Anthrax Vaccine
GAO's Survey of Guard and Reserve Pilots and Aircrew Gao ID: GAO-02-445 September 20, 2002GAO reviewed the views of pilots and aircrew members of the Air National Guard and Air Force Reserve regarding the Anthrax Vaccine Immunization Program (AVIP) of the Department of Defense (DOD). In December 1997, the Secretary of Defense announced a plan to inoculate U.S. forces against the potential battlefield use of anthrax as a biological warfare (BW) agent. In the context of the conventional battlefield, the nature and magnitude of the military BW threat has not changed materially since 1990 in terms of the number of countries suspected of developing BW capability, the types of BW agents they possess, or their ability to weaponize and deliver BW agents. In marked contrast to other mandatory DOD immunization requirements, GAO's sample survey in 2000 showed that AVIP was at that time adversely affecting the retention of trained and experienced guard and reserve pilots and aircrew members. Between September 1998 and September 2000, 16 percent of the pilots and aircrew members of the guard and reserve had (1) transferred to another unit (primarily to nonflying positions to avoid or delay receiving the anthrax shots), (2) moved to inactive status, or (3) left the military. Additionally, one in five of those still participating in or assigned to a unit in 2000 indicated their intention to leave in the near future. At the time of the survey, two-thirds of the guard and reserve pilots and aircrew members did not support DOD's mandatory AVIP or any future immunization programs planned for other BW agents. However, these negative views did not appear to indicate a general antivaccine bias. On the basis of the survey, GAO estimated that 37 percent of the guard and reserve pilots and aircrew members had received one or more anthrax shots as of September 2000. Of these recipients, 85 percent reported experiencing some type of reaction. This overall rate reported for adverse reactions following anthrax immunization was more than double the rate published in the vaccine manufacturer's product insert that was in use at the time of the survey. Respondents to the survey indicated that they had not reported most of the reactions they cited to the military chain of command through official or informal channels and that they were not reported to Food and Drug Administration's Vaccine Adverse Events Reporting System (VAERS). Reasons survey respondents gave for not reporting to the military chain of command included a lack of awareness of VAERS, a concern about the loss of flight status, a possibly adverse effect on military or civilian career, and a fear of ridicule.
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United States General Accounting Office:
GAO:
Report to Congressional Requesters:
September 2002:
Anthrax Vaccine:
GAO‘s Survey of Guard and Reserve Pilots and Aircrew:
GAO-02-445:
Contents:
Results in Brief:
Background:
Scope and Methodology:
The Anthrax Threat Has Been Limited and Stable Since 1990:
How the Anthrax Program Affected Aircrew Members‘ Decisions to Change
Military Status:
The Anthrax Vaccine Program Was Not Widely Supported:
Respondents Did Not Deem AVIP Information That DOD Provided Credible:
Respondents Reported More Adverse Events than Expected:
Conclusions:
Recommendations:
Agency Comments:
Appendix I: Scope and Methodology:
Questionnaire Development:
Sample Construction:
Survey Administration:
Weighting Responses and Potential Nonresponse Bias:
Appendix II: Estimated Percentages of Vaccination Shot Recipients
Experiencing Local and Systemic Adverse Reactions:
Appendix III: The Weighted Numbers of Local and Systemic Adverse
Reactions by Vaccination Shot Number:
Appendix IV: Anthrax Vaccine Adsorbed Revised Product Insert (Jan. 31,
2002):
Description:
Clinical Pharmacology:
Clinical Studies:
Indications and Usage:
Contraindications:
Warnings:
Precautions:
Adverse Reactions:
Dosage and Administration:
How Supplied/Storage:
Nonclinical Toxicology:
References:
Appendix V: Comments from the Department of the Army:
Related GAO Products:
Tables:
Table 1: Types of Anthrax Disease, Methods of Contraction, Symptoms,
and Outcomes:
Table 2: Aircrew Who Had Changed Status and Reported Plans to Change
Status in the Near Future:
Table 3: Pilots Who Had Changed Status and Reported Plans to Change
Status in the Near Future:
Table 4: Adverse Reactions Described in the Anthrax Vaccine Product
Insert:
Table 5: Adverse Events Exceeding 7 Days by Anthrax Vaccination Shot:
Figures:
Figure 1: Factors Influencing the Decisions of Pilots and Aircrew to
Change Status:
Figure 2: Factors Influencing the Decisions of Pilots and Aircrew to
Change Status in the Near Future:
Figure 3: Extent of Support for AVIP Reported by Pilots and Aircrew:
Figure 4: Aircrew Views on the Likelihood of Their Voluntarily Taking
Anthrax Vaccine:
Figure 5: Aircrew Satisfaction with DOD‘s Information on Anthrax
Issues:
Figure 6: Personnel with Moderate to Very Great Concern about the
Anthrax Vaccine and Health Issues:
Figure 7: Estimated and Reported Vaccine Reactions and Events:
Abbreviations:
AVIP: Anthrax Vaccine Immunization Program:
BW: biological warfare, biological weapon:
CDC: Centers for Disease Control and Prevention:
DOD: Department of Defense:
FDA: Food and Drug Administration:
NIH: National Institutes of Health:
VAERS: Vaccine Adverse Events Reporting System:
[End of section]
United States General Accounting Office:
Washington, DC 20548:
September 20, 2002:
The Honorable Dan Burton:
Chairman:
Committee on Government Reform:
House of Representatives:
The Honorable Benjamin A. Gilman:
Chairman:
Subcommittee on Middle East and South Asia:
Committee on International Relations:
House of Representatives:
The Honorable Walter B. Jones:
House of Representatives:
As you requested, we address in this report the views of pilots and
other aircrew members of the Air National Guard and Air Force Reserve
regarding the Anthrax Vaccine Immunization Program (AVIP) of the
Department of Defense (DOD). We received your requests before the
terrorist events of September 11, 2001”the destruction of the World
Trade Center towers in New York City and the attack on the Pentagon in
Washington, D.C. These tragedies were followed in October 2001 by the
mailing of anthrax-laced letters that killed five people in the United
States. The perpetrator”individual, group, or other entity”responsible
for sending the anthrax letters has not yet been identified.
Most of the information in this report was derived from the results and
analyses of survey questionnaire responses received from selected pilots
and other aircrew members of the Air National Guard and the Air Force
Reserve before the events of September and October 2001. If the survey
questionnaire on AVIP were administered today, views on some issues
discussed in this report could be different, either negatively or
positively. However, since most of the questions were, at the time,
related to and report views on contemporaneous events (for example,
information provided in 1999 and 2000 or information about adverse
reactions experienced with inoculations given before 2000), we believe
the results of the survey are still valid and useful as a measure of
the AVIP program‘s performance. This information should be of interest
to DOD and the Congress as they consider future anthrax vaccine
programs. In December 1997, the Secretary of Defense announced a plan
to inoculate U.S. forces against the potential battlefield use of
anthrax as a biological warfare (BW) agent. The mandatory AVIP”using
the only available vaccine produced by the BioPort Corporation”was
officially launched in August 1998 as a high-priority commander‘s
program. This means that unlike other mandatory vaccines routinely
given to the military, AVIP received intense attention from high
command levels and was subject to exceptional accountability
requirements. It was intended to be compulsory for all 2.4 million DOD
military service members”active duty and reserve component members,
including certain designated civilian and contractor personnel. DOD
still regards the biological agent anthrax, a disease that is usually
lethal if inhaled in sufficient quantity, as the single greatest BW
threat to U.S. military forces in the battlefield.
AVIP has been the subject of continuing controversy from its inception.
Public debate has centered on the vaccine‘s safety and effectiveness,
the extent and severity of adverse reactions experienced by vaccine
recipients, and the adequacy and accuracy of the adverse reactions that
have been reported. In addition, some Gulf War veterans are suffering
from unexplained illnesses that they believe might have been caused by
anthrax vaccinations received during the war. We have reported on many
of these issues (see the list of related GAO products at the end of the
report).
DOD temporarily restricted the mandatory anthrax program in 2000 to a
very small group (special mission individuals and researchers) because
of limited vaccine supply resulting from the closing of the vaccine
manufacturing plant. In January 2001, the Food and Drug Administration
(FDA) completed an approval and licensure process, allowing the
manufacturing plant to resume production of the anthrax vaccine. In May
2002, DOD announced the resumption of the anthrax immunization
program, limiting it to ’at risk“ troops. However, the identity of the
troops receiving the vaccine will not be disclosed for security
reasons. DOD also stated that substantial quantities of vaccine would
be reserved for civilian uses in homeland security.
Congressional concern continues about the potential effect of this
program on the retention of highly trained and experienced personnel in
the Air National Guard and Air Force Reserve.
As you requested, we examined"
1. the nature and magnitude of the anthrax battlefield threat over
time;
2. AVIP‘s impact on the retention of experienced guard and reserve
pilots and aircrew members;
3. the level of support for AVIP among guard and reserve pilots and
aircrew members;
4. the level of satisfaction that guard and reserve pilots and aircrew
members expressed regarding the information provided to them on
AVIP and the anthrax vaccine, and;
5. the number and severity of adverse events that vaccinated guard and
reserve pilots and aircrew members experienced and reported.
Results in Brief:
In the context of the conventional battlefield, the nature and
magnitude of the military BW threat has not changed materially since
1990 in terms of the number of countries suspected of developing BW
capability, the types of BW agents they possess, or their ability to
weaponize and deliver BW agents. [Footnote 1] This is particularly true
regarding the ability to accumulate and deliver sufficient quantities
of processed agent to cause mass casualties.
In marked contrast to other mandatory DOD immunization requirements,
our sample survey in 2000 showed that AVIP was at that time adversely
affecting the retention of trained and experienced guard and reserve
pilots and aircrew members. While many factors can and do influence an
individual‘s decision to participate in the military, a significant
number of pilot and aircrew members cited the required mandatory anthrax
immunization as a key reason for reducing their participation or leaving
the military altogether in 2000.
Between September 1998 and September 2000, about 16 percent of the
pilots and aircrew members of the guard and reserve had (1) transferred
to another unit (primarily to nonflying positions to avoid or delay
receiving the anthrax shots), (2) moved to inactive status, or (3) left
the military. Additionally, an estimated one in five (18 percent) of
those still participating in or assigned to a unit in 2000”that is,
those who had not already changed their status”indicated their
intention to leave in the near future. Both groups, those who had
already left and those indicating their intention to leave, ranked AVIP
as a key factor in their decision to leave or change their
participation. We estimated that about 24 percent of those who had
already left did so knowing they were doing so before qualifying for
military retirement benefits. A majority of those who had changed
status and those intending to do so were experienced pilots who held
crew qualifications of flight evaluators, flight instructors, and
aircraft commanders, representing the loss of a very seasoned
workforce. Both those who had changed status and those intending to
change status had accumulated an estimated individual average of more
than 3,000 flight hours.
At the time of our survey, two-thirds of the guard and reserve pilots
and aircrew members did not support DOD‘s mandatory AVIP or any future
immunization programs planned for other BW agents. However, these
negative views did not appear to indicate a general antivaccine bias.
To the contrary, most had a positive view”in terms of both
effectiveness and safety”toward immunization in general. From our
survey, we estimate that 77 percent would not have taken the anthrax
vaccine if it had been offered on a voluntary basis. Almost 9 of 10
reported that they would have safety concerns if an additional vaccine
for other BW agents were added to the military‘s required immunization
program. Additional analysis showed that officers were statistically
more likely than enlisted personnel to report that they would not have
taken the anthrax vaccine voluntarily.
Overall, there was general dissatisfaction with the completeness and
accuracy of the information DOD provided about AVIP and the anthrax
vaccine. We estimated from our survey that only about 4 of 10 guard and
reserve pilots and aircrew members were satisfied with the information
DOD provided on the military threat from anthrax. Considerably fewer
were satisfied with the information DOD provided regarding the anthrax
vaccine‘s effectiveness in battlefield exposures, the history and past
usage of the vaccine, the vaccine‘s short-term safety and long-term
safety, and possible side effects caused by reactions to the anthrax
vaccine. We also found that officers were statistically more likely
than enlisted personnel to question information given to them
concerning specific issues such as the vaccine‘s battlefield
effectiveness and its short-term and long-term safety.
On the basis of our survey, we estimated that 37 percent of the guard
and reserve pilots and aircrew members had received one or more anthrax
shots as of September 2000. Of these recipients, 85 percent reported
experiencing some type of reaction (local or systemic or both).
[Footnote 2] This overall rate reported for adverse reactions following
anthrax immunization was more than double the rate published in the
vaccine manufacturer‘s product insert that was in use at the time of
our survey (84 percent versus approximately 30 percent). Each shot
generated an average of four or more reported reactions. More
importantly, almost one-fifth of the reported events were categorized
as systemic and about one-fifth of these systemic reactions lasted for
more than 7 days. Some of these reactions could have negative
implications for an individual‘s work performance and job safety. The
systemic reaction rate reported through the survey represents a level
more than a hundred times higher than the 0.2 percent published in the
product insert. We were unable to determine why the AVIP reaction rates
so exceeded the product insert rates for the vaccine as approved in
1970. However, we found two studies conducted by DOD that looked at the
short-term safety of the vaccine”one in Korea and one in Hawaii. Both
reported reaction rates similar to those reported in our survey and
disclosed a markedly higher rate of reaction for female shot
recipients. [Footnote 3] Since we first reported these results from our
survey in September 2000, the manufacturer‘s product insert has been
revised to include the adverse reaction rates reported in post
licensure survey studies. [Footnote 4]
Respondents to our survey indicated that they had not reported most of
the reactions they cited to the military chain of command through
official or informal channels (such as supervisors) and that they were
not reported to FDA‘s Vaccine Adverse Events Reporting System (VAERS).
[Footnote 5] Reasons survey respondents gave for not reporting to the
military chain of command included a lack of awareness of VAERS, a
concern about the loss of flight status, a possibly adverse effect on a
military or civilian career, and a fear of ridicule.
This report contains recommendations for DOD to direct the
establishment of an active surveillance program to identify and monitor
adverse events associated with each anthrax vaccine immunization. This
program should ensure that appropriate and complete treatment and
follow-up is provided to those who have experienced adverse events and
to those who may experience them in the future.
Background:
Anthrax is an acute infectious disease caused by the spore-forming
bacterium Bacillus anthracis. It can infect humans; however, it occurs
most commonly in warm-blooded animals (herbivores) in the agricultural
regions of countries with less standardized and less effective public
health programs. Human anthrax occurs only rarely in the United States
from natural causes. However, the anthrax attacks in October 2001
through contaminated mail resulted in the death of five persons.
Human infection normally results from an occupational exposure to
infected animals or animal products. For example, workers may be
exposed to dead animals or to products such as wool, hides, leather, or
hair products (especially goat hair). There have been no reports, even
now, of the disease spreading from person to person; thus, anthrax is
most likely not spread in humans directly.
Anthrax infection can occur in three forms: (1) cutaneous, usually
through a cut or an abrasion; (2) gastrointestinal, by ingesting
contaminated meat; and (3) inhalation, by breathing anthrax spores into
the lungs. Symptoms depend on how the disease is contracted but usually
appear within 7 days. The disease can be treated with antibiotics:
tetracycline and doxycycline are preferred, but penicillin,
erythromycin, chloramphenicol, or ciprofloxacin can also be used. To be
effective, treatment should be started early. The symptoms and forms of
the disease are presented in table 1.
Table 1: Types of Anthrax Disease, Methods of Contraction, Symptoms,
and Outcomes:
Disease form: Cutaneous;
How contracted: By bacteria entering skin cut or abrasion;
Symptoms: Begins as a raised itchy bump resembling an insect bite;
develops in 1–2 days into a vesicle with black center and then a
painless ulcer;
Outcome: Death is rare with appropriate treatment; untreated death rate
is about 20%.
Disease form: Gastrointestinal;
How contracted: By consuming contaminated meat;
Symptoms: Acute inflammation of the intestinal tract;
Outcome: Death in 20%–60% of cases.
Disease form: Inhalation;
How contracted: By inhaling anthrax spores while handling contaminated
animal products; anthrax spores can be sprayed into atmosphere in
biological warfare;
Symptoms: First resembles a common cold or flu; after several days,
acute symptoms develop, such as severe breathing problems and shock;
Outcome: Death 1–2 days after onset of acute symptoms.
Source: Arnot Ogden Medical Center, [hyperlink,
http://www.www.aomc.org].
[End of table]
The Secretary of the Army is the executive agent for managing AVIP. The
dosing regimen or protocol for the anthrax vaccine calls for a series
of six shots over 18 months. An initial series of three shots is given
at 2-week intervals, followed by a series of three shots at 6-month
intervals. Annual boosters are required thereafter. As of early 2001,
more than 520,000 service members had received at least one dose of the
vaccine. However, since late 2000, DOD has had to significantly reduce
the inoculation rate because of a dwindling supply of vaccine from the
sole source manufacturer.
The original anthrax vaccine in the United States was developed by
George Wright and others in the 1950s and was first produced on a large
scale by the pharmaceutical manufacturer Merck Sharp & Dohme. [Footnote
6] A clinical study in 1962 evaluated the safety and effectiveness of
the Merck vaccine in mill workers. [Footnote 7] This study formed the
basis for subsequent licensure of a modified vaccine in 1970. The
Division of Biologics of the National Institutes of Health (NIH) issued
the original license for anthrax vaccine to the Michigan Department of
Public Health. [Footnote 8] In 1995, the facility changed its name to
the Michigan Biologic Products Institute. In 1998, the facility was
sold, and its name was changed to BioPort Corporation.
