Safety Reporting

NHMRC Safety Reporting

The National Health and Medical Research Council (NHMRC) has guidance on Safety Monitoring and Reporting in Clinical Trials Involving Therapeutic Goods (the Guidance), which is supported by the NSW Office for Health and Medical Research (OHMR) who fully supports implementation of the Guidance. Researchers and Sponsors are required to adopt the safety reporting guidelines.

The NSW Health Policy Directive on Safety Monitoring and Reporting for Clinical Trials Conducted in NSW Public Health Organisations sets a standard framework for safety monitoring and reporting in clinical trials, outlining roles and responsibilities to ensure consistent practice and protect participant wellbeing across all Public Health Organisations. The NSW Policy Directive can be accessed here.

NB: The below tables only show the events that should be reported to the HREC and RGO, For further details on the safety monitoring/reporting responsibilities of the HREC, Principal Investigator, TGA, Institution and Sponsor please refer to the guidelines here. Safety events for research studies are required to be submitted via REGIS, quick reference guides on how to submit are available here.

Definitions
• Adverse Event (AE): Any untoward medical occurrence in a patient or clinical trial participant administered a medicinal product and that does not necessarily have a causal relationship with this treatment.
• Adverse Reaction (AR): Any untoward and unintended response to an investigational medicinal product related to any dose administered. All adverse events judged by either the reporting investigator or the sponsor as having a reasonable possibility of a causal relationship to an investigational medicinal product would qualify as adverse reactions.
• Suspected Unexpected Serious Adverse Reaction (SUSAR): An adverse reaction that is both serious and unexpected.
• Unanticipated Serious Adverse Device Effects (USADEs): A serious adverse device effect which by its nature, incidence, severity or outcome has not been identified in the current version of the risk analysis report (and/or Investigator’s Brochure/Instructions for Use).
• Urgent Safety Measure (USM): A measure required to be taken in order to eliminate an immediate hazard to a participant’s health or safety.
• Significant Safety Issue (SSI): A safety issue that could adversely affect the safety of participants or materially impact on the continued ethical acceptability or conduct of the trial.
• Unexpected & Related SAEs (URSAE): An adverse event that is:
     Serious – meets the definition of a serious adverse event 
     Related – resulted from administration of the trial intervention 
     Unexpected – the event is not described in the protocol as an expected occurrence.

Summary of safety notifications to the HREC and RGO (therapeutic goods trials)

*Note: For trials where Sydney Local Health District is the Sponsor, the Sponsor functions are delegated to the Coordinating Principal Investigator

Reporting pathway for therapeutic good trials

Summary of notifications to the HREC and RGO (non-therapeutic goods trials)

*Note: For trials where Sydney Local Health District is the Sponsor, the Sponsor functions are delegated to the Coordinating Principal Investigator

Reporting pathway for non-therapeutic good trials

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 has low/minimal impact

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.

The NHMRC guidelines does not use the terms Protocol Deviation or Protocol Violation

Serious breaches should be reported to the reviewing HREC, usually by the Sponsor within 72 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.

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.

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.

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 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:

·         Corrective and Preventive Action (CAPA) form

·         SLHD Audit Preparation Tool

·         SLHD Audit-Ready training