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Summary
BACKGROUND
Vaccines are among the most effective and safe public health interven-
tions available to prevent serious disease and death. As the incidence of
vaccine-preventable diseases has declined because of the widespread use of
immunizations, potential adverse effects of the vaccines themselves have
taken on greater saliency among stakeholders. The U.S. Advisory Commit-
tee on Immunization Practices (ACIP) has created a schedule of vaccines
that should be administered at various intervals. ACIP recommends immu-
nization with vaccines that protect young children (age 6 years and under)
against 14 pathogens (see Appendix A) and strives to protect children at
the youngest age necessary to shield them from diseases when they are the
most vulnerable. The childhood immunization schedule (defined in this
report as the immunization schedule covering children from birth through
age 6 years) immunizes children in a manner consistent with demonstrated
efficacy, safety, and feasibility but also permits some degree of flexibility to
accommodate individual preferences and logistics.
With the current schedule, children may receive up to 24 immuniza-
tions by age 2 years and up to 5 injections in a single visit. Although the
number of vaccines has increased over the years to protect against a greater
number of diseases, because of technological advances children now receive
fewer antigens, which are the components of vaccines that stimulate the
immune system.
In the United States, manufacturers extensively test new vaccine prod-
ucts and then the federal government undertakes a formal process of review
1
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2 THE CHILDHOOD IMMUNIZATION SCHEDULE AND SAFETY
and approval before vaccines are made publicly available. Each new vac-
cine considered for inclusion in the immunization schedule is tested within
the context of the existing schedule and reviewed by clinical researchers,
who analyze the balance of demonstrated benefits and risks. Thus, each
new vaccine is approved on the basis of a detailed evaluation of both the
vaccine itself and the immunization schedule. Every year, the Centers for
Disease Control and Prevention (CDC) issues guidance on the vaccines to
be administered and immunization schedules for children, adolescents, and
adults, based on recommendations from ACIP.
To recommend new vaccines, ACIP uses a process in which it reviews
a comprehensive set of data associated with the vaccine, including illnesses
and deaths associated with the disease and specific high-risk groups; the
results of clinical trials, including indicators of safety, efficacy, and ef-
fectiveness; cost-effectiveness; information on vaccine use provided by the
manufacturer in the product’s labeling or package insert; and the feasibility
of incorporation of the vaccine into the existing immunization schedule.
Ongoing surveillance systems are the primary source of data on vaccine
safety postmarketing. CDC maintains three major postmarketing surveil-
lance systems: the Vaccine Adverse Event Reporting System, which is jointly
managed with the Food and Drug Administration (FDA); the Vaccine
Safety Datalink (VSD); and the Clinical Immunization Safety Assessment
Network. In addition to the surveillance systems managed by CDC, FDA
has established the Sentinel Initiative, a supplementary mechanism for
monitoring vaccine safety.
Immunization coverage among children entering kindergarten currently
exceeds 90 percent for most recommended vaccines. However, concerns
about vaccine safety have contributed to increases in the delay or refusal
of immunization, which have, in turn, contributed to a reemergence of
vaccine-preventable illnesses. For example, measles and pertussis (whoop-
ing cough) outbreaks have occurred in areas where higher proportions of
children are unimmunized.
Vaccines—like all drugs or medical interventions—are neither 100
percent risk-free nor 100 percent effective. Additionally, population-wide
prevention of vaccine-preventable diseases relies on community immunity,
also commonly referred to as herd immunity, which is the shared protec-
tive effect conferred on unimmunized individuals when a sufficiently large
proportion of the population is immunized against infectious diseases.
This phenomenon is achieved when too few people who are vulnerable to
development of a disease remain in the population to maintain the chain of
disease transmission. Community immunity is waning, however, in places
with increasing numbers of unimmunized, incompletely immunized indi-
viduals and/or individuals with waning immunity.
Even though children are required to be immunized to enter school
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SUMMARY 3
and child care, medical exemptions are allowed in all states, and almost
all states allow immunization exemptions for people who have religious
beliefs against them. Furthermore, 20 states permit exemptions for those
who object to immunizations because of personal, moral, or other beliefs.
