Office of Research (UMOR). They also may arise by petition from a U-M investigator as the investigator pursues a research design with external collaborators or performance sites.

Upon receiving a request for IRB-of-Record services, the IRB reviewing the request must decide whether it wishes to accept the obligation. In such a review the IRB should consider any relevant information including, for example:

  • The time and resources required to accept the review, given other demands;
  • The expertise required for initial and continuing review;
  • The ability to comply with requirements for "local" knowledge of the research context at the outside organization and any research sites;
  • The resources, ability, and willingness of the outside organization, the PI, and the research sites to handle complaints, review adverse events, and to monitor compliance with applicable laws and regulations and IRB requirements; and
  • The ability and willingness to comply with any additional requirements the outside organization may impose on the U-M review.

If the U-M IRB agrees to accept the responsibility, the HRPP Director will prepare a recommendation based on the IRB’s willingness to provide services and any other relevant institutional-level factors, including the ability to manage any potential conflict of interest. An arrangement to accept responsibility as the IRB-of-Record must be documented in a written agreement under which the respective responsibilities of the two organizations will be described. An inventory of such agreements is maintained by the HRPP.

3. Procedures for Ceding Authority to Another IRB

Although inquiries may arise first in UMOR or ORSP, requests to cede U-M IRB authority to the IRB associated with another entity, to a commercial IRB, or to a central IRB generally arise in U-M IRB offices in the context of IRB review of projects under their jurisdictions. Requests typically involve oversight of a single project.

First review of a request to cede authority resides with the U-M IRB with jurisdiction. Among the considerations involved in review of a request to cede authority are the following:

  • The reduction of regulatory and administrative burden by ceding review to an external IRB;
  • The appropriateness of the external IRB to review local context; qualifications of the IRB to which the review will be ceded (with due consideration given to such objective factors as accreditation status); and level of confidence in its review and determinations; and
  • The proposed arrangements for the U-M IO and U-M IRB normally having jurisdiction to monitor the outside review and oversight.

The U-M IRB with jurisdiction will notify the HRPP Director of its decision or recommendation. If the U-M IRB with jurisdiction has declined the request to cede authority, the IRB will so notify the requestor. If the U-M IRB with jurisdiction recommends approval, the HRPP Director will further review the request. If the HRPP Director disapproves the ceding request, the U-M IRB will so notify the requestor. If the HRPP Director approves the ceding request, he or she will arrange for a formal agreement between the University and the entity in which the external IRB resides, under which the respective responsibilities of the two organizations will be described.

B. Responsibilities of the HRPP and Local IRB in Multi-Site Research

Even when the University or another institution serves as IRB-of-Record for multi-site research, each organization remains responsible for maintaining a system to protect human research participants. The ceding institution retains ultimate responsibility for safeguarding the rights and welfare of human research subjects involved at its performance site and for educating members of its research community to establish and maintain a culture of compliance with applicable laws and regulations and with institutional policies relevant to the protection of human research participants. The ceding institution also remains responsible for implementing appropriate oversight mechanisms to ensure compliance with the determinations of the reviewing IRB. Thus, for example, a U-M performance site may be subject to not-for-cause compliance reviews and for-cause inspections through the University’s HRPP even if oversight of the project has been ceded to an outside IRB.

V. UNAFFILIATED INVESTIGATORS

Researchers engaged in federally-funded, U-M-initiated or U-M-centered research who are not employees of the University and not agents of an outside entity that can provide IRB review must sign an “Individual Investigator Agreement” to assure that they understand their obligations as performers of human research (the IRB may grant an exception in cases involving literacy or technology constraints.) See Guidance on Extension of an FWA to Cover Collaborating Individual Investigators and Introduction of the Individual Investigator Agreement.

For non-federally-funded research, unaffiliated investigators generally are required to sign an “Individual Investigator Agreement” but may be granted an exception by the IRB in limited cases. See the flow diagrams for IRB authorization agreements and individual investigator agreements.

VI.  RESEARCH INVOLVING COMMUNITY MEMBERS IN THE RESEARCH PROCESS

In specified studies, PIs may provide members of local communities with opportunities to assist in the development of the research protocol and study materials, implementation of the research, and dissemination of the research results. Community members engaged in the research and participating on a U-M study team sign an agreement that outlines their roles and responsibilities, identifies training and reporting requirements, and specifically indicates that any modifications to the research must be communicated to the U-M PI and approved by the IRB before implementation (See OM Part 5, Section V for information about unaffiliated investigators).

When reviewing these studies, IRBs should consider whether the community members are provided with sufficient training to perform the research functions and whether there is a clear communication plan between the community members and the PI to convey information about the conduct of the study as well as any adverse events or unanticipated problems that may have been encountered.

When community members are both study team members and subjects, IRBs should examine the study protocol and informed consent materials to ensure that there is a clear delineation between each role, attendant expectations and risks, and whether community members have been provided with sufficient information to understand the voluntary nature of each role. IRBs should ensure that community members in this dual role have been provided the contact information for the IRB in order to ask questions about their rights as a study team member and/or a subject.