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THE COMMITTEE ON HUMAN RESEARCH

UCSF GUIDANCE ON RESEARCH TOPICS AND ISSUES

General Instructions: Modification Request
(Posted February 2005; Effective February 2005, Revised July 2006)

 • Brief Overview
 • Modifications and Renewals
 • Major Modifications Treated as Renewals
 • Including Modifications with Regularly Scheduled Renewals
 • What to Submit: Major Versus Minor or Administrative Modifications
 • Definitions
 • For Studies That Initially Required Full Committee Review
 • For Studies That Initially Required Expedited Review
 • Information for Continuing Subjects
 • Exempt Studies
 • Changing or Adding Investigators or Other Personnel
 • Changing or Adding Sites
 • Enrollment Exceptions
 • Modifications Resulting from Adverse Events, Incidents, Violations, and Other Reports
 • Changes in Researchers’ Financial Interests
 • Items to Include in Modification Request
 • Hints for Speedy Approval
 • When to Submit Modifications
 • Expiration Dates
 • Where to Submit
 • Additional Information

Brief Overview

All changes to a study, even minor ones, must receive CHR approval before they are implemented. For example, changes in screening, entry criteria, procedures, protocol, recruitment letters, advertisements, consent forms, and questionnaires all require CHR review and approval.

Note: The only exception (rarely encountered) to the requirement for prior CHR review and approval is 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 cases, the actions taken should be reported to the CHR within 5 working days, and approval should be sought for permanent changes to prevent the hazards in the future.

Major, Minor, and Administrative modifications should be submitted using different kinds of applications and will receive different levels of review from the CHR, as explained in detail below.

Note: Implementing changes without CHR approval is a violation of federal regulations and University policies and can lead to the suspension of CHR approval and other serious consequences for the participants, the investigators, and the University.

Modifications and Renewals

Major Modifications Treated as Renewals
New in January 2005: The CHR now requests that all major modifications (defined below) be submitted using the Status Report for Renewals and Major Modifications regardless of whether the study’s approval is due to expire soon. The application should include all other materials required for a renewal application. When the modification is approved, the study’s expiration date can be extended (usually to a year after the modification is reviewed), as is done for any regularly scheduled renewal application.

Including Modifications with Regularly Scheduled Renewals: You can include modifications (major or minor) with the regularly scheduled renewal application. You should take care to note on the application form and status report that the application includes both renewal and modification requests.

• Advantages to submitting modifications along with a renewal:
  • Submitting modifications along with a renewal can save review time, as long as the modifications do not raise questions requiring extensive correspondence.
  
  
  
  • Only a single application and a single review are needed.



• Disadvantage to submitting modifications along with a renewal:
  • If the CHR has questions about the modification, approval for the whole study will be delayed, and the current approval may expire, in which case activities involving human research subjects must stop (unless needed for participant safety) until a new approval is obtained.



• Best Strategy: If a study’s expiration date is close, give serious consideration to holding possibly controversial modification requests until after the renewal has been approved.

See Renewals and Major Modifications Submission Checklist for specific submission requirements for renewing and modifying a study at the same time.

Important Note: Any renewal application that includes a significant modification should be submitted early enough (6 weeks before expiration) to allow time for back-and-forth correspondence if needed.

What to Submit: Major Versus Minor or Administrative Modifications

The principal investigator should evaluate whether a modification is major, minor, or administrative, using the definitions and tables of examples below (also available separately in the page Categories of Modifications). The determination depends on whether risks to participants are increased and the complexity of the changes. Major modifications require more copies and more intensive review than minor or administrative modifications. For questions about what kind of modification you have, please call the CHR office at 476-1814 and ask to be connected with a specialist handling modification requests or contact us.

Definitions
(examples follow below)

• Major Modifications to previously approved research are changes in which
  • Any increase in risk to participants is more than minimal
    (See definition of Minimal Risk.)
    
  or
  
  • any additional activity or procedure would not be eligible for
    expedited review if submitted as part of new research
    
  or
  
  • the research itself involves more than minimal risks and the changes significantly alter the study design.


• Minor Modifications to previously approved research are changes in which
  • any increase in risk to participants is no more than minimal risk
    
  and
  
  • all additional activities or procedures would be eligible for review using the expedited procedures if submitted as part of new research
    
  and
  
  • either the research itself involves minimal risks or the changes do not significantly alter the study design.


• Administrative Modifications are Minor Modifications that do not affect study participants (subjects) in any way.

Important Note: If reasonable reviewers may differ on what category applies (e.g., on whether a change increases risks so they are more than minimal) the application should be submitted for the more stringent level of review.

Examples of types of modifications follow below:

FOR STUDIES THAT INITIALLY REQUIRED FULL COMMITTEE REVIEW

FOR STUDIES THAT INITIALLY REQUIRED EXPEDITED REVIEW

Important Note: If a CHR member reviewing a "minor" or “administrative” modification request feels that it is too substantive to receive this type of review, the application will be referred for a higher level of review.

