MSU HRPP Manual Section 8-11

External IRB Submissions

When a non-exempt human research study involves multiple sites that require IRB review, the Michigan State University (MSU) Principal Investigator (PI) may want to request that MSU rely upon an external Institutional Review Board (IRB)’s review of the study. To request reliance, the MSU PI is required to submit a request to the MSU Human Research Protection Program (HRPP) office before a study is submitted to an external IRB for IRB review of MSU’s involvement. A fully executed Institutional Authorization Agreement (IAA) or reliance under the Streamlined, Multisite, Accelerated Resources for Trials (SMART) IRB must be in place and the reviewing external IRB must approve MSU’s involvement in the research prior to MSU’s engagement in the research. See HRPP Manual 1-3, Use of Institutional Authorization Agreements, for more information. The HRPP office will make a reliance acknowledgment letter available to the MSU PI through the MSU IRB online system once an agreement has been signed by both institutions or reliance is ceded under the SMART IRB and approval for MSU’s involvement has been received. Research and/or clinical investigations involving human subjects that engage MSU cannot begin until the MSU PI receives the MSU HRPP acknowledgement letter and as applicable, an executed contract and consent congruency review has been completed and all other applicable requirements and approvals for the study have been met.     

A fee may be charged for each request to use an independent (commercial) external IRB to off-set administrative costs associated with the review process and interactions with the independent external IRB. See the MSU HRPP 5-8, Institutional Review Board Fees, for requirements.

If it is determined during review of an initial study submission that reliance would be more appropriate or is required, the MSU PI will be contacted by the MSU reliance coordinator to submit a request for review by an external IRB.

If the request is for use of a Single IRB at time of the funding proposal, the submission would follow MSU HRPP Manual 2-2-F-iii, Use of a Single IRB (U.S. Department of Health and Human Services, National Institutes of Health) or 2-2-G, Revised Common Rule Single IRB Requirement.

For studies in which the National Cancer Institute (NCI) Central Institutional Review Board (CIRB) serves as the reviewing external IRB, see MSU HRPP Manual 1-5, Use of National Cancer Center Institute Central Institutional Review Board for additional NCI CIRB specific requirements.

For studies in which an independent (commercial) IRB serves as the reviewing external IRB, see MSU HRPP Manual 1-4, Reliance on Commercial IRB for additional requirements when an independent (commercial) IRB serves as the reviewing external IRB.

MSU PI Responsibilities

In addition to the specific responsibilities identified in this document, if an external IRB is designated as IRB of record, the MSU PI is responsible for assuring compliance with the determinations and requirements of the reviewing external IRB. The MSU PI must assure that they and their research team will cooperate as needed in the reviewing external IRB’s initial and continuing review (when required), review of modifications/amendments, recordkeeping, and reporting. All information requested by the MSU HRPP and by the reviewing external IRB will be provided in a timely manner.

Materials Required for Submission

To request IRB review by an external IRB, the HRP-513 - Template - External IRB Request is completed and submitted through the MSU IRB online system. The study submission is assigned a Study number and tracked within the MSU IRB online system.

The following supporting documents must be included whenever applicable:

  • Funding proposals and agreements, including submitted funding proposals, executed contract, subcontract, subaward, or notice of award if primary awardee

  • Reviewing external IRB application or protocol

  • Reviewing external IRB approval letter

  • Informed consent document(s)

Mechanism for Submission

For research studies requesting IRB review by an external IRB, the request must be completed and submitted using the MSU IRB online system. The request must be completed in full; all required questions must be completed.

Pre-Review

The MSU reliance coordinator, or another MSU IRB administrator, will be assigned as the MSU IRB coordinator on all external IRB review submissions. The MSU IRB coordinator will conduct a pre-review of the new external IRB submission. The pre-review includes but is not limited to, determining if the activity is research involving human subjects, whether the study may qualify for exemption, whether an external IRB may be relied upon as IRB of record, and to confirm whether the reviewing external IRB’s institution has an active Federalwide Assurance (FWA). Researchers may be provided comments or clarifications as part of the pre-review process.

Ancillary Review(s)

Ancillary reviewers are assigned to studies that may require additional MSU or other institutional reviews (e.g., hospital partners, biosafety or radiation review, conflict of interest, raffle or drawings), that may utilize MSU resources (e.g., MSU Health Care, Inc., Radiology), or that may be subject to additional federal requirements (e.g. Compliance office for U.S. Food and Drug Administration requirements, Health Insurance Portability and Accountability Act (HIPAA), clinical research billing compliance). These reviews are separate from an IRB review and occur even with reliance upon an external IRB. The ancillary reviewer(s) is assigned to the study by the MSU IRB coordinator. Researchers may be provided comments or clarifications as part of the ancillary review process. If the ancillary review impacts the external IRB, the MSU PI is responsible for communicating that information to the reviewing external IRB or to the PI at the reviewing external IRB’s institution. Depending on the ancillary review type and need, a response may be needed from the ancillary reviewer before an acknowledgement letter can be released.

