Modification

• What Modifications Need IRB Approval?
• Types of Modifications (Updated July 2026)
• Modifications Requiring Full Committee Review
• Modifications that can be Reviewed by Expedited Procedures
• Protocol Enrollment Exceptions
• Submitting in Research Gateway IRB (ReGI)
• Information for Continuing Subjects
• Exempt Research
• Adding or Removing Investigators or Staff
• Changing or Adding Funding Info, Changing or Adding Sites, Changing Locations within UCSF, Changes in Researchers’ Financial Interests

🛠️What Modifications Need IRB Approval?

All changes to your study, even minor ones, must receive IRB approval before you implement them. For example, changes in inclusion criteria, procedures, recruitment, advertisements, consent forms and questionnaires all require IRB review and approval.

NOTE:

• Considerable changes to the study’s research plan (e.g., Hypothesis; Aims/Objectives; Procedures; Study design; Scope; Intervention) require the submission of a new study. Modifications to an existing study must fit within the original aims of the study. For example, a No Participant Contact study cannot be modified and made into a Participant Contact study.
• Implementing changes without IRB approval is a violation of federal regulations and University policies and can lead to the suspension of IRB approval and other serious consequences for the participants, investigators and University.
• If the study has a protocol provided by a sponsor, cooperative group, or other external organization, and the modification involves changes to that protocol (e.g., changes to inclusion/exclusion criteria, changes to procedures, etc.), you must submit the revised protocol within the Modification SmartForm. Only submitting a Modification SmartForm and revising the IRB Application document is not sufficient.
• Continue to submit protocol amendments until the study is closed by the sponsor. If enrollment is permanently closed and the new information doesn’t need to be relayed to the study participants, you do not need to submit a revised informed consent form. But you do need to revise the IRB Application document and Study SmartForm (if needed).

• The IRB does not approve “planned deviations” i.e., planned departures from what the IRB has approved. Please see below for the only exceptions to this. You must follow the IRB-approved materials (e.g., IRB Application, protocol and informed consent forms). If you need to make changes, submit a Modification SmartForm that includes the revised IRB Application, the revised protocol if the study has a protocol, and any other revised study documents such as the informed consent form. For studies in which the UCSF PI does not have protocol control (e.g., some multicenter trials), and the revised protocol has not yet been issued by the sponsor/lead site, you may submit a Modification SmartForm and include a Letter of Amendment from the entity that has protocol control. The Letter of Amendment must describe the upcoming protocol change and when the revised protocol will be submitted to the IRB for review. If the changes described in the Letter of Amendment affect the IRB Study Application, informed consent form, or any other documents, you must make those changes when submitting the Letter of Amendment. 

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Exceptions: 

• Changes “necessary to eliminate apparent immediate hazards to the participant”

  • The requirement for prior IRB review and approval is not required when the changes are “necessary to eliminate apparent immediate hazards to the subject” (45 CFR 46.103.b.4, 21 CFR 56.108.a). In such rare cases, report the actions taken to the IRB within 10 working days using the Protocol Violation or Incident Reporting Form. Seek approval for permanent changes to prevent the hazards in the future.

• Minor (not significant) changes to exempt research

  • For exempt research only, you can make minor changes to the study without notifying the IRB. However, you must submit significant changes to the IRB. 

📋Types of Modifications (Updated July 2026)

NEW JULY 2026: All modifications – including major, minor, administrative, and personnel changes – are submitted using the Modification/CR Form in Research Gateway IRB. The Modification SmartForm will no longer ask you if the modification qualifies as major, minor, or administrative. 

To help aid the IRB’s review of your modification request: 

• Please thoroughly describe the changes so the IRB can determine the appropriate level of review required.
• The Principal Investigator must indicate if the changes alter the study’s overall risk/benefit ratio.

The IRB will determine the appropriate level of review based on the nature of the proposed changes and the risks associated with the research. Depending on the changes, a modification may be reviewed by an IRB reviewer using expedited review procedures or by the convened IRB at a full committee meeting.

In general, modifications that involve more significant changes to the study, increase risks to participants, or substantially alter the approved research may require review by the convened IRB. Modifications that involve less significant changes and do not substantially affect the risks, benefits, or overall design of the study may be eligible for expedited review.

Study changes are typically reviewed by the IRB panel that originally reviewed the study. 

OHRP and FDA guidance allows the IRB to use an expedited review procedure to review "minor changes in previously approved research."  The IRB makes the final determination as to whether study changes qualify as “minor changes in previously approved research.”

Below are definitions and examples review levels for modifications. 

IRB committee members identified barriers to efficiently reviewing modifications to complex trials (including umbrella trials and adaptive designs). “Umbrella trials” are studies that assign a particular treatment to a patient based on the type of cancer or unique tumor characteristics, such as molecular markers. Because there are often many treatment arms that come and go based on the study results or other data, the review of modifications can be very challenging. To facilitate IRB review, if you are submitting modifications to complex trials, in addition to completing all sections of the Modification SmartForm, please ensure that the following information is included in the section where modifications are described. Please ensure this information is in lay language, understandable to non-scientists and scientists.

