Question: What are the requirements for submitting protocol deviations?

Question:

What are the requirements for submitting protocol deviations?
- Clinical operations lead at a pharmaceutical company

Answer:

It depends on what you mean by deviation.  Some deviations from the IRB approved protocol are planned while others are unintentional or unplanned. 

Planned deviations

The FDA and HHS (45 CFR §46.103(b)(4) and 21 CFR §56.108(a)(4)), position is that, except when necessary to eliminate an apparent and immediate hazard to human subjects, deviations from the approved protocol are considered changes to the protocol. These “planned deviations” or changes to the protocol require submission to the IRB for review and approval prior to their implementation.

Unplanned deviations

For unplanned or unintentional deviations that may be discovered after they occur, the FDA and HHS regulations (45 CFR §46.103(b)(4) and 21 CFR §56.108(a)(4)) are clear that the IRB needs to be informed when the deviation represents an unanticipated problem posing risk to subjects or others.  Deviations that represent serious or continuing noncompliance also require reporting to the IRB even when the deviation is discovered after it occurs.

Beyond those explicit requirements, there is little guidance from FDA or OHRP on how handle a one-time deviation from a protocol. For example, the enrollment of a subject who does not meet the inclusion criteria for a lab test that may be out of range for the protocol but not clinically significant or a change in the timing of a study visit).  However, the WCG IRBs’ policy is that these deviations require submission, review and approval by the IRB.  These submissions are often eligible for expedited review.

About the Author

Yvonne Higgins | Quality Assurance Advisor, Compliance

Yvonne has contributed to the cause of ethics and responsibility in human research for more than 20 years. During that time, she has served as Vice President of Quality Management for Copernicus Group IRB, Executive Director of the human research protections program (HRPP) and Institutional Review Boards (IRBs) at the University of Pennsylvania, Co-Chair of the workshop and didactic planning committee for PRIM&R’s Advancing Ethical Research annual conference, and Public Health Analyst within the US Department of Health and Human Services Office for Human Research Protections (OHRP).

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