Modifications to Approved Research Process

Process for Modifications 

Learning Shot: Process for modifying IRB-approved protocols 

Also see Modification Background Information for additional guidance on what meets the criteria for expedited or full board review of a modification and in what cases should a modification be considered to be a new study. 

Prereview

A pre-review is required for all modifications that require revisions to the protocol/IRB application and/or consent. Pre-review of modifications may take up to 10 business days from the time of submission to the time of return of comments to the study team. Additional time will be needed to submit final versions and obtain IRB approval.

Modifications to Exempt or Not Engaged Projects

If the study meets the criteria of Exempt, or Non-Engaged, IRB approval is NOT required for of the following types of modifications:  

• Change in # of subjects to be enrolled
• Change of Status

For all other changes to Exempt or Not-engaged projects an updated application (tracked), together with an email describing the changes should be submitted to IRBHSR-Mods@virginia.edu. The changes will be reviewed by the IRB to ensure the study continues to meet the criteria for Exempt or Not-Engaged. You will receive documentation regarding the IRB’s receipt of the change and the IRB’s determination that t that the project continues to meet Exempt or Not-Engaged criteria. You should file this documentation with your project documentation. 

Types of Modifications (see individual sections below for specifics):

• Change in # of Subjects to be Enrolled ( e.g. sign a consent form) 
• Change of Status ( e.g. changing from open to enrollment to closed to enrollment, follow-up only) 
• Amendments and Modifications with Content Changes
• Additional Considerations for Studies Reviewed by PRC
• Study HOLD by PI

Personnel other than the Principal Investigator:

• Verify new personnel have completed IRB-HSR Training in Human Subject Research Protection Training ( See link to CITI on IRB website at http://www.virginia.edu/vprgs/irb/hsr/citi.html)
• All Personnel Changes are done via IRB PRO.
• At this point, the new personnel may begin work on the protocol ( e.g. have access to subjects or identifiable data) 
• File the document with your regulatory files. 

Change in Principal Investigator : 

• Verify new Principal Investigator has current training in Human Subject Research Protection 
• The table above indicates which documents need to be modified when the PI is changing: 
• SIGNATURE ON THE INVESTIGATOR AGREEMENT OF THE PI AND DEPARTMENT CHAIR IS REQUIRED FOR PI CHANGES - Please obtain signatures AFTER pre-review is completed.
• * The Investigator's Agreement is embedded in many protocol/IRB applications.

When applicable according to the table above, submit the following documents to irbhsr-mods@virginia.edu.

• Protocol with tracked changes and the version date updated.
• Application with tracked changes and the version date updated.
• Consent with tracked changes with the new PI information inserted in the appropriate places.
• IRB-HSR Personnel Change Form.

The documents will be reviewed and returned with comments via email to the investigator within 10 business days.  Once you have received confirmation that all necessary updates have been made to the protocol/application and/or consent, you will submit the following documents (as applicable according to the table above): 

• • • Protocol or application signed and dated by the PI and Department Chair.
    • Consent with tracked changes
    • Consent with changes accepted
    • Investigator Agreement  signed by the new PI and the Department Chair.  This agreement is usually in the IRB Application document for the study.  For a very old study this agreement may also be found in the Protocol document.  If you are unable to locate it, contact IRB Staff to provide the agreement to you from Protocol Builder. 
    • IRB-HSR Personnel Change Form

Change in # of Subjects to be Enrolled (e.g. sign a consent form) 

If requesting to increase or decrease the # of subjects to be enrolled in a protocol by, you MUST modify the IRB-HSR protocol/application and consent (if applicable) 

• • Submit the following documents to the IRB
    • Protocol with tracked changes and the version date updated and revision to number of subjects at UVA and all sites (if applicable).
    • Consent with tracked changes including the number of subjects revised.
    • IRB-HSR Enrollment Change Form. Email address for submission is on the Enrollment Change Form.

The documents will be reviewed and returned with comments via email to the investigator within 10 business days. Once you have received confirmation that all necessary updates have been made, submit the following hard copies (as applicable):

• • • Protocol with tracked changes
    • Consent(s) with tracked changes
    • Consent(s) with changes accepted
    • IRB-HSR Enrollment Change Form

Change of Status (e.g. changing from open to enrollment to closed to enrollment, follow-up only) 

Exempt or Non- Engaged, Non-Human Subject Applications You are not required to submit Change of Status to the IRB for Exempt, Not Engaged, Non-Human Subject projects. Change of Status Forms will be returned to you unprocessed. 

For all other Protocols

• • • Submit Change of Status Modification Form via email to the IRB-HSR. 
    • Attach any supporting documentation from the sponsor 
    • IF REOPENING after accidental closure or IRB approval expiration
      • You may need to complete a Continuation review if the study has not undergone Continuation review within the last 365 days. In this case, please contact an IRB administrator to provide you with the appropriate documents to complete. There may be additional documents that will be required at the time of re-opening as well.
      • In addition you must submit a Change of Status Modification Form 
    • If requesting to close the study permanently, (all participants have completed the required procedures and follow up phases of the study and analysis are completed to the point that participant's medical records or contact with study subjects will no longer be needed), complete the Closure Form for Protocols.

