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Protocol Deviations

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Preventing Protocol Deviations:

Good protocol writing anticipates where problems might occur; flexibility is added to avoid protocol deviations. In particular, there should be a reason for each inclusion and exclusion criteria and these criteria should be adhered to rigidly. Study visit windows and and blood draw windows should be wide enough to prevent inadvertent protocol deviations when subjects can't keep visit appointments.

Protocol deviations or violations (referred to from here on simply as Protocol Deviations) are any alteration or deviation from the IRB-approved research plan as defined in the study protocol. Some institutions distinguish between the terms deviation and violation; at CHOP they are considered to be equivalent. Protocol deviations are not usually anticipated and those that result in harm or have the potential for harm are considered Unanticipated Problems involving risk to subjects and others. To distinguish between those that need prompt reporting as Unanticipated Problems and those that don't, the IRB divides protocol deviations into Minor and Major deviations.

Minor deviations can occur frequently during the course of a research study. For example, subjects may fail to show up for a scheduled clinic visits or it may be difficult to get all of the required blood samples at the specified times for a PK study. Although these are protocol deviations, the IRB considers them to be minor because they cause no harm and have no potential to cause harm to the research subject or others. Major deviations, on the other hand, are events that cause or could cause harm to subjects or others or that affect the fidelity of the research. Major deviations require prompt reporting as Unanticipated Problems. Minor deviations can be briefly summarized and reported with the next continuing review. For example: "5 subjects had visits one day outside the study window because these visits would have been on a Sunday."

Major Deviations:

  • produce actual harm to a participant or others (an AE);
  • have the potential to produce harm to a subject;
  • result in the enrollment of an ineligible subject;
  • cause a subject to be withdrawn from the study;
  • prevent the subject from being evaluable for the study's primary endpoint;
  • result in enrollment of more than the IRB-approved number of subjects.

Minor Deviations:

  • don't produce or have the potential to cause actual harm;
  • don't impact the integrity of the trial;
  • often can't be avoided due to subject's schedules (e.g. soccer match) or natural events (e.g., hurricanes)

Frequently Asked Questions

  1. When should a protocol deviation be reported to the IRB?

    Major protocol deviations should be reported promptly since the IRB considers these to be Unanticipated Problems. Minor protocol deviations should be summarized in narrative form and included as part of the study report at the time of continuing review, if a continuing review is required.

  2. What should be included in the Protocol Deviation Report?

    The report should be made in eIRB in the Reportable Events workspace and should include summaries of what happened, an analysis of why it happened and of an action plan describing the steps that have been/will be taken to prevent a recurrence.

  3. Can an investigator ever deviate from the protocol-defined research plan?

    An investigator may deviate from the protocol whenever necessary to protect the subject's health, rights or welfare. For example, a study medication should be stopped if a subject develops an medically significant adverse reaction during administration. The physician should provide whatever medical treatment is needed necessary to the subject, without regard to whether the medications are permitted in the protocol. There is an obligation to deviate from the protocol in emergent or urgent situations.

  4. Can the investigator deviate from the protocol for non-emergent, non-urgent situations?

    In non-urgent/emergent situations, the investigator should obtain IRB-approval for the planned deviation. Approval from the study sponsor or medical monitor may also be necessary but by itself is not sufficient. The investigator should submit a request for a "planned deviation" which is really a request for a "single subject" or "one-time" protocol amendment. If the investigator anticipates that there will be future requests for the same deviation, then the protocol should be amended.