2. Introduction
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"Dying from a disease is sometimes unavoidable. But, dying from
an adverse drug reaction is unacceptable“
Pharmacovigilance is the science and activities related to;
o Detection,
o Assessment,
o Understanding
o Prevention of
Adverse effects or
Any other possible drug related problem.
3. Contd.
o The etymological roots are: pharmakon (Greek), “drug;” and
vigilare (Latin), “to keep awake or alert, to keep watch.”
o Pharmacovigilance is used to describe the processes for
monitoring and evaluating ADRs
o Recently, its concerns have been widened to include
herbals, traditional and complementary medicines, blood
products, biologicals, medical devices and vaccines“
(WHO, 2002)
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7. ADVERSE DRUG REACTION
o Adverse Drug Reaction: A response to a drug which is noxious
and unintended at the therapeutic level i.e. occurs at doses normally
used in man for the prophylaxis, diagnosis, or therapy of disease, or
for the modification of physiological function.
o 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.
o Side Effect :Any unintended effect of a pharmaceutical product
occurring at doses normally used in man which is related to the
pharmacological properties of the drug.
8. Severity of ADR:
o Minor: No need of therapy, antidote,
or hospitalization
o Moderate: Requires drug change , specific
treatment, hospitalization
o Severe: Potentially life threatening,
permanent damage, and
prolonged hospitalization.
o Lethal: Directly or indirectly leads
to death.
MODERATE
SEVERE
LETHAL
LETHAL
9. PREDISPOSING FACTORS FOR ADRs
o The main clinical factors which increase the chance that patients
will experience an adverse reaction are listed below:
o Age
- the elderly and neonates are at greatest risk
o Gender
- women are generally at greater risk
o Race
- ethnic origin may affect drug metabolism
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10. Contd.
o Impaired excretory mechanisms
- reduced hepatic and/or renal function
o Polypharmacy
- drug interactions
o Any previous history of an adverse drug reaction
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12. FUNCTIONS OF PHARMACOVIGILANCE
Collects reports , data, ADR’s etc.
Analyses and assesses the reports.
Promotes the safe use of drugs.
Creates appropriate structures and means of communication needed to
perform its tasks.
Identifying new information about hazards associated with medicines.
Preventing harm to the patients.
13. PHARMACOVIGILANCE - A SHARED
RESPONSIBILITY
Company - legally and morally responsible for
monitoring their product.
Regulatory authorities – are responsible for the
safety of the newly licensed drugs.
Doctors – responsible for prescription of safe drugs
to patients.
Pharmacist & nurse – responsible for monitoring of
drug therapy given to patients and identification and
reporting of ADRs.
14. AIM OF PHARMACOVIGILANCE
o To improve public health and safety in relation to
medicines, cosmetics, herbal products etc.
o Early detection of unknown adverse reactions and interactions
o Identification of risk factors and possible mechanisms underlying
adverse reaction.
o Estimation of quantitative aspects of benefit/risk analysis of information
needed to improve drug prescribing and regulation.
o To promote understanding, education and clinical training in
pharmacovigilance and its effective communication to health
professionals and the public.
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17. PHARMACOVIGILANCE - DATA SOURCES
Spontaneous Reporting Systems
• National PV Centre / Drug Authority
Drug Bulletins
Adverse Reaction Case Reports by the MA (Master Agreement)
Periodic Safety Update Report (PSUR) provided by MA holder
20. ADR Detection Methods
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• Passive surveillance
Spontaneous reporting system (SRS)
Case series
• Stimulated reporting
• Active surveillance
Sentinel sites
Drug event monitoring
Registries
• Comparatives observational studies
Cross sectional study
Case control study
Cohort study
• Targeted clinical investigations
Descriptive studies
Natural history of disease
Drug utilization study
21. SPONTANEOUS REPORTS
A communication by consumers or health care professionals to a
company or Regulatory Authority that describes one or more
ADR in a patient who was given the drug.
