A protocol deviation is any departure from the defined procedures and treatment plans as outlined in the protocol version submitted and previously approved by the Institutional Review Board (IRB). Protocol deviations can potentially place subjects at risk and undermine the scientific integrity of the study, thus jeopardizing the justification for the research.

Protocol deviations are unplanned, unintentional events. Any changes in the research protocol during the period, for which the IRB approval has already been given, may not be initiated without submission of an amendment for IRB review and approval.

The IRB recognizes that some protocol deviations pose no conceivable threat to participant safety or scientific integrity. As such, reporting is left to the discretion of the principle investigator within the context of the guidelines below. Any report of a protocol deviation to the IRB should be made in a timely fashion but no later than within 30 days of its occurrence or identification.

Examples of Reportable Protocol Deviations:

• Enrolling subjects who do not fulfill inclusion/exclusion criteria
• Participant receiving any study related activity such as treatment, procedures, testing or drug administration prior to obtaining documented IRB-approved informed consent
• Adverse Event reporting procedures not followed
• Variations in the use of a study device from protocol indication
• Variations in drug dosing/dispensing/storage requirements
• Use of prohibited medications
• Incorrectly performing or missing protocol required tests and procedures
• Incorrect handling of biological samples
• Premature "unblinding" of research treatment or data
• Loss or corruption of study data
• Protocol deviations identified by sponsor or study coordinator that may affect the safety of a participant or the integrity of study data

Examples of Non-reportable Deviations

• Withdrawal of participant for logistical reasons (e.g. moved out of town)
• Minor variation in clinic visits/follow-up (e.g., 'Day 20 Visit' on day 24) if no protocol medication, treatment or supervision is missed

Protocol Violations

A protocol violation occurs when there is a variance in a research study between the protocol that has been reviewed and approved by the Institutional Review Board and the actual activities being performed. Violations may be minor or major.

Minor protocol violations:

• Have no substantive effect on the risks to research subjects or the value of the data collected (meaning the violation does not confound the scientific analysis of the results)
• Did not result from willful or knowing misconduct on the part of the investigator(s)

Major protocol violations:

• Pose a significant risk of substantive harm to research subjects
• Damage the scientific integrity of the data collected
• Exhibit evidence of willful or knowing misconduct on the part of the investigator
• Demonstrate other serious or continued noncompliance by investigator(s) with Federal, state or local research policy, laws or regulations