Protocol Deviation
Departure from the approved clinical investigation plan.
Definition
A protocol deviation is any change, divergence, or departure from the study design or procedures defined in the clinical investigation plan that does not have prior IRB/EC approval. Deviations range from minor issues, such as a visit slightly outside its window, to major ones that affect subject safety or data integrity, such as enrolling an ineligible patient. ISO 14155 requires them to be documented, assessed and reported, and recurring deviations should drive corrective action. Under 21 CFR 812.150, deviations to protect a subject in an emergency must be reported within five working days.What this means in practice
Significant deviations affecting subject safety, rights, welfare, or data integrity must be reported to the IRB/EC and sponsor. Trends in deviations indicate a need for site retraining or protocol amendment.Examples
- A clinical research coordinator administers a study drug at a dose slightly different from that specified in the protocol for one patient, without prior approval.
- A subject in a clinical trial misses a scheduled follow-up visit, and the visit window specified in the protocol is exceeded.
- An investigator enrolls a subject who meets most, but not all, of the pre-defined inclusion criteria outlined in the clinical investigation plan.
- •Failing to document minor deviations can obscure patterns indicating systemic issues or protocol flaws.
- •Not assessing the impact of a deviation on subject safety or data integrity can lead to overlooking serious risks.
- •Delaying the reporting of significant deviations can result in non-compliance and compromise study validity.
- •Ignoring repeated deviations at a site may indicate inadequate training or a need for protocol clarification rather than isolated incidents.
- •Misinterpreting which deviations require immediate reporting can lead to under-reporting or unnecessary administrative burdens.
Frequently asked questions
Cross-references
Part of
Related terms
Grouped by themeEditor's picks
· Hand-selected related conceptsBoard that reviews and approves human-subjects research at an institution.
Good clinical practice for clinical investigations of medical devices.
International standard for the design, conduct, and reporting of clinical trials.
Clinical Trials & Evidence
· From this learning pathCompilation of clinical and nonclinical information on an investigational device given to clinical investigators, establishes what's 'anticipated' for UADE determinations.
The pre-specified outcomes that determine trial success (primary), provide supporting evidence (secondary), or generate hypotheses (exploratory).
Trial design that pre-specifies opportunities to modify aspects (sample size, arms, endpoints) based on interim data.
Any untoward medical occurrence in a subject, whether or not related to the device.
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Sources
3 sourcesEvery citation below opens the original document. Each is graded against our source-tier hierarchy so you can see what rests on binding law versus commentary.
- 1ICH E6(R3) GuidelineTier 2 VerifiedICHdatabase.ich.org
- 2ClinicalTrials.govTier 3 VerifiedNIHclinicaltrials.gov
- 3ICH GuidelinesTier 2 VerifiedICHich.org
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