**Report from an Individual Simultaneous Consultation on the Centers for
Disease Control and Prevention's**

**Immunization Safety Office Research Agenda**

**May 10 and 11, 2007, Atlanta, GA**

Prepared on December 29, 2007 by Karen R. Broder, MD, Commander, United
States Public Health Services, Senior Medical Advisor, Immunization
Safety Office (ISO), Office of the Chief Science Officer, Centers for
Disease Control and Prevention (CDC) on behalf of the ISO External
Scientific Consultants:

-   Georges Peter, MD, Professor Emeritus, The Warren Alpert Medical
    School of Brown University (moderator)

-   Kevin Ault, MD, Associate Professor, Emory University School of
    Medicine (representing obstetrics and gynecology)

-   Claire Broome, MD, MPH, Adjunct Professor, Rollins School of Public
    Health, Emory University (representing epidemiology)

-   Penelope Dennehy, MD, Professor, The Warren Alpert Medical School of
    Brown University (representing pediatric infectious diseases)

-   David Relman, MD, Associate Professor, Stanford University School of
    Medicine (representing genomics)

-   William Schaffner, MD, Professor, Vanderbilt University School of
    Medicine (representing adult infectious diseases)

-   Christopher Wilson, MD, Professor, University of Washington School
    of Medicine (representing immunology)

Disclaimer: The ideas and recommendations of this report reflect those
of the individual consultants. This report does not represent Centers
for Disease Control and Prevention (CDC) or Department of Health and
Human Services policy, nor does it necessarily reflect which ideas will
be incorporated into CDC's final Immunization Safety Office Research
Agenda. This report from the consultants will be provided to the
National Vaccine Advisory Committee Subcommittee on Vaccine Safety as
background for its scientific review of the ISO Research Agenda.

**[Table of Contents]{.underline}**

  --------------------------------------------------------------- --------
  **Topic**                                                       **Page
                                                                  \#**

  Title page                                                      1

  Table of Contents                                               2

  Executive Summary                                               3-4

  Background                                                      5

  Charge to Individual Consultants                                5

  Approach                                                        5-7

  Summary of Key Input from Brainstorming Sessions                7-15

  Life-stages Sessions                                            7-13

  Cross-cutting Sessions                                          13-15

  Summary of Input from Individual Consultant Presentations       16-20

  Pediatric Infectious Diseases                                   16

  Adult Infectious Diseases                                       17

  Obstetrics and Gynecology                                       17-18

  Immunology                                                      18

  Genomics                                                        18-19

  Epidemiology                                                    19-20

  List of Abbreviations                                           21

  List of Appendices                                              22

  Appendices                                                      \-\--
  --------------------------------------------------------------- --------

**[Executive Summary:]{.underline} Individual Simultaneous Consultation
on the Immunization Safety Office Research Agenda**

[Background]{.underline}

-   In response to an Institute of Medicine (IOM) recommendation and as
    part of its strategic planning, the Centers for Disease Control and
    Prevention's (CDC) Immunization Safety Office (ISO) is developing an
    ISO research agenda that includes, but is not limited to, the
    Vaccine Safety Datalink (VSD) project. This research agenda will
    have a 3-to-5 year horizon and is being developed with extensive
    partner and expert input.

-   After the initial phase of the process, the National Vaccine
    Advisory Committee (NVAC) will conduct a scientific review of a
    draft ISO research agenda and provide feedback to CDC.

-   To initiate the process of developing the ISO research agenda and to
    inform its development, ISO convened an individual simultaneous
    consultation with seven peer-recommended external scientists in
    Atlanta, GA on May 10 and 11, 2007.

-   One scientist served as the moderator for discussions during the
    meeting. The scientists represented the fields of pediatric
    infectious diseases, adult infectious diseases, obstetrics and
    gynecology, immunology, genomics, and epidemiology.

[Charge to Individual Consultants:]{.underline}

-   To identify vaccine safety topics and gaps in knowledge that will be
    important for public health and could be studied by ISO.

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-   To advise on prioritization of the topics.

-   To propose potential approaches to study the topics.

[Approach]{.underline}

-   During the meeting, several brainstorming discussions were held to
    generate ideas. The discussion sessions were based on 1) five life
    stages (i.e., infant, child, non-pregnant adolescent, non-pregnant
    adult, and pregnant women), and 2) cross-cutting areas (i.e.,
    vaccine safety public perception; adjuvants, other non-antigen
    vaccine components, and new vaccine technologies; surveillance; and
    clinical outcomes that occur years after vaccination)

-   Consultants completed feedback worksheets for each of these
    sessions. In addition, six consultants gave oral presentations of
    their individual recommendations.

-   An ISO medical officer reviewed consultant input from the
    discussions, presentations, and worksheets and summarized the
    suggestions into scientifically relevant categories.

-   This report:

    -   Expresses ideas that represent the individual opinions of
        consultants; no attempt was made to achieve consensus.

    -   Does not necessarily depict the topics or prioritization of
        topics that will be included on the ISO research agenda; some
        suggestions from consultants may not be relevant to the ISO
        research agenda because they are underway or have been
        adequately addressed, are outside the scope of ISO's mission, or
        are not research areas.

[Findings]{.underline}

Overall, the key vaccine safety research areas identified during the
individual simultaneous consultation were:

-   Vaccine-specific

    -   Safety monitoring for new vaccines or vaccines with new
        indications; *examples are: rotavirus vaccine, live, attenuated
        influenza vaccine (LAIV), human papillomavirus (HPV) vaccine,
        and zoster vaccine.*

    -   Safety of vaccines when used for a purpose different from one of
        the indications for which the product is approved by the Food
        and Drug Administration (FDA) (i.e., "off label" use): *examples
        include use of rotavirus vaccine in infants outside the
        FDA-approved age-range; the use of tetanus toxoid, reduced
        diphtheria toxoid and acellular pertussis vaccine (Tdap) in
        older persons; and LAIV use in persons with chronic medical
        conditions.*

    -   Safety of combination vaccines

    -   Safety of annual influenza vaccines across the life stages

    -   Safety of pandemic influenza vaccines across the life stages

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-   Host factors which might predispose an individual to vaccine adverse
    events (VAEs)

    -   Demographic factors; *examples are gender and race*

    -   Underlying medical conditions; *examples are inborn errors of
        metabolism, prematurity, asthma, and diabetes.*

    -   Genetic factors; *an example is identifying genetic
        polymorphisms associated with VAEs through the use of
        genome-wide association studies.*

-   Clinical outcomes

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-   VAEs potentially associated with particular vaccines; *examples are
    intussusception after rotavirus vaccine and wheezing after LAIV*.

-   Outcomes reported or alleged to occur after a variety of vaccines;
    *examples include demyelinating disorders, autoimmune diseases, and
    neurodevelopmental disorders.*

-   Background rates of health conditions that occur during particular
    life-stages that could be helpful to assess risk for VAEs in these
    life stages; *examples are cardiac disorders in older adults and
    thromboembolic events in adolescents using oral contraceptives.*

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-   Immune pathophysiologic mechanisms which may lead to VAEs; *an
    example is characterizing the development of the immune system at
    different stages of life, including pregnancy, and how these changes
    may relate to risk for VAEs.*

-   Safety of various adjuvants and non-antigen components of vaccines;
    *examples include, new adjuvants that contain Toll-like receptor
    agonists, conjugate proteins, and exipients.*

-   Epidemiologic research and surveillance areas; *examples are use of
    signal detection algorithms to detect potential adverse events,
    approach(es) for rapid signal assessment, design and validation of
    more specific case definitions, assessment of sources for rapid
    unbiased case ascertainment, selection of appropriate comparison
    groups, and data analysis approaches regarding association of an
    outcome with a vaccine.*

-   Risk perception; *examples include tracking public perception of
    vaccine safety issues and identifying effective strategies to
    communicate accurate risk information with the public, clinicians
    and media.* *Autism was identified as one example of a perceived
    vaccine safety concern.*

**[Background]{.underline}**

CDC's Immunization Safety Office (ISO) is responding to a recommendation
from the 2005 Institute of Medicine (IOM) report, "Vaccine Safety
Research, Data Access and Public Trust."[^1] The IOM recommended that a
subcommittee of the National Vaccine Advisory Committee (NVAC) review
and provide advice on the Vaccine Safety Datalink (VSD) project research
plan. In addition, ISO has begun a strategic planning process and it was
recognized that an ISO research agenda would be an important component
of this plan. Because effective research requires collaboration among
all the ISO research and surveillance components, ISO is developing a
comprehensive scientifically robust research agenda with extensive
partner and expert input. This agenda will include, but is not limited
to, the VSD project, and it will have a 3-to-5 year horizon. A draft ISO
research agenda will be shared with the NVAC Subcommittee on Vaccine
Safety for its scientific review. NVAC will provide input about the
draft ISO research agenda to CDC and CDC/ISO will seriously consider
this advice as it finalizes the research agenda.