THE COMMITTEE
The National Vaccine Program Office (NVPO) of the U.S. Department
of Health and Human Services (HHS) asked the Institute of Medicine
(IOM) to convene a committee of experts in pediatrics, neurology, medical
ethics, immunology, statistics, epidemiology, and public health to identify
feasible study designs to explore the safety of the U.S. childhood immu-
nization schedule. A 14-member committee was assembled to address the
statement of task. The committee’s charge is independent of the charges for
previous IOM vaccine studies, and committee members were selected to
avoid any real or perceived biases or conflicts. Strict criteria for membership
prevented members from having financial ties to vaccine manufacturers or
their parent companies, previous service on federal vaccine advisory com-
mittees, or having delivered expert testimony or written publications on
vaccine safety. The committee’s charge is detailed in Box S-1.
COMMITTEE PROCESS
To complete its charge, the committee held three information-gathering
meetings in two locations. Before the first meeting and throughout the
committee’s deliberations, the committee gathered information on public
BOX S-1
Statement of Task
The Institute of Medicine will convene an expert committee to
1. Review scientific findings and stakeholder concerns related to the
safety of the recommended childhood immunization schedule.
2. Identify potential research approaches, methodologies, and study
designs that could inform this question, including an assessment
of the potential strengths and limitations of each approach, meth-
odology and design, as well as the financial and ethical feasibility
of doing them.
3. Issue a report summarizing their findings.
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4 THE CHILDHOOD IMMUNIZATION SCHEDULE AND SAFETY
perspectives and reviewed the scientific literature on the safety of the recom-
mended childhood immunization schedule. At the public forums, the com-
mittee heard presentations by pediatricians, representatives of federal and
state agencies and public health agencies in other countries, vaccine safety
researchers, advocacy groups, vaccine manufacturers, and methodological
experts. The committee invited comments (both written and oral) from the
general public and representatives from numerous organizations with an
interest in vaccine safety.
The committee held five deliberative meetings over 6 months. To ad-
dress its charge, the committee requested from consultant Martin Kulldorff
a commissioned paper on study designs that could be used to assess the
safety of the immunization schedule (see Appendix D). The paper was
intended to provide methodological input to the committee but the paper
does not necessarily reflect the committee’s views. To solicit stakeholders’
feedback, the commissioned paper was posted on the committee’s website.
STAKEHOLDER CONCERNS
A review of the scientific literature, as well as a detailed review of the
oral and written public comments, revealed that among the various stake-
holder groups,1 parents, health care providers, and public health officials
share the sentiment that there is insufficient communication between pro-
viders and parents about the schedule’s safety. Even though the vast major-
ity of parents adhere to the ACIP-recommended immunization schedule,
some parents are concerned that the schedule may present unnecessary risks
because of the timing and number of vaccinations.
Some parents request variations in the immunization schedule, such as
a delay of one or more immunizations or the administration of fewer vac-
cinations at each visit. Some parents also refuse immunizations entirely on
the basis of the premise that their children’s risks from vaccine-preventable
diseases are less than the risks of adverse events associated with immuniza-
tions. Such decisions may reflect, in part, the significant and sustained de-
cline in vaccine-preventable diseases that immunization policy has achieved
in the past several decades and against which the risk of even extremely
rare adverse events may be seen as not worth taking. Some parents are
concerned about their child’s risk of complications after immunization on
the basis of a family history or the child’s medical condition and thereby
1 takeholder groups include researchers; advocacy groups; federal agencies and advisory
S
committees; the general public (including parents); the health care system and providers; inter-
national organizations; media; nongovernmental organizations; philanthropic organizations;
state, local, and tribal government agencies; industries, such as travel and vaccine manufactur-
ing industries; vaccine distributors; and investors in vaccine manufacturers.
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SUMMARY 5
decide to delay or omit immunizations. Other parents express a general lack
of confidence in U.S. government decisions about the safety and benefits of
the childhood immunization schedule.
The committee understands that these parental concerns are an expres-
sion of concern and a way to care for their children’s health and well-being.
