Editorial: Reporting adverse drug events to the Therapeutic Goods Administration

Full text

2
VOLUME 44 : NUMBER 1 : FEBRUARY 2021
Full text free online at nps.org.au/australian-prescriber © 2021 NPS MedicineWise
Jennifer H Martin
Chair1
Senior staff specialist2
Catherine Lucas
Lecturer1
Staff specialist2
1 Discipline of Clinical
Pharmacology, School of
Medicine and Public Health,
University of Newcastle,
New South Wales
2 Hunter New England
Health, Newcastle, New
South Wales
Keywords
adverse drug reaction
reporting systems,
drug-related side effects
and adverse reactions,
Therapeutic Goods
Administration
Aust Prescr 2021;44:2–3
https://doi.org/10.18773/
austprescr.2020.077
EDITORIAL
Reporting adverse drug events to the
Therapeutic Goods Administration
awareness that adverse events are common and
should be reported, their absence may have led to
less reporting. Medicines Safety Update is now only
published as relevant topics arise rather than in a
bimonthly scheduled publication, as was previously
the case, thereby reducing the profile of reporting.
Probably less than 5% of adverse reactions are
reported, even in countries where reporting is
mandatory.4 A European systematic review found
that the median rate of under-reporting by healthcare
professionals was 94%.5 Despite the limitations of
voluntary adverse drug reaction reporting systems,
they remain the most common and inexpensive
method of collecting data to generate safety signals.
In Australia, it is mandatory for pharmaceutical
companies to report all serious adverse events
suspected of being related to their drugs, but
reporting by health professionals has always been
voluntary. Without robust reporting mechanisms
supporting the detection of safety signals, rare
adverse drug events may remain undetected for
years, exposing patients to unanticipated risks.
Examples of high-profile drug withdrawals include
lumiracoxib (associated with severe hepatotoxicity),
which only occurred after thousands of patients in
Australia had been exposed.6
Neuropsychiatric adverse events associated
with montelukast, and euglycaemic ketoacidosis
associated with sodium-glucose co-transporter 2
inhibitors, are rare adverse effects detected only by
careful pharmacovigilance analysis. The Australian
pharmacovigilance system detected an outbreak of
hyoscine hydrobromide toxicity due to wide variations
in the concentration of the active ingredient.7
There is a need to understand the reasons for
under-reporting. We need to consider the different
motivators and barriers that influence the likelihood of
completing and sending reports to the TGA. What has
changed? For example, has the removal of the blue
card reduced awareness of pharmacovigilance?
Recognising an adverse event is a key issue, however
even when it is recognised it may not be reported.
Definitions of medicine-related harm are multiple
and varied8 and this may make medical staff anxious
if they are uncertain of the diagnosis. Available
tools include the Naranjo Adverse Drug Reaction
Probability Scale.9 A possible solution is to have
In Australia the Therapeutic Goods Administration
(TGA) monitors the safety of medicines to improve
the understanding of their possible adverse effects.
Adverse events are the harmful and unintended
consequences of medicine use. They are a leading
cause of unplanned hospital admissions and
deaths. Reporting adverse drug events to the TGA
is therefore important for making the information
known and widely available. Reports can come from
health professionals, consumers and pharmaceutical
companies. These reports are collected in the
Database of Adverse Event Notifications (DAEN). This
includes information about adverse events related
to prescribed, over-the-counter and complementary
medicines, and devices.
The TGA assesses potential signals and reports
nationally and internationally to enable a clearer
understanding of the risk of harm associated with
a drug. It is important that health professionals
report all suspected adverse events, including
known adverse events (to monitor their frequency),
for all drugs, no matter when they were registered.
It is particularly important for detecting rare and
potentially dangerous adverse effects, those occurring
after prolonged exposure, and drug–drug and drug–
disease interactions that may not have been observed
in clinical trials.1
Although it is easy to send reports to the TGA,
voluntary reporting is in decline. There are now less
than 1000 reports by medical practitioners per year.
Of the 11,662 reports in July–December 2019, only
4.6% were from medical practitioners. Although
most prescribing is in general practice, few reports
come from GPs. Reports from non-medical health
practitioners comprised 15.3%, patients made 3.4%
of notifications, pharmaceutical companies were
responsible for 64.2% of reports and 12.5% were from
other sources.2
It is unclear if the decline in reporting is because
adverse events are truly declining, or there are
behaviour changes regarding reporting. For example,
health professionals used to receive printed copies
of the publication Medicines Safety Update and the
‘bluecard’3 reporting form. The blue card is now
only available on the TGA website. If these hard
copies, which are no longer printed, were visual cues
for prescribers, perhaps raising expectations and