To initiate the process of developing the ISO research agenda and to
inform its development, ISO convened a meeting of individual expert
scientists in Atlanta, GA on May 10 and 11, 2007 (Appendices A and B).
Seven peer-recommended scientists representing the fields of pediatric
infectious diseases, adult infectious diseases, obstetrics and
gynecology, immunology, genomics, and epidemiology provided individual
simultaneous consultation. One of these scientists served as the
moderator for discussions during the meeting. In addition, seven liaison
representatives from federal agencies, advisory committees, ISO research
collaborations, and several staff persons from CDC's Immunization Safety
Office and the Office of the Chief Science Officer participated
(Appendix C).

**[Charge]{.underline}**

The charge to each external consultant was to: 1) identify emerging
vaccine safety questions and gaps in knowledge that will be important
for public health and could be studied by ISO, 2) advise on
prioritization of the topics and 3) propose some potential approaches to
study the topics.

**[Approach]{.underline}**

Before the meeting consultants received briefing materials about the ISO
program, including lists of research studies underway or planned
(Appendix D). They were asked to prepare presentations describing
important areas for vaccine safety research in their areas of expertise
and provide ideas on a framework for discussion during the meeting
(Appendix G). On the basis of input from teleconferences before the
meeting, the meeting included nine group brainstorming sessions. Five
covered life stages: infants aged \<1 year, children aged 1-10 years,
non-pregnant adolescents aged 11-18 years, non-pregnant adults aged ≥19
years, and pregnant women of all ages. Four were cross-cutting sessions
on: the role of public perception of vaccine safety in shaping the
research agenda, new vaccine technologies and non-antigen vaccine
constituents, vaccine safety surveillance, and vaccine adverse events
(VAEs) that occur years after vaccination. For each brainstorming
session, participants heard relevant background information, focusing on
vaccines recommended for routine use in the civilian population by the
Advisory Committee on Immunization Practices (ACIP).[^2] The moderator
then facilitated group discussion about the topics. At the end of each
brainstorming session, each consultant completed a feedback worksheet
asking about key research topics, prioritization, and some feasible
approaches to study the research topics (Appendix E). Liaisons and CDC
participants did not complete worksheets. In addition, six consultants
presented their individual recommendations by discipline during the
meeting (Appendix G). A detailed administrative summary of the meeting
is provided in Appendix A.

An ISO medical officer reviewed consultant input from the discussions,
presentations, and worksheets and summarized the suggestions into
scientifically relevant categories. This report provides a summary of
the full spectrum of individual input from the individual consultants to
ISO. It also contains the general themes that emerged during discussions
among all meeting participants. No attempt was made to achieve consensus
among the consultants; however, for ease of presentation in some
sections suggestions from two or more of the consultants are referred to
collectively as those from the "consultants." In practice, during the
meeting consultants thought broadly about vaccine safety issues, without
consideration of funding or program infrastructure or the ISO research
activities already underway. Some of the ideas expressed in this report
may not be relevant to the future ISO research agenda for the following
reasons: 1) they have already been adequately addressed or are underway
in ISO, 2) they are outside the scope of the ISO mission and would be
better studied by another program or agency, or 3) they are not research
activities.

**[Summary of Key Input from the Brainstorming Sessions]{.underline}**

In each section, we present a summary of the key themes that emerged
during the brainstorming sessions. For the life stages, consultant input
is categorized into five areas: 1) vaccine-specific, 2) host factors
which might predispose an individual to VAEs, 3) clinical outcomes, 4)
other research areas and 5) non-research areas. Clinical outcomes
include VAEs that have been reported or alleged to occur after a
particular vaccine or a variety of vaccines. The terms "vaccine adverse
event (VAE)" and "adverse event following immunizations (AEFI)" are used
interchangeably in this report and appendices and do not necessarily
imply that a particular clinical condition has been causally linked with
a vaccine exposure. If at least one consultant indicated the topic was a
high priority, it is marked with an **asterisk**\* in the list of
suggestions from each brainstorming session. Not all five areas were
addressed in each session. Ideas that were discussed in more than one
brainstorming section or in the consultant presentations are listed in
the most relevant session or cross-referenced. For each topic,
consultants were asked to suggest approaches that could be used:
large-linked database study, other epidemiologic study with or without
biological specimens, clinical trials and other study designs (Appendix
E). For most research topics, multiple approaches were suggested. For
some areas, basic science or behavioral research methods were
recommended.

1.  [Life Stage: Infants aged \<1 year]{.underline}

A. Background:

In May 2007, the following inactivated vaccines were routinely
recommended by the ACIP for infants aged \<1 year: diphtheria and
tetanus toxoids and acellular pertussis (DTaP), *Haemophilus influenza*
type b (Hib), pneumococcal conjugate vaccine (PCV7), inactivated polio
vaccine (IPV), hepatitis B, and trivalent inactivated influenza vaccine
(TIV) (for persons aged ≥6 months). In addition, DTaP-Hepatitis B- IPV
is currently licensed and a biologics license application (BLA) has been
submitted for DTaP-IPV-Hib. Rotavirus vaccine was the only live vaccine
routinely recommended by ACIP for infants in the United States.

B. Consultant Input: (see also Summary of Input from Individual
Consultant Presentations: Pediatric Infectious Diseases, page 16)

Vaccine-specific: Safety monitoring is needed for all newly licensed
infant vaccines.\* Specific suggested research areas are:

-   [Rotavirus vaccine]{.underline}:\* Consultants highlighted rotavirus
    vaccine safety as an important research area. The main clinical
    outcome of concern is intussusception (IS) which was associated with
    receipt of an earlier rotavirus vaccine that is no longer in use in
    the United States. A particular issue of concern is use of the
    vaccine outside the recommended age groups (e.g., administration of
    dose one after 12 weeks of age). Both large- linked databases and
    other epidemiologic study methods could be used to assess risk for
    IS after rotavirus vaccine; case control studies in populations
    larger than the VSD may be needed. Consultants noted that another
    rotavirus vaccine (human attenuated formulation) would be submitted
    for a BLA in the near future (it was submitted in 6/2007[^3]);
    comparing safety profiles between two rotavirus vaccines, if this
    second rotavirus vaccine is licensed, would be important. Other
    suggestions were to evaluate the effect of maternal rotavirus
    antibody concentrations on risk for infant reactogenicity after
    rotavirus vaccination and the extent of viral shedding in rotavirus
    vaccine recipients.

-   [Influenza vaccines]{.underline}:\* Influenza vaccine safety (TIV
    and live, attenuated influenza vaccine \[LAIV\]) is important for
    annual vaccination programs and pandemic preparedness. Consultants
    suggested researching the safety of LAIV in infants, an off-label
    population[^4]. A specific concern is risk for wheezing events,
    including reactive airway disease and asthma. Multiple approaches
    could be used to study

> [Life Stage: Infants (continued)]{.underline}
>
> influenza vaccine safety. Consultants commented that there are no data
> on safety of pandemic influenza vaccines in this population.

-   [Combination vaccines]{.underline}:\* Consultants emphasized the
    need to study the safety of combination vaccines before and after
    licensure in infants. One could assess if risk for VAEs were higher
    after combination vaccines or after the individual vaccines, using
    multiple methods. It was noted that combination vaccines might be
    more reactogenic than the individual vaccines, administered
    simultaneously. Specific clinical outcomes of concern were not
    described. It is important to figure out which component of a
    combination vaccine is associated with a particular VAE. It was
    noted that several new combination vaccines are in the pipeline,
    including a Hib/meningococcal vaccine.

-   [Bioterrorism vaccines:]{.underline}\*: VAEs after administration of
    vaccines for bioterrorism preparedness or response has generally not
    been evaluated in infants.

Host factors which might predispose an individual to VAEs:

-   [Premature infants]{.underline}:\* There is a paucity of data on
    vaccine safety in premature and low birth weight infant populations.
    Both of these populations have been increasing in size in recent
    years in the United States. It was suggested that premature infants
    may have increased rates VAEs after vaccination. A consultant asked
    if risk for apnea and bradycardia might be increased in this
    population after vaccination. Another suggestion was to evaluate the
    effect of maternal antibody on risk for reactogenicity after
    vaccination in premature infants.

-   [Low birth weight infants]{.underline}:\* Similar principles as
    described for premature infants apply. Very low birth weight infants
    were a population of particular concern.

-   [Infants with genetic and metabolic disorders]{.underline}:\*
    Similar principles as described for premature infants apply. A
    consultant raised concern that fever following vaccination in this
    population may be clinically important.

-   [Genetic risk factors:]{.underline} \* [(]{.underline}see Summary of
    Input from Individual Consultant Presentations: Genomics, pages
    18-19)

Clinical outcomes:

-   [Consultants suggested establishing baseline rates]{.underline} of
    clinical conditions that have been reported as VAEs so that accurate
    assessment of any potential risk can be determined. In particular,
    they suggested assessing baseline rates of neurodevelopmental
    disorders. One consultant advised that establishing baseline rates
    in isolation is a not useful activity (see also Summary of Input
    from Individual Consultant Presentations: Epidemiology, pages
    19-20).

