While semaglutide was listed on the PBS for type 2 diabetes in July 2020, it wasn’t until four years later that NAION, the rare but severe eye disorder linked to the GLP-1 RA class, made it onto the TGA’s radar after being flagged in a study in JAMA Ophthalmology.

The TGA then began monitoring the association, and it took another two years before product information was updated across the class this July to warn patients about the potential risk.

It’s one example – but not an unusual one – of adverse events going unnoticed or under-recognised for years.

A national Healthed survey of 1500 GPs in August found that in the past 12 months, 14% had observed at least one adverse event that was not listed in the product information.

There’s often a gap between what adverse events are identified in early clinical trials and what becomes apparent after widespread commercial use. This is why the AMA’s Code of Ethics requires doctors to report suspected adverse events, noting that mandated pre- and post-marketing studies “are inherently limited in their ability to detect rare or unexpected consequences of use of a drug or medical device,” especially in vulnerable populations.

But how often are doctors actually reporting adverse events?

The Healthed poll found that just 7% of GPs had reported at least one adverse event to the TGA in the previous 12 months. This is significantly lower than the 14% who observed an adverse event not in the PI. The survey didn’t ask about adverse events that were listed in the PI.

Australia introduced the Black Triangle Scheme in 2018 to improve adverse event reporting for new medicines and older medicines that have been approved for a new indication. Yet it has not led to a meaningful rise in the number of reports.

Dr Eyob Alemayehu Gebreyohannes of Adelaide University’s Quality Use of Medicines and Pharmacy Research Centre led a recent study of around 400 people, including consumers, doctors, pharmacists and nurses. The research found that only about half of the health professionals and just 10% of the consumers were aware of the scheme.

While the scheme aims to flag that a medicine is new and help build the safety profile, 49% of health professionals in the study incorrectly thought the black triangle symbol meant there were known safety issues associated with the drug, and 40% wrongly thought it meant the medicine was considered high risk.

Of the 138 health professional participants in the study, around 45% had never reported an adverse event.

To that end, one in four GPs surveyed by Healthed said they were “not at all familiar” with the reporting process, and only one in 10 said they were “very familiar.”

The bar to report should be low

In its code of ethics, the AMA advises that you don’t need to be sure about something to report it to the TGA.

“Cases in which there is clearly a causal relationship between use of a drug/device and an adverse event, especially a serious event, will be rare. Physicians need not be certain that there is such an event, or even that there is a reasonable likelihood of a causal relationship, to suspect that an adverse event has occurred,” the AMA says.

Dr Gebreyohannes said his research had found a gap between the value GPs place on reporting side effects to the regulator and the actual rates of reporting.

Like the Healthed survey, he said his formal and informal surveys show some healthcare professionals felt the process was too onerous and wanted better software integration.

What’s stopping GPs from reporting more?

Most GPs (68%) felt the reporting process was a “somewhat” worthwhile use of their time – with 18% describing it as very worthwhile and 14% saying it was not at all worthwhile.

Inefficiencies were a common gripe.

“I tried once and never again,” one GP in the survey commented. “It was a typical obtuse and non-intuitive pathway on the website and I gave up out of frustration after 30 mins of time wasted trying to progress.”

“It’s too complex, convoluted and time-consuming,” another said. “It discourages one to report minor adverse drug events.”

“The paperwork is complicated and can be time consuming. I appreciate the intent and support reporting – I am just not very good at it,” another GP commented.

What could make the process better?

Around 150 GPs offered suggestions to improve the system. While a handful felt the current process was already good enough, the majority felt a simpler, and more easily accessible system would help.

Many called for the integration of reporting into clinical or practice software.

While several respondents suggested a pop-up box or one-click option that would allow GPs to log an adverse event from within their clinical practice software, the best the TGA currently provides are templates for Best Practice and MedicalDirector.

These let doctors download a template form to their practice software, which pulls some information from the patient’s record, the GP enters other relevant info such as the adverse events, and it generates a report. The GP then saves the document and sends it to the TGA via email, fax or post.

Professor Mark Morgan, chair of the RACGP Expert Committee for Quality Care, said using the template would help “a little.”

But there are potentially better ways.

“When a GP ceases a regular medicine there is a pop up prompt to record the reason. It is a great idea to incorporate an option to send information to TGA.”

“The more straightforward it is to report, the more it will happen,” said Professor Morgan, professor of general practice at Bond University.

And better tracking of potential medication side effects could be achieved thanks to developments in big data – without demanding more from GPs.

“I think the voluntary reporting system for suspected adverse drug events should be supplemented by analysis of routinely collected GP data,” Professor Morgan said.

“Systems such as Primary Sense that analyse real-time de-identified primary care data could look for adverse events following the commencement of a medication,” he said. “The huge scale of Primary Sense and similar data analytic tools means that even rare adverse events are likely to be detectable.”

“The very modest cost of development of big-data approaches to adverse event monitoring would provide great value for identifying and quantifying rarer side effects.

“This passive monitoring would not rely on GPs or members of the public submitting voluntary notifications to the TGA’s Database of Adverse Event Notifications.”

Encouraging patients to make reports

Dr Gebreyohannes and his colleagues are developing a consumer-centric digital platform platform aimed at improving the detection, management and reporting of adverse drug events – and are seeking people to test it.

GPs can also help by explaining to patients that they can make a report themselves, especially regarding the specific medications and side effects the TGA is interested in, Dr Gebreyohannes said.

“These include side effects that lead to serious consequences like hospitalisation, prolonged hospitalisation, death, side effects that are not listed in the consumer medicine information leaflet or medicines that are listed under the Black Triangle Scheme,” he said.

In the meantime, Dr Gebreyohannes encouraged GPs to try the reporting process if they hadn’t already, noting it might not be as onerous as they think.