Section VIII:

Review Types/Process

WPP #: VIII-4

Title 4:

Continuing Review

Effective Date:

09-24-14

Revision History:

06-20-00; 08-29-00; 09-20-01; 06-07-04; 12-06-04; 06-21-06; 02-05-07; 06-01-08; 05-13-14

Policy Statement

All human research is subject to continuing review of research based on the level of risk as assessed by the IRB at the time of initial review, with the exception of research protocols determined to be exempt (VCU IRB WPP VIII-1). The VCU IRB considers the same criteria for consideration of approval under continuing review as under initial review in accordance with 45 CFR 46.111, including, among other things, determinations by the IRB regarding risks, potential benefits, informed consent, and safeguards for human subjects.

Description and Procedures

  1. Length (Duration) of Approval (or Other Requirement for Continuing Review):

    At initial review and at continuing review (or otherwise as warranted), the VCU IRB will plan for continuing review of research at intervals appropriate to the degree of risk (as per VCU IRB WPP#s: VIII-2 and VIII-3), but not less than once per year, and will exercise the authority to observe or have a third party observe the consent process and the research, as appropriate (given the level or risk, experience of the investigator, vulnerability of subjects, or other concerns) [45 CFR 46.109(e)].

    For research receiving full board review, the length of approval is calculated from the date of the full board review. The primary and secondary reviewers are asked to provide a recommendation for length of approval; if other than annual continuing review will be required. The appropriate length of approval is considered as part of the full board discussion of known or potential risks.

    For research approved via expedited initial review, the primary reviewer suggests length of approval (see VCU IRB WPP#: VIII-2). For research reviewed via exempt review, continuing review is not required.

  2. Research Requiring Review More Frequently Than Annually and/or at Other Intervals:

    The VCU IRB will plan for continuing review of research at intervals appropriate to the degree of risk, but not less than once per year, and will exercise the authority to observe or have a third party observe the consent process and the research, as appropriate (given the level or risk, experience of the investigator, vulnerability of subjects, or other concerns) [45 CFR 46.109(e)]. The IRB may require review more often than annually for ANY research activities, including:

    1. Research that involves withdrawal of therapy when there may be significant morbidity or mortality.
    2. Research that involves an invasive surgical procedure (that would not otherwise be done).
    3. Research in which there are serious risks to participants and no potential benefits, or
    4. More than minimal risk research involving a vulnerable population with no prospect of direct benefit to the individual participants.

    In cases such as the above, approvals may be granted for time periods less than one year or, as may be more appropriate, for a limited number of subjects over a period not to exceed one year. The primary reviewer is responsible for recommending these requirements at the time of review or as needed.

  3. Notification of Investigators:

    Principal investigators are notified of length of approval and/or limitations of approval in their initial review approval letter. Reminder notices may be sent by the ORSP as a courtesy to investigators, but are not to be relied upon.

  4. Full Board Continuing Review:

    Research previously reviewed via full board review automatically receive a full board continuing review unless the IRB panel, at a convened meeting of the IRB, determined that a study qualifies for expedited continuing review under expedited Category 9, or the primary reviewer determines that the study qualifies for expedited continuing review under expedited Category 8 (a, b, or c).

  5. Continuing Review Materials

    In conducting continuing review of research, all IRB reviewers, and full attending IRB members (if full board review is required) will review the following:

    1. IRB Continuing Review submission
    2. A status report on the progress of the research, including:
      1. The number of subjects enrolled;
      2. The number of participant withdrawals and the reasons for those withdrawals
      3. Summary reportable events, including (but not limited to):
        1. A summary of adverse events since the last IRB review.
        2. A summary of unanticipated problems involving risks to participants or others since last IRB review.
        3. A summary of complaints about the research since the last IRB review.
      4. A summary of any relevant recent literature, interim findings, and amendments or modifications to the research since the last review;
      5. Any relevant multi-center trial reports; and
      6. Any other relevant information, especially information about risks associated with the research
    3. The research plan or Sponsor's protocol (if applicable). Furthermore, upon request, any IRB member also should have access to the complete IRB protocol file and relevant IRB minutes prior to or during the convened IRB meeting.
    4. A copy of the current informed consent document. When reviewing the current informed consent document(s), the IRB will ensure the following:
      1. The currently approved or proposed consent document is still accurate and complete;
      2. Any significant new findings that may relate to the subject's willingness to continue participation are provided to the subject in accordance with HHS regulations at 45 CFR 46.116(b)(5).
    5. Any proposed amendments.
      1. Review of currently approved or newly proposed consent documents must occur during the scheduled continuing review of research by the IRB, but informed consent documents should be reviewed whenever new information becomes available that would require modification of information in the informed consent document.
    6. The IRB will consider whether verification is needed from sources other than the investigator that no material changes have occurred since previous IRB review. Examples of when the IRB may require verification from other sources include: (a) investigator has a pattern of submitting the wrong version of the protocol or consent document at time of continuing review, and (b) the investigator has a pattern of submitting reports of unanticipated problems (UPs) past the deadline for reporting UPs.
    7. The IRB will also ensure that the active research plans demonstrate that:
      1. The investigator will obtain the legally effective consent of the participant or the participant’s legally authorized representative.
      2. The circumstances of the consent process provide the prospective participant or the legally authorized representative sufficient opportunity to consider whether to participate.
      3. The circumstances of the consent process minimize the possibility of coercion or undue influence.
      4. The individuals communicating information to the participant or the legally authorized representative during the consent process will provide that information in language understandable to the participant or the representative.
      5. The information being communicated to the participant or the representative during the consent process will not include exculpatory language through which the participant or the legally authorized representative is made to waive or appear to waive any of the participant’s legal rights, or release or appear to release the investigator, the sponsor, the institution, or its agents from liability for negligence.
  6. Full Board Continuing Review Process:
    1. Reviewer comments will be prepared prior to the IRB meeting and presented verbally to the panel with the recommendation for action. Changes and/or clarifications requested by the reviewer will be documented in writing and made available to the IRB Coordinator.
    2. If there were pertinent changes to the research protocol submitted at the time of continuing review, the reviewer’s comments must include the following, if applicable:
      1. Confirmation that the research continues to meet the criteria for review found at 45 CFR 46.111 and 21 CFR 56.111;
      2. Confirmation that the research meets the requirements found at Subparts B, C and D, when applicable, and the precise information justifying each of the determinations;
      3. Confirmation that the research meets the requirements for informed consent, including consent alterations or waivers, and the precise information justifying each of the determinations;
      4. Confirmation that the research meets the requirements for assent, including whether the permission of one or both parents is required, if applicable;
      5. Approval period dates (if less than annual continuing review is recommended) or detailed limitations to approval periods (such as limitations to enrollment numbers prior to reporting back for continuing review).
    3. A full and complete discussion regarding ethical concerns and issues impacting research subjects takes place prior to a motion of the IRB, a second motion, and a final vote.
    4. Full board continuing reviews are recorded as part of the minutes of the IRB meeting in which they are conducted (as separate deliberations, actions, and votes for each protocol undergoing continuing review by the convened IRB). Continuing review determinations are communicated in writing to the principal investigator.
  7. Continuing Review via Expedited Categories 8 and 9

