91´ÎÔª

Chapter 10: Non-Compliance and Suspension or Termination of IRB Approval of Research

The following is the 91´ÎÔª (UM) Institutional Review Board (IRB) policy for noncompliance investigation procedures, in accordance with the Department of Health and Human Services (HHS), Office for Human Research Protections (OHRP), and the IRB’s Federal Wide Assurance (FWA).

Non-Compliance is a failure to comply with the requirements of an applicable law, regulation, or institutional policy pertaining to the protection of human subjects, and/or with the requirements or determinations of an IRB that results in harm to subject’s rights, safety or welfare, or on the integrity of the data. Non-compliance results from the action or inaction of anyone conducting protocol procedures.

Reported incidents will be considered possible noncompliance until a final determination is made by the IRB Chair and/or Committee. The IRB will assess the severity of the event and, if necessary, require corrective action. Serious and continuing noncompliance will be reported to the appropriate institutional officials and regulatory agencies.

When noncompliance has occurred, federal regulations and UM policy require the IRB to determine whether the incident is minor, serious, continuing, or a combination. The level of noncompliance is dependent upon intent, context, and other circumstances taken into account by the IRB.

Examples of noncompliance may include, but are not limited to, the following:

• Failure to obtain informed consent or inadequate procedures for obtaining informed consent from subjects;
• Conducting human subjects research without a UM IRB-approved protocol;
• Inadequate supervision of research that involves potential risks to subjects and others
• Conducting research, including enrollment of subjects, when a UM IRB approval has expired or has been suspended or terminated;
• Initiating changes to the research protocol without prior IRB approval unless the change is necessary to eliminate apparent immediate hazards to the subject (Note: Both the discovery of unforeseen risk and a request to update the protocol must be reported to the IRB as soon as possible);
• Failing to adhere to the conditions of approval of a protocol as specified by the UM IRB;
• Starting research under a protocol before meeting the conditions required by an IRB and receiving an IRB notification of approval;
• Failure to add research personnel to the IRB-approved protocol, including document a change in Principal Investigator (PI);
• Failing to take UM-required CITI human subjects protection training;
• Enrolling significantly more subjects than approved by IRB;
• Enrolling subjects from populations not previously approved by IRB;
• Enrolling subjects who should have been screened out from the project based on the defined exclusion criteria approved by IRB;
• Failing to have research participants sign a new consent form when new and relevant risks are discovered or failing to provide this new information to participants;
• Altering an IRB-approved consent process or an IRB-approved recruitment process without prior IRB approval.

Graduate student PIs, student Co-PIs and faculty mentors share accountability for upholding ethical standards, mitigating risk, and following approved protocol requirements. In the event that a graduate student is the PI/Co-PI in a project under investigation for noncompliance, the student and faculty will be separately contacted to gather information related to the investigation. Research misconduct investigations are handled separately from academic misconduct issues. Academic misconduct will be handled per university policy.

1. Definitions

Non-Compliance - Failure to comply with applicable laws, regulations, or UM institutional policies pertaining to the protection of human subjects, and/or with the requirements or determinations of an IRB, including deviation from the IRB-approved/exempt study procedures.

Minor Non-Compliance – Minor noncompliance is neither serious nor continuing and is a single instance of noncompliance that does not affect the rights and welfare of participants or put participants at risk of harm. Examples include, but are not limited to:

• A single instance of failing to add researchers to an IRB-approved protocol;
• Failure to secure IRB approval before beginning research for research that constitutes minimal or no risk to the participants;
• Introducing protocol changes when those changes constitute minimal or no risk to the participants;
• Making minor wording changes to recruitment materials and/or study instruments without IRB approval;
• Or first occurrences that are believed to be the result of ignorance and/or misinterpretation of the IRB regulations.

Please note that these occurrences should be reported to the IRB and corrected as soon as possible. The IRB will investigate minor non-compliance incidents in the same manner as other non-compliance events, with possible post-investigation actions listed below. Even though minor non-compliance events do not have to be reported to federal oversight agencies, the UM IRB still takes minor non-compliance seriously and will investigate accordingly.

Serious Non-Compliance - Non-compliance that has a significant adverse impact either on the rights or welfare of participants or on the integrity of the study data. This involves one or more of the following: substantive harm or genuine risk of substantive harm to the safety, rights and welfare of research participants or others; decreases potential benefits; or compromises the integrity of the human research protection program. Examples of serious noncompliance include, but are not limited to:

• One or more instances of conduct defined above as noncompliance that exposes subjects or others to risks of harm that are not an inherent part of the approved research protocol;
• Conduct defined as noncompliance above, even though subjects or others have not been exposed to risks of harm not inherent in the approved protocol, where the IRB finds that the lack of risk exposure was incidental;
• Misrepresentation of information related to the human subjects research protocol or performance of the research;
• Conducting non-exempt research without IRB approval;
• Making substantive changes to a previously approved protocol without IRB approval, and
• Conduct that adversely affected the integrity or effectiveness of human subjects protections or subjects rights or welfare.