Over time, FDA has cited the facility for repeated deviations from
applicable manufacturing standards for the vaccine. The facility
received warning letters from FDA, including one in March 1997 stating
its intent to revoke the facility‘s license. The facility closed its
plant for renovations in 1998 and since then has supported all AVIP
requirements with vaccine produced and stockpiled (some from the early
to the middle 1990s) before the plant closed. DOD had to restrict the
mandatory anthrax program because of the shortage of anthrax vaccine.
BioPort has now received FDA‘s approval to resume production. [Footnote
9]
Scope and Methodology:
To achieve our objectives, we developed, pretested, and validated a
questionnaire that we sent to a stratified random probability sample of
1,253 people from DOD‘s list of Air National Guard and Air Force Reserve
personnel. These included pilots, flight engineers, loadmasters,
navigators, crew chiefs, and others. Collectively, these individuals
represented about 13,000 service members of the total fiscal year 1999
end strength of approximately 176,000, which included about 29,000
officers and 147,000 enlisted personnel. We selected a random sample in
four strata, defined by whether a person was currently active or had
changed military status as of March 1, 1998, and had been vaccinated or
not as of February 2000.
The overall response rate from the sample of 1,253 was 67 percent. Each
response was subsequently weighted in the analysis to account
statistically for all the members of the population, including those who
were not selected. Because our results are based on a sample and
different samples could provide different estimates, we express our
confidence in the precision of our particular sample‘s results as a 95
percent confidence interval (for example, plus or minus 5 percentage
points). We are 95 percent confident that each of the confidence
intervals in this report includes the true values in the study
population. Unless we note otherwise, all percentage estimates from the
survey have a 95 percent confidence interval of plus or minus 5
percentage points.
The overall survey results can be generalized to all guard and reserve
pilots and aircrew personnel. A more complete description of the scope
and methodology is in appendix I. We conducted our work between May
2000 and July 2002 in accordance with generally accepted government
auditing standards.
The Anthrax Threat Has Been Limited and Stable Since 1990:
DOD considers inhalation anthrax in an aerosolized form to be the
greatest mass destruction BW threat to U.S. military forces, and it
bases the scope of AVIP on this threat. According to DOD, this
assessment is based on several factors, including (1) the judgment that
a few nations, hostile to the United States, consider anthrax to be a
potential weapon on the battlefield, and (2) the lethality and relative
ease of production and battlefield use.
According to DOD and other, unclassified sources, we found that in terms
of conventional battlefield use, the nature and magnitude of the anthrax
threat has been stable since 1990 and has not changed materially in
terms of the number of countries suspected of developing a BW
capability, the types of biological agents they possess, or their
ability to weaponize and deliver such agents. We have previously
reported that the use of most biological agents would require a
relatively high degree of sophistication, in terms of both expertise
and equipment, to successfully cause mass casualties. [Footnote 10]
Specialized knowledge would be needed to acquire the right biological
agent, process it, improvise a weapon or device, and effectively
disseminate it to cause mass casualties. However, as clearly
demonstrated in October 2001, the mailing of just a few letters
contaminated with refined anthrax spores can cause death and severely
disrupt business and government operations.
How the Anthrax Program Affected Aircrew Members‘ Decisions to Change
Military Status:
The anthrax program adversely affected the retention of trained and
experienced pilots and aircrew members in the guard and reserve. While
many factors can and do influence an individual‘s decision to
participate in the military, pilots and other aircrew respondents cited
the required anthrax immunization as a key reason for (1) leaving the
military altogether, (2) reducing their involvement or participation in
the military, and (3) otherwise changing their military status.
According to our survey, between September 1998 and September 2000,
when AVIP was mandatory, about 16 percent of the guard and reserve
pilots and aircrew members had transferred to another unit (primarily
to nonflying positions), moved to inactive status, or left the military
altogether. In addition, 18 percent of those still participating in
units indicated their intention to transfer, move, or leave in the near
future. About one-fifth of those who had already left did so knowingly
before qualifying for military retirement.
As shown in figure 1, we estimate that more than two-thirds, or 69
percent, of those who changed their status reported that the anthrax
shot was the major influence behind their decision to do so”more even
than those reporting family reasons as an important factor. Of those
who changed their status, 27 percent reported that anthrax immunization
was the most important factor influencing their decision to leave or
transfer. In addition, the general military immunization program was
not an important factor in their decision to change status.
Figure 1: Factors Influencing the Decisions of Pilots and Aircrew to
Change Status:
[See PDF for image]
This figure is a vertical bar graph, depicting the following data:
Factor: Other immunizations;
Major influence: 29;
Most important influence: 1%.
Factor: Unit morale;
Major influence: 53%;
Most important influence: 3%.
Factor: Individual morale;
Major influence: 52%;
Most important influence: 5%.
Factor: Workload;
Major influence: 56%;
Most important influence: 8%.
Factor: Other employment;
Major influence: 42%;
Most important influence: 12%.
Factor: Retirement;
Major influence: 32%;
Most important influence: 16%.
Factor: Family;
Major influence: 61%;
Most important influence: 16%.
Factor: Anthrax shot;
Major influence: 69%;
Most important influence: 27%.
Source: GAO 2000 survey.
[End of figure]
Further, according to our survey, an estimated 44 percent of those who
had already changed their military status or who were no longer in
military flying status because of AVIP indicated that they probably
would consider returning to a unit or to military flying status if AVIP
were not mandatory.
Our survey results also indicated that an estimated 18 percent of those
who were still participating in guard and reserve units reported that
they planned to leave the military or change their military status
within 6 months. As shown in figure 2, when asked to indicate the most
important factors for their planned decision to leave, an estimated 72
percent reported that anthrax immunizations influenced their decision
from a moderate extent to a very great extent, followed by heavy unit
workload, individual morale, and family reasons.
Figure 2: Factors Influencing the Decisions of Pilots and Aircrew to
Change Status in the Near Future:
[See PDF for image]
This figure is a vertical bar graph, depicting the following data:
Factor: Anthrax shot;
None or some: 28%;
Moderate to very great: 72%.
Factor: Workload;
None or some: 44%;
Moderate to very great: 56%.
Factor: Individual morale;
None or some: 51%;
Moderate to very great: 49%.
Factor: Family;
None or some: 51%;
Moderate to very great: 49%.
Factor: Unit morale;
None or some: 55%;
Moderate to very great: 45%.
Factor: Other immunizations;
None or some: 60%;
Moderate to very great: 40%.
Factor: Retirement;
None or some: 71%;
Moderate to very great: 29%.
Factor: other employment;
None or some: 73%;
Moderate to very great: 27%.
Source: GAO 2000 survey.
[End of figure]
Our survey indicated that the majority of guard and reserve pilots who
had already changed their military status or who were intending to do
so in the near future were experienced pilots. These were individuals
who held crew qualifications of flight evaluator, flight instructor, or
aircraft commander and had each accumulated an average of more than
3,000 flying hours, thus representing a trained and experienced
workforce.
Table 2 reflects the composition of the pilots and aircrew members who
had already changed status and those indicating plans to do so in the
near future. For the same categories”those who had changed status and
those indicating plans to do so”table 3 reflects the percentages of
pilots with the qualifications of flight evaluator, flight instructor,
and aircraft commander that require higher qualifications than the
positions of pilot or copilot.
Table 2: Aircrew Who Had Changed Status and Reported Plans to Change
Status in the Near Future:
Status: Changed: past loss;
Pilot: 51%;
Nonpilot: 49%.
Status: Intending to change: future loss;
Pilot: 69%;
Nonpilot: 31%.
Source: GAO 2000 survey.
[End of table]
Table 3: Pilots Who Had Changed Status and Reported Plans to Change
Status in the Near Future:
Status: Changed: past loss;
Role: Evaluator, instructor, commander: 87%;
Role: Pilot or copilot: 13%.
Status: Intending to change: future loss;
Role: Evaluator, instructor, commander: 95%;
Role: Pilot or copilot: 5%.
Source: GAO 2000 survey.
[End of table]
Table 2 shows that more than half of the experienced losses, as well as
the potential future losses, of aircrew members in the guard and
reserve were pilots. Table 3 discloses that the majority of the pilots
served or serve in the more experienced positions of flight evaluator,
flight instructor, and aircraft commander. In summary, in both
groups”those who had left and those intending to leave”most of the
pilot losses represented a very seasoned and experienced workforce.
The Anthrax Vaccine Program Was Not Widely Supported:
Most survey respondents reported fairly negative views concerning AVIP
and any additional biological vaccines DOD planned in the future as
well. A substantial majority of all respondents”66 percent”reported
supporting AVIP to little or no extent, as shown in figure 3. About 9
percent supported the program to a great or very great extent.
Figure 3: Extent of Support for AVIP Reported by Pilots and Aircrew:
[See PDF for image]
This figure is a vertical bar graph, depicting the following data:
Extent of support:
Little or none: 66%.
Extent of support:
Some: 14%.
Extent of support:
Moderate: 11%.
Extent of support:
Great: 5%.
Extent of support:
Very great: 4%.
Source: GAO 2000 survey.
[End of figure]
We performed additional analyses to determine whether there were
statistically significant differences in responses about the extent of
AVIP support between Air Force Reserve and Air National Guard members,
personnel who had changed their military status and those who had not,
and nonrecipients of the vaccination shot versus vaccinated personnel.
We found that Air Force Reserve personnel were considerably more likely
than Air National Guard personnel to report limited or no support for
AVIP. Further, people who had already changed military status were a
little more than twice as likely as those who had not changed status to
indicate limited support for AVIP. The same ratio held true for a
nonshot recipient when compared with an anthrax shot recipient.
Overall, a large majority of the respondents”77 percent”indicated that
they would not or probably would not have taken the anthrax vaccine
shots if AVIP were a voluntary program. Just 11 percent of the
respondents reported that they would have taken or probably would have
taken the shot on a voluntary basis; about 13 percent were uncertain.
These data are reflected in figure 4.
Figure 4: Aircrew Views on the Likelihood of Their Voluntarily Taking
Anthrax Vaccine:
[See PDF for image]
This figure is a vertical bar graph, depicting the following data:
Likelihood:
No or probably no: 77%.
Likelihood:
Uncertain: 13%.
Likelihood:
Yes or probably yes: 11%.
Source: GAO 2000 survey.
[End of figure]
We also found that officers (compared with enlisted personnel), members
of the reserve (compared with the guard), those who had changed their
military status (compared with those who had not), and nonrecipients of
the vaccine (compared with recipients) were statistically more likely to
indicate that they probably would not have taken the anthrax shot
voluntarily. For example, officers were more than twice as likely as
enlisted personnel to indicate they would not or probably would not have
taken the anthrax vaccine voluntarily. Similarly, reserve personnel were
almost twice as likely as guard personnel to answer ’no“ or ’probably
no“ to taking the anthrax vaccine voluntarily.
In addition, an estimated 86 percent, or almost 9 of 10, ’would have had
concerns“ or ’probably would have had concerns“ about safety if
additional vaccines for other BW agents were added to military
immunization requirements in the future. About three-fourths of guard
and reserve personnel reported they had immediate family and co-workers
who agreed with their views on the military‘s AVIP.
Respondents Did Not Deem AVIP Information That DOD Provided Credible:
Overall, our survey disclosed a general dissatisfaction with the
respondents‘ perception of the completeness and accuracy of information
DOD provided to the guard and reserve about AVIP before 2000. This
dissatisfaction appeared to be especially high concerning such key
factors as the military threat from anthrax, the anthrax vaccine‘s
battlefield effectiveness, the vaccine‘s history and past usage, the
short-term and long-term safety risks of the vaccine, and the possible
side effects from and reactions to the vaccine. Fewer were satisfied
with the information provided on other factors, as shown in figure 5.
Figure 5: Aircrew Satisfaction with DOD‘s Information on Anthrax
Issues:
[See PDF for image]
This figure is a vertical bar graph, depicting the following data:
Issue: Side effects;
Dissatisfied: 69%;
Neither satisfied or dissatisfied: 18%;
Satisfied: 13%.
Issue: Long-term safety;
Dissatisfied: 69%;
Neither satisfied or dissatisfied: 20%;
Satisfied: 11%.
Issue: Short-term safety;
Dissatisfied: 62%;
Neither satisfied or dissatisfied: 33%;
Satisfied: 15%.
Issue: History;
Dissatisfied: 55%;
Neither satisfied or dissatisfied: 23%;
Satisfied: 22%.
Issue: Vaccine effectiveness;
Dissatisfied: 62%;
Neither satisfied or dissatisfied: 20%;
Satisfied: 18%.
Issue: Threat;
Dissatisfied: 41%;
Neither satisfied or dissatisfied: 78%;
Satisfied: 37%.
Source: GAO 2000 survey.
[End of figure]
Our analysis also disclosed that reserve personnel were uniformly less
satisfied with the information provided to them about AVIP than were
guard personnel. Further, we found that officers were more likely than
enlisted personnel to question the information on certain issues, such
as the vaccine‘s battlefield effectiveness and its short-term and long-
term safety.
Although DOD employed a high-visibility information campaign on AVIP
and took various steps to address the controversy surrounding it, we
reported in October 1999”about a year after the official start of AVIP”
that service members were not satisfied with the information DOD had
provided to them at the time. [Footnote 11]
Subsequently, DOD expanded its communications efforts by updating the
program‘s Internet web site, opening a toll-free anthrax information
telephone line, and forming a speaker‘s bureau of anthrax experts. In
addition, DOD updated briefings for installation leaders and medical
personnel to provide more detailed information on the anthrax threat and
vaccine.
Despite DOD‘s efforts, we found that relatively few survey respondents
had visited DOD‘s Web site at the time of our survey, and few
respondents reported being satisfied with the information posted. For
example, of those who visited the Web site, 20 percent were moderately
to very satisfied with the completeness of the information, 19 percent
were moderately to very satisfied with the information‘s accuracy, and
27 percent were moderately to very satisfied with its timeliness. Just
12 percent were moderately to very satisfied that the information was
unbiased. Concerns were also expressed about the anthrax vaccine and
its possible effects on certain health issues such as fertility and the
risk of increased autoimmune disease. These issues and respondents‘
concerns are summarized in figure 6.
Figure 6: Personnel with Moderate to Very Great Concern about the
Anthrax Vaccine and Health Issues:
[See PDF for image]
This figure is a vertical bar graph, depicting the following data:
Issue: Other;
Moderate to very great concern: 84%;
None or some concern: 16%.
Issue: Autoimmune;
Moderate to very great concern: 80%;
None or some concern: 20%.
Issue: Effect on offspring;
Moderate to very great concern: 63%;
None or some concern: 37%.
Issue: Male fertility;
Moderate to very great concern: 51%;
None or some concern: 49%.
Issue: Female fertility;
Moderate to very great concern: 44%;
None or some concern: 56%.
Note: Percentages are estimates, based on GAO‘s 2000 survey.
[End of figure]
Although the survey disclosed that the respondents‘ basic views
regarding AVIP and the anthrax vaccine were quite negative, the survey
did not indicate a general antivaccine bias. On the contrary, most
respondents expressed a positive attitude toward immunization in
general in terms of both effectiveness and safety. Overall, 73 percent,
or close to three-fourths, believed that immunization is effective, and
59 percent, or about three-fifths, believed it to be safe.
Respondents Reported More Adverse Events than Expected:
According to our survey results, the reported rate and severity of
adverse events experienced by personnel who had received the anthrax
shots were considerably higher than those published in the vaccine
manufacturer‘s product insert in use at the time of the survey or
reported by DOD. [Footnote 12] For example, an estimated 84 percent of
the personnel who had had anthrax vaccine shots between September 1998
and September 2000 reported having side effects or reactions. This rate
is more than double the level cited in the vaccine product insert.
Further, about 24 percent of all events were classified as systemic”a
level more than a hundred times higher than that estimated in the
product insert. The reaction rates from our survey were also consistent
with the results of two earlier DOD studies of the anthrax vaccine. In
addition, we found that most events were not being reported to either
official or informal DOD channels, partly because most individuals were
unaware of the reporting process for documenting any such occurrences.
According to the anthrax vaccine product insert in use at the time of
our survey, a number of reactions can be expected from the anthrax
vaccine. Table 4 summarizes the type and severity of adverse events
reported in the product insert.
Table 4: Adverse Reactions Described in the Anthrax Vaccine Product
Insert:
Type: Mild local;
Percentage occurrence: 30%;
Description: Consists of small erythema, 1–2 cm in diameter; occurs
within 24 hours and begins to subside by 48 hours;
Additional Information: Erythema may increase to 3–5 cm; severity tends
to increase by 5th injection.
Type: Moderate local;
Percentage occurrence: 4%;
Description: Inflamed reactions greater than 5 cm in diameter; nodules
may occur at injection site and may persist for several weeks in a few
persons;
Additional Information: More severe reactions are less frequent and
consist of extensive edema of forearm.
Type: Systemic;
Percentage occurrence: 0.2%;
Description: Characterized by malaise and lassitude; chills and fever
have been reported in only a few cases;
Additional Information: Immunization should be discontinued in such
instances.
Source: Anthrax Vaccine Product Insert, 1999.
[End of table]
As reflected in the table, at the time of our survey 34.2 percent of all
anthrax vaccine recipients were estimated to report experiencing a
reaction”generally fairly mild and short lived. The vast majority, or
30 percent, of such reactions should consist of an area of redness 1 to
2 centimeters in diameter at the injection site. Moderate local
reactions, consisting of increased redness and the possible appearance
of persistent nodules, were expected in about 4 percent of shot
recipients. A rate of only 0.2 percent for systemic reactions was
anticipated. According to the insert, immunization should be
discontinued when systemic reactions occur. The duration of most
reactions, other than the development of a nodule, was expected to be
short and to dissipate in a few days.
