Pharmacovigilance

Dr Japhet Mangoyi

Definition
• The science and activities relating to the:
Detection
Assessment
Understanding
Prevention,

of adverse effects or any other drug-related problem

• Also called
adverse drug reaction monitoring
drug safety surveillance
side effect monitoring
spontaneous reporting
post-marketing surveillance
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 Objectives of Pharmacovigilance
•Promote rationale drug use practices
•Preventing harm from adverse reactions from
the use of authorised medicinal products
•Promoting the safe and effective use of
medicinal products

Objectives of Pharmacovigilance
• improve patient care and safety in relation to the use
of medicines and all medical and paramedical
interventions
Peripheral neuropathy (d4T/ddI)
ABC hypersensitivity
NVP rash, LF abnormalities (NVP)
Protozoal/Helminthic treatment programme
Autism in Europe and America (vaccines)
Adverse Events following Immunization (AEFI’s)

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 Adverse Reaction
• A harmful or unpleasant reaction, resulting from an intervention
related to the use of a medicinal product, which predicts hazard from
future administration and warrants prevention or specific treatment,
or alteration of the dosage regimen, or withdrawal of the product

• ADR can include medication error, harm from counterfeit drugs,

accidental overdose, quality problems and excipients

Unexpected adverse reaction

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

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 Adverse Event (AE)
• 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

• Can be any unfavourable and unintended sign (e.g. an

abnormal laboratory finding), symptom, or disease
temporally associated with the use of a medicinal
product, whether or not considered related to the
medicinal product

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

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 Serious Adverse Event or Reaction
• A serious adverse reaction is any untoward medical
occurrence that at any dose:
results in death
is life-threatening
requires in-patient hospitalization
prolongation of existing hospitalization
results in persistent or significant disability or incapacity
results in a congenital anomaly/birth defect

Serious Adverse Event or Reaction

• “Severe” is used to describe the intensity (severity) of a
specific event (as in mild, moderate or severe); the event
itself, however, may be of relatively minor medical
significance (such as severe headache)
• Seriousness (not severity) which is based on patient/event
outcome or action criteria serves as guide for defining
regulatory reporting obligation
• Life-threatening refers to a reaction in which the patient was
at risk of death at the time of the reaction; it does not refer
to a reaction that hypothetically might have caused death if
more severe
• Any suspected transmission via a medicinal product of an
infectious agent is also considered a serious adverse reaction 10

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 Signal
• Reported information on a possible causal relationship
between an adverse event and a drug, the relationship being
unknown or incompletely documented previously
• More than a single report is required to generate a signal
• What is new? And to whom?
• “Information that arises from one or multiple sources (including
observations and experiments), which suggests a new potentially causal
association, or a new aspect of a known association, between an
intervention and an event or set of related events, either adverse or
beneficial, which would command regulatory, societal or clinical
attention, and is judged to be of sufficient likelihood to justify
verifiable and, when necessary, remedial actions”
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Pharmacovigilance Methods
•Passive Surveillance
•Stimulated Reporting
•Active Surveillance
•Comperative observational studies
•Targeted Clinical Investigations
•Descriptive Studies

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 Passive Surveillance
Spontaneous reports
• An unsolicited communication by healthcare professionals to a
national pharmacovigilance centre, pharmaceutical company,
or regulatory authority that describes one or more suspected
adverse drug reactions in a patient who was given one or more
medicinal products and that does not derive from a study or
any organized data collection scheme

• Identifiues signals, risk groups, risk factors, and clinical

features of known serious adverse drug reactions

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Passive Surveillance
Case series of spontaneous reports
• Provide evidence of an association between a drug and
an adverse event (more useful for generating
hypotheses than for causal association between drug
exposure and outcome)
• e.g. anaphylaxis, aplastic anaemia, toxic epidermal
necrolysis and Stevens Johnson syndrome

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 Passive Surveillance
Targeted spontaneous reporting
• This is a variant of spontaneous reporting
• Focuses on capturing adverse drug reactions in a well
defined group of patients on treatment
• Intended to ensure that patients are monitored and
ADR’s are reported as a normal component of routine
patient monitoring and standard of care

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Stimulated reporting
On-line Reporting
• Systematic stimulation of reporting of adverse events
based on a pre-designed case definition

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 Active Surveillance
Sentinel sites
• Reviewing of medical records or interviewing patients
and/or physicians in a sample of sentinel sites to
ensure complete and accurate data on reported
adverse events
• Major weaknesses of sentinel sites are selection bias,
small numbers of patients, and increased costs

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Active Surveillance
Drug event monitoring
• Patients might be identified from electronic
prescription data, follow-up questionnaires can then be
sent to each prescribing physician or patient at pre-
specified intervals to obtain outcome information

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 Active Surveillance
Cohort event monitoring
• A modification of drug event monitoring
• Patients on a particular drug or groups of drugs are
recruited at time of initiation of e.g. antiretroviral
therapy (ART) and followed up by way of clinic or home
visits or where appropriate by phone calls
• A pre-treatment questionnaire is filled at time of
recruitment and post-treatment questionnaires are
filled at times of follow up which may either be once
e.g. for anti-malarials or life-long e.g. for
antiretrovirals
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Active Surveillance
Registries
• A patient registry is a list of patients presenting with
the same characteristic(s)
• This characteristic can be pregnancy (pregnancy
registry), a disease (disease registry) or a specific
exposure (drug registry)

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 Comparative observational studies
Cross-sectional study
• Data collected on a population of patients at a single point in
time (or interval of time) regardless of exposure or disease
status constitute a cross-sectional study
Case-control study
• Cases of disease (or events) are identified, controls are then
selected from the source population that gave rise to the
cases
Cohort study
• A population-at-risk for the disease (or event) is followed
over time for the occurrence of the disease (or event)
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Targeted Clinical Investigations

• When significant risks are identified from pre-
approval clinical trials, further clinical studies might
be done to evaluate the mechanism of action for the
adverse reaction

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 Descriptive studies
Natural history of disease
• Examination of specific aspects of adverse events, such as
the background incidence rate or risk factors for the
adverse event of interest

Drug utilization study

• Describe how a drug is marketed, prescribed, and used in a
population, and how these factors influence outcomes,
including clinical, social, and economic outcomes

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Elements of a Complete ADR report

Patient identifier
Gender, Age, weight
Length of time ADR occurred
Description of ADR
Suspected Drug
Other drugs patient was taking at the time of ADR
Patients disease condition if known
Batch number of suspected drug and name of manufacturer

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 Barriers to ADR reporting
We already know the ADR’s
What benefit is it? (Guide policy; Continuous education)
Scary to report (Expert opinion)
Failure to recognize ADR
All ‘approved’ medicines are safe
Not aware of regulations
Lethargy!!!!
Odd reactions
ADR’s may mimic a common natural disease
Long delay in the appearance of the adverse effect
Disease complexity clouds drug-related issues
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