REPORT 14 OF THE BOARD OF TRUSTEES (A-04)
Vaccine Safety
(Reference Committee E)
EXECUTIVE SUMMARY
This report responds to referred Resolution 924 (I-02), which asked that our American Medical
Association (AMA) advocate for the formation of a National Immunization Safety Board,
analogous to the National Transportation Safety Board; and seek legislation prohibiting the release
and use of pre-publication drafts of scientific studies in civil lawsuits alleging damages from
immunizations.
This report provides information on the vaccine licensure process; the roles of various federal
agencies, advisory bodies, and medical specialty societies in vaccine safety; national vaccine
surveillance mechanisms; the current approach to evaluating the relationship between vaccine
administration and possible adverse events; and the operation of the vaccine injury compensation
program. Additionally the relative merits of a national vaccine safety board are briefly explored.
This report also specifically addresses the current status of lawsuits related to the historical use of
vaccines containing thimerosal, a mercury-based preservative, as well as the use of pre-publication
drafts of scientific studies in civil lawsuits alleging damages from immunizations. The report also
provides recommendations for AMA actions.
REPORT OF THE BOARD OF TRUSTEES
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Subject:
Vaccine Safety
(Resolution 924, I-02)
Presented by:
William G. Plested, III, MD, Chair
Referred to:
Reference Committee E
(Stuart Gitlow, MD, Chair)
INTRODUCTION
At the 2002 Interim Meeting, the House of Delegates referred Resolution 924 to the Board of
Trustees. This resolution, introduced by the New York Delegation, asked:
That our American Medical Association (AMA) advocate for the formation of a National
Immunization Safety Board, analogous to the National Transportation Safety Board; and
That our AMA seek legislation prohibiting the release and use of pre-publication drafts of
scientific studies in civil lawsuits alleging damages from immunizations.
The public health value of immunizations cannot be overstated. Vaccines serve as a protection
from at least 14 diseases that once were common in the United States. Immunizations rank among
the 10 most significant public health achievements in history. However, the issue of vaccine safety
is complex and multifaceted, partly as a result of the success of the immunization programs in the
United States. With the near complete eradication of many of the vaccine-preventable diseases
(VPD) in the United States (eg, polio), attention has now been turned to the safety of the vaccines
that provide such remarkable protection from these fatal diseases. Indeed, there has been a recent
emergence of public advocacy groups that are seeking to eliminate immunization. These groups
argue that parents should be given the choice of immunizing their children, but it has been
suggested that they are actually seeking to eliminate the administration of immunizations in the
United States. In this context, it is important to emphasize that despite the effectiveness of vaccines
against potentially fatal illnesses, children and adults still die each year from these preventable
diseases, and that in the absence of the protection provided by the vaccines, these VPD would be
responsible for significant morbidity and mortality. Furthermore, public attention to vaccine safety
has resulted in stronger scrutiny on the issue, from the process of vaccine production through postlicensure surveillance. Indeed, the fact that vaccines are administered to healthy adults and
children demands that this high level of scrutiny, based on science and risk analysis, continues.
The two resolves in Resolution 924 (I-02) refer to two separate issues in the arena of vaccine
safety. The call for a national vaccine safety board has gathered some support in public circles, but
remains controversial because of concern that decisions on medical and scientific issues may end
up being made by individuals who do not necessarily have the requisite expertise. Additionally,
many believe that the role of vaccine safety assessment should remain under the supervision of the
Centers for Disease Control and Prevention (CDC) and that adequate working checks and balances
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already exist. The issue of pre-publication release of preliminary data is one that troubles many
physicians and scientists and is the direct result of current lawsuits surrounding the former use of
thimerosal as a preservative in pediatric vaccines. This report provides background information on
how vaccine safety is achieved and assessed in the United States, and with respect to the issue of
pre-publication data, on the current lawsuit involving thimerosal-containing vaccines. The report
also provides recommendations for AMA actions.
VACCINE SAFETY
The Vaccine Licensure Process
The process of vaccine licensure through the Food and Drug Administration (FDA) is extremely
lengthy and rigorous, generally taking between 5 to 10 years, and very costly to the manufacturer,
with costs estimated to be in the hundreds of millions of dollars. As such, this process remains the
first gateway to ensuring that the vaccines approved for use in the United States are safe. Even after
licensure, federal oversight of the vaccine continues as long as it remains licensed in the United
States.
