Sponsor-Investigators and Site Principal Investigators (PIs) have responsibilities for managing non-compliance within Good Clinical Practice (GCP), the protocol and trial-related standard operating procedures (SOPs) in accordance with:
The terminology used to describe non-compliance within the protocol can be confusing. The terminology used in this toolkit is aligned with the NHMRC: Reporting of Serious Breaches of Good Clinical Practice (GCP) or the Protocol for Trials Involving Therapeutic Goods.
Any breach, divergence or departure from the requirements of Good Clinical Practice or the clinical trial protocol. This definition may be expanded to include the following clarifying principles taken from TransCelerate: Protocol Deviation Process Guide:
- An event occurred (eg not theoretical).
- The event is related to the protocol or documents referenced in the protocol (eg laboratory manual).
- The event is independent of fault, blame or circumstance (eg participant refused a procedure, sample tube broke en route to central laboratory).
Depending on the trial protocol, the Sponsor-Investigator may choose to further distinguish deviations as minor or major and provide these definitions in the protocol and associated SOPs.
A report that is judged by the reporter as a possible serious breach but has yet to be formally confirmed as a serious breach by the sponsor.
A breach of Good Clinical Practice or the protocol that is likely to affect to a significant degree:
- The safety or rights of a trial participant, or
- The reliability and robustness of the data generated in the clinical trial.
Note: This definition of serious breach comes from National Health and Medical Research Council (2018), Reporting of Serious Breaches of Good Clinical Practice (GCP) or the Protocol for Trials Involving Therapeutic Goods, and differs from the definition in the Australian Code for the Responsible Conduct of Research.
The GCP does not provide a definition for deviation. Instead it refers to the term compliance, meaning 'Adherence to all the trial-related requirements, Good Clinical Practice (GCP) requirements, and the applicable regulatory requirements'.