Information for Continuing Subjects

Current participants must be informed about any significant new findings or protocol changes that might relate to their willingness to continue participation.

• If any significant new findings or protocol changes are included in your modification request, please describe how you propose to inform current subjects of this information.
• If any additional consent forms or contact letters will be used for this purpose, please attach copies for review.

See HRPP Post-Approval Reporting Requirements for additional information about reporting new findings.

Exempt Studies

If the investigator plans any modifications of activities described in a previously approved Exempt Certification Form, a new Exempt Certification Form with changes highlighted should be submitted for reconsideration. Please mark in the Application Type section of Administrative Requirements that this is a Modification/Update. The exemption can then be recertified for a new 3-year period. See Exempt Certification Application for more information.

Important Note: If you are adding activities to an exempt study, check the What Type of Application Should I Submit to see if the activities mean the study now requires Expedited or Full Committee review.

Changing or Adding Investigators or Other Personnel

Changing the Principal Investigator:

• Major vs Minor: A change of PI is a minor modification if the new PI has a background, resources, and privileges that are equivalent to the original PI’s. A change of PI is a major modification in a Full Committee study if it significantly changes the expertise or resources available to the study or requires other major changes in the conduct of the study. A Change of PI in an Expedited study is a minor modification.



• A letter signed by the outgoing Principal Investigator requesting the change in PI must accompany the modification request.



• Revised versions of consent forms, recruitment letters, and any other participant-contact documents naming the PI should be submitted for review.



• A revised Disclosure of Investigators’ Financial Interests Supplement should be submitted if needed.

Changing the Co-PI, Key Personnel , including Other Investigators:

• If the change includes the Co-PI (who should be able to assume many of the duties of the PI) or people who are named on consent forms, recruitment letters, or any other participant-contact documents, the change should be submitted as a minor modification including copies of all revised documents.



• If the PI and Co-PI stay the same and no participant-contact documents need to be revised, the change may be submitted as an administrative modification.



• A revised Disclosure of Investigators’ Financial Interests Supplement should be submitted if needed.
  

Changing or Adding Sites

You must obtain CHR approval before beginning work at a new site. Most site additions require changes in the Application (especially the first page and the Subject Information and Recruitment sections) and the consent form; many require changes in recruitment documents. See Working with Other Institutions and Application Supplement: IRB Approval Certification for UCSF Researchers Involving Non-UCSF Affiliated Sites for detailed information; what follows below is only a brief summary of common requirements.

• Required Approvals: Investigators adding sites must ensure that all necessary approvals are in place.
  • San Francisco Veterans Affairs Medical Center: Modifications adding the SF VAMC as a site should be submitted to the VA’s Clinical Research Office, which must give separate approval before work can begin at the VAMC. The VAMC has numerous requirements, including naming of an investigator with appropriate status at the VAMC and specific format and wording for consent forms, and there are restrictions on certain types of research at the VAMC.
  See Working with the Veterans Affairs Medical Center for additional information.
  
  
  • Other Institutions that Have Federalwide Assurances (FWAs) that Designate the CHR as their IRB: Several of the institutions that have agreements to use the CHR as their Institutional Review Board also have additional requirements before human research may proceed at their site. For example, the San Francisco General Hospital has an additional application process to ensure that appropriate resources are available. Researchers should become familiar with each institution’s requirements.
  
  
  
  • Institutions not affiliated with UCSF:
    • Federalwide Assurances: If federal funding is involved, each institution engaged in the research must have its own Federalwide Assurance (FWA) agreement with DHHS’s Office for Human Research Protection. Work may not begin at the new sites until the required approvals and assurances are complete.
    
    
    
    • Institutional IRBs: Some institutions require that any researcher enrolling the institution’s patients or clients or using its resources obtain approval from the institution’s own IRB. If so, a copy of the approval must be forwarded to the CHR before recruitment can begin at that site.
    
    
    
    • Collaborations: Collaborating researchers from other institutions or without an affiliation must obtain approval from their own institution’s IRB or a contract IRB. The CHR does not serve as IRB for non-UCSF researchers.
    
    
    
    • Letters of Support: A letter of support may be all that is needed from a site if all of the following conditions are met:
      • The site does not have its own IRB requirements.
      
      
      
      • UCSF investigators are responsible for all contact with participants and the additional site is simply allowing access to its clients.
      
      
      
      • The study involves no more than minimal risks and is eligible for expedited review.
      
      
      
      • There is no federal funding for the study.
    
    
    
    • The letter should be signed by a responsible official, granting access to the researchers. The letter must be on file before work can begin at that site.
      



• Major vs Minor or Administrative:
  • Most site additions are considered minor modifications.
  
  
  
  • Some site additions in themselves change study risks. For example, adding a jail or prison as a site requires special consideration and generally should be submitted as a major modification.
    

Enrollment Exceptions

For Individuals Who Do Not Meet Entry Criteria: To allow enrollment of a of a single individual who does not meet entry criteria of a CHR-approved protocol, the Principal Investigator may submit a written request for a one-time enrollment exception as a protocol modification request to the CHR. This enrollment exception request applies only to a single individual. Such a request should be rare and justified in terms of serving the best interests of the potential study participant. Changes of entry criteria for more than one patient should be submitted as regular modifications.