The Center for Biologics Evaluation and Research (CBER) of the FDA is the U.S. agency
responsible for the regulation and licensure of vaccines. Specifically, CBER reviews the
investigational new drug (IND) applications for licensure of vaccines, examines the establishments
that produce the vaccines, enforces compliance with current FDA good manufacturing practices
(cGMP), and conducts post-marketing surveillance to ensure safety.
In addition to CBER, three other federal agencies play principal roles in assisting CBER with its
responsibility of ensuring vaccine safety:
1. The CDC is responsible for disease surveillance and for the support of immunization
programs in the United States. The Advisory Committee on Immunization Practices
(ACIP) is the federal committee responsible for making recommendations to the CDC for
the routine administration of vaccines to the U.S. public;
2. The National Institutes of Health (NIH) conducts and funds biomedical research on
vaccines in the United States; and
3. The National Vaccine Program Office (NVPO) coordinates the vaccine-related efforts of
the U.S. Public Health Service and of the Interagency Vaccine Group (IAVG). The IAVG
comprises the Agency for International Development, the CDC, the Department of
Defense, the FDA, the Centers for Medicare and Medicaid Services (CMS), the NIH, and
the Office of the General Counsel of the Department of Health and Human Services
(DHHS). The National Vaccine Advisory Committee (NVAC) is responsible for studying
and providing recommendations to the NVPO on vaccine policy, and program and delivery
issues for the entire country. These issues include vaccine shortages and vaccine safety.
The IND Process
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The vaccine sponsor files an IND application with CBER. Strict review criteria must be
met before the FDA approves clinical studies for the candidate vaccine, including
scientific rationale for the vaccine, description of the manufacturing process (which must
meet all cGMP), all preclinical study data, and a plan for Phase I testing.
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CBER has 30 days to complete the initial review of the complete IND application. A
decision is then made on whether to approve the application, allowing the candidate
vaccine to enter clinical trials, or to request additional information from the sponsor to
support the application.
Following approval of the IND application, CBER review continues until the vaccine is
licensed. At any point in the licensure process, a vaccine can be placed on “clinical hold.”
For example, should CBER decide that an alteration to the manufacturing process is
necessary to enhance vaccine safety, the process can be placed on a clinical hold.
Clinical Trials
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The Institutional Review Board (IRB) at the institution where the clinical trials are to be
performed must approve the study before the candidate vaccine can enter clinical trials.
This is in addition to the CBER approval process.
The IRB also oversees the development and use of the informed consent forms that must
be completed and signed by all study participants in the clinical trials. IRB approval must
be given prior to the initiation of each phase.
Following approval from both the CBER and the study’s IRB, the vaccine sponsor takes
the candidate vaccine into Phase I clinical trials, which measure the safety,
immunogenicity, and proof of principle for the vaccine.
Phase II studies continue safety and immunogenicity studies and also examine the
optimum dose and scheduling for the vaccine.
Phase III studies are the pivotal licensure studies. They continue safety and
immunogenicity measurements and also examine the all-important efficacy of the vaccine.
Phase IV studies are post-market studies where the safety and effectiveness of the vaccine
are measured and surveillance of the vaccine is continued.
Vaccine Licensure
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All clinical studies must be completed, or be close to completion, before the vaccine
sponsor can begin the final vaccine licensure application. Additionally, all production
protocols must be developed and all manufacturing processes must be standardized. At
this point, a Biologics License Application (BLA) can be submitted to the FDA for a
license to manufacture and distribute the vaccine to the public.
The BLA must include: (1) a complete description of all manufacturing and testing
methods for the vaccine; (2) the results of all tests performed on a specified number of
production lots to ensure consistent and reliable manufacturing processes; (3) a summary
of the results of all clinical studies; and (4) the proposed labeling for the use of the
vaccine.
Scientific review of the BLA is conducted by the federal Vaccines and Related Biological
Products Advisory Committee (VRBPAC), which is administered by CBER. This
independent committee examines all the data on safety, purity, and potency of the vaccine
and provides the final recommendation to CBER on whether the vaccine should be
approved.
Prior to final approval and vaccine production, CBER conducts a final inspection of the
production facilities. The results from this inspection, together with the VRBPAC
recommendations, are then analyzed by CBER for its final decision.