However, the committee also recognizes that a delay or refusal to immunize
their children has already contributed to outbreaks of disease across the
United States that pose a risk to the health of many people, particularly
those with compromised immune systems.
The committee’s review of the literature also focused on factors that
affect public trust in vaccination campaigns and information on vaccines.
Improved communication between public health authorities and parents
will require improvements to the clarity of information as well as the build-
ing of trust and the use of a systematic approach to elicit public concerns.
Further research into questions that parents seek to answer by use of the
scientific methods of social, behavioral, and decision science is indicated.
HEALTH OUTCOMES
The committee searched for, assembled, and summarized evidence on
the association between the immunization schedule and specific health
conditions that was already published in the peer-reviewed literature. The
health outcomes that the committee chose to review were selected on the
basis of an examination of the peer-reviewed literature, previous IOM
vaccine safety studies, and public presentations at open meetings of this
committee. The number of studies that addressed aspects of the immuniza-
tion schedule varied; for some outcomes, several studies had examined the
cumulative effects of vaccines and adjuvants or preservatives, whereas very
few studies could be found for other outcomes.
The committee’s literature searches and review were intended to iden-
tify health outcomes associated with some aspect of the childhood im-
munization schedule. Allergy and asthma, autoimmunity, autism, other
neurodevelopmental disorders (e.g., learning disabilities, tics, behavioral
disorders, and intellectual disabilities), seizures, and epilepsy were included
as search terms. Furthermore, the committee reviewed papers on immuniza-
tion and premature infants.
In summary, few studies have comprehensively assessed the associa-
tion between the entire immunization schedule or variations in the overall
schedule and categories of health outcomes, and no study has directly ex-
amined health outcomes and stakeholder concerns in precisely the way that
the committee was charged to address in its statement of task. No studies
have compared the differences in health outcomes that some stakeholders
questioned between entirely unimmunized populations of children and fully
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6 THE CHILDHOOD IMMUNIZATION SCHEDULE AND SAFETY
immunized children. Experts who addressed the committee pointed not to a
body of evidence that had been overlooked but rather to the fact that exist-
ing research has not been designed to test the entire immunization schedule.
The committee believes that although the available evidence is reas-
suring, studies designed to examine the long-term effects of the cumulative
number of vaccines or other aspects of the immunization schedule have
not been conducted. Nevertheless, in its literature review, the committee
found useful designs for studies to measure exposures and outcomes and
identified strategies for expanding or adapting conventional study designs
to clearly address whether any adverse health outcomes are associated with
the overall immunization schedule.
METHODOLOGICAL APPROACHES
Moving from an analysis of stakeholder concerns and the limited sci-
entific evidence about the association between the immunization schedule
and adverse events to recommendation of specific research methods and
study designs to address that association is an ambitious task in light of
the complexity and changing nature of the recommended immunization
schedule. Variables such as the number of doses, the age of administration,
and the amount of time between doses permit the examination of a large
number of potential research questions. Among the many questions about
the current immunization schedule that could be posed, the committee
parsed the phrase “this question” in Part 2 of the statement of task (Box
S-1) into four broad research questions of interest to stakeholders. These
are identified in Box S-2.
The committee broadly considered several general research strategies
that might be used to address these questions: randomized controlled trials
(RCTs), prospective and retrospective observational studies, animal models,
and secondary analyses of existing data.
Randomized Controlled Trials
When it is possible to randomize study participants, the RCT is widely
acknowledged to be the preferred study design for determining cause and
effect. RCTs are currently used as part of the FDA approval process to
evaluate the safety and effectiveness of individual vaccines in the context
of the recommended immunization schedule. Although this is the strongest
type of study design, the committee concluded that costs, the large number
of participants that would be required, ethical concerns, and other factors
make it an inappropriate design for addressing the research questions at
hand.
RCTs require participants to be randomly assigned to a study group.
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SUMMARY 7
BOX S-2
Leading Research Questions of Interest to Select Stakeholders
1. ow do child health outcomes compare between those who re-
H
ceive no vaccinations and those who receive the full currently
recommended immunization schedule?
2. ow do child health outcomes compare between (a) those who
H
receive the full currently recommended immunization schedule and
(b) those who omit specific vaccines?
