Approved by: Human Protections Administrator, Director of OPRS, and Executive IRB Chair
AAHRPP REF#: 131
AAHRPP Elements: I.1.B., I.5.D., III.2.D
For reports involving changes to the protocol made without IRB approval to eliminate apparent immediate harm to subjects of changes, the IRB also decides whether the change was necessary to eliminate apparent immediate hazards to the subject, and whether there was insufficient time for IRB review. If these conditions are both false, the incident represents a protocol violation.
- Federal regulations [45 CFR 46 .103(b) (5); 21 CFR 56.108(b), and 38 CFR 16.103(b) (5)] require each institution to have "…written procedures for ensuring prompt reporting to the IRB, appropriate institutional officials, and the department or agency head of (i) ... any serious or continuing non-compliance with this policy or the requirements or determinations of the IRB; and (ii) any suspension or termination of IRB approval.” This document describes UIC's policy and procedures for addressing complaints and allegations of potential non-compliance with Federal and State regulations, with University policies regarding research, and with the requirements of the HSPP.
- It is UIC policy that investigators, research team members, faculty and staff must report any allegations or observations of apparent serious or continuing non-compliance in human subject research. Complaints or allegations of Non-compliance may be directed to the OPRS, IRB, OVCR Associate Director for Research Compliance, HPA or IO. Research subjects and individuals not directly involved with conducting or overseeing the research are also encouraged to report suspected non-compliance.
- This policy is applicable to all human subject research activities of UIC faculty, staff, students, or others within the jurisdiction of the UIC HSPP. The policy extends to adjunct and/or volunteer faculty when their appointment is listed among the investigator's credentials in study documents.
- NON-COMPLIANCE: Conducting research involving human subjects in a manner that intentionally or unintentionally fails to comply with federal or state regulations, VHA Handbook 1200.05, UIC HSPP policies, or the requirements or determinations of the IRB. Examples include, but are not limited to, initiating research prior to IRB approval, implementing changes in the IRB-approved protocol without prior IRB approval, using inadequate procedures for informed consent, failing to meet education and training requirements and lapses in IRB approval
- Protocol violation: Any deviations, whether accidental, unintentional or intentional, from the IRB-approved protocol that are implemented prior to IRB approval. Major protocol violations are those that cause harm to subjects or others, place them at increased risk of harm, impact the scientific integrity of the research, compromise the human subject protection program, have the potential to recur or represent possible serious or continuing non-compliance. Major protocol violations require prompt reporting and are reviewed as potential serious Non-compliance. Minor protocol violations are those not meeting at least one of the criteria in the preceding sentence and do not require reporting to the IRB. They should be reported to the sponsor as described in the protocol and written documentation of their occurrence filed with the investigator’s study records.
- SERIOUS NON-COMPLIANCE: Non-compliance that results in either substantive harm (or genuine risk of substantive harm) to the safety, rights or welfare of human subjects, research staff or others, substantively compromises the effectiveness of the HSPP or substantively impacts the integrity of the research.
- CONTINUING NON-COMPLIANCE: Persistent failure to conduct research in compliance with federal or state regulations, VHA Handbook 1200.05 (if applicable), or requirements or determinations of the IRB.
- EXAMPLES of apparent serious or continuing Non-compliance are provided in the addendum of this policy.
- Reporting occurrences or allegations.
- Investigators are required to promptly report to the IRB using the Prompt Reporting to the IRB form all findings and allegations of apparent serious or continuing Non-compliance, including major protocol violations, subject complaints, and changes to the protocol made without IRB approval to eliminate apparent immediate harm to subjects.The timeframe for reporting is within 5 working days of becoming aware of the event.
- Non-compliance may be uncovered by the IRB, the OPRS, Associate Director for Research Compliance (e.g., during ongoing review or monitoring of research or through audits or other quality assurance activities) or JBVAMC Research Compliance Officer (RCO). These findings are forwarded through the OPRS to the applicable IRB.
- Allegations of non-compliance may also be reported by members of the research team, UIC faculty, staff or administrators, sponsors, study participants, participating organizations, or other knowledgeable parties. The complaints or allegations may be provided to the Director of OPRS, OPRS staff, IRB Chair (or designee), the HPA, or IO. To facilitate reporting, informed consent documents provide a contact phone number and e-mail to discuss concerns or complaints with the research with OPRS staff. The OPRS website also provides telephone and e-mail contacts for OPRS staff members and administration, including the IO and HPA.