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If CBER determines that the vaccine meets all the requirements for approval, it is licensed
for administration to the public.
Federal Advisory Committees
Following the approval of a new vaccine, federal advisory committees facilitate its introduction to
the public and the entry of the vaccine into existing public health programs. In making their
recommendations, these committees not only evaluate safety and immunogenicity data for the
vaccine, but also evaluate the societal perspective for the vaccine, the systems in place for vaccine
delivery, the cost-effectiveness and cost-benefit analyses for the vaccines, expert opinion available
from experience with other similar vaccines, and the impact of the new vaccine on immunization
schedules.
The Advisory Committee on Immunization Practices (ACIP): The ACIP is comprised of 15
independent voting experts selected by the DHHS for their expertise in vaccination, infectious
diseases, and public health. In addition, representatives from professional organizations (such as
the American Academy of Pediatrics, the National Coalition for Adult Immunization), as well as
other federal agencies and organizations (including manufacturers), serve as nonvoting liaison
members. Recommendations for use of the vaccine involve a thorough examination of the
published and unpublished data on the safety, efficacy, effectiveness, and cost-benefits analyses of
the vaccine. These recommendations are then provided to the CDC and subsequently to the DHHS
Secretary, who either accepts or rejects them. Acceptance of the recommendations makes them
national immunization policy.
The National Vaccine Advisory Committee (NVAC): The NVAC makes recommendations to the
Director of the NVPO on vaccine policy, programs, and delivery for the United States. The
Director then reports all proceedings to the Surgeon General of the United States. The NVPO is
tasked with achieving optimum prevention of infectious diseases via immunization, and with
achieving optimum prevention of adverse events associated with vaccine use. Thus, issues
pertaining to vaccine safety fall under the purview of the NVAC and the NVPO.
The Advisory Commission on Childhood Vaccines (ACCV): This Commission gives advice to the
DHHS Secretary on issues pertaining to the National Vaccine Injury Compensation Program
(VICP). The VICP was established by Congress under the 1986 National Childhood Vaccine
Injury Act to provide compensation to children who have been injured from a vaccine administered
as part of the routine childhood immunization schedule. This no-fault compensation program went
into effect in 1988 and is funded by excise taxes imposed on vaccine manufacturers.
Other Tools to Ensure Vaccine Safety
The American Academy of Pediatrics (AAP): The AAP’s Committee on Infectious Diseases
(COID) monitors developments in the prevention, diagnosis, and treatment of infectious diseases.
The COID regularly develops and reviews policy recommendations for its members on the safety
and use of vaccines.
The American Academy of Family Physicians (AAFP): The AAFP also provides safety and use
information to its membership.
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Vaccine Information Statements (VISs): The VISs are informational sheets that are produced by
the CDC. A VIS provides general knowledge about the particular vaccine and the disease(s) that
the vaccine prevents. It also explains the risks and benefits of the vaccine and helps vaccine
recipients understand what adverse events may occur and what to be alert for. Federal law
mandates that these sheets be given to vaccine recipients or their legal representatives prior to each
dose of vaccine.
Vaccine Surveillance Mechanisms
Vaccine safety and efficacy monitoring systems continue to operate after a vaccine has been
licensed and made available to the general public. These national detection and evaluation systems
serve to ensure the continued safety of licensed vaccines. Licensure of the rotavirus vaccine
provides an example of how these systems succeed in maintaining vaccine safety. Surveillance
data following licensure of the rotavirus vaccine suggested the possible association between
intussusception and administration of this vaccine. Further observation indicated an increased risk
of intussusception following rotavirus vaccine administration, and the vaccine was withdrawn by
the manufacturer.
At least three national vaccine surveillance mechanisms are of particular note:
The Vaccine Identification Standards Initiative (VISI): This initiative is currently being
incorporated into the manufacturing process of vaccines so that in the future, each administered
vaccine will have a bar-coded sticker that can be placed on the immunization record of the
immunized patient. This will then allow the direct linkage of adverse events reported by the patient
with specific products and lots, while increasing the accuracy of the information contained in the
individual immunization records. Typically, adverse events are defined as undesirable experiences
occurring after immunization that may or may not be related to the vaccine.
