Protocol Deviations, Exceptions, Violations

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:

• Description of the deviation
• Justification or reasons for the deviation
• Notice of whether a corresponding protocol amendment will be submitted to the IRBMED
• Justification for inclusion of the subject's data in the study despite the deviation, if the investigator plans to use the data
• Report the event or pattern and how it was/will be corrected or addressed and how it will be avoided in the future

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

As an investigator, you may decide, for one subject (or more if they are seen on the same day as the discovery of the protocol error), to follow a procedure different from that set forth in your protocol. Reasons may include subject safety or a change in circumstances of the study. The sponsor may be involved in the decision to deviate.

Whenever you judge that a deviation or change from the approved research plan is necessary to eliminate apparent immediate hazards to the subject or others, you should implement the change. An amendment to the protocol and, if needed, to the informed consent document must then be submitted to IRBMED within 7 days (or as soon as possible if the revised protocol is coming from a sponsor). You must obtain IRBMED approval before implementing a deviation or change that does not serve to eliminate an immediate hazard. In some situations, it may be most appropriate for you to cease enrollment until the needed change is requested and approved. Contact the IRBMED office for further guidance.

Examples where a deliberate deviation IS permissible:

• An investigator realizes that a diagnostic blood test was not described in the protocol but is needed to regulate serum levels of the study drug.

Since this scenario involves a compromise to subject safety, the investigator may deviate from the protocol and then immediately report the deviation to the IRBMED.

• 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 approved in the protocol).

If the higher dose poses significant hazards to subjects, the investigator may decrease it and then promptly report the change to IRBMED. The investigator should ensure that the decision is in keeping with all principles of good clinical and research practice.

If, on the other hand, the study will maintain a favorable risk/benefit ratio without a change in dosage, and the investigator decides not to change the protocol, s/he must submit an ORIO, notifying IRBMED of the new information, and a consent amendment, notifying subjects of the new information, and await IRBMED approval before proceeding.

Examples where a deliberate deviation IS NOT permissible:

• The protocol indicates that a nurse will conduct intake interviews and review the consent document with subjects. The nurse retires, so the study coordinator will carry out the procedure instead.

Since this scenario involves no compromise to subject safety, the investigator must submit an amendment and await IRBMED approval before proceeding.

• A sponsor believes that study data to date indicate that a potential participant could safely participate but doesn’t meet currently approved eligibility criteria.

Since this scenario involves no compromise to subject safety, the investigator must submit an amendment and await IRBMED approval before proceeding.

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

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

What the report will include: The team member in question is relatively new to the position and was not familiar with the approved protocol. Therefore, they did not complete the case report forms appropriately. To assure this will not happen in the future; the team member will be trained on the completion of the case report forms and will be closely observed in the future to assure that all study procedures are completed appropriately and fully.

Report appointment deviations such as missed exams, tests, appointments or treatments, only when the subject is not withdrawn from the study (report withdrawn subjects in the Scheduled Continuation Review application).

Example: The clinic and lab are closed during the Holidays. All appointments will be moved to before or after the holiday for completion.

If a subject receives an incorrect dosage, medication, or intervention, due to misidentification or improper labeling, report the occurrence to the IRBMED. If the occurrence was not an adverse event (physical, social, or emotional harm or risk of harm), submit the occurrence as an ORIO. If it was an adverse event, submit it as an AE. Report the event or pattern, how it was/will be corrected or addressed, and how it will be avoided in the future.

Examples:

• Two subjects who should have received a substance abuse survey and interview instead received a 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.

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, lost laptop), 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 (734-615-4759) or anonymously (866-482-1252).

If you must commit a breach of confidentiality in order to comply with legal or ethical obligations, and if your informed consent document does not already note such a possibility, inform the IRBMED.

Examples:

• Lost laptop, which is reported to have unencrypted data on it.
• A stack of completed case report forms is left in the cafeteria.
• Investigator suspects potential child abuse during the course of a study. The report to the 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.

Report to the IRB in the event of a deviation from the IRBMED-approved consenting process or any other consenting problem. Report the event or pattern, how it was/will be corrected or addressed, and how it will be avoided in the future.

Examples:

• A subject participated in some part of a study (e.g., an eligibility screening procedure) prior to giving consent and signing the informed consent document.
• The currently approved informed consent document for the study was not used in the consenting process.
• Subjects did not receive a copy of the informed consent document used in the consenting process.
• Subject signed the informed consent document but was not given the opportunity to discuss and ask questions about the study.
• Proper records of the informed consent documents were not maintained.