MEGHA KRISHNAKUMAR

10PD019
Vaccines are among the most cost-effective and effective public
health interventions and have led to considerable decline in
vaccine-preventable diseases.

CLINICAL PROBLEMS TO BE ADDRESSED BY

PHARMACOEPIDEMOLOGICAL RESEARCH
The tolerance for adverse reactions to vaccines given to healthy
persons especially healthy adults is lower than to products
administered to persons already sick.
 higher standard of safety is required for vaccines because of
larger number of persons who are exposed.
Hence there is a need to investigate rarer adverse events
following vaccinations than for pharmaceuticals. Cost and
difficulty of study increases with rarity.
Higher standards of accuracy and timeliness are needed
because vaccine safety studies have narrow margins for error.
Vaccines have few alternate choices compared to several classes
of drugs and the decision to withdraw a vaccine may have wide
ramifications.
Establishing associations of adverse events with vaccines,
defining attributable risk is necessary in placing adverse events
in proper risk/benefit perspective.
Vaccine safety monitoring is a dynamic balancing of risks and
benefits.
Research in vaccine safety helps to distinguish true vaccine
reactions from coincidental events and estimate attributable risk,
identify risk factors that may permit development of valid
contraindications, and if pathophysiologic mechanism is known
it can develop safer vaccines.
An Institute of medicine(IOM) review of vaccine safety found
that US knowledge and research capacity is limited by:
 Inadequate understanding of biologic mechanisms underlying
adverse events
 Insufficient or inconsistent information from case reports and
case series.
 Inadequate size or length or follow up of many population
based epidemiologic studies.
 Limitations of existing surveillance systems to provide
persuasive evidence of causation.
 Few experimental studies published relative to the total
number of epidemiologic studies published.
 High profile vaccine adverse events such as
intussusceptions following rotavirus
vaccination, demonstrate the need for
surveillance systems able to detect potential
aberrations in a timely manner.
 Assessing whether any adverse event was
actually caused by vaccine is not possible
unless vaccine specific clinical syndrome e.g.
myopericarditis in healthy adult recipients of
small pox vaccine, recurrence upon
rechallenge ( e.g. alopecia, hepatitis b
vaccine) or vaccine- specific laboratory
finding (Urabe mumps vaccine virus isolation)
can be identified.
 Misclassification of exposure status may
occur if there is poor documentation of
vaccinations.
 Because outcome events (e.g.
encephalopathy) are extremely rare it may be
a challenge to identify enough cases for a
meaningful study.
 For studies of rare outcomes, case control
designs are most efficient.
 Greater difficulty in controlling factors ( e.g
low socio-economic status) leading to
delayed vaccination or non-vaccination. This
leads to under estimate of true-relative risk.
 Those who have not been vaccinated differ
substantially from vaccinated population in
risk of AEs and thus will be unsuitable as
reference group.
 SIGNAL DETECTION
Tool for comparing safety profiles of vaccines

Involves comparing the proportions of particular

symptoms out of total number of events for a given
vaccine to that observed among reports for another
vaccine or group of vaccines.

PROPOTIONAL REPORTING
RATIO METHOD
 Simple
 Ease of implementation and interpretation
 Hence widely used measure in Vaccine
adverse event reporting systems(VAERS)
 Historically ad hoc epidemologic studies were
used to assess potential vaccine adverse
events.
 Newer projects based on automated large-
linked databases provide a more flexible
framework for hypothesis testing than ad hoc
studies.
 Hence CDC initiated Vaccine Safety Datalink
(VSD) project in 1990.
 This study prospectively collects vaccination, medical
outcome( hospital discharge, outpatient visits, emergency
room visits, and deaths) and covariate data (e.g. birth
certificates, census) under joint protocol at multiple HMOs.
 VSD focused its initial efforts on examining potential
associations between immunizations and a number of
neurologic, allergic, hematologic, infections, inflammatory
and metabolic conditions and conducted a surveillance on
approximately 500,000 children from birth through 6 yrs of
age.
 VSD is also used to test new ad hoc vaccine safety hypothesis,
VAERS, changes in immunization schedules, or introduation
of new vaccines.
 VSD provides essential, powerful, costeffective complement
to ongoing evaluations of vaccine safety in the US.
 VSD is limited in capacity to assess
association between vaccination and adverse
event with delayed or insidious onset(
neurodevelopmental behavior or behavioral
outcomes)