Other research areas: Multiple approaches, including basic science and
genomics research, could be used to study the following areas:

-   [Responses to vaccine adjuvants]{.underline}\* (see Cross-cutting
    Sessions: Non-antigen Vaccine Constituents and New Vaccine
    Technologies, page 14)

-   [Simultaneous administration]{.underline} of multiple vaccines

-   [Public acceptance of vaccines]{.underline} (see Cross Cutting
    Sessions: Role of Public Perception in Shaping the Research Agenda,
    pages 13-14))

-   [Effect of mode of delivery]{.underline} on adverse events, e.g.
    oral route

[Life Stage: Infants (continued)]{.underline}

-   [Characterization of immunological immaturity and development of
    immune response]{.underline} to understand and possibly predict the
    risk for a VAE.\*

-   [Impact of vaccination on human indigenous flora and heterologous
    disease]{.underline} (most important age group to assess), and the
    role of indigenous microbiota in determining the nature of the host
    response to vaccines.

-   [Environmental risk factors which may influence the occurrence of
    VAEs.]{.underline}\*

-   [Recognition of VAEs]{.underline}: A consultant asked how well we
    are able to recognize VAEs in the infant age group.

2.  [Life Stage: Children aged 1−10 years]{.underline} (see also Summary
    of Input from Individual Consultant Presentations: Pediatric
    Infectious Diseases, page 16)

A. Background

In May 2007, excluding catch-up vaccination, ACIP recommended several
inactivated vaccines for children aged 1-10 years: DTaP, IPV, hepatitis
A, PCV7, Hib, and TIV (aged \<5 years and children with high-risk
indications). Meningococcal polysaccharide vaccine (MPS4) and
pneumococcal polysaccharide vaccine (PPV23) were recommended for certain
high-risk children. Biologics license applications (BLA) had been
submitted for DTaP-IPV-Hib and meningococcal conjugate vaccine (MCV4)
(licensed for use in children aged 2-10 years 10/07). Four live vaccines
were used in children: measles, mumps, rubella (MMR), varicella, MMRV
(combination MMR and varicella), and live, attenuated influenza vaccine
(LAIV). Recently ACIP recommended that a second dose of varicella
vaccine be administered to children aged 4-6 years. In May 2007, LAIV
was licensed for persons aged \>=5 years and a biologics license
application had been submitted to revise the license to included
children aged 12-59 months (LAIV was licensed for use in children aged
24-59 months in September 2007).

B. Consultant Input

Vaccine-specific: New vaccines are an area of interest.

-   [Influenza vaccines safety]{.underline}:\* The principles from the
    infant life stage section of the report apply (see also Summary of
    Key Input from Brainstorming Sessions \[infant life stage\], page
    7). A specific area of interest is risk for wheezing, reactive
    airway disease, and asthma after LAIV. In addition to short-term
    wheezing events, risk for long-term pulmonary consequences should be
    studied. Researching the safety LAIV in children with chronic
    diseases, such as diabetes also was suggested. Because studies have
    suggested that LAIV, may have greater efficacy than TIV in children,
    studies comparing the risk/benefit profiles of LAIV and TIV may be
    useful.

-   [Combination vaccines:]{.underline} The same principles described in
    the infant life stage section of the report apply (see also Summary
    of Key Input from Brainstorming Sessions \[infant life stage\], page
    8).

Host factors which might predispose an individual to VAEs:

-   [Chronic disease\*]{.underline}: Consultants emphasized that
    inadequate safety data are available at the time of licensure for
    children with underlying medical conditions. Risk for VAEs should be
    assessed in children with chronic conditions. Specific

[Life Stage: Children]{.underline}

> underlying conditions mentioned were diabetes type 1 and 2 and
> reactive airways disease and asthma.

-   [Premature birth:]{.underline}\* The same principles described in
    the infant life stage apply (see also Summary of Key Input from
    Brainstorming Sessions \[infant life stage\], page 8).

-   [Gender]{.underline}: Consultants suggested assessing the influence
    of gender on VAEs.

Clinical outcomes

-   [Autism and other neurodevelopmental disorders:]{.underline}\*
    Consultants suggested establishing baseline rates of
    neurodevelopmental disorders, including autism. A goal is to improve
    objective diagnostics for cases definitions. Comprehensive studies,
    including genetic studies are needed to define the etiology of these
    conditions.

-   [Establishing baseline rates of other conditions reported as
    VAEs\*]{.underline} including inflammatory bowel disease, multiple
    sclerosis and Guillain-Barré Syndrome (GBS) was suggested. One
    consultant advised that establishing baseline rates in isolation is
    a not useful activity (see also Summary of Input from Individual
    Consultant Presentations: Epidemiology, pages 19-20).

-   [Diabetes types 1 and 2:]{.underline} At least one consultant
    suggested assessing whether vaccines play any role in the
    development of diabetes.

Other Research Areas: Multiple approaches, including basic science
research and genomics, could be used to study the following areas:

-   [Impact of immunization on human indigenous microbiota]{.underline}
    and the role of indigenous microbiota in determining the nature of
    the host response to vaccines

-   [Long-term sequelae of adverse events]{.underline} (see
    Cross-cutting Session on Adverse Events that Occur Years after
    Vaccination, p 15).

3.  [Life Stage: Adolescents aged 11−18 years
    (non-pregnant)]{.underline}

A. Background:

During 2005 and 2006, ACIP recommended three new vaccines for
adolescents: tetanus toxoid, reduced diphtheria toxoid, and acellular
pertussis vaccine (Tdap, two products), tetravalent meningococcal
conjugate vaccine (MCV4), and quadrivalent human papillomavirus (HPV)
vaccine (females only). In May 2007, influenza vaccine, pneumococcal
polysaccharide vaccine (PPV23) and hepatitis A vaccines were recommended
for certain high-risk populations. In addition, a second dose of
varicella vaccine has been recommended for adolescents without a history
of varicella disease.

B. Consultant Input:

Vaccine-specific

[HPV vaccine]{.underline}:\* Safety monitoring is needed for the HPV
vaccine − a vaccine that one consultant described as a "sensitive"
vaccine. Studies should assess for rare adverse events. Optimal timing
of booster doses should also be explored. Consultants suggested studying
safety in the younger group of girls recommended for vaccination (e.g.,
aged 9 to 15 years). A BLA has been submitted for a bivalent HPV
vaccine. It contains a novel adjuvant ASO4 (contains aluminum hydroxide
and 3-deacylated monophosphoryl lipid A). Post-licensure safety
monitoring will be important if this HPV vaccine is licensed. It [Life
Stage: Adolescents (continued)]{.underline}

> was mentioned that HPV vaccine might be licensed for use in males in
> the future
>
> (see also Summary of Input from Individual Consultant Presentations:
> Obstetrics and Gynecology, pages 17-18).

-   [Td-to-Tdap interval]{.underline}:\* Consultants suggested assessing
    the safety of short intervals between these two tetanus and
    diphtheria toxoid-containing vaccines using large-linked databases
    or other epidemiologic methods.

-   [Varicella]{.underline}: Studying safety of the second dose in
    adolescents was suggested

Clinical outcomes

-   [Guillain-Barré Syndrome (GBS) and demyelinating
    disorders]{.underline}:\* Establishing baseline rates of GBS and
    other demyelinating disorders was suggested for males and females.
    Research should address mechanisms and risk factors, including
    genetic risk factors, for development of GBS. National Institutes of
    Health (NIH) involvement might be useful.

-   [Other autoimmune disorders]{.underline}: The same principles as
    described for GBS apply.

-   [Baseline rates of other conditions]{.underline}: Because many
    vaccinees may also be using oral contraceptives, establishing
    baseline rates for adverse events associated with oral contraceptive
    use would be useful to help interpret signals after vaccination
    (e.g., rates of thromboembolic events). Also consultants suggested
    establish baseline rates of adolescent psychiatric diseases\* and
    conditions, including suicide. One consultant advised that
    establishing baseline rates in isolation is not a useful activity
    (see also Summary of Input from Individual Consultant Presentations:
    Epidemiology, pages 19-20

Other research areas

-   [Adolescent perceptions:]{.underline} Explore adolescent perceptions
    of vaccine safety and the influence of these beliefs on uptake of
    adolescent vaccines\*

-   [Monitoring for HPV serotype replacement]{.underline}

4.  [Life Stage: Adults aged ≥19 years (non-pregnant)]{.underline}

A. Background

In May 2007, ACIP recommended that adults receive Td boosters, annual
influenza vaccine if aged \>=50 years, and PPV23 if \>=65 years. In
2006, ACIP had provisionally recommended the first live vaccine for
routine use in older adults: zoster vaccine. Also a single dose of Tdap
is recommended for adults aged \<65 years to replace a dose of Td. In
addition, it is recommended that adults with medical or social risk
factors receive certain other vaccines, including biodefense and travel
vaccines.

