May 2025

The IRB expects each principal investigator and the study team to comply with all ethical standards, institutional policies, applicable regulations and the approved protocol. However, a deviation from such ethical standards, institutional policy, applicable regulation, and approved protocol can occur, and such deviations must be appropriately reported, reviewed and managed.

What is a protocol deviation?

The term “protocol deviation” is not defined by either DHHS human subjects regulations (45 CFR 46) or FDA human subjects regulations (21 CFR 50). The JHM IRB defines a protocol deviation as a departure from the approved protocol’s procedures made with or without prior IRB approval. Such departures may be major or minor/administrative in nature (see below).

When and how should a PI report protocol deviations to the JHM IRB and the sponsor?

There are several types of deviations from protocol procedures recognized by the JHM IRBs, and each type has a different IRB reporting requirement:

A. Emergency Deviations require prompt reporting to the IRB promptly after they occur

1. Emergency deviations are those occurring in an emergency situation, such as when a departure from the approved protocol is required immediately to protect the life or physical well-being of a participant. In such cases there might be no time to prospectively seek the approval of the IRB before implementing the urgent deviation. If an emergency deviation was implemented without approval by the IRB, such deviation   must be reported to the JHM IRB and the sponsor  as soon as possible, but not later than 5 days after the emergency situation occurred (21 CFR 812.150(a)(4))*. The PI must submit a report to the JHM IRB  in eIRB via a Further Study Action for Protocol Event Report. Deviations of this nature are always considered to be unanticipated problems involving risks to subjects or others (see the Organizational Policy on Prompt Reporting of Reportable Events)

* (Note that the reporting standard in 21 CFR 812.150(a)(4), which applies to studies involving Investigational Device Exemptions, shall apply broadly to all emergency deviations at JHM).

B. Non- Emergent deviations require approval by the IRB before they occur

Non- emergent deviations or planned deviations are considered t changes in researchand the IRB must approve these changes before the proposed change is implemented (via submission of a Further Study Action for Change in Research in eIRB). Examples include exceptions to eligibility criteria, exceptions to the form and manner of obtaining informed consent, and exceptions to the schedule of administration of an investigational product.

If a planned major, non-emergent deviation occurs without prior IRB approval, the event is non-compliance which must be reported promptly to the IRB via Further study Action as a Protocol Event Report in eIRB. A PI’s failure to report promptly any major, non-emergent deviation for which the PI did not obtain prior approval is itself an incident of non-compliance. Incidents of non-compliance must be reported, in accordance with the Organizational Policy on Prompt Reporting of Reportable Events and such reported events will be reviewed and managed in accordance with this policy.

C. Minor or administrative protocol deviations identified after they have occurred require reporting to the IRB at continuing review

Minor or administrative deviations are those which do not “affect the scientific soundness of the research plan or the rights, safety, or welfare of human subjects.”  If a protocol deviation occurs which meets this definition and is identified after its occurrence (e.g. a minor documentation error on the consent), the deviation must still be reported to the JHM IRB at the time the continuing review application  using the Protocol Deviation Summary Sheet (R.F. 4).

What are the protocol deviation reporting requirements for commercially sponsored research?

Sponsored research agreements may require the PI to notify the sponsor of all unplanned deviations or departures from IRB approved protocol procedures. Sponsor reporting requirements for deviations may differ from JHM IRB reporting requirements. It is the PI's responsibility to comply with the reporting requirements outlined in the signed contract. Before a PI signs a research agreement, the PI is strongly advised to read and understand the contract terms. If investigators have any questions regarding a sponsor’s specific deviation reporting requirements, they should check with the sponsor and obtain clarification before the study enrollment begins.

If a deviation occurs and the study team has questions about the reporting requirements, investigators must immediately consult with the IRB and/or the sponsor in regard to the notification requirement.

 Does the FDA Good Clinical Practice (GCP) Guidance affect reporting of deviations?

Many sponsors require investigators to follow Good Clinical Practice (GCP) guidelines. The GCP Guidance for Industry states:

“The investigator should not implement any deviation from, or changes of the protocol without agreement by the sponsor and prior review and documented approval/favorable opinion from the IRB…of an amendment, except where necessary to eliminate an immediate hazard(s) to trial subjects, or when the change(s) involves only logistical or administrative aspects of the trial (e.g., change in monitor(s), change of telephone number(s)).”  (4.5.2 at  https://www.fda.gov/media/93884/download)