- Receipt and initial review of allegations of non-compliance.
- When complaints or allegations of non-compliance are received via telephone, in person or e-mail by OPRS staff from sources outside of the research team, the information is recorded on the Complaint/ / Unanticipated Problem/Event Record – Transcription Form and forwarded to the Assistant Director of the relevant IRB.
- The Assistant Director performs an initial review of the allegation including examination of the complaint form and IRB protocol file (i.e., protocol, consent documents) and, if warranted, conducts discussions with the investigator, other research team members and complainant.
- If the Assistant Director, in consultation with the Associate Director/Director and IRB Chair, determines that the allegation has no basis in fact or the complaint is a minor administrative issue that is able to be resolved by the Assistant Director and does not represent non-compliance (e.g., isolated subject payment complaint), no further action is taken.
- Complaints and allegations that are found not to be non-compliance, including minor administrative issues resolved by the Assistant Director, are entered into a log. A compilation of these complaints is provided to the IRB, the Associate Director of External Relations and Quality Improvement, and the OVCR Associate Director for Research Compliance annually to make them aware of issues and/or recurring concerns that may require new or revised policies and procedures.
- If the Assistant Director determines that the allegation represents potential non-compliance, the Assistant Director compiles any collected information for subsequent review by the Chair (or designee).
- If the investigator is asked to provide a response to the complaint, this information is included with the material provided the Chair.
- Complaints or allegations of non-compliance received directly by the IO or HPA are referred to OPRS and handled as described above.
- Receipt and initial review of investigator reports of non-compliance (including protocol violations) or changes to the protocol made without IRB approval to eliminate apparent immediate harm to subjects.
- Investigator reports of non-compliance are submitted to OPRS via the Prompt Reporting to the IRB form and forwarded to the Assistant Director of the relevant IRB.
- The Assistant Director reviews the report for completeness, contacts the investigator if necessary for additional information and makes a preliminary assessment of whether the event represents non-compliance.
- The report is then forwarded to the IRB chair or designee.
- Changes to the protocol to eliminate apparent immediate harm to subjects: the AD considers whether the change was necessary to eliminate apparent immediate hazards to the subject and whether there was insufficient time for IRB review.
- If these conditions are both true, the incident is referred to the convened IRB for a final determination.
- If these conditions are not both true, the incident represents a major protocol violation (i.e., serious Non-compliance) and is forwarded to the IRB chair or designee.
- Receipt of JBVAMC RCO Reports of Apparent Serious or Continuing Non-compliance
- The JBVAMC RCO must directly report to the facility Director within 5 business days of identifying apparent serious or continuing Non-compliance based on an informed consent audit, regulatory audit or other systematic audit of JBVAMC research.
- A copy of this report is provided simultaneously to the IRB as well as the ACOS for R&D and R&D committee.
- The Assistant Director of the relevant IRB reviews the report for completeness and contacts the RCO if necessary for additional information.
- Reports consistent with the examples of apparent serious or continuing Non-compliance provided in subparagraphs 7.f. and g. of VHA Handbook 1058.01should be referred to the convened IRB for a final determination to be made.
- The report is then forwarded to the IRB chair or designee.
- IRB Chair (or designee) review.
- The minimum materials provided to the IRB chair (or designee) to facilitate their review and evaluation of the non-compliance event:
- Original report of non-compliance;
- Any follow-up information gathered about the non-compliance issue; and
- Access to the complete research protocol file.
- Determinations that may be made by the Chair (or designee) are:
- The event does not represent non-compliance;
- The event represents non-serious and non-continuing non-compliance and no action is required;
- The event represents non-serious and non-continuing non-compliance and corrective action is required; or
- The event represents apparent serious and/or continuing non-compliance and the allegation or report of non-compliance is referred to the convened IRB for the final determination to be made; or
- The event likely represents a change to the protocol to eliminate apparent immediate harm to subjects and is referred to the convened IRB.
