When Ceding Review:
Adding BMC or BUMC as a Site through an External IRB
March 2018 Issue
There are times when an investigator from Boston Medical Center or BU Medical Campus will want to participate in a research study being conducted through an outside institution’s IRB or a third party IRB.
There is now the NIH requirement for single IRB review for federally-funded multi-site studies; but there are many other “cede review” scenarios.
The Cede Review Process
If the circumstances are appropriate, then the investigator can initiate a “cede review” request to the BMC/BU Medical Campus IRB to (1) approve the investigator to participate in the research study; and (2) to request the BMC/BU Medical Campus IRB to “cede” or delegate its review to the lead institution’s IRB or third party IRB through an IRB authorization agreement (IAA). By doing so, the research activities of the study by all the participating sites, including the BMC or BU Medical Campus investigator, are overseen by one IRB, thereby reducing duplication of reviews by multiple IRBs and increasing efficiency.
If the research study is not appropriate for review by an external IRB, and the BMC/BU Medical Campus IRB does not agree to cede review, then the investigator would have the option to submit the research study for local review by the BMC/BU Medical Campus IRB.
When the BMC/BU Medical Campus IRB agrees to cede review to another IRB, it’s a lot like parents preparing to send their children (investigators) away to a summer camp.
There’s a camp registration form (INSPIR cede application); a packing list (protocol and other study documents from the other institution, and a BMC/BU Medical Campus-specific consent); record of a doctor’s physical examination and immunizations (CITI certification, GCP training for clinical trials, CVs, licenses, and a MA researcher’s license for IND drug studies); a list of medications and food allergies (local context survey); a permission slip (authorization agreement); and expectations for letters sent home (requirements to submit in INSPIR for study personnel changes, Unanticipated Problems, and study closure).
The purpose of this article is to outline what the parents (BMC/BU Medical Campus IRB) will ask from the children (investigators) to make sure everything is ready to arrive at camp (cede review).
Cede Review Scenarios
Let’s review typical scenarios in which a BMC or BU Medical Campus investigator would be interested in being added as a site to a study being overseen by an outside institution through its own IRB or through a third-party IRB:
- When being a part of a research study being conducted by a BU Charles River Campus Principal Investigator (the BU Charles River Campus is considered an “outside institution” since they have their own FWA and IRB)
- When a BU Medical Campus graduate student is working with a principal investigator from an outside institution on a research study as part of a thesis
- When adding BMC or BU Medical Campus as a site to a federally funded study where there is a mandatory single IRB (see the October 2017 CR TIMES Feature article)
- When adding BMC or BU Medical Campus as a site to a study from a special group or consortium that was formed based on a disease or research focus for which there is a designated central IRB and a pre-signed authorization agreement with participating sites that is intended to cover all subsequent specific protocols
- When adding BMC or BU Medical Campus as a site to a study where there is a voluntary central IRB (such as a study being conducted at one of the hospitals where Partners HealthCare System, Inc. is the IRB of record)
Another scenario would be special contractual arrangements set up by the BMC/BU Medical Campus IRB:
- The BMC/BU Medical Campus IRB has an agreement with the Hummingbird IRB (HIRB), which is currently the primary Independent IRB contracted for multi-centered industry-sponsored clinical trials involving investigational drugs or devices where the industry sponsor holds the IND or IDE; and Western IRB (WIRB), which was the previous primary Independent IRB for industry-sponsored studies, but was replaced by HIRB and currently still has active studies. This is a special contractual arrangement in which HIRB and WIRB act as another “Panel” of the BMC/BU Medical Campus IRB. BMC and BU Medical Campus investigators submit INSPIR HIRB cede applications (see HIRB ).