B. Consultant Input: Consultants recommended studying safety of vaccines
used in persons who were not included in the licensed or recommended
groups (i.e., off label use of vaccine) (see also Summary of Input from
Individual Consultant Presentations: Adult Infectious Diseases, page
17).

Vaccine-specific

-   [Zoster]{.underline}:\* The safety of zoster vaccine should be
    assessed in the recommended population of adults in persons in
    groups that are not recommended for vaccination, including those
    with certain medical conditions and persons aged \<60 years. An
    additional interest is safety of the vaccine in persons with a
    history of zoster.

[Life Stage: Adults (continued)]{.underline}

-   [Influenza:]{.underline}\* The principles from the infants and
    children life stages sessions apply; a continuing concern is to
    understand the association between TIV and GBS. Consultants also
    suggested that LAIV safety should be studied in adults not currently
    recommended for vaccination, including older adults and those with
    chronic conditions that put them at risk for influenza disease. At
    least one consultant suggested that a risk-benefit analysis be
    conducted in older adults for LAIV and TIV use. Safety of new
    influenza vaccine adjuvants should be studied.

-   [Tdap]{.underline}: Safe Td-to-Tdap intervals and off-label use in
    persons aged ≥65 years should be studied.

Host factors which might predispose an individual to VAEs:

-   [Older persons]{.underline}:\* Immune function may decline with age
    in older persons and this phenomenon may impact risk for VAEs and
    should be studied.

-   [Gender differences]{.underline} in vaccine AEs are an important
    area to study since rates and etiology of the adverse event may
    differ by gender. A specific concern is the influence of gender on
    risk for local reactions and arthritis after vaccination.

Clinical Outcomes:

-   [Adult chronic diseases:]{.underline}\* Assessing associations
    between vaccines and VAEs and establishing baseline rates of various
    chronic diseases in adults were suggested. The following conditions
    were emphasized: cardiac, rheumatologic and autoimmune diseases, and
    chronic fatigue syndrome. One consultant advised that establishing
    baseline rates in isolation is not a useful activity (see also
    Summary of Input from Individual Consultant Presentations:
    Epidemiology, pages 19-20).

Other Research Areas

-   [Vaccine acceptance]{.underline}:\* Explore adult perceptions of
    vaccine safety and the influence of these beliefs on uptake of adult
    vaccines.

-   [Reporting issues for VAEs in adults]{.underline}:\* Underreporting
    of VAEs in adults may be greater than in younger age groups. It is
    important to understand reporting practices among vaccine providers
    for adults and adult vaccinees

-   [Therapeutic vaccines safety]{.underline}: Research issues may not
    be the same for therapeutic vaccines as they are for preventive
    vaccines. Therapeutic vaccines may be used for infectious or
    non-infectious diseases.

Non-research Area:

-   [Reporting practices]{.underline}: It is important to educate adult
    healthcare providers and vaccinees about the need to report VAEs to
    the Vaccine Adverse Events Reporting System (VAERS).

5.  [Life Stage: Pregnant women]{.underline}

Background

In May 2007, the only vaccine routinely recommended for pregnant women
were TIV and Td. Live vaccines are generally contraindicated during
pregnancy. Vaccines to prevent type 2 herpes virus infections are being
studied in clinical trials.[^5]

Consultant Input: (see also Summary of Input from Individual Consultant
Presentations: Obstetrics and Gynecology, pages 17-18)

Vaccine-specific

-   [TIV:]{.underline} The safety of TIV use during pregnancy,
    particularly during the first trimester should be studied. It was
    noted that only a minority of obstetricians administer influenza
    vaccine to pregnant women, even though the vaccine is routinely
    recommended for pregnant women.\*

-   [Tdap:]{.underline} The safety of Tdap use during pregnancy should
    be studied.\* A particular concern is whether maternal vaccination
    with Tdap interferes with the infant response to pertussis antigens
    in pediatric DTaP. \*

-   [HPV vaccine]{.underline}: Safety in pregnant women should be
    studied through large-linked database studies or clinical trials.

-   [Herpes simplex virus (HSV) vaccine]{.underline}: At least one
    consultant suggested that the safety of HSV vaccine in pregnant
    women should be studied in clinical trials. It was not specified if
    these studies should occur before or after potential licensure for
    this vaccine.

Other Research Issues

-   [Pregnancy registries:]{.underline} These should be used to study
    the safety of vaccines administered during pregnancy, including
    vaccines inadvertently administered.\*

-   [Infant follow-up]{.underline}: Infants should be followed long-term
    after maternal vaccination; specific putative VAEs were not
    described.

-   [Immune response]{.underline}: The nature of immune function changes
    during pregnancy and should be studied.

Non-research.

-   [Liability]{.underline}: At least one consultant noted that
    liability issues related to use of vaccines in pregnancy women
    should be addressed.\*

6.  [Cross-cutting: Role of Public Perception in Shaping the Vaccine
    Safety Research Agenda]{.underline}

Consultants commented that understanding public perceptions is important
(see summary of consultant presentations). They highlighted three main
areas that should be addressed: 1) defining the general etiology of
autism and neurodevelopment disorders, 2) conducting behavioral research
related to vaccine safety perceptions and communication, and 3)
enhancing non-research communication activities related to vaccine
safety issues.

> [Cross-cutting: Role of Public Perception in Shaping the Vaccine
> Safety Research Agenda (continued)]{.underline}

Specific suggestions were:

> [Tracking public perceptions of vaccine safety]{.underline}:\*
> Consultants noted that questions from the public about vaccine safety
> persist and proliferate to a greater degree than do questions about
> other aspects of public health. Messages from the federal government
> about vaccine safety information may not be reaching the public.

-   [Activities to assess and enhance the effectiveness of vaccine
    safety communication messages to the public, healthcare
    professionals and media]{.underline}:\* A particular area of concern
    was communication around autism issues. Focus groups could be used
    to improve the effectiveness of messages. Consultants suggested that
    messages provide clear information about autism services, the lack
    of association between vaccines and autism, and current efforts to
    understand the etiologies of autism. They should also describe the
    positive benefits of vaccination. It was suggested that ISO needs to
    advocate for clear communication of all vaccine safety information.
    A consultant suggested identifying media relations strategies that
    work to communicate risk information accurately.

-   [Public Involvement]{.underline}: At least one consultant believed
    that communication issues should drive the research agenda and that
    the public should provide input for this research agenda.

-   [Research to define the pathogenesis and biological basis of
    autism:]{.underline}\* Consultants suggested studying the etiologies
    of autism. At least one consultant believed this issue needed to be
    studied in a broad interagency manner, including evaluation of
    genetic factors. A consultant suggested conducting systematic
    reviews of existing data (see consultant presentation summaries)

-   [VAE reporting:]{.underline} At least one consultant suggested
    involving the public to enhance rates of VAE reporting.\* One
    consultant did not believe that the juice was "worth the squeeze"
    and suggested not focusing efforts on this non-research activity.

7.  [Cross-cutting: Non-antigen Vaccine Constituents and New Vaccine
    Technologies]{.underline}

Research areas:

-   [New adjuvants in vaccines]{.underline}:\* Understanding the safety
    of new adjuvants in vaccines was highlighted as an important
    research area throughout the consultation meeting. In the future it
    is anticipated that a larger number of vaccines will contain
    adjuvants, many of which will be new. The safety of adjuvants which
    are agonists of Toll-like receptors is a particularly important
    issue. An example of this type of novel adjuvant is ASO4 (aluminum
    hydroxide and 3-deacylated monophosphoryl lipid A). ASO4 is in the
    bivalent HPV vaccine (submitted for BLA); it induces an enhanced
    antibody response to HPV virus-like particles. ASO4 is currently
    used in hepatitis B vaccines in Europe. Future influenza vaccines
    will also contain new adjuvants. Defining mechanisms of
    immunopotentiation from new adjuvants is important. Improved assays
    for adjuvant responses would be useful. Understanding how new
    adjutants perform in the different age groups was suggested.

[Cross-cutting: Non-antigen Vaccine Constituents and New Vaccine
Technologies (continued)]{.underline}

-   [Other areas]{.underline}: Assessing safety of other non-antigen
    components of vaccines (e.g., aluminum, conjugate proteins like
    diphtheria toxoid, exipients and adventitious agents) was suggested.
    In the future, assessing safety of DNA vaccines may be important.

Non-research area:

-   [Roles]{.underline}: Defining ISO's role in addition to FDA's and
    NIH's role for vaccine safety research related to adjuvants and
    non-antigen components is important.

