Single IRB and Reliances

Research sites and personnel who are not part of the University of Miami (UM) are not covered by the UM’s IRB review unless the review is coordinated through the UM Human Subject Research Office (HSRO).

Likewise, if you are collaborating on a study that will involve an external central IRB, the UM HSRO must be involved in the coordination of the central IRB review.

In each instance:

• An agreement must be in place between the reviewing IRB and the relying institution. This agreement must describe the roles and responsibilities of each organization; and
• The relying institution must cede the review to the reviewing IRB.
  
  

Obtaining reliance agreements can result in delays in IRB approval. During the initial collaboration discussions, investigators should find out if agreements are already in place or if institutions need to obtain a reliance agreement with the IRB chosen to oversee the study. Many academic institutions use the SMART IRB reliance agreement to meet this requirement. The UM HSRO has signed the SMARTIRB agreement which allows the UM to review for or rely on any of the institutions that have also signed the agreement. When planning the collaboration, it is important to ask the collaborating sites if their institution is part of the SMART IRB agreement.

 Most domestic, federally funded multi-site human subject research must comply with the requirement for single IRB (sIRB) review of all participating sites. The UM IRB may choose to serve as the reviewing IRB for the collaborating research sites (or single investigators) or may choose to rely on another IRB for such review.

NIH Grant Submissions:

Single IRB (sIRB) Planning for NIH Grant Applications

The NIH requires that multi-site studies are reviewed by a single IRB to promote efficient and expeditious research.  This policy requires investigators to include a single IRB plan as part of the grant application and contract proposal submitted to the NIH.  The single IRB Plan is an attachment to Section 3.2 of the study record in the PHS HSCTI form in FORMS-E. 

The NIH’s acceptance of the plan will be incorporated as a term and condition in the Notice of Award or in the Contract Award. 

Exceptions

The mandate does not apply to exempt human subject research, many veteran sites, foreign sites, sites involving tribal nations, sites for which review by the proposed sIRB is prohibited by a federal, tribal, or state law, regulation, or policy.

Other Exceptions

In October 2020, OHRP issued an exception for research conducted during the Coronavirus Disease (COVID-19) Public Health Emergency declared by the Secretary of HHS. Funding agencies supporting the research must approve the use of this exception. NIH has confirmed that its use of this exception will be rare.

Steps in Planning a Grant Application for sIRB review

Step 1.  Contact the HSRO as soon as possible prior to submitting your grant proposal to avoid any delays in grant processing.

Step 2.  Identify the single IRB that will provide review for all sites. The NIH policy does not define which IRB should serve as the Reviewing IRB, and the decision should be made on a study-by-study basis after discussion with the lead PI, the Human Research Protection Program (HRPP) and the participating sites, depending on the specific needs of the study.  The HSRO reliance team will work with investigators to assure that the identified single IRB is qualified to review the applicable research.

Step 3.  Once the Reviewing IRB is identified, the selected IRB must be willing to serve as the sIRB.  all sites must agree to rely on the proposed Reviewing IRB. If a site is requesting an exception to the policy for this particular study, the institution should provide the reason and/or compelling justification for exclusion in the sIRB plan.

Step 4.  Draft the sIRB Plan.  The sIRB plan must be attached to the grant application as a PDF file.  If multiple projects are included in a single grant proposal, a separate file should be attached for each project outlined in the application. Required elements guidance is below, as well as suggested sIRB Plan template document.

In general, the plan for use of an sIRB should include the following elements:

• Description regarding how you intend to comply with the NIH Policy on the use of sIRB for Multi-site Research;
• Name of the IRB that will serve as the Reviewing IRB;
• Statement that all identified participating sites have agreed (or will have to agree if sites have not been selected at the time of the grant application) to rely on the proposed sIRB;
• Statement that all participating sites will, prior to initiating the study, sign an authorization/reliance agreement that will clarify the roles and responsibilities of the sIRB and participating sites (the actual reliance agreements should NOT be included with the grant application);
• Brief description of a communication plan between the sites and the IRB;
• Description of which institution or entity will maintain records of the authorization/reliance agreements and of the communication plan.

Resources:

NIH FAQ Single IRB Policy and Multi-site Research 

PHS Human Subjects and Clinical Trials Information Form Application Guide.

Pre-Submission Consultation:

Upon receiving a favorable score for funding, it is advisable to request a consultation with the reliance team prior to submission.  During this consultation meeting, the team will assist in proactively identifying any potential regulatory challenges, help develop a plan to ensure a smooth process and an expeditious turnaround time.

To schedule this meeting, contact Evelyne Bital, at (305) 243-9977 or at EBital@med.miami.edu.

