A MEDWATCH CONTINUING EDUCATION ARTICLE
Provided as a service by the National Institutes of Health/Foundation for Advanced Education in the Sciences (NIH/FAES), Bethesda, MD,
and the U.S. Food and Drug Administration (FDA), Rockville, MD
Post-marketing surveillance for adverse events after vaccination:
the national Vaccine Adverse Event Reporting System (VAERS)
BENEFITS AND RISKS OF
Upon completion of this program, Over ten million childhood vaccina- to continue to collect information on
health professionals should be able to: tions are given to children (birth through 5 vaccine-associated adverse events after
• Identify the principles of years) annually, and many million of licensure which may only occur after
post-marketing surveillance doses are given to adults. All medicinal wide-scale use of the vaccine in the gener-
• Understand the objectives of VAERS products, including vaccines, have risks al population.
and benefits. Vaccines protect many peo-
• Understand how VAERS operates ple from dangerous illnesses, but, like POST-MARKETING
drugs, can cause side effects, a small per- SURVEILLANCE
• Discuss basic limitations and strengths centage of which may be serious. The Post-marketing surveillance is a nec-
of data derived from VAERS benefit of vaccines is measured as pre- essary component of vaccine safety moni-
vented disease, and the risk of vaccination toring. The manufacturers’ label/product
• List examples of FDA regulatory is measured as potential side effects; both
actions that have been based on information approved at licensure has the
post-marketing passive surveillance are monitored as part of the US public potential to be continuously updated as
health system. significant adverse event information
• Describe how FDA disseminates which differs from what was originally
information regarding vaccine safety PRE-LICENSURE EVALUATION known at the time of approval is compiled.
to the public OF VACCINES Due to the relatively small number of
Licensure requires extensive clinical patients studied in pre-licensure studies,
• Understand how clinical practice
impacts a national post-marketing evaluation of the vaccines’ safety and rarer side effects or events that may only
surveillance system effectiveness which is completed in stages occur in a sub-group of the population not
over several years. First, laboratory and significantly represented in pre-marketing
animal studies are performed. Then can- studies (e.g., neonates and infants who
didate vaccines are tested in small groups receive hepatitis B vaccine, pregnant
of adult volunteers to establish first the women, immunosuppressed patients), or
Manette T. Niu, MD safety, and then, the efficacy of the vac- side effects that occur only with chronic or
Medical Officer cine. Finally larger-scale clinical trials, repeated exposure to a vaccine-induced
Epidemiology Branch usually randomized and placebo-con- antigen may not be revealed until the vac-
Division of Biostatistics and trolled, measure the rates of the more cine is licensed to the general public.
Epidemiology (DBE) common adverse events and the protective
Center for Biologics Evaluation and efficacy of the vaccine. The control Pre-licensing clinical trials are conducted
Research (CBER), FDA groups in these clinical trials who do not in a controlled environment, much differ-
receive vaccine are critical to distinguish- ent from data obtained from passive or
Marcel E. Salive, MD, MPH ing between vaccine-related events and an active post-marketing surveillance sys-
Chief event unrelated to vaccine but occurring tems. After licensure, vaccinated persons
Epidemiology Branch spontaneously in the study population. have diverse demographic characteristics
Division of Biostatistics and Rates of the most common vaccine reac- ( e. g. , age, race, socioeconomic back-
Epidemiology (DBE) tions, such as injection site reactions and ground), medical history (immunocom-
Center for Biologics Evaluation and fever, can be estimated before licensure, promised host), and/or multiple medical
Research (CBER), FDA but the comparatively small number of problems necessitating medication (poten-
patients enrolled in these trials generally tial drug interactions). These previously
Susan S. Ellenberg, PhD
limits detection of rare events or events unstudied components of a patient’s social
that occur after long-term exposure. Even or medical history may be risk factors
Division of Biostatistics and
the largest pre-licensure trials (>10,000 which could impact the outcome of vacci-
persons) are inadequate to assess the vac- nation and contribute to the development
Center for Biologics Evaluation and
cine’s potential to induce rare but serious of adverse events. Thus, when the product
Research (CBER), FDA
side effects. Consequently, it is essential leaves the controlled study environment of
2 Post-marketing surveillance for adverse events after vaccination: the national Vaccine Adverse Event Reporting System (VAERS)
clinical trials and is put into general clini- and strength of association aid in evaluat- tered by the Food and Drug
cal use by practitioners, the ability to ing if an association is causal, as does a Administration (FDA) and Centers for
determine the actual incidence of adverse vaccination re-challenge (“positive rechal- Disease Control and Prevention (CDC) to
events is questionable. lenge”) which elicits an identical vaccine accept all reports of suspected adverse
reaction (1,2). events after administration of any U.S.
