Study Closure, Suspension, Or Termination
IRB Study Closure, Suspension, or Termination
March 7, 2011
VANJHCS
Institutional Review Board
Standard Operating Procedures
STUDY CLOSURE, SUSPENSION, OR TERMINATION
1 PURPOSE/SCOPE
The purpose of this Standard Operating Procedure (SOP) is to delineate the procedure for study closure, study suspension, or study termination.
2 POLICY
Proposed changes to the research; including a study closure, study suspension, or study termination may not be initiated without Institutional Review Board (IRB) approval unless there is concern regarding the safety, rights, and welfare of human subjects or others, the unapproved action is necessary to eliminate the potential of apparent immediate harm to them, and the IRB will be notified immediately but no later than 5 business days of awareness of the event.
3 DEFINITIONS
Institutional Review Board (IRB): The committee formally designated by the organization to review, require modifications in, approve, disapprove, and conduct continuing oversight of human research.
Suspension of IRB approval of research: refers to the IRB placing a temporary interruption or stop of some or all previously approved research activities for concern regarding the safety, rights, or welfare of human subjects, investigators, or others pending one or more corrective actions or events. Following completion of the corrective action, the convened IRB may approve some or all of the suspended research activities. Note: Expiration of IRB approval does not in and of itself constitute Suspension or Termination.
Termination of IRB approval of research: A directive of the IRB to permanently withdraw approval for some or all research activities.
4 INVESTIGATOR-INITIATED CLOSURE, SUSPENSION, OR TERMINATION
It is the responsibility of the principal investigator (PI) to promptly notify the IRB, in writing, when study activities have ceased, are terminated, or are suspended by the investigator for any reason, including normal and anticipated study closure.
The PI is to submit a completed IRB Closure Request indicating the reason for closing the study with an updated abstract and Project Data Sheet.
Note that if a study is closed to accrual and subject follow-up or data analysis will continue, the study must remain active, and IRB approval must be maintained with annual IRB continuing review.
5 REGULATORY AUTHORITY FOR IRB CLOSURE, SUSPENSION, OR TERMINATION OF APPROVAL
At the VANJHCS, the authority to administratively close non-exempt human research for reasons unrelated to risks has been delegated to the IRB by the Research and Development (R&D) Committee with the concurrence of the Associate Chief of Staff (ACOS) R&D. The IRB shall have the authority to approve the motion to close the study to enrollment, to close the study to data analysis, or to close all aspects of the study for reasons unrelated to events involving or suggesting risk to subjects or others (e.g., administrative closure of a study with expired IRB approval.) The motion may be made by an IRB member but must be approved by a majority of IRB members at a convened IRB meeting.
As described in VA regulations Title 38 CFR 16.113 and VHA Handbook 1200.05, the IRB shall have authority to suspend or terminate approval of research that is not being conducted in accordance with the IRB's requirements or that has been associated with unexpected serious harm to subjects. Any suspension or termination of approval shall include a statement of the reasons for the IRB's action and shall be reported promptly to the investigator, ACOS R&D, Chief of Staff, R&D, R&D Committee Chair, and other entities (per Reporting to IRB and Off Station Agency SOP and VHA Handbook 1058.01). (AAHRPP II.4.D)
Note that expiration of IRB approval occurs automatically and is not an action of the IRB. Therefore, expiration of IRB approval is not a suspension or termination of IRB approval and does not need to be reported to OHRP as a suspension of IRB approval under DHHS regulations. The expiration of approval is to be reported to the sponsor promptly. (AAHRPP II.4.D)
A. Suspension
1. Investigators and all members of the research community must report AS SOON AS POSSIBLE, but no later than 5 BUSINESS DAYS after becoming aware of the any event(s)/problem(s) involving or suggesting risks to subjects or others to the IRB and ACOS R&D. Such problems include but are not limited to:
a. All on-site serious adverse events (SAEs);
b. Any event/problem that involves or suggests risks to subjects or others that has the potential to be serious, unanticipated, and related to the research;
c. Possible serious or continuing noncompliance;
d. Any interruption, suspension, or termination of the study activities by the Sponsor, grant agency, or investigator;
e. Possible research misconduct.