3. children who receive the currently recommended immunization
For
schedule, do short- or long-term health outcomes differ for those
who receive fewer immunizations per visit (e.g., when immuniza-
tions are spread out over multiple occasions), or for those who
receive their immunizations at later ages but still within the recom-
mended ranges?
4. o potentially susceptible subpopulations—for example, children
D
from families with a history of allergies or autoimmune diseases—
who may experience adverse health consequences in association
with immunization with the currently recommended immunization
schedule exist?
However, the random placement of children into a study group in which
they would receive less than the full immunization schedule or no vaccines
would not be ethical because they would be exposed to a greater risk for the
development of diseases and community immunity would be compromised.
Furthermore, parents who reject vaccination likely would not allow their
children to be randomized to the group that receives full immunization.
Additionally, health care professionals serving participants placed in the
group to receive fewer or no vaccines would have to go against professional
medical guidelines that call on them to encourage patients to follow the
recommended schedule.
Even the use of a dispersed immunization schedule that is still within
the accepted ACIP time frame for vaccinations as a trial arm would re-
quire an increased number of clinic visits, often in rapid succession over
a period of a few weeks, which could prove difficult and costly for both
the clinics and participating families and may be unacceptable to insur-
ers if its improved effectiveness—measured as a decreased rate of adverse
outcomes—was negligible. Although the use of a different schedule that still
conforms to the ACIP vaccination time frame is unobjectionable ethically,
the committee cannot endorse this method as a feasible option.
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8 THE CHILDHOOD IMMUNIZATION SCHEDULE AND SAFETY
The conduct of an RCT would require thousands of participants to
be of sufficient size to answer questions about the outcomes of different
immunization schedules, and the study would have to span at least 6 to
10 years, meaning that it would likely cost the nation tens of millions of
dollars. The risks to participants’ health, the cost and time involved, and
the ethical challenges all make the conduct of an RCT unsuitable for ad-
dressing the research questions, at least until further work with secondary
data has been conducted.
New Prospective Observational Studies
Observational studies are another form of clinical research that can
provide useful insights and information that may be used to answer re-
search questions. The committee reviewed opportunities to study groups
that choose not to vaccinate using a prospective cohort study design. How-
ever, such a study would not conclusively reveal differences in health out-
comes between unimmunized and fully immunized children for two main
reasons. First, to be informative, cohort studies require sufficiently large
numbers of participants in each study group and the sample populations
often suggested for use in a comparison of vaccinated and unvaccinated
children (such as some religious groups) are too small to adequately power
a comparative analysis, particularly in the case of rare adverse health out-
comes. Because meaningful comparisons require thousands of participants
in each study group and less than 1 percent of the U.S. population refuses
all immunizations, the detection of enough unvaccinated children would be
prohibitively time-consuming and difficult.
Second, such a study would also need to account for the many con-
founding variables that separate some populations from the average U.S.
child, including lifestyle factors and genetic variables. To be useful, a com-
parison would require children matched by age; sex; geographic location;
rural, urban, or suburban setting; socioeconomic group; and race/ethnicity.
The committee acknowledges that large-scale, long-term studies of
infants through adulthood would be informative for evaluating health
outcomes associated with immunization. A new research initiative, the
National Children’s Study, is a multicenter, congressionally funded effort
that meets these criteria. Although such studies would be the optimal design
for evaluating long-term health outcomes associated with the childhood
immunization schedule, they would require considerable time and fund-
ing, and the committee did not find adequate epidemiological evidence to
recommend investment in this type of research at this time.
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SUMMARY 9
Secondary Analyses of Existing Data
The most feasible approach to studying the safety of the childhood
immunization schedule is through analyses of data obtained by VSD. VSD
is a collaborative effort between CDC and 9 managed care organizations
that maintain a large database of linked data for monitoring immunization
safety and studying potential rare and serious adverse events. VSD member
sites include data for more than 9 million children and adults receiving
vaccinations on a variety of immunization schedules. However, children
who are vaccinated on alternative schedules (including those who are not
vaccinated) may differ in meaningful ways. Although this confounding can
be minimized through matching and controlling for variations, differences
in nonrandomly constructed cohorts cannot be fully accounted for by the
use of these data.