Plays a major role in the identification of safety signals once the
drug is marketed.
Gives alerts on rare AEs that were not detected in earlier clinical
trials or pre marketing studies.
Provides important information on at risk groups, risk factors and
clinical features of known serious ADRs.
22. CASE SERIES
Series of case reports can provide evidence of an association of a
drug and AE.
Generally more useful for generating hypothesis than for
verifying an association between drug exposure and outcome.
Certain distinct adverse events occur more frequently with drug
therapy, such as anaphylaxis, aplastic anaemia, toxic epidermal
necrosis and Stevens- Johnson Syndrome.
23. STIMULATED REPORTING
A method used to encourage and facilitate reporting by health
professionals for new products.
On line reporting of AE; Systematic stimulation of reporting of AE.
Limitations
Data are often incomplete. Not useful to generate accurate
incidence rates.
ACTIVE SURVEILLANCE
More feasible to get comprehensive data on individual AE reports.
To ascertain completely the number of AE via a continuous pre-
organised process. E g : Follow up of patients treated with a
particular drugs.
24. SENTINEL SITES
Active surveillance carried out at Institutions, Nursing homes, hospitals
etc.
Provide information such as data from specific patient subgroups, drug
abuse etc.
LIMITATIONS
Selection biasness, Small number of patients and Increased costs.
25. DRUG EVENT MONITORING
Patients are identified by electronic prescription data or automated
health insurance claims.
A follow up questionnaire can be sent to each physician or patient at
specified intervals.
Information on patient demographics, indication for
treatment, duration of therapy (including start dates), dosage, clinical
events, and reasons for discontinuation can be included in the
questionnaire.
Limitations:
Poor physician and patient response rates and unfocused nature of
data collection can obscure important signals.
26. REGISTRIES
A registry is a list of patients presenting with same characteristics.eg:
Disease registry, drug registry or pregnancy registry.
Differ from each other depending on type of patient.
Information can be obtained by using standard questionnaire.
Comparative Observational Studies
Traditional epidemiologic methods are a key component in the
evaluation of adverse events.
Observational study designs are useful in validating signals from
spontaneous reports or case series.
27. Types of designs
Cross sectional study.
Case control study.
Cohort study.
Cross-sectional study (survey)
Data collected from a population of patients at a single point in time
(or interval of time) regardless of exposure or disease status.
Primarily used to gather data for surveys or for ecological analyses
Major drawback:
Relationship between exposure and outcome cannot be directly
addressed.
28. Case-control study
Cases of disease (or events) are identified.
Controls, or patients without the disease or event of interest, are then
selected from the source population.
The controls should be selected : the prevalence of exposure among
the controls represents the prevalence of exposure in the source
population.
Exposure status of the two groups is then compared.
29. Cohort study
A population-at-risk for the disease (or event) is followed over time for
the occurrence of the disease (or event).
Information on exposure status is known throughout the follow-up and
hence incidence rates can be calculated.
Comparison cohorts of interest are selected on the basis of drug use
and followed over time.
Multiple adverse events can also be investigated using the same data
source in a cohort study.
30. Descriptive studies
Primarily used to obtain the background rate of outcome events and/or
establish the prevalence of the use of drugs in specified populations.
Natural history of disease: Focused on the natural history of
disease, including the characteristics of diseased patients and the
distribution of disease in selected populations, as well as estimating
the incidence and prevalence of potential outcomes of interest.
Drug utilization study: These studies provide data on specific
populations, such as the elderly, children, or patients with hepatic or
renal dysfunction, often stratified by age, gender, concomitant
medication, and other characteristics.
31. 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 .
32. To monitor Adverse Drug Reactions (ADRs) in population.
To create awareness amongst health care professionals about the
importance of ADR reporting in India.
To monitor benefit-risk profile of medicines.
Generate independent, evidence based recommendations on the safety
of medicines.