According to our survey, 37 percent of guard and reserve personnel
received one or more anthrax vaccine shots. Of these, 84 percent
reported side effects or adverse events”a rate more than double that
expected or cited in the product insert. On the basis of our survey,
each anthrax shot generated more than four reported events, and each
respondent had received close to four shots of anthrax vaccine. Thus,
the average respondent had reported experiencing about 17 reactions or
events thought to be attributable to the vaccine. Figure 7 compares the
estimated percentages of vaccine reactions in the product insert with
the experience reported in our survey.
Figure 7: Estimated and Reported Vaccine Reactions and Events:
[See PDF for image]
This figure is a vertical bar graph, depicting the following data:
Reactions and Events: Total;
Estimated: 34%;
Reported: 84%.
Reactions and Events: Local;
Estimated: 34%;
Reported: 76%.
Reactions and Events: Systemic;
Estimated: 0.2%;
Reported: 24%.
Source: GAO 2000 survey.
[End of figure]
We estimate that almost 44 percent of anthrax shot recipients reported
experiencing minor local redness, about 24 percent experienced the
enlarged redness associated with a moderate local reaction, and about
69 percent experienced the development of nodules. These data
considerably exceed the levels in table 4. The rates, however, are
similar and consistent with the Korea and Hawaii studies that DOD
conducted after AVIP started. For example, the Hawaii study (the
Tripler survey) disclosed a reaction rate for moderate to severe
redness ranging from 18 percent to 32 percent for shots one through
four. Our survey indicated rates ranging between 21 and 24 percent for
the same shots. The Hawaii study also reported that between 64 percent
and 66 percent of the vaccine recipients experienced a lump or knot”our
survey disclosed a range of 64 to 68 percent for the same shots. Both
the Hawaii and Korea studies found that women experienced a reaction
rate substantially higher than men did”in some instances double or
more. Our survey did not include a sufficient number of women to
address this issue.
These two DOD studies found a higher incidence of systemic reactions
than estimated in the product insert and also found that women
experienced higher rates than men did. Our survey estimated that almost
24 percent of all the events experienced were systemic”a rate more than
a hundred times that expected in the product insert in effect at the
time of our survey. Almost 19 percent of all reported reactions in our
guard and reserve survey exceeded 7 days. The rate for local reactions
lasting longer than 7 days was 17 percent and slightly greater than 23
percent for systemic reactions. The rate of event or reaction per shot
appeared to be fairly consistent, with some drop-off as the shot series
progressed, as shown in table 5.
Table 5: Adverse Events Exceeding 7 Days by Anthrax Vaccination Shot:
Event type: Local;
Vaccination shot 1: 19.0%;
Vaccination shot 2: 17.1%;
Vaccination shot 3: 16.6%;
Vaccination shot 4: 14.3%;
Vaccination shot 5: 13.6%;
Vaccination shot 6: 30.0%;
Average: 17.0%.
Event type: Systemic;
Vaccination shot 1: 26.5%;
Vaccination shot 2: 25.8%;
Vaccination shot 3: 23.1%;
Vaccination shot 4: 20.6%;
Vaccination shot 5: 12.3%;
Vaccination shot 6: 5.5%;
Average: 23.4%.
Event type: Total;
Vaccination shot 1: 20.7%;
Vaccination shot 2: 19.1%;
Vaccination shot 3: 18.2%;
Vaccination shot 4: 15.9%;
Vaccination shot 5: 13.4%;
Vaccination shot 6: 26.7%;
Average: 18.6%.
Source: GAO 2000 survey.
[End of table]
Some of these reactions could have implications for safety and effective
work performance”for example, conditions such as arm pain with limited
motion, extreme fatigue, joint pain, and memory loss lasting more than
7 days.
We found that most of the reactions were not reported to the military
chain of command through official channels (military medical personnel),
informal channels (supervisors), or FDA‘s VAERS. Since most individuals
were not reporting their reactions to military medical personnel, their
supervisors, or VAERS, the actual duration, extent, or impact on units
and individuals and the ultimate resolution of reactions are unknown.
We estimated that about 67 percent of those who experienced side effects
or reactions were unaware of VAERS. As a result, about 6 percent of
those who experienced a reaction reported it to this system”altogether
18 individuals reported submitting VAERS reports on their own, and
another 6 reported that the military submitted a report for them.
Moreover, DOD had initially limited reporting anthrax vaccine events to
VAERS to only reactions leading to either hospitalization or the loss of
48 hours or more of duty time. This restriction was subsequently
removed. In addition, our survey estimated that about 57 percent of
those who experienced an adverse reaction did not discuss it with
anyone in military health care or their individual supervisors. Some 49
percent cited concern about the loss of flight status, possible adverse
effects on their military or civilian careers, and the fear of ridicule
as reasons for not discussing vaccination shot reactions with others.
Another 49 percent indicated that the reactions they experienced were
not severe enough to seek medical help or to tell their supervisors
about.
DOD continued to use data from VAERS to monitor adverse events or
reactions to anthrax vaccination, even though it is a ’passive“
surveillance system that relies on vaccine recipients or their health
care providers to report adverse events after vaccination. Studies show
that significantly fewer adverse events are reported under such a
system when compared to an active surveillance approach in which
vaccine recipients are actively monitored to identify and track any
adverse reactions to a vaccine or medication. [Footnote 13] For
example, we estimated that almost three-fourths of vaccinated guard and
reserve personnel experienced burning in the vaccinated arm and a knot
or lump in the vaccinated arm, compared with DOD‘s report that 0.007
percent had such reactions. In November 2001, DOD reported that after
more than 2 million doses of anthrax vaccine had been administered to
more than 522,000 people, only 1,685 VAERS reports were submitted for
possible adverse events associated with the vaccine. In contrast, the
approximately 380 shot recipients in our survey disclosed more than
6,000 reactions (almost 1,300 of which were systemic) from slightly
more than 1,300 shots.
Conclusions:
According to DOD, inhalation anthrax is the greatest BW threat to U.S.
military forces. To counter this threat, DOD officially established the
mandatory AVIP in August 1998 to inoculate all 2.4 million of DOD‘s
service members, including active duty and reserve component personnel,
along with some DOD civilian and contractor employees. This major
undertaking involved scheduling and administering more than 14 million
shots to satisfy the vaccine‘s initial dosage requirements of six shots
per individual over an 18-month period, followed by an annual booster.
Accordingly, DOD initiated a large, high-visibility campaign to
communicate its views and to inform service members about the anthrax
threat and the anthrax vaccine. Among other things, DOD established a
Web site, opened a toll-free anthrax information telephone service,
formed a speakers‘ bureau of experts, and provided briefings and other
materials for installation leaders and medical personnel to use at unit
and base or installation levels.
Our findings suggest that DOD‘s communications efforts were largely
unsuccessful in convincing most guard and reserve pilots and aircrew
members that the anthrax threat was as serious as alleged or to support
AVIP as an appropriate response. Overall, there was a general and
pervasive degree of dissatisfaction among guard and reserve pilots and
aircrew members about the completeness and accuracy of most of the
information DOD provided on the anthrax vaccine and AVIP. In addition to
their response to military threat, surveyed pilots and aircrew members
expressed significant dissatisfaction with such key factors as the
battlefield effectiveness of the anthrax vaccine, its history and past
usage, its short-term and long-term safety risks, and the possible side
effects from the vaccine.
In addition, although DOD has maintained from AVIP‘s outset that the
anthrax vaccine is very safe and causes minimally adverse effects, our
survey disclosed that a significantly large number of vaccine recipients
reported experiencing adverse events. Further, the results of two DOD
studies on anthrax vaccine reactions”both of which used active
monitoring systems, as opposed to a passive system such as VAERS, for
gathering information on adverse events”are consistent with and support
the results of our survey. The rates disclosed in the survey and the DOD
studies are each significantly higher than those stated in the vaccine
product insert until recently. Such marked variances from the product
insert data suggest the possibility of change in the composition of the
vaccine from the vaccine originally approved in 1970.
In summary, AVIP appears to have adversely affected the Air National
Guard and Air Force Reserve in terms of retaining needed experienced
personnel. Sixteen percent of our survey respondents either left the
military or significantly reduced their level of participation, citing
the anthrax immunization program as an important factor in their
decision to do so. Interestingly, 45 percent of these individuals
indicated that they would consider returning if AVIP were made
voluntary. Further, at the time of our survey, 18 percent of those
still participating indicated their intention to leave in the near
future, again citing AVIP as an important factor in that decision.
Unfortunately, the actual losses and expected losses as a result of
this program represented some of the most experienced and highly
trained individuals in these services and are people not easily
replaced. It takes time and a great deal of money and other resources
to develop trained, experienced pilots and other aircrew members to
support the important missions of these reserve components,
particularly in light of the current battle against terrorism.
Recommendations:
We recommend that the Secretary of Defense direct the establishment of
an active surveillance program (unlike the passive VAERS) to identify
and monitor adverse events associated with each anthrax vaccine
immunization. This program should ensure that appropriate and complete
treatment and follow-up are provided to those who have experienced
adverse events and to those who may experience them in the future.
Agency Comments:
In comments on a draft of this report (reprinted in app. V), DOD did not
concur with our recommendation to establish a surveillance program. In
support of its position, DOD cited the following statement from the
Institute of Medicine‘s report: The Institute of Medicine ’committee
observes that no data that indicate the need for the continuation of
special monitoring programs for anthrax vaccine have emerged, but it
recognizes the real concerns for service members ordered to take the
vaccines.“ [Footnote 14] In addition, DOD stated that data from the
Defense Manpower Data Center about actual pilot separations did not
support the statements in the report in that the center‘s data show
that pilot separations before the beginning of the anthrax program in
1998 were similar to the rates during the time of the survey. DOD
further stated that our report did not address the normal or expected
rates of turnover known to occur among personnel in the Air National
Guard and the Air Force.
DOD‘s selective use of a conclusion from the Institute of Medicine
report that ’a separate AVA monitoring program is not necessary“ is
misleading. This response, while technically correct, ignores the
comprehensive recommendations that the institute‘s report actually made
to DOD. Specifically, the institute recommended that DOD (1) use VAERS
data to generate hypotheses to study further, using DOD‘s new unified
service medical reporting system; (2) regularly study those data for
new trends; (3) work with the Department of Veterans Affairs to
encourage participation in the Millennium Cohort study to better get a
handle on all the problems associated with the Gulf War and other
actions; and (4) regularly do ad hoc unit-based population monitoring
of reactions to all vaccines. [Footnote 15] In addition, the Institute
of Medicine report recommended that anthrax vaccine lots produced after
renovations at the BioPort vaccine production facility should continue
to be monitored for immunogicity and stability and that individuals
receiving these lots should be monitored for possible acute or chronic
events of immediate or later onset. Adoption of these recommendations
would satisfy our recommendation.
More importantly, DOD did not address two major findings from our
survey: (1) some of the adverse reactions that our respondents reported
persisted for more than 7 days and (2) given that a large proportion of
respondents were not reporting the symptoms to VAERS or their DOD
health care practitioners, we do not know whether these reactions were
resolved over time. Also, active monitoring would result in a more
comprehensive database for conducting specific analysis to test whether
the adverse reactions lasting for more than 48 hours are occurring among
older recipients, as suggested by a study conducted in the United
Kingdom. [Footnote 16] In that study, older recipients of the anthrax
vaccine experienced significant incapacity (inability to lift or
drive), which according to the author, would be critical for some
military populations, such as aviators. Further, several studies in the
United States and the United Kingdom now show a relationship between
anthrax vaccine and Gulf War syndrome. [Footnote 17] We recommended an
active monitoring system not for the sole purpose of identifying
adverse reaction rates, since FDA has already recognized much higher
local and systematic reaction rates and the recent product insert has
been revised accordingly, but also to proactively monitor, identify,
and treat individuals experiencing adverse reactions. Our
recommendation should lead to better lines of communications in the
chain of command and help overcome any fear or mistrust of
communicating reactions or symptoms to those responsible for medical
care. In addition, since the anthrax vaccine will be offered to
civilian first responders or health care workers, civilian doctors would
need information on adverse reactions that can be expected to follow.
[Footnote 18] DOD could be instrumental in providing information to
civilian and medical doctors about how these symptoms are resolved over
time and effective treatment approaches but only if an active
monitoring program or the recommendations of the Institute of Medicine
are fully implemented.
With regard to our survey‘s findings on pilot attrition, DOD had not
provided data to support its statement that there was no difference
between pilot separations before and during the mandatory AVIP program
by the time this report was issued. However, DOD‘s response uses the
term ’separations“ while our report uses the term ’change of status,“
which is a much broader term. We reported on percentages of pilots who
changed their status (for example, transferred to another unit, left the
military in a ’separation,“ or moved to inactive status) to avoid
anthrax vaccine. In any event, although the overall separation rates
may be the same before and after the onset of the mandatory anthrax
vaccine program, it is clear that the losses among the most experienced
pilots (in bases where AVIP was implemented) resulting from change of
status were significant at some bases, resulting in the loss of an
extremely seasoned workforce.
As we agreed with your offices, unless you publicly announce the
contents of this report earlier, we plan no further distribution of it
until 30 days from its issue date. We will then send copies of the
report to other interested congressional members and committees. In
addition, the report will be available at no charge on the GAO Web site
at [hyperlink, http://www.gao.gov].
If you or your staff have any questions about this report or would like
additional information, please call me at (202) 512-2700 or Sushil K.
Sharma, Assistant Director, at (202) 512-3460. Penny Pickett, Laurel
Rabin, and Foy Wicker also made key contributions to this report.
Signed by:
Nancy R. Kingsbury:
Managing Director:
Applied Research and Methods:
[End of section]
Appendix I: Scope and Methodology:
The best way to reliably assess the pulse and views of military
personnel is by surveying a representative sample. We developed and
administered such a survey that was designed to obtain the views of
selected Air National Guard and Air Force Reserve personnel regarding
issues associated with AVIP. The survey, which was both voluntary and
confidential, was mailed in May 2000 to a random sample of 1,253
personnel. As of September 7, 2000, 828 individuals had completed and
returned the survey. Follow-up efforts yielded an additional 15
responses. A total of 843 responses were returned, of which 833 provide
useful information.
In addition, we performed logistic regression analyses for selected
questions in our questionnaire to determine odds ratios to evaluate the
responses of certain groups in our survey population. These groups
included enlisted personnel and officers, Air National Guard and Air
Force Reserve personnel, shot recipients and nonshot recipients, and
individuals who had changed their military status and those who had
not. We conducted our work in accordance with generally accepted
government auditing standards.
Questionnaire Development:
We developed the survey with the assistance of discussion groups made
up of pilots and other aircrew members of the Air National Guard and Air
Force Reserve. It was pretested at Andrews Air Force Base, Maryland, and
further pretested and refined at guard and reserve units at March Air
Reserve Base, California; Travis Air Force Base, California; Hartford,
Connecticut; Battle Creek, Michigan; Newburg, New York; Memphis,
Tennessee; and Madison, Wisconsin.
Sample Construction:
The sample consisted of 1,253 Air National Guard and Air Force Reserve
aircrew personnel who were in the service at any time between September
1998 and February 2000. Our sample was drawn from pilot and aircrew
member populations provided by the Air National Guard and Air Force
Reserve in early 2000. In addition, the AVIP office provided
information as to vaccination status. For the sample design, we
categorized personnel in our universe by two factors: military status
(left versus onboard) and vaccine status (shot versus no shot). The
sample was adjusted for groups with differing expected rates of survey
completion and adjusted to provide a level of precision of plus or
minus 5 percentage points.
Survey Administration:
As of September 6, 2001, we had received 843 responses from eligible
respondents, an overall response rate of 67 percent. We used a
contractor to key in the data reported in the responses. We validated
the data provided to us by the contractor to ensure accuracy.
Weighting Responses and Potential Nonresponse Bias:
The survey responses were weighted to reflect the Air National Guard and
Air Force Reserve population for the survey. This weighting procedure
adjusts for the different proportions of individuals sampled from each
cell and the actual response rate for that cell in the sample design.
The survey results assumed that nonrespondents would have answered as
the respondents did. This assumption involves some unknown risk of
nonresponse bias. Weighting can be used to statistically adjust for
differing sampling rates and response rates. However, weighting cannot
adjust for possible differences between those who do and those who do
not respond to a survey.
[End of section]
Appendix II: Estimated Percentages of Vaccination Shot Recipients
Experiencing Local and Systemic Adverse Reactions:
Reaction: Local: Redness 2.5 inches or less;
Vaccination shot 1: 39.6%;
Vaccination shot 2: 33.5%;
Vaccination shot 3: 32.7%;
Vaccination shot 4: 33.5%;
Vaccination shot 5: 29.2%;
Vaccination shot 6: 42.6%;
Average % experiencing reaction: 35.2%.
Reaction: Local: Redness 2.5 inches or more;
Vaccination shot 1: 16.9%;
Vaccination shot 2: 19.7%;
Vaccination shot 3: 19.4%;
Vaccination shot 4: 17.6%;
Vaccination shot 5: 16.8%;
Vaccination shot 6: 26.2%;
Average % experiencing reaction: 19.4%.
Reaction: Local: Swelling in arm;
Vaccination shot 1: 37.7%;
Vaccination shot 2: 37.8%;
Vaccination shot 3: 36.3%;
Vaccination shot 4: 34.5%;
Vaccination shot 5: 29.2%;
Vaccination shot 6: 31.5%;
Average % experiencing reaction: 34.5%.
