This article was originally published in the May 2022 edition of the ADA's News Bulletin
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Pharmacovigilance is the study of drug safety monitoring. It occurs at many levels, from government agencies to the daily activities of health professionals and consumers. Dentists have an important role to play, to accurately identify, manage, report and prevent adverse drug reactions (ADRs) related to dentistry. How many practitioners in our profession know this? Have you ever reported an ADR to the TGA? This is the problem with pharmacovigilance: everyone thinks someone else is doing the reporting.
The only way we ever know the side effects of drugs is when they are reported in sufficient numbers to establish a 'signal' and causation. That's why it is everyone's job to report ADRs – including dentists. What happens if you don't? Well, there's an old saying amongst pharmacovigilantes: 'If you don't report an adverse drug reaction, it's like it never happened'. This might be why so few dental ADRs are well known outside dentistry, such as osteonecrosis of the jaw (ONJ). So how do you report an ADR? How much detail is required? Must you be certain the drug was the culprit? In this article, I will explain what to do.
Adverse drug events vs adverse reactions?
The umbrella term for 'things going wrong with medicines' is an adverse drug event (ADE), which is "any adverse experience with a medicine, including those due to the pharmacological actions of the drug, human error, misuse and abuse". (1) ADEs can be divided into two types: adverse drug reactions and medication errors.
An adverse drug reaction (ADR) is an "unwanted, undesirable effect of a medication that occurs during usual clinical use" (2). The key to this definition is that the ADR is due to the action of the drug. It's just what that drug would do; no one made a mistake or did anything wrong.
A medication error, however, is "a failure in the medication process that leads to or has the potential to lead to patient harm" (3). Errors occur when actions do not proceed as planned, either because the plan was faulty or the operator made mistakes, slips or lapses. (4) These are human process issues, not caused by the drug itself.
Figure 1 shows the relationship between adverse drug reactions and medication errors. We make the differentiation between errors and ADRs, so practitioners understand that when we're reporting ADRs we're not reporting people, we're dobbing in drugs.
ADRs are a major public health problem
ADRs occur frequently, contributing significantly to human suffering and economic expense. The Medication Safety Report from the Pharmaceutical Society of Australia in 2019 stated that 250,000 Australian hospitalisations per year are caused by ADEs, most of which are due to ADRs, at a cost of around $1.4 billion. (5) The same report tells us that ADRs occurring in hospital increase length of stay by 2-4 days and, in general practice, ADRs result in 400,000 GP visits a year. The tragedy is that 50% of ADRs are preventable, yet little is being done to prevent them.
How are drug side effects discovered?
In the past, drug side effects were discovered simply by people taking medicines and someone eventually attributing unwanted effects to the drug, rather than the patient, their disease or evil spirits. This process was ad hoc, slow, and unreliable, so never trust a claim that a drug/herb/substance 'must be safe because it's been used for centuries'.
Today, the side effects of drugs are largely determined during pre-marketing clinical trials. Although modern research methods encourage a more timely and structured approach to reporting and identifying potential ADRs, there are still many weaknesses in this system, including:
1 Most clinical trials run for short periods (weeks to months) so long-term or delayed adverse effects remain undetected;
2 On average, by the time a drug is marketed it has only been taken by 1,000-2,000 subjects. (7) This may sound like a lot of people, but rare adverse effects that occur, say, in 1 in 5,000 subjects may not have happened yet. It has been shown that 3,000 patients at risk are needed to detect an ADR with a frequency of 1 in 1,000 with 95% certainty (7);
3 Vulnerable populations, such as infants, children, the elderly, pregnant and breastfeeding women, are typically excluded from clinical trials. So safety issues will be unknown for these groups;
4 People with multiple diseases and/or on multiple medicines are also excluded from clinical trials. As a result, the clinical trial population may not resemble the real-life population the drug is intended to treat. In addition, ADRs due to drug-drug or drug-disease interactions are unlikely to be identified; and
5 People are more confident to report expected (Type A) ADRs in pre-marketing trials. Therefore, it is not until a drug is approved and used in the wider population that rare and unusual type B, C and D reactions are identified. This is why post-marketing surveillance is so important.
Pharmacovigilance and types of ADRs
Recognising that there are seven different types of ADRs can help with ADR detection and diagnosis, as outlined in Table 1. The two main types are Type A and B that represent about 90% of all ADRs. Note that allergic reactions are Type B effects, which are neither dose nor time related. Don't feel compelled to report mild allergic reactions such as rashes, as these are expected with every drug on the planet and tell you more about the patient than the drug.
Who reports ADRs?
Unfortunately, ADR reporting is poorly done by most health professionals. Less than 5% of all ADRs are reported, even in countries where reporting is mandatory.2 In hospitals, less than 10% of serious/severe ADRs are reported and in general practice
Despite being plagued by poor participation, ADR reporting remains the most effective, common and inexpensive method of collecting post-marketing drug safety data from the general community. Drug companies contribute most reports, but they are only legally obligated to report serious ADRs which are defined as those causing death, danger to life, admission to hospital, prolongation of hospitalisation, absence from productive activity, increased investigational or treatment costs and birth defects.10 Consumers are strongly encouraged to report their own ADRs, as they give a more accurate, first-hand account of the ADR they personally experienced. Consumers are also more motivated than most health professionals to report their ADRs and submit them more quickly.
How and to whom to report ADRs
ADRs can be reported to a patient's doctor or the suspected drug's manufacturer. However, as useful that might be, it is unlikely they would share the report with anyone else. Therefore, it is recommended that, above all, ADRs should be reported to the TGA as this means your report will not only be recorded on the central ADR repository for our country, but also shared worldwide via the WHO's Sweden-based International Centre for Drug Safety Monitoring. Worldwide data is collected on their Vigibase® and analysed constantly for drug safety signals.
At present, ADR reports can be submitted online via the TGA website, via email or over the phone. There is also an online 'blue card' or ADR reporting form which can be downloaded from the TGA website, completed by hand, and emailed, faxed or posted to the TGA. Medical practices can download and install templates into their software to create ADR reports. The cloud-based version of eMIMS provides a direct link to the TGA ADR-reporting database.
You don't have to be certain the drug is the cause, just suspicious. While an individual ADR report may not be enough to determine whether a particular drug caused an adverse event, all reports help build a picture of the product's safety profile and assist with the TGA's safety monitoring program. Every report counts.
The TGA is particularly interested to receive ADR reports relating to:
- all suspected adverse events to new therapeutic goods;
- all suspected medicine and/or vaccine interactions;
- adverse events that do not appear in or would change the drug's Product Information, Consumer Information and/or product labelling; or
- all serious adverse events, as outlined above.
An ADR report does not need to tell the patient's life story. No names of the patient or treating health professionals are required, only the name of the reporter so they can get back to you if required. Therefore, the following five aspects will give sufficient detail to convey the nature and outcome of the ADR for the TGA. These are:
1 the patient's gender and age;
2 a brief medical history;
3 a description of the adverse event, including time of onset and outcome;
4 all the medications the patient was on when the adverse event occurred; give name, dose and duration of each, highlighting timing of use and which drug is the suspected agent/s; and
5 name of the reporter, so they can contact you if necessary.
If you require any further information on this subject, or for the reference list for this article, please don't hesitate to contact Geraldine on the Pharma-Advice Service: call 0419 752 528 or email [email protected]
