Signal Management is the process of managing safety signals in pharmacovigilance. Here’s what phases it consists of and how it is performed.
What is a safety signal in pharmacovigilance
First of all, it is good to know the definition of a safety signal. A safety signal is an information suggesting a new possible association between a drug and an adverse event, or a known adverse event that occurs with greater impact or in a different way than previously recognized. In fact, it is an unexpected result, given by the analysis of various relevant sources, which must be investigated and possibly confirmed.
Signal Management: what it is
Signal Management is a fundamental process in pharmacovigilance that aims to detect, evaluate and manage information related to drug safety signals. The goal is to ensure that medicines are used safely and effectively, by promptly identifying and managing potential risks to patient health.
Signal Management Regulations
Signal Management at European level is regulated by Directive 2001/83/EC art. 107h, by Regulation (EC) 726/2004 art. 28 and by the Commission Implementing Regulation (EU) 520/2012. It is also detailed in Good Pharmacovigilance Practices (GVP) Module IX and its Addendum I.
Signal Management process
According to the GVP, Signal Management consists of the following phases:
| Activity | Description |
|---|---|
| Signal Detection | Investigation and individuation of the signal by analyzing any inherent source. |
| Signal Validation | Evaluation of the data supporting the identified signal to verify if the documentation is sufficient to confirm the existence of a cause-effect relationship. |
| Signal Analysis and Prioritization | Identification of signals that require immediate management. These include signals that present significant risks to public health or that influence the benefit-risk balance of a drug. |
| Signal Assessment | Evaluation of the signal in order to detect any new risks, or changes thereof, with a causal association related to the drug and to determine any necessary regulatory actions. |
| Recommendation for Action | Evaluation of the need to take further action. |
| Exchange of Information | Exchange of information between all interested parties involved. |
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Signal Detection
Signal Detection is the process of looking for signals. It involves constantly monitoring information from various sources, such as, for example, spontaneous case reports, clinical studies and scientific literature. The aim is to identify potential safety signals and take corrective measures in a timely manner to safeguard public health.
You can find out more by reading this article: Signal Detection: what is it
Signal Validation
Signal Validation consists in verifying the reliability and completeness of the information supporting a potential signal. This stage involves the critical analysis of the available information, the robustness of the evidence and the clinical relevance, as well as any additional supporting data. Thanks to the Signal Validation it is possible to confirm or not the existence of a new or changed cause/effect relationship.
For further information, read this article: What is Signal Validation
Signal Analysis and Prioritisation
During the signal analysis and prioritization phase, various variables are evaluated on the basis of which a priority is assigned or not to the signal. In particular, the impact of the adverse event on the patient is evaluated, taking into account the seriousness, the severity of the clinical manifestation, the reversibility of the event and the ability to prevent its occurrence. In addition, the consequences of treatment interruption on the management or progression of the disease, the presence of therapeutic alternatives and the impact on public health are considered. This last aspect requires a broad evaluation that also takes into account the use of the drug in the general population and in special populations such as pregnant women, children and the elderly.
When analyzing the importance of the signal, it is also essential to consider situations where the drug is used off-label or improperly, i.e. not in compliance with the authorizations.
In prioritizing the signal, the method used by the MHRA (Medicines & Healthcare products Regulatory Agency) can be used. It is based on a score derived from assessing the strength of the causal association between the drug and the adverse event, as well as the public health implications of marketing the drug.
Signal Assessment
The Signal Assessment consists in the evaluation of the previously identified signal. At this stage, it becomes necessary to conduct further evaluations to determine whether the information gathered is sufficient to obtain a complete picture. The necessary regulatory action is then identified.
In this phase, the Qualified Person for PharmacoVigilance (QPPV) usually consults the dossiers derived from the preclinical and clinical development to look for data that confirm or deny the possible cause/effect relationship between the drug and the adverse reaction. The cases reported in the literature are also examined and experts of both the adverse pathology and the pathology under treatment are consulted to obtain further support.
Recommendation for action
After the evaluation of the signal, the decision phase of the actions to be taken follows. It is a delicate phase as it is necessary to balance the obligation to protect the patient with the risk of adopting excessive actions, such as withdrawing the product from the market. Several times less drastic measures could adequately contain the risk, such as excluding a particular group of patients from administration.
Evaluating the actions to be taken requires the involvement of various company departments, including the regulatory, medical, manufacturing/distribution and commercial sectors. It is essential to trace and record the decisions made and establish the times within which the various company functions must complete the assigned activities.
Exchange of Information
The last phase is that of exchanging information with the competent authorities. The Marketing Authorization Holder (MAH) has the responsibility to communicate the validated signals and everything that falls under the definition of Emerging Safety Issue to the health authorities. The MAH may be required to provide periodic signal reviews, risk minimization activities, updates to healthcare professional and patient education materials, and to conduct Post Authorization Safety Studies (PASS).
Conclusions
In conclusion, Signal Management plays a crucial role in pharmacovigilance to ensure drug safety and protect patient health. The different stages of the process, from signal research and identification to evaluation, prioritization and recommendations for actions to be taken, require in-depth analysis and accurate evaluation of the data.
In this regard, it is important to underline that there are tools and resources that can simplify and optimize the Signal Management process. A safety database, such as SafetyDrugs, offers an effective solution for data collection and analysis, allowing, thanks to its Business Intelligence module, to identify and highlight potential safety signals in a timely and efficient manner. This tool can provide invaluable support in the early stage of signal identification, facilitating access to pertinent data and contributing to faster and more accurate evaluation.
If you want to learn more about how SafetyDrugs can help you in the Signal Management process, contact us or directly fill out the form below to request a demo.