8.  [Cross-cutting: Surveillance Considerations for Vaccine Safety
    Research and Adverse Events that Occur Years after
    Vaccination]{.underline}:[^6] (see also Summary of Input from
    Individual Consultant Presentations: Epidemiology, pages 19-20 and
    Summary of Key Input from Brainstorming Sessions: Life Stages, pages
    6-13)

Research Areas

-   [Case definitions]{.underline}:\* Use standardized nomenclature for
    reported vaccine AEs; use case definitions with greater specificity.
    Examples of long-term clinical outcomes of interest include
    autoimmune diseases, cancer, diabetes, and neurodevelopmental
    disorders\*

-   [Databases]{.underline}:\* Large-linked databases which can be
    rapidly accessed are needed. Obtain standardized sets of clinical
    data from vaccinees and controls, including information on gender.
    Consultants suggested expanding VSD; one consultant suggested that
    location of the sites should be more representative of the nation's
    population distribution. Consultants suggested improving systems to
    validate and standardize information from large-linked databases

-   [Background rates]{.underline} for clinical outcomes reported as
    VAEs should be characterized; improve surveillance protocols and
    databases to assess rates of chronic conditions reported after
    vaccination (see also Summary of Input from Individual Consultant
    Presentations: Epidemiology, pages 19-20).

-   [Response protocol:]{.underline} Standardize protocols for rapid
    collection of specimens and data after signals emerge; develop
    response protocols in the event that adventitious virus agents are
    identified in vaccines

-   [Genetic studies]{.underline}: Conduct genome-wide analyses to
    examine host susceptibility to VAEs; characterize genetic risk
    factors for reported AEs after vaccination

Non-research Area

-   [Phase 4 studies]{.underline}: Consider ISO's role in Phase 4
    studies. At least one consultant suggested formal CDC participation
    in Phase 4 studies. This consultant noted that expertise to do these
    studies is more likely to be with CDC vaccine subject matter
    experts, outside ISO, than within ISO. ISO might serve as a "neutral
    broker" and perhaps manage funding from vaccine manufacturers in an
    independent manner.

**[Summary of Input from the Individual Consultant
Presentations]{.underline}**

The following section presents a summary of presentations from each of
six consultants, representing six disciplines. Please see Appendix G for
the complete presentations, in their original form.

[Pediatric Infectious Diseases]{.underline}

Dr. Dennehy described eight key areas for research in order of
importance. She informally collected information from several sources to
prepare her presentation, including colleagues in pediatric infectious
diseases through the American Academy of Pediatrics (AAP) Committee on
Infectious Diseases (COID), practicing general pediatricians, and
parents.

The suggested vaccine safety research areas, in order of importance were
(#1 highest):

-   [#1 Misperception of vaccine risks by parents and the
    media:]{.underline} The most pressing concern is about vaccines and
    the development of neurodevelopmental disorders, including autism.
    She identified 3 areas of research. First is the need to understand
    why thimerosal continues to be an issue. She speculates it is due to
    a misperception of risks by parents and the media and because
    thimerosal is a "convenient scapegoat" for autism, a devastating
    diseases. Second, the cause(s) of autism must be identified. Third,
    one needs to examine how best to communicate information about
    thimerosal and other vaccine safety issues to parents, healthcare
    providers and the media.

-   [#2 Risk of intussusception (IS) after rotavirus
    vaccination:]{.underline} Risk of IS after rotavirus vaccine among
    infants vaccinated outside the recommended age ranges (6 weeks to 32
    weeks) is an area of concern. Because this practice is not uncommon,
    she suggested review of existing large-linked databases. She also
    acknowledged the importance of post-licensure surveillance for the
    risk of IS after rotavirus vaccine that is ongoing.

-   [#3 Guillain-Barré Syndrome (GBS) and demyelinating disorders after
    vaccination]{.underline}: She suggested assessing baseline rates of
    GBS and other demyelinating disorders to compare with rates after
    vaccination.

-   [#4 Adverse events after live, attenuated influenza vaccine
    (LAIV):]{.underline} A specific concern is the risk for wheezing
    after vaccination. A review of post-licensure data in VSD using a
    self-control case series approach may be useful. Another area of
    interest is safety of LAIV administered to children with underlying
    diseases such as diabetes; LAIV is not currently recommended for
    persons with chronic conditions.

-   [#5 Adverse events following immunization (AEFI) in premature and
    low birth weight infants]{.underline}

-   [#6 AEFI in children with genetic and metabolic
    diseases]{.underline}

-   [#7 AEFI with combination vaccines]{.underline}

-   [#8 Safety of pandemic influenza vaccines and bioterrorism
    vaccines]{.underline}

[Adult Infectious Diseases]{.underline}

Dr. Schaffner described several areas of research for the adult life
stage (non-pregnant). He informally conducted a "mini-survey" of
colleagues to prepare his presentation. He noted that data from other
developed countries might also inform the research agenda. He
recommended post-licensure surveillance for US-licensed vaccines and off
label use of these vaccines, emphasizing specific concerns and gaps in
knowledge for four adult vaccines. Some of these areas are related to
use of the vaccines in a manner that is not consistent with licensure or
ACIP recommendations. The vaccine-specific areas are:

-   [Zoster vaccine]{.underline}: The safety of zoster in the following
    groups was not studied before licensure: persons with underlying
    conditions, particularly subtle immunocompromise, persons with a
    history of previous zoster, and persons aged \<60 years with
    different degrees of immune function.

-   [Tdap:]{.underline} The safe interval from Td-to-Tdap (two
    diphtheria and tetanus toxoid-containing vaccines).

-   [TIV:]{.underline} The risk of GBS after TIV

-   [LAIV:]{.underline} Use of LAIV in persons aged \>=50 years and in
    persons aged 5 to 49 years with chronic conditions (e.g., diabetes)

Dr. Schaffner believes that the importance of vaccine safety research is
measured by the following criteria: questions raised by parents, the
media, and the ACIP; legislation proposed by state legislators; and
lawsuits filed. He considers the most important current vaccine safety
issue in the United States to be in the area of "thimerosal and autism."
He highlighted other perceived associations as well (e.g., hepatitis B
vaccine and multiple sclerosis). He asked questions about the criteria
that should be used for selecting areas of public concern for the ISO
research agenda. He also asked which institutions should assume
responsibility for addressing these concerns (e.g., CDC, FDA, NIH,
vaccine manufacturers). Dr. Schaffner proposed that rigorous
evidence-based reviews be conducted for all major vaccine safety
questions raised by the public and emphasized the importance of
effective communication around vaccine safety issues.[^7]

[Obstetrics and Gynecology]{.underline}

Dr. Ault discussed vaccine safety areas related to general women's
health and those specific to pregnant women. He suggested that HPV
vaccine is an important research area. The quadrivalent HPV vaccine is
recommended for females aged 9-26 years. A BLA was submitted to the FDA
for a bivalent vaccine, with a novel ASO4 adjuvant that includes a
monophosphorylated form of lipid A of *Salmonella*. A suggested research
need is to study the safety of HPV vaccine in the youngest cohort of
girls, aged 9-15 years. He acknowledged the importance of researching
other impacts of HPV vaccine including the effect of HPV vaccine
recommendations on cervical cancer screening practices and on serotype
replacement. Dr. Ault also noted that herpes simplex virus type 2
(HSV-2) vaccine trials are underway.

[Obstetrics and Gynecology (continued)]{.underline}

Physiologic and immunologic changes during pregnancy affect the mother
and fetus. Pregnant women may be more susceptible to vaccine-preventable
diseases; influenza is a prime example. Pathogens that are only mildly
pathogenic to most persons may be highly pathogenic to the fetus, such
as cytomegalovirus (CMV). Of the licensed vaccines, Dr. Ault noted that
pregnant women may benefit from influenza vaccine, HPV vaccine, Tdap,
and tetanus vaccine. They may also benefit from vaccines under
development, including vaccines to prevent Group B streptococcal, HSV,
CMV and respiratory syncytial virus (RSV) infections. For Tdap, research
should focus on the benefit of vaccination to the mother and fetus, as
well as compliance. For influenza, he suggested research is needed to
assess safety of influenza vaccine during early pregnancy and to assess
provider and patient perceptions of influenza vaccine safety.

[Immunology]{.underline}

Dr. Wilson reviewed immunological mechanisms of adverse events following
immunization. These include: bystander injury, autoimmunity, and
impeding the development of protective immunity to the infectious
disease for which a vaccine was designed to prevent (e.g., aberrant
immune response and tolerance). He also reviewed the "hygiene
hypothesis," which states that vaccines contribute to the rising
prevalence of allergic and autoimmune diseases in the developed world.
Three broad factors affect risk for adverse events following
immunization: developmental (especially at beginning and end of the life
stages), environmental, and genetic.

He suggested that greater understanding of each of these areas is
needed. In addition, he recommended that efforts focus on identifying
the genetic and environmental factors associated with autism and other
insidious diseases to address public perceptions that vaccines may
contribute to risk for these conditions. For autism, the study design
could be a large prospective cohort. Archived DNA (anonymous or coded)
could be obtained for genetic testing. In addition demographic and
clinical data could be obtained. He suggests VSD and CISA could
collaborate with NIH (e.g., through the National Children's Study[^8])
to conduct this study.

