Preparing Commercial IRB Submissions for Multi-Center Industry-Sponsored Trials Where the Sponsor Holds the IND/IDE

October 2021 Issue

Author(s):

  • Matthew Ogrodnik, MS, CIP
    Director, Office of Human Research Affairs
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As part of our Human Research Protection Program (HRPP) policies, investigators are permitted to request that the Boston Medical Center (BMC) and Boston University (BU) Medical Campus Institutional Review Board (IRB) rely on another IRB (cede review) for the IRB review. If the request is to rely on a commercial IRB, the study must either be an industry-sponsored, multi-site trial involving an Investigational New Drug Application (IND) or an Investigational Device Exemption (IDE) held by the industry sponsor, or a federally-supported multi-center trial where the commercial IRB has been selected as the IRB of record. For industry-sponsored trials, the IRB has developed modified guidance for how to submit these cede requests. This month’s feature article will provide these detailed instructions.

 

Relying on a Commercial IRB

Commercial IRBs provide independent central IRB services for institutional and commercial clients.

Principal Investigators (PIs) wishing to participate in a multi-centered industry-sponsored protocol for which the industry sponsor is the holder of an IND or an IDE, have the option of either (1) submitting an INSPIR full board application for review by the BMC/ BU Medical Campus IRB; or, (2) submitting an INSPIR cede application to rely on the review by the commercial IRB selected by the industry sponsor.  The following criteria must be met:

  1. The commercial IRB is AAHRPP-accredited (you can look this up

    here: http://www.aahrpp.org/learn/find-an-accredited-organization) AND

  2. The commercial IRB is a participant in the SMART IRB reliance platform (you can look this up here: https://smartirb.org/participating-institutions/)

NOTE: SMART IRB is a platform to enable IRB reliance among over 900 Participating Institutions who agree to collaborate in research studies with one another under a pre-signed master SMART IRB global reliance agreement. A protocol-specific SMART IRB Agreement is then created for each study. For more information, please see the Feature Article entitled, SMART IRB AND YOU - Oct 2019.

If the commercial IRB is not AAHRPP-accredited or is not listed on the SMART IRB list of Participating Institutions, then your multi-centered industry-sponsored IND or IDE submission cannot be ceded to the sponsor’s commercial IRB. The study will need to be reviewed by the BMC/BU Medical Campus IRB.

However, if you confirm that the commercial IRB is AAHRPP-accredited and a SMART IRB Participating Institution, you then have the option to request to rely on the commercial IRB. At this point, you should follow these steps:

Step One:

  1. Look up your Principal Investigator (PI) at this website to reconfirm whether the PI’s Home Institution is Boston Medical Center or BU Medical Campus (the IRB uses this website for the same purpose): https://www.bumc.bu.edu/ohra/look-up-an-investigators-home-institution/
  2. In order to qualify as the industry sponsor-selected commercial IRB, the billing arrangement must be set up so that the commercial IRB bills the industry sponsor directly for the IRB review costs. Will the commercial IRB bill the industry sponsor directly? This is needed to proceed. Please make sure that the Clinical Trial Agreement clearly outlines that the commercial IRB will bill the industry sponsor directly.
  3. Inform the sponsor that you must now obtain approval to cede review of this IND/IDE study from the BMC/BU Medical Campus IRB through an internal IRB cede application BEFORE you are able to complete any additional forms or applications requested by the industry sponsor or the commercial IRB.

Step Two:

The industry sponsor should give you a consent form template(s) for the study. These templates need to be modified to add some specific required BMC/BU Medical Campus consent language. Please use the BMC/BU Medical Campus Adult Consent Form Template to copy the following items into the sponsor’s consent form template:

  1. The Basic Information at the beginning of the consent form must include the following fields:

    1. Principal Investigator: (this should also include the PI’s email and mailing address)
    2. BMC/BU MEDICAL CAMPUS IRB INSPIR Submission “H” Number (if sponsor allows this)
    3. Commercial IRB Submission Number (if sponsor allows this)
    4. Study-Related Phone Numbers:
      1. Regular Business Hours:
      2. 24 Hours:

  2. The HIPAA Authorization language must include Boston University and Boston Medical Center, as appropriate, among the organizations with access to PHI.

  3. The Costs section must use our institutional template language. Please replace the industry sponsor’s Costs language with the Costs section from the appropriate consent template.

