(Reporting Noncompliance to Institutional Review Boards (IRBs) and Procedures for Handling Noncompliance Reports)
Adopted By: All Campus IRB
Adoption Date: December 8, 2005
Revision Date: May 5, 2006
Revised: April 10, 2008
Revised: December 2008
I. Background and Purpose of this Procedure
Both the DHHS regulations at 45 CFR 46.103(b)(5) and the FDA regulations at 21 CFR 56.108 (b), require IRBs to have procedures for prompt reporting to the IRB, appropriate institutional officials, and federal department or agency heads (i.e. OHRP, FDA, NCI) of “(i) any unanticipated problems involving risks to subjects or others, (ii) any serious or continuing noncompliance with this policy or the requirements or determinations of the IRB and (iii) any suspension or termination of IRB approval.”
This policy defines noncompliance that must be reported to the IRB, specifies reporting deadlines, and describes how the reports will be evaluated and determinations made. It also defines when and how institutional officials and the appropriate federal departments/agencies will be notified.
If a report contains facts that suggest there was “research misconduct” as that term is defined in the UW-Madison Policy, “Misconduct in Scholarly Research,” the report must be forwarded promptly to the Dean of the appropriate school or college and to the Graduate School’s Associate Dean for Research Policy. Misconduct in scholarly research is defined in the Policy as, “fabrication, falsification, plagiarism, or other practices that seriously deviate from those that are commonly accepted within the scholarly community for proposing, conducting, or reporting research. It does not include honest error or honest differences in interpretations or judgments of data.”
II. Definitions and Examples
Noncompliance. Noncompliance means any failure to follow (1) federal regulations, VA guidance, state laws or institutional policies relevant to human subjects research, or (2) the requirements and determinations of the reviewing IRB.
Examples of noncompliance with federal regulations may include: failure to obtain informed consent or inadequate procedures for obtaining informed consent from subjects; conducting human subjects research without a UW-Madison IRB approved protocol or exemption; inadequate supervision of research that involves potential risks to subjects and others; conducting research, including enrollment of subjects, when a UW-Madison IRB approval has expired or has been suspended or terminated; and initiating changes to the research protocol without prior IRB approval unless the change is “necessary to eliminate apparent immediate hazards to the subject.” [45 CFR 46.103(b)(4)] [21 CFR 56.108(a)]
Other examples may include failing to adhere to the conditions of approval of a protocol as specified by a UW-Madison IRB; starting research under a protocol before meeting the conditions required by an IRB and receiving an IRB notification of approval; failing to take IRB or institutionally required human subjects protection training; enrolling more subjects than approved by an 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; and altering an IRB-approved consent process or an IRB-approved recruitment process without prior IRB approval.
Serious noncompliance. Serious noncompliance includes noncompliance that affects the rights and welfare of participants or noncompliance that may put participants at risk of harm.
Examples of serious noncompliance include: (1) 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; (2) 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 no mitigating circumstances; or (3) misrepresentation of information related to the human subjects research protocol or performance of the research. Conducting non-exempt research without IRB approval or making substantive changes to a previously approved protocol without IRB approval generally are considered to represent serious noncompliance. Whether the conduct was inadvertent, careless or reckless, or intentional may be taken into consideration by the IRB in a determination of seriousness.
Continuing noncompliance. Continuing noncompliance means multiple or repeated instances of noncompliance, particularly after written notice from the IRB that the investigator must take action to correct noncompliance. Such multiple or repeated instances of noncompliance may occur on one protocol or on more than one protocol. Such multiple or repeated instances of noncompliance may occur simultaneously or over a period of time. Multiple or repeated instance of noncompliance may reflect the investigator’s failure to pay attention to IRB instructions or a willful disregard of those instructions. Whether the conduct was inadvertent, careless or reckless, or intentional may be taken into consideration by the IRB in a determination of continuing noncompliance.
Minor administrative noncompliance. Minor administrative noncompliance is an occasional instance of noncompliance that does not affect the rights and welfare of participants or put participants at risk of harm. Examples include a single instance of failure to submit a continuing review progress report to the IRB in time to prevent the lapse of approval, or failing to sign a protocol application as required.
