Pharmacovigilance

Definition of pharmacovigilance
The science and activities relating to the
detection, assessment, understanding and
prevention of adverse effects or any other drug-
related problem.
Pharmaco = medicine
Vigilare = to watch
alert watchfulness
forbearance of sleep; wakefulness
watchfulness in respect of danger; care; caution;
circumspection
the process of paying close and continuous
attention

Place where pharmacovigilance is used
Need of pharmacovigilance in
society
1.To prevent the deaths by using medicines due
to adverse drug reactions.
2.To monitor the clinical trials data whether the
drug is safe or nor.
3.To determine any adverse drug reaction of
particular drug through the world.
4.Safety data of drugs used in clinical trails
5. Promoting rational use of medicines and
adherence.
6. Ensuring public confidence.








The scope of pharmacovigilance
Improve patient care and safety in relation to
the use of medicines, and all medical and
paramedical interventions,
Improve public health and safety in relation to
the use of medicines,
Contribute to the assessment of benefit, harm,
effectiveness and risk of medicines,
encouraging their safe, rational and more
effective (including cost-effective) use, and
Promote understanding, education and clinical
training in pharmacovigilance and its effective
communication to the public.

Opportunities in
pharmacovigilance
1.Ther are many companies providing jobs for
pharmacovigilance graduates (cognizant,
oracle, mahindra sathyam...)
2.Any science graduate, Pharma graduate and
Medical graduate is eligible to do study
pharmacovigilance .
3.There are used in management of clinical trails
data.
4.Many companies are coming into this field
(Pharma, CRO, IT, BPO and KPO orgs).
What is an ADR
"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." WHO).
A response to a drug which is noxious and
unintended, and which occurs at doses
normally used for the prophylaxis, diagnosis
or therapy of disease, or for the modification
of physiological function.

Definations
Expected ADR : An ADR to a drug that has been
previously observed and documented, if the ADR
is already listed in the official prescribing
information, it is an expected ADR
Unexpected ADR : the nature or severity of which
is not consistent with the applicable product
information.
Major Aims Of
Pharmacovigilance
Early detection of unknown reactions & interactions

Detection of increases in frequency of known ADR

Identification of risk factors & Quantifying risks

Preventing drug induced illness

Rational & safe use of medicines
Major Aims Of
Pharmacovigilance
Assessment and communication of benefits /risks of
drugs

Educating and informing patients


10
Pharmacovigilance
Pharmacovigilance
Investigational products Marketed Products
Why pharmacovigilance?
Humanitarian concerns
Economical concerns
check if drugs on the market fulfill their intended
role in society i.e. if resources spent on drugs
produce optimal results in terms of
alleviating human suffering
reduce disease related economical loss
Protection of rights and well being of research subjects
Conduct an ongoing assessments of risks vs benefits


Clinical Development
Phases of Clinical Development
Phase I
Phase II
Phase III
Phase IV
All these phases focus on monitoring the
efficacy and the safety of the investigational
product and most of these phases last for 2-3
yrs


Limitations of premarketing clinical
trials
Short duration : Effects that develop with chronic
use or those that have a long latency period are
difficult to detect in preclinical trials
Relatively small number of patients exposed to
the drug
Rare ADR are difficult detect in these trials
Limitations of clinical trials
continued.
Narrow population
Those trials where efficacy is studied dont
cover actual evolving use
Premarketing trials generally dont include
special groups (eg children, elderly, coexisting
disease)
Not always representative of the population
that may be exposed to the drug after
approval.
Required sample size for detecting a rare adverse
drug reaction

Incidence
of ADR
Number of patients to be observed
in order to detect 1,2 or 3 cases of
ADR
1 2 3
1 in 100
1 in 200
1 in 1,000
1 in 2,000
1 in 10,000
300
600
3,600
6,000
30,000
480
960
4,800
9,600
48,000
650
1,300
6,500
13,000
65,000
Some of the drugs withdrwn post
marketing
Drug Date
approved
Date
withdrawn
Reason for
withdrawl
Fenfuramine 1973 1997 Valvular
heart
deffect
Bromfenac 1997 1998 Liver
failure
Mibafradil 1997 1998 Interaction
with other
drugs
Minimum reportable information for
ADR
An identifiable patient
An identifiable reporter
A suspect product
An adverse event.

Safety data management becomes an important
part of pharmacovigilance.

How can data help a product/patient
Defend a product from false safety claims
Influence label
Allow practitioners to feel more comfortable using a
drug
Enables better decision making around risk
management

What is the end goal
The data helps in detecting the signal
something that draws attention
Pattern of the ADRs
Trend
How frequently is the signal or pattern observed
What is the severity.
US FDA definition of signals
New unlabeled event, especially if serious
An apparent increase in the severity of a labeled
event
New drug interaction
More than a small number of serious events thought
to be extremely rare.
Identification of previously unrecognized at risk
population
Product confusion
Misuse
Concerns that risk management plan is inadequate
Other
What is the worst that can happen if
reported
If the drug is blatantly unsafe and the risk/benefit
ratio is not favorable its always better to withdraw
that drug from the market ( this will not happen
unless it really should happen
Label change
Regulatory agencies may request additional
information ( more studies, risk management
program etc.)


There are other ways to gather
additional safety information
Epidemiology studies
Registries
Surveys

Pharmacovigilance reporting
Expedited reporting
Periodic safety update reports
Both these can be from the following source
Spontaneous reports, clinical trial reports, literature
reports, registries, regulatory authorities, PMSS
The pharmacovigilance process


Case reports
Case database
Signal
detection
Signal
analysis
Action
Follow up
Communication
Reporting process
All serious adverse events should be reported
immediately to the sponsor/ regulatory
For reported deaths, the investigator should
supply the sponsor IRB/IEC with any
additional requested information( eg Autopsy
report, terminal medical report)
Notify IRBS and independent ECs of all
serious adverse events
What to report (both Serious and non
serious)
All adverse events suspected to have been caused by new
drugs and drugs of current interest
If drug is ineffective
All suspected drug interactions
Reactions to any other drugs which are suspected of
significantly affecting a patient's management, including
reactions suspected of causing:

Death
Life-threatening (real risk of dying)
Hospitalization (initial or prolonged)
Disability (significant, persistent or permanent)
Congenital anomaly
Required intervention to prevent permanent impairment or
damage.


Pharmacovigilance in practise.
Continued
Data entered in the database
Assessment of the event (expected or
unexpected).
Medical confirmation of the event.
Expedited reporting of the event.
Source country where the event occurred.
Submission to regulatory authorities.
THANK YOU