The objectives of post-marketing surveil- licensed vaccine.
lance are to identify rare adverse reactions When faced with a suspicious event, it is
not detected during pre-licensure studies, important to try to determine the back- VAERS, the national passive surveillance
monitor increases in known reactions, ground incidence rate of the event befor e system monitoring vaccine safety, is a sys-
identify risk factors or pre-existing condi- making a judgement as to causality (1,2). tem to which clinical events after vaccina-
tions that may promote reactions, Defining the relationship between vaccine tion are voluntarily reported from health
and identify particular vaccine lots with exposure and the occurrence of an event is professionals, vaccine manufacturers, and
unusually high rates or types of events. not easy, and it is often impossible with the public (2,3). The reports are submitted
the available data to reach a conclusion. to state or local public health authorities,
There are two types of post-marketing sur- Since events may act through the same vaccine manufacturers, or directly to
veillance systems typically in use: active physiological and pathological pathways VAERS, and all ultimately end up in the
and passive surveillance. Active surveil- as normal disease, they are difficult to dis- VAERS dat ab a s e. Food and Drug
lance links the vaccination status of all tinguish. The causal association between Regulations (21 CFR section 600.80) cur-
persons in a defined population to their vaccination and event may be suggested rently require that the following adverse
clinical outcomes, thus, minimizing by various criteria (Table 1)(1,2,17). events be reported to VAERS by each
under-reporting. Such a system may pro- manufacturer having a product license
vide comprehensive data, but may be very VACCINE SAFETY from FDA: all spontaneous reports of
expensive and due to the comparatively SURVEILLANCE: VAERS adverse experiences occurring within the
small number of participants, may lack The National Childhood Vaccine U.S., whether serious, non-serious,
ability to detect very rare events or deaths. Injury Act (NCVIA) of 1989 requires expected or unexpected; and all serious
Passive surveillance systems rely on health professionals and vaccine manufac- and unexpected adverse experiences
health professionals or vaccinees to volun- turers to report to the Department of occurring outside of the U.S. or reported
tarily submit reports of illness following Health and Human Services (DHHS) spe- in scientific/medical journals as case
vaccination. There is no solicitation of cific adverse events following the admin- reports or as the result of formal clinical
these reports; this system is simpler, less istration of vaccines specified in the Act. trials (Table 2)(17).
expensive, does not limit the population The Reportable Events Table, part of the
from which reports are accepted, and Act, lists reportable post-vaccination In order to encourage reporting of adverse
because of the broad pool of reporters, events and the time frames in which they events, FDA r egulations offer substantial
offers the potential for detecting rare must occur in order to qualify as being protection against disclosure of the identi-
events. However, limitations of passive reportable (Table 2)(17). In 1990, DHHS ties of both reports and patients. Since
surveillance systems include variability in established the Vaccine Adverse Event July 3, 1995, a regulation preempted state
reporting standards, reporter bias and sig- Reporting System (VAERS), co-adminis- discovery laws regarding voluntary
nificant under-reporting of events. Both
active and passive surveillance systems TABLE 1
lack specificity, that is, reported post-vac-
cination events may be coincidental and EVALUATING SIDE EFFECTS AFTER VACCINATION:
not caused by the vaccine.
TEMPORAL VERSUS CAUSAL ASSOCIATIONS (17)
Associating causality of reported post-
An adverse event can be causally attributed to vaccine more readily if:
vaccination events with a specific vaccine
is challenging and requires careful weigh- 1. Chronology of administration of agent, including beginning and
ing of all the scientific evidence, evalua- ending of treatment and adverse event onset is known
tion of the quality and consistency of the 2. Previously known toxicity of agent
data, and consideration of biologic plau-
3. Event conforms to a specific clinical syndrome whose association with
sibility of the association between vacci-
vaccination has strong biologic plausibility (e.g., anaphylaxis)
nation and event (Table 1)(1,2,17). The
stronger the vaccine-event relationship in 4. Laboratory result confirms association (e.g., isolation of vaccine strain
each case, and rarer the spontaneous inci- varicella vaccine from skin lesions of a patient with rash)
dence of the event (i.e., background rate in 5. Event recurs on re-administration of vaccine (“positive rechallenge.”)
