Continuing Review of IRB Approved Studies

SUBJECT:

Continuing Review of IRB Approved Studies

 Policy Number:
10.3.14 		Effective Date:
August 28, 2023
Supersedes:
March 24, 2022
October 21, 2011
September 10, 2010 		Page 1 of 5
Responsible Authorities:
Vice President for Research
Assistant Vice President, Research Integrity
Institutional Review Board

  1. Background

    The following federal regulations require continuing review of applicable human subjects research studies:

    • 45CFR46.108(a)3 and 21CFR56.108 state the regulations required of a continuing review process for an institution to receive federal funding.
    • Except as described in 45CFR46.109(f), Federal regulations require a continuing review to occur at least once per year

  2. Purpose

    The purpose of this policy is to identify the requirements for investigators and the IRB for the conduct of continuing review in accordance with the regulations and FAU’s policies and procedures.

  3. General Statement

    Continuing review is the ongoing monitoring mechanism by which the IRB ensures the continuing protection of subjects who participate in research. Sometimes actual risks can be better understood only after research has begun. Unexpected developments in a project or new findings can raise questions about the conduct of the research. At continuing review, the IRB can then reconsider its initial judgment. Additionally, changes in laws, regulations and guidance on human subject research can prompt the IRB to request modifications to already approved studies to ensure continued protection of human subjects.

    The IRB conducts continuing review of approved research at intervals appropriate to the degree of risk. FDA regulated research and studies which are greater than minimal risk where activities are not limited to long-term follow-up and data analysis must be reviewed at least annually. The IRB must obtain and review sufficient information to conduct substantive continuing review of research.

  4. Definitions

    Approval Date: The date on which the IRB, through either an expedited procedure or full board review, determines that a research study continues to meet all the criteria for IRB approval of research outlined in 45CFR46.111.

    Continuing Review: A regularly scheduled review of a continuing research project. The goals of continuing reviews are to ensure that the risk/benefit ratio is still acceptable, that the measures taken to safeguard subjects are adequate, that the approved protocol is followed, that the project reflects any changes that have been made in the regulations for human subjects research since the last approval, and that all of the criteria for IRB approval of research are still satisfied.

    End Approval Date: The last date study activities may occur. For example, if the IRB approval date is 7/5/2010, the end approval date is 7/4/2011. The study will expire at the end of the last day of approval.

    Expiration Date: The date when IRB approval expires. Generally, this is one year after initial approval. The IRB approval expires at 11:59 pm one day prior to this date. For example, if the IRB approval date is 7/5/2010, the expiration date is 7/5/2011 and the study expires at 7/4/2011 at 11:59 pm. Continuation of research must be evaluated, reviewed, and approved prior to this date to avoid expiration of IRB approval.

    Expired: Status in which a study is no longer considered to have IRB approval.

    IRB Approved Research: Research that the IRB, through either an expedited procedure or full board review, has determined that all the 45CFR46.111 criteria for IRB approval of research have been satisfied.

    Lapse: A temporary halt of an expired study.

    Research-Related Intervention: An activity that is required as part of the IRB approved protocol. The intervention occurs as a contribution to research results or is a follow-up to already approved research activities.

  5. Policy

    The IRB will conduct continuing review of research at intervals appropriate to the degree of risk, but not less often than once a year, when determined at initial review. The Board will determine the appropriate review interval as follows:

    • If a study was initially reviewed at a full board meeting of the IRB, then continuing review will usually be by the full board. The study may, however, become eligible for expedited review or be moved to exempt status as a result of any amendments.
    • A study previously reviewed by full board study may become eligible for expedited review if:
      1. The research is permanently closed to enrollment, all subjects have completed research-related interventions and the research remains active only for long-term follow-up subjects, or
      2. No subjects have been enrolled and no additional risks have been identified, or
      3. The remaining research activities are limited to data analysis.
    • Any approved study, whether expedited or full board, can be determined by the IRB to meet exempt status if the remaining research activities are limited to data analysis and the investigator has recorded the data in such a way that the data are not identifiable and cannot be re-linked to personal identifiers. Research that is determined by the IRB to be exempt will no longer require annual review
    • Upon review and approval of a proposed study, the IRB will set the continuing review end approval date as 364 days from the most recent approval date, unless it determines otherwise. The IRB may set a shorter continuing review if the IRB determines that a) The shorter review period will reduce possible risk to study subjects or is in the best interest of the subject, b) New information is likely to emerge that may alter the risk/benefit ratio.
    • Continuing review of research must be substantive and meaningful. Each continuing review must ensure that the criteria for approval of research listed in 45CFR46.111 are still satisfied to re-approve the study. The IRB will also consider, at a minimum, unexpected results of ongoing research, unanticipated problems, the effects of the research project itself, regulatory changes and new knowledge gained.
    • At continuing review, the IRB may elect to verify that no material changes have occurred since previous IRB review through an auditing mechanism. This may apply to a) randomly selected projects; b) complex projects involving unusual levels or types of risk to subjects; c) projects conducted by investigators who previously failed to comply with the HHS regulations or IRB requirements; and d) projects where concern about possible material changes occurring without IRB approval have been raised based upon information provided in continuing review reports, or from other sources.
    • Continuing review will be conducted by the convened IRB, with a recorded vote on each study, unless the research is otherwise appropriate for expedited review.
    • No human subject research may be conducted without prior approval from the IRB. A study that lapses past the annual review date is considered to have an expired IRB approval. Therefore, all research must stop. Subjects may not be enrolled and no research data may be collected from currently enrolled subjects until the approval is re-instated. There is no provision for any “grace” or “extended approval” period. (45CFR46.109)
    • If a study has expired, the PI may appeal to the IRB for continued subject contact during the lapse. Research procedures may only continue if, upon appeal, the IRB finds that it is in the best interests of individual subjects to continue participating in the research interventions or interactions.
    • All data collected and subjects enrolled during a lapse period, without special permission from the IRB, are considered unapproved research activities. This is a reportable protocol violation and will be communicated to all applicable Federal, State, and University regulatory bodies, as required.
    • Continuing review reminders are automatically issued by the Research Integrity Office in the Division of Research at specified intervals. However, the Principal Investigator is responsible for ensuring that the IRB receives the continuing review submission with sufficient time for review. Late submissions cannot be guaranteed a timely review.