Amendments and Modifications with Content Changes

Exempt or Non- Engaged Applications
If you need to make a change to an application that was submitted as an Exempt or Non-Engaged submission, send an email to the IRB to irbhsr@virginia.edu outlining the change you wish to make along with a tracked versions of the application. The IRB staff will review the modification and determine if the project still meets the criteria for Exempt or Non- Engaged review. You will be notified by return email of the decision. You may not implement the change until you have heard from the IRB. 

• • All Other Protocols: Content changes should be submitted to the IRB-HSR regardless of study status.
    • For studies that are open to enrollment, content changes that affect the protocol should also be made to the IRB application, and any consent documentation and other study documents including advertisements where applicable.
    • For studies that are closed to enrollment with subjects being treated, amendments to the protocol should also be made to the IRB application, and consent addendum. 
    • For studies that are in data analysis or follow-up, amendments to the protocol should be reflected in the IRB application. IF the change involves new risk, it is anticipated that a new consent addendum will be submitted as well.

Before obtaining signatures, submit the following documents to irbhsr-mods@virginia.edu for PREREVIEW:

• • • IRB-HSR Protocol/Application with tracked changes ( if applicable) 
    • IRB-HSR Consent with tracked changes (if applicable) 
    • If applicable, non-IRB  protocol (most current version) 
    • If applicable, Summary of Changes document 
    • Request for Modification Form
    • If Applicable Consent Addendum.  A consent addendum must be created if the study is closed to enrollment.  As a general rule, the consent addendum should not be used if the protocol is open to enrollment. 
    • If applicable, any supporting documents. 
  • The documents will be reviewed and returned with comments via email to the investigator within 10 business days. 
  • The investigator should make the requested changes or write a response to any request made for which they do not agree and re-submit to the IRB-HSR by email.  
  • IRB-HSR staff will re-review the documentation, verifying that all issues have been addressed. 

Once documents are received and the approval has been processed the documents will be available to the study team in IRB Pro. Study teams will receive a notification when the documents are in IRB Pro.

Template Updates 

If major changes are required in a study the investigator may re-write the IRB protocol/application and consent in Protocol Builder and submit to the IRB. The study documents will undergo a comprehensive review that will look at the many detailed aspects of the protocol, and consent form (s), if applicable, and ensure that the core principles of research with human subjects are upheld; essentially the review will be identical to the review of a new study. As with all new studies, a pre-review will be required. If the initial review of the protocol/application required the review of the full board, the review will be done by the full board. See instructions below. 
 

Re-write protocol, IRB Applications and consent via Protocol Builder https://www.irb.virginia.edu/ 

If you have not used Protocol Builder before and need help with the Template Update contact the IRB-HSR office for assistance.

If the study has oversight by the PRC verify with them if their approval is needed prior to submission to IRB-HSR.  

Before obtaining signatures, please submit electronically the following documents to irbhsrfbprereview@virginia.edufor PREREVIEW: 

• Modification Request Form
• Protocol Cover sheet 
• Protocol 
• IRB Application 
• Consent(s), if applicable 

If you are making any additional modifications (in addition to updating to the current template), include a copy of the Request for Modification Form.

If one is not included with the submission, the IRB-HSR will assume that no additional modifications are being made. 

The documents will be reviewed and comments returned via email to the investigator within 10 business days.  

The investigator should make the requested changes or write a response to any request made for which they do not agree and re-submit to the IRB-HSR by email.  

IRB-HSR staff will re-review the documents, verifying that all issues have been addressed. The modification will not be placed on the agenda until this step is completed. 

IRB-HSR staff will notify the researcher of the status of the review within 1-2 business days of receipt of the revised documents.

The PI will be required to send the following FINAL CLEAN (no track changes) documents to the IRB-HSR office via email: 

• Protocol Coversheet with questions
• Protocol
• IRB Application, signed and dated by the PI and includes IRB#/UVA Study Tracking # in header
• Consent(s) including IRB#/ UVA Study Tracking # in header
• Proposed study-specific research participant tools (e.g. questionnaires)
• PRC approval notice (if applicable)
• If applicable Request for Modification Form.

Additional Considerations for Studies Reviewed by PRC (Cancer Center Protocol Review Committee) 

If the protocol/application you intend to modify has been approved by the Cancer Center Protocol Review Committee (PRC), the modification you are planning to submit must be approved by the PRC prior to this modification being submitted to the IRB-HSR for pre-review.

Study HOLD by PI

If the PI wishes to place a study on HOLD submit a Status Change Form and the following information in writing to the IRB.
Examples of when a PI may place a study on hold: PI going on extended absence and the study will not continue during their absence under a new PI, lack of funding/ personnel for an extended period of time.

• IRB/UVA Tracking # of Study and Study title
• Statement that the PI is voluntarily placing the study on hold
• A description of the research activities that will be stopped
• Proposed actions to be taken to protect current participants
• Actions that will be taken prior to IRB approval of proposed changes in order to eliminate apparent immediate risk of harm

The IRB will review the plan and notify the PI /study team in writing of any additional steps required to protect subjects.

Version Date 8-17-21