an unvaccinated population), the fewer 6. Controlled clinical trial or epidemiologic study shows greater risk of
cases are needed to establish a causal adverse events among vaccinated vs unvaccinated (control) groups
association (1,2,17). Biologic plausibility
A MEDWATCH Continuing Education Article 3
reports held by pharmaceutical manufac- group with whom to compare event rates Simultaneous administration of mul-
turers. in the vaccinated vs. unvaccinated popula- tiple vaccine antigens
tion (2,3,9). Following the current recommenda-
LIMITATIONS AND tions for childhood vaccines, reports often
STRENGTHS OF VAERS Given the limitations of VAERS (e.g., lack involve administration of multiple vaccine
VAERS is subject to limitations of accurate information as to the number antigens, making identification of the role
inherent to passive surveillance systems of vaccine doses administered in the pop- of a specific vaccine in an adverse event
(2,3). Nevertheless, the national VAERS ulation, lack of control group, reporting difficult (2,3,7,9).
has been successful in identifying vac- bias, incomplete data, lack of consistent
cine-associated events that serve as diagnostic criteria for disease, and indirect Reporting bias
hypotheses to be tested or further investi- influences accorded sale of vaccine to Spontaneously reported information is
gated in more rigorously controlled stud- government contracts in public sector and uncontrolled and subject to the possible
ies, such as the CDC’s Vaccine Safety the manufacturers market share of vac- influence of a number of biases that can
Datalink (VSD) (a computerized medical cine), VAERS is a crude tool which may at affect reporting. Biases include length of
record linkage system of patients enrolled best estimate reporting rates of events time a product has been on the market
in 4 health maintenance organizations based on manufacturer distribution date (e.g., increased reporting rates the first 2
[HMOs]), where causality may be better (propriety information available only to years a new vaccine is licensed), temporal
determined (2-11). FDA and vaccine manufacturer), that reporting biases (e.g., events that occur
serves as a signal suggesting hypotheses within 4 weeks of vaccination are more
Limitations of VAERS to test in methodologically more rigorous likely to be reported) and reporting envi-
databases (2-11). ronment (e.g., increased reporting with
news coverage and from the public vs pri-
VAERS receives only a portion of the Deficient data quality vate sector), individual biases (e.g., vacci-
total number of events (“numerator”) The ability to assess, analyze and act on nee convinced vaccine responsible for
which occur after vaccination (2,3,7,9,13). safety issues based on spontaneous report- adverse event--initiating VAERS report or
Computing reporting rates from VAERS ing is dependent on the quality of infor- lawsuit)(2).
may be misleading, since the extent of mation submitted by reporters. Clinical
under-reporting is unknown. Compound- details and diagnosis of a given report
ing the problem of under-reporting is the
Inclusion of events not causally
may be inaccurate, non-specific or miss- related to vaccination
lack of precise data as to the number of ing. The quality of the data depends upon
vaccine doses administered in the popula- All reports are entered into the VAERS
the reporter, who may lack clinical train- database regardless of confirmed or possi-
tion (“denominator”) or the number of ing, or who may not have access to com-
persons at risk for the adverse event of ble alternative explanations as to the cause
plete clinical information. Since VAERS of illness. Temporal association by itself
interest. These limitations make receives an estimated 12,000 reports annu-
incidence rates computed from sponta- does not mean that the vaccine caused a
ally, it is difficult to ensure the accuracy symptom or event as the event may be
neously reported data problematic and completeness of the database with
(2,3,7,9). In addition, VAERS does not purely coincidental (1-3). Because of the
available resources, although checks are large number of vaccine exposures, events
receive reports for background events in performed for a few key data items (e.g.,
unvaccinated persons--there is no control temporally associated with vaccine will
type of vaccine, event severity). occur. With multiple childhood vaccines
(diphtheria-tetanus-acellular pertussis [DTaP],
oral polio virus [OPV]/inactivated polio
TABLE 2 virus [IPV], hemophilus influenzae type B
virus [HIB]), administered to nearly all
ADVERSE EVENT (AE) REPORTING REQUIREMENTS FOR infants starting at two months of age, most
VACCINE MANUFACTURERS (17) health problems in infancy, whatever their
cause, will occur in vaccinated children,
1. 15-day Alert reports: serious and unexpected (i.e., not in the product’s some of which will by chance occur in
current labeling) must be reported to FDA within 15 working days. recently vaccinated children (2).
