Modification

Submitting modifications to currently approved protocols

Federal regulations require that all modifications 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.

Directions for Submitting Modifications: Start by downloading the modification form (required after June 1,2016)

Paper Studies: 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.

HSERA Studies: Follow these steps for creating a Modification in HSERA:

1. After completing the submission form, save it to your computer. PI signature on the form is NOT required when submitting in HSERA

2. Go to HSERA.

3. In the blue menu on the left side of your screen look for "Create" under "My Submissions".

4. After clicking "Create" you will be brought to a new screen where the various electronic application types are available. Click "Modification"

5. 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".

6. 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.

7. 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.

 

If a modification for a study stored in HSERA is being planned for submission around the time of continuing review, there are 2 important pieces of information to be aware of:

1.       The changes should NOT be included in a continuing review submission. An entirely separate modification submission should be created and submitted. If anything that was not previously approved is included in a continuing review submission it will be returned.

2.       The modification should always be created and approved by the PI prior to the creation of the continuing review whenever possible. This is to ensure that any revisions to the content of your actual HSERA application as part of the modification will be reflected in the version of the continuing review that will be submitted. Failure to complete the steps this way will potentially lead to issues down the road. This is because the researcher’s editable version of an HSERA application is based on the last version that is approved by the IRB.

Steps:

Submitting Modifications to the IRB:

HS-ERA link: https://medley.isc-seo.upenn.edu/hsProtocol/jsp/fast.do

Log in using your standard Pennkey and password. If you don't have a Pennkey, click here to be directed to the appropriate site: http://www.upenn.edu/computing/pennkey/

If you are unable to log in or click create, please contact HS-ERA help for assistance:hsera_help@lists.upenn.edu

How do I create a Modification Submission?

Once logged in, click "Create" under the "My Submissions" option (top left navigation bar). This will take you to a list of protocols that you can create an action for. In order to create an amendment to an existing protocol, click "Modification".

Paper Protocol: If you have a paper protocol, please complete the modification form to include with your hardcopy modification submission to be sent to the IRB office. 

 

Do you need assistance with your submission?

 

 

If you require assistance by an IRB staff member, please contact any person listed as an Administrator on the directory page

Completing the submission:

Does your Modification require Expedited or Convened Review?

 

 

Minor modifications are defined as those that do not materially affect an assessment of the risks and benefits of the study and do not substantially change the specific aims/design of the study. Representative minor modifications include but are not limited to: 

  • The addition of research activities that would be considered exempt or expedited if considered independent from the main research protocol; 
  • A minor increase or decrease in the number of participants; Office of Regulatory Affairs, Institutional Review Board 3624 Market Street, Suite 301 South, Philadelphia, PA 19104-6006 
  • Narrowing the inclusion criteria; 
  • Broadening the exclusion criteria; 
  • Changes to the dosage form (e.g. tablet to capsule or oral liquid) of an administered drug (when the dose and route of administration remain constant); 
  • Decreasing the number of biological sample collections, provided that such a change does not affect the collection of information related to safety evaluations; 
  • An increase in the number of study visits for the purpose of increased safety monitoring; 
  • A decrease in the number of study visits, provided the decrease does not affect the collection of information related to safety evaluations; 
  • Changes in remuneration; 
  • Changes to improve the clarity of statements or to correct typographical errors, provided that such a change does not alter the content or intent of the statement; 
  • The addition or deletion of qualified investigators; 
  • The addition or deletion of study sites; 
  • Minor changes specifically requested by other University Committees with jurisdiction over research. 

Convened Board Modifications are defined as those that may affect an assessment of the risks and benefits of the study and may substantially change the specific aims/design of the study. Convened board modifications include but are not limited to: 

  • Increase in target enrollment for investigator initiated research or potentially Phase I research
  • Expanding inclusion or removing exclusion criteria where the new population may be at increased risk
  • Revised risk information with active participants
  • Minor risk revisions that may affect a subject’s willingness to continue to participate 

 

Changes made to Recruitment, Screening and Consent Documents

  • Please include a tracked or marked copy of the all modified study documents highlighting the changes being made, as well as a corresponding clean copy with all changes incorporated. 
  • It is strongly encouraged that the version number and date for all modified study documents be revised to indicate that a new version has been proposed.
  • If you make changes to your informed consent form and determine that re-consenting subjects is not appropriate, please detail the rationale for this decision in your modification form. 
  • Please include and indicate which study documents required revisions as result of the newly proposed changes.

Additional Modification Submission Tips

There are some common items that the IRB considers when reviewing most modifications. It is recommended that you make sure the following elements listed below are included in your submission. This information can be provided in a cover letter, a modification summary document, or in the Modification Summary section of the HS-ERA Modification Form. 

  • A summary of the changes made and the rationale for each change; 
  • The purpose of the request and any additional information that should be considered during the IRB review of the submission; 
  • An assessment from the PI indicating the requested level of review; 
  • A summary of any new risks or burdens posed to subjects as a result of the proposed change; 
  • A description of how any new risks are minimized. 

 

Confirmation Page on HS-ERA

Documents to upload with your Modification Submission

 

 

  • Cover Letter Outlining the Summary of Changes
  • Cover Letter Outlining the Rationale (for why the changes are being made)
  • Tracked documents (showing changes): Consent Forms, Sponsor Protocol, Recruitment Documents, Investigator’s Brochure, etc.
  • Clean documents (incorporating the changes): Consent Forms, Sponsor Protocol, Recruitment Documents, Investigator’s Brochure, etc.
  • Any documents which you plan to use for your study which have not been previously approved by the IRB
  • Any supplemental documentation for the IRB to consider (i.e. letters of approval from other institutions, medical monitor assessments, letters of action from the sponsor, etc)

 

 

 

Modification Review:

Possible Outcomes of Modification Review

 

 

 

As an outcome of modification review, the IRB may authorize the proposed changes to your research, require that additional revisions are included, or ask for further clarification/justification for your proposed changes. 

Responding to Issues Raised by the IRB

Review and Approval Criteria

The criteria for reviewing and approving an amendment are the same as those for initial review. Therefore, the IRB (or the Chair or designated member of the IRB for protocols reviewed under the expedited review procedures) must determine that all of the following requirements are satisfied: 

  • Risks to subjects continue to be minimized and reasonable in relation to anticipated benefits; 
  • Selection of subjects continues to be equitable; 
  • Informed consent will be sought from each prospective subject or the subject's legally authorized representative, in accordance with and to the extent required by appropriate local, state and federal regulations.
  • Informed consent will be appropriately documented as required by local, state and federal regulations. 
  • The research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects, when appropriate; 
  • There are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data, when appropriate
  • Appropriate safeguards for vulnerable subjects are provided. 
  • There are adequate provisions to protect the confidentiality of data and the privacy interests of subjects.

IRB notification(s) for additional information required:

If additional corrective action(s) or other responses are required by the IRB, they will be requested via the formal letter that summarizes the issues identified by the convened board or the authorized designee of the IRB (for expedited reviews).  The submission will be returned in HS-ERA for the study team to address the issues raised by the IRB. It is recommended that a cover letter be included with the response submission so that the IRB can clearly identify how each stipulation was addressed.

Do you need assistance with your submission?

If you require assistance by an IRB staff member, please contact the IRB staff member who generated the IRB correspondence.