Subject: Noncompliance Section: 9-2 Michigan State University Human Research Protection Program This policy and procedure supersedes those previously drafted. Approved by: Vice President of Research and Graduate Studies, 4-21-2005. Revision 1 approved by VP Research & Graduate Studies on 2-1-2006. Revision 2 approved by VP Research & Graduate Studies on 3-9-2008. Revision 3 approved by VP Research & Graduate Studies on 5-6-2008. Revision 4 approved by VP Research & Graduate Studies on 7-22-2011. Related Sections: 2-2-A, 4-8, 5-4, 5-6, 9-3, 9-4 The investigator and the research study team are required to comply with all ethical standards, institutional policies, governmental regulations, and conditions placed on the conduct of the human subject research. Noncompliance with human subject protection requirements (e.g., U.S. Department of Health and Human Services (DHHS) regulations, Institutional Review Board (IRB) requirements) is a violation of Michigan State University's (MSU) Federal Wide Assurance (FWA-00004556). Noncompliance presents a serious challenge to the IRB. Regardless of investigator intent, unapproved research activities involving human subjects places those subjects at an unacceptable risk. Any incident of noncompliance with human subject protection requirements must be reported to the IRB immediately. Allegations of noncompliance may be reported to the IRB office, IRB chair, or IRB members by anyone, including investigators, research staff, research subjects, students, faculty, staff, administrators, external parties, etc. See the Human Research Protection Program (HRPP) Manual 9-4 Subject Complaints. The IRB chair and others when appropriate (e.g., HRPP director, IRB, human research liaisons) investigate allegations and instances of noncompliance, determine immediate actions to protect subjects, report serious or continuing noncompliance to appropriate authorities (including government agencies), require modifications to, suspension or termination of research activities, and take other actions as needed to protect human subjects or comply with institutional policies and procedures. Definitions / Examples Noncompliance Defined as the failure to follow the federal regulations governing human subject protection requirements (e.g., 45 CFR 46, 21 CFR 50, 21 CFR 56) or the requirements and determinations of the IRB. Examples of serious noncompliance may include but are not limited to: Harm to research subjects Exposure of research subjects to a significant risk of substantive harm 1
Compromised privacy and confidentiality of the subjects Damage caused to the scientific integrity of the data collected Willful or knowing misconduct on the part of the investigator An adverse impact on ethical principles Conducting or continuing non-exempt human subject research without IRB approval Lack of legally effective informed consent from research subjects Inappropriate oversight of the research to insure the safety of human subjects and/or the integrity of the research data Continuing Noncompliance Defined as repeated noncompliance by an individual investigator either on a single protocol or 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 and suggest the potential for future noncompliance without intervention. Examples of noncompliant activities may include but are not limited to: Conducting research without IRB approval (i.e., before approval obtained, after research expires, without IRB approval) Non-use or mis-use of consent forms (i.e., consent not obtained, wrong consent form used) Failure to follow approved protocol Changing protocol without IRB approval Failure to report unanticipated problems or serious adverse events Failure to maintain adequate records Failure to renew research studies prior to expiration date Inadequate training of investigators or research staff Other failure to follow University polices and federal regulations Reporting Incidents or Allegations to the IRB Noncompliance or potential noncompliance may be self-reported by researchers, staff, employees, or research subjects, may be discovered by the IRB (e.g., through monitoring visits or other routine review or quality control activities), and may be reported to the IRB by any individual. See HRPP Manual 5-6 Contact Information for multiple mechanisms to report incidents to the IRB. The university will take reasonable steps to protect persons who file reports in good faith from retaliatory actions based on such filing. Procedures for Immediate Action The IRB chair determines if immediate actions are necessary and may consult with others (e.g., members of the IRB, HRPP director) as needed. Immediate issues to consider will be whether to: Protect subjects by suspending the protocols according to HRPP Manual 9-3 Termination or Suspension of Research. 2