2. Periodic AE reports: all non-15 day AE reports must be reported periodically
(quarterly for the first three years after approval, then annually). An adverse event may be causally attrib-
3. Scientific literature: a 15-day report based on scientific literature (case uted to vaccination more readily if certain
report; results from a formal clinical trial; epidemiology-based studies or conditions are met (Table 1). Because few
“analyses of experience in a monitored series of patients”). adverse events reported to VAERS meet
these criteria, epidemiologic evidence is
4. Post-marketing studies: pharmaceutical causation for AE “reasonable
the basis for assessing causality for the
most serious adverse events investigated.
Determination if the vaccine caused the
4 Post-marketing surveillance for adverse events after vaccination: the national Vaccine Adverse Event Reporting System (VAERS)
post-vaccination event usually cannot be ed to vaccine but all events temporally ble withdrawal of vaccine from the market
made on the basis of information acquired related to immunization, a portion of (for safety or efficacy reasons). Keeping
from individual VAERS reports, and needs which may be coincidental. Data collect- vaccine labeling/package inserts up-to-
confirmation in other methodologically ed on the VAERS form include age, sex, date is an ongoing, dynamic process that
more rigorous databases (e.g., VSD), or birth weight (in patients younger than 6 depends on new information gleaned from
clinical trials (2,3,11). years), date of vaccination, type of vac- spontaneous adverse event reports.
cine, manufacturer, lot number, number of
Strengths of VAERS previous doses of vaccine, date of onset of Dissemination of safety-related informa-
Although VAERS has methodologic symptoms, and clinical description of the tion to health care professionals and the
limitations inherent in passive surveil- event (Figure 1). Events are classified by public is an important public health goal
lance systems such as under-, biased-, and severity: death, serious (Table 3), and non- of post-marketing surveillance.
incomplete reporting, lack of consistent serious. About 15% of reports describe
diagnostic criteria, lack of a comparison serious events, and 85% are non-serious. OBJECTIVES OF VAERS AND
(control) group, and lack of data as to the An “unexpected” event is an event not RESULTS OF ANALYSES OF
precise number of doses of vaccine noted in the FDA-approved manufactur- VAERS DATA
administered to the population, VAERS ers’labeling of the vaccine. All reports of
has strengths essential to the U.S. vaccine deaths and serious events received by the Identification of new, rare vaccine
safety monitoring system (2,3). It is the FDA are followed-up by telephone and/or reactions, increased rates of known
only surveillance system which covers the written inquiry by FDA staff or VAERS
side effects, risk factors for adverse
entire U.S. population,includes the largest contractor. Letters to follow-up serious
number of case reports of events tempo- reports and obtain the recovery status are
rally associated with vaccination in the mailed to the reporters at 60 days and 1 Several investigations based on VAERS
U.S., and can assess the safety of specific year after vaccination. The signs, symp- data have uncovered previously unrecog-
vaccine lots. Other strengths include the toms, and diagnoses mentioned in the nar- nized problems that may occur in vaccine
timely availability of data from a geo- rative description of the adverse event is recipients, including: rare life-threatening
graphically diverse population, the ability coded using FDA’s Coding Symbols for thrombocytopenia after measles-mumps-
to detect possible new, unusual or rare Thesaurus of Adverse Reaction Terms rubella (MMR) vaccination (Box 1) (4),
adverse events and to generate hypotheses (COSTART). All information obtained hair loss after hepatitus B vaccination
that may be tested in other databases (2,3). from the original and follow-up VAERS (Box 2) (5), serious injuries resulting from
Spontaneous report-based surveillance report is entered as computerized data and vaccine-induced syncope or fainting (Box
programs perform an important function stored in a relational database for subse- 3) (6), and identification of the low risk of
by generating signals of potential prob- quent analysis. convulsions following receipt of DTP
lems that may warrant further investiga- and measles-containing vaccines (10).
tion. The VAERS database, excluding patient VAERS can also be used to evaluate the
identifiers, is available to the public from safety of vaccinating a new sub-group of
VAERS is the “front line” of national vac- the National Technical Information the population (e.g., universal immuniza-
cine safety surveillance and is especially Service (NTIS), telephone: (703) 487- tion of infants with hepatitis B vaccine
valuable in assessing the safety of newly 4650, or Freedom of Information (FOI) TABLE 3
marketed vaccines and rare events (2,3). staff can respond to requests for portions
Careful review of reports during the initial of the database or redacted copies of FDA CLASSIFICATION OF
months of licensed use can provide addi- VAERS forms, telephone: (301) 827- SERIOUS VAERS EVENT:
tional assurance about the safety of a new 2000. General information and the
vaccine, uncover previously unexpected VAERS form itself are available on the An event with one of the following
events which occur when a vaccine is VAERS Internet website: patient outcomes:
used in a new sub-group, or rapidly iden- http://www.fda.gov/cber/vaers.html.