The committee discussed several potential modifications that could
be introduced into this system that would enable new analyses of the key
research questions (Box S-2), including collection of additional data on the
participants. The committee found that secondary analyses within VSD
would advance knowledge of the safety of the immunization schedule and
identified enhancements to improve the data in VSD.
Animal Models
The committee also reviewed the potential for animal studies to be used
to study the childhood immunization schedule. Given the committee’s rec-
ognition of the complexity of the immunization schedule, the importance of
family history, the role of individual immunologic factors, and the complex
interaction of the immunization schedule with the health care system, the
committee determined that it was more appropriate to focus future research
efforts on human research.
Population Impacts of Alternative Schedules
The committee agreed that evaluations of the recommended immuniza-
tion schedule need to be attentive to effects at the population level as well
as the individual level. Attempts to quantify the relative safety of contrast-
ing immunization schedules need to take into account at least two separate
health outcomes: adverse events after the administration of specific vaccines
and the overall immunization schedule, and the respective impacts of alter-
native schedules on the circulation of vaccine-preventable diseases and the
consequent adverse outcomes associated with infection.
The intimate association between immunization and age-specific dis-
ease incidence needs to be addressed. Specifically, any changes in the immu-
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10 THE CHILDHOOD IMMUNIZATION SCHEDULE AND SAFETY
nization schedule that lead to an increase in exposure to preventable disease
will increase the spread of the pathogens responsible for these diseases. The
population-level impacts of such an outcome would be a simultaneous rise
in the incidence of infectious diseases and a reduction in the age at which
these illnesses are contracted. Thus, not only is the risk of exposure to
preventable diseases increased, but the severity of infection, which is age
dependent, is also likely to increase.
CONCLUSIONS ABOUT STAKEHOLDER CONCERNS
The committee identified concerns among some parents about the num-
ber, frequency, and timing of immunizations in the overall immunization
schedule. These concerns were not expressed by clinicians, public health
personnel, or policy makers in the committee’s review. Among the last three
groups, the childhood immunization schedule is considered one of the most
effective and safest public health interventions available to prevent serious
disease and death. Furthermore, the committee’s review of the literature
did not find high quality evidence supporting safety concerns about the
immunization schedule.
In its role to ensure vaccine safety, the federal government has em-
phasized the engagement of stakeholders in multiple activities. However,
an effective national vaccine program will require a more complete and
systematic collection of information about stakeholder concerns about
vaccine safety, the severity of vaccine-preventable diseases, individual- and
population-level immunization rates, the efficacy of immunization, and the
delivery and supply of vaccines recommended in the childhood immuniza-
tion schedule.
To more effectively implement immunization programs, a robust com-
munication and engagement strategy that includes careful study of safety
concerns is needed. Currently, the designs used in most studies of immuni-
zations do not permit a detailed analysis of the impact of parental concerns
on the decision to immunize their children. Most concerns about safety
are expressed by parents, but multiple stakeholders should be included
in NVPO efforts. For example, even health care providers with much
knowledge about individual vaccines may have less information about the
effects of administering multiple vaccines at a single visit or the timing of
the immunizations.
Recommendation 4-1: The committee recommends that the National
Vaccine Program Office systematically collect and assess evidence re-
garding public confidence in and concerns about the entire childhood
immunization schedule, with the goal to improve communication with
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SUMMARY 11
health care professionals, and between health care professionals and
the public regarding the safety of the schedule.
CONCLUSIONS ABOUT SCIENTIFIC FINDINGS
The committee encountered two major issues in its review of the find-
ings in the scientific literature. First, the concept of the immunization
“schedule” is not well developed. Most vaccine-related research focuses
on the outcomes of single immunizations or combinations of vaccines ad-
ministered at a single visit. Although each new vaccine is evaluated in the
context of the overall immunization schedule that existed at the time of
review of that vaccine, elements of the schedule are not evaluated once it is
adjusted to accommodate a new vaccine. Thus, key elements of the entire
schedule—the number, frequency, timing, order, and age at administration
of vaccines—have not been systematically examined in research studies.
