Protocol Violation or Incident

Overview 

Federal regulations require that changes in the conduct of an IRB-approved research study receive prior IRB review and approval. When changes to the protocol are necessary to immediately eliminate or reduce an apparent hazard to the safety of research participants or others, those changes may be initiated without prior IRB approval, but must be reported to the IRB/HRPP within 10 working days of initiation. 

Protocol violations are changes in the conduct of a IRB-approved research protocol that are under the investigator’s control and made without prior IRB approval. Incidents are any problematic or unanticipated events that are not protocol violations and that may adversely impact on the study participants or the conduct of the study. You must report all major study-related protocol violations and incidents to the IRB/HRPP. 

The IRB reviews these reports to determine whether an event meets the definition of an unanticipated problem involving risk to participants or others (UP) and/or an instance of serious or continuing noncompliance (SCNC).

What, When and How to Report

See the Post-Approval Reporting Requirements Summary Sheet for one-page summary of the information below. 

Use the Reporting Requirements chart below to determine which violations, incidents and immediate protocol changes need to be reported and how/when to submit the report.

If UCSF is not the IRB of Record, Protocol Violation/ Incidents must not be submitted to UCSF. Submit the Protocol Violation/Incident report to the IRB of Record.

The IRB of Record will notify the UCSF IRB when a determination of Serious, Continuing, and/or Unanticipated Problem is made.

Contact the IRB at (415) 476-1814 or [email protected] and speak with the QIU Analyst of the day with questions.

Note: The SF VA Medical Center (SFVAHCS) has has a shorter timeline (5 days) and different definitions than UCSF for reporting certain categories of post-approval events. See the SFVAHCS guidance page and VHA Handbook 1058.01 for specific examples.

Type of Event

When to Report

Reporting Form

Major Violation including, but not limited to incorrect intervention given, enrollment of ineligible participant, key safety procedure/lab not done or done outside window.

Within 10 working days of awareness

iRIS Protocol Violation/Incident Report Form

Immediate Protocol Change to Protect Participant Safety

Within 10 working days of occurrence

iRIS Protocol Violation/Incident Report Form

Major Incident including, but not limited to problem with consent or recruitment process, significant complaint or concern, lapse in study approval, loss of adequate resources, potential breach of confidentiality of confidentiality.

Potential breaches of privacy or confidentiality: Within 48 hours of awareness

Other Major Incidents: Within 10 working days of awareness

iRIS Protocol Violation/Incident Report Form

Reporting Reminders:

  • Submit follow-up reports for unresolved events
  • Remove subject identifiers from reports/attachments
  • Complete violation/incident info sections during Continuing Review
  • Remember outside reporting requirements to sponsors, FDA, NIH, etc.

Submitting in iRIS

Follow these steps to submit the report. For additional assistance, read the quick guide called "Submitting Post-approval Forms" in the Help section of iRIS. 

Go to My Studies under IRB Study Assistant. Open the active study for which you want to submit the report.  

Click Add New Form to start a blank form. You can copy a previous form by selecting the form you want to copy and clicking Copy Form. The copied form will open automatically.

Anyone listed on the study can sign off and submit it.  

  • Open the first study again and click on the Protocol Violation/Incident Report Form link
  • Click the "Apply to Multiple" icon next to the correct form
  • Check the boxes next to the studies for which you wish to submit this form. Click the "Save a Copy of the Selected Form" button.
  • You will then need to open each of the studies you selected, open the copied form and submit the form

What Are Protocol Violations?

Protocol violations are any unapproved changes, deviations or departures from the study design or procedures of a research project that are under the investigator’s control and that have not been reviewed and approved by the IRB. Protocol violations are divided into two categories: major (reportable) or minor (non-reportable)

Major (reportable) protocol violations are any unapproved changes in the research study design and/or procedures that are within the investigator’s control and not in accordance with the IRB-approved protocol that may affect the participant's rights, safety or well-being, or the completeness, accuracy and reliability of the study data. Report all major violations to the HRPP/IRB using the Protocol Violation/Incident Report Form in iRIS.

HRPP criteria for defining major violations include any of the following:

  1. The violation has harmed, or posed a significant or substantive risk of harm, to the research participant
  2. The violation resulted in a change to the participant’s clinical or emotional condition or status
  3. The violation has damaged the scientific completeness or soundness of the data collected for the study
  4. The violation is evidence of willful or knowing misconduct on the part of the investigator(s)
  5. The violation involves serious or continuing noncompliance with federal, state or local regulations

Minor (non-reportable) protocol violations (also known as protocol deviations) are any unapproved changes in the research study design and/or procedures that are within the investigator’s control and not in accordance with the IRB-approved protocol that do not have a major impact on either the participant’s rights, safety or well-being, or the completeness, accuracy and reliability of the study data.

      Do not report minor protocol violations to the IRB/HRPP, but document them in the study files.

      HRPP criteria for minor violations include all of the following:

      1. The violation did not harm or pose a significant risk of substantive harm to the research participant
      2. The violation did not result in a change to the participant’s clinical or emotional condition or status
      3. The violation did not damage the completeness, accuracy and reliability of the data collected for the study
      4. The violation did not result from willful or knowing misconduct on the part of the investigator(s)

      What are not considered to be protocol violations? Changes, deviations or departures from the study design or procedures that are due to a study participant’s non-adherence are not considered to be protocol violations. However, you should document study participant non-adherence to the study design and/or procedures in the research records and report this to the IRB/HRPP as an incident if the event(s) adversely impacts the study participant’s safety or well-being, or if a pattern of protocol departures indicate a need for changes in the protocol or informed consent document(s).

