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Associate professor
• 1961 - thalidomide disaster
• 1968 – WHO pilot research project for
international drug monitoring
• 1971 – WHO meeting
1.to advocate establishment of national
centers for drug monitoring
2.to provide guidelines
3.to identify the contribution that national
centers might take to the international
• 1984 – international society of
• 1992 – european society of
• 2002 – WHO pharmacovigilance
• 2004 – national pharmacovigilance
advisory committee (NHAC) with DGHS as
chairman and drug controller general of
india as member secretary
• 24 peripheral centers, 6 regional centers
and 2 zonal centers
Widening horizons
• Illegal sale of medicines and drugs of
abuse over internet
• Increasing self medication practices
• Widespread manufacture and sale of
counterfeit and substandard medicines
• Increasing use of traditional medicines
outside the confines of traditional culture
of use
• Increasing use medicines of different
systems with potential for drug
Post marketing surveillance
• Monitoring of drug safety after
introducing into the market through
various systems
• Need
1.To assess risk benefit ratio
2.To confirm safety and efficacy
3.To detect less common adverse
Methods of surveillance
• Anecdotal reporting
• Voluntary reporting
• Intensive event reporting
• Cohort studies (prospective)
• Case control studies (retrospective)
• Population statistics
• Meta-analysis
Organizations involved
• WHO – collaborating center for international drug
monitoring is Uppsala monitoring centre provides
activities and events in PV
• CIOMS – council for international organizations of
medical sciences-safety information
communication between regulators and
• ICH – international conference on harmonization
discusses scientific and technical aspects of
product registration.
• WHO-ART – WHO adverse reaction terminology
for coding clinical information to drug therapy.
Frequency of ADR
• Very common>=1/10
• Common >=1/100 and <1/10
• Uncommon >=1/1000 and <1/100
• Rare >=1/10000 and <1/1000
• Very rare <1/10000
Causality assessment
• Certain : proven on dechallenge and
• Probable : dechallenge confirms.cannot
• Possible : can be explained by concurrent
disease or other drugs
• Unlikely : not documented in literature
• Unclassified : additional data is awaited so
not documented
• Unclassifiable : additional data has come
but not fit into any categories
Methods of causality
• WHO assessment scale
• Naranjo’s scale
• European ABO system
• Karch and Lasagna’s scale
• Kramer scale
• Bayesian network
• Yale logarithm
• Spanish imputation system
question Yes No Don’t
1 Are there previous conclusion reports on this +1 0 0
2 Did the adverse event appear after the suspect drug +2 -1 0
was administered?
3 Did the AR improve when the drug was discontinued +1 0 0
or a specific antagonist was administered?
4 Did the AR reappear when drug was readministered? +2 -1 0

5 Are there alternate causes [other than the drug] that -1 +2 0

could solely have caused the reaction?
6 Did the reaction reappear when a placebo was -1 +1 0
7 Was the drug detected in the blood [or other fluids] +1 0 0
in a concentration known to be toxic?