Whether the conduct was inadvertent, careless, reckless, or intentional may be taken into consideration by the IRB in a determination of seriousness. Serious noncompliance is required to be reported to the Office of Human Research Protections (OHRP) if it is nonexempt research supported by US Human Health Services (HHS) or covered by a Federalwide Assurance (FWA).

Continuing Non-Compliance - Continuing noncompliance is multiple or repeated instances of noncompliance, particularly after written notice from the IRB that the investigator must take action to correct noncompliance. The multiple or repeated instances of noncompliance may occur on one or more protocols and may occur simultaneously or independently. The IRB will determine if the continuing noncompliance also constitutes serious noncompliance. Continuing noncompliance is required to be reported to the OHRP if it is nonexempt research supported by HHS or covered by a FWA.

Unanticipated Problems (UPs) - any incident, experience, or outcome that meets all of the following criteria: (1) Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB-approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied; (2) Related or possibly related to participation in the research (in this guidance document, possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research); AND (3) Suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.

Unanticipated Problems occurring in research do not in and of themselves constitute IRB noncompliance or research misconduct. However, if a PI fails to report an unanticipated problem in a timely manner to the IRB, or if an unanticipated problem is caused by a failure to follow IRB approved research protocols, these actions may represent noncompliance with IRB policy. Breaches of confidentiality are always unexpected, even if outlined in the informed consent.

2. Procedures

Reporting Requirements

Investigators, research staff and any other member of the UM IRB or IRB office are required to report any potential, observed, suspected, or apparent non-compliance to the IRB. This refers to all non-compliance, whether or not it may be serious and/or continuing non- compliance. All institutional members, research participants and others are encouraged to report any potential, observed, suspected, or apparent non-compliance.

Reports of non-compliance may also arise from: (i) calls or online reports to the Montana University System Compliance Hotline, the confidential institutional hotline for reporting compliance concerns; or (ii) as a result of internal or external audits; or (iii) through direct communication to the IRB. Regardless of how reports arise, all allegations of non-compliance related to research with human participants must be referred to the IRB. The allegation may be referred to other institutional offices for evaluation and management as appropriate.

Reports of non-compliance must contain enough information to determine whether the report is sufficiently credible and specific so that potential documentation of non-compliance may be identified and acted upon.

Protocol deviations and noncompliance should be reported to the IRB as soon as possible. An initial report should be made to the IRB Office by email within one (1) week (7 calendar days) of when the investigator became aware of the event. Any event involving serious injury or danger to the subject must be reported immediately. The initial report must be followed by a formal Incident Report submission in Cayuse Human Ethics within no more than two (2) weeks (fourteen (14) calendar days) of when the investigator became aware of the event. Reports of possible noncompliance should include a complete description of the event and include sufficient detail to allow the IRB to make an assessment.

In some cases, reporting requirements may be met by submitting a preliminary report to the IRB office, IRB, and other officials/agencies involved, with a follow-up report submitted at a later date when more information is available. These determinations will be made on a case-by-case basis, with the IRB Chair, Associate Vice President (AVP) for Research Compliance, institutional official(s) and/or others involved as appropriate. The primary consideration in making these judgments will be the need to take timely action to prevent avoidable harms to research subjects and others.

Investigation

Upon receipt of the noncompliance report the IRB office will notify the IRB Chair of the alleged noncompliance and determine if the report requires further investigation with immediate action, further investigation but no immediate action, or no action. The IRB will attempt to resolve alleged instances of noncompliance without interrupting the conduct of the study, especially if the rights, safety, and welfare of subjects may be jeopardized by the interruption. All reports of potential noncompliance as well as the outcome of investigations that are substantiated will be noted in the protocol record.

If a determination of further investigation with immediate action is made an emergency IRB meeting will be scheduled to:

• discuss an allegation of noncompliance and/or serious adverse event;
• or determine whether an activity should be suspended. The UM IRB may appoint a delegate and/or subcommittee to proceed with an investigation.

If an investigation is warranted, the IRB may collect information through:

• interviews with people affiliated with the allegation;
• interviews with human participants or participating organizations; and
• consent records, data records, and any other relevant documentation.

If the IRB Chair has an actual or perceived conflict of interest, the Institutional Official will delegate the responsibility of the investigation to an IRB member who does not have a conflict of interest. The Institutional Official, legal counsel, complainant, and the person against whom the allegation is being made may be invited to participate in the investigation. 

