ORIO Guidance: Protocol Deviations

Protocol deviations include both purposeful and accidental variances in the procedures outlined for a study in its IRBMED approved protocol, or the IRBMED application(s), or by State or Federal regulations. Different terms are used in to refer to these variances including "Protocol Exceptions" and "Protocol Violations."

Regulations require IRBMED approval of all proposed changes in research activity PRIOR to implementation, including those that are sponsor approved. When changes are necessary to eliminate apparent immediate hazards to the subject, implement the change and report by a formal submission within 7 days after the action is taken. Amendments may not be implemented prior to obtaining the approval, including those changes perceived to reduce risk (other than those taken to eliminate apparent immediate hazards).

The IRBMED requests the following information regarding protocol deviations/violations:

The sub-categories and examples below illustrate common types of occurrences

Deliberate Procedural Deviation:

The investigator decides to follow a different procedure than that set forth in the protocol for one or more subjects. Reasons may include subject safety or a change in circumstances of the study. These decisions are sometimes made in collaboration with a sponsor.

Whenever the investigator judges a deviation or change from the approved research plan is necessary to eliminate apparent immediate hazards to the subject or others, she should implement the change. An amendment to the protocol and, if needed, to the informed consent document must then be submitted to the IRBMED within seven days. Changes desired for any other reason that do not serve to eliminate an immediate hazard must not be implemented prior to IRBMED approval of the change. In some situations, it may be most appropriate for the investigator to temporarily cease enrollment until the needed change is requested and approved. Contact the IRBMED Office for further guidance.

Examples:

  • Investigator realizes that a diagnostic blood test was not described in the protocol but is needed to regulate serum levels of the study drug.
  • The protocol indicates that a nurse will conduct in-take interviews and review the consent document with subjects. The nurse retires so the study coordinator does the procedure instead.
  • Sponsor believes that study data to date indicates a potential participant could safely participate but doesn't meet currently approved eligibility criteria.
  • Newly published information indicates that one of the drugs used on a study has the same efficacy with significantly fewer side effects when administered at a lower dose than had been the previous standard of care (and the dose planned for in the protocol). If the investigator believes that subject safety requires decreasing the dose immediately, she can implement the change and then promptly report to the IRB. Note that such decisions should be carefully considered in light of good clinical and research practice. (Also note: If the investigator believed that risks to subjects were still balanced by the benefits of the study, then the IRB should receive an information update and the consent should be amended [and submitted to the IRB] to inform subjects of the new information.)

Accidental Procedural Deviation:

A member of the research team inadvertently follows a different procedure than that set forth in the approved protocol for one or more subjects. Report the event or pattern and how it was/will be corrected or addressed and how it will be avoided in the future.

Example:

  • A subject is enrolled in the study but does not meet the eligibility criteria stated in the protocol and/or informed consent document.

Appointment/Visit Deviations That Impact The Experimental Design:

Report appointment deviations, i.e. 'missed' exams, tests, appointments or treatment, only when the subject is NOT withdrawn from the study (report withdrawn subjects in the Scheduled Continuation Review application). Click on the link for more information.

Dosage/Intervention Errors:

When a subject or group of subjects is given the incorrect dosage of medicine, given an incorrect drug or intervention, when the drug or dose is misidentified or improperly labeled, AND an adverse event (physical, social, or emotional harm or risk of such harm ) did not occur, submit the event to the IRBMED as an ORIO (if an adverse event occurred, report as an AE). Report the event or pattern and how it was/will be corrected or addressed and how it will be avoided in the future.

Examples:

  • Two subjects who should have received the substance abuse survey and interview instead received the sexual abuse survey and interview.
  • The pharmacy provided the wrong medication. It was administered to three healthy control subjects on three different days without incident before the study nurse discovered the error.

Breach of Confidentiality or Privacy:

If confidential information about a subject is revealed in inappropriate settings, or to persons without a need to know, or by data exposure (computer security breach, documents left unsecured), report this event or pattern and how it was/will be corrected or addressed. NOTE: Immediately after identifying a breach contact the UMHS Privacy Office at 734-615-4759 or anonymously at 866-482-1252 (e.g., laptop missing that has unencrypted data on it).

If confidentiality must be breached in order to comply with legal or ethical obligations, inform the IRBMED if that possibility was not described in the informed consent document.

Example:

  • Investigator suspects potential child abuse during the course of a study. The report to UM's Child Protection Team should be reported to the IRBMED if this type of disclosure or the need to disclose information under state or federal law was not noted in the informed consent document.

Consenting/Assenting Process Deviations Or Problems:

Report to the IRBMED whenever a deviation from the IRBMED-approved consenting process has occurred or other consenting problem has been encountered. Report the event or pattern and how it was/will be corrected or addressed and how it will be avoided in the future.

Example:

  • A subject participated in some part of a study (e.g. an eligibility screening procedure) prior to giving permission and signing the Informed Consent Document.
  • The current IRBMED-approved Informed Consent Document for the study was not used in the consenting process.
  • Subjects were not provided with a copy of the Informed Consent Document used in the consenting process.
  • Subject properly signed the Informed Consent Document but was not given the opportunity to discuss and ask questions regarding the study.
  • Proper records of the Informed Consent Documents were not maintained.

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