tify problems not observed during pre- 1. Fatal
licensure. Recent reviews re-affirm the Based on careful review of spontaneous 2. Life-threatening
safety of hepatitis B vaccines in neonates reports, FDA can initiate various actions: 3. Persistent or significant
and infants (7), and hepatitis A vaccine in manufacturers’ labeling or packaging disability/incapacity
the general population (8). change(s), conducting or requesting
manufacturer-sponsored post-marketing 4. Requires or prolongs
OVERVIEW OF VAERS epidemiologic investigations (hypotheses
VAERS receives approximately testing in more ri go rous databases) 5. Congenital anomaly/birth
12,000 reports annually, and since 1991 (2,3,11), issuing a Safety Alert or “Dear defect
has received at least 75,000 rep o rt s . Health Professional” letter, inspecting 6. Requires intervention to
However, VAERS solicits reports of manufacturers’ facilities/records, or work- prevent an outcome listed
events not only known to be causally relat- ing with a manufacturer regarding possi- above
A MEDWATCH Continuing Education Article 5
after the vaccine had been initially used in lance system is essential, as the first hint
adult health care workers)(7), assessing of a potential problem usually originates BOX 2:
the safety of newly licensed vaccines (e.g., with the astute clinician who reported the
hepatitis A  , varicella [FDA, unpub- case to the appropriate source. Post-mar- HAIR LOSS AFTER
lished data], DTaP ), or comparing the keting surveillance relies on health profes- IMMUNIZATION (5)
safety of two brands of vaccine (9). sionals to report suspicious events, thus One day after a 30 year-old female
improving the quality of reported data, nurse’s first dose of hepatitis B
Identification of vaccine lots with and contributing significantly to safe- (HepB) vaccine, she developed mild
guarding public health in vaccine safety. hair loss, arthralgias, fatigue and
increased numbers of types of report- weakness which lasted 1 week. One
ed events day after her second HepB dose she
Since 1993, FDA staff have performed BOX 1: SEVERE had recurrent hair loss, and 2 weeks
weekly review of the numbers and types THROMBOCYTOPENIA AFTER later, recurrent arthralgias, fatigue and
of reported events in specific vaccine lots MMR II IMMUNIZATION (4) weakness. Alopecia progressed for a
based on distribution data provided by few months until approximately half
A cluster of VAERS reports of severe of her hair had a diffuse, thinned
vaccine manufacturers (proprietary data). thrombocytopenia (TP) after MMR II
Evaluating lot-specific reports is problem- appearance. Her hair later regrew
immunization prompted FDA review. without treatment or workup.
atic as vaccine lot size greatly varies 55 reports coded thrombocytopenia or
(range: 3,000-700,000 doses), and more thrombocytopenia purpura were
reports are usually received for a large lot retrieved from 8,581 reports for
than a small one. To date, no lot has been measles-containing vaccines. 55%
found to be unsafe. This result is not sur- occurred in children < 2 years old BOX 3:
prising given the stringency of the manu- (range 1-40 years) and cases were
facturing and testing requirements to evenly distributed between males and SYNCOPE AFTER
females. 42 reports noted onset of IMMUNIZATION (6)
which vaccines are subject. Nevertheless,
symptoms 3 to 32 days after vaccina-
because of the possibility of such a prob- tion (median time to diagnosis, 12 697 cases of syncope after vaccina-
lem arising, regular attention to lot-specif- days), 41 cases necessitated hospital- tion were reported. 77.4% were
ic reports is an important aspect of FDA’s ization, 17 patients were treated with younger than 20 years, and 57.5%
program of vaccine safety monitoring. intravenous immu n og l o bulin and/or were female. Hospitalization was
steroids and one 12 year-old male had reported in 9.6%. Of the 571 syncope
splenectomy. events with known interval to onset,
There ha ve only been four FDA-initiated
Two serious complications were 511 occurred 1 hour or less after vac-
recall of vaccines since 1987: One lot was
reported: a l year-old male (platelet cination, and 323 (63.2%) occurred
recalled after FDA detected particulates, within the first 5 minutes after vacci-
another lot was mislabeled, the third was count, 1,000/mm3, 12 days after immu-
nization) had severe gastrointestinal nation. Tonic or clonic movements
recalled because of violations in manufac- were reported in 30.4% of syncopal
hemorrhage requiring blood transfu-
turing practices at a production plant that episodes occurring 15 minutes less,
sions; a 15 month-old male (platelet
was found after an FDA inspection, and count, 5,000/mm3,) had pulmonary and in 12.8% of those occurring 15
the fourth was because of a decrease in hemorrhage. There were 2 deaths: a 17 minutes or longer after vaccination
vaccine potency over time. year-old male with history of recurrent (p<0.01).