8 Was the reaction more severe when the dose was +1 0 0

increased, or less severe when the dose was
9 Did the patient have a similar reaction to the same +1 0 0
or similar drugs in any previous exposure?
10 Was the adverse event confirmed by objective +1 0 0
• > 9 = definite
• 5-8 = probable
• 1-4 = possible
• 0 = unlikely
Schedule Y requirement
• Unsuspected adverse event is
communicated from
1.Sponsor to regulatory authorities
within 14 days
2. Investigator to sponsor within 24
3. Investigator to ethics committee
within 7 days
Partners in
• The WHO quality assurance and safety :
medicines team
• The uppasala monitoring centre
• National pharmacovigilance centres
• The pharmaceutical industry
• Hospitals and academia
• Health professionals
• Patients
• Others partners
Benefits of monitoring
• Improvement in patient care and safety in
relation to use of medicines and interventions.
• Improvement of public health and safety.
• Assessment of benefit, harm, effectiveness and
risk of medicines.
• Encouragement of safe rational and more cost
effective use of medicines
• Increase public awareness through
• Education and clinical training in pharacovigilance
• Empowerment and involvement of practitioners,
patients and public
How to recognize ADR
• Ensure the medicine ordered is the medicine
received and actually taken by the patient.
• Verify the onset of suspected ADR was after the
drug was taken, not before and discuss carefully
the observation made by the patient.
• Determine the time interval between the
beginning of drug treatment and the onset of
• Evaluate the suspected ADR after discontinuing
the drugs or reducing the dose and monitor the
patient’s status. If appropriate restart and
monitor the recurrence.
• Analyze the alternative causes that could on their
own have caused the reaction.
• Use relevant up to date literature
and personal experience on the
drugs and ADR to verify previous
reports on the reaction-through
pharmacovigilance center and drug
information center.
• Report any suspected ADR to the
reporting center in the hospital or
national ADR center.
Ethics in pharmacovigilance
• The Erice declaration provides framework of values and
practice for collection, analysis and subsequent
communication of drug safety issues.
• It asserts scientific and clinical issues on the one hand and
right of the public to be openly and fully informed on the
• It requires the active commitment of all involved
regulators, policy makers, health personnel, journalists and
(not last) pharmaceutical manufacturers.
• Information about drug safety programmes should be
easily available to the public so that the central role of
patient in safe and rational use of drugs is understood.
• Available information is not always reliable and scientifically
valid. Direct advertising to the consumer resulting self
medication, illicit sale of medicines over internet and over
prescribing by doctor on demand.
The Erice Declaration(1997)
• Challenges all these players
– Public health administration
– Health professionals
– The pharmaceutical industry
– Government
– Drug regulators
– The media
– Consumers to strive towards the highest ethical,
professional and scientific standards in protecting and
promoting the safe use of medicines
The declaration urges governments and others involved in
determining policies relating to the benefit, harm,
effectiveness and risk of medicines to account for what
they communicate to the public and patients.
Protecting patient
Pharmacovigilance in clinical
Educational strategies
• Integrating pharmacovigilance in UG
• Basic training of health professionals
• Training of health workers
• Consumer education and information
• Drug bulletins to prescribers and
• Drug information centers to be established
What is ADR monitoring ?
• Systemically collecting information
about adverse drug experiences with
the aim of, through feed back to the
parties involved, contribute to
continuously improving drug therapy.
Aim : To detect
• Serious unexpected ADRs
• Increased or unexpectedly high
frequency of known significant ADRs
• To prepare list of ADRs not
previously reported
• To disseminate the information
through regular bulletins, reports,
and articles in the press
Need for monitoring
• Short coming of premarketing studies-
which reveal most common and acute
untoward effect
• Increase cost of patient care
• Medication : 10-57% is self medication
• Our country has vast population, poverty
and rich research ground
• Accelerated approval and rapid
introduction of new drugs
• Paucity of ADR data
Who reports ?
• Doctors-hospital level,MO from
• Dentists
• Drug manufacturers
• Pharmacists and nurses
Types of ADR
Type Type of Features examples
A Augmented Common, predictable, low Bradycardia–β-
mortality blockers
B Bizarre Uncommon, unpredictable, high Anaphylaxis -
morbidity & high mortality Penicillin
C Chronic Dose related & time related Dyskinesia -
D Delayed Time Related Teratogenesis

E End of use Withdrawal of chronic therapy Corticosteroids

F Failure Unexpected failure of therapy Oral contraceptive
failure - Rifampin
What to report ?
• New drugs – all suspected adverse
• Established drugs
- All serious reactions-well recognized
- All reactions to vaccines
- Unexpected high frequency of a known
adverse reaction
- All reactions to pregnant & lactating
women including new born
Where to report ?
• Nearest ADR monitoring centers
• Peripheral centers
• Regional centers  national center at
new Delhi
• Directly on internet
Reasons not to report
• Uncertain association
• Too trivial to report
• Too well known to report
• Unaware- existence of national center
• Unaware- of the need of to report of
• Not enough time
• Non availability of ADR forms
• Too bureaucratic
• Legal issues
• Lack of feed back
Thank you