The IRB will fully investigate and review reports of possible non-compliance to determine if the event was not non-compliance, minor non-compliance, serious non-compliance, or continuing non-compliance. If necessary, the IRB will require corrective action.

Findings and Corrective Actions

If the IRB finds that no noncompliance occurred because: (1) the reported non-compliance was unsubstantiated, (2) the investigator deviated from the protocol in order to eliminate immediate and apparent hazards to subjects, or (3) continued participation of enrolled subjects in research for which approval has expired was necessary to protect the best interests of enrolled subjects, the following actions by the IRB may include but are not limited to:

• Requiring no further action.
• Requiring submission of an amendment to the protocol or consent form.
• Requiring submission of a continuing review application.
• Permitting or disallowing use of data collected during (2) and (3) above.

If minor non-compliance is found to have occurred, action by the IRB may include but are not limited to:

• Requiring a corrective action plan to be submitted which includes a detailed explanation of the non-compliance event and actions taken or proposed to prevent reoccurrence.
• Requiring remedial training (e.g., online educational program, attendance at workshop, one-on-one training).
• Requiring re-consent of subjects.
• Requiring the submission of an amendment to the protocol or consent form.
• Not permitting publication or dissemination of the results of the research.
• Requiring the destruction and disposal of data collected while the protocol was non-compliant.

Whenever appropriate, investigators will be assisted so that they can achieve compliance without the need for more serious sanctions. However, if the investigator fails to cooperate with IRB requests to correct minor non-compliance, this inaction will be treated as continuing non-compliance and potentially research misconduct.

If serious and/or continuing non-compliance is found to have occurred, actions by the IRB may include but are not limited to:

• Establishing a corrective action plan.
• Asking the investigator to voluntarily halt the research until the investigator is in compliance.
• Requiring the investigator to participate in and complete further training.
• Requiring more frequent review of the project.
• Implementation of monitoring of the research and/or the informed consent process.
• Requiring the investigator(s) to provide additional information to current and/or past participants and/or re-consenting of participants.
• Disallowing use of the data collected during noncompliance.
• Not permitting publication or dissemination of the results of the research.
• Limiting the investigator’s human subject research privileges.
• Writing letters of censure.
• Making recommendations to the Institutional Official (IO) for further sanctions, stipulations, or restrictions to the Investigator’s privilege to conduct human subjects research.
• Sharing information of noncompliance with other institutional units as deemed necessary, including for a Research Misconduct investigation.
• Suspension of the research.
• Termination of the research.

The IRB and, when appropriate, the institution will act promptly to ensure remedial action regarding any breach of regulatory or institutional human subject protection requirements. The IRB also has the authority to suspend or terminate approval of research that is not being conducted in accordance with the IRB policies, is not in compliance with federal regulations, or deviates from the approved protocol.

All serious and/or continuing noncompliance must be reported promptly to the AVP for Research, the Institutional Official and, for federally funded research, the appropriate department, agency head or sponsor. Reports will only be made to OHRP for research that is regulated by these oversight agencies per FWA. Sponsor reporting requirements may apply if required by project terms and conditions or applicable regulations.

IRB Reporting Obligations

It is the responsibility of the IRB Manager and/or Chair, in consultation with the IRB office, to compile a final report for the AVP for Research and, if necessary, the Institutional Official. The Institutional Official may need to submit the final report to OHRP. The final report to OHRP must include:

• the name of the institution;
• the research project title and/or grant proposal that was originally suspended;
• the name of the principal investigator of the protocol;
• the research project number assigned by the IRB; and
• any corrective actions the institution is taking to remediate the immediate problem and ensure that the incident will not happen again with that principal investigator or with other researchers.

In the report, the IRB will determine one of the following actions:

• There was no evidence to support the allegation.
• The allegation was not supported; however, it may require additional action by administration.
• The allegation was valid and requires additional action.

Unanticipated problems involving risks to subjects or others, any serious and/or continuing noncompliance, and any suspension or termination of IRB approval are reportable to the appropriate federal department or agency head(s) and to the UM Institutional Official. The Institutional Official may need to report the suspension to OHRP or another regulatory agency. HHS regulations require that any suspended human participant research that is conducted or supported by HHS be reported to OHRP immediately (HHS regulations, 45 CFR 46.103(a) and (b)(5)).

Regulatory Background

HHS regulations at 45 CFR 46.103(a) and (b)(5) require that institutions have written procedures to ensure that the following incidents related to regulatory requirements pertaining to research conducted under an OHRP- approved assurance are promptly reported to OHRP: any unanticipated problems involving risks to subjects or others; any serious or continuing noncompliance with this policy or the requirements or determinations of the IRB; and any suspension or termination of IRB approval.