3Full text free online at nps.org.au/australian-prescriber
VOLUME 44 : NUMBER 1 : FEBRUARY 2021
EDITORIAL
1. Linger M, Martin J. Pharmacovigilance and expedited drug approvals.
AustPrescr 2018;41:50-3. https://doi.org/10.18773/austprescr.2018.010
2. Therapeutic Goods Administration. Half yearly performance snapshot:
July to December 2019. Canberra: Commonwealth of Australia; 2020.
https://www.tga.gov.au/publication/half-yearly-performance-snapshot-july-
december-2019 [cited 2021 Jan 4]
3. Mackay K . Showing the blue card: reporting adverse reactions. Aust Prescr
2005;28:140-2. https://doi.org/10.18773/austprescr.2005.107
4. Wiktorowicz ME, Lexchin J, Paterson M, Mintzes B, Metge C , Light D, et al.
Research networks involved in post-market pharmacosurveillance in the
United States, United Kingdom , France, New Zealand, Australia, Norway and
European Union: lessons for C anada. Edmonton (AB): Canadian Patient Safety
Institute; 2008. https://www.patientsafetyinstitute.ca/en/toolsResources/
Research/commissionedResearch/postMarketingSurveillance/Pages/
researchResults.aspx [cited 2021 Jan 4]
5. Hazell L, Shakir SA . Under-reporting of adverse drug reactions:
a systematic review. Drug Saf 2006;29:385-96. https://doi.org/10.2165/
00002018-200629050-00003
6. Withdrawal of lumiracoxib in Australia. Australian Adverse Drug Reactions
Bulletin 2008;27(2):6-7. https://www.tga.gov.au/publication-issue/australian-
adverse-drug-reactions-bulletin-vol-27-no-2#a2 [cited 2021 Jan 4]
7. McEwen J, Thompson BR, Purcell PM, Kelly LF, Krauss AS. Widespread
hyoscine hydrobromide toxicity due to contract manufacturer malpractice :
the travacalm episode. Drug Saf 2007;30:375-8 . https://doi.org/10.2165/
00002018-200730050-00002
8. Falconer N, Barras M, Martin J, Cottrell N. Defining and classifying terminology
for medication harm: a call for consensus. Eur J Clin Pharmacol 2019;75:137-45.
https://doi.org/10.1007/s00228-018-2567-5
9. Naranjo C A, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method
for estimating the probability of adverse drug reactions. Clin Pharmacol Ther
1981;30:239-45. https://doi.org/10.1038/clpt.1981.154
10. Molokhia M, Tanna S, Bell D. Improving reporting of adverse drug reac tions:
Systematic review. Clin Epidemiol 2009;1:75-92. https://doi.org/10.2147/
CL E P. S 47 75
11. Vallano A, Cereza G, Pedròs C, Agustí A, Danés I, Aguilera C, et al. Obstacles
and solutions for spontaneous reporting of adverse drug reactions in the
hospital. Br J Clin Pharmacol 2005;60:653-8. https://doi.org/10.1111/
j.1365-2125.2005.02504.x
12. Hines PA, Guy RH, Brand A, Humphreys AJ, Papaluca-Amati M . Regulatory
Science and Innovation Programme for Europe (ReScIPE): a proposed model.
Br J Clin Pharmacol. Epub 2019 Aug 19. https://doi.org/10.1111/bcp.14099
REFERENCES
standard descriptors adopted by practitioner groups
and regulatory organisations to support better
awareness, quality improvement and patient safety.8
Health professionals possibly report proportionally
more serious adverse events, due to the impact on
patient care, and because the TGA website stipulates
particular interest in serious adverse events. However,
this skews the reported data. This means that the
DAEN may contain a higher ratio of serious to non-
serious adverse event reports and also rare rather
than common reactions. A further limitation is that a
search of the DAEN will not provide information about
the severity of adverse events, or the dose, strength
or duration of use of a medicine. Reports for drugs
accessed via the Special Access Scheme, Authorised
Prescriber Scheme, Clinical Trial Notification Scheme
or the Clinical Trial Exemption Scheme are not
published in DAEN. This lack of publication may
potentially be a disincentive to reporting.
Whereas publicity about a possible adverse event
may increase reporting, there is a well-characterised
progressive decline in adverse event reporting,
following an initial peak, after a drug’s regulatory
approval. Other factors potentially contributing to
low reporting rates by health professionals include
a lack of time relative to other clinical priorities,8
their awareness and perceived importance of
pharmacovigilance,8,10 and a lack of feedback
about pharmacovigilance activities.11 There may be
limited awareness of adverse drug event reporting
mechanisms and uncertainty about the cause of
events, particularly when there is multimorbidity
and polypharmacy.10 An adverse event may cause
misplaced concern regarding potential legal liability.11
To improve safety for patients, health professionals
should be encouraged to report adverse drug events.
We suggest education, starting at university, that
any suspected adverse event related to a medicine
should be reported, even if the reaction is already
known. A lack of awareness of the need to report
adverse drug reactions may have led to some clinical
pharmacology departments specifically teaching
about pharmacovigilance and the importance of
reporting. Role modelling by more senior clinicians
demonstrating reporting on ward rounds, in the
early postgraduate years, might also encourage new
graduates to report adverse events.
A longer term strategy to improve reporting is to
consider adding successful aspects of an international
pharmacovigilance system to the current Australian
system. For example, a collaboration between the
European Medicines Agency, the European Medicines
Regulatory Network and academic research centres,
provisionally termed the Regulatory Science and
Innovation Programme for Europe (ReScIPE),12 is an
interesting model and broader than pharmacovigilance
reporting. This model could be explored for more
in-depth and clinically relevant approaches to
reporting. Other jurisdictions such as New Zealand
also have specific pharmacovigilance committees. An
Australian committee could be reinstated to raise the
profile of drug safety in Australia.
For the present, reports can be made online via the
TGA website or via email. There is an online blue card
reporting form which can be downloaded from the
TGA website and emailed, faxed or posted to the TGA.
Medical practices can download and install templates
in their software to create adverse drug reaction
reports. Health professionals can subscribe to the
online version of Medicines Safety Update for advice
on drug safety and information about emerging
safetyconcerns.
Conflict of interest: none declared