Exceptions

What is an exception request?

An exception request is a prospective, one time, intentional action or process that departs from the IRB approved study protocol, intended for a single occurrence.

Prospective- This means that the study team plans to perform study activity outside of the parameters and procedures set forth in the IRB-approved protocol. If an exception is submitted to the IRB for approval after it has already taken place, it is then considered a deviation regardless of whether sponsor or other monitoring approvals were obtained in advance.

Intentional- An exception request will not be approved if it was unintentional. For example, if a subject is enrolled and later it is discovered that they met an exclusion criteria but will be allowed to continue on the study- this should be submitted as a deviation NOT an exception as this was not planned prospectively and was unintentional. Retrospectively submitting a deviation as an exception request will not be approved.

One-time request intended for a single occurrence- Each time an exception is to be implemented separate IRB approval must be obtained. If the same exception request is submitted multiple times for the same study, the IRB may suggest or require a change to the protocol to eliminate the need for repeat or common exceptions.

How do I submit an exception request?

Electronic Submission via HSERA-Start by downloading and completing the exception request form (required after June 1, 2016) 

If your study was originally submitted through the online application system (HS ERA) the exception request should be submitted using the HS-ERA Exception Request Application.

Step 1. Log into In HS ERA.

Step 2. Under “My Submissions” in the blue column on the left side of the screen choose “Create”.

Step 3. On the next page select “Exception”.

Step 4. On the next page Search for and select the relevant protocol.

Step 5. Complete all text box fields on page 1 with "See attached Form" then click "Next" at the bottom of the page

Step 6. Attach the completed exception request form and any related documents by clicking the green "attach form" button. After all your documentataion has been attached, click the blue "I accept" button.

Step 7. After clicking "I Accept" the application will be sent to the Pi for approval (if the PI was not the person who created it) Once the PI approves the submission it will be received by the IRB for review.

Paper Submission- Start by downloading and completing the exception request form.Once complete the exception request form and all supporting documentation should be sent to the IRB office via standard mai or inter-office mail.

E-mail Submission-Start by downloading and completing the exception request form.If time is of the essence and you need a rush exception(approval in less than 24 hours), the completed exception request form should be emailed to the IRB Director, Associate Director and Assistant Director along with all supporting documentation. In the case of rush exceptions it may not be feasible to obtain PI signature on the form. In these situations please include an email from the PI approving the exception request as a supporting document. Please be sure to CC the PI on your exception request email to the IRB. When submitting via email for a study registered through HS ERA, a formal submission of the exception through HS ERA will still be required after the exception request has been processed. When submitting via email a signature on the form may be required if the PI is not going to be the one sending the email submission.
What information must be included with the exception request submission?
For review of exception requests the IRB requires the following information:

  • Documented approval from the study sponsor, medical monitor and other oversight entities as applicable
  • A description of the exception including references to the current protocol, proposed date, rationale, clarification as to why the action is one time, and any plans for communicating the exception to subject
  • Assessment of increased risk involved in the exception
  • Assessment of subject benefit from the exception
  • Assessment of impact of the exception on data integrity
  • Declaration of time sensitivity and applicable rationale

Other factors that may influence the review of an exception are;

  • submission of revised consent or addendum to the consent
  • plans to modify the protocol permanently

How does the IRB review exception requests?
Rush exception requests received via email are assigned for immediate processing.
For all exception requests that are not time-sensitive, IRB review and screening of the submission will occur in alignment with standard IRB processing. Upon receipt of an exception request, the action will be assigned to the appropriate IRB administrator and for screening and an assessment of the level of IRB review required.
The level of review required for exception requests (expedited or convened) is dependent upon the following factors:

  • The time sensitivity of the request
  • The level of risk involved in both the study itself and the planned alteration.
  • Whether the exception request is thought to be in the best interest of the subject
  • Whether the exception request holds out the prospect of direct benefit to the subject
  • Whether the risk/benefit ratio specifically related to the exception request is favorable

Expedited Review: Exceptions with potential safety implications require review by an IRB Chair or appropriate IRB physician scientist member. The following exceptions are eligible for expedited review:

  • Exception requests where the planned exception poses no more than minimal risk to the subject
  • Exception requests where the planned exception may pose greater than minimal risk to the subject but the request is time sensitive and
  1. The exception is in the best interest of the subject and/or the prospect of direct benefit exists
  2. The risk/benefit ratio for the proposed exception request is favorable

Convened Review: Review will be conducted by the full Board at the next planned meeting.

  • Exception requests where the planned exception may pose greater than minimal risk to the subject and any of the following apply:
  1. It is unclear whether the exception is in the subject's best interest or whether there is the prospect of direct benefit to the subject 
  2. It is unclear whether the risk/benefit ratio is favorable
  3. The request is not time sensitive and there is sufficient time to allow convened IRB review to occur

 

Steps:

Submitting Exception Requests to the IRB

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

Submission Process

Click "create" and "exception" and select the appropriate protocol from the picklist.  If the protocol is not available in the picklist, it is either a paper submission or the submitter does not have edit access to the protocol.

Paper Studies

Paper Studies: Please use the Modification Form and complete the section specific to exceptions. 

NOTE: Exceptions of an urgent nature may be submitted via email.

Who do I contact with questions?

If you require assistance with submitting an exception, or to determine if an exception is required, please see the directory and contact any Senior Administrator.

Creating an exception submission

What is required for an exception submission?

The exception form needs to be completed in its entirety, including the time frame requested for review, reason for the exception and specific commentary related to why an exception is necessary and whether a modification may be implemented moving forward.

 

Who can I contact with questions?

If you need assistance completing the exception form, please contact any Administrator listed in our directory.

Confirmation Page – Documents to include

What documents do I include with an exception request?

Any required approvals need to be uploaded to the request, which may include Sponsor approval, Medical Monitor approval, etc.  Any additional notes from the PI related to the exception request should be provided as well (if not included in the exception request form).

 

Who do I contact with questions?

If you require assistance to determine what documents to include with your exception request, please contact any Administrator listed in our directory.

IRB Review Process

What happens during IRB review?

The IRB will consider the exception and either contact the PI/study team for further information if needed or may approve the request.  A standard approval letter for the exception will be forwarded upon approval.  The approval letter may require that a modification be submitted.  In addition, if a rush exception request is submitted via email for an HS-ERA study, the approval letter will note requirement of submission of an exception in HS-ERA for documentation purposes.

 

 

Who can I contact with questions?

If you require assisance during the IRB review process or interpreting an IRB requirement in your approval letter, contact the IRB staff member who signed the approval letter.

Responding to Issues Raised By the IRB

Request for additional information

Given the rush nature of most exception requests, HS-ERA submissions will NOT be returned to the submitter, but additional information will be requested outside of HS-ERA and uploaded to the submission for documentation purposes.  Paper submissions will result in an email to the PI/study team to request additional information/documentation, if necessary.

 

Who can I contact with questions?

If you require general exception request assisance ,contact any Administrator listed in our directory