Immunization Registries: These confidential computerized systems contain information about an
individual’s immunization record and his or her compliance with the vaccination schedules. Thus,
registries provide important information that can help assess who received which vaccine and at
what location, enabling adverse events to be tracked.
The Vaccine Adverse Event Reporting System (VAERS): The most significant national system
currently in place for monitoring vaccine safety is the VAERS. VAERS is an independent reporting
system established by Congress in 1986 to ensure scientific objectivity in evaluating vaccine
safety. Adverse events can range from simple pain at the administration site to more severe
reactions such as seizures. All adverse events can be reported to VAERS, analyzed, and made
known to the public. VAERS accepts reports of adverse events from physicians, vaccine
recipients, and parents. The VISs issued before the provision of vaccine detail how to report events
to VAERS. It is important to note that an adverse event by definition may or may not be causally
associated with the vaccine in question. The evaluation of causality lies with other systems
described later.
Not only does VAERS serve as a registry of potential adverse events following immunizations, it
also helps the FDA and the CDC generate hypotheses for the potential associations between
adverse events and vaccine administration. Additionally, VAERS serves to identify previously
unidentified vaccine-related reactions, highlight unusual increases in previously reported events,
and identify pre-existing conditions that may predispose a vaccine adverse event.
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VAERS direct report forms are mailed to approximately 200,000 primary care physicians,
emergency room directors, and state health departments every year. Copies of the form are also
found in the Physicians’ Desk Reference and the AAP’s Red Book, and can be accessed through the
Internet (https://secure.vaers.org/VaersDataEntryintro.htm). Reporters are urged to submit their
reports as soon as possible after the event, but manufacturers are required to submit reports to
VAERS within 15 days of receiving a serious adverse event report.
However, it must be acknowledged that VAERS has limitations. As a passive reporting system,
the database is subject to underreporting, biased reporting, poor report quality, and differences in
reporting rates due to external influences such as the news media. Nevertheless, the database
retains its usefulness in that it generates potential associations between reported adverse events and
vaccines that can then be tested by more robust scientific means.
Evaluating Causality from Surveillance
The Vaccine Safety Datalink (VSD) Project: This collaboration between the CDC and several
health maintenance organizations (HMOs) is directed at testing the hypotheses that are raised by
the adverse event reports. The VSD database combines information on patient vaccination records,
health outcomes, and patient characteristics (eg, birth certificate and census information) to test
hypotheses associating a vaccine with an adverse event. More than 7.5 million people are involved
in the project through eight participating HMOs. The VSD acts as a large-scale post-surveillance
database and captures information that allows for calculation of incidence rates, attributable risks,
and background rates of illness in the absence of vaccination. However, despite its size, the VSD
database is still not large enough to test certain hypotheses regarding very rare events.
Many VSD studies have been published in the peer-reviewed literature on topics including the
necessity for the second dose of measles/mumps/rubella (MMR) vaccine and the alleged
association between vaccines and autism and diabetes.
Clinical Immunization Safety Assessment (CISA) Centers: This network of academic centers with
clinical expertise in vaccine adverse events was initiated in 2001. In collaboration with the CDC,
CISA centers seek to improve scientific understanding of vaccine safety at the individual patient
level. The network serves as the intermediate step between passive reporting like the VAERS and
more rigorous vaccine safety epidemiological investigations.
Once fully established, CISA centers will evaluate VAERS reports, or cases referred to them by
health care professionals. Cases with merit will then undergo a more enhanced follow-up and
targeted clinical evaluation to better understand the mechanisms and risk factors for the particular
adverse event.
The Institute of Medicine (IOM): In 1986, as part of the National Childhood Vaccine Injury Act, a
committee was established within the IOM to specifically review the scientific literature on
vaccine-related adverse events. In 1991 and 1993, this IOM committee released reports stating that
inadequate data existed to accept or reject 66% of the adverse events that were evaluated.
Additionally, many gaps in knowledge and research were identified by the IOM as needing to be
filled before more conclusive assessments could be made pertaining to vaccine safety.