Reaction: Local: Burning in arm;
Vaccination shot 1: 60.7%;
Vaccination shot 2: 60.6%;
Vaccination shot 3: 58.1%;
Vaccination shot 4: 57.8%;
Vaccination shot 5: 57.0%;
Vaccination shot 6: 63.4%;
Average % experiencing reaction: 59.6%.
Reaction: Local: Arm pain or limited motion;
Vaccination shot 1: 36.1%;
Vaccination shot 2: 35.5%;
Vaccination shot 3: 36.0%;
Vaccination shot 4: 33.2%;
Vaccination shot 5: 29.2%;
Vaccination shot 6: 26.2%;
Average % experiencing reaction: 33.7%.
Reaction: Local: Itching in arm;
Vaccination shot 1: 27.6%;
Vaccination shot 2: 28.3%;
Vaccination shot 3: 29.0%;
Vaccination shot 4: 27.4%;
Vaccination shot 5: 25.6%;
Vaccination shot 6: 26.8%;
Average % experiencing reaction: 27.4%.
Reaction: Local: Knot or lump in arm;
Vaccination shot 1: 54.5%;
Vaccination shot 2: 55.3%;
Vaccination shot 3: 55.3%;
Vaccination shot 4: 51.7%;
Vaccination shot 5: 52.1%;
Vaccination shot 6: 63.4%;
Average % experiencing reaction: 55.4%.
Reaction: Systemic: Chills;
Vaccination shot 1: 7.7%;
Vaccination shot 2: 6.8%;
Vaccination shot 3: 8.2%;
Vaccination shot 4: 8.4%;
Vaccination shot 5: 6.5%;
Vaccination shot 6: 5.7%;
Average % experiencing reaction: 7.2%.
Reaction: Systemic: Fever;
Vaccination shot 1: 9.3%;
Vaccination shot 2: 9.6%;
Vaccination shot 3: 10.3%;
Vaccination shot 4: 9.6%;
Vaccination shot 5: 6.6%;
Vaccination shot 6: 5.7%;
Average % experiencing reaction: 8.5%.
Reaction: Systemic: Extreme fatigue;
Vaccination shot 1: 14.5%;
Vaccination shot 2: 16.6%;
Vaccination shot 3: 16.4%;
Vaccination shot 4: 13.8%;
Vaccination shot 5: 8.9%;
Vaccination shot 6: 0.6%;
Average % experiencing reaction: 11.8%.
Reaction: Systemic: Dizziness;
Vaccination shot 1: 3.1%;
Vaccination shot 2: 2.8%;
Vaccination shot 3: 3.3%;
Vaccination shot 4: 4.3%;
Vaccination shot 5: 2.6%;
Vaccination shot 6: 0.6%;
Average % experiencing reaction: 2.8%.
Reaction: Systemic: Headaches;
Vaccination shot 1: 9.6%;
Vaccination shot 2: 8.4%;
Vaccination shot 3: 9.8%;
Vaccination shot 4: 8.5%;
Vaccination shot 5: 5.2%;
Vaccination shot 6: 0.6%;
Average % experiencing reaction: 7.0%.
Reaction: Systemic: Blurred vision;
Vaccination shot 1: 2.3%;
Vaccination shot 2: 2.4%;
Vaccination shot 3: 2.9%;
Vaccination shot 4: 2.5%;
Vaccination shot 5: 1.4%;
Vaccination shot 6: 0.3%;
Average % experiencing reaction: 2.0%.
Reaction: Systemic: Numbness in extremities;
Vaccination shot 1: 3.6%;
Vaccination shot 2: 3.3%;
Vaccination shot 3: 3.4%;
Vaccination shot 4: 3.2%;
Vaccination shot 5: 1.7%;
Vaccination shot 6: 6.3%;
Average % experiencing reaction: 3.6%.
Reaction: Systemic: Joint pain;
Vaccination shot 1: 16.1%;
Vaccination shot 2: 16.3%;
Vaccination shot 3: 17.3%;
Vaccination shot 4: 18.0%;
Vaccination shot 5: 13.0%;
Vaccination shot 6: 16.7%;
Average % experiencing reaction: 16.2%.
Reaction: Systemic: Memory loss;
Vaccination shot 1: 4.0%;
Vaccination shot 2: 3.7%;
Vaccination shot 3: 4.3%;
Vaccination shot 4: 4.3%;
Vaccination shot 5: 3.7%;
Vaccination shot 6: 0.6%;
Average % experiencing reaction: 3.4%.
Reaction: Systemic: Blackouts:
Vaccination shot 1: 0.8%;
Vaccination shot 2: 0.4%;
Vaccination shot 3: 0.4%;
Vaccination shot 4: 0.6%;
Vaccination shot 5: 1.2%;
Vaccination shot 6: 0%;
Average % experiencing reaction: 0.6%.
Reaction: Systemic: Ringing in ears;
Vaccination shot 1: 5.4%;
Vaccination shot 2: 4.5%;
Vaccination shot 3: 4.6%;
Vaccination shot 4: 3.1%;
Vaccination shot 5: 2.7%;
Vaccination shot 6: 0.6%;
Average % experiencing reaction: 3.5%.
Reaction: Systemic: Insomnia;
Vaccination shot 1: 4.3%;
Vaccination shot 2: 3.7%;
Vaccination shot 3: 3.4%;
Vaccination shot 4: 2.5%;
Vaccination shot 5: 3.8%;
Vaccination shot 6: 0%;
Average % experiencing reaction: 2.9%.
Reaction: Systemic: Nausea;
Vaccination shot 1: 4.3%;
Vaccination shot 2: 4.5%;
Vaccination shot 3: 4.7%;
Vaccination shot 4: 5.5%;
Vaccination shot 5: 6.4%;
Vaccination shot 6: 5.7%;
Average % experiencing reaction: 5.2%.
Reaction: Systemic: Other;
Vaccination shot 1: 4.1%;
Vaccination shot 2: 3.5%;
Vaccination shot 3: 4.9%;
Vaccination shot 4: 5.3%;
Vaccination shot 5: 5.0%;
Vaccination shot 6: 0%;
Average % experiencing reaction: 3.8%.
Source: GAO analysis.
[End of table]
[End of section]
Appendix III: The Weighted Numbers of Local and Systemic Adverse
Reactions by Vaccination Shot Number:
Estimated number receiving each vaccination shot, #1: 4,678;
Estimated number receiving each vaccination shot, #2: 4,492;
Estimated number receiving each vaccination shot, #3: 4,316;
Estimated number receiving each vaccination shot, #4: 2,933;
Estimated number receiving each vaccination shot, #5: 1,389;
Estimated number receiving each vaccination shot, #6: 336.
Reaction type and duration: Local, Redness 2.5 inches or less, less
than 24 hours:
Estimated number receiving each vaccination shot, #1: 663;
Estimated number receiving each vaccination shot, #2: 605;
Estimated number receiving each vaccination shot, #3: 570;
Estimated number receiving each vaccination shot, #4: 376;
Estimated number receiving each vaccination shot, #5: 142;
Estimated number receiving each vaccination shot, #6: 38;
Total number of reactions: 2,394.
Reaction type and duration: Local, Redness 2.5 inches or less, 1-3
days:
Estimated number receiving each vaccination shot, #1: 680;
Estimated number receiving each vaccination shot, #2: 538;
Estimated number receiving each vaccination shot, #3: 502;
Estimated number receiving each vaccination shot, #4: 356;
Estimated number receiving each vaccination shot, #5: 173;
Estimated number receiving each vaccination shot, #6: 52;
Total number of reactions: 2,301.
Reaction type and duration: Local, Redness 2.5 inches or less, 4-7
days:
Estimated number receiving each vaccination shot, #1: 290;
Estimated number receiving each vaccination shot, #2: 250;
Estimated number receiving each vaccination shot, #3: 195;
Estimated number receiving each vaccination shot, #4: 159;
Estimated number receiving each vaccination shot, #5: 35;
Estimated number receiving each vaccination shot, #6: 17;
Total number of reactions: 946.
Reaction type and duration: Local, Redness 2.5 inches or less, 7 days
or more:
Estimated number receiving each vaccination shot, #1: 217;
Estimated number receiving each vaccination shot, #2: 112;
Estimated number receiving each vaccination shot, #3: 146;
Estimated number receiving each vaccination shot, #4: 91;
Estimated number receiving each vaccination shot, #5: 55;
Estimated number receiving each vaccination shot, #6: 36;
Total number of reactions: 657.
Reaction type and duration: Local, Redness 2.5 inches or less, total
weighted number:
Estimated number receiving each vaccination shot, #1: 1,850;
Estimated number receiving each vaccination shot, #2: 1,505;
Estimated number receiving each vaccination shot, #3: 1,413;
Estimated number receiving each vaccination shot, #4: 982;
Estimated number receiving each vaccination shot, #5: 405;
Estimated number receiving each vaccination shot, #6: 143;
Total number of reactions: 6,298.
Reaction type and duration: Local, Redness 2.5 inches or less, percent
7 days or more:
Estimated number receiving each vaccination shot, #1: 11.7%;
Estimated number receiving each vaccination shot, #2: 7.4%;
Estimated number receiving each vaccination shot, #3: 10.3%;
Estimated number receiving each vaccination shot, #4: 9.3%;
Estimated number receiving each vaccination shot, #5: 13.6%;
Estimated number receiving each vaccination shot, #6: 25.2%.
Reaction type and duration: Local, Redness 2.5 inches or more, less
than 24 hours:
Estimated number receiving each vaccination shot, #1: 112;
Estimated number receiving each vaccination shot, #2: 158;
Estimated number receiving each vaccination shot, #3: 112;
Estimated number receiving each vaccination shot, #4: 91;
Estimated number receiving each vaccination shot, #5: 38;
Estimated number receiving each vaccination shot, #6: 2;
Total number of reactions: 513.
Reaction type and duration: Local, Redness 2.5 inches or more, 1-3
days:
Estimated number receiving each vaccination shot, #1: 282;
Estimated number receiving each vaccination shot, #2: 334;
Estimated number receiving each vaccination shot, #3: 350;
Estimated number receiving each vaccination shot, #4: 228;
Estimated number receiving each vaccination shot, #5: 140;
Estimated number receiving each vaccination shot, #6: 69;
Total number of reactions: 1,403.
Reaction type and duration: Local, Redness 2.5 inches or more, 4-7
days:
Estimated number receiving each vaccination shot, #1: 220;
Estimated number receiving each vaccination shot, #2: 200;
Estimated number receiving each vaccination shot, #3: 181;
Estimated number receiving each vaccination shot, #4: 126;
Estimated number receiving each vaccination shot, #5: 54;
Estimated number receiving each vaccination shot, #6: 17;
Total number of reactions: 798.
Reaction type and duration: Local, Redness 2.5 inches or more, 7 days
or more:
Estimated number receiving each vaccination shot, #1: 176;
Estimated number receiving each vaccination shot, #2: 192;
Estimated number receiving each vaccination shot, #3: 194;
Estimated number receiving each vaccination shot, #4: 71;
Estimated number receiving each vaccination shot, #5: 2;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 635.
Reaction type and duration: Local, Redness 2.5 inches or more, total
weighted number:
Estimated number receiving each vaccination shot, #1: 790;
Estimated number receiving each vaccination shot, #2: 884;
Estimated number receiving each vaccination shot, #3: 837;
Estimated number receiving each vaccination shot, #4: 516;
Estimated number receiving each vaccination shot, #5: 234;
Estimated number receiving each vaccination shot, #6: 88;
Total number of reactions: 3,349.
Reaction type and duration: Local, Redness 2.5 inches or more, percent
7 days or more:
Estimated number receiving each vaccination shot, #1: 22.3%;
Estimated number receiving each vaccination shot, #2: 21.7%;
Estimated number receiving each vaccination shot, #3: 23.2%;
Estimated number receiving each vaccination shot, #4: 13.8%;
Estimated number receiving each vaccination shot, #5: 0.9%;
Estimated number receiving each vaccination shot, #6: 0%.
Reaction type and duration: Local, Swelling in arm, less than 24 hours:
Estimated number receiving each vaccination shot, #1: 463;
Estimated number receiving each vaccination shot, #2: 446;
Estimated number receiving each vaccination shot, #3: 447;
Estimated number receiving each vaccination shot, #4: 301;
Estimated number receiving each vaccination shot, #5: 157;
Estimated number receiving each vaccination shot, #6: 35;
Total number of reactions: 1,879.
Reaction type and duration: Local, Swelling in arm, 1-3 days:
Estimated number receiving each vaccination shot, #1: 537;
Estimated number receiving each vaccination shot, #2: 617;
Estimated number receiving each vaccination shot, #3: 513;
Estimated number receiving each vaccination shot, #4: 334;
Estimated number receiving each vaccination shot, #5: 104;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 2,105.
Reaction type and duration: Local, Swelling in arm, 4-7 days:
Estimated number receiving each vaccination shot, #1: 349;
Estimated number receiving each vaccination shot, #2: 294;
Estimated number receiving each vaccination shot, #3: 291;
Estimated number receiving each vaccination shot, #4: 181;
Estimated number receiving each vaccination shot, #5: 55;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 1,170.
Reaction type and duration: Local, Swelling in arm, 7 days or more:
Estimated number receiving each vaccination shot, #1: 413;
Estimated number receiving each vaccination shot, #2: 339;
Estimated number receiving each vaccination shot, #3: 288;
Estimated number receiving each vaccination shot, #4: 197;
Estimated number receiving each vaccination shot, #5: 90;
Estimated number receiving each vaccination shot, #6: 71;
Total number of reactions: 1,398.
Reaction type and duration: Local, Swelling in arm, total weighted
number:
Estimated number receiving each vaccination shot, #1: 1,762;
Estimated number receiving each vaccination shot, #2: 1,696;
Estimated number receiving each vaccination shot, #3: 1,568;
Estimated number receiving each vaccination shot, #4: 1,013;
Estimated number receiving each vaccination shot, #5: 406;
Estimated number receiving each vaccination shot, #6: 106;
Total number of reactions: 6,551.
Reaction type and duration: Local, Swelling in arm, percent 7 days or
more:
Estimated number receiving each vaccination shot, #1: 23.4%;
Estimated number receiving each vaccination shot, #2: 20.0%;
Estimated number receiving each vaccination shot, #3: 18.4%;
Estimated number receiving each vaccination shot, #4: 19.4%;
Estimated number receiving each vaccination shot, #5: 22.2%;
Estimated number receiving each vaccination shot, #6: 67.0%.
Reaction type and duration: Local, Burning sensation in arm, less than
24 hours:
Estimated number receiving each vaccination shot, #1: 2,211;
Estimated number receiving each vaccination shot, #2: 2,099;
Estimated number receiving each vaccination shot, #3: 1,995;
Estimated number receiving each vaccination shot, #4: 1,304;
Estimated number receiving each vaccination shot, #5: 702;
Estimated number receiving each vaccination shot, #6: 194;
Total number of reactions: 8,505.
Reaction type and duration: Local, Burning sensation in arm, 1-3 days:
Estimated number receiving each vaccination shot, #1: 498;
Estimated number receiving each vaccination shot, #2: 498;
Estimated number receiving each vaccination shot, #3: 406;
Estimated number receiving each vaccination shot, #4: 301;
Estimated number receiving each vaccination shot, #5: 90;
Estimated number receiving each vaccination shot, #6: 19;
Total number of reactions: 1,812.
Reaction type and duration: Local, Burning sensation in arm, 4-7 days:
Estimated number receiving each vaccination shot, #1: 41;
Estimated number receiving each vaccination shot, #2: 58;
Estimated number receiving each vaccination shot, #3: 55;
Estimated number receiving each vaccination shot, #4: 55;
Estimated number receiving each vaccination shot, #5: 0;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 1,170.
Reaction type and duration: Local, Burning sensation in arm, 7 days or
more:
Estimated number receiving each vaccination shot, #1: 90;
Estimated number receiving each vaccination shot, #2: 69;
Estimated number receiving each vaccination shot, #3: 52;
Estimated number receiving each vaccination shot, #4: 35;
Estimated number receiving each vaccination shot, #5: 0;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 246.
Reaction type and duration: Local, Burning sensation in arm, total
weighted number:
Estimated number receiving each vaccination shot, #1: 2,840;
Estimated number receiving each vaccination shot, #2: 2,724;
Estimated number receiving each vaccination shot, #3: 2,508;
Estimated number receiving each vaccination shot, #4: 1,695;
Estimated number receiving each vaccination shot, #5: 792;
Estimated number receiving each vaccination shot, #6: 213;
Total number of reactions: 10,772.
Reaction type and duration: Local, Burning sensation in arm, percent 7
days or more:
Estimated number receiving each vaccination shot, #1: 3.2%;
Estimated number receiving each vaccination shot, #2: 2.5%;
Estimated number receiving each vaccination shot, #3: 2.1%;
Estimated number receiving each vaccination shot, #4: 2.1%;
Estimated number receiving each vaccination shot, #5: 0%;
Estimated number receiving each vaccination shot, #6: 0%.
Reaction type and duration: Local, Arm pain or limited motion, less
than 24 hours:
Estimated number receiving each vaccination shot, #1: 524;
Estimated number receiving each vaccination shot, #2: 455;
Estimated number receiving each vaccination shot, #3: 573;
Estimated number receiving each vaccination shot, #4: 334;
Estimated number receiving each vaccination shot, #5: 142;
Estimated number receiving each vaccination shot, #6: 35;
Total number of reactions: 2,063.
