Single IRBs and IRB Authorization Agreements

 

Effective January 25, 2018, the NIH has mandated that all domestic sites participating in a non-exempt, multi-site research study (where study activities outlined in a single protocol are carried out at multiple institutions) use a single IRB (sIRB).

Effective January 20, 2020, OHRP will require a sIRB for all domestic sites participating in a non-exempt, cooperative research study (two or more institutions coordinate to complete a portion of the research outlined in a specific protocol).

Authorization Agreements

An authorization agreement refers to the formal written agreement that documents respective authorities, roles, responsibilities, and communication between an institution/organization serving as the IRB of Record (Reviewing IRB) and the institution relying on that IRB (Relying IRB). This term includes: reliance agreement, cooperative agreement, master services agreement (MSA), master joint agreement (MJA), or umbrella agreement.

Researchers seeking to rely on the IRB of another institution or have Penn State's IRB serve as the reviewing IRB for another institution must have an IRB authorization agreement. These agreements are executed between a Reviewing IRB and one or more Relying Institutions and delineate the roles and responsibilities of the involved parties. The agreements can be for a single research study or for multiple studies (e.g., a master reliance agreement). The authorization agreement is negotiated and finalized by the Penn State IRB and reviewed by Penn State’s legal counsel, as needed. 

Authorizations agreements do not replace the need for IRB approval, and all human subjects research protocols still require a submission in CATS IRB, regardless of who may serve as the reviewing IRB. Even with an authorization agreement, researchers must still obtain IRB approval from the reviewing IRB and an acknowledgement of that approval from the HRPP before beginning any study activities and before funds can be released. The PSU principal investigator remains responsible for ensuring all of Penn State’s institutional requirements are met before beginning the research and throughout the course of the research activities.

Note:  It is not uncommon for new authorization agreements to take months. Researchers are advised to keep this in mind when considering a reliance request. While the Human Research Protection Program (HRPP) is working on developing processes for serving as the Reviewing IRB, we are currently only able to offer this option in a very limited number of cases and researchers anticipating the need for a single IRB should plan to use a commercial IRB or another accredited institution’s IRB at this time.

sIRB Review Process

sIRB review is more than just an IRB review. It includes other components, such as those depicted in the image below.

Picture of different regulatory stakeholders included in the Single IRB review process

sIRB vs Local Review

The image below depicts the different responsibilities of the sIRB compared to the local institution. 

A picture of Single IRB review versus local IRB review

Multi-Site Research

Multi-site studies use the same research procedures (i.e., protocol) outlined in a single protocol that is carried out at multiple institutions.

Examples of Multi-site Research

  • Protocols implemented at multiple locations that address the same research questions, involve the same methodologies, and evaluate the same outcomes, such as clinical trials
  • Sites that are accruing research participants for studies that are identical except for variations due to local context consideration

Cooperative Research

Cooperative or collaborative research is where two or more institutions coordinate to complete a portion of the research outlined in a protocol at their respective locations.

Examples of Cooperative Research

  • A study where one institution gathers the data and another institution analyzes the data
  • Protocols that are split between institutions, where one institution may collect a portion of the data, and another institution collects a different portion of the data

Note that the Single IRB requirement only applies to institutions engaged in non-exempt human subject research. For guidance determining if your involvement qualifies as "institutional engagement" in human subjects research, refer to the video provided by the Office for Human Research Protections.

 

Request to Rely (R2R)on an External IRB

Policies regarding willingness to serve as a Reviewing IRB are specific to each institution. To request that an institution’s IRB serve in this capacity, work with the IRB at that institution (and the principal investigator at that institution, if applicable) to confirm their policy before proceeding. The Penn State IRB makes the final determination regarding whether to be a Reviewing IRB or a Relying IRB when Penn State is engaged in the human subject research study in question.

For questions about Penn State HRPP reliance processes, please contact:

 

 

5-step R2R at the PSU HRPP

Investigators should be aware that reliance arrangements frequently require additional work on the part of the local study team, including submission to the PSU HRPP and the external IRB, as well as managing communication between these offices. For minimal risk research, review times for external IRB protocols can exceed review times for minimal risk projects approved by a local IRB.

The section entitled, ‘Reliance on an External IRB for Review of Human Subject Research Studies’ in the Investigator Manual (HRP-103) provides the criteria that Penn State’s IRB considers when deciding to cede review to an external IRB. Typically, we require that the Reviewing IRB is part of an AAHRPP accredited institution or organization. See the AAHRPP website for a list of accredited institutions/organizations. 

NOTE: The PSU HRPP will only enter into reliance arrangements when our site is engaged in non-exempt human subject research. See "Worksheet – Exemption Determination (HRP-312)" within the CATS library to assess whether the activities carried out by our site meets any of the listed criteria. If so, local IRB review should be sought instead.

Investigators requesting a reliance determination should complete a Reliance Request Form. This form must be completed PRIOR to a submission in CATS IRB.

Penn State’s HRPP CANNOT guarantee their willingness to support the use of the sIRB without the submission of this form. If an institution is listed under the "External IRB" list in CATS IRB, there is still a need to complete the Reliance Request Form and confirm the details related to the authorization agreement that will be used. Determinations are made on a case-by-case basis. Penn State will not enter into authorization agreements for research determined to be exempt.

If you are not ready to submit a protocol, but are submitting a grant proposal that includes a single IRB plan, the HRPP has issued a statement confirming our understanding of the NIH single IRB policy and agreeing to rely on sIRBs that meet certain criteria (e.g., using SMART IRB Agreement). The full statement is available for download and may be included in grant applications.

