HRPP Manual Section 6-9-F

Special Considerations: 
Multiple Research Sites When MSU is the Lead

This policy applies to non-exempt human subject research conducted at external sites where the Michigan State University (MSU) Principal Investigator (PI) is responsible for the overall conduct of the study (e.g., lead researcher in a multi-site study, primary awardee of an externally sponsored activity). External sites are considered to be locations external to Michigan State University (MSU) (e.g., not on MSU campus, not within an MSU facility, location not under the jurisdiction or control of MSU) or are external institutions that are engaged in human research or that otherwise require IRB approval. The Institutional Review Board (IRB) staff, IRB member, or IRB chair determine whether an external site is engaged in the research using the U.S. Office for Human Research Protection (OHRP) guidance, “Engagement in Research.”

There are different requirements based on whether the external site is engaged in the human subject research led by an MSU investigator. MSU PI conducting research at external sites that are not considered engaged in the research project may be required by the IRB to provide information to the IRB about communication with the site, when appropriate. Before any human research at the site begins, the MSU PI must obtain permission to allow research to be conducted at each site as appropriate (e.g., hospital impact statements).

When an MSU PI responsible for the overall conduct of the study plans to conduct human subject research at an external site(s) that is engaged in the research, communication with the engaged external site(s) is important for the protection of human research subjects. The investigator must provide sufficient information to the IRB about the engaged external sites to enable this communication. In addition, the site may require IRB review as a part of their institutional requirements, even when the institution would not be considered engaged using the OHRP guidance, and the responsibilities described below would become applicable to the activity. The requirement for Single IRB review may also apply to these multi-site collaborative studies. See HRPP Manual 2-2-F-iii" “Use of a Single IRB (U.S. Department of Health and Human Services, National Institutes of Health)” and 2-2-G “Revised Common Rule Single IRB Requirement.” If an External IRB is serving as the Single IRB, the External IRB may have requirements in addition to those described below.  

When an MSU PI is responsible for the overall conduct of a multi-site study, the MSU PI is responsible for coordinating among the sites to assure that human research protection requirements are met. Such coordination should include, but is not limited to, the following requirements and considerations:

  1. Obtain IRB approval from MSU or submit a request for MSU to rely upon an External IRB. See HRPP Manual 1-3 “Use of Institutional Authorization Agreements” or 1-4 “Reliance on External Independent (Commercial) Institutional Review Boards.”

  2. When MSU is the IRB of record, within the MSU IRB online system:

    1. List engaged sites external to MSU and whether they are conducting their own external IRB review or relying on an MSU IRB.

    2. List engaged external key personnel as external team members. See HRPP Manual 4-10 “Designation as Key Project Personnel on Non-Exempt IRB Projects.”

  3. Obtain any other site-specific permission to allow research to be conducted at each site as appropriate (e.g., hospital impact statements, credentialing).

  4. If Single IRB does not apply to the study, ensure IRB review is obtained at engaged external sites unless other appropriate reliance arrangements are made.

    1. If the local IRB will review the research study, provide MSU IRB with an approval letter(s) from that site.

    2. If the institution chooses to rely on the MSU IRB for review, there must be a fully executed Institutional Authorization Agreement or reliance under the SMART IRB agreement, unless an individual investigator agreement may be used. See the Human Research Protection Program (HRPP) Manual 1-3 “Use of Institutional Authorization Agreements” for requirements.

  5. When appropriate, collaborate with the site to obtain a Federalwide Assurance (FWA) or work with the site to obtain Individual Investigator Agreements.

    1. When an MSU investigator works with an external engaged site on a research study and there is an expectation for that site to do research again and the research is federally funded or otherwise requires an FWA, the site must obtain an FWA.

    2. When an MSU investigator works with an external engaged site on a research study and there is an expectation for that site to do research again but the research is not federally funded or otherwise does not requires an FWA, the site does not need to obtain an FWA.

    3. When there is no expectation for the site to do research again or the research is not federally funded or does not otherwise require an FWA, when MSU is the IRB of record, the MSU HRPP will work with the MSU investigator to obtain Individual Investigator Agreements for individuals engaged in the research at the external institution, unless the external site requests an Institutional Authorization Agreement. Investigators do not have signatory authority to sign the agreements for MSU. IRB staff will complete this type of agreement if necessary to be signed by the individual who is engaged in research. Contact the IRB staff for more information.

  6. Collaborate with each site to ensure all investigators and research staff at all sites have required human subjects training and other training as needed. See HRPP Manual 11-1-A “Education: Investigators and Research Staff” for MSU requirements.

