I Have Ceded Review: Now What Do I Do?

October 2023 Issue

Author(s):

  • Matt Ogrodnik, MS, CIP
    Director, Office of Human Research Affairs

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Introduction

Previous editions of the CR TIMES have discussed how to complete your initial cede request submission, and how to set up reliance collaborations with other participating SMART IRB members. However, IRB approval of your initial cede request is just the beginning of the process when you cede review to the external Reviewing Institutional Review Board (IRB) of a multi-site study.   Navigating your ongoing responsibilities to the external Reviewing IRB and your local BMC/BU Medical Campus Relying IRB requires just as much understanding of cede review requirements as the initial submission – if not more. This month’s Feature Article will discuss the responsibilities that are retained and ceded by the Relying IRB, as well as our BMC/BU Medical Campus Human Research Protection Program (HRPP) Policies regarding when amendments or other notifications still need to be submitted to the BMC/BU Medical Campus Relying IRB when an external Reviewing IRB is your IRB of record.

 

Retained and Ceded Responsibilities

 

When BMC/BU Medical Campus enters into a reliance agreement to cede its IRB review of our local research activities in a multi-site study to an external Reviewing IRB, the reliance agreement establishes the responsibilities of both institutions. This delineation of responsibilities between the Relying IRB and the external Reviewing IRB is incorporated into our HRPP policies, and forms the basis for the involvement of the BMC/BU Medical Campus Relying IRB throughout the life of the study. 

Responsibilities Retained by the Relying BMC/BU Medical Campus IRB

  • Evaluation of initial requests to cede review; and

  • Determinations that the study meets the requirements for waivers of HIPAA authorization for research uses and disclosures of subjects’ protected health information. This is captured in the HIPAA Compliance section of the INSPIR application; and

  • Conflict of interest reporting and evaluation: Investigators are required to report their financial interests; and BMC and BU are responsible for evaluating whether the interests constitute Financial Conflicts of Interest that require management, and if so, for communicating management plans to the reviewing IRB; and

  • Reviews performed by special routing; and

  • Monitoring research: The compliance provisions of Section 11 apply to all human subjects research conducted by BMC/BUMC investigators, including ceded research

    • For QA Reviews, the QA Review Report will inform the study team which findings are reportable to the IRB of record; and

    • In addition, a summary of reportable findings will be provided to the IRB of record; and

  • For targeted audits, the BMC and BUMC HRPP will notify the IRB of record of any potential noncompliance with applicable human subjects protection regulations or with the requirements or determinations of the IRB of record; and

  • Investigator qualifications:

    • The process for ceding review includes providing training for investigators and research staff and assuring that all study staff meet the qualifications and training requirements, including personnel added to the study after initial approval; and

  • Organizational conflicts of interest: BMC and BU are responsible for notifying the external IRB of any organizational conflicts of interest.

Responsibilities Ceded by the Relying BMC/BU Medical Campus IRB

  • Performing the scientific review of the protocol; and

  • Ensuring concordance between any applicable grant and the protocol; and

  • Reviewing potential noncompliance, including complaints, protocol deviations*, and results of audits, and making determinations of noncompliance according to the policies and procedures of the IRB of record; and

    *One important thing to keep in mind is that when you cede IRB review to an external IRB, you need to follow their policies and procedures and their time frame for reporting protocol deviations, unanticipated problems, and other reportable events

  • Evaluating the protections provided by management plans for conflicts of interests, and imposing additional requirements if necessary to protect the rights and welfare of subjects; and

  • Obtaining any additional approvals from the Department of Health and Human Services (DHHS) when the research involves pregnant women, fetuses, and neonates; or children; or prisoners; and

  • Reporting to regulatory agencies and sponsors concerning serious or continuing noncompliance, unanticipated problems, and suspensions or terminations of IRB approval

    • The IRB of record is expected to provide the BMC/BU Medical Campus HRPP the opportunity to review and comment on the report before it is sent to regulatory agencies or sponsors.

 

Requirements After Initial Cede Approval

 

Most institutions have an initial IRB cede review submission process.  At BMC/BU Medical Campus, an IRB cede application is generated in the electronic INSPIR system when the following option is chosen in Review Path Section 4.1:

“BMC/BU Medical Campus (the Relying Institution) cedes IRB review to another institution (the Reviewing Institution) under an Authorization Agreement.”