  4. If the industry sponsor’s consent form includes language about the Genetic Information Nondiscrimination Act (GINA) and the research will take place in Massachusetts, then the GINA language must be edited to include the Massachusetts-specific information (see Section 8.2.4 and consent templates).

  5. In the QUESTIONS section: Questions need to be referred to the commercial IRB instead of the BMC/BU Medical Campus IRB. Please ensure this is the case. If not, then please copy the following block of text (without quotations) into the questions section, and replace the italicized text with the commercial IRB’s information:

    “You may also contact (name of commercial IRB) IRB:

    Commercial IRB name
    Commercial IRB Mailing address
    Commercial IRB Phone Number
    Commercial IRB Email

    The IRB is a group that helps monitor research. You should call or email if you want to talk to someone who is not part of the study about your rights as a research subject, questions, and/or concerns or complaints regarding this research study.”

If the study has the potential for direct benefit to the individual subjects, please also ensure that the consent form (and study protocol) do not mandate sample or data retention for future uses that are unrelated to the specific aims of this study. Per our HRPP policies, if the study has the potential for direct benefit to the subject, the study must make it optional for the subject to agree to sample or data retention; that is, the potential subject can agree to participate in the main study, but not allow the retention of their data or samples. If this is *not* the case, then please reach out to the IRB at medirb@bu.edu for assistance.

At this point, you should send the modified consent form to the industry sponsor to ensure that they accept the changes. If they do not accept any of these changes, then please reach out to medirb@bu.edu for assistance.

Step Three

The next step is to create a Velos application for the study. This is not part of the IRB review process, but is an important part of the process for the BMC Clinical Trial Office. If you need assistance with this, please reach out to cto@bmc.org.

  1. Create a Velos application (“Study Initiated” state) and upload the four required documents:

    1. Budget
    2. Protocol
    3. The Consent Form that was modified in STEP TWO
    4. Clinical Trial Agreement

If the PI’s home institution is BMC, the BMC Clinical Trial Office will review the “Compensation for Injury” section in the consent form.

If the PI’s home institution is BU Medical Campus (see STEP ONE), then please also send your consent form to BU Industry Engagement for review of the “Compensation for Injury” language:

BU Industry Engagement:   Attorney Bill Segarra; Phone: (617) 353-6151; email segarra@bu.edu

The BMC CTO or BU Industry Engagement may contact you with changes made to these sections based upon their review of the study documents.  If this happens, then you must send the modified consent form to the industry sponsor for approval of any changes.

Once the consent form language has been agreed to by the industry sponsor, then please attach the consent form into the INSPIR cede application (see next STEP FOUR). You do not need to wait for the BMC CTO or BU Industry Engagement consent form review process to be completed to move on to STEP FOUR.

STEP FOUR

It is now time to prepare your INSPIR application. Please note the following:

1. If you created your Velos application in STEP THREE BEFORE you created your INSPIR application, you will have received an IRB Number (H#) from INSPIR associated to your submission in Velos. Please use this H# for the instructions below.

2. All study-related documents should be attached in the Initial Review Submission Packet screen after the Application is completed.

APPLICATION

  1. Section 1.0 – General Information

    1. Study Nickname: Enter the name of the commercial IRB and add any additional text (e.g., the commercial IRB Study Nickname)

  2. Section 2.0 – Set up Department(s) Access

  3. Section 3.0 – Grant Key Personnel access to the study

  4. Section 4.0 – Review Path Determination

    1. Section 4.1 – Be sure to check the 2nd option, “BMC/BU Medical Campus (the Relying Institution) cedes IRB review to another institution (the Reviewing Institution) under an Authorization Agreement.”

    2. Section 4.2, 4.3, and 4.4 – must answer NO. If the answer is NOT No, the study is not eligible to cede review to a commercial IRB.

  5. Section 5.0 – Required Training and Conflict of Interest

  6. Section 6.0 – BMC/BU Medical Campus to cede review

    1. Section 6.1 – must answer YES. Please add the study’s commercial IRB# (their version of the “H#”)

    2. Section 6.2 – must answer YES.

    3. Section 6.3 – must answer YES, then select the commercial IRB from the dropdown menu.

      • If the commercial IRB you are looking for is not included in the dropdown menu, then please contact the IRB at medirb@bu.edu.

