Vaccine
Safety > VSD
CDC Research on the Safety of
Thimerosal Containing Vaccines
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At
a glance: CDC has conducted a
study using computerized data from 3 HMOS
to see whether there were associations
between vaccines that used thimerosal as
a preservative and a wide range of neurodevelopmental
disorders. Results found no consistent
significant associations across the HMOs.
Other studies of the safety of thimerosal
containing vaccines are underway. |
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Contents of this page: |
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Related
pages and information: |
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What
research is CDC doing to assess the
safety of thimerosal-containing vaccines? |
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Vaccine Safety Datalink (VSD) screening study.
CDC has conducted a study using
computerized data from 3 HMOS to see whether there were associations between
vaccines that used thimerosal as a preservative and a wide range of neurodevelopmental
disorders. Results (published in 2003) found no consistent significant associations
across the HMOs.
Details on
this study follow on this
page.
- The
thimerosal follow-up study compares performance on a number of neurodevelopmental
measures (such as speech and language skills, attention, coordination, tics, and hearing)
among children who were exposed to different amounts of thimerosal through vaccination
and other exposures. This study was designed to look more closely at inconsistent findings
from the earlier, 2003 VSD study listed above. It does not assess autism or Autism Spectrum
Disorders (ASD) as possible outcomes of thimerosal exposure through vaccination. The study
includes over 1,000 children 7 to 10 years of age. The researchers collected information
from the children’s medical records, gave them standardized tests, and interviewed their
parents about things that could influence the results of the study (such as a mother’s diet
during pregnancy and parental health seeking behavior). Although CDC funded this study, 13
non-CDC expert consultants gave input on the study design, conduct, and analysis. All of the
information (data) needed for this study has been collected. Initial preliminary results are
being reviewed by the expert consultants and the CDC study investigators. Researchers will continue
to analyze the data and final results are expected to be published in 2006.
- The
thimerosal and autism case-control
study. The possibility that exposure to mercury may cause autism has
probably caused the greatest concern about exposure to thimerosal as a preservative
in childhood vaccines. Although the weight of scientific evidence, including results
from the VSD study, do not support this association, autism can be difficult to diagnose
and study data based on autism diagnosis from medical computerized databases can be difficult
to verify. This study is designed to address these issues.
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Vaccine
Safety Datalink (VSD)Study |
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November
2003
- CDC
takes vaccine safety seriously, and this
study, a part of the Vaccine Safety Datalink
project, is an example of CDC's ongoing efforts
to examine issues of concern to parents and
healthcare providers.
- The results
of this study are consistent with the weight
of scientific evidence to date, which does
not support that neurodevelopmental disabilities
such as autism are caused by vaccines containing
thimerosal. Additional studies are being
conducted to help answer additional questions
and to ensure that a comprehensive assessment
of thimerosal-related health issues is done.
- Today, none
of the vaccines used routinely in the U.S.
to protect preschool children against 12
infectious diseases actually contain thimerosal
as a preservative. In addition, the measles-mumps-rubella
(MMR), polio, pneumococcal conjugate (PCV)
and varicella (chickenpox) vaccines never
contained thimerosal.
Questions
and Answers on the Vaccine Safety Datalink
Study |
- What
were the major findings and conclusions from
the CDC’s Vaccine Safety Datalink study?
The
final results of this study found no consistent
statistically significant associations between
exposure to vaccines that contained thimerosal
as a preservative and a wide range of neurodevelopmental
problems, including autism, attention deficit
disorder (ADD), language delays, sleep disorders,
emotional disorders, and tics. None of the
results found any associations with autism
or ADD. Since it is necessary to first establish
there is an association between two things
(often called “variables”), the
results from this study suggest there is
not a “cause and effect” relationship
between thimerosal and autism or ADD.
In the first phase of the research, there
were some statistically significant associations
between exposure to thimerosal-containing
vaccines and two categories of neurodevelopmental
problems, “tics” and language
delay. However, these results were not consistent—that
is, the relationships were only found with
one of the health maintenance organization
(HMO) databases, rather than in all three
that were used in the study. Such a pattern
suggests that an association does not exist,
but that further research should be done.
As
a result of the inconsistent finding involving
“tics” and language delay, one
of the major conclusions was that additional
research be done to further examine the issue
of exposure to thimerosal in vaccines. The
CDC is currently involved in this additional
research.