[Genomics]{.underline}

Dr. Relman described two goals of vaccine safety research: 1) to
identify features of the host that help predict vaccine efficacy, as
well as host susceptibility to vaccine-preventable diseases and to VAEs,
and 2) to identify features of vaccines and approaches for vaccine
development that enhance vaccine efficacy and minimize VAEs. Features of
the host that might help predict susceptibilities, efficacy, and adverse
events are: host genotype, patterns of host gene and protein expression,
and patterns of diversity among the indigenous microbiota.

Genomics enables novel assessments of host vulnerabilities (to disease,
to adverse

events) and enhanced vaccine design. It offers the possibility of early,
post-immunization prediction of adverse events (or of continued good
health) and early detection of chronic insidious adverse conditions.
Genome-based patterns of host response may yield new insights into the
mechanism of VAEs. He outlined the following challenges for the use of
genomic approaches for vaccine safety research: timely specimen
collection and [Genomics (continued)]{.underline}

appropriate storage; sufficient number of appropriate specimens,
including controls; ethical, social and legal implications; and data
analysis

[Epidemiology]{.underline}

Dr. Broome described epidemiology as a "cross-cutting discipline." When
a vaccine safety signal is detected (e.g., from VAERS), epidemiology
provides the approach to assess whether it is real, causal, and
determine the magnitude of risk compared with the benefit of the
vaccine. Epidemiologic approaches are listed below:

-   Design and validation of case definitions

-   Estimation of expected rate (i.e., background rate, clustering
    post-vaccination receipt)

-   Selection of the appropriate comparison group

-   Data analysis regarding association with vaccine

> Dr. Broome suggested the following research areas:

-   [Signal detection:]{.underline} Automated aberration detection
    algorithms in electronic databases could be used to detect increases
    in various diagnostic categories. One could investigate
    collaborative systems for aberration detection as similar approaches
    could be used to detect vaccine or drug adverse events, toxic
    exposures or new diseases. This could take advantage of the
    investment in bioterrorism event detection algorithms.

-   [Design and validation of case definition]{.underline}: New
    diagnostic tests focused on increased specificity rather than
    sensitivity could be used (e.g., could PET scans be useful for
    defining autistic spectrum disorders?).

-   [Unbiased case ascertainment]{.underline}: One could investigate
    feasibility and utility of population based linked electronic health
    records (EHR) for case ascertainment, in collaboration with VSD.

-   [Estimation of expected rate]{.underline}: The EHR approach could be
    used to assess the expected rate of conditions of interest in the
    population, adjusted for age, gender, race, seasonality, secular
    trends, etc.

-   [Selection of the appropriate comparison group]{.underline}: Explore
    options for obtaining data of population frequency of risk factors,
    including behaviors. Data from the Behavioral Risk Factor
    Surveillance Survey (BRFSS) and National Health Interview Survey
    (NHIS) and clinical information systems may be useful. Availability
    of these data may determine whether cohort or case control
    approaches are feasible or necessary.

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-   [Data analysis regarding association with vaccine]{.underline}:
    Creative approaches to evaluate alleged associations between
    vaccines and chronic diseases are needed. Two additional research
    areas are: 1) statistical and modeling techniques to address
    conditions with multiple causes, such as GBS; and risk factors with
    multi-collinearity and 2) development of criteria and approaches for
    a "rapid screen" of an alleged association to assess need to proceed
    to full study.

[Epidemiology (continued)]{.underline}

During and after the meeting Dr. Broome commented on the lack of
usefulness of "establishing baseline rates" in advance of identifying a
potential VAE. Dr. Broome explained that baseline rates in isolation are
generally not useful. To establish a comparable "baseline rate" one
needs to address seasonality, secular trends, and adjustment for age,
race, gender, etc. One also needs to use comparable case definitions
with appropriate specificity for the adverse event and to address likely
confounders. For example, a confounder for GBS is co-existent
circulating infections. Rather than focusing on baseline rate, Dr.
Broome suggested that the goal be to be able to select appropriate
comparison groups when needed to address specific concerns about VAEs.
To achieve this goal, ISO should continue to expand the large-linked
database capacity and refine its rapid accessibility and flexibility.

**[List of Abbreviations]{.underline}**

  -------------- --------------------------------------------------------
  ACIP           Advisory Committee on Immunization Practices

  AEFI           adverse events following immunization

  BLA            Biologics License Application

  CDC            Centers for Disease Control and Prevention

  CISA           Clinical Immunization Safety Assessment

  EHR            electronic health record

  FDA            Food and Drug Administration

  GBS            Guillain-Barré Syndrome

  Hib            *Haemophilus influenza* type b

  HPV            quadrivalent human papillomavirus

  IOM            Institute of Medicine

  IPV            inactivated polio vaccine

  IS             intussusception

  ISO            Immunization Safety Office

  LAIV           live, attenuated influenza vaccine

  MCV4           tetravelent meningococcal conjugate vaccine

  MMR (V)        measles, mumps, rubella (and varicella) vaccine

  NIH            National Institutes of Health

  NVAC           National Vaccine Advisory Committee

  NVPO           National Vaccine Program Office

  OCSO           Office of the Chief Science Officer

  PCV7           pneumococcal conjugate vaccine

  PPV23          pneumococcal polysaccharide vaccine

  Td             adult tetanus and diphtheria toxoids vaccine

  Tdap           tetanus toxoid, reduced diphtheria toxoid, and acellular
                 pertussis vaccine

  TIV            trivalent inactivated influenza vaccine

  VAE            vaccine adverse event

  VAERS          Vaccine Adverse Event Reporting System

  VSD            Vaccine Safety Datalink

  \*             An asterisks is used to designate that at least one
                 consultant indicated that the topic was a high priority.
  -------------- --------------------------------------------------------

**[List of Appendices]{.underline}**

Appendix A: Administrative Summary from an individual simultaneous
consultation on CDC's Immunization Safety Office Research Agenda

Appendix B: Meeting agenda

Appendix C: Meeting participants: consultants and liaisons

Appendix D: Table of contents from briefing materials

Appendix E: Brainstorming feedback worksheet (template)

Appendix F: Endorsement from consultants that report represents
individual input

Appendix G: Presentations from six consultants (in original form)

**[Appendix A:]{.underline}**

**[Administrative Summary from an Individual Simultaneous Consultation
on CDC's Immunization Safety Office Research Agenda]{.underline}**

On May 10 and 11, 2007 CDC's Immunization Safety Office (ISO) hosted an
individual simultaneous consultation to obtain input on the future ISO
research agenda. The meeting occurred in Atlanta, on CDC's Roybal
campus. The meeting followed the general organization listed in the
meeting agenda (Appendix B), except small modifications were made to
accommodate consultant schedules. The three main agenda items were:
presentations from ISO/Office of the Chief Science Officer (OCSO) staff
and a keynote speaker for information; consultant brainstorming sessions
based on life stages or cross-cutting topics; and presentations from
individual consultants, followed by discussion.

Seven invited individual consultants, representing six different
disciplines, attended the meeting (Appendix C). One consultant, Dr.
Peter, served as the moderator for the discussion sessions of the
meeting. The disciplines were: pediatric infectious diseases, adult
infectious diseases, obstetrics and gynecology, epidemiology, immunology
and genomics. Dr. Schaffner, representing adult infectious diseases,
only attended on the first day and Dr. Ault, representing obstetrics and
gynecology, missed several hours of the first day due to schedule
conflicts; the other 5 consultants participated in all sessions during
both days. Seven invited liaison representatives from Federal advisory
committees and agencies and two ISO research networks (VSD and CISA)
also attended the full meeting (Appendix C). Dr. Walt Orenstein,
director of the Emory Program for Vaccine Policy and Development, Emory
University School of Medicine and former director of the National
Immunization Program, CDC delivered a keynote speech during the
information session; he did not attend the discussion parts of the
meeting. CDC staff on the ISO research agenda development team and
meeting organizers were invited to participate in the full meeting (see
below). Other ISO staff persons were invited to hear the opening
background presentations, but did not attend the discussion sessions.

On May 10, 2007, the meeting convened at about 8:00 am. Dr. Iskander,
Acting Co-director, ISO and Dr. Popovic, Chief Science Officer, CDC each
welcomed the consultants and provided background information. After
these remarks, Dr. Broder read the following information to consultants,
*"the charge to each consultant is to identify emerging vaccine safety
research questions that will be important for public health and could be
studied by ISO but are not currently being addressed. We will not be
seeking a consensus of the gathered experts, but rather will be seeking
each person's individual expert advice.  If during the meeting a
consultant does not have time to express his/her individual input, we
will be happy to follow-up with that person after the meeting to obtain
his/her input."* The rest of the morning generally followed the agenda
and the group adjourned for lunch at about 12:10 pm.

At approximately 1:00 pm, Dr. Broder reviewed procedures for
brainstorming; a slide noted "*individual input desired, not seeking
consensus*" Following this presentation, Dr. Broder verbally summarized
information about potential real or perceived conflicts of interests
from each of the seven consultants, based on information voluntarily
provided before the meeting. Mr. Malone, representing CDC's Office of
the General Counsel attended this session.