    4. Section 6.3 – must select that this is an Industry-sponsored multi-center trial that has an IND or IDE that is held by the Sponsor and the commercial IRB has been selected by the sponsor, and that the sponsor will bill the commercial IRB directly.

      • Please ensure this billing arrangement is outlined in the Clinical Trial Agreement.

    5. Section 6.6 – Make a selection based on whether the BMC/BU Medical Campus investigators will conduct research activities at BMC/ BU Medical Campus.

    6. Section 6.7 – Make a selection based on whether subjects will be recruited at a BMC/BU Medical Campus location(s).

  7. Section 7.0 - Research Activities By BMC/BU Medical Campus Researchers

    1. Section 7.1 – Insert “See industry sponsor protocol.” If any activities described in the protocol will *not* be conducted at BMC/ BU Medical Campus, then please clarify here.

    2. Section 7.2 – Answer all questions in this section.

Note: The section numbering may be different going forward, depending on your answers to the previous Sections.

  1. Section – Special Populations

    1. Answer all application sections. Different questions about institution-specific policies will appear based on your answers in Section 7.2. You will either need to agree to follow our HRPP policies, or, provide a justification for an exception to our policies.

  2. Section – Funding Source

    1. Select “Industry”

      1. Study Type: Select “Other”

      2. “Does this study meet the definition of a clinical trial as defined by NIH?” – Select “yes,” then insert the NCT number in the text box, if available. If not yet available, please add “pending”.

    3. Insert the details for your industry sponsor funding

    4. Select the appropriate Grants Office

  3. Section – Recruitment Procedures/Materials: Provide a description of how you will recruit participants at BMC/BU Medical Campus.  This section is very important.  Do not reference the attached protocol, as recruitment activities are site-specific.   The BMC/BU Medical Campus IRB retains responsibility over local recruitment methods and materials.

Complete the section which appears in your application:

  1. Section – Drug or Biological Agents; OR
  2. Section – Device Studies

Once you complete the drug or device section and click ‘Save and Continue’, you will be taken to the Initial Review Submission Packet.

INITIAL REVIEW SUBMISSION PACKET

  1. Study Application

  2. Consent Documents:

    1. Adult Consent

    2. if applicable: Parental Permission Form (consent for child)

    3. if applicable: Assent

  3. Other Study Documents:

    1. The industry sponsor’s protocol.

    2. The Investigator Brochure for the study drug (if applicable).

    3. The sponsor’s consent templates, as approved by the commercial IRB.

    4. IND documentation, if the study involves an IND and the IND# is not in the protocol

  4. Additional Special Routing:

    1. Please select ‘Yes’ for all of the applicable Special Routing sign-offs.

When all the above steps are complete and the application is ready, then please ask the PI to submit it in INSPIR to begin the electronic sign-off process.  You can follow these instructions to track the progress of the study in the INSPIR system:  How to check the status of a submission

STEP FIVE

Your INSPIR cede application will be reviewed by an IRB Analyst and an IRB Board Chair.   When it is determined that the cede application is finalized and approved to move forward, then the BMC/BU Medical Campus IRB will send the SMART IRB reliance acknowledgement letter to the commercial IRB for signature.

Upon receipt of the commercial IRB’s signed SMART IRB reliance acknowledgement letter, the BMC/BU Medical Campus IRB  will then notify you to proceed with any processes that are required by the industry sponsor or the commercial IRB (such as completing a separate application in their electronic system) to start the site approval process.  Please do not begin the site approval process in the commercial IRB’s system until you receive confirmation from the BMC/BU Medical Campus IRB.

STEP SIX

Once you complete any processes required by the commercial IRB, they will then send you the following:

  1. Approval documentation that BMC/BU Medical Campus has been added as a site (in the form of an approval letter); and

  2. Approved version(s) of the BMC/BU Medical Campus-specific consent/assent forms.

Please send these documents to the IRB Analyst assigned to your cede submission and who previously instructed you to proceed with the commercial IRB’s site approval process.

The IRB Analyst will upload the commercial IRB’s approval documents for your site to your INSPIR cede application, and will confirm whether the language in the approved consent is consistent with the version pre-approved by the BMC/BU Medical Campus IRB. If it is, then the IRB Analyst will send you a cede approval outcome letter.