Top
- What
do the study’s results mean for parents?
The
study did not find consistent evidence to
suggest that thimerosal might cause any of
the conditions studied. In particular, the
study found that thimerosal exposure was
not associated with autism, which adds to
the evidence from other studies that thimerosal
does not increase the risk of autism.
Since
1999 thimerosal has been removed from the
majority of recommended childhood vaccines
for preschool children. In fact today, with
the exception of some flu vaccine, none of
the routinely recommended childhood vaccines
used in the U.S. to protect preschool children
against 12 infectious diseases contain thimerosal
as a preservative. These include vaccines
for measles, mumps, rubella, chickenpox,
hepatitis B, diphtheria, tetanus, pertussis
(whooping cough), Haemophilus influenzae
type b (Hib), polio, influenza (flu) and
pneumococcal disease. In some of the recommended
childhood vaccines minute amounts of thimerosal
can be found; this is an unavoidable byproduct
of the production process and has nothing
to do with thimerosal being used as a preservative
in the vaccines. No harmful effects have
ever been reported or found with these amounts
of thimerosal in vaccine.
Top
- This
study looked at thimerosal in vaccines. Why
is there a concern about this vaccine preservative?
There
was a concern because thimerosal contains
a type of mercury called ethylmercury. Since
exposure to small amounts of mercury can
be harmful, concerns were raised about the
very tiny amount of ethylmercury in thimerosal.
However, the safety concerns related to thimerosal
were not based on any evidence that connects
thimerosal to harmful health outcomes. Rather,
the concerns were related to federal government
guidelines and theoretical estimates about
how much mercury people can be safely exposed
to without possible risk of serious health
effects.
In
1999, the Food and Drug Administration (FDA)
conducted a review of the mercury content
in drugs and medicines, including vaccines.
As part of this review, the FDA concluded
that the use of thimerosal as a preservative
in some recommended childhood vaccines could
result in a six-month-old infant being exposed
to an amount of mercury that exceeded the
Environmental Protection Agency (EPA) recommendations.
However, this same amount would not exceed
the FDA, the Agency for Toxic Substances
and Disease Registry (ATSDR), or the World
Health Organization (WHO) guidelines for
methylmercury intake (Ball et al., 2001).
Thimerosal contains ethylmercury. Methylmercury
is a related compound and has been more thoroughly
researched than ethylmercury. Thus federal
safety standards are based on information
we have about methylmercury.
The
FDA’s review found no evidence of harm
caused by the small amounts of thimerosal
in vaccines, except for minor local reactions
(Ball et al., 2001). In July 1999, as a precautionary
measure, the Public Health Service (including
the CDC and FDA), the American Academy of
Pediatrics, and vaccine manufacturers agreed
that thimerosal levels in vaccines should
be reduced or eliminated, and the FDA committed
to expediting the review of new vaccines
that do not contain thimerosal.
Although
there is no evidence that any vaccine or
vaccine additive increases the risk of neurodevelopment
disorders, such as autism, CDC recognizes
that this issue is of concern to parents
and others. As a result, CDC is committed
to investigating this issue to the fullest
extent possible, using the best scientific
methods available.
For
more information on thimerosal in vaccines,
visit:
http://www.cdc.gov/nip/vacsafe/concerns/thimerosal/faqs-thimerosal.htm#2
Top
- This
study was based on computerized data from
the Vaccine Safety Datalink (VSD) project.
What is the VSD?
The
Vaccine Safety Datalink (VSD) Project is
a collaborative project involving the Centers
for Disease Control and Prevention (CDC)
and several large health maintenance organizations
(HMOs). The VSD was established primarily
to assess vaccine safety issues in the United
States through analyses of large-linked databases
collected at the HMOs as part of their routine
administration of health services. The databases
contain the vaccination and medical records
of millions of children and adults.
The
VSD is a cost-effective and valuable tool
for monitoring vaccine safety and evaluating
research questions. The computerized data
sets that make up the VSD data base, however,
are not collected for specific research purposes
and as a result have certain limitations
to how they can be used. Definitive vaccine
safety studies in the VSD usually require
additional data collection, such as detailed
review of hardcopy medical records or standardized
interviews of parents. Neither of these data
sets are available in the computerized data
bases.
