HRPP Manual Section 8-7

Renewed Approval

Revised Common Rule (2018 Requirements)
(e) An IRB shall conduct continuing review of research requiring review by the convened IRB at intervals appropriate to the degree of risk, not less than once per year, except as described in §46.109(f).

(f)

(1) Unless an IRB determines otherwise, continuing review of research is not required in the following circumstances:

(i) Research eligible for expedited review in accordance with §46.110;

(ii) Research reviewed by the IRB in accordance with the limited IRB review described in §46.104(d)(2)(iii), (d)(3)(i)(C), or (d)(7) or (8);

(iii) Research that has progressed to the point that it involves only one or both of the following, which are part of the IRB-approved study:

(A) Data analysis, including analysis of identifiable private information or identifiable biospecimens, or

(B) Accessing follow-up clinical data from procedures that subjects would undergo as part of clinical care.

(2) [Reserved]” 45 CFR 46.109(2018 Requirements)

Pre-2018 Common Rule
(e) An IRB shall conduct continuing review of research covered by this policy at intervals appropriate to the degree of risk, but not less than once per year, and shall have authority to observe or have a third party observe the consent process and the research. 45 CFR 46.109(e)(Pre-2018 Requirements), 21 CFR 56.109(f)

Revised Common Rule Requirements for Renewed Approval
Continuing renewed approval is required at least annually for research that requires review by the convened IRB, unless it meets the criteria listed below. The IRB may require additional review at more frequent intervals if the assessment of risk warrants it. See HRPP Manual 8-5 “Initial Review” for consideration of when review may be required more often than annually.

Unless the IRB determines otherwise, continuing renewed approval is not required for:

  • Research eligible for expedited review in accordance with §46.110;
  • Research that has progressed to the point that it involves only one or both of the following, which are part of the IRB-approved study:
    • Data analysis, including analysis of identifiable private information or identifiable biospecimens, or
    • Accessing follow-up clinical data from procedures that subjects would undergo as part of clinical care.

Modifications, reportable events (e.g. unanticipated problems involving risks to subjects or others, noncompliance) and study closure must still be submitted to the IRB, even if the study does not require continuing renewed approval. See HRPP Manual 8-6 “Modifications to an Approved Study,” 8-9 “Closure” and Section 9: Urgent Situations. The IRB will also typically require a status check to determine if the human subject research activities are still ongoing or if the study could be closed.

If the IRB determines continuing review is required for research that otherwise would not require continuing review as described in 45 CFR 46.109(f)(1)(2018 Requirements), the IRB will document the rationale for conducting continuing review of that research. A standard form will be used to document the determination.

Pre-2018 Common Rule Requirements for Renewed Approval
Institutional Review Board (IRB) approval is valid for a maximum period of one year. However, the IRB may require additional review at more frequent intervals if the assessment of risk warrants it. See HRPP Manual 8-5 “Initial Review” for consideration of when review may be required more often than annually.

Applicability of the Revised Common Rule (2018 Requirements)
See HRPP Manual Section 4-11 “Applicability of the Revised Common Rule (2018 Requirements)” for a description of whether the Revised Common Rule (2018 Requirements) or the Pre-2018 Common Rule Requirements apply.

The following sections describe the requirements when renewed approval is required.

Required Renewed Approval
Principal investigators (PI) who would like to continue non-exempt human research and/or a clinical investigation beyond the expiration of IRB approval must receive renewed approval prior to the research study’s expiration. The approval period will be listed on approval letters sent to researchers, including both the approval date and the approval end (expiration) date.

When renewed approval review is required, it must be conducted until the study can be closed.  Please see HRPP Manual Section 8-9 “Closure” for more information.

Continuing Review Reminders
Continuing review reminders are routinely sent by the MSU IRB online system to researchers to assist in meeting the continuing review requirement. Such continuing review reminders include research study specific information (e.g., title, expiration date) as well as a reminder to investigators that research activities must stop on the expiration date if a continuing review is not approved by the IRB. Several continuing review reminders are typically sent prior to expiration. Continuing review reminders are sent via email and the IRB cannot ensure successful delivery or receipt. Ultimately, it is the responsibility of the PI to ensure a continuing review submission is submitted prior to the research study’s expiration date. See HRPP Manual 3-1 “MSU Human Research Protection Program Plan” for a description of the MSU IRB online system.