      1. Study participant did not return for a scheduled study visit.
      2. Participant refused a blood draw.

          What Are Incidents?

          Major (reportable) incidents are any problematic or unanticipated events involving the conduct of the study or participant participation that may occur during the course of the research project. Report all major incidents to the HRPP/IRB.

          Some examples of study-related incidents include, but are not limited to:

          1. Receipt of a significant complaint or concern from a potential or enrolled study participant, such as a complaint/concern that may adversely impact the participant’s safety, rights or welfare. Reminder: Investigators are obligated to make a good faith effort to resolve any study-related concern or complaint they receive.
          2. Inappropriate behavior of study participants and/or research personnel.
          3. Problems during study recruitment or the informed consent process.
          4. Problems with the study design in which a majority of participants have difficulty adhering to the study schedule of procedures.
          5. Potential breach of study participant’s privacy or confidentiality (see below).
          6. Withdrawal or significant reduction in, resources necessary to adequately and safely conduct study activities.
          7. Changes to the protocol to eliminate or reduce an apparent immediate hazard to the safety of research participants or others (see below).

          Potential breaches of privacy or confidentiality of study participants’ Protected Health Information (PHI) are “major (reportable) incidents” that must be submitted to the IRB.

          The review of these incidents it time sensitive: Submit a Protocol Violation/Incident Report Form in iRIS within 48 hours of the PI’s awareness of the potential breach.

          The IRB collaborates with the UCSF Privacy Office to investigate these incidents to meet state and federal regulatory obligations. Investigations must be completed within a short time frame in order to avoid penalties and/or late reporting fines for the institution.

          Some examples of major incidents involving privacy or confidentiality:

          • Failure to properly execute a HIPAA Research Authorization Form due to
            • Missing a participant’s signature or date
            • Missing initials next to an information type in Section C that has been or will be accessed by the research team
            • Accessing items in Section B that are not approved for access or release by the participant
          • Failing to obtain a properly executed consent form due to missing a participant’s signature or date
          • Mailing, emailing or otherwise communicating identifiable study participant information to an unauthorized individual (e.g., incorrect participant, incorrect mailing address, incorrect e-mail address, etc.)
          • Failing to redact identifiable study participant information sent to a study sponsor (only if the IRB Application and consent form require de-identification)

            You must also report any unanticipated problem involving potential risk to participants or others.

              Minor (non-reportable) incidents are any events involving the conduct of the study or participant participation that may occur during the course of the research project but which is not problematic or involve significant potential to harm the participant(s) or others. Do not report minor incidents to the IRB/HRPP.

              Receipt, and subsequent resolution by the study team, of a participant complaint regarding late study payment.

              IRB/HRPP Review and Definitions

              The IRB/HRPP will review the Protocol Violation/Incident Report Form. Track the report using the Submission History feature in iRIS. 

              Acknowledge the report — no letter is issued.

              Request additional information about the violation or incident or other related information.

              Refer the violation or incident report (or other related information) to the IRB if it appears to meet the HRPP’s institutional definition of an unanticipated problem (UP) involving risk to participants or others and/or an instance of serious or continuing noncompliance. The IRB may query you for additional information and will inform you if one of these determinations is made.

              Report event to OHRP, appropriate University officials and study sponsors and FDA (for studies under FDA regulatory oversight) if a full IRB panel review determines that the event report is an UP or (after investigation) determines an instance of serious or continuing noncompliance.

              Flag the report and monitor the study for additional violation or incident reports.

              Require a modification to the study protocol and/or informed consent document.

              Temporarily suspend enrollment and/or study treatment.

              Permanently suspend or terminate approval of research that has been associated with unexpected serious harm to participants and/or serious or continuing noncompliance.

              Definitions

              An unexpected, research-related event where the risk exceeds the nature, severity, or frequency described in the protocol, study consent form, Investigator’s Brochure or other study information previously reviewed and approved by the IRB.

              Noncompliance is defined as: failure to follow state or federal regulation, or the University policies, or the requirements of the VHA Handbook 1200.5, or determinations of the IRB for the protections of the rights and welfare of study participants.

              Serious Noncompliance is defined as: failure to follow state or federal regulations or University policies or determinations of the IRB for the protection of the rights and welfare of study participants and that, in the judgment of the IRB, results in, or indicates a potential for a) a significant risk to enrolled or potential participants or others, or b) compromises the effectiveness of the UCSF HRPP or the University.

              Continuing Noncompliance is defined as: a pattern of noncompliance that continues to occur after a report of noncompliance and a corrective action plan have been reviewed and approved by the IRB.

              See VHA Handbook 1058.01 and SFVAHCS guidance.

              Continuing Noncompliance: Continuing noncompliance is a persistent failure to adhere to the laws, regulations, or policies governing human research.

              Serious Noncompliance: Serious noncompliance is a failure to adhere to the laws, regulations, or policies governing human research that may reasonably be regarded as:

              (1) Involving substantive harm, or a genuine risk of substantive harm, to the safety, rights, or welfare of human research subjects, research staff, or others; or

              (2) Substantively compromising the effectiveness of a facility’s human research protection or human research oversight programs.

              Unanticipated (Unexpected): The terms “unanticipated” and “unexpected” refer to an event or problem in VA research that is new or greater than previously known in terms of nature, severity, or frequency, given the procedures described in protocol-related documents and the characteristics of the study population.

               

              Last updated: December 15, 2021