After these procedural issues were discussed, the consultant discussion
portion of the meeting commenced. The remainder of the afternoon
followed the meeting agenda, except the order of the last two
presentations was switched (presentation from Dr. Schaffner occurred
before discussion of the role of public perception in shaping the
research agenda). Dr. Peter moderated these discussion sessions in a
manner that allowed for each consultant to provide individual input. The
main discussion occurred among consultants; however, liaisons and
ISO/OCSO staff participated at the discretion of Dr. Peter when their
input was felt to be useful. The first day of the meeting adjourned at
about 5:00 pm.

On May 11, 2007 at about 8:00 am the meeting resumed. Following brief
administrative updates, consultant presentations and group brainstorming
sessions occurred. Dr. Peter continued to moderate these discussions.
The topics followed the meeting agenda, except the brainstorming
discussion about the life-stage of pregnancy followed, rather than
preceded, Dr. Ault's presentation. At about 12:30 pm, the meeting
adjourned.

During both days of the meeting, each consultant completed feedback
worksheets at the end of each brainstorming session he/she attended.
Liaisons and ISO/OCSO participants did not complete worksheets. The
discussion framework and scientific ideas generated during these
brainstorming discussions are presented in the body of this report.

A list of participating consultants and liaisons is provided in Appendix
C. The following persons from ISO/OCSO attended some or part of the
scientific discussion sessions:

-   Dixie Snider, MD, MPH, Senior Advisor, OCSO, CDC

-   James Stephens, PhD, Associate Director for Science, OCSO, CDC

-   John Iskander, MD, MPH, Acting Co-director, ISO, OCSO, CDC

-   Kristin Pope, MEd, Acting Co-director, ISO, OCSO, CDC

-   Brigid Batten, MPH, Orise Fellow, ISO, OCSO, CDC

-   Karen R. Broder, MD, Senior Medical Advisor, ISO, OCSO, CDC

-   Jae Duncan, Program Coordinator, ISO, OCSO, CDC

-   Paul Gargiullo, PhD, Acting Team Leader, Vaccine Safety Datalink
    (VSD) Project, ISO, OCSO, CDC

-   Jane Gidudu, MD, MPH, Acting Team Leader, The Brighton
    Collaboration, ISO, OCSO, CDC

-   Laura Leidel, RN, FNP-C, MPH, Epidemiologist, ISO, OCSO, CDC

-   Nancy Levine, PhD, Policy Analyst, ISO, OCSO, CDC

-   Claudia Vellozzi, MD, MPH, Acting Team Leader, Clinical Immunization
    Safety Assessment (CISA) Network, ISO, OCSO, CDC

**[Appendix B: Meeting Agenda]{.underline}**

**Immunization Safety Office (ISO) External Scientific Consultancy
Meeting**

Centers for Disease Control and Prevention

1600 Clifton Road, Atlanta GA

Roybal Campus

Building 19, Room 247 and 248

**Final Agenda**[^9]

**Day 1: Thursday May 10**

+---------------+---------------+-----------------+-------------------+
| Time          | Agenda Item   | Purpose         | Presenter(s)      |
+===============+===============+=================+===================+
| *             | **            |                 |                   |
| *8:00-12:00** | Presentations |                 |                   |
|               | about the     |                 |                   |
|               | Immunization  |                 |                   |
|               | Safety Office |                 |                   |
|               | (ISO)**       |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 8:00-8:10     | Welcome from  | Information     | Dr. Iskander,     |
|               | ISO           |                 | Acting            |
|               |               |                 | Co-director,      |
|               |               |                 | Immunization      |
|               |               |                 | Safety Office     |
|               |               |                 | (ISO)             |
+---------------+---------------+-----------------+-------------------+
| 8:10-8:25     | Welcome from  | Information     | Dr. Popovic,      |
|               | Office of the |                 | Chief Science     |
|               | Chief Science |                 | Officer, CDC      |
|               | Officer       |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 8:25-8:35     | Organization  | Information     | Dr. Broder,       |
|               | of Meeting    |                 | Senior Medical    |
|               | and           |                 | Advisor, ISO      |
|               | Compliance    |                 |                   |
|               | with          |                 |                   |
|               | Requirement   |                 |                   |
|               | for           |                 |                   |
|               | Individual    |                 |                   |
|               | Simultaneous  |                 |                   |
|               | Consultation  |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 8:35-8:45     | Introductions | Information     | Dr. Broder and    |
|               |               |                 | meeting           |
|               |               |                 | participants      |
+---------------+---------------+-----------------+-------------------+
| 8:45-9:00     | Immunization  | Information     | Dr. Iskander      |
|               | Safety Office |                 |                   |
|               | Program       |                 |                   |
|               | Overview      |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 9:00-9:15     | CDC's         | Information     | Dr. Broder        |
|               | Immunization  |                 |                   |
|               | Safety Office |                 |                   |
|               | Development   |                 |                   |
|               | of a Research |                 |                   |
|               | Agenda        |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 9:15-9:45     | Vaccine       | Keynote speaker | Dr. Orenstein,    |
|               | Safety        | presentation    | Professor of      |
|               | Monitoring -- |                 | Medicine and      |
|               |               |                 | Pediatrics        |
|               | Perspectives  |                 |                   |
|               | from a Former |                 | Director, Emory   |
|               |               |                 | Vaccine Policy    |
|               | Immunization  |                 | and Development   |
|               | Program       |                 |                   |
|               | Director      |                 | Associate         |
|               |               |                 | Director, Emory   |
|               |               |                 | Vaccine Center    |
+---------------+---------------+-----------------+-------------------+
| 9:45-10:00    | Break         |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 10:00-10:20   | Summary of    | Information     | Dr. Broder        |
|               | the Institute |                 |                   |
|               | of Medicine   |                 |                   |
|               | Immunization  |                 |                   |
|               | Safety        |                 |                   |
|               | Reviews:      |                 |                   |
|               | 2001-2004     |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 10:20-10:35   | Clinical      | Information     | Dr. Vellozzi,     |
|               | Immunization  |                 | Acting CISA Team  |
|               | Safety        |                 | Lead              |
|               | Assessment    |                 |                   |
|               | (CISA)        |                 |                   |
|               | network       |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 10:35-10:50   | Clinical      | Questions and   | Dr. Vellozzi and  |
|               | Immunization  | Answers         |                   |
|               | Safety        |                 | Dr. Dekker, CISA  |
|               | Assessment    |                 | Principal         |
|               | (CISA)        |                 | Investigator,     |
|               | network       |                 | Stanford          |
|               |               |                 | University School |
|               |               |                 | of Medicine       |
+---------------+---------------+-----------------+-------------------+
| 10:50-11:10   | Vaccine       | Information     | Dr. Gargiullo,    |
|               | Safety        |                 | Acting VSD Team   |
|               | Datalink      |                 | Lead              |
|               | (VSD) project |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 11:10-11:30   | Vaccine       | Questions and   | Dr. Gargiullo and |
|               | Safety        | Answers         | Dr. Jackson, VSD  |
|               | Datalink      |                 | PI,               |
|               | (VSD) project |                 |                   |
|               |               |                 | Group Health      |
|               |               |                 | Center for Health |
|               |               |                 | Statistics,       |
|               |               |                 | Seattle, WA (VSD  |
|               |               |                 | PI)               |
+---------------+---------------+-----------------+-------------------+
| 11:30-11:40   | Vaccine       | Presentation    | Dr. Iskander      |
|               | Adverse Event |                 |                   |
|               | Reporting     |                 |                   |
|               | System        |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 11:40-11:50   | Brighton      | Presentation    | Dr. Gidudu        |
|               | Collaboration |                 | (Acting Brighton  |
|               |               |                 | Collaboration     |
|               |               |                 | Team Lead)        |
+---------------+---------------+-----------------+-------------------+
| 11:50-12:00   | Vaccine       | Questions and   | Drs. Iskander and |
|               | Adverse Event | Answers         | Gidudu            |
|               | Reporting     |                 |                   |
|               | System        |                 |                   |
|               | (VAERS) and   |                 |                   |
|               | the Brighton  |                 |                   |
|               | Collaboration |                 |                   |
+---------------+---------------+-----------------+-------------------+
| **            | **Lunch**     |                 | Ms. Duncan to     |
| 12:00-12:50** |               |                 | coordinate in     |
|               |               |                 | Room 256          |
+---------------+---------------+-----------------+-------------------+
| *             | **            |                 |                   |
| *12:50-5:00** | Brainstorming |                 |                   |
|               | Sessions**    |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 12:50-1:00    | Procedures    | Information     | Dr. Broder and    |
|               | for           |                 | Dr. Peter,        |
|               | Brainstorming |                 | Professor         |
|               | Sessions      |                 | Emeritus, the     |
|               |               |                 | Warren Alpert     |
|               |               |                 | Medical School of |
|               |               |                 | Brown University  |
+---------------+---------------+-----------------+-------------------+
| 1:00-1:10     | Disclosure of | Information and | Dr. Broder        |
|               | Consultant    | Discussion      |                   |
|               | Va            |                 |                   |
|               | ccine-related |                 |                   |
|               | Interests     |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 1:10-1:50     | Life Stage 1: | Discussion      | Dr. Peter         |
|               | Infant Aged   | among           | moderates         |
|               | \<12 Months   | consultants     |                   |
|               | of Age        |                 | Dr. Broder        |
|               |               |                 | presents          |
|               |               |                 | information       |
|               |               |                 |                   |
|               |               |                 | Dr. Vellozzi      |
|               |               |                 | takes notes       |
|               |               |                 | during discussion |
|               |               |                 | for all to see    |
+---------------+---------------+-----------------+-------------------+
| 1:50-2:30     | Life Stage 2: | Discussion      | Drs. Peter        |
|               | Child 1-10    | among           | moderates         |
|               | Years of Age  | consultants     |                   |
|               |               |                 | Drs. Broder and   |
|               |               |                 | Vellozzi          |
|               |               |                 | facilitate        |
+---------------+---------------+-----------------+-------------------+
| 2:30-2:40     | Break         |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 2:40-3:20     | Life Stage 3: | Discussion      | Drs. Peter        |
|               | Adolescents   | among           | moderates         |
|               | 11-18 Years   | consultants     |                   |
|               | of Age        |                 | Drs. Broder and   |
|               |               |                 | Vellozzi          |
|               |               |                 | facilitate        |
+---------------+---------------+-----------------+-------------------+
| 3:20-4:00     | Life Stage 4: | Discussion      | Drs. Peter        |
|               | Adults ≥19    | among           | moderates         |
|               | years of Age  | consultants     |                   |
|               |               |                 | Drs. Broder and   |
|               |               |                 | Vellozzi          |
|               |               |                 | facilitate        |
+---------------+---------------+-----------------+-------------------+
| 4:00-4:40     | Across the    | Discussion      | Drs. Peter        |
|               | Life Stages   | among           | moderates         |
|               | A: Role of    | consultants     |                   |
|               | Public        |                 | Drs. Broder and   |
|               | Perception in |                 | Vellozzi          |
|               | Shaping the   |                 | facilitate        |
|               | Immunization  |                 |                   |
|               | Safety        |                 |                   |
|               | Research      |                 |                   |
|               | Agenda        |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 4:40-5:00     | *             | Information     | Dr. Schaffner,    |
|               | *Presentation |                 | Vanderbilt        |
|               | from          |                 | University School |
|               | Consultant:** |                 | of Medicine       |
|               | Adult         |                 |                   |
|               | Infectious    |                 |                   |
|               | Diseases      |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 5:00          | Adjourn Day 1 |                 |                   |
+---------------+---------------+-----------------+-------------------+
|               |               |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 7:00-9:00     | Dinner Top    |                 | Ms. Leidel to     |
|               | Spice         |                 | coordinate        |
|               |               |                 |                   |
|               | 3007 North    |                 |                   |
|               | Druid Hills   |                 |                   |
|               | Road,         |                 |                   |
|               | Atlanta, GA   |                 |                   |
|               |               |                 |                   |
|               | 404-728-0588  |                 |                   |
+---------------+---------------+-----------------+-------------------+