- When the non-compliance is non-serious and non-continuing, corrective actions implemented by the chair (or designee) may include, but are not limited to:
- Oversight or educational measures;
- Changes to the protocol or consent process to prevent future occurrences of non-compliance;
- More frequent monitoring of the research; or
- Modification of the continuing review schedule.
If the investigator is unable or unwilling to work with the IRB Chair, then the Non-compliance is handled as continuing non-compliance.
- When the non-compliance is judged likely to be serious or continuing, the chair (or designee) will determine if immediate action is needed to protect the rights and welfare of human subjects until the meeting of the convened board. Immediate actions to be considered include:
- Suspension of part (e.g., new subject recruitment) or all of the research (refer to UIC policy Administrative Hold, Suspension, or Termination of IRB Approval);
- Notification of currently enrolled subjects when information related to the compliance issue may relate to the subject’s willingness to continue to participate in the research.
- If the Chair (or designee) deems that further investigation of the matter is warranted, they may submit a written request to the OVCR Quality Improvement Program (QIP) or the RCO (if the JBVAMC is a performance site) to conduct an investigation or audit of the event. The written request will include, at a minimum, the AD’s report and a charge for the inquiry (i.e., why the investigation or audit is being requested, what additional information the IRB is requesting to be obtained during the investigation or audit).
- Documentation and PI notification of IRB Chair (or Designee) review and determinations.
- For events determined to be neither serious nor continuing, the finding of the chair (or designee) is documented in writing and copies provided to the investigator, Academic Department Head, other relevant UIC oversight committees (e.g., investigational drug service, radiation safety, cancer center), UIC HPA, JBVAMC R&D Committee (if JBVAMC is a performance site), NU OPRS (if NU is a performance site) and UIC OPRS protocol file. The IRB is notified of the Chair’s actions at the next scheduled meeting via the agenda.
- For events being referred by the Chair to the convened IRB, the investigator is notified of the determination, including any immediate actions taken by the Chair (i.e., suspension) and solicited by the Chair or IRB staff for any updated information.
- For events being referred by the Chair to the QIP or RCO (if the JBVAMC is a performance site), the investigator is notified by OPRS on behalf of the Chair of the determination and informed that they will be contacted by a member of the QIP or the RCO (if the JBVAMC is a performance site).
- Convened IRB review.
- When apparent serious or continuing non-compliance is reviewed by the convened IRB, two primary reviewers are assigned to conduct a thorough review of the packet of information and present the compliance issue to the full board. The IRB members receive at a minimum:
- Original report of non-compliance;
- Follow-up information gathered about the non-compliance issue;
- Protocol summary;
- QIP and RCO (if the JBVAMC is a performance site) findings and recommendations (as applicable); and
- Access to the complete research protocol file.
- For reports involving changes to the protocol made without IRB approval to eliminate apparent immediate harm to subjects, the IRB should consider whether the change was necessary to eliminate apparent immediate hazards to the subject, and whether there was insufficient time for IRB review. If these conditions are both true, the incident does not represent non-compliance. If these conditions are not both true, the incident represents a major protocol violation (i.e, serious non-compliance).
- For reports involving changes to the protocol made without IRB approval to eliminate apparent immediate harm to subjects, the IRB should consider whether the change was necessary to eliminate apparent immediate hazards to the subject, and whether there was insufficient time for IRB review. If these conditions are both true, the incident does not represent Non-compliance. If these conditions are not both true, the incident represents a major protocol violation (i.e, serious Non-compliance).
- The IRB may make any of the following determinations:
- No non-compliance has occurred;
- Non-compliance has occurred, but the non-compliance is neither serious nor continuing (refer to V.C. for possible corrective actions);
- Non-compliance has occurred that is serious and/or continuing.
- When the non-compliance is determined by the convened IRB to be serious and/or continuing, the IRB considers whether to implement one or more of the following actions:
- Suspension of research approval (refer to UIC policy, Administrative Hold, Suspension, or Termination of IRB Approval);
- Termination of research approval (refer to UIC policy, Administrative Hold, Suspension, or Termination of IRB Approval);
- Notification of currently enrolled subjects when information related to the non-compliance issue may relate to the subject’s willingness to continue to participate in the research.
