20Complaints, Non-Compliance, Suspensions Or Terminations of COMIRB Approval of Research

20Complaints, Non-Compliance, Suspensions or Terminations of COMIRB Approval of Research

20.1Complaints

The Chair of the panel and the Director of the COMIRB Office will promptly handle (or delegate staff to handle), and, if necessary, investigate all complaints, concerns, and appeals received by the COMIRB. This includes complaints, concerns, and appeals from investigators, research participants and others.

Complaints reported to COMIRB will be evaluated to determine if the complaint involves unanticipated problems involving risks to participants or others or allegations of noncompliance. If the complaint meets the definition of non-compliance, it will be considered an allegation of non-compliance according to section 20.2. If the complaint meets the definition of an unanticipated problem involving risk to subjects or others, it will be handled according to Section 19.

20.2Non-Compliance

All members of the research community of the participating institutions involved in human subject research are expected to comply with the highest standards of ethical and professional conduct in accordance with federal and state regulations and institutional and COMIRB policies governing the conduct of research involving human subjects.

The Principal Investigator is responsible for reporting any non-compliance by study personnel to the COMIRB.

Reports of non-compliance must be submitted to the COMIRB Office within 5 working days of discovery of this noncompliance. The report must include a complete description of the noncompliance, the personnel involved and a description of the non-compliance.

Non-compliance is defined as failure to comply with any of the regulations and COMIRB policies described in this document, including VHA Handbook 1200.05 for VA research, and failure to follow the determinations of the COMIRB. Non-compliance may be minor or sporadic or it may be serious or continuing.

Serious Non-compliance is defined as failure to follow any of the regulations and policies or failure to follow the determinations of the COMIRB and which, in the judgment of either the COMIRB Chair(s) or the convened panel, increases risks to participants, decreases potential benefits, or compromises the integrity of the human research protection program. Research being conducted without prior IRB approval is considered serious non-compliance.

Continuing Non-compliance is defined as a pattern of non-compliance that, in the judgment of the panel Chair(s) or convened panel, suggests a likelihood that instances of non-compliance will continue without intervention. Continuing non-compliance also includes failure to respond to a request to resolve an episode of non-compliance within 30 days.

Allegation of Non-compliance is defined as an unproved assertion of non-compliance.

Finding of Non-compliance is defined as an allegation of non-compliance that is proven true or a report of non-compliance that is clearly true. (For example, a finding on an audit of an unsigned consent document, or an admission of an investigator that the protocol was willfully not followed would represent reports of non-compliance that would require no further action to determine their truth and would therefore represent findings of noncompliance.)

20.2.1Review of Allegations of Non-Compliance

The COMIRB Chair(s) and Director will review the allegation and make a determination as to the truthfulness of the allegation. The initial findings of fact will be conducted in conjunction with the appropriate affiliate compliance office(s). [For the VAMC, this will involve collaboration with the VA Research Office.] The findings of fact may include requesting additional information from the PI, other members of the research team, interviewing subjects or an audit of the research in question.

If in the judgment of the COMIRB Chair(s) and Director, the reported allegation of non-compliance is not true, no further action will be taken. If in the judgment of the COMIRB Chair(s) and Director, the reported allegation of non-compliance is true, the non-compliance will be processed according to the process described below.

If in the judgment of the COMIRB Chair(s) and Director, any allegation or findings of noncompliance warrants suspension of the research before completion of any review or investigation to ensure protection of the rights and welfare of participants, the COMIRB Chair or Director may suspend the research as described below and reported to the next IRB panel.

All allegations of non-compliance will be reviewed by the Compliance Board consisting of all COMIRB Chair(s), Exempt/expedited reviewers, the Director and senior COMIRB administration, Assistant Vice Chancellor for Regulatory Compliance and the Institutional Official unless one of these individuals has a conflict of interest with the study or the investigator. If a conflict of interest is declared then that individual will be excluded from the investigation, discussion and determination.

They will review all relevant documents, which may include:

All documents relevant to the allegation;

The last approval letter from the COMIRB;

The last approved COMIRB application and protocol;

The last approved consent document.

The last approved Investigator’s Brochure, if applicable;

The grant, if applicable;

Any other pertinent information (e.g., questionnaires, DSMB reports, etc.);

and

Initial findings of fact

The COMIRB Chair(s) and Director or Compliance Board will also make a preliminary determination to report to regulatory agencies and institutional officials in accordance with section 20 below. The initial report must be submitted within 30 days of the allegation or 30 days after the initial finding in fact.

20.2.2Review of Findings of Non-Compliance

All findings of non-compliance referred to the Compliance Board will be reviewed at a meeting of the Compliance Board. All members will receive documentation necessary to evaluate the report, which may include:

All documents relevant to the allegation;

The last approval letter form the COMIRB;

The last approved COMIRB application;

The last approved consent document and

Recommendations from the Compliance Board At this stage, the

Compliance Board may:

Find that there is no issue of non-compliance;

Find that there is noncompliance that is neither serious nor continuing and an adequate corrective action plan is in place;

Find that there may be serious or continuing non-compliance and direct that a formal inquiry (described below) be held; or

Request additional information.

If in the judgment of the Compliance Board, the reported finding of non-compliance is not serious, not continuing, and the proposed corrective action plan seems adequate, no further action is required.

