Modification

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 Subject Contact study cannot be modified and made into a Subject 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, and the changes affect the protocol (e.g., changes to inclusion/exclusion criteria, changes to procedures, etc.), you must submit the revised protocol within the Modification Form. Only submitting a Modification Form and revising the IRB application 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.
  • 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 Study Application/protocol and informed consent forms). If you need to make changes, submit a Modification Form that includes the revised IRB Study 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 Form 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. 

Exceptions: 

Changes “necessary to eliminate apparent immediate hazards to the subject”

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 November 2024)

Evaluate whether the proposed changes constitute a major modification, minor modification, personnel change, addition of relying sites, or administrative modification using the definitions and examples below. 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 to help guide the Principal Investigator in determining what form to submit in iRIS, based on the proposed study changes.

If using the Modification Form, the Principal Investigator must determine if the changes alter the study’s overall risk/benefit ratio.

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 form, 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

Major Modifications

Definition

1. Any increase in risk to participants is more than minimal; OR;


2. Any additional activity or procedure would not be eligible for expedited review if submitted as part of new research, OR 


3. The research itself involves more than minimal risk and the changes significantly alter the study design. 

Examples

1. Increasing major risks or discomforts 


2. Adding or deleting major procedures or diagnostic tests


3. Restarting a study after a hold for safety concerns


4. Changing, adding, or deleting drugs, devices, or other treatments being studied may be considered a minor change if it involves substituting approved treatments used in standard ways. This also includes any changes that involve altering the active ingredient or other changes defined in 310.3 as a 'new drug substance'

Process 

Submit a Modification Form in iRIS.

On the form, check the box for "Major Modification."

Reviewed by the full committee at a convened meeting. Approval letter issued. 

Minor Modifications

Definition

1. Any increase in risk to participants is no more than minimal risk, AND 


2. All additional activities or procedures would be eligible for expedited review if submitted as part of new research, AND;


3. Either the research itself involves minimal riskor the changes do not significantly alter the study design.

Examples

1. Changing minor procedures or activities without adding more-than-minimal risks 


2. Reducing risks or adding minor risks


3. Changing wording in the consent form, application or other documents


4. Adding a new advertisement

Process

Submit a Modification Form in iRIS. 

On the form, check the box for "Minor Modification."

Reviewed by a small number of IRB members using expedited review procedures. Approval letter sent.

Personnel Changes

Definition

Additions or removals of Key Study Personnel (KSP)

Examples

1. Change in Principal Investigator (PI)


2. Change in Investigators or staff who are Key Study Personnel (KSP)

Process

Submit a Personnel Changes Form in iRIS.

Reviewed by a small number of IRB members or staff. Approval letter sent for all Key Study Personnel changes.

Add Relying Site 

Definition

Addition of outside sites (sites that are not at UCSF and are not a UCSF-affiliate) that are seeking to rely on the UCSF IRB.

Note: Advance agreement for UCSF to serve as the IRB of record is required before you submit this form. If you have not yet had a consultation with a UCSF IRB Analyst about this, review the Reliance Request page and submit the appropriate consultation request form. 

Example

Adding an outside study site that will rely on UCSF as the IRB of Record for that site.

Process

Submit an Add Relying Site form in iRIS.

Reviewed by a small number of IRB members or staff. IRB approval letter sent.

Administrative Modifications

Definition

Minor changes that do not affect study participants in any way.

 

Examples

1. Changing procedures that do not affect participants (e.g., method of shipping samples)


2. Fixing typographical, grammatical or spelling errors

Process

Submit a Modification Form in iRIS.

On the form, check the box for "Administrative" changes.

Reviewed by a small number of IRB members or staff using expedited review procedures. Approval letter sent; however, no letter is sent for optional modifications to change research support staff or study contacts who are not Key Study Personnel.

Submitting in iRIS

Follow these steps to submit a modification after your study is approved. For additional assistance, read the quick guide called "Submitting Post-approval Forms" in the Help section of iRIS or on the iRIS Help webpage.

1. Open the study via IRB Study Assistant (Go to My Studies under the IRB Study Assistant. Open the active study you want to modify.)

