Protocol Non-compliance & Serious Breaches

PROTOCOL NON-COMPLIANCE IN CLINICAL TRIALS

Protocol deviations / violations 
A Protocol ‘deviation’ or ‘violation’ is any breach, divergence or departure from the requirements of Good Clinical Practice (GCP) or a study protocol. Protocol deviations/violations can be minor or major. A minor deviation/violation does not impact patient safety, data integrity, or study objectives. A major deviation/violation has or has the potential to affect patient safety, data integrity, study outcomes, or regulatory compliance. 

GCP requires all deviations to be reported to and collated by the sponsor so that corrective and preventative action can be implemented and so that their impact on the analysis of the data can be considered when the clinical study report is produced.

The Principal Investigator should perform a risk assessment to determine the severity and impact and whether the deviation/violation constitutes a serious breach. 

Serious Breaches 
Serious breaches should be reported in accordance with NHMRC Guidelines document: Reporting of Serious Breaches of Good Clinical Practice (GCP) or the Protocol for Trials Involving Therapeutic Goods 2018. The NHMRC guidance does not use the terms Protocol Deviation or Protocol Violation.

A serious breach is 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 a clinical trial.

It is the responsibility of the Principal Investigator to (i) report any suspected breach to the sponsor within 72 hours of becoming aware of it and (ii) to report to their institution (via the Research Governance Officer) within 72 hours any serious breach that has been confirmed by the sponsor as occurring at their site.

Serious breaches should be reported to the reviewing HREC, usually by the Sponsor within 7 calendar days of confirming a serious breach has occurred. The HREC will review the serious breach to evaluate its impact on the continued ethical acceptability of the study and to satisfy itself that the serious breach is managed appropriately.

Reporting Responsibilities

*SLHD-sponsored clinical trials
Where SLHD has agreed to sponsor an investigator-initiated clinical trial, the Coordinating Principal Investigator / Principal Investigator (at SLHD) must take on sponsor reporting responsibilities in accordance with GCP (Sections 2.5 & 3.9).

The Principal Investigator must document all protocol deviations/violations and submit a report to the SLHD HREC and RGO with their annual or quarterly (RPAH) report. The Principal Investigator should perform a risk assessment to determine the severity and impact and whether the deviation/violation constitutes a serious breach. If a serious breach has been determined, the Principal Investigator must report it to the HREC and TGA (if CTN) per the reporting timeframes above. A Corrective and Preventive Action (CAPA) plan should be submitted with the report.  

SLHD researchers are recommended to use the following resources to monitor their trials and conduct self-assessments:

•    TransCelerate Protocol Deviations Guidance & Log Proforma 
•    TransCelerate Protocol Deviation Process Guide
•    Corrective and Preventive Action (CAPA) form
•    SLHD Audit Preparation Tool 
•    SLHD Audit-Ready training