  6. Accountability

    The Principal Investigator (PI) will be responsible for:

    • Monitoring when a continuing review is due for each research study in which he/she serves as PI.
    • Submitting a Continuing Review to the IRB:
      • If re-approval is desired, the PI must submit the continuing review form and related documentation 30 days prior to the end approval date. Applications submitted after the 30 day timeline cannot be guaranteed IRB review prior to end approval of the study. This is especially true for studies requiring full board review.
      • If re-approval is not desired, the PI should submit a request for closure. If this application is not submitted before the end approval date, the study will be considered expired. Research Integrity will close the study in accordance with IRB policy for closure of studies.
      • Applications must be submitted through Novelution with all appropriate documentation.

    The Institutional Review Board will be responsible for:

    • Determining the appropriate level of IRB review for a continuing study.
    • Considering whether a study submitted for continuing review, whether full-board or expedited, continues to fulfill the criteria for approval of research outlined in 45 CFR 46.111.
    • Requesting additional precautions, if warranted, and reassessing special requirements it had previously imposed on the research protocol.
    • Establishing the Continuing Review Date (Expiration Date).
    • Abstaining from continuing review of any project in which the member has a conflicting interest, except to provide information requested by the IRB.

    The Research Integrity office will be responsible for:

    • Ensuring that reminders are issued automatically to the PI via Novelution 30, days prior to the study’s end approval date.
    • Reviewing incoming requests for continuing review and facilitating the review process in accordance with internal SOPs.
    • Closing the study file in accordance with the IRB policy for closure of studies.

  7. Procedures

    • The PI should submit the Continuing Review form via Novelution 30 days prior to the study end approval date.
    • If the continuing review is submitted 30 days prior to end approval , the PI may continue research under the current IRB approval until the end approval date. The IRB will make every effort to review the submission within 30 days to avoid study lapse.
    • If the continuing review is submitted less than 30 days prior to end approval , the PI may continue research under previous IRB approval until the study reaches its end approval date. The PI should include a note indicating their intent to cease data collection should the study expire before the IRB can approve the study’s continuation.
    • If re-approval is not desired, the PI should submit a request for closure . The PI will receive an acknowledgment from the IRB regarding the study closure. If this request is not submitted before the end approval date the study will be considered expired, and the file will be closed.
    • If the continuing review is not submitted prior to the end approval date, the project is considered expired and all research activities, including non-interventional activity such as identifiable data analysis, must stop . If the PI wishes to continue the project, they should submit for a new project in Novelution and reference the expired study. If data has already been collected on the project that has expired, this data may be merged with the new project data. The project will receive a new expiration date.

    The PI should also submit a closure for the expired project and include an explanation as to why IRB approval expired, and a plan to prevent future expirations.

  8. Policy Renewal Date: As needed.

  9. References

    45CFR46.108(a)3
    21CFR56.108
    45CFR46.115
    21CFR56.107(e)
    45CFR46.109e)(f)
    21CFR56.109(f)

    Office for Human Research Protection (OHRP) Continuing Review Guidance (2010)

POLICY APPROVAL

Initiating Authority

Gregg Fields, Ph.D., Interim Vice President for Research
8/31/2023

Executed signature pages are available in the Initiating Authority Office(s)

Appendix A

Study expirations are issued for “greater than minimal risk” projects and may be issued for “minimal risk” projects. As referenced in this policy, when required, an IRB must conduct continuing review of research at intervals appropriate to the degree of risk, but not less than once per year.

For minimal risk projects, if the IRB member(s) makes a determination the project requires annual review, the PI will be issued a one-year expiration as detailed in this policy. In making this decision, one or more IRB members use “CHECKLIST: IRB REVIEWER CRITERIA FOR APPROVAL (HRP-200)”. A continuing review may be required for one or more of the following reasons:

  1. Required by other applicable regulations (e.g., FDA).
  2. The research involves topics, procedures, or data that may be considered sensitive or controversial.
  3. The research involves particularly vulnerable subjects or circumstances that increase subjects’ vulnerability.
  4. An investigator has minimal experience in research or the research type, topic, or procedures.
  5. An investigator has a history of noncompliance.

If it is determined a minimal risk project does not require annual review, a continuing review of three (3) years will be requested. The purpose of a three-year review is to provide the IRB with a mechanism to assess the progress of a project.

An overview of requirements is as follows:

One Year Continuing Review** Three Year Continuing Review No Continuing Review
  1. Studies determined greater than minimal risk*. These reviews must be reviewed at a fully convened IRB meeting.
  2. Minimal risk* studies in which one or more IRB members determine a project must be reviewed on an annual basis as outlined in CHECKLIST: IRB REVIEWER CRITERIA FOR APPROVAL (HRP-200).
  1. Minimal risk* studies in which one or more IRB members determine a project does not require review on an annual basis.
 Projects determined Exempt from IRB Review.
*Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. **Unless otherwise determined by a fully convened IRB that continuing review must occur more frequently than one year.