PHARMACOVIGILANCE METHODS

AND SAFETY DATA GENERATION

CONTENTS:

• INTRODUCTION
• TYPES OF PHARMACOVIGILANCE METHOS
• PASSIVE SURVEILLANCE
• TYPES OF PASSIVE SURVEILLANCE
• STIMULATED REPORTING
• ACTIVE SURVIELLANCE
• TYPES OF ACTIVE SURVEILLANCE
• COMPARATIVE OBSERVATIONAL STUDIES
• TYPES OF COMPARATIVE OBSERVATIONAL STUDIES
• TARGETED CLINICAL INVESTIGATION DESCRIPTIVE
STUDIES
• SAFETY DATA GENERATION
• PRECINICAL TRIALS
• CLINICAL TRIALS
• POST MARKETING SURVEILLANCE
• REFERENCES
INTRODUCTION:
Pharmacovigilance Methods :
◦ The methods which are used for assessment ,detection and evaluation of the safety of a product are
called Pharmacovigilance methods.
◦ These methods are based upon the specifications and the need of the product specifications and
study .
◦ Pharmacovigilance methods are a part of Pharmacovigilance plan. The sponsors have to submit a
detailed report on whole process of the Pharmacovigilance plane including these methods.
◦ According to ICH guidelines Pharmacovigilance methods are latest and briefly explained
mechanism of working of committee so that they investigate each and every aspect of plan and then
approve the proposed methods for study.
 PASSIVE
SURVEILLANCE
Types of
Pharmacovigilanc STIMULATED
REPORTING
Methods
DESCRIPTIVE
ACTIVE STUDIES
SURVEILLANCE

COMPARATIVE
OBSERVATIONAL
STUDIES

TARGETED
CLINICAL
INVESTIGATION
Passive Surveillance:
◦ Passive surveillance means that no active measures are taken to look for adverse effect other than the
encouragement of health professionals and others to report safety concerns.
◦ Most common form of pharmacovigilance.
◦ Commonly referred as “voluntary reporting”.

TYPES OF PASSIVE SURVEILLANCE:

1. Spontaneous reports
2. Case series
3. Targeted spontaneous reporting
SPONTANEOUS REPORTS:
◦ Spontaneous reports is an ADR reporting system that monitors the safety of medicines.
◦ In this system, the patient or healthcare workers or Pharmaceutical company establishes one way
communication with regional or central regulatory authorities to report ADR.
◦ Plays a predominant role in drug safety signal detection to provide early warning and signals of drug
toxicity which remained unrecognized during clinical trials.
◦ Based on suspected ADR.
REPORTING FORMS MUST INCLUDE FOLLOWING DETAILS:
1. Patient details: age,sex,medication and patient history.
2. Suspected drug details: Dose, duration of treatment .
3. Details of suspected reactions:Description of event,seriousness and outcome.
CASE SERIES:
◦ Method in which reports of patients who had the similar drug exposure
are evaluated for clinical outcomes that are useful to generate drug safety
signals.
◦ By verifying if particular adverse reaction is a result of drug exposure.
◦ However,case series rarely assure if the drug exposure is the only cause of
the adverse outcome.
◦ Therefore,more intense studies have to be conducted to assure the findings
of case series.
Types of Case Series:
There are two type of case series:
1. Exposure – based sampling : includes the patients who were exposed to same drug regardless of
adverse outcome.
2. Outcome – based sampling: includes patients who had similar outcomes regardless of drug exposure.
Design of Case Series:
◦ It is a descriptive study in which the detailed information of individual patients are collected such
as,age ,gender,ethnic origin ,diagnosis of disease,treatment duration, response to treatment and
information of regular follow up.
◦ Furthermore, it is also necessary to mention by which means the information is collected ,i .e.
Either by telephonic interview or chart review.
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 .
◦ Health professionals in charge of the patients are sensitized to report specific safety concerns.
◦ Method is intended to ensure that patients are monitored and ADRs are reported as a normal
component of routine patient monitoring and standard of care .
◦ This focused approach has the same objectives and flow of information as for spontaneous
reporting .
◦ Requires no active measures to look for the particular syndromes.
Stimulated Reporting :

• In this method,the adverse events of the newly marketed drugs are reported online by the
health-care professionals.
• Furthermore,during the post-marketing surveillance the pharmaceutical companies
regularly provide health care workers with the safety information of newly launched drug
and ask them to monitor the related adverse events and report them.
• Besides, the representative of the respective pharmaceutical company can directly pay a visit
by informing health care professionals through fax and direct mails.
• This method resembles spontaneous reporting system,as the reporting of adverse events
starts soon after the marketing of the drug .
Active Surveillance:

• Active surveillance works completely in contrast with that of passive surveillance.

• It monitors the adverse events continuously through pre-organised management
program.
• In which the survey of the followup of patients who were being treated with specific
drug is conducted.
• Besides,the patents who are still under treatment are requested to complete a breif
survey form.
• As the active surveillance is conducted in a stepwise procedural manner,it is
considered as more reliable and feasible reporting system to that of passive
surveillance.
Types of Active Surveillance:

1.SENTINEL SITES

2.DRUG EVENT MONITORING

3.REGISTRIES
 COMPARATIVE
OBSERVATIONAL
STUDIES

• Comparative observational studies are the epidemiological methods that are used to
analyse and describe the occurrence of a disease in a population .

• The main objective of observational study is to validate drug safety signals reported from
spontaneous reports or case series.

• The most important and frequently used studies are CROSS-SECTIONAL

STUDIES,CASE-CONTROL STUDIES AND COHORT STUDIES.
1.CROSS – SECTIONAL STUDY:

• It is a survey in which the data of the patients is collected at a focal point by a signal person or a
department Serving as coordinator to obtain accurate information which can be reliable to gather
the data for survey.

• These studies are useful to analyse the disease occurrence at any point of time.

• However the only drawback of cross-sectional study is that it cannot explain the relationship
between drug exposure and the outcome (adverse events).
2.CASE – CONTROL STUDY:

• It is a retrospective study in which patients with particular disease are compared to group who
have no disease but are exposed to the risk factor of the disease.

• This type of study is not only useful to investigate the relevance between the drug exposure and
the outcome,but also to recognise the risk factors of adverse events.

• The risk factors can include medical conditions such as hepatic and renal dysfunction.

• This method is useful to study various drug exposures.

• It is comparatively fast,easy and cheap method of collecting data .

• However, the only disadvantage is difficulty in finding appropriate control group.

3.COHORT STUDY :
• In cohort study, the population who is at risk for a specific disease or event is monitored for
occurrence of a disease over a period of time .

• As the patients follow-up is monitored ,exposure to one or more drugs can be known which is
useful to calculate incidence rate of disease or event.

• Besides,it is also useful to investigate safety issues in special population.

• It provides multiple outcomes with unbiased data of drug exposure.

• On the other hand , the disadvantage of cohort study is, it is expensive,may continue for
years as it involves large number of subjects.
TARGETED CLINICAL
INVESTIGATION

DESCRIPTIVE
STUDIES:
• NATURAL HISTORY
OF DISEASE
• DRUG UTILIZATION
STUDY
SAFETY DATA GENERATION :