Reaction type and duration: Local, Arm pain or limited motion, 1-3
days:
Estimated number receiving each vaccination shot, #1: 564;
Estimated number receiving each vaccination shot, #2: 592;
Estimated number receiving each vaccination shot, #3: 491;
Estimated number receiving each vaccination shot, #4: 359;
Estimated number receiving each vaccination shot, #5: 157;
Estimated number receiving each vaccination shot, #6: 36;
Total number of reactions: 2,199.
Reaction type and duration: Local, Arm pain or limited motion, 4-7
days:
Estimated number receiving each vaccination shot, #1: 356;
Estimated number receiving each vaccination shot, #2: 337;
Estimated number receiving each vaccination shot, #3: 332;
Estimated number receiving each vaccination shot, #4: 194;
Estimated number receiving each vaccination shot, #5: 87;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 1,306.
Reaction type and duration: Local, Arm pain or limited motion, 7 days
or more:
Estimated number receiving each vaccination shot, #1: 247;
Estimated number receiving each vaccination shot, #2: 209;
Estimated number receiving each vaccination shot, #3: 156;
Estimated number receiving each vaccination shot, #4: 87;
Estimated number receiving each vaccination shot, #5: 19;
Estimated number receiving each vaccination shot, #6: 17;
Total number of reactions: 735.
Reaction type and duration: Local, Arm pain or limited motion, total
weighted number:
Estimated number receiving each vaccination shot, #1: 1,691;
Estimated number receiving each vaccination shot, #2: 1,593;
Estimated number receiving each vaccination shot, #3: 1,552;
Estimated number receiving each vaccination shot, #4: 974;
Estimated number receiving each vaccination shot, #5: 405;
Estimated number receiving each vaccination shot, #6: 88;
Total number of reactions: 6,303.
Reaction type and duration: Local, Arm pain or limited motion, percent
7 days or more:
Estimated number receiving each vaccination shot, #1: 14.6%;
Estimated number receiving each vaccination shot, #2: 13.1%;
Estimated number receiving each vaccination shot, #3: 10.1%;
Estimated number receiving each vaccination shot, #4: 8.9%;
Estimated number receiving each vaccination shot, #5: 4.7%;
Estimated number receiving each vaccination shot, #6: 19.3%.
Reaction type and duration: Local, Itching in arm, less than 24 hours:
Estimated number receiving each vaccination shot, #1: 567;
Estimated number receiving each vaccination shot, #2: 572;
Estimated number receiving each vaccination shot, #3: 554;
Estimated number receiving each vaccination shot, #4: 340;
Estimated number receiving each vaccination shot, #5: 145;
Estimated number receiving each vaccination shot, #6: 19;
Total number of reactions: 2,197.
Reaction type and duration: Local, Itching in arm, 1-3 days:
Estimated number receiving each vaccination shot, #1: 324;
Estimated number receiving each vaccination shot, #2: 307;
Estimated number receiving each vaccination shot, #3: 375;
Estimated number receiving each vaccination shot, #4: 211;
Estimated number receiving each vaccination shot, #5: 69;
Estimated number receiving each vaccination shot, #6: 17;
Total number of reactions: 1,303.
Reaction type and duration: Local, Itching in arm, 4-7 days:
Estimated number receiving each vaccination shot, #1: 231;
Estimated number receiving each vaccination shot, #2: 247;
Estimated number receiving each vaccination shot, #3: 178;
Estimated number receiving each vaccination shot, #4: 145;
Estimated number receiving each vaccination shot, #5: 71;
Estimated number receiving each vaccination shot, #6: 19;
Total number of reactions: 891.
Reaction type and duration: Local, Itching in arm, 7 days or more:
Estimated number receiving each vaccination shot, #1: 167;
Estimated number receiving each vaccination shot, #2: 145;
Estimated number receiving each vaccination shot, #3: 145;
Estimated number receiving each vaccination shot, #4: 109;
Estimated number receiving each vaccination shot, #5: 71;
Estimated number receiving each vaccination shot, #6: 35;
Total number of reactions: 672.
Reaction type and duration: Local, Itching in arm, total weighted
number:
Estimated number receiving each vaccination shot, #1: 1,289;
Estimated number receiving each vaccination shot, #2: 1,271;
Estimated number receiving each vaccination shot, #3: 1,252;
Estimated number receiving each vaccination shot, #4: 805;
Estimated number receiving each vaccination shot, #5: 356;
Estimated number receiving each vaccination shot, #6: 90;
Total number of reactions: 5,063.
Reaction type and duration: Local, Itching in arm, percent 7 days or
more:
Estimated number receiving each vaccination shot, #1: 13.0%;
Estimated number receiving each vaccination shot, #2: 11.4%;
Estimated number receiving each vaccination shot, #3: 11.6%;
Estimated number receiving each vaccination shot, #4: 13.5%;
Estimated number receiving each vaccination shot, #5: 19.9%;
Estimated number receiving each vaccination shot, #6: 38.9%.
Reaction type and duration: Local, Knot or lump in arm, less than 24
hours:
Estimated number receiving each vaccination shot, #1: 548;
Estimated number receiving each vaccination shot, #2: 465;
Estimated number receiving each vaccination shot, #3: 461;
Estimated number receiving each vaccination shot, #4: 249;
Estimated number receiving each vaccination shot, #5: 157;
Estimated number receiving each vaccination shot, #6: 35;
Total number of reactions: 1,915.
Reaction type and duration: Local, Knot or lump in arm, 1-3 days:
Estimated number receiving each vaccination shot, #1: 337;
Estimated number receiving each vaccination shot, #2: 381;
Estimated number receiving each vaccination shot, #3: 345;
Estimated number receiving each vaccination shot, #4: 282;
Estimated number receiving each vaccination shot, #5: 192;
Estimated number receiving each vaccination shot, #6: 19;
Total number of reactions: 1,556.
Reaction type and duration: Local, Knot or lump in arm, 4-7 days:
Estimated number receiving each vaccination shot, #1: 553;
Estimated number receiving each vaccination shot, #2: 624;
Estimated number receiving each vaccination shot, #3: 653;
Estimated number receiving each vaccination shot, #4: 499;
Estimated number receiving each vaccination shot, #5: 159;
Estimated number receiving each vaccination shot, #6: 36;
Total number of reactions: 2,524.
Reaction type and duration: Local, Knot or lump in arm, 7 days or more:
Estimated number receiving each vaccination shot, #1: 1,110;
Estimated number receiving each vaccination shot, #2: 1,013;
Estimated number receiving each vaccination shot, #3: 929;
Estimated number receiving each vaccination shot, #4: 485;
Estimated number receiving each vaccination shot, #5: 216;
Estimated number receiving each vaccination shot, #6: 123;
Total number of reactions: 3,876.
Reaction type and duration: Local, Knot or lump in arm, total weighted
number:
Estimated number receiving each vaccination shot, #1: 2,548;
Estimated number receiving each vaccination shot, #2: 2,483;
Estimated number receiving each vaccination shot, #3: 2,388;
Estimated number receiving each vaccination shot, #4: 1,515;
Estimated number receiving each vaccination shot, #5: 724;
Estimated number receiving each vaccination shot, #6: 213;
Total number of reactions: 9,871.
Reaction type and duration: Local, Knot or lump in arm, percent 7 days
or more:
Estimated number receiving each vaccination shot, #1: 43.6%;
Estimated number receiving each vaccination shot, #2: 40.8%;
Estimated number receiving each vaccination shot, #3: 38.9%;
Estimated number receiving each vaccination shot, #4: 32.0%;
Estimated number receiving each vaccination shot, #5: 29.8%;
Estimated number receiving each vaccination shot, #6: 57.7%.
Reaction type and duration: Systemic, chills, less than 24 hours:
Estimated number receiving each vaccination shot, #1: 167;
Estimated number receiving each vaccination shot, #2: 77;
Estimated number receiving each vaccination shot, #3: 159;
Estimated number receiving each vaccination shot, #4: 140;
Estimated number receiving each vaccination shot, #5: 54;
Estimated number receiving each vaccination shot, #6: 17;
Total number of reactions: 614.
Reaction type and duration: Systemic, chills, 1-3 days:
Estimated number receiving each vaccination shot, #1: 107;
Estimated number receiving each vaccination shot, #2: 124;
Estimated number receiving each vaccination shot, #3: 106;
Estimated number receiving each vaccination shot, #4: 71;
Estimated number receiving each vaccination shot, #5: 19;
Estimated number receiving each vaccination shot, #6: 2;
Total number of reactions: 429.
Reaction type and duration: Systemic, chills, 4-7 days:
Estimated number receiving each vaccination shot, #1: 71;
Estimated number receiving each vaccination shot, #2: 71;
Estimated number receiving each vaccination shot, #3: 71;
Estimated number receiving each vaccination shot, #4: 36;
Estimated number receiving each vaccination shot, #5: 0;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 249.
Reaction type and duration: Systemic, chills, 7 days or more:
Estimated number receiving each vaccination shot, #1: 17;
Estimated number receiving each vaccination shot, #2: 35;
Estimated number receiving each vaccination shot, #3: 17;
Estimated number receiving each vaccination shot, #4: 0;
Estimated number receiving each vaccination shot, #5: 17;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 86.
Reaction type and duration: Systemic, chills, total weighted number:
Estimated number receiving each vaccination shot, #1: 362;
Estimated number receiving each vaccination shot, #2: 307;
Estimated number receiving each vaccination shot, #3: 353;
Estimated number receiving each vaccination shot, #4: 247;
Estimated number receiving each vaccination shot, #5: 90;
Estimated number receiving each vaccination shot, #6: 19;
Total number of reactions: 1,378.
Reaction type and duration: Systemic, chills, percent 7 days or more:
Estimated number receiving each vaccination shot, #1: 4.7%;
Estimated number receiving each vaccination shot, #2: 11.4%;
Estimated number receiving each vaccination shot, #3: 4.8%;
Estimated number receiving each vaccination shot, #4: 0%;
Estimated number receiving each vaccination shot, #5: 18.9%;
Estimated number receiving each vaccination shot, #6: 0%.
Reaction type and duration: Systemic, fever, less than 24 hours:
Estimated number receiving each vaccination shot, #1: 203;
Estimated number receiving each vaccination shot, #2: 167;
Estimated number receiving each vaccination shot, #3: 197;
Estimated number receiving each vaccination shot, #4: 157;
Estimated number receiving each vaccination shot, #5: 54;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 778.
Reaction type and duration: Systemic, fever, 1-3 days:
Estimated number receiving each vaccination shot, #1: 180;
Estimated number receiving each vaccination shot, #2: 178;
Estimated number receiving each vaccination shot, #3: 176;
Estimated number receiving each vaccination shot, #4: 72;
Estimated number receiving each vaccination shot, #5: 38;
Estimated number receiving each vaccination shot, #6: 19;
Total number of reactions: 663.
Reaction type and duration: Systemic, fever, 4-7 days:
Estimated number receiving each vaccination shot, #1: 71;
Estimated number receiving each vaccination shot, #2: 71;
Estimated number receiving each vaccination shot, #3: 71;
Estimated number receiving each vaccination shot, #4: 36;
Estimated number receiving each vaccination shot, #5: 0;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 249.
Reaction type and duration: Systemic, fever, 7 days or more:
Estimated number receiving each vaccination shot, #1: 19;
Estimated number receiving each vaccination shot, #2: 36;
Estimated number receiving each vaccination shot, #3: 19;
Estimated number receiving each vaccination shot, #4: 36;
Estimated number receiving each vaccination shot, #5: 0;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 110.
Reaction type and duration: Systemic, fever, total weighted number:
Estimated number receiving each vaccination shot, #1: 35;
Estimated number receiving each vaccination shot, #2: 52;
Estimated number receiving each vaccination shot, #3: 52;
Estimated number receiving each vaccination shot, #4: 17;
Estimated number receiving each vaccination shot, #5: 0;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 156.
Reaction type and duration: Systemic, fever, percent 7 days or more:
Estimated number receiving each vaccination shot, #1: 8.0%;
Estimated number receiving each vaccination shot, #2: 12.0%;
Estimated number receiving each vaccination shot, #3: 11.7%;
Estimated number receiving each vaccination shot, #4: 6.0%;
Estimated number receiving each vaccination shot, #5: 0%;
Estimated number receiving each vaccination shot, #6: 0%.
Reaction type and duration: Systemic, extreme fatigue, less than 24
hours:
Estimated number receiving each vaccination shot, #1: 159;
Estimated number receiving each vaccination shot, #2: 213;
Estimated number receiving each vaccination shot, #3: 211;
Estimated number receiving each vaccination shot, #4: 139;
Estimated number receiving each vaccination shot, #5: 36;
Estimated number receiving each vaccination shot, #6: 2;
Total number of reactions: 760.
Reaction type and duration: Systemic, extreme fatigue, 1-3 days:
Estimated number receiving each vaccination shot, #1: 233;
Estimated number receiving each vaccination shot, #2: 213;
Estimated number receiving each vaccination shot, #3: 211;
Estimated number receiving each vaccination shot, #4: 71;
Estimated number receiving each vaccination shot, #5: 35;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 763.
Reaction type and duration: Systemic, extreme fatigue, 4-7 days:
Estimated number receiving each vaccination shot, #1: 72;
Estimated number receiving each vaccination shot, #2: 88;
Estimated number receiving each vaccination shot, #3: 54;
Estimated number receiving each vaccination shot, #4: 54;
Estimated number receiving each vaccination shot, #5: 36;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 304.
Reaction type and duration: Systemic, extreme fatigue, 7 days or more:
Estimated number receiving each vaccination shot, #1: 214;
Estimated number receiving each vaccination shot, #2: 231;
Estimated number receiving each vaccination shot, #3: 231;
Estimated number receiving each vaccination shot, #4: 140;
Estimated number receiving each vaccination shot, #5: 17;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 833.
Reaction type and duration: Systemic, extreme fatigue, total weighted
number:
Estimated number receiving each vaccination shot, #1: 678;
Estimated number receiving each vaccination shot, #2: 745;
Estimated number receiving each vaccination shot, #3: 707;
Estimated number receiving each vaccination shot, #4: 404;
Estimated number receiving each vaccination shot, #5: 124;
Estimated number receiving each vaccination shot, #6: 2;
Total number of reactions: 2,660.
Reaction type and duration: Systemic, extreme fatigue, percent 7 days
or more:
Estimated number receiving each vaccination shot, #1: 31.6%;
Estimated number receiving each vaccination shot, #2: 31.0%;
Estimated number receiving each vaccination shot, #3: 32.7%;
Estimated number receiving each vaccination shot, #4: 34.7%;
Estimated number receiving each vaccination shot, #5: 13.7%;
Estimated number receiving each vaccination shot, #6: 0%.
Reaction type and duration: Local, dizziness, less than 24 hours:
Estimated number receiving each vaccination shot, #1: 57;
Estimated number receiving each vaccination shot, #2: 39;
Estimated number receiving each vaccination shot, #3: 38;
Estimated number receiving each vaccination shot, #4: 38;
Estimated number receiving each vaccination shot, #5: 36;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 208.
Reaction type and duration: Local, dizziness, 1-3 days:
Estimated number receiving each vaccination shot, #1: 36;
Estimated number receiving each vaccination shot, #2: 54;
Estimated number receiving each vaccination shot, #3: 88;
Estimated number receiving each vaccination shot, #4: 52;
Estimated number receiving each vaccination shot, #5: 0;
Estimated number receiving each vaccination shot, #6: 2;
Total number of reactions: 232.
Reaction type and duration: Local, dizziness, 4-7 days:
Estimated number receiving each vaccination shot, #1: 17;
Estimated number receiving each vaccination shot, #2: 17;
Estimated number receiving each vaccination shot, #3: 0;
Estimated number receiving each vaccination shot, #4: 0;
Estimated number receiving each vaccination shot, #5: 0;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 34.
Reaction type and duration: Local, dizziness, 7 days or more:
Estimated number receiving each vaccination shot, #1: 35;
Estimated number receiving each vaccination shot, #2: 17;
Estimated number receiving each vaccination shot, #3: 17;
Estimated number receiving each vaccination shot, #4: 35;
Estimated number receiving each vaccination shot, #5: 0;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 104.
Reaction type and duration: Local, dizziness, total weighted number:
Estimated number receiving each vaccination shot, #1: 145;
Estimated number receiving each vaccination shot, #2: 127;
Estimated number receiving each vaccination shot, #3: 143;
Estimated number receiving each vaccination shot, #4: 125;
Estimated number receiving each vaccination shot, #5: 36;
Estimated number receiving each vaccination shot, #6: 2;
Total number of reactions: 578.
Reaction type and duration: Local, dizziness, percent 7 days or more:
Estimated number receiving each vaccination shot, #1: 24.1%;
Estimated number receiving each vaccination shot, #2: 13.4%;
Estimated number receiving each vaccination shot, #3: 11.9%;
Estimated number receiving each vaccination shot, #4: 28.0%;
Estimated number receiving each vaccination shot, #5: 0%;
Estimated number receiving each vaccination shot, #6: 0%.
Reaction type and duration: Local, headaches, less than 24 hours:
Estimated number receiving each vaccination shot, #1: 184;
Estimated number receiving each vaccination shot, #2: 146;
Estimated number receiving each vaccination shot, #3: 178;
Estimated number receiving each vaccination shot, #4: 123;
Estimated number receiving each vaccination shot, #5: 52;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 683.
Reaction type and duration: Local, headaches, 1-3 days:
Estimated number receiving each vaccination shot, #1: 124;
Estimated number receiving each vaccination shot, #2: 1064;
Estimated number receiving each vaccination shot, #3: 175;
Estimated number receiving each vaccination shot, #4: 71;
Estimated number receiving each vaccination shot, #5: 19;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 495.