Study Personnel

The MSU PI is responsible for ensuring the initial and ongoing qualifications of investigators and research staff. This includes assuring that members of the research team have appropriate qualifications and expertise to conduct the research, are knowledgeable about laws, regulations, codes and guidance governing the research, and are knowledgeable about MSU’s policies and procedures that impact the study. All individuals engaged in human subject research activities must receive and maintain current human subject training, must disclose conflict of interest in accordance with the MSU HRPP Manual 10-1, Conflict of Interest, and are subject to MSU HRPP requirements, see MSU HRPP Manual 4-1, Applicability. This includes complying with any conflict of interest management plans that may result.  It is the responsibility of the MSU PI to maintain oversight over all study personnel and to assure and to maintain appropriate tracking that these requirements are met (e.g., documentation of training completion, conflict of interest).

Personnel changes should be reported to the reviewing external IRB as required by the external IRB. Personnel changes do not need to be reported to the MSU HRPP unless any of the following apply:

  • Change in the MSU principal investigator

  • Addition of a non-MSU individual to the study team if:

    • The individual is from an institution that is not already relying on the external IRB or they are not affiliated with any institution, and

    • The change could impact MSU, such as situations where MSU is the awardee institution of external funding or the MSU PI is the lead PI of the study. The lead PI is the individual who has ultimate responsibility for the conduct and integrity of the study.

In such instances, the change must be submitted to the MSU HRPP to determine whether the addition will impact the reliance. Investigators should contact the MSU HRPP with any questions.

Determination of Reliance

The MSU HRPP director is assigned as an ancillary reviewer to review the external IRB submission to determine if MSU can rely upon the external IRB. The MSU HRPP manager may be assigned if the MSU HRPP director is unavailable. See MSU HRPP Manual 1-3, Use of Institutional Authorization Agreements and 1-4, Reliance on External Independent (Commercial) Institutional Review Boards, for considerations when determining reliance upon another institution’s IRB. If the external IRB has already been agreed upon as the Single IRB, that designation will be relied upon unless the proposed study is substantially different than what was originally proposed as part of the Single IRB designation process.

Researchers may be provided comments or clarifications as part of the ancillary review process. A response is required from the MSU HRPP director regarding whether MSU can rely upon the external IRB. If the MSU HRPP director determines that it would not be appropriate for MSU to rely upon the requested external IRB, the MSU IRB coordinator will inform the MSU PI of the determination. The MSU PI may be asked to submit a new study submission to an MSU IRB for review, to rely upon a commercial (independent) external IRB, to identify another external IRB as the IRB of record, or it may be determined that MSU is not engaged in non-exempt human subject research.

If the MSU PI disagrees with the determination, they may request consideration by the MSU Institutional Official (IO). The MSU IO retains final authority to determine whether MSU may rely upon the external IRB.

If the external IRB may be relied upon as the IRB of record for the study, the MSU IRB coordinator will notify the investigator and the external IRB as defined by the agreement.  

Reliance Agreement

A fully executed IAA or reliance under the SMART IRB must be in place and the reviewing external IRB must approve MSU’s involvement in the research prior to MSU’s engagement in the research. See MSU HRPP Manual 1-3, Use of Institutional Authorization Agreements and 1-4, Reliance on External Independent (Commercial) Institutional Review Boards. When appropriate, the MSU IRB coordinator contacts the external IRB to inquire about possible reliance and IAA or use of the SMART IRB Agreement, if not already in contact with the external IRB. The MSU IRB coordinator will obtain the contact information from the reviewing external IRB, when needed.

Consent Review

Even if MSU is relying upon an external IRB, if informed consent will be obtained, the informed consent document must address MSU’s involvement in the study. The MSU IRB coordinator reviews the consent form(s) for local context (if applicable) including whether the subject injury clause is congruent with the contract/subcontract, whether Certificate of Confidentiality or data sharing is applicable (reviewed by the MSU HRPP manager), inclusion of individuals with oversight of research responsibilities in the confidentiality section, and whether costs or compensation is congruent with the contract/subcontract (reviewed by the Compliance Office). The MSU HRPP director and/or MSU HRPP manager will be consulted on any questions about consent language. MSU legal counsel may be consulted when needed.

