Calculation of adverse event incidence for veterinary medicines
Explanation for animal owners and veterinary health professionals on how the VMD calculates adverse event incidence rates for veterinary medicines
What are adverse events?
No medicine is 100% risk-free. Adverse events are observations that are unfavourable and unintended that happen after giving a medicine to an animal.
These events may be seen, for example, in the animal being treated, in other animals, the person handling the medicine or in the environment.
They include both reactions and times when the medicine has not worked as expected and can range from mild issues to more serious problems.
How adverse events are categorised
The VMD uses internationally recognised categories to describe how often adverse events occur:
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very common (more than 1 in 10 animals treated displaying adverse event(s))
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common (more than 1 but less than 10 animals in 100 animals treated)
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uncommon (more than 1 but less than 10 animals in 1,000 animals treated)
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rare (more than 1 but less than 10 animals in 10,000 animals treated)
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very rare (less than 1 animal in 10,000 animals treated, including isolated reports).
Frequency categories are allocated based on the results of an adverse event incidence or adverse event incidence percentage calculation (see table 1). Incidence percentages are 100 times greater than incidences but are equivalent and do not represent 100 times increase.
Table 1: demonstrating the adverse event incidence and adverse event incidence percentages for each frequency category
| Number of adverse events per number of estimated animals treated | Adverse event incidence range for this category | Adverse event incidence percentage range for this category | |
|---|---|---|---|
| Very common | More than 1 in 10 | Greater than 0.1 | Greater than 10% |
| Common | 1 to 10 per 100 | 0.01-0.1 | 1 to 10% |
| Uncommon | 1 to 10 per 1000 | 0.001-0.009 | 0.1 to 0.9% |
| Rare | 1 to 10 per 10,000 | 0.0001-0.0009 | 0.01 to 0.09% |
| Very rare | Less than 1 per 10,000 | Less than 0.0001 | Less than 0.01% |
How incidence rates are calculated
Adverse event incidence rates are calculated using this formula:
Incidence % = (Number of animals reacted ÷ estimated number of animals treated) x 100
The VMD does not receive exact data on medicine usage, as there is no system in place to determine how many doses of each individual product are administered by veterinary professionals and members of the public. Therefore, an estimated number of animals treated is calculated using sales data and a “dose factor”. The dose factor accounts for how a product is typically used according to its instructions - for example, whether an animal needs one dose or several doses.
Where possible the dose factor remains the same throughout a product’s authorisation, which allows calculation results to be compared over time. There may be situations where a dose factor needs to be changed, for example if the way a product should be used changes.
Adverse event incidence percentages contextualise adverse events in relation to the number of animals treated. For example, if Product A has 10 adverse event reports and Product B has 20 adverse event reports, Product B might seem like it has more frequent adverse events. However, if Product B was used to treat 1,000 times more animals than Product A, then adverse events are actually less frequent with Product B.
Further technical detail on how the estimated number of animals treated is calculated can be found in Annex 3 of the following guidance: Technical_guidance_for_completion_of_the_Pharmacovigilance_Sales_Submission__PSS.pdf.
What data is included
Calculations may include all reported adverse events, even when the medicine might not have caused the problem. This includes:
- where an adverse event has occurred that is already listed on the Summary of Product Characteristics
- where more than one product was used
- when the product was used off-label, that is using a medicine in a way that is not specified on the product’s label, including prescribing of unauthorised medicines following the prescribing cascade
- where, on further evaluation, there were other reasons for the adverse event occurring such as underlying illnesses or an alternative cause for the clinical signs seen.
Duplicate cases are combined, however if there is doubt as to whether two cases are true duplicates then both cases will be included. Reports may contain more than one animal per report, and therefore the number of animals with an adverse event will be greater than the total number of reports.
Important data limitations
Unless otherwise stated, publication of incidence rates is not confirmation that a medicine caused an adverse event. Evaluation, and subsequent regulatory action, if necessary, is dependent on the accuracy and quality of data provided by the veterinary professionals and animal owners. The VMD encourages all reporters to provide as much clinically relevant information as possible when reporting an adverse event.
The VMD always considers the likelihood of underreporting when assessing any concerns. Reporting frequency can also vary over time, for example if a product is new to the market or there is social media interest.
VMD databases change over time as new and follow-up information is constantly being received and reviewed.
Taking regulatory action
The VMD considers many factors beyond adverse event incidence percentages when deciding whether to take action about a medicine’s safety. Therefore, there is no specific threshold for regulatory actions to be triggered. Sufficient scientific evidence is always required as all decisions must be evidence-based. The fact that adverse events have occurred following administration of a product, does not necessarily mean that those adverse events were caused by the product.
The VMD constantly undertake monitoring and surveillance actions, such as signal detection and data mining of their database of adverse events, including statistical analysis and review of individual reports.
Clinical decision-making
Although incidence calculations can be useful to provide a general safety and efficacy profile of a medicine, it is important for any clinical decisions regarding the use of a veterinary medicine to be based on a benefit/risk discussion specific to the animal or group of animals being administered the medicine.
The published adverse event incidence rate for any medicine does not predict the risk for an individual animal, as many factors affect whether a particular animal will experience problems. For specific animals, advice from your veterinarian or other prescriber considering the individual circumstances is always important. The VMD does not provide advice on individual clinical scenarios or outcomes of adverse events, nor does it provide updates on individual adverse event reports.
Comparison of VMD data to other data sources
Incidence figures provided by the VMD may be different to those provided by different regulatory authorities, pharmaceutical companies, data previously published by the VMD and other authorities within the United Kingdom. This can happen for several reasons including:
- VMD published data can change if new or follow-up reports and information are received or if we improve the way we calculate figures.
- Other regulatory authorities in countries outside of the UK follow their own laws and guidelines, which affect how they collect and present medicine safety information. This means, what data is published and what information is included on a medicine’s label or information leaflet can vary across jurisdictions. The current GB legislation is the Veterinary Medicines Regulations, which is similar to that of comparative European countries. The VMD remain the regulator for veterinary medicines in Northern Ireland and pharmaceutical companies have a responsibility to fulfil the pharmacovigilance requirements of both the VMD and Regulation (EU) 2019/6 where necessary.
Publication of adverse event incidence rates
Publications will be updated, when necessary, with the latest information available. Adverse event incidence percentage calculations rely on sales data submitted by Marketing Authorisation Holders on at least a yearly basis; the deadlines vary for each authorised veterinary medicine.