- Other actions the IRB may take include, but are not limited to:
- Imposition of ethics and/or human subjects research education for the investigator and/or research staff;
- Modification of the protocol;
- Modification of the consent process;
- Providing information to past participants;
- Requiring re-consent of current participants;
- Modification of the continuing review schedule;
- Monitoring of the research;
- Monitoring of the consent process; and/or
- Referral to other UIC officials or committees for possible review.
- The corrective action plan should include timelines for the investigator to respond to the IRB and follow-up evaluation of the implementation and completion of the actions by the investigator.
- Review of the non-compliance issue is documented in the IRB meeting minutes.
- A communication documenting the IRB’s determination, the reason for the determination and the corrective action plan is generated and sent to the investigator within 10 working days of the convened IRB’s determination. Copies of the communication are sent to the Director of OPRS, Academic Department Head, HPA, other relevant UIC oversight committees (e.g., investigational drug service, radiation safety, cancer center), JBVAMC R&D Committee (if JBVAMC is a performance site), EC (UIC IRB#4), NU OPRS (if NU is a performance site), relevant IRB and the UIC OPRS protocol file.
- Serious or continuing non-compliance is reported by the Director of OPRS to appropriate IOs and federal agencies as described in the policy, Reporting of Unanticipated Problems/Events, Suspensions, Terminations, and Non-compliance.
- Reports to IOs, OHRP, FDA and other federal agencies will be made promptly. In the event a situation requires extended time to investigate or resolve, a preliminary report will be sent and followed by a final report. In no event will a preliminary report to IOs, the supporting agency head, or OHRP be delayed beyond 30 days of the OPRS receiving notice of a reportable event.
- JBVAMC RESEARCH: Special Reporting Considerations
- When the IRB determines that serious or continuing Non-compliance has occurred, the Chair or designee must report the problem or event directly (without intermediaries) to the JBVAMC facility Director within 5 business days of the determination. Copies of this communication are sent to the JBVAMC ACOS for R&D and R&D Committee. The UIC Human Protection Administrator (HPA) serves as the chair’s designee for this reporting.
- The JBVAMC facility director must report the determination to the appropriate ORO RO, with a simultaneous copy to the VISN Director and ORD, within 5 business days after receiving notification from the IRB.
- If the IRB requires additional time beyond the first convened meeting after receiving the report to investigate or resolve whether serious or continuing Non-compliance occurred, an initial report should be sent to the facility Director that a report of apparent serious or continuing Non-compliance has been received and provide a preliminary determination or indicate the disposition of the matter has not been determined.
- The IRB must reach a determination that serious or continuing Non-compliance did or did not occur within 45 days after receiving the report of apparent Non-compliance.
- Any remedial actions must be completed within
- 90-120 days after the IRB’s determination for Non-compliance involving a specific study or research team.
- 120-180 days after the IRB’s determinations for programmatic Non-compliance.
- Roles of the IO and the IRB.
- No other entity within the UIC may override a decision by the IO that limits, imposes conditions or in any way restricts a investigator’s privileges, or imposes conditions or restrictions upon an investigator or their research.
- Likewise, no other entity, including the IO, may override determinations or corrective actions related to the investigator’s human subject research protocols imposed by the IRB that limits, imposes conditions or in any way restricts an investigator’s privileges, or imposes conditions or restrictions upon an investigator's research protocols.
- Confidentiality and retaliation .
- The prompt review of complaints and allegations of non-compliance is critical for maintaining the integrity of UIC's HSPP and the IRB's ability to protect the human research subjects. A climate free from fear of sanction is required to foster reporting and ensure a fair review of complaints and allegations. Retaliation against any person who in good faith reports potential non-compliance (i.e., “whistleblower”) is prohibited. Whistleblowers who report human subject protection concerns also have access to other mechanisms at UIC for protection from retaliation under The State Officials and Employees Ethics Act (Ethics Act) 5 ILCS 430/15-5. See the University of Illinois Office of Business and Financial Services Policies and Procedures, section 9.6, at http://www.obfs.uillinois.edu/manual/central_p/sec9-6.html#bb.
- Allegations of non-compliance should remain confidential to the extent possible. Generally, complainants decide if they wish to remain unidentified or have their identity known. However, in order for a respondent involved in an allegation of non-compliance to have a meaningful opportunity to be heard, it may be necessary to identify the complainant. If the complainant is a subordinate of the respondent, the IRB will, to the best of its ability, protect the identity of the complainant while conveying the substance of the allegations and information gained to the respondent. The IRB cannot guarantee the anonymity of the complainant.
