Naganand.

Jayakumarswamy
Pharmacovigilance :is the study of the safety
of marketed drugs under the practical
conditions of clinical use in large
communities
Pharmacovigilance: is concerned with the
development of science and regulation in the
area of drug safety.
Pharmacovigilance aims at the detection,
assessment and prevention of adverse effects
and other problems related to the use of
medicines.
 Thalidomide tragedy (1961-62): The greatest
of all drug disasters.
 Thalidomide had been introduced and
welcomed as a safe and effective hypnotic
and antiemetic. It rapidly became popular
for the treatment of nausea and vomiting in
early pregnancy.
 Tragically the drug proved to be a potent
human teratogen that caused major birth
defects in an estimated 10,000 children
 Phocomelia was a characteristic feature
 Sulfanilamide tragedy: Elixir sulfanilamide was
an improperly prepared sulfanilamide medicine
that caused mass poisoning in the United States
in 1937. It caused the deaths of more than 100
people. The public outcry caused by this incident
and other similar disasters led to the passing of
the 1938 Federal Food, Drug, and Cosmetic Act
 The thalidomide disaster led,in Europe and else
where ,to the establishment of the drug
regulatory mechanisms of today.
 These mechanisms require that new drugs shall
be licensed by well –established regulatory
authorities before being introduced into clinical
use
 List of a few licenced medicines withdrawn
after marketing for drug safety reasons:
1. Secholex(polidexide)-1975
2. Zomax-1983
3. Halcion-1991
4. Kava kava-2001-due to liver toxicity
5. Vioxx(rofecoxib)-2004-due to incresed
cardiovascular risks
6. Bextra(valdecoxib)-2005-due to Stevens-
Johnson syndrome
 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 the treatment.
 Adverse reaction: WHO technical report:A
response to a drug 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
 Expected: As opposed to “unexpected”, an event
that is noted in the investigatorse brochure or
labeling (package insert or summary of product
characteristics).
 Unexpected adverse reaction: the nature or severity
of which is not consistent with the domestic labeling
or market authorization, or expected from
characteristics of the drug.
 Signal: Reported information on possible causal
relationship between an adverse event and a drug,
the relationship being unknown or incompletely
documented previously. Usually more than one single
report is required to generate a signal depending
upon the seriousness of the event and quality of
information.
 Data mining: is used to describe various
automated or semiautomated techniques to
generate signals from existing databases.
For each AE, the calculation of the proportion of
that AE as a function of all Aes reported for a
drug is calculated and compared with the
proportion of that AE for all other drugs in the
database
Example: liver failure for drug X was reported as
95 times out of the 1,418total AEs for drug X.The
proportion is 95/1,418=0.067 and is called
“Score” or “Statistic”.
This score can be used as a comparison for other
drugs in database.
For a signal to be generated the score should be >1
 Type A: (Drug reactions)-Pharmacological
adverse effects.
1. Common->1%
2. Dose relationship
3. Suggestive time relationship
4. Reproducible
 Type B: (“Patient Reactions”)
1. Immunoallergic reactions
2. Idiosyncrasy
3. Rare<1%
1. Unexpected
2. Causality uncertain
3. Not reproducible experimentally
4. Characteristic-serious

 Type C adverse effects (Statistical effects)

1. Often long latency
2. Mechanism unknown
3. Difficult to reproduce experimentally
 Passive surveillance
1. Spontaneous reporting
2. Case reports
3. Case series
 Stimulated reporting
 Active surveillance
 Comparative observational studies
1. Cross sectional studies
2. Case control study
3. Cohort study
 FDA:The Food and Drug Administration (FDA or
USFDA) is an agency of the United States
Department of Health and Human Services, one
of the United States federal executive
departments, responsible for protecting and
promoting public health through the regulation
and supervision of food safety, tobacco products,
dietary supplements, prescription and over-the-
counter pharmaceutical drugs (medications),
vaccines, biopharmaceuticals, blood
transfusions, medical devices, electromagnetic
radiation emitting devices (ERED), veterinary
products, and cosmetics.
 EMEA: The European Medicines Agency is a
decentralised body of the European Union
located in London
 MHLW: Ministry of Health, Labor and
Welfare,Japan
 CDSCO: The government of India with the
assistance of world bank has initiated the
National pharmacovigilance programme. The
central drugs standard control organization
(CDSCO) is coordinating the country wide
pharmacovigilance programme under the aegis of
Ministry of health and family welfare, DGHS New
delhi
 Vigibase: The Uppasala monitoring
centre(UMC, on behalf of WHO) has over 3
million AE case reportes from over 75
countries. The data are supplied by national
health authorities. Most of the data are from
the United states and supplied by the
FDA.The UNC does not review or assess the
individual cases put into database, but it
does pharmacovigilance analyses and
signaling.