Continuing Review FAQs

1. Submit the Continuing Review application as soon as possible. Extension of the IRB expiration date may only be achieved by submission of a continuing review. Other submission types (modification, exception request, deviation) cannot serve as a renewal submission.
2. If any activity has occurred during the lapse in approval, those activities should be documented in the appropriate section of the continuing review form for committee review. Likewise, the study team should provide a root cause for the lapse in approval as well as a preventative action plan as to how they will avoid delayed submissions in the future. If a study has expired more than once, please comment on whether the existing corrective action plan needs to be corrected.
3. If there are participants active on research intervention / treatment that cannot cease due to safety reasons, the Principal Investigator (PI) must contact the IRB as soon as possible to request an Exception Request for these participants to continue on active treatment during the lapse. The PI should provide rationale as to why continuation during the lapse is in the best interest of the participants, and how ceasing research treatment would create increased risk to the participants.

How to Submit an Exception Request

The Penn IRB defines “enrolled” as an appropriately informed individual agreeing to participate in a study. In other words, an enrolled participant is an individual who may be eligible for participation, has provided informed consent, and may have participated in some or all study procedures including procedures that determine eligibility (if applicable). It is this definition of enrolled that should be used to determine the number of participants to be enrolled as indicated on all study documents. This definition allows for consistency of enrollment review across all projects and ensures that for studies that may include “screening procedures” or “pre-screening procedures,” the individual is “enrolled” in the study to allow these study procedures to be done.

Current federal guidelines include that at the time of continuing review, “the IRB’s responsibility to protect human subjects should include the IRB’s review of trial progress. For example, expected rates of enrollment and dropout are generally identified for most studies. A marked difference between the actual and expected rates of enrollment or dropout, either at an individual site or in the study as a whole, may indicate a problem requiring further investigation.”

The IRB recognizes that commercial sponsors, and others, may have a different definition, such as considering an individual “enrolled” in a study when the participant has been assigned to a study arm or has taken their first dose of the study drug. If the sponsor provides such definition, the study team may include that description and expected number in the HSERA application and continuing review progress report.

However, as noted above, the study documents including the Continuing Review Form must reflect the enrollment number of those individuals who are appropriately informed and agree to participate in a study. Study teams may differentiate between screen failures and eligible subjects in their progress reports.

The IRB recommends that study teams avoid submitting concurrent modification / continuing review submissions in the HSERA system, unless absolutely necessary, due to complications that can occur. There are no restrictions on concurrent modification / continuing review submissions for paper studies.

The HSERA system will allow a modification to be submitted concurrently while a continuing review is pending (or vice versa). However, a soft stop and a warning will appear. You may proceed, but it is important to understand the complexities of moving forward, as detailed below.

PLEASE NOTE: IF YOU ARE WAITING ON A MODIFICATION APPROVAL AND YOUR CONTINUING REVIEW SUBMISSION DUE DATE IS APPROACHING, DO NOT WAIT TO SUBMIT YOUR CONTINUING REVIEW SUBMISSION.

If you must submit concurrent modification / continuing review submissions, please note the following:

1. It is the recommendation of the IRB that you create and submit the modification before creating the Continuing Review (CR) application. This is to make sure that the changes made within the HSERA modification submission are carried over into the continuing review application. If you do not create the modification before creating the CR application, you may lose changes that you made in HSERA if you created the CR first. It is also recommended that the modification be submitted no less than 30 days prior to your continuing review submission due date (submission due dates are 6 weeks prior to study expiration for GTMR research and 4 weeks prior to study expiration for minimal risk research). 
2. Please also carefully review your modification for any potential issues that could lead to your modification being returned. A returned modification with a concurrent CR further complicates the situation.
3. It is strongly recommended that the continuing review application be created after the approval letter for the modification has been uploaded for the reasons mentioned above. HOWEVER, IF YOUR CONTINUING REVIEW SUBMISSION DUE DATE IS APPROACHING, DO NOT WAIT TO SUBMIT YOUR CONTINUING REVIEW SUBMISSION. It is important to ensure that your study does not expire.
4. You must reach out to the IRB staff so that they may facilitate the processing of these submissions and ensure that the correct documents are approved in the continuing review submission. For greater than minimal risk studies requiring convened board review, please email BOTH the coordinator and administrator for the study’s assigned board https://irb.upenn.edu/directory. For minimal risk research, please email PROVOST-IRB@pobox.upenn.edu.

Long-term follow-up excludes: “Research interventions*  [i.e., procedures] that would not have been performed for clinical purposes (standard care), even if the research interventions involve no more than minimal risk.” If research specific procedures are being conducted, participants are not considered to be in long-term follow up, as defined by OHRP’s Continuing Review Guidance.

 

*An intervention, as described in 45 CFR 46.102(e)(2), is defined as:

• “Physical procedures by which information or biospecimens are gathered (e.g., venipuncture);
• Manipulations of the subject or the subject’s environment that are performed for research purposes.”

 

Long-term follow-up includes:

• “Research interactions [45 CFR 46.102(e)(3) Communication or interpersonal contact between investigator and subject] that involve no more than minimal risk to subjects (e.g., quality of life surveys); and
• Collection of follow-up data from procedures or interventions that would have been done as part of routine clinical practice to monitor a subject for disease progression or recurrence, regardless of whether the procedures or interventions are described in the research protocol.” (i.e., collection of follow-up data from the medical record such as survival follow-up)

 

See OHRP’s Continuing Review Guidance (2010) linked below for reference.

OHRP Guidance on Continuing Review

The continuing review form requires study teams to report the number of participants actively participating in study procedures, or the number of “active” participants. Many protocols, such as controlled trials, have a schedule of research procedures that delineate a main interventional period and a follow-up period. Some protocols may not have a follow up period. 

 

The IRB defines “active” participants as those who are still undergoing the main study procedures, such as administration of a study drug or device product, treatment, procedure (e.g., venipuncture, other specimen collection, imaging, etc.), surgery, or behavioral intervention.

 

Once these main study procedures are complete, the participant may be in follow-up, if the protocol delineates a follow-up period. Follow-up might include physical procedures by which information or biospecimens are gathered (e.g., venipuncture, other specimen collection, imaging, etc.). In this case, participants can be reported as in follow up at the time of continuing review. 

 

If the follow-up period is restricted to solely interactions (phone calls, surveys, interviews, etc.), and/or collection of data from existing records, participants can be reported as in long-term follow up at the time of continuing review.