The second major issue that the committee encountered was uncertainty
over whether the scientific literature has addressed all health outcomes and
safety concerns. The committee could not tell whether its list was complete
or whether a more comprehensive system of surveillance might have been
able to identify other outcomes of potential significance to vaccine safety. In
addition, the conditions of concern to some stakeholders, such as immuno-
logic, neurologic, and developmental problems, are illnesses and conditions
for which etiologies, in general, are not well understood.
Finally, the committee found that evidence assessing outcomes in sub-
populations of children who may be potentially susceptible to adverse
reactions to vaccines (such as children with a family history of autoim-
mune disease or allergies or children born prematurely) was limited and is
characterized by uncertainty about the definition of populations of interest
and definitions of exposures and outcomes.
In summary, to consider whether and how to study the safety and
health outcomes of the entire childhood immunization schedule, the field
needs valid and accepted metrics of the entire schedule (the “exposure”)
and clearer definitions of health outcomes linked to stakeholder con-
cerns (the “outcomes”) in rigorous research that will ensure validity and
generalizability.
Recommendation 5-1: To improve the utility of studies of the entire
childhood immunization schedule, the committee recommends that the
National Vaccine Program Office develop a framework that clarifies
and standardizes definitions of
• key elements of the schedule,
• relevant health outcomes, and
• populations that are potentially susceptible to adverse events.
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12 THE CHILDHOOD IMMUNIZATION SCHEDULE AND SAFETY
CONCLUSIONS ABOUT RESEARCH METHODS
Vaccine safety is critically important, but a determination of safety is
ultimately a value judgment. For example, some might believe that a serious
adverse event that occurs once in 1 million doses is “safe enough” relative
to the benefit of preventing a serious disease, whereas others may consider
that risk unacceptably high. The committee did not set a specific numerical
target or goal for what should be considered “safe enough.” Instead, based
on the literature, the committee made a judgment that failed to link adverse
effects to schedule exposures or multiple immunizations, concluding that
there is no evidence that the schedule is not safe.
The committee identified four broad research questions of interest to
stakeholders (Box S-2) and discussed general research approaches that
could be used to address these questions. Setting of priorities for research
will be challenging. The committee proposes a process for setting research
priorities that incorporates epidemiological and other evidence (formal
systematic reviews), biological plausibility, feasibility, and stakeholder con-
cerns. Before HHS agencies, such as CDC, FDA, the National Institutes of
Health, and NVPO, initiate further research on the entire immunization
schedule, a thorough review of the biological plausibility of the associa-
tion of a particular outcome with an aspect of the immunization schedule
should be conducted.
Recommendation 6-1: The committee recommends that the Depart-
ment of Health and Human Services incorporate study of the safety
of the overall childhood immunization schedule into its processes for
setting priorities for research, recognizing stakeholder concerns, and
establishing the priorities on the basis of epidemiological evidence,
biological plausibility, and feasibility.
The decision to initiate further studies should depend on the evaluation
of three considerations that the committee identified through its review of
stakeholder concerns and scientific findings:
1. epidemiological evidence of potential adverse health outcomes
associated with elements of the immunization schedule (such as
postmarketing signals or indications of an elevated risk from ob-
servational studies);
2. biological plausibility supporting hypotheses linking specific as-
pects of the immunization schedule with particular adverse health
outcomes; and
3. expressed stakeholder concerns about the immunization schedule’s
safety, which should initiate efforts to explore the previous two
considerations.
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SUMMARY 13
The committee acknowledges the evidence that reduced immunization
coverage is associated with increases in the incidence of vaccine-preventable
disease and found inconsistent and anecdotal evidence to imply that the rec-
ommended immunization schedule is not safe. Moreover, existing adverse
event detection systems provide confidence that the existing childhood im-
munization schedule is safe, and the committee recognizes that the federal
government invests considerable resources to ensure vaccine safety. How-
ever, some stakeholders have suggested that further research is warranted,
such as a comparison of vaccinated children with unvaccinated children or
children immunized on alternative schedules.
