HerbalEGram: Volume 9, Number 10, October 2012

In August 2012, the Australian Government’s Therapeutic Goods Administration (TGA) launched its online Database of Adverse Event Notifications.¹ The database contains adverse event notifications relating to various “therapeutic goods,” which include conventional and botanical medicinal products for human use, reported from January 1971 up until 3 months prior to the date of database access. Of the database's current 251,000 adverse event notifications, 1,677 — approximately 0.67% — include herbal medicines reported to have been taken at the time of the adverse event.²

Different from side effects, which are the known and documented undesirable effects of a medicine or other ingested product, adverse events are “unwanted and sometimes harmful outcomes” that “may or may not be related to a medicine.”³ Because adverse event reports lack proof of causality, the TGA informs site visitors that “an adverse event report does not mean that the medicine is the cause of the adverse event.” While an adverse event could be due to the ingestion of the noted medicine, other factors could result in an adverse event, such as an underlying illness, the use of concomitant medications and/or foods, allergies and sensitivities, or a manufacturing issue independent of the inherent effects of the suspect natural ingredient. Or, TGA suggests, “It may be a coincidence that the adverse event occurred when the medicine was taken.”⁴  

“Causal relationships are not always easy to determine especially if the opportunity for rechallenge is not there,” said Alan Bensoussan, PhD, director of the University of West Sydney’s Centre for Complementary Medicine Research (email, August 20, 2012). “Yet, it would be a shame to lose this data which may contribute to early signals of potential problems. This data is useful particularly to regulators and manufacturers, who are charged directly with the responsibility to be aware of, and respon[d] to, adverse events, most specially [if] these adverse events are of a serious nature or of a minor nature but more frequent occurrence.”

In analyzing each adverse event report, TGA denotes a level of possible relation between the medicine and adverse event by labeling the medicine with one of the following classifications³:

1) Suspected: there is a possibility that the medicine caused the adverse event.

2) Not suspected: this medicine was taken at the time of the adverse event, but it is not suspected to be related to the adverse event.

3) Interaction: an interaction between two or more medicines is suspected to have caused the adverse event; this is usually based on a history in the literature of interactions between the medicines concerned.

According to the TGA, “If there is no suspected link between any medicine and the adverse event, that report will not be included in data analysis.”⁵ The adverse event notifications available in the online database were reported by individual consumers, health professionals, and therapeutic goods companies, and include a range of adverse events, from minor flatulence and nausea to death.

A database search in August 2012 for the word “herb” returned 817 herbal medicine products for which adverse events have been reported (as of press time).² During the approximate 41 years of recorded information, 1,677 cases of adverse events in which an herbal medicine was reported and 1,364 in which only an herbal medicine was reported (which, according to TGA, suggests that “there is a possibility that the medicine caused the adverse event”).² This represents just 0.67% of the 251,000 total reports. (Because some patients’ reports list multiple adverse events [i.e., nausea, cramping, etc.], these figures do not represent the number of separate adverse events, but rather the number of reports.⁴)

“The number of adverse events reported for herbal medicines in Australia is extremely low compared to the number of pharmaceutical [adverse drug reactions] (ADRs),” said Dr. Bensoussan. “Whilst it is likely there is some degree of under-reporting of herbal ADRs by the community, studies consistently report the significantly lower levels of ADRs with herbal medicines compared to pharmaceutical drugs. This is consistent with their premarket evaluation and regulation as low-risk products. Unless there appear particularly serious adverse events, or repeated events with a product or ingredient, these data generally do not raise serious concern.” 

Of the 1,689 adverse event reports associated with herbal medicines, 11 deaths have been reported since 1971.² The database features various terms describing death from the Medical Dictionary for Regulatory Activities (MedDRA) — which are used internationally to describe medical products, conditions, and devices — including myocardial infarction, cardiac arrest, etc. MedDRA also emphasises that deaths are considered outcomes.

“The AE describes the adverse clinical presentation that may or may not be triggered by the intervention,” said Dr. Bensoussan. “The outcome of that clinical presentation may be complete recovery or permanent injury or death. Hence the separation between the initial presentation and the outcome. These outcomes may not be causally related to herbal medicines use. Assuming they were all caused by herbal intervention, this would still represent a very low level of mortality compared with pharmaceutical and other medical interventions.”

The TGA launched the online database in order to increase the government’s transparency and release more information to the public so that citizens can better understand TGA operations and decisions. According to TGA’s website, “It is also hoped that access to this information will support the quality use of medicines and stimulate reporting of adverse events.”¹

—Lindsay Stafford Mader


References

1. Database of Adverse Event Notifications. Therapeutic Goods Administration website. Available at: www.tga.gov.au/daen/daen-entry.aspx. Accessed August 13, 2012.

2. Database of Adverse Event Notifications List of Reports. Search term “herb” from January 1, 1971 to May 22, 2012. Australian Government. Department of Health and Ageing, Therapeutic Goods Administration.

3. About adverse events: what is an adverse event? Database of Adverse Event Notifications: consumer questions and answers. Updated August 1, 2012. Available at: www.tga.gov.au/safety/daen-consumer-qa.htm. Accessed August 7, 2012.

4. About the Database of Adverse Event Notifications. Therapeutic Goods Administration website. Available at: www.tga.gov.au/safety/daen-about.htm. Accessed August 13, 2012.

5. Overview of how TGA manages adverse event reports. Therapeutic Goods Administration website. Available at: www.tga.gov.au/safety/daen-report-management.htm. Accessed August 13, 2012.