Reaction type and duration: Local, headaches, 4-7 days:
Estimated number receiving each vaccination shot, #1: 71;
Estimated number receiving each vaccination shot, #2: 54;
Estimated number receiving each vaccination shot, #3: 36;
Estimated number receiving each vaccination shot, #4: 19;
Estimated number receiving each vaccination shot, #5: 2;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 182.
Reaction type and duration: Local, headaches, 7 days or more:
Estimated number receiving each vaccination shot, #1: 71;
Estimated number receiving each vaccination shot, #2: 71;
Estimated number receiving each vaccination shot, #3: 36;
Estimated number receiving each vaccination shot, #4: 36;
Estimated number receiving each vaccination shot, #5: 2;
Estimated number receiving each vaccination shot, #6: 2;
Total number of reactions: 218.
Reaction type and duration: Local, headaches, total weighted number:
Estimated number receiving each vaccination shot, #1: 450;
Estimated number receiving each vaccination shot, #2: 377;
Estimated number receiving each vaccination shot, #3: 425;
Estimated number receiving each vaccination shot, #4: 249;
Estimated number receiving each vaccination shot, #5: 75;
Estimated number receiving each vaccination shot, #6: 2;
Total number of reactions: 1,578.
Reaction type and duration: Local, headaches, percent 7 days or more:
Estimated number receiving each vaccination shot, #1: 15.8%;
Estimated number receiving each vaccination shot, #2: 18.8%;
Estimated number receiving each vaccination shot, #3: 8.5%;
Estimated number receiving each vaccination shot, #4: 14.5%;
Estimated number receiving each vaccination shot, #5: 2.7%;
Estimated number receiving each vaccination shot, #6: 0%.
Reaction type and duration: Local, blurred vision, less than 24 hours:
Estimated number receiving each vaccination shot, #1: 55;
Estimated number receiving each vaccination shot, #2: 55;
Estimated number receiving each vaccination shot, #3: 55;
Estimated number receiving each vaccination shot, #4: 36;
Estimated number receiving each vaccination shot, #5: 17;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 218.
Reaction type and duration: Local, blurred vision, 1-3 days:
Estimated number receiving each vaccination shot, #1: 0;
Estimated number receiving each vaccination shot, #2: 0;
Estimated number receiving each vaccination shot, #3: 35;
Estimated number receiving each vaccination shot, #4: 0;
Estimated number receiving each vaccination shot, #5: 0;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 35.
Reaction type and duration: Local, blurred vision, 4-7 days:
Estimated number receiving each vaccination shot, #1: 19;
Estimated number receiving each vaccination shot, #2: 19;
Estimated number receiving each vaccination shot, #3: 19;
Estimated number receiving each vaccination shot, #4: 19;
Estimated number receiving each vaccination shot, #5: 2;
Estimated number receiving each vaccination shot, #6: 1;
Total number of reactions: 79.
Reaction type and duration: Local, blurred vision, 7 days or more:
Estimated number receiving each vaccination shot, #1: 35;
Estimated number receiving each vaccination shot, #2: 35;
Estimated number receiving each vaccination shot, #3: 17;
Estimated number receiving each vaccination shot, #4: 17;
Estimated number receiving each vaccination shot, #5: 0;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 104.
Reaction type and duration: Local, blurred vision, total weighted
number:
Estimated number receiving each vaccination shot, #1: 109;
Estimated number receiving each vaccination shot, #2: 109;
Estimated number receiving each vaccination shot, #3: 126;
Estimated number receiving each vaccination shot, #4: 72;
Estimated number receiving each vaccination shot, #5: 19;
Estimated number receiving each vaccination shot, #6: 1;
Total number of reactions: 436.
Reaction type and duration: Local, blurred vision, percent 7 days or
more:
Estimated number receiving each vaccination shot, #1: 32.1%;
Estimated number receiving each vaccination shot, #2: 32.1%;
Estimated number receiving each vaccination shot, #3: 13.5%;
Estimated number receiving each vaccination shot, #4: 23.6%;
Estimated number receiving each vaccination shot, #5: 0%;
Estimated number receiving each vaccination shot, #6: 0%.
Reaction type and duration: Local, numbness in extremities, less than
24 hours:
Estimated number receiving each vaccination shot, #1: 60;
Estimated number receiving each vaccination shot, #2: 41;
Estimated number receiving each vaccination shot, #3: 39;
Estimated number receiving each vaccination shot, #4: 54;
Estimated number receiving each vaccination shot, #5: 17;
Estimated number receiving each vaccination shot, #6: 17;
Total number of reactions: 228.
Reaction type and duration: Local, numbness in extremities, 1-3 days:
Estimated number receiving each vaccination shot, #1: 2;
Estimated number receiving each vaccination shot, #2: 2;
Estimated number receiving each vaccination shot, #3: 19;
Estimated number receiving each vaccination shot, #4: 3;
Estimated number receiving each vaccination shot, #5: 2;
Estimated number receiving each vaccination shot, #6: 2;
Total number of reactions: 30.
Reaction type and duration: Local, numbness in extremities, 4-7 days:
Estimated number receiving each vaccination shot, #1: 35;
Estimated number receiving each vaccination shot, #2: 35;
Estimated number receiving each vaccination shot, #3: 36;
Estimated number receiving each vaccination shot, #4: 36;
Estimated number receiving each vaccination shot, #5: 2;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 144.
Reaction type and duration: Local, numbness in extremities, 7 days or
more:
Estimated number receiving each vaccination shot, #1: 71;
Estimated number receiving each vaccination shot, #2: 71;
Estimated number receiving each vaccination shot, #3: 52;
Estimated number receiving each vaccination shot, #4: 0;
Estimated number receiving each vaccination shot, #5: 2;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 198.
Reaction type and duration: Local, numbness in extremities, total
weighted number:
Estimated number receiving each vaccination shot, #1: 168;
Estimated number receiving each vaccination shot, #2: 149;
Estimated number receiving each vaccination shot, #3: 146;
Estimated number receiving each vaccination shot, #4: 93;
Estimated number receiving each vaccination shot, #5: 23;
Estimated number receiving each vaccination shot, #6: 21;
Total number of reactions: 600.
Reaction type and duration: Local, numbness in extremities, percent 7
days or more:
Estimated number receiving each vaccination shot, #1: 42.3%;
Estimated number receiving each vaccination shot, #2: 47.7%;
Estimated number receiving each vaccination shot, #3: 35.6%;
Estimated number receiving each vaccination shot, #4: 0%;
Estimated number receiving each vaccination shot, #5: 8.7%;
Estimated number receiving each vaccination shot, #6: 9.5%.
Reaction type and duration: Local, joint pain, less than 24 hours:
Estimated number receiving each vaccination shot, #1: 180;
Estimated number receiving each vaccination shot, #2: 164;
Estimated number receiving each vaccination shot, #3: 180;
Estimated number receiving each vaccination shot, #4: 175;
Estimated number receiving each vaccination shot, #5: 71;
Estimated number receiving each vaccination shot, #6: 54;
Total number of reactions: 824.
Reaction type and duration: Local, joint pain, 1-3 days:
Estimated number receiving each vaccination shot, #1: 178;
Estimated number receiving each vaccination shot, #2: 140;
Estimated number receiving each vaccination shot, #3: 175;
Estimated number receiving each vaccination shot, #4: 106;
Estimated number receiving each vaccination shot, #5: 17;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 616.
Reaction type and duration: Local, joint pain, 4-7 days:
Estimated number receiving each vaccination shot, #1: 128;
Estimated number receiving each vaccination shot, #2: 161;
Estimated number receiving each vaccination shot, #3: 161;
Estimated number receiving each vaccination shot, #4: 126;
Estimated number receiving each vaccination shot, #5: 38;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 614.
Reaction type and duration: Local, joint pain, 7 days or more:
Estimated number receiving each vaccination shot, #1: 268;
Estimated number receiving each vaccination shot, #2: 265;
Estimated number receiving each vaccination shot, #3: 230;
Estimated number receiving each vaccination shot, #4: 121;
Estimated number receiving each vaccination shot, #5: 54;
Estimated number receiving each vaccination shot, #6: 2;
Total number of reactions: 940.
Reaction type and duration: Local, joint pain, total weighted number:
Estimated number receiving each vaccination shot, #1: 754;
Estimated number receiving each vaccination shot, #2: 730;
Estimated number receiving each vaccination shot, #3: 746;
Estimated number receiving each vaccination shot, #4: 528;
Estimated number receiving each vaccination shot, #5: 180;
Estimated number receiving each vaccination shot, #6: 56;
Total number of reactions: 2,994.
Reaction type and duration: Local, joint pain, percent 7 days or more:
Estimated number receiving each vaccination shot, #1: 35.5%;
Estimated number receiving each vaccination shot, #2: 36.3%;
Estimated number receiving each vaccination shot, #3: 30.8%;
Estimated number receiving each vaccination shot, #4: 22.9%;
Estimated number receiving each vaccination shot, #5: 30.0%;
Estimated number receiving each vaccination shot, #6: 3.6%.
Reaction type and duration: Local, memory loss, less than 24 hours:
Estimated number receiving each vaccination shot, #1: 55;
Estimated number receiving each vaccination shot, #2: 38;
Estimated number receiving each vaccination shot, #3: 55;
Estimated number receiving each vaccination shot, #4: 54;
Estimated number receiving each vaccination shot, #5: 17;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 219.
Reaction type and duration: Local, memory loss, 1-3 days:
Estimated number receiving each vaccination shot, #1: 2;
Estimated number receiving each vaccination shot, #2: 19;
Estimated number receiving each vaccination shot, #3: 2;
Estimated number receiving each vaccination shot, #4: 0;
Estimated number receiving each vaccination shot, #5: 17;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 40.
Reaction type and duration: Local, memory loss, 4-7 days:
Estimated number receiving each vaccination shot, #1: 35;
Estimated number receiving each vaccination shot, #2: 35;
Estimated number receiving each vaccination shot, #3: 35;
Estimated number receiving each vaccination shot, #4: 17;
Estimated number receiving each vaccination shot, #5: 0;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 122.
Reaction type and duration: Local, memory loss, 7 days or more:
Estimated number receiving each vaccination shot, #1: 93;
Estimated number receiving each vaccination shot, #2: 76;
Estimated number receiving each vaccination shot, #3: 93;
Estimated number receiving each vaccination shot, #4: 54;
Estimated number receiving each vaccination shot, #5: 17;
Estimated number receiving each vaccination shot, #6: 2;
Total number of reactions: 335.
Reaction type and duration: Local, memory loss, total weighted number:
Estimated number receiving each vaccination shot, #1: 185;
Estimated number receiving each vaccination shot, #2: 168;
Estimated number receiving each vaccination shot, #3: 185;
Estimated number receiving each vaccination shot, #4: 125;
Estimated number receiving each vaccination shot, #5: 51;
Estimated number receiving each vaccination shot, #6: 2;
Total number of reactions: 716.
Reaction type and duration: Local, memory loss, percent 7 days or more:
Estimated number receiving each vaccination shot, #1: 50.3%;
Estimated number receiving each vaccination shot, #2: 45.2%;
Estimated number receiving each vaccination shot, #3: 50.3%;
Estimated number receiving each vaccination shot, #4: 43.2%;
Estimated number receiving each vaccination shot, #5: 33.3%;
Estimated number receiving each vaccination shot, #6: 0%.
Reaction type and duration: Local, blackouts, less than 24 hours:
Estimated number receiving each vaccination shot, #1: 19;
Estimated number receiving each vaccination shot, #2: 19;
Estimated number receiving each vaccination shot, #3: 19;
Estimated number receiving each vaccination shot, #4: 19;
Estimated number receiving each vaccination shot, #5: 17;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 93.
Reaction type and duration: Local, blackouts, 1-3 days:
Estimated number receiving each vaccination shot, #1: 0;
Estimated number receiving each vaccination shot, #2: 0;
Estimated number receiving each vaccination shot, #3: 0;
Estimated number receiving each vaccination shot, #4: 0;
Estimated number receiving each vaccination shot, #5: 0;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 0.
Reaction type and duration: Local, blackouts, 4-7 days:
Estimated number receiving each vaccination shot, #1: 0;
Estimated number receiving each vaccination shot, #2: 0;
Estimated number receiving each vaccination shot, #3: 0;
Estimated number receiving each vaccination shot, #4: 0;
Estimated number receiving each vaccination shot, #5: 0;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 0.
Reaction type and duration: Local, blackouts, 7 days or more:
Estimated number receiving each vaccination shot, #1: 17;
Estimated number receiving each vaccination shot, #2: 0;
Estimated number receiving each vaccination shot, #3: 0;
Estimated number receiving each vaccination shot, #4: 0;
Estimated number receiving each vaccination shot, #5: 0;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 17.
Reaction type and duration: Local, blackouts, total weighted number:
Estimated number receiving each vaccination shot, #1: 36;
Estimated number receiving each vaccination shot, #2: 19;
Estimated number receiving each vaccination shot, #3: 19;
Estimated number receiving each vaccination shot, #4: 19;
Estimated number receiving each vaccination shot, #5: 17;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 110.
Reaction type and duration: Local, blackouts, percent 7 days or more:
Estimated number receiving each vaccination shot, #1: 47.2%;
Estimated number receiving each vaccination shot, #2: 0%;
Estimated number receiving each vaccination shot, #3: 0%;
Estimated number receiving each vaccination shot, #4: 0%;
Estimated number receiving each vaccination shot, #5: 0%;
Estimated number receiving each vaccination shot, #6: 0%.
Reaction type and duration: Local, ringing in ears, less than 24 hours:
Estimated number receiving each vaccination shot, #1: 107;
Estimated number receiving each vaccination shot, #2: 107;
Estimated number receiving each vaccination shot, #3: 55;
Estimated number receiving each vaccination shot, #4: 38;
Estimated number receiving each vaccination shot, #5: 19;
Estimated number receiving each vaccination shot, #6: 2;
Total number of reactions: 328.
Reaction type and duration: Local, ringing in ears, 1-3 days:
Estimated number receiving each vaccination shot, #1: 36;
Estimated number receiving each vaccination shot, #2: 36;
Estimated number receiving each vaccination shot, #3: 54;
Estimated number receiving each vaccination shot, #4: 0;
Estimated number receiving each vaccination shot, #5: 17;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 143.
Reaction type and duration: Local, ringing in ears, 4-7 days:
Estimated number receiving each vaccination shot, #1: 19;
Estimated number receiving each vaccination shot, #2: 19;
Estimated number receiving each vaccination shot, #3: 19;
Estimated number receiving each vaccination shot, #4: 2;
Estimated number receiving each vaccination shot, #5: 2;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 61.
Reaction type and duration: Local, ringing in ears, 7 days or more:
Estimated number receiving each vaccination shot, #1: 91;
Estimated number receiving each vaccination shot, #2: 38;
Estimated number receiving each vaccination shot, #3: 71;
Estimated number receiving each vaccination shot, #4: 52;
Estimated number receiving each vaccination shot, #5: 0;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 252.
Reaction type and duration: Local, ringing in ears, total weighted
number:
Estimated number receiving each vaccination shot, #1: 253;
Estimated number receiving each vaccination shot, #2: 200;
Estimated number receiving each vaccination shot, #3: 199;
Estimated number receiving each vaccination shot, #4: 92;
Estimated number receiving each vaccination shot, #5: 38;
Estimated number receiving each vaccination shot, #6: 2;
Total number of reactions: 784.
Reaction type and duration: Local, ringing in ears, percent 7 days or
more:
Estimated number receiving each vaccination shot, #1: 36.0%;
Estimated number receiving each vaccination shot, #2: 19.0%;
Estimated number receiving each vaccination shot, #3: 35.7%;
Estimated number receiving each vaccination shot, #4: 56.5%;
Estimated number receiving each vaccination shot, #5: 0%;
Estimated number receiving each vaccination shot, #6: 0%.
Reaction type and duration: Local, insomnia, less than 24 hours:
Estimated number receiving each vaccination shot, #1: 39;
Estimated number receiving each vaccination shot, #2: 38;
Estimated number receiving each vaccination shot, #3: 38;
Estimated number receiving each vaccination shot, #4: 19;
Estimated number receiving each vaccination shot, #5: 17;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 151.
Reaction type and duration: Local, insomnia, 1-3 days:
Estimated number receiving each vaccination shot, #1: 19;
Estimated number receiving each vaccination shot, #2: 3;
Estimated number receiving each vaccination shot, #3: 3;
Estimated number receiving each vaccination shot, #4: 0;
Estimated number receiving each vaccination shot, #5: 17;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 42.
Reaction type and duration: Local, insomnia, 4-7 days:
Estimated number receiving each vaccination shot, #1: 55;
Estimated number receiving each vaccination shot, #2: 55;
Estimated number receiving each vaccination shot, #3: 38;
Estimated number receiving each vaccination shot, #4: 19;
Estimated number receiving each vaccination shot, #5: 19;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 186.
Reaction type and duration: Local, insomnia, 7 days or more:
Estimated number receiving each vaccination shot, #1: 87;
Estimated number receiving each vaccination shot, #2: 69;
Estimated number receiving each vaccination shot, #3: 69;
Estimated number receiving each vaccination shot, #4: 35;
Estimated number receiving each vaccination shot, #5: 0;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 260.
Reaction type and duration: Local, insomnia, total weighted number:
Estimated number receiving each vaccination shot, #1: 200;
Estimated number receiving each vaccination shot, #2: 165;
Estimated number receiving each vaccination shot, #3: 148;
Estimated number receiving each vaccination shot, #4: 73;
Estimated number receiving each vaccination shot, #5: 53;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 639.
