HRPP Manual Section 9-8
Protocol Deviations or Violations
A protocol deviation/violation is any change, divergence, or departure from the study design or procedures of a research protocol that has not been approved by the IRB. The principal investigator (PI) is responsible for reporting the protocol deviation/violation to the IRB using the Protocol Deviation/Violation reporting form. The IRB chair or IRB member will review this form to determine if additional information or further reporting is necessary. If a protocol deviation/violation may be noncompliance, HRPP Manual 9-2 “Noncompliance” must be followed. Protocol deviations/violations which may meet the definition of an unanticipated problem involving risks to subjects or others must be reported promptly and HRPP Manual 9-1 “Unanticipated Problems Involving Risks to Subjects or Others” must be followed.
Urgent protocol deviations/violations that may affect the subject's rights, safety, or well-being and/or affect subject’s willingness to participate in the study should be reported within 72 hours.
Examples of protocol deviations/violations include but are not limited to:
- Failure to follow the approved study procedure
- Study procedure conducted out of sequence
- Omitting an approved portion of the protocol
- Failure to perform a required lab test
- Missing lab results
- Enrollment of ineligible subject (e.g., subject’s age was 6 months above age limit)
- Study visit conducted outside of required timeframe
- Failure of subject to return study medication
- Over-enrollment
- Dosing errors that have been cleared by the Sponsor
- Failure to perform or collect required labs or other statistics
- Sponsor approved changes in protocol
- Data collection that occurs outside of the planned time window or location
- Failure to obtain informed consent prior to initiation of study-related procedures
- Enrollment of a subject who did not meet all inclusion/exclusion criteria
- Performing study procedure not approved by the IRB
- Failure to report a unanticipated problem involving risks to subjects or others to the IRB and/or sponsor
- Drug/study medication dispensing or dosing error
- A research subject received an excluded concomitant medication
- Incorrect storage of study medications
- Study visit conducted outside of required timeframe that, in the opinion of the PI, may affect subject safety
- Failure to follow safety monitoring plan
See HRPP Manual 9-5, “Unapproved Change in Protocol” for requirements when an immediate change in a research study is necessary to eliminate a hazard to subjects.
If the sponsor has contractually required compliance with International Conference on Harmonization Good Clinical Practice (ICH GCP) E6 (R3), the investigator should document all protocol deviations. In addition to those identified by the investigator themselves, protocol deviations relevant to their trial participants and their conduct of the trial may be communicated to them by the sponsor (see ICH GCP E6 (R3) section 3.11.4.5.1(b)). In either case, the investigator should review the deviations, and for those deviations deemed important, the investigator should explain the deviation and implement appropriate measures to prevent a recurrence, where applicable (see ICH GCP E6 (R3) section 3.9.3). (ICH GCP E6(R3) section 2.5.3). For more information, see HRPP Manual 2-4 “International Conference on Harmonization Good Clinical Practice E6.”
This policy and procedure supersedes those previously drafted.
Approved By: Vice President of Research and Graduate Studies, 7-19-2011.Revision 1 approved by VP Research & Graduate Studies on 12-9-2015. Revision 2 approved by Assistant VP Regulatory Affairs on 7-21-2016. Revision 4 approved by Associate VP Research Regulatory Support on 5-17-2026.