by M. Miles Braun, MD MPH
The Vaccine Adverse Event Reporting System (VAERS) was
started in 1990 as a national passive surveillance system
for adverse events occurring after vaccination1,
2. VAERS is administered jointly by
the Centers for Disease Control and Prevention's National
Immunization Program and the Food and Drug Administration's
Center for Biologics Evaluation and Research.
reports are received by VAERS each year:10-15% involve
hospitalization, permanent disability or considered
life-threatening, about 2% involve deaths. Reports of
adverse event are accepted by VAERS regardless of whether
the vaccination is shown to have caused the adverse event.
Reporting to VAERS is voluntary and anyone may report
vaccine adverse events. Reports are made by physicians,
nurses, vaccine manufacturers, parents, persons affected by
adverse events and others. The simple one-page reporting
form may be found at the end of the Physicians Desk
Reference or may be ordered by telephoning 1-800-822-7967.
Additional information about VAERS is available at http://www.fda.gov/cber/vaers.html, and the
VAERS form may be downloaded or printed from this website.
The most salient positive attributes of VAERS are
Vaccines recently licensed in the
United States are highly scrutinized in VAERS. Some of the
reasons for this include:
- Prelicensure studies include thousands to tens of
thousands of vaccine administrations. However, because
adverse events occur in less than one per 20,000
vaccinations, it is possible that none will be detected
- Individuals in subgroups, such as those with certain
medical conditions, may not have been represented in the
- The numerous possible combinations of vaccines (as
well as drugs and biologics) that may be concomitantly
administered with the new vaccine may not have been
represented in the prelicensure trials.
Several vaccines have been licensed since the
inception of VAERS including vaccines against hepatitis B
(infant indication), hepatitis A, varicella, and acellular
pertussis vaccines. Postlicensure evaluations using VAERS
data of hepatitis B vaccine in infants3 and of acellular pertussis vaccine
for the 4th and 5th pertussis doses4 have confirmed the safety of the
vaccines for the general population; other such
postlicensure evaluations are ongoing.
Timeliness And Availability of Data. Reports to
VAERS are rapidly coded and computerized. After computer
entry, the reports are available for analysis the following
day by scientists at both the Centers for Disease Control
and the Food and Drug Administration. The general public may
access VAERS data (except for personal identifiers) by
acquiring computerized datasets through the National
Technical Information Service (Tel. 703-487-4650). Certain
data requests may also be filled in accordance with the
Freedom of Information Act (Tel. 800-827-2000).
Lot Surveillance. Largely because of the
timeliness of the data, the Food and Drug Administration
uses VAERS in its ongoing surveillance of all vaccine lots
in use in the United States. Serious reports received by
VAERS are reviewed weekly. Serious non-fatal reports and
death reports are tabulated by vaccine lot and, when
concerns are raised about a particular lot, reporting rates
are calculated (taking into account the amount of time the
lot has been in use). To date, such surveillance using VAERS
has identified no lot-specific vaccine problems.
Rare Disease Registry Useful For Case Series.
Adverse events following vaccination are rare and some are
extremely rare, occurring in about 1-10 per 1,000,000
vaccinations or less. Examples of such rare adverse events
include anaphylaxis and Guillain-Barré syndrome. For
such rare events, a national surveillance system such as
VAERS is especially useful to gather enough cases for useful
study. In certain circumstances, such case series may serve
as the "case" component of case-control studies that search
for causal factors in vaccine reactions.
The Vaccine Adverse Event Reporting System also serves as
a registry of rare adverse events following immunization.
Case series of VAERS reports may be compiled to elucidate
the events' characteristics, etiologies, and possible
preventive measures. For example, a case series of reports
to VAERS of thrombocytopenia following immunization with
attenuated measles virus-containing vaccines demonstrated
that the severity of this thrombocytopenia could be more
severe than was previously recognized5. Another study from VAERS was the
first case series to study syncope after immunization. The
syncope study demonstrated the very close temporal
association between syncope and vaccination, the greater
reporting of this adverse event among children and young
adults, and, perhaps most importantly, the rare occurrence
of severe injuries such as skull fracture6. Alopecia following vaccination was
first described in a case series from VAERS7. The evidence for this
vaccine-adverse event association was strengthened by the
demonstration of "positive rechallenge" in several of the
When 2 or more administrations of a vaccine (or drug) to
the same person are followed by the same adverse event, as
occurred with several cases in the alopecia-vaccination case
series mentioned above, positive rechallenge may be said to
occur. Positive rechallenge represents stronger evidence
than the simple temporal association of a single adverse
event occurrence, and therefore positive rechallenge
represents a useful pharmacoepidemiologic indicator when
analyzing case series information.
Geographic and Demographic Coverage. VAERS is a
national reporting system which covers vaccinations
occurring in the entire United States - in the public and
private sectors, as well as the military. A descriptive
epidemiologic overview of VAERS8 demonstrated that reporting rates
were significantly higher in some states than others and
that the states with highest reporting rates had higher
proportions of reports from the public sector. In addition
to domestic reports, international reports of serious
vaccine adverse events involving vaccines licensed in the
U.S. are also submitted to VAERS by vaccine manufacturers.
Seriously mistaken conclusions can be made by
interpreting VAERS data without taking the important
limitations of VAERS into account.