  7. Develop a plan to manage information that is relevant to the protection of subjects with all research sites, such as:

    1. Develop a mechanism of reporting and responding to, unanticipated problems, adverse events, potential noncompliance, suspension or termination of IRB approval, and complaints from all sites.

    2. Develop a mechanism of coordinating information and applications for all modifications and continuing reviews (when required) at all involved IRBs or with the Single IRB.

    3. When there are site specific requirements (e.g. local context information in the informed consent), develop plans to assure that site specific document(s) are approved by the IRB before use and that any modification to the site specific document(s) is approved by the IRB before the changes are implemented.

    4. Develop a plan for management of interim results.

  8. Develop a plan to assure that records relating to the research are retained as required by law, regulation, contract, or other requirements. See HRPP Manual 4-7-A “Recordkeeping for Investigators” for MSU requirements.

    1. If sites will be obtaining informed consent from subjects, develop plans to assure that all signed consents are appropriately and securely maintained to maintain confidentiality.

    2. Develop plans with sites to assure that records relating to the research are accessible for inspection at reasonable times and in a reasonable manner (e.g. site visit from the MSU Human Research Protection Program, audit from federal department or agency conducting or supporting the study, audit from the U.S. Food and Drug Administration (FDA) when the study is regulated by the FDA).

  9. When appropriate, develop a data safety monitoring plan. See HRPP Manual 6-7 “Data and Safety Monitoring” for requirements.

  10. If human biospecimens are transported, shared, exchanged, or transferred:

    1. Arrange for Material Transfer Agreements when needed. Consult with the MSU Innovation Center for requirements as needed.

    2. Arrange for secure and appropriate transport. Consult with MSU Biosafety Office for requirements as needed.

    3. Arrange for appropriate storage and security.

    4. Develop a confidentiality plan (e.g., to protect identifiers, if any).

  11. If protected health information are accessed at sites that are subject to Health Insurance Portability and Accountability Act (HIPAA) requirements:

    1. Ensure that an approved HIPAA Authorization Form or Waiver of Authorization is granted. Consult with MSU HRPP Compliance Office and/or the covered entity for requirements as needed.

    2. Work with sites to ensure authorization or waiver.

  12. Develop plans for data security at all sites, including transfer of data when applicable.

    1. Physical materials – locked file cabinets, limited access, use of laptops, etc.

    2. Electronic data – passwords, encryption, firewalls, access, storage, etc. Protect data stored on removable media using encryption. Consult with MSU IT for requirements as needed.

    3. Arrange for Data Use Agreements when needed. Consult with the MSU Innovation Center for requirements as needed.

    4. Establish reasonable administrative, technical, and physical safeguards to prevent unauthorized use or disclosure of data.

  13. If a central database or repository will be used among the sites, develop a plan for a secure central database when applicable. Consult with MSU IT for requirements as needed.

    1. Secure data transmission or transportation.

    2. Security parameters for central database.

    3. Limited access to identifiable data.

    4. Who has access to data for research purposes and in what form. (e.g., anonymous).

When there is reliance with another institution, the IRB staff communicates with the engaged external sites in order to fulfill requirements stipulated in the Institutional Authorization Agreement or SMART IRB agreement with the external IRB, e.g., provide copies of relevant IRB determinations regarding approval, continuing review (when required) including protocol modifications, interim results,  unanticipated problems involving risks to subjects or others, suspensions, terminations, closure, required modifications, reports to government agencies, etc.

When the study is reviewed by the MSU IRB:

  1. The IRB chair, IRB staff, IRB reliance coordinator, HRPP manager, or HRPP director may communicate with the engaged external sites, investigators, and/or IRBs, in order to:

    1. Obtain information regarding reports of potential unanticipated problems, noncompliance, termination or suspension, and emergency use of investigational drugs or devices.

    2. Coordinate corrective action plans as necessary.

    3. Fulfill any other activity necessary to protect research subjects.

  2. The IRB evaluates the PI’s plan for the management of information that is relevant to the protection of human subjects to determine whether the plan is adequate.

Additional Considerations

For research studies subject to the requirements of the U.S. Department of Defense, see HRPP Manual 2-2-A “U.S. Department of Defense.”

This policy and procedure supersedes those previously drafted.

Approved By: Vice President of Research and Graduate Studies, 4-4-2007. Revision 1 approved by VP Research & Graduate Studies on 3-9-2008. Revision 2 approved by VP Research & Graduate Studies on 7-22-2011. Revision 3 approved by Assistant VP Regulatory Affairs on 12-10-2015. Revision 4 approved by Senior VP for Research and Innovation on 1-18-2019. Revision 5 approved by Assistant VP Regulatory Affairs on 12-6-2021.

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