Reaction type and duration: Local, insomnia, percent 7 days or more:
Estimated number receiving each vaccination shot, #1: 43.5%;
Estimated number receiving each vaccination shot, #2: 41.8%;
Estimated number receiving each vaccination shot, #3: 46.6%;
Estimated number receiving each vaccination shot, #4: 47.9%;
Estimated number receiving each vaccination shot, #5: 0%;
Estimated number receiving each vaccination shot, #6: 0%.
Reaction type and duration: Local, nausea, less than 24 hours:
Estimated number receiving each vaccination shot, #1: 90;
Estimated number receiving each vaccination shot, #2: 106;
Estimated number receiving each vaccination shot, #3: 106;
Estimated number receiving each vaccination shot, #4: 87;
Estimated number receiving each vaccination shot, #5: 69;
Estimated number receiving each vaccination shot, #6: 17;
Total number of reactions: 475.
Reaction type and duration: Local, nausea, 1-3 days:
Estimated number receiving each vaccination shot, #1: 39;
Estimated number receiving each vaccination shot, #2: 57;
Estimated number receiving each vaccination shot, #3: 76;
Estimated number receiving each vaccination shot, #4: 54;
Estimated number receiving each vaccination shot, #5: 3;
Estimated number receiving each vaccination shot, #6: 2;
Total number of reactions: 231.
Reaction type and duration: Local, nausea, 4-7 days:
Estimated number receiving each vaccination shot, #1: 52;
Estimated number receiving each vaccination shot, #2: 36;
Estimated number receiving each vaccination shot, #3: 17;
Estimated number receiving each vaccination shot, #4: 19;
Estimated number receiving each vaccination shot, #5: 17;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 141.
Reaction type and duration: Local, nausea, 7 days or more:
Estimated number receiving each vaccination shot, #1: 19;
Estimated number receiving each vaccination shot, #2: 2;
Estimated number receiving each vaccination shot, #3: 2;
Estimated number receiving each vaccination shot, #4: 2;
Estimated number receiving each vaccination shot, #5: 0;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 25.
Reaction type and duration: Local, nausea, total weighted number:
Estimated number receiving each vaccination shot, #1: 200;
Estimated number receiving each vaccination shot, #2: 201;
Estimated number receiving each vaccination shot, #3: 201;
Estimated number receiving each vaccination shot, #4: 162;
Estimated number receiving each vaccination shot, #5: 89;
Estimated number receiving each vaccination shot, #6: 19;
Total number of reactions: 872.
Reaction type and duration: Local, nausea, percent 7 days or more:
Estimated number receiving each vaccination shot, #1: 9.5%;
Estimated number receiving each vaccination shot, #2: 1.0%;
Estimated number receiving each vaccination shot, #3: 1.0%;
Estimated number receiving each vaccination shot, #4: 1.2%;
Estimated number receiving each vaccination shot, #5: 0%;
Estimated number receiving each vaccination shot, #6: 0%.
Reaction type and duration: Local, other, less than 24 hours:
Estimated number receiving each vaccination shot, #1: 19;
Estimated number receiving each vaccination shot, #2: 20;
Estimated number receiving each vaccination shot, #3: 36;
Estimated number receiving each vaccination shot, #4: 17;
Estimated number receiving each vaccination shot, #5: 0;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 92.
Reaction type and duration: Local, other, 1-3 days:
Estimated number receiving each vaccination shot, #1: 35;
Estimated number receiving each vaccination shot, #2: 35;
Estimated number receiving each vaccination shot, #3: 35;
Estimated number receiving each vaccination shot, #4: 15;
Estimated number receiving each vaccination shot, #5: 35;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 157.
Reaction type and duration: Local, other, 4-7 days:
Estimated number receiving each vaccination shot, #1: 69;
Estimated number receiving each vaccination shot, #2: 69;
Estimated number receiving each vaccination shot, #3: 88;
Estimated number receiving each vaccination shot, #4: 52;
Estimated number receiving each vaccination shot, #5: 0;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 278.
Reaction type and duration: Local, other, 7 days or more:
Estimated number receiving each vaccination shot, #1: 69;
Estimated number receiving each vaccination shot, #2: 35;
Estimated number receiving each vaccination shot, #3: 54;
Estimated number receiving each vaccination shot, #4: 69;
Estimated number receiving each vaccination shot, #5: 34;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 261.
Reaction type and duration: Local, other, total weighted number:
Estimated number receiving each vaccination shot, #1: 192;
Estimated number receiving each vaccination shot, #2: 159;
Estimated number receiving each vaccination shot, #3: 213;
Estimated number receiving each vaccination shot, #4: 155;
Estimated number receiving each vaccination shot, #5: 69;
Estimated number receiving each vaccination shot, #6: 0;
Total number of reactions: 788.
Reaction type and duration: Local, other, percent 7 days or more:
Estimated number receiving each vaccination shot, #1: 35.9%;
Estimated number receiving each vaccination shot, #2: 22.0%;
Estimated number receiving each vaccination shot, #3: 25.4%;
Estimated number receiving each vaccination shot, #4: 44.5%;
Estimated number receiving each vaccination shot, #5: 49.3%;
Estimated number receiving each vaccination shot, #6: 0%.
Source: GAO analysis.
[End of table]
[End of section]
Appendix IV: Anthrax Vaccine Adsorbed Revised Product Insert (Jan. 31,
2002):
Description:
Anthrax Vaccine Adsorbed (BioThrax) is a sterile, milky-white
suspension (when mixed) made from cell-free filtrates of microaerophilic
cultures of an avirulent, nonencapsulated strain of Bacillus anthracis.
The production cultures are grown in a chemically defined protein-free
medium consisting of a mixture of amino acids, vitamins, inorganic salts
and sugars. The final product, prepared from the sterile filtrate
culture fluid, contains proteins, including the 83kDa protective
antigen protein, released during the growth period. The final product
contains no dead or live bacteria. The final product is formulated to
contain 1.2 mg/mL aluminum, added as aluminum hydroxide in 0.85% sodium
chloride. The product is formulated to contain 25 mg/mL benzethonium
chloride and 100 mg/mL formaldehyde, added as preservatives.
Clinical Pharmacology:
Epidemiology:
Anthrax occurs globally and is most common in agricultural regions with
inadequate control programs for anthrax in livestock. Anthrax is a
zoonotic disease caused by the Gram-positive, spore-forming bacterium
Bacillus anthracis. The spore form of Bacillus anthracis is the
predominant phase of the bacterium in the environment and it is largely
through the uptake of spores that anthrax disease is contracted. Spore
forms are markedly resistant to heat, cold, pH, desiccation, chemicals
and irradiation. Following germination at the site of infection, the
bacilli can also enter the blood and lead to septicemia. Antibiotics
are effective against the germinated form of Bacillus anthracis, but
are not effective against the spore form of the organism.
The disease occurs most commonly in wild and domestic animals,
primarily cattle, sheep, goats and other herbivores. In humans, anthrax
disease can result from contact with animal hides, leather or hair
products from contaminated animals, or from other exposures to Bacillus
anthracis spores. It occurs in three forms depending upon the route of
infection: cutaneous anthrax, gastrointestinal anthrax and inhalation
anthrax.
Cutaneous anthrax is the most commonly reported form in humans
(> 95% of all anthrax cases). It can occur when the bacterium enters a
cut or abrasion on the skin, such as when handling contaminated meat,
wool, hides, leather or hair products from infected animals or other
contaminated materials. The symptoms of cutaneous anthrax begin with
an itchy reddish-brown papule on exposed skin surfaces and may appear
approximately 1–12 days after contact. The lesion soon develops a small
vesicle. Secondary vesicles are sometimes seen. Later the vesicle
ruptures and leaves a painless ulcer that typically develops a
blackened eschar with surrounding swollen tissue. There are often
associated systemic symptoms such as swollen glands, fever, myalgia,
malaise, vomiting and headache. The case fatality rate for cutaneous
anthrax is estimated to be 20 percent without antibiotic treatment.
Gastrointestinal anthrax usually begins 1–7 days after ingestion of meat
contaminated with anthrax spores. There is acute inflammation of the
intestinal tract with nausea, loss of appetite, vomiting and fever
followed by abdominal pain, vomiting of blood and bloody diarrhea.
There can also be involvement of the pharynx with sore throat,
dysphagia, fever, lesions at the base of the tongue or tonsils and
regional lymphadenopathy. The case fatality rate is unknown but
estimated to be 25 percent to 60 percent.
Inhalation (pulmonary) anthrax has been reported to occur from 1 to 43
days after exposure to aerosolized spores.[Reference 1] Studies in
rhesus monkeys indicate that a small number of inhaled spores may
remain viable for at least 100 days following exposure.[Reference 2]
However, information on how long spores remain viable in the lungs of
humans is unavailable and the incubation period for inhalation anthrax
is unknown. Initial symptoms are non-specific and may include sore
throat, mild fever, myalgia, coughing and chest discomfort lasting up
to a few days. The second stage develops abruptly with findings such as
sudden onset of fever, acute respiratory distress with pulmonary edema
and pleural effusion followed by cyanosis, shock and coma. Meningitis
is common. The fatality rate for inhalation anthrax in the United
States is estimated to be approximately 45 percent to 90 percent. From
1900 to October 2001, there were 18 identified cases of inhalation
anthrax in the United States, the latest of which was reported in 1976,
with an 89 percent (16/18) mortality rate. Most of these exposures
occurred in industrial settings”i.e., textile mills. [Reference 3] From
October 4, 2001 to December 5, 2001, a total of 11 cases of inhalation
anthrax linked to intentional dissemination of Bacillus anthracis
spores were identified in the United States. Five of these cases were
fatal. [Reference 4]
Mechanism of Action:
Virulence components of Bacillus anthracis include an antiphagocytic
polypeptide capsule and three proteins known as protective antigen (PA),
lethal factor (LF) and edema factor (EF). Individually these proteins
are not cytotoxic but the combination of PA with LF or EF results in
the formation of the cytotoxic lethal toxin and edema toxin,
respectively. Although an immune correlate of protection is unknown,
antibodies raised against PA may contribute to protection by
neutralizing the activities of these toxins. [Reference 5] The
contribution of Bacillus anthracis proteins other than PA, that may be
present in BioThrax, to the protection against anthrax has not been
determined.
Clinical Studies:
A controlled field study using an earlier version of a protective
antigen-based anthrax vaccine, developed in the 1950s, that consisted
of an aluminum potassium sulfate-precipitated cell free filtrate from
an aerobic culture, was conducted from 1955 to 1959. This study
included 1,249 workers (379 received anthrax vaccine, 414 received
placebo, 116 received incomplete inoculations [with either vaccine or
placebo] and 340 were in the observational group [no treatment]) in
four mills in the northeastern United States that processed imported
animal hides. [Reference 6] During the trial, 26 cases of anthrax were
reported across the four mills”five inhalation and 21 cutaneous. Prior
to vaccination, the yearly average number of human anthrax cases was
1.2 cases per 100 employees in these mills. Of the five inhalation
cases (four of which were fatal), two received placebo and three were
in the observational group. Of the 21 cutaneous cases, 15 received
placebo, three were in the observational group, and three received
anthrax vaccine. Of those three cases in the vaccine group, one case
occurred just prior to administration of the scheduled third dose, one
case occurred 13 months after an individual received the third of the
scheduled 6 doses (but no subsequent doses), and one case occurred prior
to receiving the scheduled fourth dose of vaccine. In a comparison of
anthrax cases between the placebo and vaccine groups, including only
those who were completely vaccinated, the calculated vaccine efficacy
level against all reported cases of anthrax combined was 92.5 percent
(lower 95 percent CI = 65 percent).
From 1962 to 1974, based on information reported to Centers for Disease
Control and Prevention (CDC), 27 cases of anthrax occurred in mill
workers or those living near mills in the United States. Of those, 24
cases occurred in unvaccinated individuals, one case occurred after the
person had been given one dose of anthrax vaccine and two cases
occurred after individuals had been given two doses of anthrax vaccine.
No documented cases of anthrax were reported for individuals who had
received the recommended six doses of anthrax vaccine. These
individuals received either an earlier version of a protective antigen-
based anthrax vaccine or BioThrax.
In an open-label safety study conducted by the CDC, BioThrax was
administered in 0.5 mL doses according to a 0, 2, 4 week initial dose
schedule followed by additional doses at 6, 12 and 18 months to complete
the 6 dose vaccination series. Annual boosters were administered
thereafter. In this study, 15,907 doses of BioThrax were administered to
approximately 7,000 textile employees, laboratory workers and other
at-risk individuals and the incidence rates of local and systemic
adverse reactions were recorded. (See Adverse Reactions)
A randomized clinical study was conducted by the U.S. Army Medical
Research Institute of Infectious Diseases (USAMRIID) from 1996 to 1999
in 173 volunteers to evaluate changes to the vaccination schedule and
route of vaccine administration. Of those, 28 were enrolled into the
study arm to receive the licensed schedule (initial injections at 0, 2
and 4 weeks followed by additional doses at 6, 12 and 18 months) and
were subsequently monitored for the occurrence of local and systemic
adverse events. (See Adverse Reactions)
Indications and Usage:
BioThrax is indicated for the active immunization against Bacillus
anthracis of individuals between 18 and 65 years of age who come in
contact with animal products such as hides, hair or bones that come from
anthrax endemic areas, and that may be contaminated with Bacillus
anthracis spores. BioThrax is also indicated for individuals at high
risk of exposure to Bacillus anthracis spores such as veterinarians,
laboratory workers and others whose occupation may involve handling
potentially infected animals or other contaminated materials.
Since the risk of anthrax infection in the general population is low,
routine immunization is not recommended.
The safety and efficacy of BioThrax in a post-exposure setting has not
been established.
Contraindications:
The use of BioThrax is contraindicated in subjects with a history of
anaphylactic or anaphylactic-like reaction following a previous dose of
BioThrax, or any of the vaccine components.
Warnings:
Preliminary results of a recent unpublished retrospective study of
infants born to women in the U.S. military service worldwide in 1998
and 1999 suggest that the vaccine may be linked with an increase in the
number of birth defects when given during pregnancy (unpublished data,
Department of Defense). Although these data are unconfirmed, pregnant
women should not be vaccinated against anthrax unless the potential
benefits of vaccination have been determined to outweigh the potential
risk to the fetus.
Animal reproduction studies have not been conducted with BioThrax.
Precautions:
Before administration, the patient‘s medical immunization history should
be reviewed for possible vaccine sensitivities and/or previous
vaccination-related adverse events, in order to determine the existence
of any contraindications to immunization.
Pregnant women should not be vaccinated against anthrax unless the
potential benefits of vaccination clearly outweigh the potential risks
to the fetus.
BioThrax should not be administered to individuals with a history of
Guillain-Barré Syndrome (GBS) unless there is a clear benefit that
outweighs the potential risk of a recurrence.
History of anthrax disease may increase the potential for severe local
adverse reactions.
Patients with impaired immune responsiveness due to congenital or
acquired immunodeficiency, or immunosuppressive therapy may not be
adequately immunized following administration of BioThrax. Vaccination
during chemotherapy, high-dose corticosteroid therapy of greater than
2-week duration, or radiation therapy may result in a suboptimal
response. Deferral of vaccination for 3 months after completion of such
therapy may be considered. [Reference 7]
The administration of BioThrax to persons with concurrent moderate or
severe illness should be postponed until recovery. Vaccination is not
contraindicated in subjects with mild illnesses with or without low-
grade fever. [Reference 7]
This product should be administered with caution to patients with a
possible history of latex sensitivity since the vial stopper contains
dry natural rubber.
Epinephrine solution, 1:1000, should always be available for immediate
use in case an anaphylactic reaction should occur.
Pregnancy:
Pregnancy Category D.
See Warnings.
Nursing Mothers:
It is not known whether exposure of the mother to BioThrax poses a risk
of harm to the breast-feeding child. However, administration of non-live
vaccines (e.g., anthrax vaccine) during breast-feeding is not medically
contraindicated. [Reference 7]
Pediatric Use:
Safety and effectiveness in pediatric patients have not been
established.
Geriatric Use:
No data regarding the safety of BioThrax are available for persons aged
> 65 years.
Adverse Reactions:
Pre-Licensure:
Local Reactions:
In an open-label safety study, 15,907 doses of BioThrax were
administered to approximately 7,000 textile employees, laboratory
workers and other at-risk individuals (see Clinical Studies). Over the
course of the 5-year study, there were 24 reports (0.15 percent of
doses administered) of severe local reactions (defined as edema or
induration measuring greater than 120 mm in diameter or accompanied by
marked limitation of arm motion or marked axillary node tenderness).
There were 150 reports (0.94 percent of doses administered) of moderate
local reactions (edema or induration greater than 30 mm but less than
120 mm in diameter) and 1,373 reports (8.63 percent of doses
administered) of mild local reactions (erythema only or induration
measuring less than 30 mm in diameter).
Systemic reactions:
In the same open label study, four cases of systemic reactions were
reported during a 5-year reporting period (< 0.06 percent of doses
administered). These reactions, which were reported to have been
transient, included fever, chills, nausea and general body aches.
Post-Licensure:
Recently (1996-99), an assessment of safety was conducted as part of a
randomized clinical study conducted by the U.S. Army Medical Research
Institute of Infectious Diseases (USAMRIID) (see Clinical Studies). A
total of 28 volunteers were enrolled to receive subcutaneous doses of
BioThrax according to the licensed schedule. Each volunteer was
observed for approximately 30 minutes after administration of AVA and
scheduled for follow-up evaluations at 1-3 days, 1 week and 1 month
after vaccination. Four volunteers reported seven acute adverse events
within 30 minutes after the subcutaneous administration of BioThrax.
