WPP #: VIII-9
Investigations of General, Serious or Continuing Noncompliance
06-20-00; 07-26-00; 09-20-01; 06-07-04; 04-30-06; 06-21-06; 01-30-08; 04-22-14; 08-08-14
Investigators and researchers are required to comply with all ethical standards, institutional policies, governmental regulations, and conditions place on the conduct of research involving human participants. Failure to adhere to these requirements may constitute noncompliance. All instances of suspected noncompliance must be reported to the Office of Research Subjects Protection (ORSP) or the IRB. The ORSP will initiate a process to investigate the situation. Suspected serious or continuing noncompliance will be referred to the convened IRB for review. IRB determinations of serious or continuing noncompliance will be reported to regulatory authorities as required by VCU’s Federalwide Assurance and to research sponsors as required by federal requirements or award documents [as required by 46 CFR 46.103(b)(5) and 21 CFR §56.108(b)(3)].
Procedures and Guidance
- Noncompliance: failure on the part of the PI or any member of the research team to:
- adhere to the terms of the VCU IRB approval and/or
- abide by applicable laws, regulations, or VCU policies.
Examples of noncompliance include, but are not limited to:
- Failure to obtain IRB approval prior to initiating research activities;
- Continuing research activities beyond study expiration date without obtaining continuing review approval;
- Failure to obtain informed consent when required;
- Failure to file an unanticipated problem reports;
- Implementing changes to the protocol or research documents without prior approval; and
- Failure to adhere to the approved protocol.
General noncompliance may vary in severity based upon the overall risk potential of the noncompliance and its frequency. Noncompliance determined to be general in nature and not serious and/or continuing is not reportable to regulatory authorities or sponsors.
- Serious Noncompliance: failure to adhere to the terms of the VCU IRB approval and/or abide by applicable laws, regulation, or VCU policies when that failure increases risk to participants or adversely affects the rights and welfare of the participants. Examples may include, but are not limited to:
- Conducting a research protocol without oversight of a functional investigator;
- Conducting a study without informed consent;
- Protocol violation that adversely affects the integrity of the research data.
Serious noncompliance is a finding that is determined by the convened IRB Panel. The finding of serious noncompliance must be reported to regulatory authorities and the sponsor.
- Continuing Noncompliance: repeated noncompliance by an individual investigator either on a single protocol or across multiple protocols, or a pattern of ongoing activities that indicate a lack of understanding of human subjects protection requirements that may affect research subjects or the validity of the research. Continuing noncompliance is a finding that is determined by the convened IRB Panel. The finding of continuing noncompliance must be reported to regulatory authorities and the sponsor.
- Noncompliance: failure on the part of the PI or any member of the research team to:
- Evaluations and Investigations of Allegations of Noncompliance
- Incoming allegation of noncompliance: When suspected or actual noncompliance is reported to ORSP or the IRB, the recipient informs the Director of the ORSP in order to initiate an inquiry and gather pertinent information. Noncompliance may be found or alleged in a number of ways, including: 1) as an Unanticipated Problem involving risks to subjects or others, i.e. protocol violation, 2) during post-approval monitoring visits, or 3) may be reported by a concerned individual. Reasonable efforts will be taken to protect the confidentiality of any persons who allege non-compliance or file reports or grievances, as well as the confidentiality of the investigator and those interviewed during the investigative process.
- Initial evaluation by ORSP and IRB Chair/designee: The ORSP Director, with assistance from the IRB Chair/designee as needed, evaluates the severity of the allegation or report to determine if immediate actions are necessary to ensure the ongoing protection of research participants.
- Fact Finding: The ORSP initiates fact-finding activities, which may include reviewing study documentation and corresponding with the principal investigator and research personnel to determine whether the allegation is substantiated. The IRB Chair/ IRB reviewer(s) may participate with the ORSP as needed. Possible outcomes of the fact finding may include:
- Dismissal of an unsubstantiated allegation;
- Referral to other appropriate university processes (e.g., misconduct investigation);
- No further action required (i.e., for minor violations);
- Corrective actions required (i.e., for minor violations);
- Further investigation required;
- Refer to convened IRB if based on an unanticipated problem involving risk to subjects or others or may involve serious and/or continuing noncompliance.
The investigator will be notified in writing of the fact finding outcome. When the fact finding results in referral to the convened IRB, the PI should be informed that the allegation of noncompliance being presented to the IRB is subject to a determination of serious and/or continuing noncompliance. At a minimum, the investigative report to be given to the IRB should first be shared with the investigator to ensure accuracy of information to be reported to the IRB. The investigator should also be involved in the development of a corrective action plan if one is included in documentation forwarded to the IRB. Documentation of the fact finding and outcome will be maintained with a study file.
- IRB review of noncompliance associated with an unanticipated problem report and of serious and/or continuing noncompliance
- All members of the IRB are provided with relevant submission documentation pertaining to the noncompliance.
- The IRB will review all relevant documentation surrounding the allegation, including any report resulting from ORSP fact finding in order to assess the seriousness of the noncompliance and consider possible corrective actions. The IRB (or PI) may request the PI’s presence at the convened Panel meeting in order to provide clarifications.
- The IRB should determine whether the noncompliance is serious and/or continuing based on the definitions provided. A first-time offense may be determined to be “serious noncompliance” if risk to participants was significantly increased or if subjects’ rights or welfare were seriously compromised. The convened IRB may make the determination at the first report of the occurrence, or the final determination may be made after the completion of an inquiry or investigation.
- The IRB will determine whether the investigator satisfactorily resolved the noncompliance, if applicable, and whether corrective actions are needed. Possible actions imposed by the IRB in response to a determination of serious or continuing noncompliance may include, but are not limited to:
- Research study specific corrective action
- Education of the investigator(s) and research team
- Modification to the protocol or other study documents
- Require that subjects be re-contacted and provided with updated information or re-consent subjects
- Notification of current subjects when such information may relate to subjects’ willingness to continuing participating in the research
- Providing additional information to past subjects
- Limit or prohibit publication of data
- Discarding data or samples associated with the noncompliance
- Suspension or termination of the research
- Letter of reprimand to the investigator, which may be copied to the department chair
- Disqualify the investigator(s) from conducting research involving human subjects at VCU
- Require periodic monitoring or auditing
- Enforce more frequent continuing review
- If the IRB determines that serious and/or continuing noncompliance has occurred, a formal report to OHRP and other oversight entities is required.
- If the noncompliance is determined to be neither ‘serious’ or ‘continuing,’ the IRB, assisted by the ORSP, should develop a corrective action plan for general noncompliance, with the cooperation of the PI. Possible additional actions taken by the IRB and/or the ORSP include, but are not limited to: 1) a compliance audit; 2) a letter of reprimand, which may be copied to the department chair; and 3) participation in additional training.
- All reports of general or serious and/or continuing noncompliance should also be considered to determine if the criteria for an unanticipated problem involving risk to subjects or others are met. See WPP VIII-7: Unanticipated Problems Involving Risk to Subject or Others.
- Every effort is made to work directly with investigators or research staff who self-report all forms of non-compliance and/or with the management of unanticipated problems. Resources may be made available to assist with corrective actions, when necessary, through the self-reporting process.