Reportable deviations or exceptions to protocols. Some protocol exceptions and deviations are reportable as potential noncompliance as outlined in the Health Sciences IRBs Guidelines for Reporting Protocol "Exceptions" and "Deviations" in Clinical Trials. These reportable protocol deviations or exceptions will be reported and processed pursuant to the provisions described in this Noncompliance Policy.
A minor deviation or exception from the protocol under FDA regulations. This refers to an exception or deviation granted by a sponsor of a clinical trial subject to FDA regulations. The sponsor and investigator must conclude that this deviation from or exception to the protocol does not present a significant safety risk to subjects or potential subjects. This type of deviation or exception does not have to be reported to the IRB, nor will the IRB acknowledge this type of deviations or exceptions if they are reported.
III. Reporting Guidelines
A. When and where reports are to be made.
Initial reports of noncompliance should be made to the IRB that has been involved in reviewing the research protocol or exemption. Reports can be made to the chair, the IRB director, or a member of the IRB staff. When no application has been submitted to an IRB, the report should go to the IRB that normally would have jurisdiction over the protocol or exemption. Reports should be made promptly after discovery of the alleged noncompliance.
Reports of noncompliance should be made within 48 hours of receiving notice of the alleged noncompliance, if the alleged noncompliance requires immediate intervention to prevent serious harm to participants or others. In all other cases, reports of noncompliance should be made within fourteen (14) days after discovery of the alleged noncompliance.
B. Self-reporting obligations of investigators and research study staff.
Investigators or study staff must report noncompliance to the IRB as defined above. The report should be in writing and contain the following:
1. Detailed information about the noncompliance, including relevant dates.
2. Any corrective action, planned or already taken, to ensure that the noncompliance is corrected and will not occur again.
3. An assessment of whether any subjects or others were placed at risk as a result of the noncompliance or suffered any physical, social, or psychological harm.
4. Any other relevant information.
C. Others who may identify and report noncompliance.
Others who may report instances of noncompliance include IRB members or staff (such as when discovery is made during a protocol review); subjects or potential subjects or others, such as family members; members or staff of another IRB; UWHC, UWMF, or the VA patient relations offices; sponsors and other auditors; and others not involved with the research project but having information about possible noncompliance.
The written reports filed by individuals other than investigators or study staff should include:
1. Detailed information about the alleged noncompliance, including relevant dates.
2. How the person reporting obtained the information provided in the report.
3. Information about any injury, potential harm, or risk to the subject or others.
4. How the reporter may be contacted for further information, if needed.
5. Any other relevant information.
IV. IRB Procedures for Handling Allegations and Reports of Noncompliance
A. Review by IRB Staff
1. The IRB staff generally conducts the first review of reports of noncompliance.
a. The IRB staff reviews each report of noncompliance and, if necessary, conducts an investigation of the report. If the report did not come from the investigator, the IRB staff will obtain the investigator’s response to the report if it appears there is a basis in fact for the allegation. The IRB staff may obtain input from the IRB chair, convened IRB, or others (e.g., Legal Counsel, HIPAA Privacy Officer) during its review of noncompliance reports.
b. If the IRB staff determines that there is no basis for finding that noncompliance, as defined in this policy, has occurred, no action is required and the case is closed.
c. If the IRB staff determines that the report constitutes minor administrative noncompliance, as defined in this policy, the IRB staff will either resolve the noncompliance issue by contacting the investigator without further consultation with the IRB chair or IRB or will send the report with its determination to the IRB for review.
d. If the IRB staff determines that the report may constitute serious or continuing noncompliance, as defined in this policy, the IRB staff, with or without consultation with the IRB chair, will forward the issue to the IRB for review at its next scheduled meeting. If there is any doubt on the part of the IRB staff whether the report involves serious or continuing noncompliance, the report will be referred to the IRB for consideration.
e. If the IRB staff believes that the report may require immediate action to protect participants, the IRB staff will immediately refer the report to the IRB chair or to IRB director, if the director is not the individual initially reviewing the case.
