Types Of Signal In Pharmacovigilance
Pharmacovigilance is concerned with detecting the possible risks associated with a drug or treatment. Risks are monitored and assessed throughout the development and post-market phase. The aim of this is to determine the safety profile of the drug, identifying any potential adverse reactions and side effects that the drug may cause.
Additionally, any beneficial reactions are also monitored in order to assess the drug’s efficacy and ability to improve the condition.
To assess this, pharmacovigilance researchers track and evaluate safety ‘signals’ as part of routine, which provides vital reporting data on any adverse or beneficial reactions that have occurred in association with a particular drug. This ensures that regulatory authorities and researchers have access to the most up-to-date data on the drug’s risks and benefits.
What Is A Signal?
As part of pharmacovigilance, researchers actively search for and identify safety signals across an extensive range of data sources. Signal detection involves monitoring adverse and beneficial events that have been reported or detected during research. With this data, researchers build a full profile of the drug’s safety and develop an optimal signal management plan.
A signal in pharmacovigilance is information arising from one or multiple sources, including observations and experiments, which suggests a new potentially causal association. Signals can also suggest a new aspect of a known association between an intervention and an event or set of related events, either adverse or beneficial, that is judged to be of sufficient likelihood to justify verificatory action.
New aspects of a known association may include changes in the frequency, distribution (such as gender, age and country), duration, severity or outcome of the adverse reaction.
Types of Signal
Pharmacovigilance researchers assess various types of signals in order to gather an in-depth understanding of how the drug performs in human use.
Types of signal can include adverse events, which are reactions that pose a negative impact on the patient’s health, wellbeing, quality of life, or the condition itself. On the other hand, beneficial events are types of signals that indicate a positive impact on the patient’s health, wellbeing and condition.
Pharmacovigilance signals can be generated through several different methods of both qualitative and quantitative analysis. A mixed methodology is often applied in order to gather the most extensive range of data possible surrounding the drug’s safety and efficacy.
Common qualitative methods include spontaneous reporting, whereby the signal is generated from ongoing reports of adverse or beneficial events as they occur or are detected. This is often supported by data mining and statistical activities, such as systematic literature reviews and meta-analyses of clinical trial data in order to generate a more extensive scope of how the drug interacts with patients.
Spontaneous reporting systems
The most common form of signal detection in pharmacovigilance comes from spontaneous reporting systems (SRS). Spontaneous reporting provides a qualitative type of pharmacovigilance signal sourced from volunteer’s own reports of adverse or beneficial drug reactions.
Alongside self-reports from volunteers, large adverse drug reaction databases such as EudraVigilance are used to detect pharmacovigilance signals. Other sources of signals in spontaneous reporting can come from published articles, the FDA Adverse Event Reporting System (FAERS), and VigiBase.
Many spontaneous reporting systems are electronic, forming a centralised online database of pharmacovigilance signals, although some studies may use paper-based methods to detect signals.
When an adverse event occurs, or is detected in a database, this is tracked in the clinical trial’s spontaneous reporting system. Throughout the trial’s progression, this builds up a dataset of adverse reaction reports, whereby researchers analyse commonalities, reaction frequencies and reactions amongst patient groups in order to evaluate the safety of the drug and prioritise signals during signal management.
Reporting Adverse Reactions
Reports of adverse events associated with the drug are monitored throughout the clinical trial and ongoing post-market research in order to assess the overall safety of the treatment.
These could be adverse events that have not previously been found to have a causal association with the drug, or these could be adverse events that have already been identified. For adverse reactions that have already been reported, these might be of significance due to their occurrence within a patient group that have not previously signaled that adverse event.
Monitoring new and recurring adverse event signals also helps researchers evaluate the frequency and severity of reactions.
Adverse signals are commonly reported to EudraVigilance, a centralised spontaneous reporting system used for suspected adverse drug reaction reports. EudraVigilance is used for authorised or trial medicines in the European Economic Area (EEA).
As a centralised database, adverse signals reported in EudraVigilance’s system are used by the Contract Research Organisation (CRO), member states and the healthcare industry. With a full report of adverse events all in one database, each stakeholder stays informed of the drug’s risks and benefits throughout the process. This kind of transparency can often help speed up the approval process.
As signals are monitored throughout the development process, this helps CROs devise an optimised clinical trial design that effectively addresses the risk-benefit balance of the drug.
Reporting Beneficial Reactions
Spontaneous reporting is not confined to adverse event signals. Beneficial events are also reported as a type of signal in pharmacovigilance. In spontaneous reporting, beneficial events can be reported by participants themselves, or detected by researchers from clinical trial data and other medical sources.
Adverse event signals help test for safety, whereas beneficial event signals help test for efficacy, whereby there is a possible causal link between the drug and its positive impact on a certain condition or its symptoms.
Beneficial types of signal carry significant importance in getting market approval for the drug, since clinical trials must provide data that proves the treatment is at least, or more, effective than the current standard treatment offered for a particular condition.
Clinical trials will determine the exact intended effects that the treatment would ideally deliver. These intended effects would be considered beneficial event signals, although types of signal might show previously unforeseen beneficial reactions that weren’t predicted or outlined in the trial’s definition of intended effects.
Pharmacovigilance researchers use multiple information sources to detect signals across an extensive range of data.
As well as spontaneous reporting, researchers may review existing scientific literature and published articles in order to detect previously reported adverse or beneficial effects of the trial medication.
Conducting thorough reviews of published literature helps identify any signals that have potentially not been detected through spontaneous reporting.
Additionally, researchers may carry out systematic reviews of existing clinical trials, conducting an extensive meta-analysis of pooled clinical trial data to identify potential adverse event signals.
Pharmacovigilance signal data stored by the Clinical Research Organisation (CRO) is used to accurately track the trial drug throughout every phase and assess the balance of risk against its benefits.
Not only is pharmacovigilance necessary as a legal requirement in clinical trials, managing signals enables researchers to confirm or disprove any potential new safety issues concerning the drug. From this data, the necessary action can be taken to minimise the risk with an effective signal management plan.
This involves assessing the types of signals that have been reported and detected throughout the process and prioritising each signal type based on the level of risk posed to patients and public health.
Have a Question?
For any questions about the types of signals in pharmacovigilance, get in touch with our team. As an experienced contract research organisation with expertise in pharmacovigilance management, we are here to help.