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More recently, the CDC and the NIH commissioned the IOM to set up an Immunization Safety
Review Committee, a panel of independent experts tasked with reviewing hypotheses pertaining to
vaccine safety. This Committee is meeting three times a year over a three-year study period (20012004) and each meeting is dedicated to a single adverse event hypothesis. For each vaccine-safety
question, the Committee reads and discusses the relevant epidemiologic evidence for or against a
causal relationship, as well as any case reports and clinical evidence. The Committee also hears
presentations from the authors of key published papers, as well as ongoing, unpublished research.
Based on these meetings, the Committee has issued many reports on the subject of vaccine safety.
These include the well reported studies titled “MMR Vaccine and Autism,” “ThimerosalContaining Vaccines and Neurodevelopmental Disorders,” “Multiple Immunization and Immune
Dysfunction,” “Hepatitis B Vaccine and Demyelinating Neurological Disorders,” “Simian Virus40 Contamination of Polio Vaccine and Cancer,” “Vaccinations and Sudden Unexpected Death in
Infancy,” and “Influenza Vaccine and Neurological Complications.”
The Vaccine Injury Compensation Program (VICP)
No discussion on vaccine safety would be complete without a brief description of the VICP. To
receive compensation from the VICP, injured persons file claims with the DHHS Secretary within
three years of injury or two years of death. Persons (or their families) must pursue claims through
the VICP and these claims must be resolved via the VICP before they can pursue any claims
against the vaccine manufacturers or anyone involved with vaccine administration. Claimants are
then given 60 days to accept or reject the judgment or award offered via the VICP. Once this
decision is made, it is irrevocable. Those who accept any compensation under VICP cannot pursue
any further compensation. Those rejecting the judgment can then bring civil action for damages
against the manufacturer and/or vaccine administrator. However, the findings of the VICP will not
be admissible in the civil action.
VICP is successful partially because the program actually qualifies more vaccine-injured children
for compensation than would the tort system. The tort system requires that plaintiffs show that the
defendant(s) did something wrong AND the wrong caused the plaintiff’s injury. VICP only
requires that claimants show that they were injured by the vaccine. Additionally, a table of
acknowledged injury criteria acceptable for compensation has been established for each vaccine,
simplifying the claim procedure.
Claimants are entitled to damages limited to the actual costs of care and treatment and
rehabilitation not covered by public or private insurance. Monetary caps limit damages for pain
and suffering and for wrongful death. Punitive and derivative claims (eg, by family members for
loss of companionship) are not permitted under VICP. The VICP compensation fund is sustained
via an excise tax on vaccines covered by the program.
The Salmon-Moulton-Halsey National Vaccine Safety Board Model
In a paper that has not yet been published, Salmon et al propose a model for a National Vaccine
Safety Board to separate the “risk management” issues of immunization programs from the “risk
assessment” issues. The authors suggest that because one of the primary responsibilities of the
National Immunization Program (NIP) of the CDC is to control infectious diseases through
vaccination, the NIP may be compromised in its post-licensure surveillance for serious adverse
events. Thus, Salmon et al recommend that post-licensure vaccine safety studies be conducted by
another body other than the NIP, and perhaps even other than the CDC. This would effectively
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separate the risk management aspect of immunization programs (the administration and advocacy
for vaccinations) from the risk assessment aspect (the surveillance for vaccine adverse events).
They believe that the current network for ensuring vaccine safety and public confidence in vaccines
should be strengthened before a loss of credibility results due to perceived competing priorities or
conflicting interests.
Salmon et al point out that the CDC has had recent successes in epidemiological investigations of
many important vaccine safety issues and that it has successfully maintained VAERS with the
FDA. However, they argue that to guarantee that the handling of future vaccine safety issues will
be viewed favorably by the public, an independent body to investigate vaccine safety issues needs
to be established. Salmon et al therefore propose the establishment of a National Vaccine Safety
Board whose “mission to monitor vaccine safety could be achieved by: (1) funding and conducting
vaccine safety investigations; (2) bringing together experts from government, industry, and
academia to review all available scientific information, and determine causal associations between
vaccines and adverse events; (3) make recommendations to government and industry to improve
vaccine safety; and (4) disseminate safety findings to the public.” Salmon et al further propose that
this vaccine safety board can be modeled after the National Transportation Safety Board and must
have the authority to use a party system (wherein the Board would lead an investigation by
collecting expertise from government, industry, and academia) and have the independent funding
to conduct and oversee such safety investigations. However, the exact details of implementing such
a vaccine safety board are not described in the article.
