A study violation (also commonly referred to as a study or protocol deviation) is defined as an unplanned or unforeseen failure by the Principal Investigator or other study personnel to follow the specified procedures approved by the IRB for the study. Such violations often represent non-compliance and they differ from amendments since they usually apply to only a single occurrence or subject and are not intended at the time to modify/change the study.
It is the responsibility of the Principal Investigator to determine which is applicable between the two general categories of study or protocol violations/deviations:
1) Major Violations/Deviations:
These are violations that may impact subject safety, condition or status, affect the integrity of study data, pose a significant risk of harm and thereby change the risk/benefit ratio and/or affect a subject's willingness to participate in the study. Examples of major violations include (but are not limited to):
a. Failure to obtain informed consent
b. Informed consent was obtained after initiation of study procedures
c. Informed consent for IND/IDE studies was obtained by someone other than individuals authorized by the IRB to obtain consent
d. Enrollment of a subject who did not meet all inclusion/exclusion criteria
e. A study procedure was performed without IRB approval
f. Failure to report a serious adverse event to the IRB and sponsor
g. Failure to perform a required lab test
h. Drug/study medication dispensing or dosing error
i. Study visit conducted outside of the required timeframe
j. Failure to follow the safety monitoring plan
Major study violations must be reported by the Principal Investigator to the HSRO and to the sponsor (if applicable) as outlined in the sponsor’s protocol within 10 working days of discovery with the exceptions that:
Study violations that have resulted in the death of a subject or a life-threatening event, even if anticipated, must be reported to the IRB pursuant to the "serious adverse events" policy within 24 hours of the knowledge of the event. If the cause of death is not available, this should not delay the reporting of the event.
The HSRO shall screen reports of major study violations to determine if immediate action is required and then forward the report for review to the IRB Chair or designee who shall determine whether immediate and/or further action is required, whether minimal risk changes in the study protocol or informed consent documents are required and/or whether the report should be deferred to the convened IRB. If immediate action is recommended by the HSRO staff or the IRB Chair/designee, the report shall be forwarded either by the HSRO to the Associate Vice Provost for Human Subject Research or the Assistant Provost for IRB Affairs or to the IRB Chair or designee who may take one or more actions which may include (but are not limited to):
a. Implement immediate action to ensure the ongoing safety of research participant
b. Call an emergency meeting of the convened IRB meeting to act upon the report
c. Present the report to the convened IRB at the next scheduled meeting
d. Request additional information from the Principal Investigator or others
e. Require establishment of a monitoring committee or the involvement of another entity to ensure subject safety
Reports of major study violations not requiring immediate action shall be reviewed by the IRB Chair or designee who may defer this review to the convened IRB when deemed appropriate. The IRB Chair or designee or the convened IRB may ask investigators and/or Data Safety Monitoring Boards for additional clarifying information and may require modifications to the protocol and/or consent documents if it is apparent that risks are greater than those originally stated. The IRB may suspend or terminate a protocol if these actions are required to eliminate untoward risks to human subjects. All changes to the protocol or consent documents must receive prior approval by the IRB before implementation.
All actions of the IRB Chair or designee regarding study violations shall be reported to the convened IRB. All actions of the IRB Chair or designee and/or the convened IRB shall be promptly communicated to the Principal Investigator in writing.
2) Minor Violations/Deviations:
These are violations that may not impact subject safety, compromise the integrity of study data and/or affect a subject's willingness to participate in the study. Examples of minor violations may include (but are not limited to):
a. Implementation of unapproved recruitment procedures
b. Missing pages of executed consent form
c. Inappropriate documentation of informed consent, including missing signatures of a subject or investigator
d. Consent form copy not given to the person signing the form
e. Someone other than the subject dated the consent form
f. Use of invalid consent form, i.e. consent form without IRB approval stamp, or outdated/expired consent form
g. Failure to follow the approved study procedure that, in the opinion of the PI, does not affect subject safety or data integrity
h. Study procedure conducted out of sequence
Principal Investigators are cautioned that the above examples listed as possibly being 'minor violations/deviations" may, in some circumstances, impact on subject safety, or affect a subject's willingness to participate in the study. If these circumstances apply, then the violations/deviations must be considered to be "major" and must be reported by the Principal Investigator to the HSRO pursuant to the policy on "major violations/deviations" (see above).
Minor violations shall be reported by the Principal Investigator with the continuing review.