Madhuri.Miriyala

Pharmacovigilance
 WHO defines pharmacovigilance as the science and activities
relating to the detection, assessment, understanding and
prevention of adverse effects of marketed medicines or those
under trial.
 The drug regulatory agencies have the responsibility of having a
well-established pharmacovigilance system to monitor adverse
reactions of drugs, during the drug development phase and later
during the life time of a marketed drug.

Pharmacovigilance
 collects, records, codes ADEs / ADRs
 analyses and assesses the reports
 promotes the safe use of drugs
 creates appropriate structures and means of
communication needed to perform its tasks

Aims of Pharmacovigilance
 to improve patient care and safety
 to improve public health and safety
 to contribute to the assessment of benefit, harm,
effectiveness and risk of medicines
 to promote education and clinical training
 to promote effective communication to the public
 to promote rational and safe use of medicines

P-vigilance ---- A shared responsibility
 Company – legally and morally responsible for
monitoring their product
 Regulatory authorities – are responsible for the
safety of the drugs they license
 Doctors – responsible to patients
 Pharmacist & nurse – responsible to patients

P-vigilance ---- now a specialist discipline
 Large drug companies have special
departments
 CROs establishing vigilance groups
 Doctors – part of their practicing protocol

Pharmacovigilance - Data Sources
 Spontaneous Reporting Systems
• National PV Centre / Drug Authority
• from the published scientific literature.
 Drug Bulletins
 Adverse Reaction Case Reports by the MA(master
agreement) holder (e.g. collected by sales
representatives)
 Periodic Safety Update Report (PSUR) provided by
MA holder

Basic Model of Pharmacovigilance

PHARMACOVIGILANCE METHODS
 Passive surveillance
Spontaneous Reports
Case series
 Stimulated Reporting
 Active surveillance
Sentinel sites
Drug event monitoring
Registries
 Comparative observational studies
Cross-sectional study (survey)
Case-control study
Cohort study
 Targeted Clinical Investigations
 Descriptive studies
Natural history of disease
Drug utilization study

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.

CASE SERIES
 Series of case reports can provide evidence of an
association of a drug and AE.
 generally more useful for generating hypotheses than
for verifying an association between drug exposure
and outcome
 certain distinct adverse events occur more frequently
with drug therapy, such as anaphylaxis, aplastic
anemia, toxic epidermal necrolysis and Stevens-
Johnson Syndrome events such as these are
spontaneously reported for detailed and rapid follow-
up.

STIMULATED REPORTING
 A method used to encourage and facilitate reporting
by health professionals for new products, or for
limited time period.
 Methods – On line reporting of AE, systematic
stimulation of reporting of AE.
Drawbacks:
Data are often incomplete.
Not useful to generate accurate incidence rates.

ACTIVE SURVEILLANCE
 To ascertain completely the number of AE via a
continuous pre-organised process. Eg:Follow up of
patients treated with a particular drug.
 More feasible to get comprehensive data on individual
AE reports.

SENTINEL SITES
 Active surveillance carried out at Institutions,
Nursing homes, hospitals etc.
 Provide information such as data from specific patient
subgroups, drug abuse etc.
Weakness:
Selection bias,
Small number of patients
Increased costs

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.
 A modification of Drug Event Monitoring is
Cohort Event Monitoring (CEM), an active
pharmacovigilance method promoted by the
World Health Organisation and other
agencies.

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.
 types of designs
1. cross-sectional studies
2. case-control studies
3. cohort studies (both retrospective and prospective)

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.
 Adv:best used to examine the prevalence of a disease
at one time point or to examine trends over time,
when data for serial time points can be captured.

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
using the odds ratio.

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

TARGETED CLINICAL INVESTIGATIONS
 When significant risks are identified from pre-
approval clinical trials, further clinical studies might
be called for to evaluate the mechanism of action for
ADRs.
 Pharmacodynamic and pharmacokinetic studies might
be conducted
 Specific studies to investigate potential drug-drug
interactions and food-drug interactions might be
called for

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.
1. 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
1. 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.

Merci!