This initial cede application process helps our IRB determine whether we agree to cede; or in some cases, whether we agree to participate in the study at all. The initial cede application collects information on our site’s activities, requests confirmation that the research team will comply with certain local policies and state laws, facilitates routing to ancillary reviewers, and helps ensure all other ceded responsibilities are satisfied at the start of the study.

Once the initial request to cede review has been granted, and the external Reviewing IRB has approved the addition of your site to the multi-site study, then our Relying IRB will send a confirmation of when you may begin research activities. At this point, you will need to juggle your responsibilities to both the external Reviewing IRB and our Relying BMC/BU Medical Campus IRB.

When the BMC and BU Medical Campus IRB has entered into a reliance agreement with another IRB that acts as the IRB of record, the Principal Investigator (PI) must comply with all reporting requirements of the external IRB of record. This includes, for example, deviations, AEs/SAEs, Unanticipated Problems (UPs), and subject enrollment totals.

However, you are still responsible for the following reporting requirements to the Relying BMC/BU Medical Campus IRB. These are broken down below by “reportable events” (which are incidents that require prompt reporting), and reports on study progress or proposed changes to the study.

Reportable Event Requirements:

  • Submit Reportable Events and New Information (RENI) forms to report any UPs or changes made to eliminate an apparent immediate hazard to subjects that occur at the BMC or BU Medical Campus site (“internal Unanticipated Problems” and “internal immediate apparent hazards to subjects”)

    • This requirement is in addition to required reporting to the external IRB of record according to its reporting requirements for (UPs) and changes made to eliminate an apparent immediate hazard to subjects.

  • Submit RENI forms to report any serious and/or continuing noncompliance determinations made by the external reviewing IRB in relation to event(s) that occur at the BMC or BU Medical Campus site
    • This form must be submitted to the IRB within 7 days of the investigator or research staff becoming aware of the external reviewing IRB determination.

Requirements for Reporting Study Progress and Proposed Study Changes:

  • Submit a Status Check-In Report form prior to the status check-in due date (which is 3 years from the date that the initial cede approval is granted); and

  • Submit a Final Report after the external IRB of record closes the study.

Lastly, the study team is required to submit certain types of proposed study changes to the Relying BMC/BU Medical Campus IRB for review and approval *prior* to implementing the changes. These changes are submitted using the same Change Request and Amendments form that you would use to submit proposed changes to the BMC/BU Medical Campus IRB for review for studies that are not ceded.

An amendment is needed if the proposed changes:

  • Affect compliance with local policies or seek to modify previously-granted policy exception requests for enrollment of:

    • Decisionally-impaired subjects who require the use of Legally Authorized Representatives (see Section 9.5); and

      • Policy: BMC/BU Medical Campus policies specify who is an allowable Legally-Authorized Representative as follows:

        • Court-appointed guardian and previously-designated research proxy for any category of research
        • General healthcare proxy, only for research that holds out the prospect of direct benefit
        • Next of kin, only for research that holds out the prospect of direct benefit or for research where consent of the subject could be waived under BMC/BU Medical Campus policies

    • Non-English speaking subjects (see Section 8.4.5); and

      • Policy: BMC/BU Medical Campus policies require the following for enrollment of non-English speaking subjects:

        • Minors may not be interpreters
        • Adult family members may be interpreters only if the study does not require an interpreter with a medical background.
        • The use of the short form is not allowed without prior approval of the BMC/BU Medical Campus IRB

    •  Wards of the State (see Section 9.2.3); and

      • Policy: BMC/BU Medical Campus policies require that children who are wards of the Massachusetts Department of Children & Families may be enrolled in research only if either parental permission will be obtained for enrolling their children in research or the Department of Children & Families will obtain prior judicial approval for enrolling the children when the parents cannot be located, or when the children are in custody for surrender for adoption or for termination of parental rights.

    • Limited- and non-readers (see Section 8.4.6); and

      • Policy: BMC/BU Medical Campus policies require that for greater than minimal risk research, either an impartial witness must be present throughout the consent process or an alternative method of ensuring comprehension is used if the consent form is read to a potential subject.