Opinions on Establishment of a National Vaccine Safety Board
Numerous organizations and individual experts have expressed concern about the potential
problems that might be caused by creation of a vaccine safety board, especially with the existing
safety systems in place. The IOM’s Immunization Safety Review, for example, is the independent
body convening vaccine experts to review scientific evidence pertaining to vaccine safety. Many
believe that the current systems are more than adequate and that this approach will cause
significant trouble for physicians because it makes the fundamental assumption that the vaccine is
the cause of any reported problem. The potential thus exists that the blame would be immediately
placed on the vaccine (and indirectly on the physician administering the vaccine) when it is not that
clear-cut. Vaccine safety is not as distinct as the occurrence of a plane crash--the National
Transportation Safety Board being one model being put forward for a national vaccine safety
board.
The idea of a vaccine safety board arose because numerous anti-immunization groups claimed that
they had no access to the data to properly evaluate vaccine safety and that a safety board would
establish an independent group of people with no conflicts of interest to facilitate that evaluation.
Anti-immunization groups have sought to undermine public confidence in vaccine safety by
emphasizing the alleged conflict of interest that exists for the medical and scientific experts who
conduct vaccine safety research and investigations. However, it is absolutely vital for the CDC and
other federal agencies to have the most highly qualified vaccine safety experts involved in the
integration of safety information into policy. Also, the federal government needs the ability to act
immediately should a vaccine safety issue arise, based on immediate advice solicited from the
advisory committees. The creation of a safety board could hamper access to these individuals by
the federal government, as a national vaccine safety board might exclude vaccine researchers,
public health experts, and other immunization experts (due to perceived conflict of interest) from
the safety evaluation process. A rapid public health response may preclude the necessary time
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needed to assemble the experts to provide guidance to the Board. This was well demonstrated when
the CDC acted rapidly to remove the rotavirus vaccine. Ironically, the very system that halted the
use of rotavirus vaccine did not receive the same criticisms of conflict of interest when a vaccine
was eventually removed from public use.
It has been suggested that the proper way to address the aforementioned concerns is not through a
safety board but to give the people who oppose or question the safety of vaccination greater access
to the relevant data and offer them the opportunity to seek grants to pursue their own research
agenda on vaccine safety.
Finally, the current independent assessment of vaccine safety is provided by the IOM. A national
vaccine safety board would assume that role; however, integrating the safety board into the
manifold systems already in place to secure vaccine safety might be complex and demand
significant resources. Many question the value of this undertaking, given that vaccine adverse
events are rare and important decisions need to be made about how vigorously each claim should
be investigated. Ultimately, vaccine safety has to compete with other vaccination needs (eg, the
actual purchase of vaccines), which pits spending resources on an unknown (alleged vaccine
adverse event) against a known (lives saved due to vaccines purchased and administered).
Regardless, it is important that our AMA remain engaged in discussions on the possible
establishment of a National Vaccine Safety Board to ensure that the best approaches to assuring the
safety of vaccines in the United States are considered.
NVAC Subcommittee on Vaccine Safety
The NVPO’s NVAC is establishing a subcommittee to further explore the issue of vaccine safety,
which will include a discussion of the issue of a national vaccine safety board. The director of the
NVPO, Bruce Gellin, MD, MPH, is aware of our AMA’s interest in the issues of vaccine safety
and specifically in the issue of the safety board. As such, our AMA has been extended an offer to
participate in the discussions and deliberations of this subcommittee when it is established in 2004.
CDC Examination of the Handling of Vaccine Safety
In Spring 2004, the CDC will create an external panel to discuss and review the way vaccine safety
is handled within the agency. AMA staff has been invited to participate on this panel.
Thimerosal Law Suits and Access to Pre-Publication Data
Thimerosal in Vaccines: Thimerosal was used as a preservative in some multi-dose vials of
pediatric vaccines, but all pediatric vaccines are now thimerosal free. Thimerosal is still used in
some vaccines administered to adults, such as the influenza vaccine, but in reduced amounts.
Concern about thimerosal arose in 1997, when as part of the FDA Modernization Act, the FDA
reviewed the risk of all mercury-containing food and drugs. Accordingly, thimerosal use in
vaccines was evaluated to ascertain if the mercury in thimerosal could pose a risk of
neurodevelopmental disorders in children receiving vaccines containing thimerosal. It is important
to note that thimerosal’s mercury compound is ethylmercury and not methylmercury, the form on
which, until recently, all available mercury toxicity studies were performed.