If the study involves a contract from an external sponsor, the MSU HRPP is also responsible for reviewing the executed contract and the MSU study consent form(s) to assure congruency (e.g., subject injury language). If the contract is not fully executed at the time of the initial request to use an external IRB, the fully executed contract must be submitted so the contract and consent review may be conducted. A finalized contract is required before submitting to an independent (commercial) IRB. If changes to the consent forms are required as a result of the contract review, revised consent forms will need to be submitted to the external IRB for approval. See MSU HRPP Manual 1-4, Reliance on external Independent (Commercial) Institutional Review Boards for contract and consent requirements. See MSU HRPP Manual Section 3-1, MSU HRPP Plan for more information about the contract and consent review process.

MSU requirements related to HIPAA authorizations also apply to external IRB submissions. This includes limitations on combining an authorization for the use or disclosure of protected health information for a research study with a consent document. See MSU HRPP Manual 6-4, Informed Consent and 7-6-A, Individual Authorization.

Submission to External IRB

The MSU PI submits external information as required by the external IRB (e.g., independent IRB, NCI CIRB) and/or coordinates with the Sponsor, Clinical Research Organization (CRO), or PI at the external IRB site to assure that the appropriate IRB documents are submitted to the external IRB to add MSU’s involvement in the study (e.g., new study submission, modification). For independent (commercial) IRBs, the signed HRP-513 - Template - External IRB Request that indicates that MSU HRPP approval to use the independent IRB will be provided to the investigator to include with the independent external IRB submission. A finalized contract is required before submitting to an independent (commercial) IRB. See MSU HRPP Manual 1-4, Reliance on external Independent (Commercial) Institutional Review Boards.

The MSU PI must provide any requested revisions to the consent form(s) to the external IRB for review and approval, or to the Sponsor, CRO, or PI at the external IRB site. The MSU PI also must provide the external IRB with requested information about other local requirements or local research context issues relevant to the reviewing external IRB’s determination, prior to or as part of IRB review. If local policies that impact the external IRB review are updated, the MSU PI is responsible for notifying the reviewing external IRB or notifying the PI at the external IRB site. The MSU HRPP may also provide information about local context when requested by the reviewing external IRB and may provide updates when local laws or policies that impact the local context are changed.

The MSU PI provides a copy of the IRB submission to the reviewing external IRB to the MSU HRPP when the materials are not otherwise accessible to the MSU HRPP. The approval document and the approved consent form(s) must be uploaded into the MSU IRB online system prior to release of the acknowledgement letter.

MSU HRPP Reliance Acknowledgement

The MSU HRPP office will send a notification and make available a reliance acknowledgment letter in the MSU IRB online system once:

  • A reliance agreement that encompasses MSU’s involvement has been fully executed by both institutions (e.g., study specific reliance agreement, SMART IRB Letter of Acknowledgment or via the SMART IRB online system, agreement that the study falls under an already executed Institutional Authorization Agreement), and

  • Approval from the external IRB for MSU’s involvement has been received.

Research and/or clinical investigations involving human subjects that engage MSU (including enrollment of research subjects) cannot begin until the MSU PI receives the MSU HRPP acknowledgement letter and as applicable, the executed contract and consent congruency review has been completed and all other applicable requirements and approvals for the study have been met.   

Data Safety Monitoring Reports

The MSU PI must assure that any data safety monitoring reports that they receive are provided to the reviewing external IRB or to the PI at the external IRB site in accordance with the external IRB’s requirements.

Consent

When MSU researchers are responsible for enrolling research subjects and consent will be obtained, the MSU researchers must obtain, document, and maintain records of consent for each subject or each subject’s legally authorized representative in the manner required by the external IRB.

If any changes are made to the MSU local context in the informed consent document(s) or any informed consent document(s) are added, the MSU HRPP must be notified. Acknowledgement from the MSU HRPP must be received prior to implementation of the revised or new informed consent document(s). 

Reportable Events

MSU researchers are responsible for submitting reportable events to the reviewing external IRB or to the PI at the external IRB site in accordance with the reviewing external IRB’s requirements and timelines. This includes reporting any unanticipated problems involving risks to subjects or others, non-compliance, subject complaints, protocols deviations, or other events as required by the reviewing external IRB and the reliance agreement.

In addition to reporting obligations with the reviewing external IRB, there is still an ongoing obligation to report the following immediately to the MSU HRPP:

  • Any audit (e.g., NIH or FDA)

  • Potential unanticipated problem involving risks to subjects or others

    (UPIRSO)

  • Potential subject complaint

  • Potential serious or continuing noncompliance with the federal regulations or the requirements or determinations of the IRB

  • Suspension or termination of IRB approval

  • Change in MSU principal investigator

  • Additional non-MSU research site(s) or non-MSU personnel in some circumstances  

  • Enrollment of prisoners

  • Potential conflicts of interest for MSU investigators or research staff

  • Changes in funding (e.g. contract amendments, new or additional funding)

  • New consent form(s) or changes to approved consent forms that impact MSU local context consent language

When Reportable New Information is received for an external IRB study, the MSU reliance coordinator will consult with the MSU HRPP director, MSU HRPP manager, and/or MSU IRB chair when needed. The IAA or the SMART IRB Agreement will be reviewed as needed to determine if additional actions are needed.