If the allegation of non-compliance was protocol specific, it is reported at the next convened panel meeting of the panel responsible for that protocol. If the allegation of non-compliance relates to an investigator the issue will be reported by the appropriate Chairs to each panel that is responsible for protocols involving that investigator in accordance with section 20.2.5. If the Compliance Board requests a formal inquiry the procedure described below, will be followed.

20.2.3Inquiry Procedures

A determination may be made by the Compliance Board that an inquiry is necessary based on several issues that may include but are not limited to:

Subjects’ complaint(s) that rights were violated;

Report(s) that investigator is not following the protocol as approved by the

COMIRB;

Unusual and/or unexplained adverse events in a study;

FDA audit report of an investigator;

Repeated failure of investigator to report required information to the

COMIRB.

A subcommittee is appointed consisting of at least one panel chair, panel members, and non-members including representation from the affiliate research compliance office, to ensure fairness and expertise. The subcommittee is given a charge by the Compliance Board, which can include any or all of the following:

Review of protocol(s) in question;

Review of FDA or sponsor audit report of the investigator, if appropriate;

Review of any relevant documentation, including consent documents, case report forms, subject’s investigational and/or medical files etc., as they relate to the investigator’s execution of her/his study involving human subjects;

Interview of appropriate personnel if necessary;

Preparation of either a written or oral report of the findings, which is presented to the full panel at its next meeting;

Recommend actions if appropriate.

20.2.4Final Review by Compliance Board

The results of the inquiry will be reviewed at a Compliance Board meeting where the board will receive a report from the subcommittee. The compliance board may take one or more of the following actions:

Request for additional information;
Acceptance of the proposed corrective action plan;
Modifications to the proposed corrective action plan;
Broadening of the investigation
Request a correction action plan from the investigator;
Make recommendations to the panel(s) responsible for the protocol(s) at issue.
Determine if the non-compliance is serious or continuing

[Findings of serious or continuing non-compliance will be reported in accordance with section 21 below.]

20.2.5Final Review by convened IRB panel(s)

The COMIRB compliance staff person will ensure that the results of the inquiry and/or report and/or recommendations of the Compliance Board will be reviewed at the appropriate convened IRB panel(s). All IRB members will be provided with a copy of the report, the original audit report, result of any investigation, and recommendations of the Compliance Board. If the non-compliance involves a specific protocol, a copy of the protocol and consent document may also be provided to all IRB members (as needed). If the results of the inquiry or the report from the Compliance Board substantiates the finding of serious or continuing non-compliance and the IRB panel concurs, the IRB panel’s possible actions could include, but are not limited to:

Request a corrective action plan from the investigator;

Verification that participant selection is appropriate and observation of the

actual informed consent;

An increase in data and safety monitoring of the research activity;

Request a directed audit of targeted areas of concern;

Request a status report after each participant receives intervention;

Modify the continuing review cycle;

Request additional Investigator and staff education;

Notify current subjects, if the information about the non-compliance might

affect their willingness to continue participation;

Modification of the protocol;

Modification of the information disclosed during the consent process;

Requiring current participants to re-consent to participation;

Suspend the study (See below); or

Terminate the study (See below)

The investigator is informed of the COMIRB determination and the basis for the determination in writing and is given a chance to respond. If the panel determines that the non-compliance was serious or continuing or if an initial report had been sent to regulatory agencies and institutional officials, the results of the final review will be reported according to COMIRB policy outlined in section 21.

20.3Suspension or Termination

Suspension of COMIRB approval is a directive of the convened panel or panel Chair or COMIRB Director either to temporarily or permanently stop some or all previously approved research activities short of permanently stopping all previously approved research activities. Suspended protocols remain open and require continuing review. Termination of COMIRB approval is a directive of the convened panel to stop permanently all activities in a previously approved research protocol. Terminated protocols are considered closed and no longer require continuing review.

The panel Chair or COMIRB Director may suspend research to ensure protection of the rights and welfare of participants. Suspension directives made by the panel Chair or COMIRB Director must be reported to a meeting of the convened appropriate panel.

When study approval is suspended by the convened panel or individual ordering the suspension, in addition to stopping further enrollment on the study, the convened panel or individual ordering the suspension will determine what, if any, research activities can continue, determine if subjects currently participating should be notified that the study has been suspended. The convened panel or individual ordering the suspension will consider whether procedures for withdrawal of enrolled subjects are necessary to protect their rights and welfare of subjects, such as: transferring participants to another investigator; making arrangements for care or follow-up outside the research; allowing continuation of some research activities under the supervision of an independent monitor; or requiring or permitting follow-up of participants for safety reasons.

If follow-up of subjects for safety reasons is permitted/required by the convened panel or individual ordering the suspension, the convened panel or individual ordering the suspension will require that the subjects should be so informed and that any adverse events/outcomes be reported to the panel and the sponsor.

Research may only be terminated by the convened panel. Terminations of protocols approved under expedited review must be made by the convened COMIRB.

When study approval is terminated by the convened panel, in addition to stopping all research activities, the convened panel ordering the termination will notify any subjects currently participating that the study has been terminated. The convened panel ordering termination will review and approve a plan for withdrawal of any enrolled subjects are necessary to protect their rights and welfare of subjects, such as: transferring participants to another investigator; making arrangements for care or follow-up outside the research.

20.4Reporting

Serious or continuing noncompliance with regulations or the requirements or determinations of the COMIRB; and suspensions or terminations of COMIRB approval will be reported to the appropriate regulatory agencies and institutional officials according to the procedures outlined in the policy document entitled “Reporting to Regulatory Agencies and Institutional Officials”.