Notify officials who will take appropriate action (e.g., notify Contract and Grant Administration). At any other time during the inquiry or investigation process the IRB chair or IRB may determine that it is necessary to act to protect subjects by terminating or suspending the protocols according to HRPP Manual 9-3 Termination or Suspension of Research. Investigation of Allegations of Noncompliance to Determine if Allegation has Basis in Fact The IRB chair will perform an initial investigation of the alleged noncompliance in order to determine whether the allegation is substantiated or has a basis in fact. Materials reviewed by the IRB chair include all relevant materials (e.g., IRB file, communications, relevant research materials [e.g., survey, consent], audit reports). The IRB chair may gather more information through discussions or correspondence with the principal investigator. The IRB chair may request review by others (e.g., human research liaisons, IRB member(s), the IRB). If the IRB chair determines that such review is necessary, the individual will receive all relevant materials (e.g., IRB file, communications, relevant research materials [e.g., survey, consent], and audit reports). If any individual feels that he/she is not qualified to review the research study, the IRB staff should be notified. The IRB chair will be consulted to determine an appropriate replacement. If additional expertise is not available, the policy and procedures for obtaining additional expertise will be followed, HRPP Manual 5-4 Additional Expertise. The investigator(s) may submit in writing his/her account and explanation of the events possibly constituting noncompliance. At his/her request, the investigator(s) may also appear before the IRB. Investigator(s) under investigation for noncompliance may choose to be accompanied, or represented, by faculty or legal counsel in presenting to the convened IRB. The investigator must notify the IRB in advance if this is the case. Or, the investigator(s) may have a member of the IRB, typically the representative from his/her college, institution, or the chair of the IRB, present on their behalf to the convened IRB. The IRB chair, alone or in consultation with the IRB, determines whether the allegation is substantiated or has a basis in fact (incident involved noncompliance). If the allegation has a basis in fact, the procedures for substantiated noncompliance will be followed to determine whether the noncompliance is serious or continuing. Procedures for Substantiated (or Self-Reported) Noncompliance If a reported incident involved noncompliance, a determination of whether the noncompliance was serious or continuing is made promptly based on the definitions in the section Definitions / Examples above. Incidents of noncompliance that do not clearly meet the definition of serious or continuing should be documented in the IRB file and corrected as appropriate (e.g., 3
require investigator signature on application) The IRB chair, IRB staff, or the human research liaison will communicate with the investigator(s) to determine the appropriate corrective action when necessary. See section Procedures for Corrective / Protection Actions, below for possible corrective actions. The actions taken will be appropriate for the type, severity, and frequency of the noncompliance. Incidents of noncompliance that may meet the definition of serious or continuing noncompliance must be reported to the IRB chair. Investigation The IRB chair reviews all relevant materials (e.g., IRB file, communications, relevant research materials [e.g., survey, consent], audit reports) and may gather additional information through discussions or correspondence with the investigator, if needed. The IRB chair may request review by others as needed (e.g., IRB members, human research liaisons). If the IRB chair determines that such review is necessary, the individuals will receive all relevant materials (e.g., IRB file, communications, relevant research materials [e.g., survey, consent], audit reports). If any individual feels that he/she is not qualified to review the research study, the IRB staff should be notified. The IRB chair will be consulted to determine an appropriate replacement. If additional expertise is not available, the policy and procedures for obtaining additional expertise will be followed, see HRPP Manual 5-4 Additional Expertise. Convened IRB Review The IRB chair presents the potentially serious or continuing noncompliance to the convened IRB for review or may request that another individual present such information (e.g., human research liaison, IRB member). Materials provided to IRB members include all relevant materials, e.g., communications, relevant research materials [e.g., survey, consent], audit reports and the IRB file will be available for review (if necessary). Further Investigation The IRB may require further investigation prior to making a determination of whether the noncompliance was serious or continuing. If further investigation is required, the IRB may: Request the individuals continue his/her investigation Impanel an investigative sub-committee of the IRB to review all relevant materials, e.g., IRB file, communications, relevant research materials (e.g., survey, consent), audit reports, etc. Request that the human research liaisons perform an investigation Obtain additional expertise (See HRPP Manual 5-4 Additional Expertise ) The IRB chair or the investigative sub-committee will report back to the convened IRB with recommendations (i.e., severity and frequency of noncompliance, corrective/protective actions). 4