Support the CDSCO for formulating safety related regulatory
decisions for medicines.
Create a national centre of excellence at par with global drug safety
monitoring standards
33. 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 industries.
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.
34. India's Central Drugs Standard Control Organization
(CDSCO)
o Headquartered in New Delhi, the CDSCO is India's main regulatory body
for pharmaceuticals and medical devices.
o The Drug Controller General of India (DCGI) is responsible for the
regulation of pharmaceuticals and medical devices.
o The DCGI is advised by the Drug Technical Advisory Board (DTAB) and
the Drug Consultative Committee (DCC).
o The CDSCO establishes safety, efficacy, and quality standards for
pharmaceuticals and medical devices.
o It publishes and updates the Indian Pharmacopoeia, a list of regulated
pharmaceuticals and devices.
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37. Product recall due to toxicity
A product recall is a request to return to the maker a batch or an
entire production run of a product, usually due to the discovery of
safety issues.
The recall is an effort to limit liability for corporate negligence
(which can cause costly legal penalties) and to improve or avoid
damage to publicity.
Recalls are costly to a company because they often entail
replacing there called product or paying for damage caused by use,
although possibly less costly than consequential costs caused by
damage to brand name and reduced trust in the manufacturer.
39. Drug name Withdrawn Remarks
Thalidomide 1950s–1960s
Withdrawn because of risk
of teratogenicity; returned
to market for use
in leprosy and multiple
myeloma under
FDA orphan drug rules.
Lysergic acid
diethylamide (LSD)
1950s–1960s
Marketed as a psychiatric
drug; withdrawn after it
became widely used
recreationally.
Diethylstilbestrol 1970s
Withdrawn because of risk
of teratogenicity.
Phenformin and Buformin 1978
Withdrawn because of risk
of lactic acidosis.
Ticrynafen 1982
Withdrawn because of risk
of hepatitis.
40. Phenacetin 1983
An ingredient in "A.P.C." tablet; withdrawn
because of risk of cancer and kidney disease.
Methaqualone 1984
Withdrawn because of risk
of addiction and overdose.
Zimelidine 1983
Withdrawn worldwide because of risk
of Guillain-Barré syndrome.
Nomifensine (Merital) 1986
Withdrawn because of risk of haemolytic
anaemia.
Triazolam 1991
Withdrawn in the United Kingdom because
of risk of psychiatric adverse drug reactions.
This drug continues to be available in the
U.S.
Terodiline (Micturin) 1991 Prolonged QT interval.
Temafloxacin 1992
Withdrawn in the United States because of
allergic reactions and cases of haemolytic
anemia, leading to three patient deaths.
41. restat (Alredase) 1997
Withdrawn because of risk of
severe hepatotoxicity
rfenadine (Seldane, Triludan) 1998
Withdrawn because of risk of cardiac
arrhythmias; superseded by fexofenadine
befradil (Posicor) 1998
Withdrawn because of dangerous interactions
with other drugs
retinate 1990s Risk of birth defects; narrow therapeutic index
capone (Tasmar) 1998 Hepatotoxicity
mazepam (Restoril,
hypnos, Normison,
mestan, Tenox, Norkotral)
1999
Withdrawn in Sweden and Norway because of
diversion, abuse, and a relatively high rate of
overdose deaths in comparison to other drugs
of its group. This drug continues to be
available in most of the world including the
U.S., but under strict controls.
temizole (Hismanal) 1999
Arrhythmias because of interactions with
other drugs
42. Conclusion
Current progress in pharmacovigilance is marked by
increasing use of databases and by attempts to make the
process more proactive and organized.
Attempts are being made to augment the spontaneous, random nature
of the generation of pharmacovigilance data and to make the process
more systematic and structured.
There has been a coming together of academic, regulatory and
industrial interests across many countries to produce the guidance
documents for the conduct of pharmacoepidemiology studies.
