SIGNAL MANAGEMENT

   WHAT IS SIGNAL?


 A Signal is defined by WHO as “reported information on a possible causal relationship between an adverse event (AE) and a medicine, of which the relationship is unknown or partly documented preliminary”


  • 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 


Healthcare professionals, consumers ,and cases are encouraged to report adverse responses via national spontaneous reporting systems. 


WHAT IS SIGNAL MANAGEMENT IN PHARMACOVIGILANCE?


It is a set of activities that are performed to determine whether there are new risks associated with the medical product or known risk have changed based on examination of individual case safety reports(ICSRs) ,aggregated data from active surveillance system or studies ,and scientific literature information or other data sources

 

SIGNAL MANAGEMENT PROCESS


  • Signal detection

  • Signal Validation 

  • Signal Analysis

  • Signal Prioritization

  • Signal Assessment

  • Recommendation for action

  • Exchange of information




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 SIGNAL DETECTION 

 Health administrations and Marketing Authorization Holders perform signal discovery, the process of looking for and identifying signals from any available source. Frequently sources are reviews of ICSRs, aggregated data, new studies and scientific literature .

METHOD OF SIGNAL DETECTION 

  • Commonly signal detection is done in two methods 

                   1. Traditional pharmacovigilance methods

                   2. Data mining algorithms

SIGNAL VALIDATION:

 

Once you confirm that there is a signal, you must examine the information to determine if there is sufficient documentation in the available data for further research of the safety signal. 


1 .PREVIOUS AWARENESS: is the assessment of whether the signal only tells us something we already knew because defined information can already be in, for example, the Risk Management Plan or labeling for a product.


2.  STRENGTH OF THE EVIDENCE: means that when evaluating the value of a signal it is needed to take a lot of factors into consideration such as:

The total number of cases;

The quality of the information 

Consistency between cases 

Biological or pharmacological mechanism.


3. CLINICAL RELEVANCE AND CONTEXT: the assessment focuses on consideration if the event is serious, how severe it is, what is the duration, outcomes, interactions or risk to a specific population for example such as children. If a signal is validated, it means that there is enough confirmation to proceed with the analysis of the signal.


SIGNAL CONFIRMATION: 


The process of deciding whether or not a validated signal entered in European pharmacovigilance issues tracking tool (EPITT) requires further analysis and prioritization by PRAC.

SIGNAL ANALYSIS AND PRIORITIZATION:

Safety signals are prioritized according to their urgency. It is necessary to separate safety signals that may have a big impact on case's or public health, or can significantly affect the risk-benefit balance of a medical product. The safety signal analysis and prioritization process will, therefore, determine the need for additional analysis and the timeframes for it.

SIGNAL ASSESSMENT:

Further evaluate a validated signal so as to identify the need for additional data collected or for any regulatory action 

  • Assessment of the available pharmacological, nonclinical and clinical data and information from other sources 

  • Review appropriate internal and external sources to obtain further information 

  • Document the risk assessment of the signal per products safety signal investigator report and recommended no further action ,or further action to prevent or minimize patient risk as described in the next section ,recommended for action

  • Assess the significance of a signal to obtain a potential link to a complex disease to previous stage or response to clinical complications of adverse reaction of interest

RECOMMENDATION FOR ACTION:

Appropriate action as recommended by the regulatory authorities is taken 

  • Including the possibility of suspending the marketing authorization of the medicinal product


EXCHANGE OF INFORMATION:

 Based on Emerging safety issues : implication for public health ,benefit-risk profile, outcome of signal assessment .The results are communicated to appropriate regulatory authority and public including healthcare professionals and patients.     

                                                                                                                                                                          REFERENCES :

  1. Guildeline on good pharmaovigilance practices (gvp) module ιχ – signal management

  2. https://www.biomapas.com/what-is-a-safety-signal/

  3. https://www.sciencedirect.com/science/article/pii/S2667318521000052

  4. Artificial intelligence in the lifesciences vol 1,december 2021,100005


                                                                                                                

                                                                          

 

                                                                                         Name:  B.Aiswarya

                                                                                        Qualification: Pharm.D Intern

Student ID: 214/1222

                                                                                      Email id : beriaishwaryarao@gmail.com


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