Version (#, date)
Replaces (#, date)
Summary of changes
Describe the procedures for IRB evaluation,
handling and making a determination of
allegations of Non-compliance; describing the
process for coordinating activities between the
IO and IRB.
Revised Procedure Section II.D. to include the
OVCR Associate Director of Research Compliance. Added procedure steps for
notifying the HSEIC that action is needed.
Added Assistant Director of Quality
Assurance/ Quality Improvement title.
||Updated to bring into compliance with VHA Handbook 1058.01, dated 5/21/10.
||Removal of all references to the HSEIC, HSIC, and Appeals Committee as these committees are disbanded. Addition of the QIP and RCO as resources. Correction of titles within the policy.
Examples of Apparent Serious Non-compliance (VHA Handbook 1058.01, 11/15/11)
- Any finding of non-compliance with human research requirements by any VA office (other than ORO) or any other Federal or state entity (e.g., FDA). Subsequent reports to ORO based on findings made by entities external to the facility must include a copy of the official findings.
- Initiation of VA human subject research, regardless of level of risk or number of subjects, without written notification from the ACOS for Research that the project may begin.
- Initiation of VA human subject research, regardless of level of risk or number of subjects, without approval by the IRB.
- Initiation of research interactions or interventions with one or more subjects prior to obtaining required informed consent.
- Lack of a required, signed informed consent document or lack of a required, signed Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule authorization for one or more subjects.
- Use of an informed consent document, for one or more subjects, whose content was not approved by the IRB.
- Failure to report one or more unanticipated SAEs or unanticipated serious problems involving risks to subjects or others as required by this Handbook.
- Participation by one or more members of the research team in the conduct of an active protocol without the required credentialing, privileging, or scope of practice, or engaging in activities outside the approved scope of practice.
- Continuation of interactions or interventions with human subjects beyond the specified IRB approval period.
- Implementation of substantive protocol changes without IRB approval, except where necessary to prevent immediate hazard to a subject.
- Involvement of prisoners or children in VA research, or conduct of international VA research, without the required approval by the VHA Chief Research and Development Officer (CRADO).
- Any Non-compliance involving substantive harm, or a genuine risk of substantive harm, to the safety, rights, or welfare of human research subjects, research staff, or others;
- Any non-compliance that substantively compromises the effectiveness of the facility’s human research protection or human research oversight programs.
- Serious programmatic non-compliance. Examples include, but are not limited to:
- Conduct of IRB business by an improperly constituted committee or with less than a quorum of voting members present.
- Improper designation of research as exempt under 38 CFR 16.101(b).
- IRB approval of a waiver of informed consent, a waiver of documentation of informed consent, or a waiver of HIPAA Privacy Rule Authorization when the respective approval criteria at 38 CFR 16.116(c) or 16.116(d), 38 CFR 16.117(c), or 45 CFR 164.512(i)(1)(i) are not met or are not documented.
- Programmatic failure to provide for and document Privacy Officer (PO) and Information Security Officer (ISO) review of proposed human subject research.
- Any programmatic non-compliance involving substantive harm, or a genuine risk of substantive harm, to the safety, rights, or welfare of human research subjects, research staff, or others;
- Any programmatic Non-compliance that substantively compromises the effectiveness of the facility’s human research protection or human research
Examples of Apparent Continuing Non-compliance (VHA Handbook 1058.01, 5/21/10)
- Failure to implement IRB-required changes to an on-going protocol within the time period specified by the IRB.
- Deficiencies in informed consent or HIPAA authorization procedures or documentation for ten or more subjects (e.g., outdated informed consent or HIPAA content; lack of required informed consent elements; lack of information required by VA; lack of signature of individual obtaining consent).
- Failure to maintain documentation required by the IRB or by the IRB-approved protocol for ten or more subjects (e.g., inadequate medical record documentation where required; inadequate case report forms where required).
- Failure to implement remedial actions within the periods specified at subparagraphs 5d(1) or 5d(2) in the absence of the justification described at subparagraph 5d(3).