For
more information on the VSD, see Vaccine
Safety Data Sharing Process.
Top
- What
was the purpose of the Vaccine Safety Datalink
(VSD) database study?
The
purpose of this Vaccine Safety Datalink database
study was to determine whether there were
associations between vaccines that used thimerosal
as a preservative (i.e., an ingredient to
prevent the growth of harmful bacteria and
fungi) and a wide range of neurodevelopmental
problems, including autism, attention deficit
disorder, language delays, sleep disorders,
emotional disorders, and tics. Researchers
from CDC and participating Health Maintenance
Organizations (HMOs) analyzed the computerized
vaccination and medical records of over 140,000
children from birth up to 9 years of age.
Top
- There
have been reports that one of the CDC scientists
who worked on this study now works for a
vaccine manufacturer and that this was never
mentioned in the publication of the study.
Is this true?
Yes.
From the time the study started to the time
it was published took about 4 years and during
that time one of four CDC scientists involved
in the study left CDC to work for a pharmaceutical
company called GlaxoSmithKline (GSK). In
addition to the CDC scientists there were
also researchers from three health maintenance
organizations (HMOs) who participated.
Dr.
Thomas Verstraeten, the researcher who left
CDC in 2001 to work for GSK, worked at CDC
during the critical time when the study was
designed and the data were analyzed. As a
result, the journal Pediatrics, which published
the study on November 4, 2003, listed Dr.
Verstraeten’s affiliation as the CDC.
Pediatrics, like many professional journals,
has a policy of identifying an author’s
affiliation at the time a study was conducted
(rather than their affiliation when the article
is published). This article was thoroughly
peer reviewed before it was published. However,
to avoid any perceived conflict of interest,
CDC should have assured that Dr. Verstraeten’s
current employment status, as well as his
status when the work was carried out, were
both disclosed in the journal article. Once
Dr. Verstraeten’s began working at
GSK, his involvement in this study was limited
to reviewing drafts of the manuscript.
Top
- Did
the study find any evidence that indicated
that exposure to thimerosal in vaccines was
associated with autism?
No.
In one of the first analyses of the data
there was a weak result that found a possible
increased risk for autism among children
who received vaccines at the highest level
of thimerosal (> 62.5ug) by the third
month of life, but this result was not statistically
significant and was later found to have been
based on incorrect data. Scientists have
a responsibility to assure that all findings
and results are based on accurate data—especially
before publishing them.
These
early findings were not supported by later
analyses of additional cases with more accurate
data which showed that children, who received
vaccines containing thimerosal, either by
three months of life or by seven months of
life, were not at increased risk for developing
autism. There was no suggestion of an increased
risk for autism even among those children
who received vaccines with the highest levels
of thimerosal by seven months of age (i.e.,
those receiving 162.5 ug, 175 ug, or more
than 175 ug thimerosal by 7 months of age).
These results, however, cannot be considered
definitive since the study was not specifically
designed to assess a complex condition such
as autism but to guide the development of
follow-up studies at CDC. These studies will
investigate more rigorously possible associations
between thimerosal in vaccines and a number
of neurodevelopmental disorders.
Top
- The
research in the VSD study began in 1999.
Did the results or findings of the study
change over time?
Yes,
thanks to suggestions from other scientists,
researchers, and organizations, improvements
were made in the databases, research methods,
and statistical procedures used to analyze
the data. It is accepted and sound scientific
practice, especially with complex and important
research issues, to seek and use the advice
and recommendations from both internal and
external reviewers to strengthen a study
as much as possible before publishing a final
paper. In this case, four major improvements
were made after the initial findings were
presented in 1999:
- The
methods used to analyze the data were refined
and improved based on expert input from
inside CDC and from outside CDC.
- Errors
in the data were corrected (e.g., mistakes
in medical records, errors regarding the
thimerosal content of certain vaccines)
to make the results more accurate.
- Suggestions
by reviewers were incorporated into the
analysis to address and reduce potential
biases (e.g., differences in health care
seeking behavior among parents that could
lead to some children going to the doctors
more often and therefore being diagnosed
more often).
- More
children with diagnoses of interest were
identified as the study progressed and
the children at the HMOs became older.
Top
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There were
two phases to this study. Why was a second
phase added?