While the FDA review found no evidence of neurodevelopmental harm caused by thimerosal in
vaccines, the public outcry fueled by anti-immunization groups led the Public Health Service
B of T Rep. 14- A-04 -- page 10
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agencies, the AAP, and vaccine manufacturers to agree that thimerosal in vaccines should be
reduced or eliminated as a precautionary measure. This decision was one of the primary causes for
the vaccine shortages that occurred in 2001 and 2002, as manufacturers struggled with their
manufacturing processes to eliminate thimerosal in the final formulations of their vaccines.
Significantly, since the FDA review, numerous studies have now been performed on this issue,
including one by the IOM’s Immunization Safety Review Committee. This committee found that
while the biological plausibility that thimerosal used in vaccines could cause neurodevelopmental
disorders existed, there was no evidence to support that occurrence in recipients of thimerosalcontaining vaccines. The study did cite the lack of data on the form of mercury contained in
thimerosal, ethylmercury, as a primary reason that a more definitive conclusion could not be
reached.
Since the IOM report, at least two studies have specifically focused on ethylmercury. One showed
that epidemiologically, there has been no correlation between the use of thimerosal in vaccines and
an increase in neurodevelopmental disorders. More significantly, another study showed that
ethylmercury behaves differently from methylmercury in the body. Indeed, this study indicated
that unlike methylmercury, ethylmercury is cleared from the plasma very rapidly after vaccine
administration and does not appear to persist. Most experts agree that, taken together, these data
indicate that it is improbable that thimerosal use in vaccine is responsible for neurodevelopmental
disorders, such as autism, in children.
Thimerosal Legal Action: Nonetheless, various claims have been filed in federal claims court
against the manufacturers of vaccines, bypassing the VICP and claiming that either the MMR
vaccine or thimerosal in vaccines caused autism in the injured parties. The argument given in the
claims for bypassing the VICP was that thimerosal was a contaminant of vaccines and thus
compensation for alleged harm need not be pursued through the VICP. Since then, the DHHS has
issued a statement that thimerosal is indeed an ingredient of vaccines and not a contaminant, but
the claims have continued.
As part of this legal action, the plaintiffs’ lawyers have filed a motion that the DHHS produce all
documents, emails, internal memoranda, and other correspondence that discuss studies, proposed
studies, and requests for funding dealing with MMR vaccine or thimerosal-containing vaccines
causing or contributing to autism or pervasive developmental disorder (PDD). Immediately,
concerns were raised about the release of preliminary or pre-publication data. A hearing was held
on January 31, 2003, in which the Department of Justice presented to the Office of Special Masters
of the United States Court of Federal Claims the possible harms that could result to the DHHS and
the general public should data representing unfinished research be released prematurely.
At the hearing, the DHHS not only presented legal reasons as to why the plaintiffs’ request should
not be supported, it also stated that public health and scientific advancement are best served when
data are released to, or shared with, other public health agencies, academic researchers, and other
appropriate private researchers in an open, timely, and proper way. However, while doing so the
need also exists to maintain high standards for data quality, which can be assessed by the abovementioned qualified individuals, but may not be so readily obvious to the uninformed. In addition,
the confidential and proprietary nature of biomedical research makes widespread dissemination of
preliminary data inappropriate. It was argued that the need exists to ensure the privacy of
individuals who provide personal information and to protect the information relevant to national
security, criminal investigations, or misconduct inquiries.
B of T Rep. 14- A-04 -- page 11
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Specifically, it was emphasized that scientific information released to the public must be of the
highest quality and that scientific integrity must be maintained under all circumstances. If data are
released prematurely to the public, there is the potential for public harm because:
1. Scientific processes and research practices should ensure the quality, integrity, and
accuracy of scientific information disseminated to the public. If preliminary information is
released to the general public before the accuracy and quality of the information are
assured, misinterpretations or incorrect assumptions or conclusions about a critical public
health issue are possible.
2. Scientific research undergoes rigorous peer review and institutional clearance processes
before general release. Without this type of review and quality assurance, the public could
be harmed by potential misinformation, misinterpretation, or misuse of research findings
that are not ready for publication.