Accuracy of Reports. VAERS is a passive
surveillance system, and the large number of reports to
VAERS precludes checking the specifics of the vast majority
of reports, especially the less serious ones. Few reports to
VAERS include full medical record documentation, and some
doubtless include errors. In addition, the VAERS forms often
have missing data; even simple data such as age, sex,
vaccination date and adverse event onset date are missing
for about 11%, 8%, 10% and 14%, respectively, of domestic
Underreporting. Underreporting is an inherent
problem of passive surveillance systems, including VAERS.
The degree of underreporting varies according to the adverse
event. For example, one study estimated that 68% of cases of
vaccine-associated polio are reported to VAERS, but only 4%
of MMR-associated thrombocytopenia are reported9. This variability in undereporting
can make it hazardous to assume that the relative
frequencies of adverse events in VAERS reflects their
relative rates of occurrence. In addition, for new products
on the market, increased reporting of adverse events may
occur; this has been termed the "Weber effect"10.
Overreporting. Adverse events may be included in
the VAERS database that are not accurate descriptions of the
event that occurred, and erroneous diagnoses may be
reported. For example, a case of simple fainting after
vaccination may be incorrectly reported as anaphylaxis, a
potentially life-threatening condition.
Overreporting may also result from reports that describe
adverse events for which a definitive diagnosis has not yet
been reached. For example, if the reporter writes on the
reporting form a diagnosis of "rule out meningitis", that
VAERS report will be computer coded as meningitis. Unless
specific follow-up is received indicating that meningitis
was ruled out, the meningitis coding term will remain
associated with the computerized VAERS report.
Adverse Event Incidence And Trends. As a result
of the overreporting and underreporting issues described
above, drawing conclusions from VAERS data about how many
adverse events occurred in the United States must be done
extremely carefully. Similarly, because the factors
affecting overreporting and underreporting may vary over
time, drawing conclusion from observations of changes, or
lack of changes, in the frequency of adverse events in VAERS
over time (trends) may be hazardous. In addition, numbers of
adverse events reported to VAERS will at least partially
reflect the number of doses of vaccine administered. For
example, VAERS reports reflect the current trend of a
decline in usage of whole-cell pertussis-containing vaccines
and a simultaneous increase in the use of acellular
pertussis vaccines; however, it would be incorrect to draw
conclusions about the relative safety of these vaccines from
such trend data. Finally, the number of doses of vaccine
administered according to age is not part of the VAERS
database, and therefore actual rates of adverse events are
not strictly calculable.
Causal vs. Temporal Association. To encourage
complete reporting to VAERS reporters are not expected, or
asked to, make a determination about whether the adverse
event they report is caused by vaccination. Although certain
adverse events are clearly due to vaccination, such as
injection site reactions, a large proportion of adverse
events cannot be clearly causally linked to vaccination; the
most that can be concluded is that the adverse event
followed vaccination. This lack of clear causality is
particularly common among serious adverse events and deaths,
and is largely due to the fact that there are no laboratory
tests or clinical signs that can determine whether the
majority of vaccine adverse events were caused by
vaccination. These difficulties can lead investigators, when
there is sufficient interest, to mount epidemiologic studies
to determine whether vaccination is associated with specific
For example, hundreds of reports of Sudden Infant Death
Syndrome (SIDS) have been made to VAERS since 1990. Because
SIDS occurs in an age range during which vaccination also
occurs, the occurrence of SIDS in temporal association with
vaccination may simply reflect chance. Indeed, the
possibility of a link between SIDS and DTP vaccination was
assessed by a committee of the Institute of
Medicine11. The committee
evaluated epidemiologic studies of this issue and came to
the conclusion that the evidence "does not indicate a causal
relation" between SIDS and DTP vaccine.
Many steps occur to assure the safety of
vaccines--starting with laboratory testing, animal studies,
and several phases of clinical testing in humans. Subsequent
to a vaccine's licensure by FDA, each lot of vaccine goes
through pre-release testing. VAERS is the repository of
reports of adverse events associated with these vaccines.
VAERS reports are monitored by FDA and CDC. Despite its
important limitations, VAERS' multiple useful aspects make
it an important component of the federal vaccine safety
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Adverse Event Reporting System (VAERS). Vaccine
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3. Niu MT, Davis DM, Ellenberg S. Recombinant hepatitis B
vaccination of neonates and infants: emerging safety data
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4. Rosenthal S, Chen R, Hadler S. The safety of acellular
pertussis vaccine vs whole cell pertussis vaccine. Arch
Pediatr Adolesc Med 1996;250:457-60.
5. Beeler J, Varricchio F, Wise R. Thrombocytopenia
following immunization with measles vaccines: review of VAERS reports (1990-1994). Pediatr Infect Dis J
6. Braun MM, Patriarca PA, Ellenberg SS. Syncope after
immunization. Arch Ped Adolesc Med 1997;151:255-9.
7. Wise RP, Kiminyo K, Salive ME. Hair loss after routine
immunizations. JAMA 1997;278:1176-8.
8. Braun MM, Ellenberg SS. Descriptive epidemiology of
adverse events following immunization: reports to the
Vaccine Adverse Event Reporting System, 1991-1994. J Pediatr
9. Rosenthal S, Chen R. The reporting sensitivities of
two passive surveillance systems for vaccine adverse events.
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10. Weber JCP. Epidemiology of adverse reactions to
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Inflammation Research 1984;6:1-7.
11. Institute of Medicine. Adverse Effects of Pertussis
and Rubella Vaccines. Howson CP, Howe CJ, Fineberg HV, eds.
Washington:National Academy Press, 1991.