    Category 8: Continuing Review of research previously approved by the convened IRB as follows:

    • where (i) the research is permanently closed to the enrollment of new subjects; (ii) all subjects have completed all research-related interventions; and (iii) the research remains active only for long-term follow-up of subjects; or
    • where no subjects have been enrolled and no additional risks have been identified; or
    • where the remaining research activities are limited to data analysis.

    Category 9: Continuing Review of research, not conducted under an investigational new drug application or investigational device exemption where categories two (2) through eight (8) do not apply but the IRB has determined and documented at a convened meeting that the research involves no greater than minimal risk and no additional risks have been identified.

  8. Expedited Continuing Review:
    1. Expedited continuing review submissions are assigned to the original panel that conducted the initial IRB review. Expedited research projects will be reviewed by the Chairperson of a VCU IRB Panel or by an experienced member of the IRB designated by the Chairperson.
    2. Reviewer's actions are limited to approving research or requiring modifications to secure approval.
    3. Research previously approved via expedited review is considered eligible for expedited review at the time of its regular continuing review, if, during the course of the study, the risks of the study have not increased.
      1. Expedited initial approvals trigger expedited continuing review unless the investigator proposes changes in the study that cause the review type to be modified to full board review. At the time of continuing review, the reviewer must verify that the research meets all applicability criteria for one or more approvable categories of research based upon review of the continuing review report. The Expedited review category must be confirmed and documented.
      2. If the initial review was conducted via Full Board review and is now proposed for Expedited continuing review, the reviewer must verify that the research meets all applicability criteria for the Expedited review category (8 or 9) based upon review of the continuing review report. The Expedited review category must be confirmed and documented.
    4. If there is any protocol-related information requiring clarification, the reviewer should contact the principal investigator (or appropriate designee directly).
    5. Final review comments by the expedited reviewer must be documented in writing. All continuing review reports (reviewed via expedited review) are reported to a convened Panel meeting and are available to all Panel members and alternate members (upon request).
    6. The list of all expedited continuing review reports that were received prior to the next meeting of each panel are attached as part of the agenda of the meetings at which they are reported.
  9. DMSB, DMC, and Other Boards:

    When the IRB is conducting continuing review in multi-center trials monitored by a DSMB, DMC, or other similar body or sponsor where relevant data/information may not be readily available to local investigators, the VCU IRB may request/require and rely upon a current statement from the DSMB or sponsor indicating that it has reviewed study-wide adverse events, interim findings, and any recent literature that may be relevant to the research (in lieu of requiring that this information be submitted directly to the IRB and in addition to reports of local, on-site events and unanticipated problems).

  10. Lapse in Continuing Review

    When continuing review of a research protocol does not occur prior to the end of the approval period specified by the IRB, IRB approval expires automatically, and all research activities must stop (including recruitment, enrollment, interactions and interventions on current participants, and data analysis). Investigators who believe that current participants will be placed at risk by stopping research procedures should immediately contact the IRB chairperson and/or prepare a written justification for continuation (in accordance with the VCU IRB approval letter), whichever is the most necessary immediate action based upon the research schedule. The IRB chairperson (or designee) will review the justification, and notify the investigator in writing whether current participants can continue. The ORSP will provide a formal notice of expiration of approval on the date that expiration occurs as a clear alert to principal investigators of the situation. Such expiration of IRB approval does not need to be reported to OHRP as a suspension of IRB approval under HHS regulations, as per OHRP guidance.

References

HHS 45 CFR 46.109(e)
FDA 21 CFR 56.109(f) 
OHRP Guidance on Continuing Review (November 10, 2010)
VCU IRB WPP VIII-2 Initial Review-Expedited
VCU IRB WPP VIII-1 Initial Review – Exempt