The UM PI must also work closely with their contact at the University’s Office of Research Administration  to ensure the IRB review plan is included in the proposal and the expenses related to IRB review are included in the budget.

Reliance Agreement: May be referred as an IRB Authorization Agreement (IAA) or IRB Reliance Agreement. This is a written agreement between two or more institutions that is used to document the delegation of IRB review responsibilities.  Some agreements are designed to cover all future multi-center studies involving two or more sites. These agreements are usually referred to as Master Reliance Agreements.     UM has entered into several Master Reliance Agreements with the below entities:

• Western IRB (WIRB)
• Advarra (Formerly Chesapeake IRB, Schulman IRB, and QUORUM IRB)
• NCI-CIRB
• SMART IRB Agreement
• National Marrow Donor Program (NMDP)

Individual Investigator Agreement (IIA): This agreement may apply to research conducted under a PI from UM and involves one or more collaborating individuals who will be engaged in the research on behalf of an institution that does not have its own IRB or that does not hold a Federalwide Assurance. If the non-assured institution does not wish to establish a FWA with the Office of Human Research Protections (OHRP0, an individual Investigator Agreement may be established.  This agreement will allow the UM FWA to cover the non-assured, collaborating individual or institutional investigators.

Multi-site: means that the same research procedures (i.e., protocol) are being conducted at more than one site and that each site is under the control of a local participating investigator.

Single IRB (sIRB) or Central IRB: The institution review board that is designated to provide the regulatory and ethical review for all sites participating in a multisite study.

External IRB: Any non-UM institution review board. An external IRB can be a commercial, central, other academic, or hospital-based IRB.

Federalwide Assurance: a statement of principles governing the institution in the discharge of its responsibilities for protecting the rights and welfare of human subjects of research conducted at or sponsored by the institution.

Relying Site: The institution, hospital where research will take place and which will rely on an external IRB (Central IRB) which will serve as the Reviewing IRB for a multi-center study.

Reviewing IRB or IRB of record: The IRB that is responsible for the review, approval and regulatory oversight of a multi-site research study and serving more than one site. Sometimes referred to as the IRB of Record.

Overall or Lead PI: The principal investigator with ultimate responsibility for the overall conduct, safety, regulatory oversight and data integrity for a multi-center research study.

Lead site: The institution that receives the grant or contact directly from a funding agency and then establishes subawards or subcontracts with the participating sites

Local Context: Information about the location and the institution where the research will be conducted, including local law and institutional policies governing human subject research, and demographic information about the local community.

Local Context Required Language: The language required by UM to be present in informed consents for studies reviewed by an external IRB.

Point of Contact (POC): Person responsible for facilitation of communication between either the research study team(s)or the communication between the IRB of Record and the relying IRB. The Point of Contact could represent the lead study team coordinator or the IRB staff member identified as the point of contact.

SMART IRB Agreement: A national platform sponsored by the NIH, which provides a streamlined process for ceding or accepting authorization for IRB oversight among collaborating institutions.  UM is part of the SMART IRB Reciprocal Agreement.

Engagement: an institution is engaged in non-exempt human subjects research when its employees or agents, for the purposes of a research project, obtain: data about the subjects of the research through intervention or interaction with them; identifiable private information about the subjects of the research; informed consent of human subjects or if the site receives an award through a grant, contract, or cooperative agreement directly from HHS for non-exempt human subjects research, even where all activities involving human subjects are carried out by employees/agents of another institution

Required Language for Consent Documents

UM Local Context Information

IRB Authorization Agreement

Individual Investigator Agreement

Request for Waiver of Authorization

SMART IRB Letter of Acknowledgement Template

HRP-216 (External IRB Reliance Application)

HRP-217 (Reliance Questionnaire for Internal IRB Review)

HRP-218 (Relying Site Information Questionnaire)

Interests Disclosure Form (IDF) for Investigators Not Affiliated with UM

Single IRB plan

NCI CIRB Local Context Documents

Standalone HIPAA

MSC HIV Consent

NCI CIRB Boilerplate Language - English

NCI CIRB Boilerplate Language - Spanish

Additional Information for Research Subjects

WIRB Information

WIRB Boilerplate Template

WIRB translaton process memo

Guide for Researchers

NMDP Local Conext Documents

NMDP Boilerplate Template

When considering whether to use the UM IRB as the reviewing IRB, investigators should be aware that they will incur additional responsibilities. For example, the UM investigator or an established coordinating center will be responsible for coordinating the submissions from each site and submitting information into the UM HSRO’s electronic system, ePROST. In addition, the UM investigator will be responsible for ensuring that participating sites receive IRB communications such as approval letters and approval documents, unless another mechanism is used.