Please note: you are only approved to begin human subjects research study activities once you have received the cede approval outcome letter from the BMC/ BU Medical Campus IRB.

STEP SEVEN

The IRB Analyst will include Special Notes in the cede approval outcome letter, as well as in a follow-up INSPIR correspondence. These Special Notes outline post-approval requirements:

  1. If you add study personnel to a ceded study, then you must submit an Internal Study Personnel Change form in INSPIR before submitting the change to the Commercial IRB, so that we can comply with our agreement with the Commercial IRB by ensuring training certifications and COI disclosures are completed.

  2. If there is an amendment that requires review and sign-off from a department that has not previously been involved in the review of the study (e.g., radiation safety, biosafety, pharmacy, departmental approvals, nursing review, Clinical Trials Office), then you must submit an INSPIR Change Request and Amendment form to notify us before implementing the amendment. You must also submit an INSPIR Change Request and Amendment for local context review of any proposed recruitment methods (including changes in populations such as Cognitively Impaired or Non-English Speakers) that differ from what had been submitted initially to the IRB.

  3. If an Unanticipated Problem occurs at this site that involves potential harm to a local subject, then you must submit a RENI to report the incident to us, as well as reporting to the reviewing IRB. The purpose of this is to give us an opportunity to help mitigate the harm without delay.

  4. When the study is closed by the Commercial IRB, then submit a Final Report for your INSPIR ceded application. (This Final Report is a very short form to close the ceded study in INSPIR.)

Please reach out to the IRB Analyst if you ever have any questions about what needs to be submitted to the BMC/BU Medical Campus IRB for a study that is ceded to a commercial IRB.

 

OTHER REQUIREMENTS

As with studies that are not ceded to an external IRB, you must ensure that all study staff who are engaged in human subjects research remain up to date with their training requirements:

Study personnel must be current with CITI Medical Campus certification/recertification.

Study personnel must be current with GCP Medical Campus training for clinical trials.

There are also special requirements for adding BU-Charles River Campus (CRC) investigators to the study. BMC/BU Medical Campus IRB cannot provide IRB oversight for BU-CRC investigators who are engaged on behalf of BU-CRC (such as BU-CRC faculty, or BU-CRC students who are receiving academic credit).

  • BU-CRC students can be added as internal study personnel only if they are engaged in research (interacting with subjects for the purpose of collecting data or accessing identifiable data) and have a BMC ID#; or if they are conducting research activities on behalf of BU Medical Campus and not for BU- CRC academic credit.  They should follow these instructions to set up their INSPIR accounts so that their names will be listed in the system to add them to the INSPIR application in Section 3.2:  How to get access to INSPIR II.  They are also subject to the same Medical Campus CITI training requirements for internal study personnel.

  • The SMART IRB reliance acknowledgement letter between the BMC/BU Medical Campus IRB and the commercial IRB only covers internal BMC/BU Medical Campus investigators.  Therefore, BU-CRC students seeking BU-CRC academic credit; BU-CRC faculty, physicians, and employees; and independent or volunteer investigators cannot be added to the INSPIR commercial IRB IND or IDE cede application.  Instead, the BU-CRC IRB and the independent or volunteer investigators will need to enter into reliance agreements directly with the commercial IRB.  

 
Massachusetts Controlled Substances Registration

BMC and BU Medical Campus Principal Investigators (PI) must have their own Massachusetts Controlled Research Licenses for IND protocols to be in compliance with the updated Massachusetts state law. Please ensure that if the PI is conducting ANY drug study that has an IND, that the proper Massachusetts Research License will be obtained or an existing license will be updated as soon as possible after IRB approval. For information, see BU CR Times Feature Article: MCSR Research License. You may also contact the MCSR Research License Administrator for assistance:  Karla Damus, damusk@bu.edu, (617) 358-5337.

 

Summary

Researchers at BMC and BU Medical Campus have the option to rely on another IRB (cede review) for certain types of studies. If the request is to rely on a commercial IRB and the study is industry-sponsored, the study must be a multi-site trial involving an Investigational New Drug Application (IND) or an Investigational Device Exemption (IDE) held by the industry sponsor. Our local cede review process for these types of studies involves a number of special steps that need to be followed in order to facilitate oversight by an external commercial IRB. While submitting to two IRB’s has the potential to become more complicated, if you follow the steps outlined above, the process will be much more efficient.