2. If the IRB Chair or designee determines that suspending the study is necessary to protect subjects or others from the potential of apparent immediate harm, the IRB Chair or designee will:
a. Document the determination using the Event/Problem Form and/or the IRB Primary Reviewer Worksheet for Serious or Continuing Noncompliance as applicable;
b. Impose immediate action to protect subjects from the potential of apparent immediate harm;
c. Communicate with the IRB at a convened meeting.
d. Communicate with the investigator about the determination and the step(s) to take in the timeframe appropriate for the matter;
e. Communicate the incident to the ACOS R&D, the Chief of Staff, the R&D Committee Chair, and other entities (per Reporting to IRB and Off Station Agency SOP and VHA Handbook 1058.01).
3. The convened IRB, ACOS R&D, or the R&D Committee may suspend approval of research not being conducted in accordance with IRB or regulatory requirements or that has been associated with unexpected problems or serious harm to subjects. (AAHRPP II.4.D)
· Suspensions by the ACOS R&D or R&D Committee must be reported to the IRB staff who will place the suspension on the agenda of the next available convened IRB meeting. The convened IRB will review the suspension or termination and determine whether it should continue and what additional actions should be taken. (AAHRPP II.4.D)
B. Termination
The IRB may vote to terminate approval of research not being conducted in accordance with IRB or regulatory requirements or that has been associated with unexpected problems or serious harm to subjects. The IRB shall notify the PI in writing of the termination and shall include a statement of the reasons for the IRB's actions. The PI will be provided an opportunity to respond in person or in writing.
6 SUBJECT ISSUES RELATED TO TERMINATION OR SUSPENSION OF IRB APPROVAL
1. The person ordering or continuing a suspension must consider whether any actions are needed to protect the rights and welfare of currently enrolled subjects currently involved in the research. (AAHRPP II.4.D) Such actions may involve:
a. Transferring subjects to another investigator
b. Making arrangements for clinical care outside the research
c. Allowing continuation of some research activities under the supervision of an independent monitor
d. Recommend modification of study documents
e. Re-consent of subjects
f. Manner for notification of subjects (including when it will take place and how it will be documented)
2. Once notified of the suspension, the PI must immediately submit to the IRB Chair or designee, a list of research subjects for whom suspension of current research activities would cause harm. Continuation of research interventions or interactions in those subjects should only continue when the IRB or IRB Chair or designee, in consultation with the Chief of Staff, finds that it is in the best interest of individual subjects to do so. (It is possible that the IRB could suspend enrollment, but allow current subjects to continue or could suspend one arm of a study based on unexpected serious harm but allow the other two arms to continue enrollment and study activities.) (AAHRPP II.4.D)
3. The PI must communicate to the IRB the procedures for withdrawal of enrolled subjects. These procedures must be designed to protect the subjects’ rights and welfare.
4. The IRB will determine and advise the investigator as to whether subjects must be informed of the termination or suspension.
5. The IRB will, in consultation with appropriate institutional officials and the PI, make a determination as to whether follow-up of patients for safety reasons on a terminated study is permitted and/or required.
6. The PI will inform subjects of a terminated study of any follow-up that will occur.
7. The PI will report any unanticipated serious adverse events or unanticipated problems involving risks to subjects or others and outcomes to the IRB, the sponsor and others as required by the protocol and regulatory requirements when follow-up of subjects for safety reasons is permitted and/or required by the IRB. (AAHRPP II.4.D)
7 REPORTING
For a description of reporting procedures when there has been a suspension or termination of IRB approval, please see research SOP titled REPORTING RESEARCH EVENTS TO OVERSIGHT COMMITTEES AND THE OFFICE OF RESEARCH OVERSIGHT.
http://www.vbri.org/Research/documents/Procedure_Reporting_to_oro.doc
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