B. Review by IRB Chair
1. The IRB chair will review a report referred to the chair by the IRB staff to determine whether the report requires immediate action to protect participants.
a. If a report suggests that participant safety is at risk, the IRB chair may immediately suspend the research, pursuant to the UW-Madison Suspension and Termination of Research Policy.
b. Any suspension of research by the IRB chair must be promptly reported to the IRB and the Institutional Official (IO). See, UW-Madison Suspension and Termination of Research Policy.
c. If the IRB chair immediately suspends research to protect participant safety, the chair will promptly notify the investigator of the suspension.
d. If the IRB chair immediately suspends research to protect participant safety, the IRB chair’s decision and the reasons for the decision will be scheduled for discussion at the next meeting of the IRB. The IRB will determine whether to lift or continue the suspension. The IRB will promptly notify the investigator and the IO of its decision. IRB discussion and resolution of issues of noncompliance relating to the suspension may be scheduled for a subsequent IRB meeting.
C. Review by Full IRB
1. The IRB will review reports of noncompliance referred to it by the IRB staff or IRB chair.
2. Materials reviewed
a. ED IRB and SBS IRB
i. The ED/SBS Office forwards the report of noncompliance and all related materials to all members of the reviewing IRB, including any alternate substituting for an IRB member, except for the complete protocol file, which is reviewed by one member of the reviewing IRB. The complete protocol file is available from the ED/SBS Office to any IRB member who wishes to review it before or during the convened meeting.
b. HS IRB and MR IRB
i. Reports of noncompliance that need review by the full IRB are first assigned to staff reviewers by the HS IRB Office Director.
ii. The HS IRB Office forwards to the assigned staff reviewer the report of noncompliance and all related materials in addition to the complete protocol file.
iii. Staff reviewers prepare a summary and detailed analysis of each report.
iv. The HS IRB Office Director also assigns each report to primary reviewers, who are IRB members and who review the report in a preliminary review session (PRS) held prior to a scheduled meeting of the full IRB. The assigned primary reviewers are provided the following information:
• The complete protocol file
• Copy of the report of noncompliance and any other relevant supporting materials
• A staff reviewer report that provides a detailed summary and expert analysis of the report assigned to the primary reviewers
v. In the preliminary review session (PRS), the primary reviewers evaluate each staff reviewer report in conjunction with the report of noncompliance. The primary reviewers prepare written assessments of each noncompliance report and make recommendations to the full IRB regarding (a) whether the noncompliance described in the report is serious, (b) whether the noncompliance is continuing, (c) what are the appropriate remedies, and (d) whether reporting to federal agencies is required. As part of their assessment, primary reviewers may request additional information or review by someone with a specific expertise.
vi. The noncompliance report, copies of all related documents, the staff reviewers’ summary along with written assessments and recommendations by the PRS are sent to the full IRB, including any alternate substituting for an IRB member. Copies of protocol files for those reports scheduled for review by the full IRB are available to all IRB members, including any alternate substituting for an IRB member, from the HS IRB Office before or during the convened meeting.
3. If a report suggests that participant safety is at risk, the IRB may immediately suspend or terminate the research, pursuant to the UW-Madison Suspension and Termination of Research Policy. Any suspension or termination of research by the IRB must be promptly reported to the IO. See, UW-Madison Suspension and Termination of Research Policy.
4. Before making a determination of serious or continuing noncompliance or suspension or termination of research, the IRB may invite the investigator to present additional materials and to appear in person. The IRB members may ask questions of the investigator.
5. After reviewing a report, the IRB will make determinations on the following issues:
a. Whether the report constitutes serious or continuing noncompliance;
b. Appropriate remediation measures, such as:
i. Requiring modifications to the protocol
ii. Revising the continuing review timetable
iii. Modifying the consent process
iv. Modifying the consent document
v. Providing additional information to current participants (e.g. whenever the information may relate to the participant’s willingness to continue participation)
vi. Providing additional information to past participants
vii. Requiring additional training of an investigator and/or study staff
viii. Reconsidering approval
ix. Requirement that current participants re-consent to participation
x. Monitoring of the research
xi. Monitoring of the consent
xii. Referral to other organizational entities (e.g., legal counsel, risk management, institutional official)
xiii. Other actions appropriate for the local context
c. Whether suspension or termination of research is warranted (See, Suspension or Termination of Research Policy), and
d. Whether further reporting to federal agencies and department heads is required under the UW-Madison Reporting to Federal Authorities Policy.
NOTE: Any suspension or termination of research by the IRB must be promptly reported to the IO. See, UW-Madison Suspension and Termination of Research Policy.
NOTE: An IRB cannot suspend an investigator’s privileges to conduct human subjects research. The IRB must bring any recommendation to suspend research privileges to the IO.
