Which Studies Require Continuing Review
The Final Rule revised the requirements for Continuing Review, eliminating it for some studies. Based on the regulatory changes, the following types of studies still require continuing review:
- FDA regulated research;
- Greater than minimal risk research (including research reviewed under Expedited category 8(b));
- Minimal risk research reviewed under Expedited category 9;
- Research reviewed under the pre-2018 Common Rule; or
- Research where the IRB has determined that Continuing Review is required (i.e. any study with an expiration date).
Which Studies Do Not Require Continuing Review
The following types of studies do NOT require continuing review:
- Minimal risk research reviewed under the 2018 Common Rule (see above for exclusions);
- Greater than minimal risk research where remaining activities are limited to data analysis/long-term follow up and the IRB has determined that Continuing Review is no longer required (e.g. no expiration date); or
- Exempt studies.
Studies That Do Not Require A Continuing Review
Progress Update Activity
To enable the CHOP Research Institute to track which human subjects research studies remain active and ongoing, a brief progress update in eIRB will be required for studies that have not had any IRB submissions (e.g., amendments) during the previous 2 years. Sixty days prior to the two year mark, the PI will begin receiving reminders to submit a progress update in eIRB. The progress update involves answering one to two questions. For more details see Studies That Do Not Require a Continuing Review below.
Studies That Require a Continuing Review
The IRB's initial approval letter includes the duration of the approval period for studies which require continuing review. This includes research that is FDA regulated, greater than minimal risk, or reviewed under the pre-2018 Common Rule. 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 expiration date indicates the end of the approval period for studies which require continuing review. Continuing reviews do not need to be submitted for studies without an expiration date unless specifically required by the IRB. The PI is responsible for submission of the complete continuing review application regardless of receipt of eIRB notification.
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 requiring continuing review 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 request for continued treatment for a therapeutic or treatment study (i.e. a study for which the IRB has determined that there is a prospect for direct benefit) may be granted by the IRB Chair or designee.
What is Continuing Review?
Continuing review is a time for study teams to tell the IRB what has happened since the IRB's previous review & approval, which could be the IRB's initial approval. At time of continuing review, the IRB ensures that the study still meets all of the regulatory criteria for approval, including the additional protections for vulnerable populations, such as for children (when applicable). When providing a progress report for a continuing review, 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 eIRB. The frequency of continuing review for the research is determined by the IRB. FDA regulated research and federally funded research approved under the pre-2018 Common Rule require continuing review at least annually. Minimal risk research that is not federally funded or FDA-regulated and was reviewed under the pre-2018 Common Rule may have an approval period of up to 3 years.
It is up to the IRB to determine the appropriate review cycle based on the inherent risks of the research, past experience with the investigator(s), as well as the nature of the study's funding (if any). The IRB may require a more frequent review cycle for some studies. For example it might require review after enrollment of a specified number of subjects or it might require a 6 month or shorter time interval between Continuing Review. IRB SOP 404: Continuing Review of Approved Research provides more information on Continuing Review.
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, it may prolong 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 of Continuing Reviews
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 the only remaining activity is analysis that does not involve any identifiable private information, the study may qualify 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.
What cannot be reported as part of a Continuing Review?
Changes to the Research
Changes cannot be made to a study or a consent form as part of a continuing review application. 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 use the "Update Study" activity 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 should be submitted prior to study expiration date.
If a study expires with an outside IRB of record, this may result in CHOP reevaluating the authorization agreement and requiring IRB oversight 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 studies which have expiration dates.
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 data without identifiers), 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.
CHOP needs to be able to track which research studies involving human subjects are active and ongoing at the institution. For studies that do not require continuing review, a brief progress update in eIRB will be required if a study has not had any IRB submissions in 2 years. This is required for all human subjects research which does not require continuing review including Exempt studies.
Every time a submission is sent to the IRB (e.g. amendment, reportable event) the two year clock will be reset. Sixty days prior to the two year mark the PI will begin receiving reminders to submit a progress update in eIRB. The Progress Update activity involves 1-2 questions the PI must answer. The PI will be asked “Is human subjects research activity ongoing (e.g interaction with subjects or their identifiable data/biospecimens)?” If they select “Yes” it will reset the two year clock. If they select “No” they will see one additional question: “If all human subjects research activities are complete, are you requesting to close the study?” If they select “Yes” the study will be automatically closed in eIRB. Completing this activity will trigger an automatic acknowledgement (i.e. it will not be reviewed by anyone in the IRB office) and will be documented in the eIRB workspace.
Once a study is closed either via a completion or the Progress Update activity, human subjects research may no longer be conducted as part of that study.
Progress Update reminders will be sent to study team (PI, lead investigator & study coordinator) periodically from 60 days prior to due date to 89 days post-due date. Failure to submit a progress update more than 89 days past the two year of no activity mark will result in automatic closure of the study. Once the study is closed, human subjects research may no longer be conducted as part of that study.
NOTE: For studies that do not require a continuing review, any events that occur over the course of the study which do NOT require prompt reporting to the IRB must be internally tracked and documented by the study team in sufficient detail to stand up to a monitoring visit or audit, but do not need to be reported to the IRB (unless required by the sponsor).
However, events which meet prompt reporting requirements should continue to be submitted as Reportable Events in in eIRB. These include events that are serious, unexpected, AND related/possibly related to the research; unanticipated problems involving risks to subjects or others; major protocol deviations; changes in subject status; ORC monitoring reports that mandate prompt reporting; events the sponsor requires the study team to submit to the IRB, and requests for prospective protocol deviations.