Protocol deviation and violation.

WHAT IS THE DIFFERENCE BETWEEN PROTOCOL DEVIATION AND PROTOCOL VIOLATION?

Some suggested definitions are as follows:

Food and drug administration

Compliance Program Guidance Manual

Bioresearch monitoring clinical investigators

A protocol deviation/violation is generally an unplanned excursion from the protocol that is not implemented or intended as a systematic change

Protocol deviation is also used to refer to any other, unplanned, instance(s) of protocol noncompliance

EFGCP Audit Working Party 2001

Protocol violation: Serious non-compliance – may lead to exclusion of patients from eligibility analysis and/or their discontinuation from the study

Protocol deviation: Less serious non-compliance – may not render a patient ineligible

Norman M. Goldfarb Journal of Clinical Research Best Practices Nov 2005

Protocol deviation. A protocol deviation occurs when, without significant consequences, the activities on a study diverge from the Institutional Review Board-approved protocol, e.g., missing a visit window because the subject is traveling. Not as serious as a protocol violation.

Protocol violation. A divergence from the protocol that materially (a) reduces the quality or completeness of the data, (b) makes the Informed Consent Form inaccurate, or (c) impacts a subject's safety, rights, or welfare. Examples of protocol violations may include the following:

Inadequate or delinquent informed consent

Inclusion/exclusion criteria not met

Unreported serious adverse events

Improper breaking of the blind

Use of prohibited medication

Incorrect or missing tests

Mishandled samples

Multiple visits missed or outside permissible windows

Materially inadequate record keeping

Intentional deviation from protocol, Good Clinical Practice, or regulations by study personnel

Subject repeated non-compliance with study requirements