What is the difference between a protocol deviation and a protocol violation?
In the December 2008 Compliance Program Guidance Manual or Clinical Investigator Inspections, the agency does not differentiate between a protocol deviation and violation. “A protocol deviation/violation is generally an unplanned excursion from the protocol that is not implemented or intended as a systematic change.
A protocol deviation could be limited prospective exception to the protocol. Like protocol amendments, deviations initiated by the clinical investigator must be reviewed and approved by the IRB and the sponsor prior to implementation, unless the change is necessary to eliminate apparent immediate hazards to the human subject (21 CRF 312.66) or to protect the life or physical wellbeing of the subject, and generally communicated to the FDA. Protocol deviation is also used to refer to any other, unplanned instances of protocol noncompliance. For example, situations in which the investigator failed to perform tests or examinations as required by the protocol, or failures on the part of the study subjects to complete scheduled visits as required by the protocol, would be considered protocol deviations.”
The critical piece here is how the sponsor and site define a protocol deviation/violation in their SOPs and more importantly that these deviations are evaluated by the PI and the sponsor to determine if a corrective action is indicated or an amendment to the protocol. My experience has been that during the Sponsor – PAI the FDA Investigator will request a list of protocol deviations and will look for evidence of sponsor follow-up to these deviations. Consistent protocol deviations from a specific investigator warrant consideration to terminating the site. Frequent protocol deviations cannot result in good quality data. Both sponsor and site organizations should have a process in place for identifying, tracking, and reporting protocol deviations/violations. Most importantly there should be a process for evaluating the FDA Guidance for Industry Electronic Source Documentation in Clinical Investigations.
Do you have the processes in place to support these requirements? Whether you are a sponsor or a site, this newly issued draft guidance applies to you. This newly released guidance permits the direct documentation of data into the eCRF. However, both the site and the sponsor must have the processes in place to ensure continued data integrity. Sites must maintain a list of data originators, the site must have processes in place around password security and systems access, the Investigator must conduct ongoing review of data as it is recorded to ensure the safety of the subjects, real-time transmission of data must be managed in such a way as to ensure only reviewed data is released to the sponsor. These processes are critical to ensuring compliance with this new draft guidance. Keep in mind that even a draft guidance represents the agencies current thinking on a process.
Justin Time GCP can help you ensure that you have the processes in place to meet this guidance.