Central IRB Fees

Effective June 1, 2021, UM will apply a new IRB fee schedule to serve as Central IRB for multi-site research. The new fee schedule will apply to new studies submitted on or after this date and studies reaching grant renewal.  These fees must be incorporated into the grant or contract budget when conducting multi-site trials where UM will be the IRB of record.

 The updated fees associated with these types of submissions are provided below.

Complete fee schedule information can be found on our website: University Fees

The fees will be charged for industry funded and federally-funded studies for which the UM serves as the IRB of record for external sites.  If the study is federally funded, the HSRO will not charge for review of the UM site as this cost is included in the university’s indirect cost.

Please ensure you include complete billing information for relying sites in the eProst section that asks about funding. 

What the Central IRB review fee covers

Reliance Consultation & Administrative reviews

• Negotiating the Reliance Agreement for each site
• Providing guidance to the coordinating center or study contact
• Obtaining complete reliance submissions

Initial Site Review

• Reviewing site-specific protocol and supporting documents
• Reviewing site-specific informed consent documents and recruitment material
• Reviewing and applying site-specific local context

Ongoing Central IRB review

• Reviewing study modifications and reports
• Conducting continuing review
• Regulatory monitoring

Grant Budget Guidance

Federally-funded Research

Federal Departments and Agencies are expecting that funding proposals to include fees for sIRB review as direct costs.  The NIH provided detailed information about IRB charges.  This site includes information about:

• The appropriate budget category on the SF424 (R&R) form for IRB fees;
• Which costs should be charged as direct vs. indirect costs under different IRB review scenarios;
• The relationship with the $500,000 cap on direct costs; and
• Where to document the sIRB cost information on the budget forms.

If you have questions, contact:

• The NIH financial officer identified in your FOA or RFP and/or
• Your department’s contact person at the UM Office of Research Administration.

Documenting the sIRB selection in the funding application

The Single IRB Plan in the funding application should designate the proposed sIRB and contain a statement that each participating site is willing to rely on the proposed IRB.

Steps to take when preparing a proposal for a federally funded grant for multi-site non-exempt human subject research:

1. When collaborating institutions are identified, coordinate a discussion to select the reviewing IRB.
2. If the UM HSRO is chosen, contact the Evelyne Bital at (305) 243-9977 or eBital@med.miami.edu to discuss the proposed research.
3. Each collaborating investigator should contact their IRB to discuss the plan for IRB review.
4. If all collaborating institutions agree, obtain the contact information for coordinating the reliance and provide that information to Evelyne Bital.
5. Ensure your contact at ORA is aware of the IRB review plan.

How is the UM Central IRB Billed

If the UM is the primary awardee, the fees associated with reviewing the relying sites will be charged as direct costs to the grant. 

The Finance department will send payment request to the UM PI’s department.  Central IRB fees for all sites will be paid from the lead PI’s budget.  Individual payment requests will not be sent to each participating site PI.

The initial payment will be requested within 30 days after approval of the overall study which includes the UM site.  After a study is approved, an annual fee will be assessed for the lifetime of the study to cover services provided in the previous year.

After the grant is funded, the lead PI must:

Contact the HSRO reliance team to request use of the UM Central IRB.  Alert us that you have received funding and are ready to begin the process of establishing the central IRB review with UM for all sites.

Requesting use of UM as Central IRB

If you are interested in using the UM IRB to review a multi-site study or reviewing the research activities of a collaborating independent external investigator, you will need to open a UM local submission in the eProst electronic system, complete and upload the Reliance Questionnaire for Internal IRB Review (HRP-217).  HSRO staff will review the completed form and determine whether the research qualifies for a reliance. Once this determination is made, the HSRO staff will contact you with a decision and provide instructions on how to proceed.

UM may agree to serve as the central IRB in the following scenarios:

• Study is federally funded and single IRB review is required per single IRB mandate.
• Study is industry funded and UM is prime awardee or an engaged site.
• Legacy arrangements where UM already serves as the central IRB.
• Other extenuating circumstances are considered on a case by case basis. The complexity of the protocol and the number of sites will factor into this decision.

If the research qualifies for a reliance, the following actions will happen:

• HSRO staff will determine whether the UM HSRO has a reliance agreement in place with each of the relying sites and will follow-up with the sites if an agreement is needed.
  
  
• The UM site or coordinating center liaison must submit all study documents through the UM HSRO’s electronic system, ePROST.
  
  
• Each site must complete and submit a Relying Information Questionnaire (HRP - 218).
  
  
• Each site must provide a letter to the UM indicating they agree to allow the UM IRB to oversee the study conducted at their site (cede letter).
  