TP secondary to antiphospholipid syn- Six patients suffered skull fracture,
POST-MARKETING REPORTING drome died from sepsis 4 days after cerebral bleeding or cerebral contu-
immunization; a 4 year-old male died 7 sion after falls; 3 of these patients
OF ADVERSE EVENTS: THE required neurosurgery. Falls occurred
CRITICAL ROLE OF HEALTH days after receiving vaccine from
E s ch e ri chia coli 0157:H7 infection 15 minutes or less after vaccination in
PROFESSIONALS complicated by pseudomembranous or near the clinic or office. Ages
The FDA has the regulatory responsi- colitis. ranged from 12 to 28 years; 5 of 6
bility to ensure the safety of vaccines. Platelet counts reported for 42 per- were male. Follow-up revealed sub-
Determination of whether an event was sons ranged from 1,000 to 102,000 mm3; stantial residual impairment in 2
caused by the vaccine is not a pre-requi- 29 had platelet counts ≤20,000/mm3. patients.
These findings suggest that individuals Prevention of injury from syncope
site for filing a VAERS report. VAERS
with a history of TP, regardless of etiol- after vaccination may be possible.
solicits reports for all events temporally Vaccinators should be aware that
related to vaccination, some of which may ogy, may have recurrent episodes of TP
after immunization, and deserve a care- patients exhibiting pre-syncopal signs
be coincidental (1-3). Any index of sus- and symptoms (hypotension, brady-
ful risk-benefit analysis before receiv-
picion that a serious event or death may be cardia, anxiety, pallor, cool clammy
ing vaccine. These reports r epresent
related to vaccination is reason for the 0.07% of reports for measles-contain- skin) around the time of immunization
health professional to submit a VAERS ing vaccines received by VAERS, and may need to be seated or lie down
report. The role of the health professional suggest that post-vaccination TP is a after immunization until free of symp-
in supporting the national passive surveil- rare event. toms.
6 Post-marketing surveillance for adverse events after vaccination: the national Vaccine Adverse Event Reporting System (VAERS)
FDA EVALUATION OF
REPORTS OF ADVERSE TABLE 4
EVENTS HOW TO OBTAIN VAERS FORMS AND INSTRUCTIONS
The uncontrolled nature of sponta-
neously reported data places great impor- Copies of VAERS form (Figure 1) can be obtained from:
tance on the evaluation of submitted VAERS
reports of adverse events. These analyses, P.O. Box 1100
applied on a case-by-case basis, are based Rockville, Maryland 29849-1100
on experience and knowledge of the vac-
cine being monitored and awareness of Copies of VAERS form and instructions may also be obtained by:
the limitations of the data. A major objec- • Mail: Call 800-822-7967 or FAX request to: 877-721-0366
tive of the national VAERS is to dissemi-
• If no access to 800 number: Call (301) 562-1086
nate vaccine safety information based on
these analyses to the scientific community • Internet: Visit the VAERS Website at www.vaers.org
and the public through publications and Where to send VAERS forms:
COMPARISON OF VAERS AND P.O. Box 1100
MEDWATCH SURVEILLANCE Rockville, Maryland 29849-1100
SYSTEMS Questions about reporting?
FDA maintains two national passive
Epidemiology Branch, ATTN: VAERS
surveillance systems monitoring the post-
marketing safety of medicinal products: Center for Biologics Evaluation and Research
VAERS and MEDWATCH (a system U.S. Food and Drug Administration
which monitors the safety of medical 1401 Rockville Pike, HFM-210
products and devices that are not vac- Rockville, Maryland 20852-1448
cines). Both systems mandate that manu- Phone: (301) 827-3974
facturers, distributors, pharmaceutical
FAX: (301) 827-3529
packers, and device user facilities of FDA-
approved medical products report adverse
events according to specific reporting
requirements (Table 2).