These included erythema (3), headache (2), fever (1) and elevated
temperature (1). Of these events, a single patient reported the
simultaneous occurrence of headache, fever and elevated temperature
(100°F).
Local Reactions:
The most common local reactions reported after the first dose (n = 28)
in this study were tenderness (71 percent), erythema (43 percent),
subcutaneous nodule (36 percent), induration (21 percent), warmth
(11 percent) and local pruritus (7 percent). The most frequently
reported local reactions after the second dose (n = 28) were tenderness
(61 percent), subcutaneous nodule (39 percent), erythema (32 percent),
induration (18 percent), local pruritus (14 percent), warmth (11
percent) and arm motion limitation (7 percent). After the third dose (n
= 26), the most frequently reported local reactions were tenderness (58
percent), warmth (19 percent), local pruritis (19 percent), erythema
(12 percent), arm motion limitation (12 percent), induration (8
percent), edema (8 percent) and subcutaneous nodule (4 percent). Local
reactions were found to occur more often in women. No abscess or
necrosis was observed at the injection site.
Systemic Reactions:
All systemic adverse events reported in this study were transient in
nature. The systemic reactions most frequently reported after the first
dose (n = 28) were headache (7 percent), respiratory difficulty (4
percent) and fever (4 percent). After the second dose (n = 28), the
most frequently reported systemic reactions were malaise (11 percent),
myalgia (7 percent), fever (7 percent), headache (4 percent), anorexia
(4 percent) and nausea or vomiting (4 percent). After the third dose (n
= 26), the most frequently reported systemic reactions were headache (4
percent), malaise (4 percent), myalgia (4 percent) and fever (4
percent). There was one report of delayed hypersensitivity reaction
beginning with lesions 3 days after the first dose. The subject was
reported to have diffuse hives by day 17, 3 days after the second dose,
and had swollen hands, face and feet by day 18 and discomfort
swallowing. The subject did not receive any subsequent scheduled doses.
Post-Licensure Adverse Event Surveillance:
Data regarding potential adverse events following anthrax vaccination
are available from the Vaccine Adverse Event Reporting System (VAERS).
[Reference 8] The report of an adverse event to VAERS is not proof that
a vaccine caused the event. Because of the limitations of spontaneous
reporting systems, determining causality for specific types of adverse
events, with the exception of injection-site reactions, is often not
possible using VAERS data alone. The following four paragraphs describe
spontaneous reports of adverse events, without regard to causality.
From 1990 to October 2001, over 2 million doses of BioThrax have been
administered in the United States. Through October 2001, VAERS received
approximately 1,850 spontaneous reports of adverse events. The most
frequently reported adverse events were erythema, headache, arthralgia,
fatigue, fever, peripheral swelling, pruritus, nausea, injection site
edema, pain/tenderness and dizziness.
Approximately 6 percent of the reported events were listed as serious.
Serious adverse events include those that result in death,
hospitalization, permanent disability or are life-threatening. The
serious adverse events most frequently reported were in the following
body system categories: general disorders and administration site
conditions, nervous system disorders, skin and subcutaneous tissue
disorders, and musculoskeletal, connective tissue and bone disorders.
Anaphylaxis and/or other generalized hypersensitivity reactions, as
well as serious local reactions, were reported to occur occasionally
following administration of BioThrax. None of these hypersensitivity
reactions have been fatal.
Other infrequently reported serious adverse events that have occurred in
persons who have received BioThrax have included: cellulitis, cysts,
pemphigus vulgaris, endocarditis, sepsis, angioedema and other
hypersensitivity reactions, asthma, aplastic anemia, neutropenia,
idiopathic thrombocytopenia purpura, lymphoma, leukemia, collagen
vascular disease, systemic lupus erythematosus, multiple sclerosis,
polyarteritis nodosa, inflammatory arthritis, transverse myelitis,
Guillain-Barré Syndrome, immune deficiency, seizure, mental status
changes, psychiatric disorders, tremors, cerebrovascular accident
(CVA), facial palsy, hearing and visual disorders, aseptic meningitis,
encephalitis, myocarditis, cardiomyopathy, atrial fibrillation, syncope,
glomerulonephritis, renal failure, spontaneous abortion and liver
abscess. Infrequent reports were also received of multisystem disorders
defined as chronic symptoms involving at least two of the following
three categories: fatigue, mood-cognition, musculoskeletal system.
Reports of fatalities included sudden cardiac arrest (2), myocardial
infarction with polyarteritis nodosa (1), aplastic anemia (1), suicide
(1) and central nervous system (CNS) lymphoma (1).
Post-Licensure Survey Studies:
In addition to the VAERS data, adverse events following anthrax
vaccination have been assessed in survey studies conducted by the
Department of Defense in the context of their anthrax vaccination
program. These survey studies are subject to several methodological
limitations”e.g., sample size, the limited ability to detect adverse
events, observational bias, loss to follow-up, exemption of vaccine
recipients with previous adverse events and the absence of unvaccinated
control groups. Overall, the most reported events were localized, minor
and self-limited and included muscle or joint aches, headache and
fatigue. Across these studies, systemic reactions were reported in 5 to
35 percent of vaccine recipients and included reports of malaise,
chills, rashes, headaches and low-grade fever. Women reported these
symptoms more often than men.
Reporting Adverse Events:
Adverse events following immunization with BioThrax should be reported
to the Medical Affairs Division of BioPort Corporation (517) 327-1675
during regular working hours and (517) 327-7200 during off hours.
Adverse events may also be reported to the U. S. Department of Health
and Human Services (DHHS) Vaccine Adverse Event Reporting System.
Report forms and reporting requirement information can be obtained from
VAERS through a toll free number 1-800-822-7967.
Dosage and Administration:
Dosage:
Immunization consists of three subcutaneous injections, 0.5 mL each,
given 2 weeks apart followed by three additional subcutaneous
injections, 0.5 mL each, given at 6, 12, and 18 months. Subsequent
booster injections of 0.5 mL of BioThrax at 1-year intervals are
recommended.
Administration:
Use a separate 5/8-inch, 25- to 27-gauge sterile needle and syringe for
each patient to avoid transmission of viral hepatitis and other
infectious agents. Use a different site for each sequential injection
of this vaccine and do not mix with any other product in the syringe.
1. Shake the bottle thoroughly to ensure that the suspension is
homogeneous during withdrawal and visually inspect the product for
particulate matter and discoloration. If the product appears discolored
or has visible particulate matter, Discard The Vial.
2. Wipe the rubber stopper with an alcohol swab and allow to dry before
inserting the needle.
3. Clean the area to be injected with an alcohol swab or other suitable
antiseptic.
4. Holding the needle at a 45° angle to the skin, inject the vaccine
subcutaneously.
5. Do Not inject the product intravenously. Follow the usual
precautions to ensure that you have not entered a vein before injecting
the vaccine.
6. After injecting, withdraw the needle and briefly and gently massage
the injection site to promote dispersal of the vaccine.
How Supplied/Storage:
Anthrax Vaccine Adsorbed (BioThrax TM ) is supplied in 5 mL multidose
vials.
This Product Is To Be Stored AT 2.2°C TO –15°C (36° TO 4°F). Do not
freeze. Do not use after the expiration date given on the package.
Nonclinical Toxicology:
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Animal studies have not been performed to ascertain whether BioThrax
has carcinogenic action, or any effect on fertility.
References:
1. Meselson, M., and others. 1994. The Sverdlosk Anthrax Outbreak of
1979. Science 266:1201–8.
2. Henderson, D.W., S. Peacock, and F. C. Belton. 1956. Observations on
the Prophylaxis of Experimental Pulmonary Anthrax in the Monkey. J.
Hygiene, 54:28–36.
3. Brachman, P. S. 1980. Inhalation Anthrax. Ann. NY Acad. Science,
353:83–93.
4. Update: Investigation of Bioterrorism-Related Anthrax”Connecticut,
2001. MMWR 2001; 50:1077-9.
5. Brachman, P. S., and A. M. Friedlander. 1999. Anthrax. In Vaccines,
3rd ed., Plotkin and Orenstein (eds.), pp. 629–37.
6. Brachman, P. S., and others. 1962. Field Evaluation of a Human
Anthrax Vaccine. Amer. J. Public Health, 52:632–45.
7. Centers for Disease Control and Prevention. General Recommendations
on Immunization Recommendations of the Advisory Committee on
Immunization Practices (ACIP). MMWR 1994; 43 (No. RR-1).
8. Chen, R. T., and others. 1994. The Vaccine Adverse Event Reporting
System (VAERS). Vaccine 12(6): 542–50.
Revision: January 31, 2002.
Rx Only”Federal (U.S.A.) law prohibits dispensing without a
prescription.
Manufactured by:
Bioport Corporation:
Lansing, Michigan 48906:
U.S. License No. 1260:
50483-04:
[End of section]
Appendix V: Comments from the Department of the Army:
Department Of The Army:
Office Of The Assistant Secretary:
Manpower And Reserve Affairs:
111 Army Pentagon:
Washington, DC 20310-0111:
July 15, 2002:
Reply To Attention Of:
Ms. Nancy Kingsbury:
Managing Director:
Applied Research and Methods:
U.S. General Accounting Office:
Washington, D.C. 20548:
Dear Ms. Kingsbury:
This is the Department of Defense (DoD) response to the General
Accounting Office (GAO) draft report, GAO-02-445, dated 11 June 2002,
"Anthrax Vaccine: GAO's Survey of Guard and Reserve Pilots and Aircrew"
(GAO Code 460501).
The Department of Defense is committed to giving the best possible care
to servicemembers who develop a problem after receiving this or any
vaccine. The Department agrees with the GAO that those who have
experienced adverse events to the anthrax vaccine and those who may
experience them in the future should have appropriate and complete
treatment and follow-up.
The Department recognizes the importance of our need to continually
improve our education efforts among our servicemembers and their
families to increase understanding of the anthrax threat, anthrax
vaccine and the Anthrax Vaccine Immunization Program.
The Department nonconcurs with the report's primary recommendation.
After performing a comprehensive analysis and review of data, the
National Academy of Sciences reported in March 2002, "The committee
observes that no data that indicate the need for the continuation of
special monitoring programs for AVA have emerged, but it recognizes the
real concerns for service members ordered to take the vaccines."
Data from the Defense Manpower Data Center (DMDC) regarding actual
pilot separations do not support the GAO report. The DMDC data shows
pilot separations before beginning the AVIP in 1998 are similar to the
rates during the time of the survey. The GAO report does not address
these normal or expected rates of turnover known to occur among
personnel in the Air National Guard and the Air Force Reserve.
Signed by:
Reginald J. Brown:
Assistant Secretary of the Army:
(Manpower and Reserve Affairs):
GAO Anthrax Vaccine:
GAO's Survey Of Guard/reserve Pilots And Aircrew Members:
GAO-02-445:
Department Of Defense Comments On The GAO Recommendation:
Recommendation 1: The GAO recommended that the Secretary of Defense
direct the establishment of an active surveillance program (unlike the
passive VAERS) to identify and monitor adverse events associated with
each anthrax vaccine immunization. (p.42/GAO-02-445)
DOD Response: Nonconcur. After performing comprehensive analysis and
review of data, the National Academy of Sciences reported in March
2002, "The committee observes that no data that indicate the need for
the continuation of special monitoring programs for AVA have emerged,
but it recognizes the real concerns for service members ordered to take
the vaccines."
Further, DoD has assembled 18 safety studies using both active and
passive surveillance. Active data collection has already occurred at
Tripler Army Medical Center, Camp Casey in Korea, and elsewhere. A
comprehensive and automatic review of every inpatient and outpatient
medical visit, both anthrax vaccinated and unvaccinated servicemembers,
around the globe is included in one of the 18 studies using the Defense
Medical Surveillance System. These and other studies were reported in
detail to the National Academy of Sciences. The Centers for Disease
Control and Prevention (CDC) is currently coordinating a 5-site, active
surveillance human safety, reactogenicity and immunogenicity trial to
address changes in route of administration and dose reduction. The
current FDA-licensed 6-dose vaccination series will be administered to
one of the subgroups.
DoD takes its responsibility seriously to provide for an open
assessment of the safety of anthrax vaccine. Safety studies in addition
to the first 18 are in progress and will be published in the peer-
reviewed literature when completed. To enhance the care delivered to
service members in the interval after any vaccination, DoD and the
Centers for Disease Control and Prevention (CDC) collaborated to create
a center for excellence in vaccine care at the Walter Reed Army Medical
Center. This center of excellence is known as the Vaccine Healthcare
Center, the first of what may become a triservice network of similar
centers. It is the combination of additional research and enhanced care
that will provide the best possible prevention programs and care
delivery.
[End of section]
Related GAO Products:
Anthrax Vaccine: Changes to the Manufacturing Process. GAO-02-181T.
Washington, D.C.: Oct. 23, 2001.
Anthrax Vaccine: Preliminary Results of GAO‘s Survey of Guard/Reserve
Pilots and Aircrew Members. GAO-01-92T. Washington, D.C.: Oct. 11,
2000.
Medical Readiness: DOD Continues to Face Challenges in Implementing
Its Anthrax Vaccine Immunization Program. GAO/T-NSIAD-00-157.
Washington, D.C.: Apr. 13, 2000.
Medical Readiness: DOD Faces Challenges in Implementing Its Anthrax
Vaccine Immunization Program. GAO/NSIAD-00-36. Washington, D.C.:
Oct. 22, 1999.
Anthrax Vaccine: Safety and Efficacy Issues. GAO/T-NSIAD-00-48.
Washington, D.C.: Oct. 12, 1999.
Medical Readiness: Issues Concerning the Anthrax Vaccine.
GAO/T-NSIAD-99-226. Washington, D.C.: July 21, 1999.
Contract Management: Observations on DOD‘s Financial Relationship
with the Anthrax Vaccine Manufacturer. GAO/T-NSIAD-99-214.
Washington, D.C.: June 30, 1999.
Medical Readiness: Safety and Efficacy of the Anthrax Vaccine.
GAO/T-NSIAD-99-148. Washington, D.C.: Apr. 29, 1999.
Gulf War Illnesses: Questions about the Presence of Squalene Antibodies
in Veterans Can Be Resolved. GAO/NSIAD-99-5. Washington, D.C.: Mar.
29, 1999.
[End of section]
Footnotes:
[1] U.S. General Accounting Office, Medical Readiness: Safety and
Efficacy of the Anthrax Vaccine, GAO/T-NSIAD-99-148 (Washington, D.C.:
Apr. 29, 1999).
[2] A local reaction affects only the general area around the point of
injection and may be experienced as redness, itching, or the like. A
systemic reaction is more serious because it affects bodily systems
after absorption or ingestion and may be experienced as chills, fever,
nausea, dizziness, and so on.
[3] The first DOD study of anthrax vaccine reactions was conducted in
Korea. A physician collected data for this study in 1997. The second
study, in Hawaii, was called the Tripler Army Medical Center Anthrax
Survey (Tripler survey). Both reported reaction rates considerably
higher than the vaccine product insert rates.
[4] See appendix IV for the revised product insert.
[5] VAERS is a passive surveillance system to alert FDA and the Centers
for Disease Control and Prevention (CDC) of adverse events that may be
associated with licensed vaccines. Health care providers, patients, or
families, who are encouraged to report any adverse events after a
person receives a vaccine, report information voluntarily to VAERS.
[6] Merck Sharp & Dhome is a subsidiary of Merck & Co., Inc.
[7] Anthrax infection has most commonly occurred in settings like wool
mills, where workers may be exposed to infected animal products.
[8] Before FDA was established as the licensing authority for vaccines,
NIH performed that function.
[9] FDA has revised the adverse reactions section in the product insert
to reflect a higher incidence of local and systemic reactions.
[10] GAO/T-NSIAD-99-148.
[11] U.S. General Accounting Office, Medical Readiness: DOD Faces
Challenges in Implementing Its Anthrax Vaccine Immunization Program,
GAO/NSIAD-00-36 (Washington, D.C.: Oct. 22, 1999).
[12] While the accuracy of memory may degrade over time, in this case
this effect was minimized because of the highly publicized nature of
the program, and our survey was administered while respondents were
still receiving the shots.
[13] S. Rosenthal and R. Chan, ’The Reporting Sensitivities of Two
Passive Surveillance Systems for Vaccine Adverse Events,“ American
Journal of Public Health 85, no. 12 (1995): 1706-09; R. T. Chan and
others, ’The Vaccine Adverse Event Reporting System (VAERS),“ Vaccine
12 (1994): 542–50; R. T. Chan, ’Special Methodological Issues in
Pharmacoepidemiology Studies of Vaccine Safety,“ in
Pharmacoepidemiology, ed. B. L. Strom (New York: John Wiley & Sons,
1994).
[14] Institute of Medicine, The Anthrax Vaccine: Is It Safe? Does It
Work? (Washington, D.C.: 2002).
[15] The Millennium Cohort Study is a survey sponsored by DOD. It will
monitor a total of 140,000 U.S. military personnel during and after
their military service for up to 21 years to evaluate the health risks
of military deployment, military occupations, and general military
service.
[16] M. J. World, ’Anthrax Immunization in the Older Warrior,“ North
Atlantic Treaty Organization: RTO Meeting Proceedings 33, Operational
Issues of Aging Crewmembers, Oct. 11–14, 1999.
[17] L. Steele, ’Prevalence and Patterns of Gulf War Illness in Kansas
Veterans: Association of Symptoms with Characteristics of Person,
Place, and Time of Military Service,“ American Journal of Epidemiology
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[End of section]
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