Signal Detection in Pharmacovigilance

Signal detection in Pharmacovigilance involves looking at the adverse reaction data for the patterns that suggest new safety information.

What Is A Signal?

The term is most commonly associated with drugs during the post-marketing phase, although it may also be used during pre-marketing clinical trials. The definition of a signal as provided by the CIOMS Working Group 8 is:

“…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 could be a problem which has never previously been suspected to be associated 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 than anticipated. The signal may be generated from qualitative analysis of spontaneous reports or quantitative analysis through data mining and statistical activities.

SIGNAL DETECTION AND SIGNAL MANAGEMENT:

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 risks associated with a particular drug have changed Sources for the detection of signals can come from:

·        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) other                relevant sources

    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. Relevant information may also be made available from other sources, such as poisons centres.

Signals arising from spontaneous reports also could be detected via:

·        Monitoring large adverse drug reaction databases such as Eudravigilance and the          FDA AERs system
·         Published articles
·        PSURs
·       Ongoing benefit-risk monitoring

The process for managing signals within pharmaceutical companies and regulatory authorities / pharmacovigilance centres must systematically address the following steps:

•         Signal detection
•        Validation and Confirmation
•         Analysis
•         Prioritisation
•         Assessment
•         Recommending action

Basic principles of pharmacovigilance

                      Basic Principles of Pharmacovigilance

PHARMACOVIGILACE:

The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drugrelated problem.

Ø  collects, records, codes ADEs / ADRs

Ø  analyses and assesses the reports

Ø  promotes the safe use of drugs

Ø creates appropriate structures and means of communication needed to perform its tasks

GOALS OF PHARMACOVIGILANCE :

Ø  to improve patient care and safety

Ø  to improve public health and safety       

Ø  to contribute to the assessment of benefit, harm, effectiveness and risk of medicines  

Ø  to promote education and clinical training

Ø  to promote effective communication to the public

Ø to promote rational and safe use of medicines

ADVERSE DRUG REACTION :

Adverse Reaction means a response to a medicinal product which is noxious and unintended and which occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease or for the restoration, correction or modification of physiological function.

 DATA SOURCES IN PHARMACOVIGILANCE :

Ø Spontaneous Reporting Systems

 • National PV Centre / Drug Authority

• from the published scientific literature and

Ø  Adverse Reaction Case Reports by the MA holder (e.g. collected by sales representatives)

Ø Periodic Safety Update Report (PSUR) provided by MA holder

ROLE OF SPONTANEOUS REPORTING :

Ø  covers all drug use of all populations

Ø  13/18 of the most important ADRs before 1982 have been ’signaled’ for the first time by SRs

Ø  More than 50% of all ’alert’ black boxes in the PDR derive from SRs

AE / ADR-REPORTS ASSESSMENT :

Ø  Seriousness / Severity

• ICH

• NCI

Ø  Frequency

Ø  Causality

Ø Pattern, e.g. pre-disposing risk factor

MINIMUM CRITERIA TO REPORT AN ADVERSE DRUG:

Ø  ‡ an identifiable source

Ø  ‡ an identifiable patient

Ø  ‡ a suspected product

Ø ‡ a suspected reaction

SERIOUS ADVERSE REACTION :

Serious adverse reaction means an adverse reaction which results in death, adverse reaction which results in death, hospitalisation, or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a congenital anomaly / birth defect.          

WHAT IS SIGNAL :

A signal is a set of data constituting a hypothesis that is relevant to the rational and safe use of a drug in humans.

A signal is reported information on a possible causal relationship between an adverse event and a drug, of which the relationship is unknown or incompletely documented previously.

SIGNAL GENERATION :

Ø three convincing ADR-reports

Ø  specified ADR-Reports Prescriptions

Ø  specified ADR-Reports (PRRs) all Reports

Ø  specified Reports / Exposed Persons Background Incidence

REFERENCES :

Ø  Volume 9 – PHARMACOVIGILANCE

Ø  CIOMS: Reporting Adverse Drug Reactions: Definition of Terms and Criteria for their use

Ø CIOMS: Geneva 1999

Taqdeer and Hard work

Kuch Log kehte hai qeesmat naseeb taqdeer kuch nahi hota nahi kuch matter karta hai, saab mehnat our hard work se milta hai, par har kisi ka yaqeen alag alag hai, Har kisi ki soch alag alag hai.


Kuch log mehnat kar k saab pate hai, our kuch apni taqdeer se, jaise kisi ne mehnat lagan our hard work se saab pa liya our kisi ne wahi saab naseeb se.

Kisi ko koi cheez hard work se milti hai to kisi ko wohi cheez naseeb se. Par insaan ne har hal me khush hona our khush rehna seekhna chaiye,

Q ke nahi aap kisi ki mehnat cheen sakte ho our nahi kisi ka naseeb/Taqdeer badal sakte ho.Jo apka hai wo apka hi hai use koi cheen nahi sakta, our jo apka nahi use aap kisi se cheen nahi sakte.

Findings :

1- Destiny and hard work always goes together.

2- Hard work always pays off.

3- Always be Happy with your Destiny.