The IRB will then make the determination of whether the noncompliance is serious and/or continuing. IRB Determinations The IRB determines whether the noncompliance is serious or continuing. This is based on the definitions provided above. The IRB will determine whether the investigator satisfactorily resolved the noncompliance, if applicable, and whether corrective/protective or other actions are needed. The IRB chair will communicate with the investigator regarding appropriate corrective / protective actions when necessary. Corrective/protective actions include but are not limited to: Require research study specific corrective action. Require plan for corrective action, based on the type and nature of the issues. Require education of the investigators and research team. Require modification of the protocol. Require that subjects be re-contacted and provided with updated information or re-consent to participation.. Notification of current subjects when such information may relate to subjects willingness to continue to take part in the research. Modification of the information disclosed during the consent process. Providing additional information to past subjects. Requiring current subjects to re-consent to participation. Limit or prohibit publication of data to protect subject s rights and privacy. Suspension or termination of the research. Disqualify the investigator(s) from conducting research involving human subjects at the university. Require periodic monitoring or auditing, such as modification of the continuing review schedule or monitoring of the research or consent process. Referral to other organizational entities. Other actions as needed. Corrective/protective actions taken will be appropriate for the type, severity, and frequency of the noncompliance. The IRB may decide that the investigators found in serious or continuing noncompliance should not be allowed to submit new protocols or renew or revise current research studies until all concerns have been addressed taking into account the best interests of the subjects currently enrolled. See HRPP Manual 9-3 Termination or Suspension of Research for requirements. Reporting Serious or continuing noncompliance will be reported (e.g., to appropriate institutional officials, federal agencies) pursuant to HRPP Manual 4-8 Reporting Policy. Coordination with Other Institutional Officials 5
Any possible research misconduct discovered during the IRB s noncompliance investigation can be reported to the MSU Research Integrity Officer (RIO) as an allegation of misconduct. These allegations can be presented to the RIO by the chair, member or staff of the IRB, staff of the HRL, human subjects of the research, or any other individual. The misconduct investigation will be performed independently of IRB procedures (i.e., the IRB will conduct the noncompliance investigation and the RIO will conduct the research misconduct investigation.). If possible noncompliance with IRB requirements, University policies and /or federal regulations protecting human subjects of research is discovered during a misconduct investigation, the RIO will notify the appropriate individuals as outlined by the Faculty Handbook, VI. Research and Creative Endeavors, Procedures Concerning Allegations of Misconduct in Research and Creative Activities. No one in the University may approve research that has been disapproved by the IRB (45 CFR 46.112). Investigators who believe that the IRB has acted contrary to provisions of 45 CFR 46 or contrary to terms of its Assurance to the federal government (FWA-00004556) may contact the MSU Office of Regulatory Affairs, 517-432-4500 or the Office for Human Research Protection at NIH, 301-496-7005. Investigators who believe that the IRB has acted contrary to provisions of 21 CFR 50 and 56 may contact the MSU Office of Regulatory Affairs, 517-432-4500 or the FDA, 301-827-1685. Communications with Investigators An investigator who believes that the IRB has erred in its finding of noncompliance may submit a written request asking the IRB to reconsider within 30 days of the noncompliance determination. The request should clearly indicate the facts or the interpretation in dispute, providing supporting evidence where applicable. The IRB provides notice to investigators of its determinations and corrective/protective actions, if any. Additional Considerations For research subject to the requirements of the U.S. Department of Defense, see HRPP Manual 2-2-A U.S. Department of Defense. 6