Vaccine Adverse Event Reporting System
The effectiveness of a national post-
A Cooperative Program of the Centers for Disease Control and
marketing surveillance program is direct-
Prevention and the Food and Drug Administration
ly dependent on the active participation of
health professionals. Despite the limita- Call 1-800-822-7967 for VAERS Reporting Information
tions of spontaneous reports, FDA’s pro-
gram for vaccine surveillance provides
vital information of clinical importance. VAERS
The identification of signals in adverse P.O. Box 1100
event surveillance may initiate further Rockville, MD 20849-1100
investigation of potential problems
VAERS FAX: (877) 721-0366
in vaccine safety or efficacy, and the sub-
sequent dissemination of safety-related VAERS E-mail: email@example.com Web: www.vaers.org
information to the scientific community
and the public. This process begins with
and is dependent upon voluntary submis-
sion of reports of possible vaccine-associ- CDC NIP Website FDA CBER Website
ated events to VAERS by the astute, con- http://www.cdc.gov/nip http://www.fda.gov/cber
scientious health professional.
A MEDWATCH Continuing Education Article 7
Figure 1: VAERS Form
8 Post-marketing surveillance for adverse events after vaccination: the national Vaccine Adverse Event Reporting System (VAERS)
A MEDWATCH Continuing Education Article 9
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5. Wise RP, Kiminyo KP, Salive ME. The safety of acellular pertussis 16. Chen R, Rosenthal S. An errant
Hair loss after routine immunization. vaccine vs whole-cell pertussis critique that misses the mark. Arch
JAMA 1997; 278:1176-1178. vaccine. Arch Pediatr Adoles Med Pediatr Adoles Med 1996; 150:464-
6. Braun MM, Patriarca P, Ellenberg SS.
Syncope after immunization. Arch 11.Chen RT, Glasser JW, Rhodes PH, 17. Goldman SA, Kennedy DL,
Pediatr Adolesc Med 1997; Davis RL, Barlow WE, Thompson Graham DJ, Gross TP, Kapit RM,
151:225-259. RS, et al. Vaccine Safety Datalink Love LA, et al. The Impact of
Project: a new tool for improving adverse event reporting.
vaccine safety monitoring in the MEDWATCH Continuing Education
United States. Pediatrics 1997; article, October 1996.
10 Post-marketing surveillance for adverse events after vaccination: the national Vaccine Adverse Event Reporting System (VAERS)
CONTINUING MEDICAL EDUCATION (CME) QUESTIONS & ANSWERS
1. Which of the following is NOT a 5. Which of the following statements is 8. All of the following are FDA actions
known limitation of pre-marketing FALSE with regard to VAERS? that can result from careful analysis of
clinical trials? spontaneous adverse event reports
A. An event that is life-threatening EXCEPT:
A. Ability to detect common or requires hospitalization or
adverse reactions. prolonged hospitalization, or A. Requesting manufacturer-spon-
permanent disability is consid- sored post-marketing studies.
B. Small study size. ered serious.
C. Short study duration. B. Requiring manufacturer to com-
B. An event must be causally
D. Narrow set of indications. pensate for damages suffered
related to vaccine to be reported because of a vaccine-related
E. Evaluates diverse populations. to VAERS adverse event.
C. VAERS can assess the safety of
2. Which of the following statements is C. Change in label/product information.
specific vaccine lots.
TRUE? D. Working with manufacturer on
D. Manufacturers are required to the issuance of a Safety Alert
A. Post-marketing passive report serious adverse events to that outlines the serious safety
surveillance is conducted under VAERS. issue involved.
controlled conditions in defined E. The identity of the vaccinee is
populations. E. Recalling a vaccine lot.
B. The ability to detect adverse 9. All of the following are methods by
events after vaccination is 6. Objectives of VAERS includes all of
the following EXCEPT: which the FDA disseminates vaccine
enhanced with the routine use of
multiple vaccines. safety-related information to health
A. Identification of increased rates care providers EXCEPT:
C. Adverse event detection relies of known side effects.
on accurate reporting from health A. Publications in scientific
care providers. B. Identification of risk factor
that may promote disease. literature.
D. The number of doses of vaccine C. Identification of new, rare B. Presentations at public forums.
administered to the public is
accessible to the public. vaccine reactions. C. VAERS Website on the internet.