It is possible to make this comparison through analyses of patient infor-
mation contained in large databases such as VSD, but it would be unethical
and infeasible to conduct an RCT, as summarized above and detailed in
Chapter 6. Because an RCT would increase the risk of preventable diseases
in individuals and in the community and entail significant amounts of time,
money, and other resources, the committee concludes that new RCTs of the
childhood immunization schedule are not justified at this time.
Recommendation 6-2: The Department of Health and Human Services
should refrain from initiating randomized controlled trials of the child-
hood immunization schedule that compare safety outcomes in fully
vaccinated children with those in unvaccinated children or those vac-
cinated by use of an alternative schedule.
The committee concludes that secondary analyses of existing data
are more promising approaches to examination of the research questions
identified by the committee in future studies of the childhood immuniza-
tion schedule. VSD is a useful collaborative project for conducting both
postmarketing surveillance and longer-term targeted research. The ability
to augment the routinely collected administrative data in VSD with parent
interviews and reviews of medical records for selected study populations is
an important strength.
VSD is currently the best available system for studying the safety of the
immunization schedule in the United States. VSD should strive to improve
its generalizability to the U.S. population by enhancing the quality of its de-
mographic information or by expanding its scope to include more diversity
in its study populations. Secondary analyses with data from other existing
databases could also be feasible, ethical, and cost-effective in investigating
several of the research questions that the committee identified.
The committee recognizes that the currently funded managed care orga-
nizations’ commitment to VSD studies needs to remain high to continue and
build on existing efforts. The committee concludes that VSD is a valuable
component of the federal research infrastructure and will be the best-suited
source of data for studying the childhood immunization schedule. VSD’s
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14 THE CHILDHOOD IMMUNIZATION SCHEDULE AND SAFETY
utility will be expanded with the addition of more detailed demographic
data and family medical histories.
Recommendation 6-3: The committee recommends that the Depart-
ment of Health and Human Services (HHS) and its partners continue to
fund and support the Vaccine Safety Datalink project to study the safety
of the recommended immunization schedule. Furthermore, HHS should
consider expanding the collaboration with new health plan members
and enhancing the data to improve its utility and generalizability.
CONCLUDING OBSERVATIONS
The committee’s efforts to identify priorities for recommended re-
search studies did not reveal an evidence base suggesting that the child-
hood immunization schedule is linked to autoimmune diseases, asthma,
hypersensitivity, seizures, child developmental disorders, learning disorders
or developmental disorders, or attention deficit or disruptive behavior dis-
orders. Although stakeholder concerns should be one of the elements used
to drive searches for scientific evidence, these concerns alone, absent epide-
miological or biological evidence, do not warrant the initiation of high-cost
research studies. The committee concludes that the use of existing data from
database systems to conduct observational studies offers the best means for
ongoing research efforts about the immunization schedule’s safety.
The committee found no significant evidence to imply that the recom-
mended immunization schedule is not safe. Furthermore, existing surveil-
lance and response systems have identified known adverse events associated
with vaccination. The federal research infrastructure is a strong system. A
key component is the VSD project, which with ongoing support will be
able to feasibly address the committee’s research questions identified in
Box S-2. Although the committee concluded that protecting children from
vaccine-preventable diseases is of higher importance than testing alterna-
tive immunization schedules without epidemiological or biological evidence
indicating a safety problem, VSD should continue to examine the health
outcomes of people who choose alternative schedules.
Looking to the future, the committee supports the work of the federal
research infrastructure to ensure that stakeholders are involved in all stages
of the development, implementation, evaluation, and dissemination of the
immunization schedule. As electronic medical records become more com-
monly used, they may provide an opportunity to capture complete immu-
nization data linked with hospital discharge records, which will be useful
to future studies. Newer initiatives such as the National Children’s Study
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SUMMARY 15
and the Post-Licensure Rapid Immunization Safety Monitoring (PRISM)
program also hold promise in providing further study opportunities.
The childhood immunization schedule may become more complex
over time as scientific advances are made and new vaccines are developed
and incorporated into the schedule. Feasible research approaches to study
potential adverse health outcomes will emerge only with sustained and
substantial federal commitment to research on vaccine safety.
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