In
science, it is important to be able to repeat
(that is, replicate) research findings in
order to show that they did not occur by
chance alone. If you obtain the same results
more than once, using similar methods but
a different dataset, you can have more confidence
in your findings and be better able to make
strong conclusions. In a review of preliminary
analysis results by a panel of CDC scientists,
the suggestion was made that it would be
important to attempt to replicate the results
in an independent data set. This is why a
second phase of the study was conducted using
data from a third HMO.
Due
to the smaller number of children in the
third HMO, researchers could only assess
the most common outcomes associated with
thimerosal in the first part of the study.
No association was found with autism in the
first part of the study, and it was not investigated
in the second part of the study. The third
HMO pioneered the development of electronic
medical records and had the required computerized
databases (vaccinations and health care encounters)
similar to those that had been used in the
two VSD HMOs in Phase I of the study. This
long history of active use of the databases
for multiple needs provided many opportunities
for feedback and continued improvements in
data quality. These qualities in turn made
this HMO a good candidate for the Phase II
study when the need arose.
Top
- Can
people outside CDC use the VSD data to conduct
their own research?
Yes.
In 2002, the CDC and the participating HMOs
established a data sharing program to make
the VSD database available to any member
of the public who follows the established
procedures for the Vaccine Safety Datalink
Data Sharing program. External researchers
can submit research proposals to conduct
new studies of vaccine safety or to reanalyze
study-specific datasets from published VSD
studies. External researchers have the opportunity
to submit research proposals for new vaccine
safety hypotheses that include any or all
of the data variables available in the VSD.
Data are extracted from the entire VSD database
and provided to external researchers in response
to specific Institutional Review Board (IRB)-approved
research protocols.
In compliance with federal regulations, access
by external researchers to the VSD data files
or to datasets from VSD published studies
requires review and approval by the appropriate
IRBs of the relevant HMOs. The IRBs have
the responsibility to protect the confidentiality
and privacy of their members’ medical
records and to adhere to the rules and regulations
of their specific institution; therefore,
each of the HMO IRBs must review any request
for access to the VSD data files that contain
information on its HMO members.
Upon
approval by the relevant IRB protocol, datasets
are prepared according to the external researcher’s
approved research protocol. External researchers
access the approved VSD data at the Research
Data Center (RDC) located at the National
Center for Health Statistics (NCHS). The
RDC, established in 1998 by NCHS, is a research
facility located at the CDC’s NCHS
facility in Hyattsville, Maryland.
Further
details about the VSD data sharing process
can be found in "Guidelines
for Data Sharing Program for External Researchers:
Access to CDC’s Vaccine Safety Datalink
Data"
Top
- Do
any of the currently routinely recommended
childhood vaccines contain thimerosal as
a preservative?
Today,
with the exception of some influenza (flu)
vaccines, none of the vaccines routinely
used in the U.S. to protect preschool children
against 12 infectious diseases contain thimerosal
as a preservative. These include vaccines
that protect children from the measles, mumps,
rubella, chickenpox, hepatitis B, diphtheria,
tetanus, pertussis (whooping cough), Haemophilus
influenzae type b (Hib), polio, influenza
(flu), and pneumococcal disease. No serious
harmful effects have ever been reported or
found with these doses of thimerosal in vaccines.
In addition, the measles-mumps-rubella (MMR),
polio, varicella (chickenpox) and pneumococcal
conjugate (PCV) vaccines never contained
thimerosal.
Top
- Are
there any vaccines recommended for preschool
children that contain thimerosal as a preservative?
Yes.
Recently the Advisory Committee on Immunization
Practices recommended flu vaccine for children
6 to 23 months of age and all children at
high risk for complications from influenza.
Although some flu vaccines contain the preservative
thimerosal, the amounts found in these vaccines
are considered safe for use in children.
For parents, physicians, and other healthcare
providers who have concerns, there is some
flu vaccine available that does not contain
thimerosal as a preservative.
There
is no indication that the small amounts of
thimerosal found in some flu vaccines have
any association with any harmful health effects
on children of this age.
Top
- Has
there been an independent report on the possible
association between exposure to thimerosal
as a preservative in vaccines and serious
health outcomes?
Yes.
One was conducted by the Institute of Medicine
(IOM) in 2001. ((Immunization Safety Review:
Thimerosal-Containing Vaccines and Neurodevelopmental
Disorders 2001).
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