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• Once a study has received initial IRB approval, any new change/modification to the study or consent form is considered an a modification, and the proposed modification must be submitted to the IRB for review.
• The NIH IRB must approve the modification before any change can be initiated or before updated materials can be used except when necessary to eliminate apparent immediate hazards to a subject.
• You are responsible for ensuring timely submission to the IRB of all modifications.

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For modifications to research determined to be exempt (whether reviewed by exempt procedures or limited IRB procedures), the following materials must be submitted via the NIH electronic IRB system:. For any forms or documents being uploaded include the word "exempt" in the title.

• Modification Submission Form Study Application attached to the Modification Formincluding applicable changes
• Revised research protocolproject
• Other revised documents, When the proposed research involves prospective collection of data, include the following documentation, as applicable:
  1. Revised document outlining the elements of informed consent (e.g., consent form, information sheet, verbal script, etc.)
  2. Revised recruitment material, as applicable (e.g., flyers, posters, scripts, social media ads), as applicable
  3. Revised study instruments used to collect data from research subjects (e.g., surveys, interview forms, questionnaires, assessments)
• Any other documents or information that the IRBO requests

What are the required materials that I must submit for

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a modification to my non-exempt human subjects research study?

For modifications to previously approved non-exempt human subjects research (whether reviewed by the convened IRB or by expedited procedures), submit the following materials via the NIH electronic IRB system: 

• Modification Submission Form Study Application should be updated to reflect changes and must be included as part of the modification submissionincluding applicable changes
• Revised protocol, as applicable
• Revised informed consent and/or assent documents (e.g., consent, parental permission, information sheets, verbal script), as applicable
• If your protocol is a covered protocol and a new NIH investigator is being added, documentation of the Deputy Ethics Counselor (DEC) clearance is required. (See this earlier section of the manual for information on the DEC clearance process.)
• Any other documents or information that the IRBO requests

What are the required materials that I must submit for modifications to my non-exempt human subjects research study when adding a participating site to initiate multi-site research or to expand any existing multi-site protocol?

The process for adding non-NIH participating sites (pSites) in the electronic IRB system is described in the manuals available on the IRBO website.  When the NIH IRB is the Reviewing IRB, and you are adding a participating site, whether to initiate multi-site research or to expand an existing multi-site protocol, make certain the modification includes the following documentation:

• Submit Basic Site Information using the eIRB submission form.

• Upload supporting documents including the following:

      1. pSite Protocol Addendum (using the IRBO template;

      2. pSite Consents/ Assents (if applicable);

      3. pSite Recruitment materials (if applicable) which is is documentation confirming that the pSite’s institutional requirements have been met and that local context information provided

• Letter of support from the participating site where the research will be conducted indicating that local site requirements have been met.
• The NIH model consent form template that includes the participating site's required site-specific language (e.g., subject injury language, conflict of interest language), as applicable.
• The participating site's completed local context questionnaireNote: The NIH IRB will only approve the addition of a participating site after it has received confirmation that the local context information provided,

  has been approved by the relying institution

   andThe institutional requirements of the relying institution have been met.

  ; this can be documented via a letter, email, memo,  etc.;

     4. pSite HRPP Clearance (via letter or email)

  
  

• Any other documents or information that the IRBO requests.

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• The IRB Coordinator will send back modifications if the PI or any investigator is delinquent with their required HRPP training.
• If any investigators are added to the study after IRB approval, they need to complete the required training as indicated in Policy 301, Education Program and be added to the Study Personnel Page/Key Study Personnel Page via an modificationby submitting a modification form.

What format should I use for my protocol and/or consent form when submitting

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a modification?

• The protocol and consent document must be in clean Microsoft Word format. (However, if you are submitting a tracked pdf that the sponsor has provided for IRB submission, this may be included with tracked changes noted.)
• When submitting documents to the NIH electronic IRB system, each electronic regulatory file must have a consistent format, including naming of folders and files, to ensure required information is maintained and easily accessible.
• For proper nomenclature study teams are required to use when submitting documents to the NIH IRB. Refer to the section of the OHSRP website which outlines required nomenclature for protocols, consent forms and other study documents titled How to Name Documents for Submission to the IRB.

