Glossary
Protocol deviation
Any departure from the processes or procedures a study protocol defines, from a visit outside its window to enrolling someone who missed a criterion.
What does Protocol deviation mean in clinical research?
The CDISC Glossary defines a protocol deviation as a variation from processes or procedures defined in a protocol. Deviations usually do not preclude the overall evaluability of subject data for efficacy or safety, and good clinical practice recommends summarizing them by site and by category in the study report.[1]
They are frequent. A Tufts CSDD working group found that Phase II and Phase III protocols average 75 and 119 protocol deviations respectively, involving nearly one-third of enrolled patients, with oncology trials the highest. The study also found a strong positive relationship between the number of investigative sites and the number of deviations.[2]
Eligibility deviations matter most for enrollment, because a participant enrolled without meeting an inclusion or exclusion criterion may have to be withdrawn or have their data questioned. Practical note: many of those trace back to evidence missed or misread during screening, so document the source for every criterion before randomization. Identify links each criterion decision to the chart evidence behind it.
Sources
- 1.NCI Thesaurus C50996: Protocol Deviation (CDISC Glossary) · National Cancer Institute EVS / CDISC, 2026Quote: "A variation from processes or procedures defined in a protocol. Deviations usually do not preclude the overall evaluability of subject data for either efficacy or safety, and are often acknowledged and accepted in advance by the sponsor. NOTE: Good clinical practice recommends that deviations be summarized by site and by category as part of the report of study results so that the possible importance of the deviations to the findings of the study can be assessed."
- 2.Benchmarking Protocol Deviations and Their Variation by Major Disease Categories · Therapeutic Innovation & Regulatory Science (Tufts CSDD), via PubMed, 2022Quote: "The results of this working group study show that phase II and III protocols have a mean total of 75 and 119 protocol deviations, respectively, involving nearly one-third of all patients enrolled in each clinical trial." Also: "A strong positive relationship was shown between the number of investigative sites and the number of protocol deviations."