Important Note: If a one-time change is needed urgently for subject safety and there is no time to obtain CHR approval, the change should be implemented immediately and then reported to the CHR within 5 working days. See Reporting Violations and Incidents in Research Protocols for additional information.

What to Submit for Enrollment Exceptions: The request may be submitted in a letter or on the Modification Request for Minor and Administrative Changes form.

To Speed the Process: If approval is needed quickly, call the CHR office (476-1814) and ask to speak to the person handling modification requests. This person will determine whether it can be handled this way, provide instructions to e-mail or fax the letter or modification request form, and contact one of the CHR chair or vice chairs to provide speedy review.

Process: The chair can approve the request if it constitutes a minor change to the study; see tables above for examples of minor changes. The chair may decide that the change requires a higher level of review, and additional documentation may be requested.

When the CHR approves an enrollment exception, data should be collected using the standard case report forms and reported in the scientific evaluation of the study.

Sponsor Review: Most changes in entry criteria also require approval from the study sponsor or cooperative group.

Modifications Resulting from Adverse Events, Violations, Incidents, and Other Safety Reports and Letters

When a modification is required based on a safety report (a report of an adverse event, protocol violation, or incident; a DSMB or DMC report; an action letter from a sponsor, or any other safety report), please submit the modification at the same time as the report, if possible. See What to Submit: Major Versus Minor or Administrative Modifications above or Categories of Modifications to determine what type of modification is needed.

If the report and the modification cannot be submitted at the same time, a cover letter should be included both when you submit the report and when you submit the modification request, explaining why it is/was necessary to delay the modification submission to a later date.

Changes in Researchers’ Financial Interests

Any changes in any of the researchers’ financial interests related to the study should be reported to the Conflict of Interest Advisory Committee (COIAC) officer; see the COIAC web site for additional information.) The COIAC will advise the PI and the CHR if modifications in the CHR study are needed.

In addition, if at the time of a modification or renewal application there are changes in researchers’ financial interests that have not yet been reported to the CHR, the appropriate box in “Financial Interests” section of the modification form should be checked and the Disclosure of Investigators’ Financial Interests Supplement should be submitted, including any revised information. An extra copy of the Supplement should be included with the application to the CHR, so that it can be forwarded to the Conflict of Interest Advisory Committee (COIAC) for review.

Disclosure of financial interests to the COIAC is required so that the CHR can be sure that research participants will be informed of all circumstances that might affect their decision about whether to participate in the study.

Items to Include in Modification Requests

For complete listings of what to submit see the checklist for the type of modification you have. (For types of modifications, see the tables above.)

Renewals and Major Modifications Submission Checklist

Minor and Administrative Modifications Submission Checklist

Hints for Speedy Approval

• Check all previously approved documents and revise them to reflect the new information. Be complete.



• Check the Application field by field. It asks many specific questions and should be revised to describe your study as you will actually be doing it.



• To facilitate committee review, specific changes in modified documents should be bolded, highlighted, or struck through as appropriate.



• If modifications of the study will include work that also requires approval from the Biosafety Committee (BSC), Radiation Safety Committee (RSC) or both the RSC and the Radioactive Drug Research Committee (RDRC), the current approval number(s) should be indicated on the updated application or Cover Page.

When to Submit Modifications

Note: A modification request must be submitted before any change in a study is implemented. Implementing changes without CHR approval is a violation of federal regulations and University policies and can lead to the suspension of CHR approval and other serious consequences for the participants, the investigators, and the University.

The only exception (rarely encountered) to the requirement for prior CHR review and approval is 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 cases, the actions taken should be reported to the CHR within 5 days using the Protocol Violation or Incident Reporting Form, and approval should be sought for permanent changes to prevent the hazards in the future.

Requests for approval of modifications may be submitted at any time.

• Modifications and Renewals: As discussed above,
  • Modifications of any sort may be submitted at the same time as a renewal.
  
  
  
  • Major modifications should be submitted using the Status Report for Renewals and Major Modifications so that the study expiration date can be extended when the modification is approved.



• Several changes to a single study can be included in the same request.



• Hold additional requests until the first request has been approved.
  

Expiration Dates

Major Modifications should be submitted using the Status Report for Renewals and Major Modifications. The expiration date can then be changed when the modification is approved, usually to a year after the modification is reviewed by the committee.

Minor and Administrative Modifications: The expiration date will not be changed when the modification is approved, because the required documentation and the level of review are less than is required for a renewal.

Where to Submit

All modification requests should be forwarded to the Committee on Human Research, Box 0962 (San Francisco, CA 94143). Applications also can be delivered to the Committee on Human Research at the Laurel Heights campus, 3333 California Street, Suite 315.

Additional Information

For additional information or clarification about how to modify an application, please call the CHR office at 476-1814 and ask to be connected with the specialist handling modification requests, or contact us.