Multisite research

MU asks about two types of multisite studies in the application. Multisite research can include:

• Studies where most/all of the protocol is carried out at two or more sites (this includes studies needing approval for site-specific changes/documents and/or consenting participants at their site(s)).
• Studies where only a portion of the study is carried out at two or more sites (sharing responsibilities and activities), such as assisting UM investigator(s) with study design, recruitment, data analysis, etc.

To qualify as multisite, all sites must be engaged in research. In general, an institution is engaged when its researchers obtain: 

• Data about the subjects of the research through intervention or interaction with them.
• Identifiable private information about the subjects of the research.
• The informed consent of human subjects for the research. 

Contact the IRB for assistance with this determination. 

Additional guidance on engagement:

• Human subjects research and engagement in research FAQs
• Information from the Office of Human Research Protections, U.S. Department of Health and Human Services

On January 20, 2020, the sIRB review requirement for all multisite research projects sponsored by federal-common-rule agencies went into effect. The requirement is in place to streamline the IRB review process and avoid duplicate review by an IRB at each site. The National Institutes of Health (NIH) also requires the review of an sIRB. This common rule requirement applies to expedited and full board research. Exempt studies may enter into a single IRB arrangement on a case-by case basis.

There are three exceptions to the sIRB requirement:

• International, engaged sites outside the U.S.
• Individual IRB review is required by law (e.g., American Indian or Alaskan Native tribal law).
• A federal agency determines and documents that the sIRB model is not appropriate.

Please see our single IRB and reliance procedures webpage for more information.

The IRB selected to serve as the sIRB must have an active federalwide assurance (FWA) filed with the Office for Human Research Protections (OHRP). 

MU will rely on another IRB only if they are accredited by the Association for the Accreditation of Human Research Protection Programs (AAHRPP). The determination is made in consultation with the MU IRB office. 

Many times, the sponsor will initially select the sIRB, then the researcher will request approval by the MU IRB by submitting either:

• The Initial Reliance Request form (if relying on an external IRB)
• The Initial Request for MU to be the IRB of Record form 

See next FAQ for more details.

Please start by completing our Initial Request for MU to be the IRB of Record form. See our MU as the single IRB submission process webpage for step-by-step instructions.

The MU IRB may charge fees for certain studies to cover the costs associated with the review and related administrative responsibilities. The fees will be shared with you after completion of the initial request form. See our IRB fees page for more information.

Please note: MU IRB will only serve as the IRB of record for studies where the university is engaged in the research. MU IRB will not serve as the IRB of record for international sites. They must obtain their own IRB approval (or its equivalent).

Studies where external sites are conducting most/all of the protocol

(This includes studies needing approval for site-specific changes/documents and/or consenting participants at their site(s))

1. You must seek and obtain IRB approval for the MU site first with the study protocol and MU site-specific documents.
    
   • As part of MU's initial approval, model documents (i.e., consent document, recruitment flyers) must be submitted for approval. However, please consult with your IRB compliance manager on when to upload model documents. It may be easier to wait until all revisions are made to the MU site-specific documents, so multiple revisions aren’t required on the model documents during the review process.
      
2. Once the MU study is approved, you can add external sites using the Amendment for External Sites form.
    
   • Please upload a completed Local Context form along with the external site-specific documents.
   • You also will need to upload a tracked version of the site-specific documents showing where changes were made to the model documents.

Note: External investigators are not added to the MU IRB system. The relying site’s IRB should be managing the completion of IRB training and qualifications for their investigators. Rare exceptions are made if the investigator does not have an IRB.
 

Studies where external sites will only conduct a portion of the study

1. You will begin the reliance agreement process with external sites(s) while your MU application is under review.
    
   1. The MU investigator should send the Local Context form to participating sites for completion/signatures.
   2. Once the signed Local Context form is uploaded to the application, we will begin negotiating the reliance agreement.
   3. Your MU application cannot be approved until the signed reliance agreement(s) is in place.
   4. Model documents are not accepted, and you do not submit an amendment for external sites for studies where external sites are only conducting a portion of the study. (If you need approval for site-specific documents/consents, you will need to indicate external site is conducting most/all of the protocol on the application).

Please see our MU IRB is the single IRB – submission process page for additional information.