<!h2>Roadblocks to Ceding Review
However, if the following scenarios exist, then it may be problematic or impossible for the BMC/BU Medical Campus IRB to accommodate ceding review:
- If the other IRB is an “Independent IRB” (one that reviews but is not part of an institution that conducts research, in contrast to an IRB comparable to the BMC/BU Medical Campus IRB which is at a hospital or academic medical center, or at a for-profit or non-profit institution, which both oversees and conducts research), unless the BMC/BU Medical Campus IRB already has an authorization agreement with the Independent IRB (such as HIRB or WIRB), or unless it is designated as an NIH mandatory single IRB for a federally-funded study. There is also concern about delegating to commercial Independent IRBs when its reputation or the quality of IRB reviews may be questionable or unknown, which may put the safety of research subjects at risk.
- If the other IRB is not a participating institution of Smart IRB, the nationwide standardized IRB Authorization Agreement platform—particularly if the other IRB is at a hospital or academic medical center. Currently there are over 394 participating institutions who have agreed to operate under the same standardized Smart IRB authorization agreement in collaborating with one another in research studies (see www.smartirb.org)—the BMC and BU Medical Campus are members. If the other IRB is not a Smart IRB member and presents the BMC/BU Medical Campus IRB with a non-standard authorization agreement, then it will require BMC or BU attorney review, depending on the Principal Investigator’s affiliation, and may result in delays as attorneys negotiate with the other institution on revisions to the authorization agreement terms.
- If the BMC or BU Medical Campus Principal Investigator wants to cede to an outside IRB, then they cannot also add External Investigators from a different outside institution or from the Boston HealthNet Community Health Centers. The External Investigators from the different outside institution or from the Boston HealthNet Community Health Centers who are engaged in research will have to obtain their own cede authorization agreement with the outside IRB—they cannot be “piggybacked” under the BMC or BU Medical Campus’s cede agreement with the outside IRB because the External Investigators from the different outside institutions and the Community Health Centers have different FWA numbers.
- If the other institution’s multisite study involves solely chart reviews, then it is unlikely that the BMC/BU Medical Campus IRB will be willing to cede review to give another IRB control over what access will be given to BMC patient data. Instead of ceding review, the Principal Investigator will be requested to complete an INSPIR Chart Review application, and obtain a BMC Research Data Use Agreement from the BMC Clinical Trials Office to be signed by the other institution.
- If the activities of the BMC or BU Medical Campus investigator are determined to be “Not engaged in research”; for example, if the investigator is only serving as a “consultant” (such as one who will help design the study or analysis tools); or will perform analysis on deidentified data. Another example is if the investigator will refer subjects to the other institution from one of their approved studies who have previously consented to be contacted for follow-up studies--if needed, the investigator can, instead, submit an Not Human Subjects Research (NHSR) INSPIR application if documentation from the BMC/BU Medical Campus IRB is required.
- If BMC or BU Medical Campus is the primary grant or funding awardee or where the grant/contract specifies that BMC or BU Medical Campus will act as the Reviewing IRB.
- Research that qualifies for Exempt Review if the other institution is not a Smart IRB member, since the Smart IRB authorization agreement covers exempt research; or if the other institution’s policies do not permit ceding for exempt research.
The Relying Institution
The business of the BMC/BU Medical Campus Human Research Protection Program (HRPP) is twofold and performed according to federal, state, and institutional regulations and policies: (1) to provide institutional review and oversight of human subjects research conducted by investigators under its jurisdiction--namely, Boston Medical Center, and Boston University Medical Campus; and (2) to ensure the rights, safety, and welfare of its research subjects.
How does this change when the BMC/BU Medical Campus IRB cedes review to another institution’s IRB?
The IRB of the other institution (called the Reviewing IRB) is responsible for overall IRB oversight of the research study, including its participating sites.
