Modifications

Amendments to studies initially submitted in HSERA must be submitted in HSERA via a modification submission. Instructions on this are below. Additionally, the following attachments should be included:

Modification Form

All modification submissions require the use of the most recent version of the IRB Modification Form. The HSERA modification electronic form is outdated and does not require all the necessary fields for the IRB to conduct a review. After completing the submission form, save it to your computer. PI signature on the form is NOT required when submitting in HSERA.

Tracked and Clean versions of Revised Documents

Please provide both tracked and clean copies of all documents to facilitate IRB review, including protocols, informed consents, IBs, and other participant facing materials. The IRB strongly prefers that teams utilize the Track Changes feature in the Review menu in Microsoft Word.

*Note: If a Sponsor declines to provide a tracked document, please note this in the summary. Further summary/explanation of revisions may be required by the IRB in order to process the modification.

Summary of the Proposed Changes

• A Summary of Changes outlines both the proposed changes as well as the rationale for proposed changes.
• A Summary of Changes may be provided in the modification form (above) for simpler amendments or in a separate document for more complex amendments. If the summary of changes does not adequately detail the changes as well as the rationale for proposed changes, the IRB will return your submission.

Summary of Changes Template

While use of this template is not required at this time, the IRB encourages teams to use the provided template to format and organize a summary of changes for clinical trials and other complex protocols. Utilizing this format will ensure that all required information is provided to the IRB. Ensuring your summary includes this information facilitates the IRB review process in that it can: 1) decrease the amount of time it takes for IRB staff and members to review; and 2) decrease the likelihood of returns and questions.

Document List

If the study is greater than minimal risk, or your sponsor requires a document list in the letter, a document list must be provided for the IRB correspondence letter or modification form. This listing should be in a format that the IRB may copy and paste into the IRB approval letter. Study teams are responsible for the accuracy of the document list.

• Modification Request Form, dated 1/1/2020
• Cover Letter, dated 1/1/2020
• Protocol version 8, dated 1/1/2020, tracked and clean
• Protocol version 8, SOC, dated 1/1/2020
• Product Name IB, version 10, dated 1/1/2020
• Main ICF, version dated 1/1/2020, tracked and clean
• Screening ICF, version dated 1/1/2020, and clean

How to Submit

Step by step instructions on how to submit your revised documents in HSERA as well as how to revise the HSERA application.

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
8. 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”
9. 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
10. 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
11. 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.

Guidance on how revised documents should be submitted for studies submitted prior to the implementation of HSERA.

For older studies that pre-date the existence of HSERA, the submission may be submitted via email to the IRB PO Box. PI signature is required for all paper submissions.

Click below for guidance on how to submit personnel changes to the IRB, including Principal Investigator (PI) changes.

Frequently Asked Questions about Modifications

Below are frequently asked questions about modification submissions.

This section contains guidance on when modifications should be submitted for studies reviewed under exempt and limited review categories.

Federal regulations require modifications for studies that have undergone Limited Review. Please consult your initial approval letter to determine if your study underwent Limited Review. If you are still not sure, please reach out to the original reviewer or a senior analyst.

Modifications to exempt studies are typically not required. As the IRB has determined the study to meet criteria for exemption, the study team can make non-significant changes to their protocol and study documents without notifying the IRB or requesting formal approval.

Examples of changes that do not require IRB review:

• 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 new recruitment strategies that follow IRB guidance.
• Increasing or decreasing the number of subjects without altering the target population.

Researchers may submit modifications to IRB exempt protocols that are not required. For example, researchers may want IRB reassurance that the changes are acceptable, or they may want to add new personnel to the protocol so that they can gain access to HS-ERA. IRB staff assigned exempt modifications are encouraged to process these items for acknowledgement in timely manner and to obtain necessary information via email in order to facilitate these requests.

Significant changes to the exempt protocol, changes that impact a limited IRB review determination, or changes that impact HIPAA-compliance status require assessment by the IRB through modification of the protocol in HS ERA. Changes that increase the risk of the study, enroll a vulnerable population, or otherwise require expedited or convened review should be submitted for IRB review under a new initial protocol submission.

Examples of changes that require IRB review:

• Removal of the consent process, or use of deception or incomplete disclosure.
• Adding sensitive questions to a survey or interview process (e.g. questions regarding illegal activities; traumatic events such as childhood, sexual, or domestic abuse; suicide; or other probing questions that could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects’ financial standing, employability, educational advancement, or reputation).
• Collection of new elements of protected health information under a HIPAA Waiver.
• Changes to the data storage plan for studies that received a limited IRB review.
• Addition of new personnel who are not affiliated with the Penn health system, if the study involves the use of protected health information.

THE ABOVE LIST IS NON-EXHAUSTIVE. RESEARCHERS ARE ENCOURAGED TO CONSULT WITH A SENIOR ANALYST REGARDING PROPOSED CHANGES TO IRB EXEMPT STUDIES.

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. Click below for examples.

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)

Guidance on timelines for submitting “New Information” that identifies new risks or that may affect a subject’s willingness to take part in the study (e.g., action letter, revised IB with impact on the protocol and/or consent, revised procedures, etc.).

When a change of protocol is planned it should be submitted to the IRB for review in a timely manner, especially if the changes include revisions that

1. affect the risk/benefit ratio of the study (e.g., result in a change to the protocol);
2. affect alternatives to study participation for subjects;
3. represent new information that should be provided to subjects; or
4. affect the local conduct of the study.

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.

Changes Resulting from New Information
Changes that are the result of new information that identifies new risks or that may affect a subject’s willingness to take part in the study (e.g., action letter, revised IB with impact on the protocol and/or consent, revised procedures, etc.) should be submitted to the IRB by the study team as soon as possible. Submission to the IRB of such new information is expected to occur no later than 90 days from either 1) receipt from a sponsor, lead PI, etc. or 2) identification of the new information when there is not an external sponsor or lead site. This timeframe should allow the research team sufficient time to prepare the change of protocol application materials and obtain approval by a scientific review committee, when required, prior to review by the IRB.

Please note that some new information may require immediate notification to participants. Principal Investigators should consider this and (when applicable) consult with the sponsor / lead PI or the IRB as necessary.

Exceptions to the 90 day submission timeline may be appropriate in certain circumstances (e.g., when no one has been enrolled on the study and enrollment will be held until the new information is approved by the IRB; when no one is actively participating in the study and the new information doesn’t apply to subjects on study, etc.). Principal Investigators should consider the impact on participants in these cases and consult with the sponsor / lead PI or the IRB as necessary.

As necessary, if version dates on documents appear significantly delayed, please clarify for the IRB date of receipt from the sponsor. The IRB may ask for this clarity if this is not provided.