What is Pharmacovigilance ?

The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problems.
Recently its concerns have been widened to include herbals, traditional and complementary medicines, blood products, biological medical devices and vaccines. (Source: The Importance of Pharmacovigilance, WHO 2002)

Need for Pharmacovigilance

Unreliability of preclinical safety data : Small and specified sample size Pressure from various groups to reduce time for approval

Changing pharmaceutical marketing strategies : Launch in many countries at a time Changing physician and patient preferences : Increasing use of drugs to improve quality of life Shift of supervised to self-administered therapy Easy accessibility : Increasing conversion of prescription drugs to OTC drugs Easy access by internet

Some basic definitions :

Adverse event : Any untoward medical occurrence that may present during treatment with a pharmaceutical product but which does not necessarily have a causal relationship with this treatment. Adverse (drug) reaction (ADR) A response which is noxious and unintended, and which occurs at doses normally used in humans for the prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function. (WHO, 1972).

 Serious Adverse Event or Reaction :

A serious adverse event or reaction is any untoward medical occurrence that at any dose: results in death requires inpatient hospitalisation or prolongation of existing hospitalisation results in persistent or significant disability/incapacity is life-threatening

Unexpected adverse reaction :

An adverse reaction, the nature or severity of which is not consistent with domestic labelling or market authorization, or expected from characteristics of the drug.

Suspected Unexpected Serious Adverse Reaction :

A serious adverse event becomes a SUSAR if the serious event is suspected (possibly, probably or definitely) to be related to the investigational medicinal product and is unexpected i.e. not previously documented in any information on protocol

 Causality assessment : The evaluation of the likelihood that a medicine was the causative agent of an observed adverse reaction. Causality assessment is usually made according established algorithms. Dechallenge :

The withdrawal of a drug from a patient; the point at which the continuity, reduction or disappearance of adverse effects may be observed. Rechallenge :
The point at which a drug is again given to a patient after its previous withdrawal

Types of ADR
TYPE Type A (Augmented) Type B (Bizzare) CHARACTERISTIC Predicted by pharmacological mechanisms Not expected from the known pharmacological mechanisms EXAMPLE Hypotension by - blockers

Hepatitis caused by halothane

Type C (Chronic)
Type D (Delayed)

Continuous drug use

Occurrence after the cessation of treatment

Dementia by anticholinergics
Ophthalmopathy after chloroquine

Type E (End of dose)

Type F (Failure of therapy)

Characterized by withdrawal reactions

Results from ineffective treatment

Hypertension and restlessness in opiate abstainer

Accelerated hypertension because of inefficient control

Certain

Unassessable or Unclassifiable

Probably or likely

The WHO causality assessment system

Conditional or Unclassified Possible

Unlikely

What should be reported?

Unknown, unexpected New drugs Serious (also when known) Fatal, life-threatening Hospitalisation Persistent incapacity or disability Dependence Malformations Unexpected beneficial effects Unexpected ineffectiveness

Where to report ?
In India , after completing the form sholud be
returned to the same Pharmacovigilance centre from where it was obtained. The forms are accepted only at the 28 peripheral centres Some centre like JIPMER, Pondicherry and AIMS, Kochi have web-based facility for ADR reporting.

How to Report ?
As per the ICH guidelines the Pharmacovigilance method can be categorized as :
Passive Surveillance
Intensified Reporting Spontaneous Reporting Case Series Stimulated Reports Sentinel Sites Drug Event Monitoring Registries Cross-sectional Study Case-control Study Cohort

Active Surveillance
Comparative Observational Studies Descriptive Studies Targeted Clinical Investigations

Natural History of Disease Drug Utilization Study

Spontaneous reporting system

Reporting Adverse Event during a Clinical Trial

Investigator

immediately or within 24 hours

Study Monitor

Death and life-threatening, associated (by Investigator) Cases Immediately or within 24 hours to entry site

immediately or within 24 hours

Sponsors Safety Officer

immediately or within 24 hours

Global HQ

Signal detection
Reported information on a possible causal association between an adverse event and a drug, the relationship being unclear or incompletely documented previously Process of signal detection

Signal generation

Signal strengthening

Signal testing, evaluation and explanation

National Pharmacovigilance Program

The CDSCO, Ministry of Health and Family Welfare, Govt. of India launched the National Pharmacovigilance Program on 23 November, 2004 . It is largely based on the recommendations made in the WHO document titled Safety Monitoring of Medicinal Products Guidelines for Setting up and Running a Pharmacovigilance Centre. Three interactive workshops were conducted by CDSCO/WHO for training the participants of the program . The World Bank has committed to provide $ 1,00,000 for this project

Functions of National Pharmacovigilance Centre at CDSCO

Monitor the adverse drug reaction . Review Periodic Safety Update Reports (PSURs) submitted by pharmaceutical companies . Maintain contacts with international regulatory bodies working in pharmacovigilance and exchange information on drug safety.

Assess the regulatory information relating to safety in order to determine what action, if necessary, needs to be taken to improve safe use.

WHO Programme for International Drug Monitoring

Launched in 1968 What is it?

Provides a forum to, collaborate in the monitoring of drug safety.

Collects individual case reports of suspected ADRs Maintains a database Consists of a network of National centers and UMC

Functions of WHO

UPPSALA MONITORING CENTRE

Set up in 1978 Situated in Sweden

Activities: Coordinating the WHO programme for International Drug Monitoring Collecting , assessing and communicating information Alerting regulatory authorities

AREAS OF WORK
Receipt, analysis and recording of worldwide adverse event data

Maintenance and screening of international database

Publication of previously unknown adverse events in SIGNAL

Editing, updating and publishing the WHO Drug Dictionary

Publishing scientific articles

VigiBase
VigiBase is the name for the WHO international ADR database. It is the largest and most comprehensive database developed and maintained by UMC. VigiBase is a unique collection of international drug safety data. The data is available in a wide range of services, from advanced neural network analysis to basic. Its common uses are signal detection, updating PSUR and comparing the reports

What happens when a sufficient amount of ADR is received ?

Added to drugs label or package insert The regulatory authority can ask the manufacturer to distribute letters to all physicians and pharmacists

The regulatory authority can ask the manufacturer to develop a formal surveillance program

If risks outweigh the benefits then the drug is withdrawn from the market

PHARMACOVIGILANCE
Deals only with the adverse

POST MARKETING SURVEILLANCE

Deals with safety,

drug reaction
Carried out throughout and

efficacy and market value of the drug Conducted during Phase IV of clinical trial
It is the sponsors

after the trial

National Pharmacovigilance

Programme conducts pharmacovigilance

responsibility to disseminate the information on ADRs

Thank You