What is the purpose of Modification submissions?
Federal regulations require that all changes to approved research, during the period for which approval has already been given, may not be initiated without prior IRB review and approval (except where necessary to eliminate apparent immediate hazards to human participants).
Modifications to any protocol, procedure, personnel or related study document should be submitted to receive IRB approval prior to implementation.
Some Modification submissions may not technically be changing any aspect of the study but are still required. Such as providing DSMB reports, notes to file, Memos from the sponsor, letters from the FDA or other oversight organization. Submitting these things in real time throughout the year will help to reduce the number of documents you need to coordinate and include at the time of Continuing Review and will improve regulatory compliance.
What level of IRB review is required?
Both the IRB Modification Form and the HSERA electronic modification application request that you identify the level of IRB review required for your modification submission so that it can be properly assigned.
If a change may represent more than minimal risk to subjects, it must be reviewed and approved by the IRB at a convened meeting. This applies to both minimal risk and greater than minimal risk studies. The IRB must review and approve proposed changes before the change can be implemented, unless the change is necessary to eliminate an immediate hazard to the research participants. In the case of a change implemented to eliminate an immediate hazard to participants, please review the separate guidance for how to submit Exception requests.
Examples of changes that may require convened board review:
-Increase in target enrollment for early phase (first in human, Phase 1-2) research
-Significant increase in target enrollment for an investigator-initiated greater than minimal risk protocol
-Revised acute or long-term risk information that may change the risk/benefit ratio or affect a subject’s willingness to participate
-Significant changes to the protocol design that may affect the risk/benefit ratio or criteria for IRB approval, including changes to the selection criteria
-Introduction of new procedures that do not qualify for expedited review under the designated expedited review categories (e.g., biopsy, CT scan, X ray, MRI with contrast, etc.)
-Adding a non-significant risk medical device used in an investigational manner to a protocol (these determinations must be made at the convened level)
-Changes to the following section of an IB: Summary of Data and Guidance for the Investigators
Examples of changes that may be eligible for expedited review
-Increase in target enrollment at Penn where overall enrollment target is not exceeded
-Administrative changes: changes in personnel, editorial edits to study documents
-Expanding inclusion or removing exclusion that improves the safety of the protocol or where a new population has the same expected risk as the previous, based on similarities of condition
-Revised acute risk information where all subjects have completed the study or are in long-term follow-up (in essence, the risk information doesn’t apply to these subjects)
-Minor risk revisions that do not affect the risk/benefit ratio, and no subjects are enrolled to date
-Non-substantive changes to the protocol design that do not affect the risk/benefit ratio or criteria for IRB approval
-Introduction of new procedures that qualify for expedited review under the designated expedited review categories (e.g., non-sensitive questionnaires, venipuncture within the limits outlined in expedited category 2, collection of saliva, non-contrast MRI, etc.)
-Non-substantive changes to an IB (e.g., changes to clinical and non-clinical study summaries that do not affect the Summary of Data and Guidance for the Investigators)
How to Submit a Modification in HSERA
- After completing the submission form, save it to your computer. PI signature on the form is NOT required when submitting in HSERA
- Go to HSERA.
- In the blue menu on the left side of your screen look for "Create" under "My Submissions".
- After clicking "Create" you will be brought to a new screen where the various electronic application types are available. Click "Modification"
- After clicking "Modification" you will be brought to a screen with a list of all HSERA studies for which you are listed as either PI, Co-PI or Study Contact (note that Key Personnel cannot create submissions). Check to make sure your filter is clear. Then enter the protocol # you wish to make a Modification for and click "Filter".
- After clicking "Filter" with the specific protocol number entered, you should see one entry with columns showing the PI name, Submission date, Title, and a Select column - click the white and yellow "Select" button.
- After clicking the "Select" button you will be taken to the first page of the Modification Application
- Page 1 requires that users answer questions similar to those questions in the downloaded form that you already completed. The IRB will refer to you your attached form – NOT the electronic answers on page 1 of the modification application. Currently the system requires responses to all questions on page 1. You should fill in any text boxes with “NA” or “0” or “See attached” to get through this section quickly (In the future the system will be updated to remove these questions and provide an area to attach your completed form). All the relevant information that the IRB requires will be provided in your attached form. When you get to the end of page 1, click “Next”
- Page 2 of the Modification application is actually the first page of the most recent version of the 10 page HSERA application that was submitted for IRB review when the project began. You must make the necessary changes to the content on each page (aka Basic Info, Personnel, Bio, Protocol, Procedures, ETC..) so that your HSERA application is always up to date and reflects the changes being submitted with the modification
- Sometimes changes to the HSERA application are not necessary when submitting a modification. In this case you should just keep clicking “Next” on every page until you come to the “Confirmation” Page
- The Confirmation page is the final page of the application. Here you will attach the completed Modification form (from step 1) as well as the appropriate documents related to the Modification. Please be mindful to upload documents under the appropriate header to facilitate the IRB's review of these documents. After attaching all your documents, go to the bottom of the page and click “I accept” – your Modification submission is now complete.
How to submit a Modification for Paper study
For older studies that pre-date the existence of HSERA, a physical paper submission should be sent to the IRB office. After completing the submission form, please print and send to the IRB office with one copy of each required supporting document.PI signature is required for all paper submissions.
Can I submit a modification at the same time as Continuing Review?
Due to complications that occur with submission of modifications at the same time as continuing review, the IRB strongly suggests avoiding submitting both types of submissions at the same time. Unless you are instructed by an IRB staff member to create and submit a modification at the same time as your continuing review, study teams should instead mention the basic elements of the planned modification in the progress report that is required for all continuing reviews and wait to create and submit the modification until after the continuing review has been approved.