However, the BMC/BU Medical Campus HRPP (the Relying Institution) still has the responsibility for ensuring the following:
- That its investigators and research staff comply with BMC/BU Medical Campus training requirements (human subjects protection certification and GCP training for clinical trials)
- That all BMC/BU Medical Campus institutional special routing approvals are met (such as the department chair, IBC, Pharmacy, GCRU, etc.) as applicable, depending on the research activities being conducted at BMC/BU Medical Campus
- That investigators have submitted conflict of interest financial disclosure forms
- That if a BMC/BU Medical Campus-specific consent form is required, that all the inserted BMC/BU Medical Campus-specific sections are appropriate and have attorney review as needed (such as the Basic Information on the first page, costs, compensation for injury, HIPAA and questions sections)
- That, if required, a Local Context Survey form is completed by both the investigator and the BMC/BU Medical Campus IRB which describes local, institutional, and state policies and laws applicable to the research study about which the Reviewing IRB must be aware and take into consideration in its review of the BMC/BU Medical Campus site
- That if the Reviewing IRB is a non-participant of Smart IRB, that its non-standard authorization agreement is referred for attorney review and approval (BMC or BU, depending on PI affiliation), including negotiating any revisions to the terms of the agreement with the attorneys of the Reviewing IRB
Therefore, every BMC and BU Medical Campus Principal Investigator must submit an INSPIR cede review application to address the above responsibilities that are required as the Relying Institution before ceding review.
Post-Cede Review Approval
Once the Authorization Agreement is signed and the study is ceded to the Reviewing IRB, most amendments, continuing review applications, etc. will be submitted to the Reviewing IRB. However, there will still be instances when the Principal Investigator must continue to submit in INSPIR:
- Internal study personnel changes for ceded studies: Since BMC/BU Medical Campus is responsible for ensuring training and conflict of interest requirements are met, investigators must submit all personnel changes, just as for non-ceded studies. The INSPIR acknowledgement letter will confirm that any new personnel have been certified to meet the BMC/BU Medical Campus institutional requirements. It is important to submit any changes to the BMC/BU Medical Campus IRB for approval BEFORE submitting the change to the Reviewing Institution.
- Reports of internal unanticipated problems: These must be reported to the BMC/BU Medical Campus IRB as well as to the Reviewing IRB. The terms of the authorization agreement may indicate whether the Reviewing IRB and the Relying Institution have the option to work together or separately to conduct audits, implement corrective actions, and address reporting requirements to institutional officials and agencies.
- Final Report: When the BMC/BU Medical Campus site’s participation has ended and a closure report has been submitted to the Reviewing IRB, then a Final Report must be submitted in INSPIR to close out the study.
The BMC/BU Medical Campus-Specific Consent
For a cede application, the BMC or BU Medical Campus investigator should obtain a copy of the approved Reviewing IRB’s consent form template and any instructions/guidelines on what sections can be modified to insert the BMC/BU Medical Campus requirements. Then, the investigator should proceed to create the BMC/BU Medical Campus-specific consent using the Reviewing IRB’s template with these considerations, and attach it to the cede application:
- The first page does not need to include the BMC/BU Medical Campus header logo, but does need to include the standard Basic Information listing the same protocol title, INSPIR number, Principal Investigator’s name, address, email, phone number, and 24-hour phone number for more than minimal risk studies.
- The BMC/BU Medical Campus IRB will specifically review the Costs, Compensation for Injury, HIPAA, and Questions sections.
The investigator should obtain and attach these documents from the Reviewing IRB:
- Reviewing IRB initial approval letter
- Reviewing IRB current continuing review approval letter (if the initial approval letter has expired)
- Reviewing IRB approved consent form
- Local context survey, if required by Reviewing IRB. The investigator should complete the form as much as possible, then attach it for the BMC/BU Medical Campus IRB to finish completing the form.
- Reviewing IRB non-standard authorization agreement (if not a Smart IRB participant).
The INSPIR cede review application is the basis for the BMC/BU Medical Campus IRB to determine whether it can delegate its IRB review oversight of BMC or BU Medical Campus investigators to another IRB. Upon agreeing to become the Relying Institution, however, the BMC/BU Medical Campus HRPP still retains significant responsibilities. Just like parents sending kids off to summer camp, the BMC/BU Medical Campus IRB will make sure every “i" is dotted and “t” is crossed, with the cooperation of investigators.