6. Record of determination
a. IRB minutes should reflect discussion and determination by the IRB on each of the following issues:
i. Whether noncompliance occurred
ii. If the IRB determines noncompliance occurred, whether:
• It was serious
• It was continuing
• Reporting to the UW-Madison Institutional Official is required
• Reporting to federal agencies is required
• Reporting to other campus or affiliate entities (e.g., the VA) is required
• Any further action is needed to prevent the noncompliance from recurring
• New information has resulted that may affect subjects’ willingness to participate in the study and how this information should be disseminated to subjects or others
7. After making its determinations, the IRB will:
a. notify the investigator in writing of the IRB’s decisions, with copies to the chair of the investigator’s department and/or research unit, and the investigator’s dean or director, and
b. if further reporting is required, report its decisions to the IO for further reporting pursuant to the UW-Madison Reporting to Federal Authorities Policy. (See, Section V, below).
D. Review by IRB Subcommittee
In noncompliance cases that are likely to be complicated or sensitive, the IRB chair or IRB may convene a subcommittee of the IRB to consider the case and make recommendations to the IRB regarding how to proceed, including the type of information and action required or whether a formal investigation is warranted. If the IRB chair convenes a subcommittee to consider the potential noncompliance, the full IRB will be informed of this decision at the next possible meeting. The full IRB will review the matter as described in Section IV.C., above, and make the necessary final determinations described in Section IV.C.5, above.
E. Appeal to Human Research Protection Program Advisory Committee
1. A decision of the IRB may be appealed by the investigator to the Human Research Protection Program Advisory Committee (Advisory Committee).
2. The notice to the investigator of the IRB decision will inform the investigator that he or she has 10 business days from receipt of the notice to appeal the IRB’s decision to the Advisory Committee. The investigator may appeal the IRB’s decision by sending the Advisory Committee a written notice of appeal, including the basis of the investigator’s appeal. The basis for an appeal is limited to one or more of the following:
a. that the UW-Madison IRB has failed to follow its own procedures
b. that the UW-Madison IRB has incorrectly applied federal regulatory criteria or state law, or
c. that the UW-Madison IRB has incorrectly applied UW-Madison policies.
3. If an investigator appeals the IRB’s decision, the investigator’s written appeal will be considered at a regularly scheduled Advisory Committee meeting and the Advisory Committee will review the appeal following the procedures described in the Advisory Committee Charter, Section A.2. The Advisory Committee will notify the investigator of the outcome of the appeal.
4. If the Advisory Committee receives a notice of appeal from the investigator, the Advisory Committee will notify the IRB and the IO of the request and of the final outcome.
F. Need for Additional Information
If, at any point in the review process, additional information is necessary to make the required findings, recommendations, determinations or reports, additional information may be requested from the investigator or other sources.
V. Reports of Serious or Continuing Noncompliance and/or Suspension or Termination of Approval to UW-Madison Officials and Federal Departments/Agencies
The Institutional Official will report any serious or continuing noncompliance, suspension and termination of previously approved research to the appropriate UW-Madison officials and to the appropriate federal department or agency heads pursuant to the UW-Madison Reporting to Federal Authorities Policy.
VI. Other Issues
A. Conflict of interest. Any IRB or Advisory Committee member who has a conflict of interest relating to the matter under review will excuse him or herself from the proceedings as required by the UW-Madison IRB Conflict of Interest Policy.
B. Confidentiality for complainants and witnesses. Generally, the individual under review should have access to the identity of the person who made the allegations and others who provide information. However, if such persons wish to maintain their anonymity, the IRB will make every effort to protect their identities, while at the same time affording the individual under review access to the substance of the allegations and information presented against him or her. The IRB cannot guarantee anonymity.
C. Nonretaliation. IRBs and appointed panels must have the ability to protect human subjects and, therefore, must be able to secure all the factual information necessary to make fair and objective determinations. Retaliation against those who make allegations in good faith and who have relevant information is illegal and will not be tolerated at UW-Madison. If there is any indication that retaliation might occur, the IRB chair should send a letter to the appropriate persons cautioning that, should any retaliation occur, sanctions may be imposed either internally or externally.
D. Exceptions. The Advisory Committee may make exceptions to this policy when it deems such exceptions appropriate or necessary.