2. Start a new form (see tables above for which form to use, based on the proposed study changes.)

3. Complete the Form (This is a dynamic form that will build automatically based on how you answer each question.)

4. Attach new or revised documents or applications (Attach any new or revised documents or applications in the appropriate section (e.g. attach the revised IRB Application in the "Revisions to the Application Form" section). Do NOT track your changes. See the Initial Submission Checklist for a list of documents that require IRB review. Reminder: If you are changing study personnel, revise and attach the IRB Application Form.)

5. Submit the form (Anyone listed on the study can sign off and submit the Modification Form.)

Reminders:

You can combine several changes to your study in one modification request, but only submit one Modification Form at a time

You can make several changes to your study at one time — describe each change in detail on the Modification Form. However, in general, do not submit more than one Modification Form at a time, particularly if both modifications involve the IRB Application form or the same document. Hold additional modifications until the first request has been approved. Contact the analyst assigned to the modification with que

Submit modifications resulting from an adverse event, violation, incident or other safety report at the same time as that report, when possible

Some modifications are required based on a report of an adverse event, protocol violation or incident; a DSMB or DMC report; an action letter from a sponsor; or other safety report. Submit the modification at the same time as the report, whenever possible. If the report and the modification are not submitted concurrently, explain in both the report and modification why it is/was necessary to delay the modification submission to a later date.

Information for Continuing Subjects

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 (use the Personnel Changes form)
  • 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: 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) — follow the steps below in iRIS to grant access to new study team members.

Changing or Adding Investigators or Staff

Some of these changes require submission of a modification or Personnel Changes form. Click on the role of the individual you are changing for more info.

Changing or Adding Funding Info 

You must submit a modification to the IRB to add a new funding source to an approved study. The IRB must approve the modification before the Office of Sponsored Research (OSR) may accept the new award. OSR administrators have access to iRIS and can verify approval of the new funding source.

Submit a Modification Form and describe the new funding source. Attach the following items:

1. A revised IRB Application 

"Funding" section:

  1. Indicate "Yes" for the federal funding question if your study receives any federal funds, even if they come through a subcontract or another source from the prime awardee.
  2. Add the new funding source. If your study includes a subcontract, specify the prime sponsor, such as the NIH.
  3. For all studies with funding through UCSF, either the Award Number (A Number) OR the Proposal Number (P Number) is required. The A Number should be added when other changes are being submitted.
  4. If applicable, list the grant title and PI, and explain any significant discrepancies between the IRB application and the grant or contract.

Key Study Personnel sections: The PI of the award must be listed as an investigator on the IRB Application, so update sections 3 and 4, if necessary.

2. Consent documents (if applicable)

Update the consent document(s) if the sponsor info needs to be changed.

Removing a Funding Source: Please do not remove a funding source from the IRB Application if funding has ended. You can remove a sponsor if the study was never funded (e.g. a grant was submitted, but not funded).

Changing RAS Proposal numbers (P#) to Award numbers (A#): The IRB requires either a P# or an A# at the time the funding source is added, not both, but the A Number is needed at the time of the next Modification.  Do not submit a Modification only to add the A Number but please include it at the time that other changes are being made.

Changing or Adding Sites

Most site additions require changes in the consent form and the Application — especially the "Sites," "Procedures," "Sample Size and Eligibility" and "Recruitment" sections — and completion of an "Outside Site Information" subform. You may also need to change your recruitment documents.

In general, the IRB at the new site must approve the study before work can begin there. See the Working With Other Institutions page for more info. 

If you are adding a site that is affiliated with UCSF, see the UCSF Affiliated Institutions page.

Changing Locations within UCSF

If you move to another UCSF campus (e.g., from Parnassus to Mission Bay), the study site and address need to be updated in the consent form. A modification form needs to be submitted, but can be batched with your next, upcoming submission. A separate modification form does not have to be submitted solely to update the address.

Changes in Researchers’ Financial Interests

Report any changes the researchers’ financial interests related to the study to the Conflict of Interest Advisory Committee (COIAC). The COIAC will advise the PI and the IRB if modifications in the study are needed.

If there are changes in researchers’ financial interests that have not yet been reported to the IRB at the time of a modification, update the IRB Application and describe the change in the Modification Form. 

Last updated: December 12, 2024