Continuing Review

Follow-up will be conducted with external IRB studies to assure continuing oversight and approval by the reviewing external IRB. The MSU reliance coordinator will track the expiration of IRB approval (if applicable). When continuing review is required, the MSU reliance coordinator will follow-up via email or through the MSU IRB online system with the MSU PI to confirm the status of the study and the new external IRB expiration date. The email communication will be uploaded into the study’s record in the MSU IRB online system. If the current continuing review approval letter is provided, it will be uploaded into the MSU IRB online system as an Update.

If changes have been made to the MSU local context in the consent form, the MSU reliance coordinator will obtain the renewed approved versions of the consent form(s) and review them to determine if additional actions are needed. If the MSU PI does not indicate that any changes have been made to the MSU local context, no further action is needed and renewed versions of the consent form(s) do not need to be provided.

When continuing review is not required, the MSU reliance coordinator will typically follow-up annually via email or through the MSU IRB online system with the MSU PI to confirm the status of the study (i.e., still open with the external IRB). The email communication will be uploaded into the study’s record in the MSU IRB online system.

If the external IRB transitions the study to the Revised Common Rule (2018 Requirements) and eliminates continuing review, the MSU reliance coordinator will review the IAA (if not under SMART IRB) for language regarding continuing review. The MSU HRPP director will be consulted as needed, and follow-up with the external IRB regarding an amendment to the IAA will occur if needed.

Ancillary reviewers will be added as needed.

Research Sites

Any research site(s) that will be engaged in research and/or clinical investigation with human subjects that are in addition to those initially approved with the external IRB must be submitted to the MSU HRPP if the change could impact MSU. Changes that could impact MSU include situations where MSU is the awardee institution of external funding or the MSU PI is the lead PI of the study. The lead PI is the individual who has ultimate responsibility for the conduct and integrity of the study. In such instances, the MSU HRPP needs to determine whether the addition will impact the reliance. Investigators should contact the MSU HRPP with any questions.

Updates

The MSU PI is responsible for reporting promptly to the reviewing external IRB any proposed changes to the research, or for collaborating with the PI at the external IRB site to promptly report to the reviewing external IRB any proposed changes. The MSU PI cannot implement changes to the research (including changes in the consent document) without prior external IRB review and approval, except where necessary to eliminate apparent immediate hazards to the subjects.

The MSU reliance coordinator may create an Update in the MSU IRB online system for an external IRB study to enter information or at the request of the MSU PI.

A new informed consent document must be submitted to the MSU HRPP as an update before its implementation to assure that MSU local context requirements are included.

Ancillary reviewers will be added as needed. The MSU reliance coordinator will consult with the MSU HRPP director and/or MSU HRPP manager when needed.

Review by Other MSU Officials

For an external IRB study that is subject to a reliance agreement, MSU officials may not approve the research subject to the reliance agreement if it has not been approved by the reviewing external IRB.

Site Visits

The MSU HRPP Compliance office conducts post approval site visits for certain IRB approved studies. This includes studies reviewed by an external IRB. The site visits may be conducted in addition to, or in cooperation with, the reviewing external IRB, when appropriate. See MSU HRPP Manual 8-10, Site Visits, for more information.

Closure

Studies reviewed by an external IRB may be closed when either the study is closed with the external IRB or a modification is approved by the external IRB that indicates MSU is no longer engaged in research with human subjects.

The MSU PI should notify the MSU HRPP when the study may be closed and upload the closure letter or modification approval letter into the external IRB study in the MSU IRB online system.

The MSU reliance coordinator will review the information to confirm that the study may be closed. If the study may be closed, the study record will be closed in the MSU IRB online system.

Record Retention

All records relating to the research must be appropriately managed and retained, including for external IRB studies. See MSU HRPP Manual 4-7-A, Recordkeeping for Investigators, for more information.

Questions

Researchers and research staff who want to obtain answers to questions, express concerns, and convey suggestions regarding the use of the external IRB should contact the MSU reliance coordinator. The MSU HRPP director may also be contacted with programmatic inquiries. Contact information is available on the MSU HRPP website.

Approved By

Vice President for Research and Innovation on 12-13-2021. Revision 1 approved by Associate VP Research Regulatory Support on 2-13-2024.

This policy and procedure supersedes those previously drafted.

Related HRPP Manual Sections