Pharmacovigilance Methods

Objective
 To establish a functional reporting system to monitor the safety of all medicines
 To learn more about the safety profile of new medicines in the early post-
marketing phase
 To learn more about the ADR profile of a specific medicine(s) in your population
 To estimate the incidence of a known ADR to a specific medicine in your
population
 To gather more information on the safety profile of a new chemical entity in
t h e early post-marketing phase

 To make use of existing electronic health records and registries to support

pharmacovigilance activities

Methods
 Passive surveillance
Spontaneous reports

Case series
 Stimulated reporting
 Active surveillance
Sentinel sites
Drug event monitoring Registries
 Targeted clinical investigations
 Comparative observational studies Cross sectional study
Case control study
Cohort study
 Descriptive studies
Natural history of disease, Drug utilization study
Passive Surveillance

Passive surveillance systems refer to systems that collect and analyze individual case
reports of adverse reactions that are sent to the system voluntarily by physicians and patients.
Pharmaceutical companies as well as government agencies maintain passive surveillance
systems.
Spontaneous Reports

Spontaneous reporting is defined as “A system whereby case reports of ADRs or events are
voluntary by health care professionals and pharmaceutical companies to the National
Pharmacovigilance Centre” (NPC).
Spontaneous reporting has three steps:
• Data Acquisition- This depends largely on the input of information derived from the
reports submitted by the health professionals, who have encountered, what they suspect
is an ADR.
• Data assessment- It involves the assessment of the individual case reports and
assessment of pooled data obtained from various sources, such as an international
database of the WHO.
• Data interpretation- It is based on available data and assessment made, a signal
related to ADR may be generated.
Pharmacovigilance aims at detecting the ADR of marketed drugs. It is generally based
on spontaneous reporting system (SRS) that consists of the spontaneous reporting, by
health professionals, of events that are supposed to be the adverse effects of marketed
drugs.
To report ADR’s in India:
 Through Suspected Adverse Drug reaction reporting form.
 National Pharmacovigilance program was initiated.
 Central Drugs Standard Control Organization (CDSCO) was coordinating 2 Zonal
centers, 5 regional centers, and 28 peripheral centers established for monitoring ADR
reporting in India.
To report ADRs in the United Kingdom ‘yellow card’ has been used for this purpose since
1964.
The ‘blue card’ system is used in Australia and Malaysia.
In the United States, the “Med watch” form is used.

 A communication by consumers or healthcare professionals to a company or

Regulatory Authority, that describes one or more ADR in a patient, who has
given the drug.
 It 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.
 Spontaneous reporting of adverse drug reactions (ADR) is an effective means of
ensuring postmarketing surveillance of drugs, and health professionals play a
cardinal role in voluntary reporting of ADR.

Case series
 Series of case reports can provide evidence of an association of a drug and AEs.
 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 anemia and Stevens-Johnson syndrome events such as
these are spontaneously reported for detailed and rapid follow-up.
 Well-established general principles for evaluating case reports of adverse drug
reactions are generally applicable to the study of vaccines.
 Elements to be considered in evaluating causation in case reports include the
following:
(1) previous clinical experience with the vaccine
(2) alternative etiologic candidates
(3) prior history of the recipient
(4) timing of receipt of the vaccine with respect to the onset of the event
(5) characteristics of the adverse event, both clinical and pathologic
(6) dechallenge (removing or ceasing the exposure; this element is less relevant
to the evaluation of vaccines because vaccine exposure occurs at a single point
exposure, rather than regularly for a period of time as a drug might be)
(7) rechallenge (again, this occurs less commonly with vaccines, but this
element can sometimes be helpful in the evaluation if a vaccine is
readministered).

Stimulated Reporting
 A method used to encourage and facilitate reporting by health professionals for
new products, or for limited period.
  Online reporting of AE, systematic stimulation of reporting of AEs.
 Drawbacks- data are often incomplete.
Not useful to generate accurate incidence rates.

Stimulated reporting of an AE case triggered by a specific occurrence such as:

 A direct healthcare professional communication (DHPC)
 A publication in the press
 Survey of healthcare professionals by company representatives
 Invitation from patient organizations to their members
 Reporting made during early phase post-marketing vigilance (EPPV)

Active surveillance
 To ascertain completely the no. of AEs via a continuous pre-organized
process.
E.g. follow up of patient 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 and
Hospitals etc. provides information such as data from specific patient subgroups, drug
abuse etc.

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, dosage, clinical events, and reasons for discontinuation
can be included in the questionnaire.

Registries: - A registry is a list of patients presenting with same characteristics. E.g.

Disease registry, drug registry, pregnancy registry etc. Differs from each other depending
on type of patient.

Comparative Observational Studies:-

 Traditional epidemiologic methods are a key component in the evaluation of
AEs.
  Observational study designs are useful in validating signals from spontaneous
reports or case series.

Cross Sectional Studies:-

 Data collected from a population of patients at a single point in time regardless of
exposure or disease status.
 Primarily used to gather data for surveys or for ecological analysis. 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:- In this case of disease are identified. Controls or patients without
the disease or event of interest, are selected from the source population. Exposure status of
the two groups is compared using the odds ratio.

Cohort Study:- A population at risk for the disease is followed over a time for the
occurrence of the disease or events. Information on exposure status is known throughout
the follow up and hence incident rates can be calculated.
Comparison cohorts of interest are selected on the basis of drug use and followed over
time. Multiple AEs can also be investigated using the same data source in a cohort study.