Failure to Obtain Renewed Approval
If a PI does not provide continuing review information to the IRB or the IRB has not approved a continuing review submission by the expiration date:

  • All human research activities must stop. Stopping all human research activities includes recruitment, advertisement, screening, enrollment, consent, interventions, interactions, and analysis of identifiable private data.
  • Interventions and interactions on current subjects can continue only when the IRB finds an over-riding safety concern or ethical issue involved such that it was in the best interests of individual subjects to continue.
  • Under no circumstances can the IRB allow the enrollment of new subjects into expired research studies.

After expiration of the IRB approval, all human research activities, including interacting or intervening with subjects and obtaining, using, studying, or analyzing identifiable private information about subjects or identifiable biospecimens, must stop. If the PI believes that it is in the best interest of the individual subjects to continue participating in research interventions or interactions, he/she should notify the IRB immediately. The IRB chair will make the decision of whether to allow continuation, with consultation from other members of the IRB when appropriate. In any case, enrollment of new subjects cannot occur after the expiration of IRB approval.

For policies and procedures on closure of research studies, see HRPP Manual 8-9 “Closure.”

Materials Required for Submission
To apply for renewed approval of a research study, the PI must complete a continuing review submission and if appropriate, data and safety monitoring reports.

The continuing review submission (i.e. status report) completed by the PI contains the following information:

  • Number of subjects enrolled total and since last approval at the investigator’s sites and study-wide
  • Confirmation that certain items are true, or an explanation if they are not, including:
    • No subjects experienced unexpected harm
    • Anticipated adverse events have not taken place with greater frequency or severity than expected
    • No subjects withdrew from the study
    • No unanticipated problems involving risks to subjects or others
    • No complaints about the study
    • No publications in the literature relevant to risks or potential benefits
    • No interim findings
    • No multi-center trial reports
    • No data safety monitoring reports
    • No regulatory actions that could affect safety and risk assessments
    • No other relevant information regarding this study, especially information about risks
    • In the opinion of the PI, the risks and potential benefits are unchanged
    • All modifications to the protocol have been submitted to the IRB
    • All problems that require prompt reporting to the IRB have been submitted

The MSU IRB online system includes the study and protocol template for non-legacy studies that incorporates all modifications that have been approved by the IRB. A summary is required for legacy studies (i.e. studies that had been reviewed in the previous MSU IRB online system). See HRPP Manual 3-1 “MSU Human Research Protection Program Plan” for a description of the MSU IRB online system and legacy studies.

For research where the IRB has not waived consent, a current copy of the consent form may be available through the MSU IRB online system. For studies where a copy is not available, a current copy of the consent form should be included with the continuing review submission. The consent form, however, does not need to be included if the research study is closed to accrual and only undergoing data analysis or long term follow up where subjects have already given their consent. If there are questions of whether a current copy of the consent form is needed, the IRB staff should be consulted.

If there are any changes to the research study (e.g., consent form, target population, recruiting methods, surveys or study instruments, study protocol) that have not yet been submitted to the IRB, a modification submission and any modified documents (e.g. newly proposed consent form, revised survey) should be submitted with the continuing review. Any change to the research study must be approved by the IRB before the requested modification may be implemented. See HRPP Manual 8-6 “Modifications to an Approved Research Study.”

Mechanism(s) for Submission
MSU IRB continuing review submissions must be submitted via the MSU IRB online system. The continuing review submission must be completed in full; all required questions must be completed. The MSU IRB online system will not allow submission of an incomplete submission.  The PI or PI proxy must confirm through the submission process that they will conduct the study in accordance with the responsibilities of researchers. See HRPP Manual 4-6, Responsibilities of Researchers. Only the PI or PI proxy may submit a continuing review submission.

Submission Processing
The HRPP staff checks for completeness (e.g., all questions completed, HRP-527 – Template – Explanation for Items Left Unchecked in Question 4). Incomplete submissions will be returned.

Ancillary Review(s)
If the continuing review submission impacts an area where an ancillary reviewer is typically assigned for initial review, the ancillary reviewer(s) is assigned to the study by the IRB coordinator. Depending on the ancillary review type and need, a response may be needed from the ancillary reviewer before an approval letter can be released. See HRPP Manual 8-5 “Initial Review” for more information.

Change in Review Level
At the time of continuing review, the IRB or IRB chair may determine that a research study’s level of review may be changed. See HRPP Manual 8-2 “Expedited Review Procedure” or 8-3 “Committee Review Procedure” for procedures to change the level of review.

Materials Provided to IRB Members
The assigned reviewer will access the continuing review submission, current consent form (if applicable), and any supporting documents via the MSU IRB online system. The reviewer will also have access to the complete IRB file for review, including any protocol modifications previously approved by the IRB. The reviewer accesses and reviews the research study.