3. Research that involves the collection of data from human subjects must always be carefully
guarded against privacy and confidentiality violations. Institutional and peer reviews are
critical measures that ensure these protections, while untimely release of research data
jeopardizes this process, raising numerous ethical and legal issues.
Current Status of the Thimerosal Claims: Much of the data (the Verstraeten study) that were the
subject of this lawsuit have now been published in the November 2003 issue of Pediatrics.
Consequently, some of the controversy over access to data has since diminished. The petitioners'
counsel has submitted a motion to compel discovery, which includes access to the thimerosal
screening analysis data (among a laundry list of other things) used in the Verstraeten study.
Discussions had been under way to allow access to the final data at the Research Data Center but
the requests/discovery seem to continually expand. The Department of Justice has now scheduled
a hearing on the issue on June 7, 2004. The CDC has promised to update the AMA on this matter
and depending on the status of the process, it may be appropriate for the AMA to submit testimony
in support of the DHHS’ position on pre-publication release of medical and scientific data, in line
with the second resolve of Resolution 924 (I-02).
RECOMMENDATIONS
The Board of Trustees recommends that the following recommendations be adopted in lieu of
Resolution 924 (I-02) and that the remainder of this report be filed:
1. That our American Medical Association continue to work with the federal government and
other key stakeholders to monitor the issue of vaccine safety, including the feasibility of
creating a national vaccine safety board, and to take appropriate action where necessary.
(Directive to Take Action)
2. That our AMA participate in the National Vaccine Advisory Committee’s subcommittee on
vaccine safety (currently scheduled to be established in Summer 2004) and the Centers for
Disease Control and Prevention’s external review on vaccine safety. (Directive to Take
Action)
3. That our AMA continue to work with the federal government and other key stakeholders to
monitor and respond strongly against the inappropriate release of pre-publication/preliminary
scientific data. (Directive to Take Action)
Fiscal Note: $48,026
B of T Rep. 14- A-04 -- page 12
AMA Fiscal Note Documentation
Resolution/Report: BOT Report 4 (A-04)
Title: Vaccine Safety
Staff Contact/Extension: L.J Tan, x4147
Total Fiscal Note:
$48,026
Specific Actions Planned if Adopted
Work with relevant agencies and organizations to
monitor the issue of vaccine safety, including the
feasibility of creating a national vaccine safety
board. Staff to participate in NVAC and CDC
meetings on vaccine safety. Staff to monitor issue
of inappropriate release of prepublication/preliminary scientific data and respond if
necessary.
Summarize below all costs, specifying whether this is a one-time expenditure or
ongoing.
Incremental Expenses:
Salaries and Wages (only for additional
staff)*
$
Fringe Benefits (29% of above)
$
Travel and Meetings
$
One time cost for travel to three
4,000
meetings. Should number of meetings
increase this cost will have to be
increased
Membership and Grants
$
Publication Costs
$
IF an amicus is determined to be the
approriate response and needs to be
prepared and filed and IF external
consultation is necessary. Estimate of
$
cost provided by AMA legal staff.
Professional Fees
25,000
Printing and Production
$
Postage
$
Promotion
$
Supplies
$
All Other Expenses
TOTAL Incremental Expenses
CURRENT STAFFING COSTS**
TOTAL REVENUE (if any)
$
$
29,000
$
19,026
Does not include cost of a follow up
report if requested by BOT or HOD
$
$
TOTAL FISCAL NOTE
48,026
* - This would require new complement positions or use of contract labor.
** - From Staff Cost Template spreadsheet
Additional notes:
B of T Rep. 14- A-04 -- page 13
Staff Costs
Fiscal Note for BOT Report 4 - Vaccine
Safety
Input estimated number of hours required at each
staff level to complete the project.
Hours
Staff Assistants
Professional Staff
Senior Professional Staff
77
Middle Management
Senior Management
Legal
200
Rate
$
18
$
25
$
33
$
50
$
105
$
65
Staff
Cost
$
$
$
2,541
$
$
$
13,000
Estimated salaries
$
15,541
Fringe benefits
$
4,507
Total staff costs
$
20,048
IF an amicus is determined to
be the approriate response
and needs to be prepared
and filed. Estimate of time
provided by AMA legal
staff.