    • Students, trainees, and employees (see Section 9.6); and
      • Policy: BMC/BU Medical Campus policies requires that the appropriate Dean or Chief sign off on research where students or residents are targeted for recruitment. BMC/BU Medical Campus policies generally do not allow for enrollment of students or employees (faculty or staff) who report directly to one of the study investigators.
    • Patients of specialty substance use disorder clinics or providers (see Section 7.2.2.10); or
      • Policy: Use of data under 42 CFR Part 2: Confidentiality Of Substance Use Disorder Patient Records requires special permissions.
  • Affect compliance with local policies or seek to modify previously-granted policy exception requests for individuals involved in the consent discussion for studies involving drugs, devices, or surgical procedures
      • Policy: For these studies, a Licensed Independent Professional (LIP, for example, physician, dentist, physician assistant, nurse practitioner) must discuss the purpose, risks, benefits, and alternatives with potential subjects.
  • Affect information provided regarding the plan to prevent disclosure of HIV testing status to any non-Boston Medical Center research staff prior to written consent being obtained. The BMC/BU Medical Campus IRB needs to ensure that the study is compliant with the Massachusetts state law for disclosure of HIV testing status; or
  • Affect information provided regarding the plan to share data with a third-party vendor or software application or program, The BMC/BU Medical Campus IRB needs to ensure that either an approved vendor/app/program is being used, or, that the study team is working with the appropriate Privacy or Information Technology office to obtain approval for use of the third-party; or
  • Affect information provided regarding recruitment procedures, or add new or modify existing recruitment materials. The BMC/BU Medical Campus IRB retains responsibility over review and approval of recruitment methods and recruitment materials when we cede review, as this is a major area of local context oversight. Many institutions have differences in permissible recruitment methods and materials based on their understanding of the preferences of their local subject population. Therefore, even when relying, we need to review all proposed changes. As part of this process, the BMC/BU Medical Campus IRB also ensures that the proper approval from the relevant Communications Office is in place; or
  • Affect information provided for a waiver of authorization for use and disclosure of Protected Health Information (see Section 8.5.2.2). An amendment is needed if you seek to modify an existing waiver or request a new waiver because the BMC/BU Medical Campus IRB retains the responsibility for granting waivers of authorization for ceded research; or
  • Require review by a special routing individual or entity that was not involved during the initial review process (see Section 7.2.2.2). The BMC/BU Medical Campus IRB is responsible for ensuring that special routing to these individuals or entities takes place; and if an entirely new special routing department is involved, an amendment is needed to facilitate this process; or
  • Add new or modify existing investigator or research staff Financial Conflicts of Interest as determined by Boston Medical Center/Boston University Faculty Review Committee on Research Financial Conflicts of Interest. The Relying IRB is responsible for communicating Financial Conflict of Interest management plans to the Reviewing IRB, so we will need to know whether there are new or revised plans to be managed; or
  • Affect information provided regarding organizational conflicts of interest; or
  • Add totally new study cohorts and/or new consent forms. The IRB will need to review these new research activities and new consent forms in the same way that we reviewed the original study cohort and/or consent forms during the initial cede evaluation.

The easiest way to think about whether an amendment is needed for a ceded study is to consider whether the proposed changes affect the information that is already included in your existing approved IRB cede application.  However, please reference the above list to act with certainty regarding whether you need to submit a cede amendment to the Relying BMC/BU Medical Campus IRB; or, reach out to medirb@bu.edu to discuss the changes and the need for an amendment *prior* to making the submission.

 

Conclusion

Receiving your IRB approval letter for an initial cede submission is an exciting step in the process, as the BMC/BU Medical Campus IRB (as the Relying IRB) is confirming that you may now begin research activities as a relying site of a multi-site study.  However, this is not the end of your communications with your local BMC/BU Medical Campus Relying IRB, even though the designated external Reviewing IRB for the multi-site study becomes your IRB of Record. In order to remain compliant, you need to understand the responsibilities of the Relying IRB and the external Reviewing IRB; and ensure that the ongoing requirements of both IRBs are satisfied.