Noncompliance, Protocol Exceptions and Deviations
IRB Member Fact Sheet--Version Date: January 2013
Federal regulations require the reporting of serious and continuing noncompliance to the IRB, institutional officials and certain federal agencies and department heads. Because the federal regulations do not define noncompliance, institutional policy must be applied. This document describes the campus policy regarding noncompliance, how the term is defined, and requirements for IRB review.
Definition of Noncompliance
The University of Wisconsin-Madison defines noncompliance as “any failure to follow (1) federal regulations, state laws or institutional policies relevant to human subjects research, or (2) the requirements and determinations of the reviewing IRB.” When noncompliance has occurred, federal regulations require IRBs to determine whether the incident is serious, continuing, or both. The UW-Madison defines serious noncompliance as non-compliance that affects the rights and welfare of participants or that may put participants at risk of harm. Continuing noncompliance is defined by the UW-Madison as 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 protocol or on more than one protocol and may occur simultaneously or over a period of time.
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
- initiating changes to the research protocol without prior IRB approval unless the change is necessary to eliminate apparent immediate hazards to the subject
- 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
- altering an IRB-approved consent process or an IRB-approved recruitment process without prior IRB approval
Examples of serious noncompliance include:
- 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 no mitigating circumstances
- 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
- conduct that adversely affected the integrity or effectiveness of human subjects protections or subjects rights or welfare
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. An example is a single instance of failure to submit a continuing review progress report to the IRB in time to prevent the lapse of approval.
Protocol Exceptions and Deviations vs. Noncompliance
The Health Sciences IRBs have recognized that investigators frequently enroll subjects, usually with permission from the study sponsor, who may deviate from a single eligibility criterion in a minor way or who may have a study visit outside the timeframe required by the study. Consequently, the Health Sciences IRBs determined that if the investigator and sponsor agree that a single instance of an "exception" or "deviation" from the protocol does not present a safety risk to the subject or potential subject it does not require reporting to the Health Sciences IRBs. These deviations and exceptions are not considered noncompliance, but rather an expected aspect of industry-sponsored clinical research. Repeated instances of the same exception or deviation, however, are considered noncompliance.
IRB Determinations about Noncompliance
If the IRB makes an initial assessment of the noncompliance report as representing potentially serious or continuing noncompliance as defined above, the committee renders a preliminary determination. The investigator is then provided with an opportunity to respond to this preliminary finding and provide additional relevant information or detail any potential mitigating circumstances that might not have previously been considered. The IRB will review this response and make a final determination regarding the noncompliance. If the IRB makes a final determination that a report constitutes serious and/or continuing noncompliance, it must also make recommendations regarding whether the Institutional Official will report the noncompliance to the OHRP, the VA, the FDA and any other federal department or agency that funds or supports the research in which the noncompliance occurred.
In addition to making a determination of serious and/or continuing noncompliance, the committee also must decide what further action is required.
Actions related to the protocol can include:
- Requesting the investigator make modifications to the protocol
- Requiring more frequent review of the protocol (e.g., more often that the minimal of annual review)
Requesting the investigator modify the consent process or consent documents
- Requiring the investigator to provide additional information to current and/or past participants or re-consenting to participation
- Requesting further corrective actions by the study team
- Reconsideration of IRB approval
- Implementation of monitoring of the research
- Implementation of monitoring of the consent process
- Suspension of the research
- Termination of the research
- Referral of the matter to the Institutional Official via the Human Research Protection Program Advisory Committee for further consideration.
The IRB may require additional action, such as protocol or consent form revisions, even without a finding of serious or continuing noncompliance.
NOTE: Although the IRB can suspend the research study, only the Institutional Official has the authority to suspend an individual’s privileges to conduct research.
IRB Review of Corrective Action Plans:
As part of the noncompliance report to the IRB, investigators are required to outline a corrective action plan to prevent similar errors from occurring in the future. The IRB reviews this for adequacy and may require revision if not found to be sufficiently robust. Corrective action plans may include:
Additional education of the investigator and/or the research staff
- Additional monitoring of support staff by the investigator, including more frequent staff meetings or review of work by an auditor
Revisions to internal documents for processes
For further information about noncompliance, please contact the Health Sciences IRBs Office at (608) 263-2362 or consult HS IRB website at Adverse Event and Other Incident Reporting