What is the process when changes to the protocol require approval by other committee(s) as part of

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a modification submission?

• Identification of which additional ancillary reviews are needed will be based on the modifications you are making to the protocol and/or consent form.
• IRB review of your modification may be delayed until such ancillary review approvals are received.
• The requirements for each type of ancillary review are set by the specific review committee.
• See the section regarding Ancillary Reviews in the Initial Review section of this investigator manual.

What happens after the IRB receives my submission for

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a modification?

• NIH IRBO is responsible for screening all submissions to determine whether the modification needs to be reviewed by the convened IRB or can be processed via expedited review.
• Once all documents relevant to the modification gets submitted in the NIH electronic IRB system, the internal review process begins:

1. Analyst Pre-Review: The IRBO Analyst conducts a pre-review of all documents submitted via the NIH electronic IRB system and verifies the submission meets minimum standard to be considered complete for pre-review. The analyst verifies all sections in the Modification Form modification form are properly completed. All necessary updates to the consent, recruitment documents and questionnaires/data collection instruments should be attached as applicable. Revised documents should be named properly. Ensure there is consistency with all documents submitted.
2. Potential withdrawal: For any missing or incomplete documents, the submission is considered "incomplete" and will be returned to the study team to address the Pre-review changes being requestedrequest for clarification. It is the responsibility of the study team to respond to requests for clarifications or corrections from the IRBO. At its discretion, the IRBO may administratively withdraw submissions from IRB consideration when the PI is non-responsive to requests from the IRB or from IRBO staff for 30 calendar days. The investigator will be notified by the IRBO if the submission is administratively withdrawn.
3. Addressing Pre-review Change (Stipulations)Requests for Clarifications: Before your submission is reviewed by the IRB, the Analyst may ask you to make some changes that will be sent as a stipulationRequest for Clarification.
   • When you are responding to changes/stipulationsthese request:
     1. Respond to Study Application study information questions directly in the NIH electronic IRB system.
     2. Provide written responses, when appropriate.
     3. If a tracked document is provided by the IRBO Analyst…use it!
     4. Review the changes, accept the changes, and upload a clean (and tracked) version of the document into the application.
     5. If you don't want to accept changes…provide a justification.
     6. Make sure you address/respond to ALL requests for clarifications/changes/stipulations.
     7. Return to the IRB in a timely manner.
4. Analyst Pre-Review of StipulationsRequest for Clarification/Study Team Responses - Responses to the stipulations which you submitted are reviewed by the IRB Analyst. Once the analyst confirms that required corrections have been made/addressed and all supporting documents are available, the submission is assigned a review level (Expedited or Full Board) review.
5. IRB Review - When conducting its review, the convened NIH IRB, or expedited reviewer must review the submission materials in order to determine that all regulatory and policy requirements for approval of research are met, or whether more information is needed to make a determination.

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• If the proposed change to the research adversely impacts risk/benefit or if the changes are more than a minor change, the modification is sent to full board. This could include research that was previously expedited.
• If the proposed change to the research is a minor change that does not adversely impact risk/ benefit, it may be considered for expedited review.
• If your level of review does not follow the above parameters, please contact the IRBO Analyst.

Levels of Review:

What happens when my modification to my non-exempt research study undergoes Full Board Review?

• At Full Board Review the Board votes as per below:
  • ApprovedApproved with stipulations
  • Modifications required to secure approval
  • Deferred
  • Disapproved
• IRB Approval - If the modification is approved, the NIH IRBO will issue the " NIH IRB Modification Approval Letter" addressed letter addressed to the PI. The letter is sent via the NIH electronic IRB system. The outcome letter indicates the approval date, review level of the modification (Full Board vs Expedited Review). Any action item(s) such as required re-consent of subjects, will be stated in the modification approval letter.

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