  
• The reliance team will review all study documents, request changes when appropriate and the IRB will review the protocol and the UM site (parent study).
  
  
• The determination letter will be provided for the overall study.
  
  
• Once the overall study is approved and a reliance agreement is in place for each site, the HSRO will create external participating site (p-site) page in eProst under the umbrella of the overall parent study.
  
  
• Each p-site will have its own site page where site specific documents will be uploaded by the study liaison for initial review and approval of the p-site. Correspondence for initial approval of the p-site and all subsequent p-site related submissions will be sent to the coordinating center/study liaison, which is the responsible party for distributing documentation to each relying p-site.

Ongoing Review and Oversight:

Ongoing reviews include continuing review, modifications, and reporting of new informations.

The coordinating center/study liaison is responsible for ensuring that required submissions to the UM CIRB occur on behalf of the entire study.

If you are interested in obtaining review from an external IRB for research that will be conducted by a UM site, you will need to open a UM local submission, complete and submit a Reliance Application for External IRB Review (HRP-216). HSRO staff will review the form and determine whether the research qualifies for a reliance. Once this determination is made, the HSRO staff will contact you with a response and provide further directions.

UM May agree to cede review in the following scenarios:

• Study is federally -funded and external review is required per single IRB mandate
• The study is an industry-funded multi-site study and the sponsor is requiring the UM to rely on an external IRB as a condition of participation. - Sponsor must provide a statement requiring external IRB review.
• Legacy arrangements where UM IRB already agreed to cede review.
• Other extenuating circumstances considered on a case by case basis. The complexity of the protocol will factor into this decision.

Please note: When an independent, commercial IRB completes the review, the HSRO charges a one-time $1,500 administrative fee for processing submissions for external review.

If the research qualifies for a reliance, the following actions must happen:

• The UM site must submit the study to the external IRB, according to that IRB’s requirements. The submission should include:
  1. The notice received from the HSRO approving the reliance (signed HRP-216).
  2. The documents and information required by that IRB.
     
     
• The UM site should carefully review the research and the consent document to see if it complies with the HSRO requirements The UM site will likely need to add the required HSRO language to the consent document before submitting  it to the reviewing IRB (see required language for consent documents) 

• HSRO staff will determine whether the UM HSRO has a reliance agreement with the reviewing IRB and will follow-up with the IRB if an agreement is needed.
  
  
• The HSRO staff will provide a signed Cede Review Letter to the external IRB if required.   
  
  
• Prior to conducting the review, the reviewing IRB may require information about the University of Miami’s local context (see UM local context informaton).
  
  
• HSRO staff will conduct an administrative review of UM Site documents to ensure the research is consistent with all applicable requirements. When the review is complete, the HSRO will confirm external IRB review.
  
  
• While waiting for external IRB approval the study team should obtain required ancillary approvals.
  
  
• The UM study team must upload the following upon receipt from the external IRB:
  • Approval notice from external IRB
  • Protocol
  • Consent Document (s)
  • Recruitment Materials
  • Subject-facing documents
    
    
• The HSRO will conduct an administrative review of the approval documents to ensure the research is consistent with all applicable requirements. When the review is complete, the HSRO will send an acknowledgement notice and finalize the documents.  The study may start once the HSRO, sponsor, and reviewing IRB approve the start-up.

Ongoing Activities after external IRB initial approval

During the course of the research, the site must submit the following as a modification into UM HSRO’s electronic system, eProst:

• Any document that needs to be uploaded into VELOS as a modification.
• Reports of non-compliance that could meet the UM’s definition of serious or continuing non-compliance
• IRB suspensions or terminations of a study
• IRB determinations of unanticipated problems involving risks to subjects or other

Note: The HSRO will not review modified documents.  The HSRO acknowledges external IRB approval of the modified documents. The documents are submitted through eProst only so the documents can be transferred electronically into VELOS.  If you have a question about a modified document, please contact the HSRO.

Any changes affecting non-UM documents (i.e., new study wide PI, study funding, study scope (drugs or devices information), overall template ICF, study-wide documents, with the exception of the protocol) do not need to go through the UM IRB and will not update to VELOS. These changes are uploaded in eProst utilizing the “Update Study Details” activity.

Continuing Review

UM does not require continuing reports for studies reviewed by an external IRB.  It is the PI’s responsibility to submit continuing report to the reviewing IRB.

Confirmation of closure and conclusion of external IRB oversight needs to be submitted via the Continuing Review data activity in eProst.

 Resources

• NIH website, Single IRB Policy for Multi-Site Research

eProstUpdate Study Details Process for External IRB Studies (IRB8.2.4)

eProstSubmission Process for External IRB Modifications (IRB8.2.4)