The detection and evaluation of new drug safety signals is a routine task in pharmacovigilance. Nevertheless, both guidelines: EU GVP and UA Guideline on good pharmacovigilance practices of the Ministry of Health of Ukraine 42-8.7:2018 take this process to the category of critical. Therefore, it is necessary to understand what to consider the signal and how to detect it.
The definition of a signal for pharmacovigilance differs in various institutions. For example, the World Health Organization (WHO) defines a signal as information on a possible, previously unknown or not fully documented, causal link between the adverse event and the use of the drug. Usually more than one report is required to create a signal, depending on the seriousness of the adverse event and the reliability of the information. According to the definition of the European Medicines Agency (EMA), “a safety signal is information on a new or known adverse event that may be caused by the use of the drug and requires further investigation.” Another variant of the definition is presented by the Uppsala Monitoring Center (UMC). According to it, the signal is “a hypothesis of the risk that may be caused by the use of the drug, which is proved by data and arguments originating from one or more reports.”
Though these leading organizations provide different definitions of a signal, it is possible to distinguish the its common mandatory characteristics. Namely: a signal is certain information received from different sources, about the potential harm caused by the use of the drug, which requires further assessment.
Detection of new signals in pharmacovigilance is very important after a drug has been marketed. Only after it is used by various patients unexpected threats, features, drug-drug interactions can be detected.
WHO Pharmaceuticals Newsletter regularly publishes information on newly found safety signals on the WHO website. You may also found it in scientific and medical publications, authorities websites, clinical trials, scientific congresses, and in popular press. Therefore it is very important to carry out proper constant literature monitoring in accordance with the GVP principles.
Search for new safety signals
Several factors should be taken into account when searching for new safety signals. Namely, new unpredictable adverse drug reactions, or previously unknown aspects of known adverse drug reactions; life-threatening or fatal cases require thorough research. Also we need to pay close attention to cases of severe adverse reactions. For example, toxic epidermal necrosis, Stevens-Johnson syndrome, granulocytopenia, etc. Group side reactions, originating from one source / one region and have similar characteristics may indicate the substandard drugs circulation.
Detection of new safety signals in pharmacovigilance does not mean that it was the drug that actually caused a reaction. After all, according to the definition – each signal requires further assessment! Usually, the first step is assessing the cause-effect relationship. It will show whether there is a theoretical relationship between the use of the drug and the adverse reaction occurence. If such a link is not seen as possible, further steps to assess the signal will not make sense.