D. Assessment of vaccine lot safety. D. Work with manufacturers on the
E. Once a vaccine is marketed, its
initial/product information does E. Conduct of controlled studies to issuance of “Dear Health
not change. determine if an event was Professional” letters.
caused by the vaccine. E. None of the above -- ALL are
3. All of the following are known limi- used by the FDA to inform
tations of passive surveillance systems 7. Which of the following is FALSE? health care providers of new
based on spontaneous reports safety information.
EXCEPT: A. Careful consideration of the
limitations of VAERS is relevant 10. The effectiveness of VAERS is
A. Includes the entire U.S. to accurate interpretation of
dependent on all of the following
population. VAERS data.
B. Under-reporting. B. A large number of VAERS
C. Bias. events cannot be interpreted as A. Active participation of health
D. Lack of consistent diagnostic clear-cut evidence that an event professionals to report vaccine-
criteria for disease. is causally related to vaccination. associated events to VAERS.
E. Lack of denominator data. C. Biological plausibility and B. Adequately financing the high
strength of association are very costs needed to maintain
4. All of the following are known important in adverse event VAERS.
strengths of spontaneous (passive) report evaluation.
surveillance systems based on C. Careful consideration of the
D. It is possible to interpret VAERS limitations of VAERS while
spontaneous reports EXCEPT: data without knowing the number interpreting data.
A. Cost-effective in detecting rare, of persons who were vaccinated
(“denominator” data). D. Ensuring confidentiality against
serious adverse events. disclosure of patient identifies.
B. Hypothesis generation E. Follow-up epidemiologic
(identification of a signal). investigations may stem from E. Filing of complete VAERS
identification of unusual VAERS reports including clinical
C. Studies geographically diverse diagnosis and details of the
course of events.
D. Relatively immune to bias.
E. Large portion of voluntary
reports from conscientious,
astute health professionals.
A MEDWATCH Continuing Education Article 11
This publication was developed by FDA/CBER. Continuing medical education is sponsored by the NIH/FAES Continuing
Medical Education (CME) Committee.
NIH/FAES is accredited by the Accreditation Council for Continuing Medication Education (ACCME) to sponsor continuing
medical education for physicians.
The NIH/FAES designates this educational activity for a maximum of 1.0 hours in category 1 credit toward the American
Medical Association (AMA) Physician’s Recognition Award. Each physician should claim only those hours of credit
actually spent in the educational activity.
To receive certification of CME credit the participant must:
• Answer at least 7 of the 10 self-assessment questions correctly.
• Provide the required information on the answer sheet below.
• Participants receiving a failing grade will be notified.
PUBLICATION DATE:OCTOBER 31, 1998
NOTE: THIS PROGRAM EXPIRES ON OCTOBER 31, 2001
• Do not mail answer sheet if it was previously faxed or submitted via internet.
• Continuing education credit for this article can be awarded only once.
• To check on the status of your certificate, call FDA/CBER/DBE at (301) 827-3974.
¡ Please cut along dotted line
Post-Marketing Surveillance: VAERS
APPLICATION FOR CONTINUING EDUCATION CREDIT
1. ______ 2. ______ 3. ______ 4. ______ 5. ______ 6. ______ 7. ______ 8. ______ 9. ______ 10. ______
Date:_________________________ Phone Number:___________________________________________
Name (including degree):___________________________________________________________________
City:_____________________________ State:____________________ Zip Code:____________________
Amount of time spent completing this CE program: _____hours (must be completed for CME credit)
The information presented is relevant to my clinical practice _____Y _____N
1. Was the material new for you? _____Y _____N
2. Was the material presented clearly? _____Y _____N
3. Was the material covered adequately? _____Y _____N
4. Can you explain the importance of vaccine post-marketing surveillance? _____Y _____N
5. Are you able to define your responsibility to report adverse events? _____Y _____N
6. Are you able to discuss basic limitations and strengths of VAERS? _____Y _____N
7. Do you understand the objectives of VAERS? _____Y _____N
8. Are you able to describe ways in which FDA informs health professionals
about vaccine safety? _____Y _____N
9. Are you able to describe what impact post-marketing passive surveillance
systems have on your clinical practice? _____Y _____N
10. Would you like to see more CE courses from FDA? _____Y _____N
Mail the completed answer sheet by 10/31/01 to:
FDA/CBER/DBE, 1401 Rockville Pike, HFM-210, Rockville, MD 20852 or FAX it to (301) 827-3529
or submit your answers online (www.fda.gov/medwatch)