• Provide a brief general scientific rationale for submitting these changes
• Describe how the proposed changes fit into the overall progress of the study
• Describe any removals or additions of study treatment or patient populations
• Include citations for published articles that support these changes if available

👥Modifications Requiring Full Committee Review

👤Modifications that can be Reviewed by Expedited Procedures

Protocol Enrollment Exceptions

As of June 13, 2026, the UCSF IRB does not accept protocol enrollment exception requests. If a Principal Investigator (PI) wishes to enroll a participant who does not meet the IRB-approved eligibility criteria, the protocol must first be revised to incorporate the proposed changes to the eligibility criteria and include a justification for those changes. The IRB will review the revision and, if appropriate, approve the updated eligibility criteria before any participant who does not meet the previously approved criteria may be enrolled. Participants who do not meet the currently IRB-approved eligibility criteria may not be enrolled until the IRB has reviewed and approved the revised protocol. 

💻Submitting in Research Gateway IRB (ReGI) 

Please refer to the ReGI user guides for detailed instructions and screenshots. 

Here are some submission tips: 

• Before creating a new Modification SmartForm: If someone other than the PI will submit this to the IRB, they must be listed as a PI Proxy for the study. If not done already, the PI should add the study team members of their choosing to the PI Proxy role. See the user guide: Assign PI Proxies.
• While completing the Modification SmartForm: Answer the Modification scope question carefully – it cannot be changed after you save the page. 
• Complete the form and answer every question – even those without red asterisks – unless a question is not applicable to your study.
• When revising Microsoft Word documents, enable Track Changes so all revisions are visible.
• If you are uploading a new version of a document that has already been submitted, click Update to upload it as a revision. Do not upload it as a new document.
• See the Initial Submission Checklist for a list of documents that require IRB review. 

Reminders:

• You may combine multiple study changes into a single Modification SmartForm, but only one Modification SmartForm may be submitted at a time. The only exception is that a Modification SmartForm limited to study team member changes may be submitted while another Modification SmartForm for other study changes is under review.
• If you make several changes to your study at one time, describe each change in detail on the Modification SmartForm. Hold additional modifications until your modification has been approved. Contact the IRB Coordinator assigned to the modification with questions.
• Some modifications are required in response to Reportable New Information (RNI), such as an adverse event, protocol violation, incident, DSMB/DMC report, sponsor action letter, or other safety report. Whenever possible, submit the Modification SmartForm at the same time as the RNI report.
  • If applicable, link the Modification SmartForm to the RNI report using the Associated Studies field in the RNI Form.
  • If the RNI report and Modification SmartForm cannot be submitted at the same time, explain the reason for the delay in both submissions.

👥Information for Continuing Participants

Per federal regulations, research participants must be informed when there is a significant new finding during the course of research that may affect their willingness to participate [45 CFR 46.116 (b) (5)]. Examples of significant new findings include:

• New risks or previously described risks that are now found to occur with greater frequency or severity.
• Changes to the protocol that may affect a subject’s willingness to participate in the research.

If any significant new findings or protocol changes are included in your modification request:

• Describe how you propose to inform current subjects of this information.
• Attach any additional consent forms (see our consent form addendum template) or contact letters that will be used for this purpose.

The level of urgency will determine how the information is communicated to participants. See the Adverse Event Reporting Requirements for additional information.

🟢Exempt Research

Only for studies that the IRB has certified as exempt, researchers can make minor changes to the study without notifying the IRB. However, significant changes must be submitted to the IRB. See the examples below.

All changes must follow UCSF guidance, and some changes are not allowed in the consent materials.

Examples of significant changes to Exempt Research: Submit to the IRB

• Adding a new subject population
• Adding new procedures
• Adding a new funding source
• Adding new collaborators or outside sites (each site must obtain their own Exempt Certification or IRB Approval)
• Adding questions about sensitive aspects of the subjects’ behavior – such as illegal conduct, drug use, sexual behavior or use of alcohol – to a survey or interview
• Change in PI
• Disclosing a new financial interest
• Any change that makes the study no longer eligible for exemption
• Revising aims
• Changes to payment (adding, revising, or removing)

Examples of minor changes to Exempt Research (do not submit to the IRB)

• Editorial or administrative revisions to consent documents or other study documents
• Adding non-sensitive questions to a survey or interview, or revising current questions
• Adding a new recruitment material that follows IRB guidelines
• Increasing or decreasing the number of subjects, unless you are adding a new subject population
• Study team/personnel changes (except a change in PI)
  • Note: If new study team members need to edit or access materials in ReGI, you will need to submit a Modification SmartForm to add them to the study (follow the steps below).

🪪Adding or Removing Investigators or Staff

Some of these changes require submission of a Modification SmartForm. Click on the role of the individual you are changing for more info. Review the Research Gateway IRB user guides for step-by-step instructions and screenshots.