Reporting Adverse Events

An adverse event can be defined as an unintended occurrence associated with the use of a therapeutic good. This may be related to the use of a medicine, vaccine, or medical device. Adverse events are a leading cause of unplanned hospital admissions and deaths. Some studies suggest that medication-related adverse events contribute to between 10% and 30% of all hospital admissions in older patients.

Improving the understanding of adverse events is an important part of ongoing monitoring activities. The Therapeutic Goods Administration (TGA) regulates therapeutic goods in Australia and collects adverse event reports. Reporting suspected adverse events to the TGA is important as it allows safety issues to be identified early. Reports can be submitted by consumers, healthcare professionals, pharmaceutical companies, and medical device suppliers.

What is the purpose of reporting?

When a therapeutic good is first registered on the Australian Register of Therapeutic Goods, information on its safety and efficacy may be limited to clinical trials. Clinical trials do provide important information on adverse events. However, they cannot detect all possible adverse events for a number of reasons, including:

• The duration of a clinical trial may not be sufficient to detect events that take time to develop
• The trial population may not be large enough to detect very rare events
• The population may not be diverse enough to detect events that are more likely in specific patient groups (e.g. those with certain comorbidities, specific age groups, etc.).

This is why ongoing safety monitoring activities are so important. The TGA collects adverse event reports in the Database of Adverse Event Notifications (DAEN). There is a separate database for medicines and medical devices. Reports can be made for all medicines. This includes prescription and non-prescription medicines and complementary medicines such as herbal preparations and nutritional supplements.

The TGA is particularly interested in reports related to:

• New therapeutic goods (the Black Triangle Scheme helps to identify prescription medicines that are new or being used in a different way. For these medicines, the black triangle symbol appears on the product information (PI) and consumer medicine information (CMI) with a reminder to report adverse events);
• Medicine and/or vaccine interactions;
• Unexpected adverse events (i.e. those that do not appear in the product information or product labelling); and
• Serious adverse events (including those suspected of causing death, hospitalization, absence from productive activity, increased investigational or treatment costs, and birth defects).

The TGA encourages reporting of all suspected adverse events. It is not necessary to be certain that a particular therapeutic good caused the adverse event. Even where causality is uncertain, an individual report is still valuable as it contributes to the overall safety data for that therapeutic good. Each report helps the TGA assess the possible role the therapeutic good played in causing the adverse event and helps expand the known safety profile of the therapeutic good.

How to report:

Adverse event reports for medicines and vaccines can be submitted online. Reports can be quickly submitted without registering. However, registering yourself as a user provides additional features such as pre-populating your contact details and the ability to save drafts and view or amend previously submitted reports.

Alternatively, reports related to a vaccine can be submitted via email, fax, or mail using the National Adverse Events Following Immunisation (AEFI) reporting form. Reporting adverse events for vaccines provided under the National Immunisation Program (NIP) can be done via the local health authority who will then share the information with the TGA.

When submitting an adverse event report to the TGA, it is helpful to provide as much detail as possible. The following information is considered the minimum required:

• Your contact details (so that further information can be sought if required);
• Patient identifier (e.g. initials, date of birth, or age. The patient’s name should not be used);
• Details of the product involved; and
• Details of the suspected adverse event.

Outcomes:

The TGA uses information from adverse event reports to identify potential safety signals. When a safety signal is recognised, a detailed evaluation is conducted to establish the therapeutic good’s possible role in the event.

In Australia, it is mandatory for sponsors to report serious adverse events suspected of being related to their therapeutic good. However, reporting by healthcare professionals and consumers is voluntary. It is thought that less than 5% of adverse reactions are actually reported. Under-reporting has the potential to allow rare adverse events to go undetected for longer.

The following actions may be taken by the TGA in response to a safety signal:

• Publishing a Medicines Safety Update or Safety Alert on the TGA website
  • For example, a safety alert was recently published to highlight the potential for liver injury with Garcinia gummi-gutta (Garcinia cambogia) or hydroxycitric acid (HCA).
• Communicating the new safety information to healthcare professionals. This may include details of how to prevent an adverse event or assess risk factors in patients.
• Updates to the product labelling or PI and CMI documents
  • For example, an updated warning regarding the rare risk of cardiovascular death was added to the PI for azithromycin. In this case, there was insufficient evidence to establish or exclude causality. However, the warning provides further information to prescribers and may prompt clinicians to consider screening high-risk patients.
• Limiting the population the product can be used in
  • For example, oral promethazine products should not be used in children under six years of age due to the increased risk of adverse events in this population
• Suspending or cancelling the registration of the product
  • For example, the TGA cancelled the registration of pholcodine cough medicines in 2023 for safety reasons. An investigation found a link between pholcodine use and anaphylactic reactions to neuromuscular blockers during general anaesthesia. The decision to cancel pholcodine products took into account the severity of the potential reaction, the limited efficacy of the product, and the ready availability of therapeutic alternatives.
• Recalling a product
• Requiring the sponsor to conduct postmarket studies if additional information is required

Conclusion:

Reporting adverse events is essential for the ongoing safety monitoring of therapeutic goods. It helps to identify less common adverse events and populations that may be more susceptible. Healthcare professionals are encouraged to submit adverse event reports to support the ongoing monitoring of therapeutic goods in Australia.

If you would like to learn more about reporting adverse events, the Australian Commission on Safety and Quality in Health Care provides an online learning module.