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Chapter XIX - Deviations and Violations

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A deviation is an incident involving a departure from the IRB-approved protocol in the actual conduct of the study. Deviations may result from the action of the participant, investigator, or staff. Deviationsinclude:

Deviations are considered major when the unapproved change(s) in previously approved research activities, implemented without IRB approval, may potentially adversely affect participant’s rights, safety, welfare, willingness to continue participation, or affect the scientific design of the study and/or the integrity of the resultant data. Major deviations should be promptly reported to the GA IRB.

Deviations are considered minor when the unapproved change(s) in previously approved research activities, implemented without IRB approval, do not adversely affect participants or the integrity of the study data. Minor deviations should be reported tothe GA IRB at the time of continuing review.

An incident involving an intentional deviation from the IRB-approved protocol that was not implemented in response to an emergency and that may impact a participant’s rights, safety, and/or welfare, makes a substantial alteration to risks to participants, or affects the scientific design of the study and/or the integrity of the resultant data. Violations may also be repeated deviations (major or minor) of the same nature. Violations can represent serious or continuing non-compliance with the federal regulations and guidelines for ethical conduct of human participant research.

Deviations that meet the definition of a major deviation, and all protocol violations, mustbe reported to the GA IRB promptly following the Investigator’s knowledge of the event, no matter how the deviation or violation was discovered (e.g. discovered by the sponsor during a monitoring visit, discovered by the Principal Investigator,etc.).

The Principal Investigator must submit to the GA IRB a report that includes a description of the major protocol deviation(s), the plan to mitigate its negative effects, if any, and the plan to minimize or eliminate future occurrences. Examples of major deviations include, but are not limited to:

  • Failure to obtain or document informed consent prior to any study-specific tests/procedures;
  • Failure to perform a required lab test that, in the opinion of the principal investigator may affect participant safety or data integrity;
  • Recurrence of minor deviations.

Emergency situations that required changes necessary to eliminate or reduce anapparent immediate harm or hazard for participants (e.g., immediate reduction in the study drug dose due to new safety information or serious side effects) must be promptly reported to the GA IRB following the Investigator’s knowledge of the deviation. Implementing changes to protect participants involved in research is always a higher priority than securing prior IRB approval. However, such changes must be reviewed by the GA IRB promptly following their occurrence.


If the deviation involved an emergency administration or use of an FDA-regulated test article, the Principal Investigator must report to the IRB within five working days (21 CFR 50.23 and 56.104).

The GA IRB Chair can review the deviation or violation report and remediation plan or refer the report for review by the convened IRB.

The convened GA IRB or the Chair can accept the deviation report and remediation plan without modification. Alternatively, the convened IRB, or the IRB Chair or designee, can require changes to the remediation plan. The protocol may be suspended until the IRB’s requirements have beenimplemented.

If it is necessary to make a permanent change to the study procedures to avoid harm to other participants, then an amendment to the protocol must be submitted as soon as possible. If appropriate to maintain safety of the participants, new participant enrollment should be temporarily stopped by the investigator until the amendment isapproved.

Deviations that meet the definition of a minor deviation, and that are not reoccurring, should be reported to the GA IRB at the time of continuing review. Minor deviations should be described in summary form with sufficient detail so that the deviation is understandable. Any major deviations that occurred during the same approval period should be included in this summary for completeness. Examples of minor deviations may include, but are not limited to:

  • Blood samples obtained at times close to but not precisely at the time points specified in the protocol;
  • Routine safety lab work for a participant who has a history of previously normal lab values was either missed or was performed outside the protocol-defined window, but did not introduce any new safety concerns for the participant;
  • Visit outside of study window but has no impact on the participant orstudy;
  • Study procedure conducted out ofsequence.

As soon as a Principal Investigator learns of a planned compliance inspection, site visit, or audit of his/her study by another government agency, e.g., AHRPO, FDA, OHRP, etc., s/he should immediately inform the IRB office by telephone (Genetic Alliance Institutional Review Board at +01(202) 966-5557).

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