The IRB's initial approval letter includes the duration of the approval period. The eIRB sends out notifications to the Principal Investigator, Lead Investigator and Lead Study Coordinator at intervals prior to the end of the approval period. The PI is are responsible for submission of complete continuing review application regardless of receipt of eIRB notification. Delays in response can jeopardize IRB approval. Without continuing review and approval, a study cannot continue.
Submission of Continuing Review Progress Reports
PIs are encouraged to submit Continuing Reviews for full board studies at least 45 days prior to IRB approval expiration. For studies reviewed using Expedited Procedures, the submission should be submitted at least 30 days prior to approval expiration.
Expiration of IRB Approval
If the IRB has not reviewed and approved a research study by the expiration date, the research must stop, unless the IRB finds that it is in the best interests of individual subjects to continue participating in the research interventions or interactions. Enrollment of new subjects cannot occur after the expiration of IRB approval.
A continuing review is a time for study teams to tell the IRB what has happened since the previous review, or initial approval. At time of continuing review, the IRB ensures that the study still meets the regulatory criteria for approval including additional protections for vulnerable populations (such as children), if applicable. When providing a progress report, the following information should be highlighted: the current progress of the study including what has happened since the last review, any achievements (such as meeting enrollment goals), or any areas of deficiency (such as why enrollment is behind schedule).
The IRB's continuing review of research must be substantive and meaningful. To do that, the IRB must receive sufficient information to conduct its review. The CHOP IRB includes an application for continuing review within the eIRB electronic IRB management system. The frequency of continuing review for the research is determined by the IRB at the time of the initial approval. At CHOP all new studies, regardless of funding source are approved for no more than one year. Subsequently the IRB may alter the frequency of the reviews for research that is not federally funded or FDA-regulated. For these studies, the IRB may approve a period of up to 3 years for minimal risk research and up to 1 year for greater than minimal risk research. For federally funded or FDA-regulated research the approval period can not be greater than 12 months.
The IRB determines the review cycle based on the inherent risks of the research, past experience with the investigators, as well as the funding status. The regulations require that federally funded or FDA-regulated research must be reviewed at least annually. A study may have a more frequent review cycle, for example after enrollment of a specified number of subjects or after a shorter time interval. CHOP IRB SOPs allow for up to a 3 year review cycle for studies that are not greater than minimal risk provided that they aren't federally funded.
During its review of the study progress report, the IRB ensures that all study team members have required human subjects training. If CITI training is expired or if a required training (such as study coordinator training) is missing, this will prolong the review process. Ensuring that study staff members are up to date on required training before submission, can expedite the review process.
The IRB also reviews the consent form and other study materials in detail. If any language is out of date, then changes may be required. Changes to the study cannot be performed as part of continuing review; changes to study materials requires the submission of a separate amendment.
Tips for submissions
What to Report with a Continuing Review:
- If there have been any issues during the past year that impact enrollment, these should be summarized them in the study progress report.
- When, "Analysis involving subjects' personally identifiable or coded data (data linked to identifiers)" is selected, it is the IRB’s understanding that the master list is still intact (if applicable) and there is a need to continue to use subject identifiers as part of cleaning the database or as part of the analysis. The study must remain open while identifiable data is being used.
- When "Analysis involving de-identified data (data that cannot be linked to subjects)" is checked, it is the IRB’s understanding that the master list or the link between the master list and the subjects' identifiable data has been destroyed. If the ongoing research no longer involves the use of identifiable data, the study qualifies for closure (see below).
- When reporting the number of subjects, please only report the number of subjects who have been enrolled since the previous CR. The number of enrolled subjects is the total number of subjects. This number is commonly the number of subjects who signed a consent form, or, in the case of studies where the IRB has waived the requirement for consent, the number of medical records that were reviewed. The number of evaluable subjects is the number of subjects that can be used as part of the study analysis. This can be the same or less than the number of enrolled subjects, but it can never be greater.
- A cover letter is not required, but is permitted. If there is information the investigator would like to provide to assist the IRB with its review, a cover letter is appropriate.
- The submission will also require study teams to verify that the funding source for the study is still correct. If there are any changes to the funding, the changes can be submitted in an amendment at the same time as the CR.
- Please do NOT check "enrollment temporarily suspended" unless the study is suspended for a regulatory reason or due to a safety concern). If the investigators have paused enrollment (e.g. due to lack of staff or a lapse in approval) this selection should not be used. Checking "enrollment temporarily suspended" at time of CR will require an amendment to be approved by the IRB prior to re-opening enrollment.
- If your study has a DSMB, please provide the most recent report for review.
- Projects that are exempt or that are determined to not be human subjects research do not require continuing review submissions.
What cannot be reported with a Continuing Review
Changes cannot be made to a study or a consent form with a continuing review. An amendment needs to be submitted as a separate activity in eIRB in order to make a change in the research. The amendment can be submitted at the same time as the continuing review.
Reportable Events that meet the definition of an unanticipated problem involving risks to subjects or others need to be reported through eIRB using the reportable event pathway and should not be reported to the IRB for the first time through a continuing review. Only minor adverse events, protocol deviations and other events that do not impact subject safety or study validity, such as a study visit outside of an approved visit window, should be reported at the time of continuing review. A Reportable Event can be submitted to the IRB at the same time as the continuing review.
Continuing Approval when an External IRB is the Reviewing IRB
A formal continuing review submission is not required for studies where an external IRB is the Reviewing IRB. Instead, the study team only needs to "Update Study" in eIRB. The approval letter from the Reviewing IRB along with the most recent study progress report and consent form(s) need to be uploaded. The approval letter from the Reviewing IRB must be submitted prior to study expiration date.
If a study expires with an outside IRB of record, this may result in CHOP cancelling the authorization agreement and requiring full IRB review at CHOP.
Study Completion (Closure)
A study can be closed when all human subjects activities have been completed. This includes analysis or use of identifiable data, subject records, test results or other identifiable information. Completion reports need to be submitted to the IRB to close out expedited and full board studies.
The completion report should include the progress made on the study since the last continuing review, a discussion of which activities are still ongoing (such as analysis of de-identified data), and the reason for closing the study (completion of human subjects research activities). If the study has resulted in a publication, the IRB recommends attaching the publication with the completion submission. This can be attached in eIRB Section 8.01.
Lapses in IRB Approval of Research
- A lapse in approval occurs when a continuing review is not approved by the expiration date.
- The expiration date can be found in eIRB as well as in the approval letters for initial review, continuing reviews and amendments.
- It is the Principal Investigator’s responsibility to ensure that the study is submitted to the IRB prior to expiration.
- To avoid lapses in approval, continuing review submissions should be submitted 30-45 days before the expiration date, to allow time for review and stipulations, should any be identified.
- If the IRB issued a stipulation letter indicating that the study was "Approved with Modifications" and the expiration date has passed, the study still has IRB approval and study activities can continue to occur. However, a stamped consent form will not be issued until the study is fully approved. If consent is required for study enrollment, new subjects cannot be enrolled until the stamped consent form is issued and final approval is granted.
- If the IRB has reviewed and deferred a continuing review submission, research activities must stop after the expiration date and cannot begin again until the IRB determines the study is approved or approved with modifications. This is considered a lapse in IRB approval.
Reactivating a Closed Study
Reactivation of closed studies is handled on a case-by-case basis. If a study was recently closed and a justification can be provided for requesting the re-opening of the study (e.g. need to confirm the results of laboratory tests in the subjects' medical charts), the IRB will review the request. Please contact the previously assigned IRB Analyst or Contact the IRB office to discuss any requests for reactivation.