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Chapter 11 - Continuing Reviews (CR)

Overview

Key Points

  • Protocols require periodic review by the IRB to ensure that the protocol continues to meet the criteria for approval.
  • Depending on the risk of the study, the continuing review process may require approval by a fully convened IRB or may undergo an expedited review process.
  • Failure to submit a continuing review in a timely matter can result in a lapse in IRB approval.
What is a Continuing Review?
  • Continuing Review (CR) is the ongoing, scheduled IRB review of a previously approved non-exempt human subjects research study, at intervals appropriate to the degree of risk, but not less than once per year (364 Days), except as described in 45 CFR 46.109(f) for research that is subject to the 2018 Common Rule.
  • The IRB will look at the progress of a previously approved protocol over the past year. They will also be checking to make sure that the protocol meets current regulations and policies. The fully convened IRB may perform this review, or it may be reviewed by an expedited reviewer under certain circumstances.
Why is Continuing Review required?

Continuing Review (CR) provides an opportunity for the IRB to reassess the totality of the project and ensure that, among other things, risks to subjects are minimized and are still reasonable in relation to anticipated benefits, if any, and the knowledge that is expected to result from the research. At the time of continuing review, the IRB considers whether there is any new information provided by the investigator, or otherwise available to the IRB, that would alter the criteria of IRB approval of the research. The CR provides the IRB with:

  • The chance to review information from any monitoring entity as well as unanticipated problems that have occurred since the last CR to determine if there is any change in the risk: benefit relationship of the research.
  • The opportunity for the IRB to ensure investigators are using the most recently approved version of the consent document.
  • Chance to review any unresolved subject complaints.
  • Ongoing enrollment data to assess whether enrollment is consistent with what is planned
  • Information about/reason for any subject withdrawals that might suggest problems related to conduct of the research.
When does a protocol require a Continuing Review?
  • All research subjected to FDA regulation requires at least an annual CR, regardless of whether the research is subject to the pre-2018 or 2018 Common Rule.
  • If the study is under the pre-2018 Common Rule, all non-exempt research requires a continuing review.
  • If the study is under the 2018 Common Rule, all non-exempt research that requires full board review requires a continuing review.
  • TIP: If your protocol has an expiration date, your protocol requires continuing review. The outcome letter from the approval of the Initial Review will contain the expiration date of the CR.
What protocols only require an Annual Progress Report instead of a full CR?
  • Unless the IRB determines otherwise, if the study is under the 2018 Common Rule and falls into one of the categories below, no continuing review is required, but an annual progress report may still be required by the NIH IRB.
    • Eligible for expedited review (Unless it is FDA regulated or determined to be expedited under category 9 or category 8b)
    • Research under limited IRB Review
  • Research that has progressed to only data analysis with identifiable information/specimens, or research is limited to only follow-up data collection from subjects undergoing clinical care.
  • In this case the same Progress Report Form is used but required information will be more limited.
  • TIP: If your protocol does not have an expiration date, only an Annual Progress Report is required. You will receive a reminder in iRIS before the due date of the Annual Progress Report.
How often must my protocol go through Continuing Review?
  • The IRB determines the timeframe of the subsequent CR at time of protocol review. Most protocols will be reviewed every 12 months. However, the timeframe may be shortened by the IRB if the IRB determines that more frequent review is required. Possible reasons the IRB may require more frequent CR is if the protocol is high risk, or the protocol requires prompt modifications. This will be indicated on the outcome letter from the IRB meeting and the exact expiration date will be provided.
  • The expiration date cannot be extended and there is no grace period.
  • The time between two CRs can be no more than 364 Days. The expiration date will be set from either the date of the Full Board IRB meeting or the date the submission is approved by the expedited reviewer. The date will be included in the Continuing Review Approval letter.
  • You will receive a reminder in iRIS that the due date for the CR is approaching. It is recommended that you submit the Progress Report Form in the electronic IRB system at least six weeks before the due date to ensure that the protocol does not expire.
What happens if the Continuing Review is not approved by the expiration date and there is a lapse in IRB approval?
  • If the CR is not approved by midnight the day the protocol expires, all research activities and enrollment must be stopped until approval is granted by the IRB.
  • However, when it is in the best interests of already enrolled subjects to continue in the research during the period of lapse in IRB approval, the IRB has the authority to, or the PI may request from the IRB, permission to continue participation of already enrolled subjects during this period.
  • If a study has lapsed due to the PI's failure to obtain timely CR, the IRB may elect not to review other active or new studies submitted by the PI until the CR is resolved.
  • If the study lapses more than 45 days, the PI must submit a new initial review in order for the research to continue.
  • If the study does lapse, this event is not considered noncompliance requiring expedited submission of an event report in the electronic IRB system.
What forms must be submitted in the electronic IRB system for a Continuing Review?
  • Note that no changes to the protocol or consent form(s) are permitted as part of the Continuing Review (CR). However, any changes can be submitted as a separate amendment and both submissions may be reviewed at the same meeting.
  • Progress Report (Check box format)
    • Updated demographic information on enrolled subjects and study accrual
    • High-level summary of reportable events and adverse events (See Tips & Tricks for When Submitting to the NIH IRB.)
    • Any unresolved subject complaints
    • DEC clearance for covered protocols
    • DSMB/SMC/IMC Review (consistent with the protocol DSMP)
    • Progress of Research and Justification to continue
    • Updates on Publications or Risk information
  • Study Application
    • Double check that the study personnel is listed completely and correctly in the proper sections.
    • Review for updates or changes since the last CR. These most likely would be from an Amendment that was approved during the review period.
    • For multicenter studies. make sure the information related to the sponsor, the coordinating entity, and other sites is up to date and correct.
  • Attachments
    • Redacted consents (See Tips & Tricks for When Submitting to the NIH IRB.)
      • The latest consent and/or assent of all available document types. (i.e., Healthy Volunteer, Standard, Screening, Recipient, Donor, etc.)
      • If there has been no enrollment during the Continuing Review period, this is not required.
    • DEC clearance for covered protocol
    • DSMB/SMC/IMC Report
    • For multicenter studies: If the NIH is the coordinating center and there are sites under local IRB review, provide the CR approval letters from the local IRBs or Ethics Committees.
    • Any supporting documentation from sponsors or manufacturers including updated investigational brochures.
    • Audit results relevant to the continuation of the research.
What happens after the IRB receives my CR submission?
  • The submission will undergo a pre-review by one of the IRBO Analysts. They will make sure that the submission is correct and contains all the needed components. They will also anticipate the needs of the IRB and may request additional information by sending back pre-review stipulations to the research team.
  • The submission will then be assigned to an IRB meeting or an expedited reviewer. You will be able to see the date that the submission will be reviewed in the electronic IRB system.
  • Once the IRB reviews the submission, the following outcomes will be communicated by an outcome letter in the electronic IRB system:
    • Reviewed-Response Required: This means that they have reviewed the study, but certain information is required, or action needs to take place before your study is approved.
    • Approval with Stipulations: The study has been approved, but there are certain actions that are required for this approval. The CR approval period may be shortened to make sure these actions occur.
    • Approval: The study has been approved until the next CR.


Chapter 12 - Study closures (routine)