All medicines and vaccines have risks and benefits. Before a medicine or vaccine is approved for use it must be tested in clinical trials to determine its effectiveness. Information about potential risks is known from the clinical trial data and assessed before the medicine or vaccine is approved for use.
Known information about each medicine and vaccine is published for health professionals in a manufacturer’s data sheet, available on the Medsafe website (www.medsafe.govt.nz). Consumer medicine information is usually also published.
As the use of a medicine or vaccine increases, more information becomes available on its safety profile. Some adverse reactions are rare and may not be seen until a very large number of people have received the medicine or vaccine. This is one of the reasons why it is important to monitor all medicines and vaccines after they have been approved (registered). Note that some vaccines that are approved for use by Medsafe may not be available for distribution by the manufacturer or supplier.
Most countries have a safety monitoring system, which includes a voluntary spontaneous reporting scheme, to help identify any possible safety concerns. In New Zealand, Medsafe is the medicines regulator responsible for monitoring information to ensure that approved vaccines remain acceptably safe for use in New Zealand. Vaccine safety is never reviewed in isolation from the expected benefits of the vaccine; it is always looked at in terms of the benefit/risk balance.
In addition, the WHO plays an important role in vaccine safety through its Strategic Advisory Group of Experts on Immunization and the Global Advisory Committee on Vaccine Safety.
Two terms are used to describe spontaneous reports. Adverse events are undesirable events experienced by a person, which may or may not be causally associated with the vaccine. Adverse reactions are undesirable effects resulting from medicines or vaccines (ie, they are causally associated).
Spontaneous reports are case reports of adverse events that people have experienced while or after taking a medicine or having a vaccine. Medsafe contracts the collection, review and analysis of this information to the New Zealand Pharmacovigilance Centre at the University of Otago in Dunedin.
Health care professionals and consumers are encouraged to report adverse events following immunisation (AEFI) to the Centre for Adverse Reactions Monitoring (CARM), which is part of the New Zealand Pharmacovigilance Centre. Pharmaceutical companies also submit adverse event reports.
Data published by the WHO shows that New Zealand has one of the highest spontaneous reporting rates per capita in the world. It has been estimated that, in general, only around 10 percent of all adverse reactions are reported. However, it is not necessary for all adverse reactions to be reported for a potential safety signal to be spotted.
Further information about suspected adverse reactions (and events following immunisation) reported in New Zealand can be found in the Suspected Medicine Adverse Reaction Search (SMARS) on the Medsafe website (www.medsafe.govt.nz/projects/B1/ADRDisclaimer.asp). See section 2.5 for details about what information should be reported to CARM.
Medsafe and CARM analyse spontaneous reports in conjunction with other information to determine whether there are any new potential safety signals. Medsafe seeks the advice of independent experts, through the Medicines Adverse Reactions Committee, or may form working groups of experts to provide advice. Medsafe works closely with other regulatory authorities from around the world.
Medsafe undertakes a risk–benefit assessment of safety signals to decide if action is required. Further information on risk–benefit assessment is provided on the Medsafe website (www.medsafe.govt.nz/Consumers/ Safety-of-Medicines/Medsafe-Evaluation-Process.asp).
Most safety signals are not supported by any additional information and no action is taken, although Medsafe may continue to monitor the issue closely. A small number of possible safety signals are confirmed as real. In these cases, Medsafe has a number of regulatory actions it can take, including withdrawing the product.
Spontaneous reports have been shown to be a very simple way of identifying potential or possible safety signals with medicines, and over 90 countries have a spontaneous reporting system. They can be used to monitor the safety of medicines in real-life use over the lifetime of the medicine, and for all types of people.
The limitations of using spontaneous reports include under-reporting, a lack of reliable information on the extent of use of the medicine, and wide variations in the clinical details provided about the event and the history of the patient. Spontaneous reports are heavily subject to reporting bias, such as media or other attention on an issue. They are also not very effective at detecting adverse reactions that occur a long time after starting the medicine.
For these reasons, such reports are only used to identify safety signals. These signals require further formal epidemiological study before they can be validated or discounted. Information obtained from spontaneous reports needs to be interpreted with caution.
Spontaneous report patterns can be variable and they depend on many factors. Summaries of reported events following immunisation are not lists of known or proven adverse reactions to vaccines. They cannot be used to determine the frequency of adverse reactions to vaccines in the whole population, and they cannot be used to directly compare the relative safety of vaccines. They must not be interpreted and used as such.
Health care professionals and consumers are encouraged to report any suspicions that an event they have experienced may have been caused by vaccination. Therefore, reports sent to CARM may be:
With any vaccine, the adverse events that are generally reported include:
In New Zealand it is less likely that any new rare side-effects to vaccines will be detected because the number of people immunised is small compared to the number immunised in other countries. Therefore, Medsafe uses international data available from the WHO, other regulators and pharmaceutical companies to help assess any reports of rare events following immunisation and to determine if they may be new events linked to immunisation.
There will always be a number of coincidental events reported, because vaccines are given to large sections of the population. In some cases vaccines are specifically targeted at people with underlying medical conditions (eg, the influenza vaccine). The challenge is to be able to distinguish these coincidental ‘background’ events from those that may have been caused by the vaccine. There are a range of research methods for assessing the risk of an event after a vaccine compared with the risk with no vaccine exposure.
The time between immunisation and an event can be important in determining whether the event was coincidental. Most reactions to vaccines occur within a very short time of immunisation, usually within days. In some circumstances a longer timeframe between immunisation and reaction onset has been considered where there is a scientific basis to support it.5
Another approach to assessing vaccine safety is to compare the number of reports for a specific event with the expected background rate for that event. When doing this it is important to ensure that definite diagnoses of the events reported were made and to adjust the background rate for any differences in population groups and seasonal variations.6 Table 1.4 shows the number of coincidental events that might be expected as background rate events within one day, one week and six weeks after receipt of a hypothetical vaccine.
|Number of coincident events |
since a vaccine dose
|Baseline rate used for estimate|
|Within 1 day||Within 7 days||Within 6 weeks|
|Guillain-Barré syndrome (per 10 million vaccinated people)||0.51||3.58||21.50||1.87/100,000 person-years (all ages; UK Health Protection Agency data)|
|Optic neuritis (per 10 million female vaccinees)||2.05||14.40||86.30||7.5/100,000 person-years in US females|
|Spontaneous abortions (per 1 million vaccinated pregnant women)||397||2780||16,684||Based on data from the UK (12% of pregnancies)|
|Sudden death within 1 hour of onset of any symptoms (per 10 million vaccinated people)||0.14||0.98||5.75||Based on UK background rate of 0.5/100,000 person-years|
Source: Black S, Eskola J, Siegrist C-A, et al. 2009. Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines. The Lancet 374(9707): 2115–22.
International convention defines the seriousness of reports based on the outcome or nature of the reported event as documented in the report, irrespective of whether there is any association to the medicine or vaccine.
CARM considers a report to be serious based on the following international criteria:
Because a report is defined as serious based on what is reported, it is possible to have both serious and non-serious reports for the same event/person.
There is a risk of serious allergic reactions with all medicines and vaccines, and with some foods. With vaccines the risk of anaphylaxis is estimated to be around one to three reactions per one million doses administered. All vaccinators are trained and equipped to treat anaphylaxis if it does occur. This is the main reason people are asked to wait for 20 minutes following any immunisation, and why there is at least one health professional and one other adult with CPR training on site.