Planned Protocol Deviations

A “planned deviation” occurs when an investigator prospectively and intentionally plans to deviate from the protocol requirements. Examples include enrollment of a subject who does not meet eligibility criteria, conducting a procedure out of the defined window, or allowing a prohibited concomitant medication.  Most planned deviations are one-time requests for a single participant.

For clinical investigations, the PI must obtain IRB approval before purposefully deviating from the protocol unless the deviation is to prevent imminent harm to subjects.  (See 21 CFR 312.66) Sponsor approval of planned deviations is also necessary.

In This Section 

How Do I Submit a Planned Deviation Request?

Submit an Modification to the IRB before implementing any changes.

What Information Must be Included in the Submission?

  • Documented approval from the study sponsor, medical monitor and other oversight entities, as applicable
  • A description of the deviation including:
    • Page and section of the protocol where the applicable procedure is described
    • Proposed date of the deviation
    • A rationale for the deviation
    • Clarification as to whether the request is for a single participant
    • Any plans for communicating the planned deviation to the subject
  • A statement indicating whether the deviation will result in increased risk to the participant and a description of the risks
  • Description of the benefit to the participant that might result from the planned deviation
  • Description of the impact of the planned deviation on data integrity

If the deviation needs to occur within the next 10 days, send an IRBNet project mail requesting a rush review along with a rationale for the rush and the proposed date of the deviation.

Example:  Page 16, Section 5.3 of the protocol requires subjects to be randomized within 21 days of screening.  Due to a recent hospitalization with pneumonia, patient XYZ will be at least 29 days from window before she can be randomized. The sponsor has approved enrollment of this subject up to 35 days from screening if her chest x-ray is unchanged from baseline and her CBC is within normal limits.  We plan to randomize and dose this patient on Wednesday, 01/03/2017, which will be 32 days from screening.  The risks will not be increased with this plan because the study medication is not expected to affect this participant’s immune or respiratory system.  The subject can clearly benefit from staying in this study because there are no other alternatives available to treat her renal insufficiency.  This deviation is not expected to have any effect on data integrity.  We would appreciate a rush review of this submission so that approval is received before 01/03/2017.

Other issues to consider when submitting a request for a planned deviation:

  • Whether the participant should be provided with a revised consent form or an addendum to the consent that includes a description of the deviation
  • Whether the protocol should be permanently modified

How Does the IRB Review Planned Deviation Requests?

Rush requests for planned deviations are assigned for immediate processing.

For all planned deviation requests that are not time-sensitive, IRB review and screening of the submission will follow IRB Administration’s normal procedures. Upon receipt of a planned deviation request, the submission will be assigned to the appropriate IRB administrator for screening and an assessment of the level of IRB review required.

What Will the IRB Consider When Reviewing Planned Deviations?

  • The time sensitivity of the request
  • The level of risk involved in both the study itself and the planned alteration.
  • Whether approval of the planned deviation is in the best interest of the subject
  • Whether the planned deviation request holds out the prospect of direct benefit to the subject
  • Whether the risk/benefit ratio specifically related to the planned deviation request is favorable