Signal Detection and Signal Management

Mar 27, 2019

Sr. Manager, Project Physicians, Pharmacovigilance Client Services

Pharmacovigilance involves the collection of data on Adverse Reactions, which must then be analyzed and evaluated to create meaningful safety information.

Signal detection in Pharmacovigilance involves looking at the adverse reaction data for patterns that suggest new safety information and specifically whether the new information changes the benefit to risk ratio associated with the use of a pharmaceutical product.

What Is A Signal?

It’s useful to draw an analogy from the discipline of Seismology; the scientific study of earthquakes and the propagation of waves through the Earth. Seismographs are the recorded representations of these waves, challenging the scientists to look through all the noise produced and focus on aspects of those recordings that represent the signal of a pending earthquake. The noise to signal ratio in Seismology, not unlike Pharmacovigilance, may be quite large, suggesting the need for a systematic approach to analysis.

The term “Signal” is most commonly associated with drugs during the post-marketing phase, although it may also be used during clinical trials. The definition of a signal as provided by the Council for International Organizations of Medical Sciences (CIOMS) 8 Working Group:

Information that arises from one or multiple sources (including observations and experiments), which suggests a new potentially causal association, or 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.

This may be an adverse event which has not previously been shown to have a causal association with the product; or a known event which is now occurring within a patient group for whom it has not been documented before or perhaps occurring with greater frequency or severity than anticipated.

The signal may be generated from qualitative analysis of spontaneous reports or quantitative analysis through data mining and statistical activities.

What Is Signal Management in Pharmacovigilance?

The process of signal management in pharmacovigilance is a set of activities, which aim to determine whether there are new risks associated with a particular drug, or whether known risks associated with a particular drug have changed.

Sources for the detection of signals:

  • Spontaneous reporting
  • Active monitoring systems
  • Interventional studies (clinical trials)
  • Non-interventional studies (pharmacoepidemiology studies)
  • Non-clinical studies (e.g. animal toxicology studies)
  • Systematic reviews (i.e. thorough review of the published literature)
  • Meta-analyses (i.e. mathematical pooling of all the clinical trial data)

Healthcare professionals are encouraged to report adverse reactions via national spontaneous reporting systems. Consumers and patients may also report adverse reactions in this way as well as via a wide variety of media, including the Internet.

Signals arising from spontaneous reports may also be evaluated via:

  • Monitoring large adverse drug reaction databases such as EudraVigilance and the FDA AERs system
  • Published articles
  • Periodic Safety Update Reports (PSURs)

Ongoing Benefit-Risk Monitoring

The process for managing signals must systematically address the following:

  • Signal detection
  • Validation and Confirmation
  • Analysis
  • Prioritization
  • Assessment
  • Recommendation(s) for action

All steps taken and recommendations made must be accurately tracked and documented at every stage. The ultimate goal is to confirm or refute whether there is a new issue with the safety of a medicine so that action might then be taken to reduce the risk to patients.

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