If the Reviewing IRB is requiring a specific letter of support be signed for a grant proposal, or the criteria outlined in the attached statement are not met, please submit the request via the Reliance Request Form at least two weeks before the grant submission deadline.

A CATS submission should only occur after the PSU HRPP has agreed to the reliance arrangement proposed within STEP TWO.

All human subject research being reviewed by an external IRB, through either a master reliance agreement with a commercial IRB, the SMART IRB Reliance Agreement, or through study-specific reliance agreements with other institutions, must submit an external IRB submission to the HRPP office through CATS for registration and review of local requirements (e.g. conflict of interest, education requirements, state law, institutional policy, ancillary office review). The external IRB submission will be reviewed and returned to you with instruction to submit to the reviewing IRB. Any documents required by the Reviewing IRB should be included with your submission (e.g. local context forms, reliance documents requiring IRB/institutional signatures).

Visit the CATS IRB Help Center to review the "External IRB Submissions" job aid for more information about submitting an external IRB submission to the PSU HRPP.

For federally funded research, the external IRB submission should only be submitted to the PSU HRPP after the funding agency has agreed to the proposed sIRB plan.
 

Reliance on an external IRB is specific to the ethical review of the study, as specified under the HHS regulations at 45 CFR Part 46 and/or FDA regulations at 21 CFR Part 56. Questions about how to submit to the external (Reviewing) IRB should be directed to that IRB. The reliance arrangement may involve standard operating procedures (SOPs) that describe with whom and how to communicate with the external IRB. In addition, the external IRB may have its own distinct steps/processes in its submission process.

Reliance requests that do not fall under an existing Master Agreement with PSU

PSU standard language will be required in the consent forms approved by the external IRB. This language should match the PSU template consent language from the following sections as applicable:

  • Source of Funding
  • Compensation for Injury
  • Compensation for Participation
  • Radiation Safety Language (provided after the local Radiation Safety review)
  • Authorization to Use and Disclose Information for Research Purposes 
     

Reliance requests that fall under an existing Master Agreement with PSU

The IRBs listed below have existing master agreements with Penn State and therefore have PSU standard consent language and local context information on file. Please reach out to the point of contacts listed below for questions related to submitting to one of these IRBs. For questions about PSU requirements or CATS IRB submissions please reach out the appropriate HRPP staff.

When using WIRB:
When using Advarra:
  • What is the process to use Advarra?

    • Once you are ready to submit to Advarra, please visit www.cirbi.net
    • Select either the investigator application or protocol application, depending on what you wish to submit to Advarra
    • CIRBI helpdesk can be reached at Email: cirbi@advarra.com or toll free at 1-866-99CIRBI (1-866-992-4724)
  • For any questions on how to submit, please contact institutions@advarra.com

 

When using NCI CIRB:

 

Final versions of the study documents approved by the external IRB, alongside the external IRB approval letter, should be attached prior to resubmission of the external IRB submission in CATS. Final acknowledgement of the submission cannot occur until all applicable ancillary reviews have been completed. Because ancillary reviews are by definition ancillary to the IRB review, all criteria for setting ancillary reviews is the same regardless of whether an external IRB is being used.

Please note that research activities cannot begin at any PSU location until acknowledgment of this final submission has been provided, even if the external IRB has provided their review/approval of the protocol.

Post-Approval R2R Requirements

After an Acknowledgement of Reliance on an External IRB is issued, the following changes must be submitted to the IRB Office for review:

  • Protocol amendments and revised consent forms (NOTE: for researchers at Penn State Health and the College of Medicine, the IRB will set an ancillary review for Payor Coverage Analysis and other applicable ancillary reviews)
  • Changes in study team members (for a training status check)
  • Changes in funding sources
  • Changes in the financial interest of study team member(s) including the PI

 

Visit the CATS IRB Help Center to review the "External IRB Submissions" job aid for more information about submitting a modification to the PSU HRPP for an external IRB submission.

At this time, the PSU HRPP is not requiring submission of a continuing review/administrative review for research reviewed by an external IRB. Researchers should consult with the external IRB regarding continuing review submission requirements.

R2R Resources

SMART IRB

SMART IRB is an initiative developed under an award from the National Center for Advancing Translational Science (NCATS) of the National Institutes of Health (NIH) to support single IRB review in facilitation of multi-site human subjects research.

The Penn State HRPP signed on to the SMART IRB Agreement as a Participating Institution. Using the SMART IRB Agreement as the ‘Reliance Agreement’ is an option if the other Participating Institutions have signed on and also agree to use the SMART IRB Agreement for a given study. A decision to use the SMART IRB agreement is made on a study-by-study basis by each Participating Institution.

Investigators are advised to visit the Resources section of the SMART IRB website for template documents that may be useful in the reliance process, including templates for the sIRB section of a grant application: https://smartirb.org/resources/

Using SMART IRB agreement does NOT replace or negate the internal submission process at Penn State regardless of whether Penn State is the Reviewing IRB or relying on an external IRB. Investigators should never assume that the agreement can or will be used for a given study or convey to others, including a funding agency, that the agreement will be used, without explicit documented agreement from each Participating Institution. NOTE: There are currently three listings for Penn State as participating institutions signed onto SMART IRB, please be sure to select the appropriate institution:

  • Penn State College of Medicine
  • Penn State Milton S. Hershey Medical Center
  • The Pennsylvania State University [covers University Park and all other campus locations except the Penn State College of Medicine and Penn State Health]