You can access the Local Context form (LCF) within the multisite question of the MU IRB application or Amendment for External Sites form. Send it to the external site principal investigator for completion and signatures.

All external sites must have an active federalwide assurance (FWA). You will indicate the FWA number on the LCF. If the site does not have an FWA, they can apply for one on OHRP's website. FWAs must include the site’s institutional official (e.g., President, CEO, Provost, Vice President, Dean of Research, etc.). The institutional official assures that human subjects research to which the FWA applies is conducted in accordance with the terms of assurance.

LCF part 1

Must be completed by the external site administration or institutional official.

• Training, qualifications and conflict of interest — Most external sites with an IRB/HRPP should be able to monitor their own human subjects research training and investigator conflicts. If they don’t have an IRB/HRPP, please contact the MU IRB for further consultation.
• Local site information — You will note in this section if the site is part of SMART IRB. MU is a participating institution in the SMART IRB V3.0 online platform where investigators and institutions can request, track and document reliance/authorization agreements. The SMART IRB V3.0 reliance agreement clearly defines roles and responsibilities and eliminates the need for the Institutional Official to sign reliance agreements for each study. SMART IRB is often used with MU multisite research and is documented in eCompliance for each project utilizing this agreement. More information on the SMART IRB online reliance system 

LCF part 2 

Must be completed by the external site investigator if the site will conduct most/all of the protocol (or if site needs approval for site-specific changes/documents and/or consenting participants at their site. Use this section to document any changes specific to the external sites).

Preparing an IRB application to include multisite research can take additional time. Study teams should plan accordingly and consult with their IRB compliance manager prior to submission.

The investigator will work with the local principal investigator (PI) to aid in executing the IRB reliance agreement. This can happen at any time during the review and approval process.

If relying sites are part of the SMART IRB V3.0 platform, this agreement is preferred. If a master agreement is already in place with the site, this will be referenced with no additional agreement needed.

If the external site is not part of SMART V3.0 or a master agreement, the MU IRB will initiate our template for a reliance agreement and send to the local PI to obtain signature from the external site’s institutional official. It must be signed by the institutional official listed on the site’s FWA.

Model consent forms and documents should be submitted with the initial application or on a regular amendment form. The model documents should follow the MU site documents exactly, except for a few areas highlighted in yellow to show the external sites where they can insert their site-specific information. External sites should only be editing content in the highlighted areas unless more changes are specified in the Local Context form.

Once approved, model documents should be shared with the external site to add their site-specific information, which should then be submitted for approval to MU IRB on the Amendment for External Sites form. (Make sure highlighting and instructions are removed prior to submitting. A tracked version also should be submitted so we can ensure only editable areas were modified.)

Please see our model consent instructions.

If you already have an MU approved study and would like to add an external site, either to conduct most/all of the protocol or only a portion, and would like MU to serve as the sIRB, please consult with the IRB to ensure the external site is in fact engaged in research and to make sure the site meets the requirements for MU to serve as the sIRB. If applicable, you will receive a fee estimate at this time.

If MU IRB agrees to serve as sIRB, you will then submit a regular amendment to update the application and protocol to include the external site’s involvement in the project. Model consents/documents should also be submitted at this time, if required.

Please see previous question for specific instructions for sites only conducting a portion of the study versus sites conducting most/all of the protocol: “What are some tips for streamlining the IRB review of my multisite study?” 

The MU team will act as a single liaison for relying sites. Responsibilities:

• Report local and relying site-specific proposed changes, unanticipated problems and non-compliance matters to the MU IRB, according to MU policies.
• At continuing review, submit the required site-specific information for IRB review.
• Communicate all MU IRB decisions and determinations to the relying site's study teams.
• Utilize a process/system to share IRB-approved documents, IRB approval notices and other IRB communications.
• Ensure all relying site investigators are trained on MU IRB policies and procedures, protocol conduct, study procedures, changes to the protocol and reporting requirements.
• Monitor progress and oversee the conduct of the study at the MU site and all relying sites.
• Ensure the integrity and accuracy of data.
• Document regular communication with relying sites.
• Comply with all stipulations outlined in the reliance agreement and MU IRB acknowledgement letter.