How Review is Conducted
IRB members shall receive and review the full protocol, submission, or protocol summary with sufficient and relevant information necessary to determine whether the proposed research continues to fulfill the criteria for approval.

For requirements on the materials to be distributed to IRB members and review procedures for expedited and full board continuing review submissions, see the following sections of the HRP Manual:

5-5            Meetings
8-2            Expedited Review Procedure
8-3            Full Board Review Procedure

IRB Member Considerations
The IRB member(s) is required to review and approve protocols using the criteria at federal regulations 45 CFR 46 and, for FDA research studies, 21 CFR 50 and 56. If the human subject research is conducted, supported, or otherwise subject to regulation by a federal department or agency, there may be requirements in addition to 45 CFR 46 that are specific to the federal department or agency. See HRPP Manual 2-2 “Federal Guidelines and Regulations.” The criteria for IRB approval must be met to approve or recommend approval of the submission. The IRB member(s) should utilize HRPP Manual 6 “IRB Evaluation Criteria.” If there have been any modifications, the IRB member(s) should utilize the appropriate policy in HRPP Manual 6 “IRB Evaluation Criteria” to review the proposed change (e.g., informed consent section for changes to the informed consent process).

The IRB considers the following points in performing continuing review:

  • Assessment of actual risks and benefits against anticipated risks and benefits
  • Whether there have been any:
    • Harm to subjects
    • Problems or accidents
    • Unanticipated problems, adverse events, change in the research environment, or new knowledge that the research study poses greater risk to subjects than expected when the study was previously approved and if so, whether shared with subjects
    • Significant new findings that might relate to subjects’ willingness to continue and if so, has or will the information be provided to subjects or will subjects re-consent
    • Complaints by the subjects or their representatives related to their participation in the study
  • Progress reports
  • Accuracy of consent form and need for modification
  • Alteration of risks level as a result of requested changes; see HRPP Manual 8-6 “Modifications to a Research Study” for policies and procedures relating to changes

The consent form will be evaluated to determine if the consent is still accurate and complete. Based on the continuing review submission, the consent form will be evaluated to determine if findings that might relate to the subject’s willingness to continue should be included in the consent form. The evaluation will be based on the information provided in the continuing review submission, including information on new findings, any changes to the research study, risks, and benefits. If it is determined that new information should be provided, the IRB will consider whether the information should be provided to all past subjects as well as new enrollees or only to new enrollees. If information is to be provided to past subjects, the IRB should consider whether an information sheet or a re-consenting process is needed.

If information provided at the time of continuing review (e.g., subject complaints, unanticipated problems, evidence of increased risk) indicates that subjects may be at risk, an immediate issue to consider will be whether to:

  • Stop accrual of subjects and/or restrict activities
  • Suspend approval of the protocol
  • Notify officials who will take appropriate action (e.g., notify Contract and Grant Administration)

The IRB chair may reach this decision with consultation from other members of the IRB.  At any time during the continuing review process the IRB chair or IRB may determine that it is necessary to act to protect subjects by suspending the protocol. If this occurs, the policy and procedures of HRPP Manual 9-3 “Termination or Suspension of IRB Approval” are followed.

Additional Considerations
See HRPP Manual 8-5 “Initial Review” for consideration of when review may be required more often than annually.

Research studies may require verification from sources other than the investigator that no material changes have occurred since previous IRB review. This requirement may have been imposed during the initial review of the research study or at any time after initial review. To determine when further verification is needed, the IRB will consider:

  • Concerns raised during the initial review due to the sensitive nature of the study (e.g., if the investigator described safeguards to assure the protection of research subjects, verification that safeguards are in place)
  • High risk research studies (e.g. Phase I)
  • Clinical investigations where the investigator is also the sponsor
  • Previous noncompliance
  • Complaints
  • Others as the IRB sees fit

This policy and procedure supersedes those previously drafted.

Approved By: Vice President of Research and Graduate Studies, 4-21-2005. Revision 1 approved by VP Research & Graduate Studies on 11-2-2005. Revision 2 approved by VP Research & Graduate Studies on 3-9-2008. Revision 3 approved by VP Research & Graduate Studies on 5-6-2008. Revision 4 approved by VP Research & Graduate Studies on 9-3-2009. Revision 5 approved by VP Research & Graduate Studies on 7-22-2011. Revision 6 approved by Assistant VP Regulatory Affairs on 4-5-2014. Revision 7 approved by VP Research & Graduate Studies on 12-11-2015. Revision 8 approved by Assistant VP Regulatory Affairs on 6-27-2018. Revision 9 approved by Senior VP for Research and Innovation on 1-18-2019.

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