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Serious Adverse Events: Safety Monitoring & Reporting

A Serious Adverse Event (SAE) is a negative reaction to a medicinal product or device that can result in hospitalization, injury/harm or even death in extreme cases.

In Australia, the National Statement on Ethical Conduct in Human Research 2007 recognises that the Human Research Ethics Committee (HRECs) have a responsibility to oversee clinical trials and ensure that the potential risks are acceptable before granting approval for a clinical trial to go ahead.

Furthermore, the International Good Clinical Practise (GCP) guidelines outline the duties and responsibilities of the Sponsors and Investigators who must have processes put in place in the event of a serious adverse event occurring.

At Novotech CRO, our clinical trial solutions include Serious Adverse Event (SAE) reporting and Local Medical Monitoring (LMM) which ensures that the clinical trials who utilise our services are conducted with the safety of participants being a priority.

Types of Adverse Events

Safety Critical Adverse Events

Any adverse event which has been identified in the clinical trial protocol as being crucial to the safety evaluations that need to be reported to the Sponsor in compliance with the reporting requirements outlined in the protocol.

Adverse Event (AE)

An unfavourable sign (abnormal test results) or symptoms that occur during a clinical trial as a result of using the investigational medical product.

Serious Adverse Event (SAE)

Any event that results in hospitalization, disability or in extreme cases, death or life-threatening illness. Events that may not be life threatening or require hospitalization may also be labelled as ‘serious adverse events’, especially if they endanger the participant or require intervention.

Suspected Unexpected Serious Adverse Reactions (SUSARs) and Unanticipated Serious Adverse Device Effects (USADEs)

When a serious adverse event occurs as a result of the investigational drug or device, and its symptoms, severity or frequency is not consistent with the information found in the Investigator’s Brochure or in the up-to-date Australian Product Information document.

Important Documentation

Product Information (PI)

The Australian Product Information (PI) document is an approved summary of the scientific information which is crucial for the safe and effective use of a drug. This document should be used Australia-wide for all Investigational Medicinal Product (IMP) clinical trials. The PI can replace an Investigator’s Brochure (IB) if the investigational product has already been approved for public use.

Investigator’s Brochure (IB)

An Investigator’s Brochure (IB) is a collection of clinical and non-clinical data which focuses on the investigational products used in a clinical trial. It provides Investigators and trial staff with information to help their understanding of the clinical trial protocol, including dose, dose administration and safety monitoring.

Reference Safety Information (RSI)

References the information found in an Investigator’s Brochure or an approved Australian Product Information document which details possible adverse reactions and the frequency and nature of those adverse reactions.

Safety Monitoring and Reporting Responsibilities

Responsibilities of the Trial Sponsor

  • The trial Sponsor establishes safety monitoring processes which are adapted to the risk levels and size of each individual clinical trial.
  • In smaller clinical trials or Phase I trials, risks may be easier to identify during close monitoring, while the risks during larger trials or later phases are better understood through statistical analysis of treatments. Trial Sponsors should determine the most effective ways to carry out monitoring and be able to justify their monitoring process to the Human Research Ethics Committee (HREC).
  • Sponsors need to analyse all the safety information from Investigators as well as from other sources.
  • Ensure that the trial protocol has clear sections which outline
  • Assessment and management of the risks.
  • Safety reporting definitions, processes, responsibilities and reporting timelines
  • Serious adverse events that don’t need to be reported straight away.
  • Keep detailed and up-to-date documentation on all adverse events.
  • Assess and categorise the safety reports from Investigators.
  • Report all suspected unexpected serious adverse reactions to the Therapeutic Goods Administration (TGA).
  • Review the Investigator’s Brochure annually and update it accordingly. Provide the HREC and Investigators with the updated Investigator’s Brochure or Product Information document (when applicable).
  • Provide the HREC with an annual safety report which includes a description and analysis of new findings, a discussion of the impact of the safety data to the trial’s risk-benefit ratio and a description of the safety measures taken to minimise risks. This report allows the HREC to decide whether the clinical trial’s safety plan is being managed and followed effectively.
  • Notify the TGA, HREC and Investigators of any major safety issues that have an impact on the participants or the trial. These include:
  • Urgent Safety Measure (USMs): Notify the TGA, HREC and Investigators within 72 hours of the measures being implemented.
  • Temporary Pause of a Trial for Safety Reasons: Notify the TGA, HREC and Investigators within 15 days and inform them why the trial has been halted and what other measures are being taken.
  • Early Termination of a Trial for Safety Reasons: Notify the TGA, HREC and Investigators within 15 days of the termination and let them know why the trial has ended and what measures are being taken.

Responsibilities of the Principal Investigator

  • Assess all safety issues and respond in accordance with the Good Clinical Practice (GCP) guidelines.
  • Provide the Sponsor with relevant safety monitoring information so that a safety analysis can be carried out.
  • Assess all adverse events that occur at the clinical trial site.
  • Report all serious adverse events and urgent safety measures carried out by the site to the Sponsor within 24 hours of the event occurring.
  • Report to the Sponsor all safety critical events and any required information on reported fatalities.
  • Report all serious safety issues and Suspected Unexpected Serious Adverse Reactions (SUSARs) to the institution within 72 hours of the incident occurring.

Responsibilities of the Human Research Ethics Committee (HREC)

  • Need to be satisfied with the Sponsor’s safety monitoring and processes during the clinical trial.
  • Assess the safety of future and current clinical trials.
  • Analyse whether the risk-benefit ratio is satisfactory.
  • Ensure that the Sponsor has the proper processes in place to manage any risks.
  • Approve the Sponsor’s ongoing safety monitoring methods.
  • Keep reviewing the informed consent process and documentation when new potential risks and benefits are discovered.
  • Assess whether the risk-benefit ratios are consistent with ethical approval.
  • Inform the TGA, Investigators and institutions when approval is withdrawn.

Responsibilities of the Institutions

  • Ensure that clinical trial sites understand and act in accordance with Sponsor requirements.
  • Should be informed of any issues that require management.
  • Assess whether safety reports have an impact on any legal risks, conduct of research, or the trial’s site authorisation.
  • Develop guidelines on safety reporting and monitoring in clinical trials for Investigators.

Responsibilities of the Therapeutic Goods Administration (TGA)

  • Conduct an audit of a clinical trial when there are safety concerns.
  • Stop a trial from operating when it’s in the public’s interest.

CRO Companies and Serious Adverse Events (SAEs)

The trial Investigator can report any Serious Adverse Events to a CRO company directly which allows them to review each SAE in a timely manner. The CRO Company must then inform the Clinical Research Associate (CRA) who will then update the Case Report Forms (CRFs) accordingly.

Alternatively, the CRO Company can enter SAEs into a participant-specific safety database and then send regular updates to the Sponsor.


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