**Day 2: Friday May 11**

+---------------+---------------+-----------------+-------------------+
| Time          | Agenda Item   | Purpose         | Presenter(s)      |
+===============+===============+=================+===================+
| 8:00-8:35     | **            | Discussion      | Drs. Peter        |
|               | Brainstorming | among           | moderates         |
|               | Session:**    | consultants     |                   |
|               |               |                 | Drs. Broder and   |
|               | Life Stage 5: |                 | Vellozzi          |
|               | Pregnancy     |                 | facilitate        |
+---------------+---------------+-----------------+-------------------+
| *             | **            |                 |                   |
| *8:35-10:30** | Presentations |                 |                   |
|               | from          |                 |                   |
|               | Consultants** |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 8:35-8:55     | Pediatric     | Information and | Dr. Dennehy, The  |
|               | Infectious    | Questions and   | Warren Alpert     |
|               | Diseases      | Answers         | Medical School of |
|               |               |                 | Brown University  |
+---------------+---------------+-----------------+-------------------+
| 8:55-9:15     | Obstetrics    | Information and | Dr. Ault, Emory   |
|               | and           | Questions and   | University School |
|               | Gynecology    | Answers         | of Medicine       |
+---------------+---------------+-----------------+-------------------+
| 9:15-9:35     | Immunology    | Information and | Dr. Wilson,       |
|               |               | Questions and   | University of     |
|               |               | Answers         | Washington School |
|               |               |                 | of Medicine       |
+---------------+---------------+-----------------+-------------------+
| 9:35-9:55     | Genomics      | Information and | Dr. Relman,       |
|               |               | Questions and   | Stanford          |
|               |               | Answers         | University School |
|               |               |                 | of Medicine       |
+---------------+---------------+-----------------+-------------------+
| 9:55-10:15    | Epidemiology  | Information and | Dr. Broome,       |
|               |               | Questions and   | Rollins School of |
|               |               | Answers         | Public Health,    |
|               |               |                 | Emory University  |
+---------------+---------------+-----------------+-------------------+
| 10:15-10:30   | Break         |                 |                   |
+---------------+---------------+-----------------+-------------------+
| **            | **            |                 |                   |
| 10:30-12:00** | Brainstorming |                 |                   |
|               | Sessions:     |                 |                   |
|               | Across the    |                 |                   |
|               | Life Stages** |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 10:30-11:00   | Across the    |                 | Drs. Peter        |
|               | Life Stages   |                 | moderates         |
|               | B:            |                 |                   |
|               | C             |                 | Drs. Broder and   |
|               | onsiderations |                 | Vellozzi          |
|               | for Vaccine   |                 | facilitate        |
|               | Safety        |                 |                   |
|               | Surveillance  |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 11:00-11:30   | Across the    |                 | Drs. Peter        |
|               | Life Stages   |                 | moderates         |
|               | C: Safety of  |                 |                   |
|               | Non-antigen   |                 | Drs. Broder and   |
|               | Vaccine       |                 | Vellozzi          |
|               | Constituents  |                 | facilitate        |
|               | and New       |                 |                   |
|               | Vaccine       |                 |                   |
|               | Technologies  |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 11:30-12:00   | Across the    |                 | Drs. Peter        |
|               | Life Stages   |                 | moderates         |
|               | D: Adverse    |                 |                   |
|               | Events that   |                 | Drs. Broder and   |
|               | Occur Years   |                 | Vellozzi          |
|               | after         |                 | facilitate        |
|               | Vaccination   |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 12:00-12:15   | Plans for     | Information     | Drs. Broder and   |
|               | Completing    |                 | Peter             |
|               | Report and    |                 |                   |
|               | Closing       |                 |                   |
|               | Remarks       |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 12:15-12:30   | Shuttle pick  |                 |                   |
|               | up to Emory   |                 |                   |
|               | Conference    |                 |                   |
|               | Center        |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 12:30-2:00    | Lunch at Le   |                 | Ms. Leidel to     |
|               | Giverny       |                 | coordinate        |
|               | Bistro        |                 |                   |
|               |               |                 |                   |
|               | Emory Inn     |                 |                   |
|               |               |                 |                   |
|               | 1615 Clifton  |                 |                   |
|               | Road          |                 |                   |
|               |               |                 |                   |
|               | 404-325-7252  |                 |                   |
+---------------+---------------+-----------------+-------------------+
| 2:00pm\*      | Adjourn Day 2 |                 |                   |
+---------------+---------------+-----------------+-------------------+

\* Guests should try to schedule flights after 5:00 pm EDT.

  ------------------------- -------------------------- ------------------------------------- ------------------------ ------------------------------------------------------------------------------------------- -----------------------
  **[Appendix C: ISO                                                                                                                                                                                              
  EXTERNAL SCIENTIFIC                                                                                                                                                                                             
  CONSULTANCY PARTICIPANT                                                                                                                                                                                         
  LIST OF CONSULTANTS AND                                                                                                                                                                                         
  LIAISONS]{.underline}**                                                                                                                                                                                         

                                                                                                                                                                                                                  

  **[Name]{.underline}**    **[Degree]{.underline}**   **[Title/Affiliation]{.underline}**   **[Role]{.underline}**   **[Email Address]{.underline}**                                                             **[Phone
                                                                                                                                                                                                                  Number]{.underline}**

                                                                                                                                                                                                                  

  AULT, Kevin               MD                         Associate Professor of Gynecology and Invited Independent      [[kevin.ault@emory.edu]{.underline}](mailto:kevin.ault@emory.edu)                           1.404.616.5419 -Office
                                                       Obstetrics, Emory University School   Consultant for                                                                                                       1.404.521.3589 -Fax
                                                       of Medicine, Atlanta, GA              Obstetrics and                                                                                                       
                                                                                             Gynecology                                                                                                           

                                                                                                                                                                                                                  

  BART, Kenneth             MD, MPH, MSHPM             Consultant, National Vaccine Program  Invited Liaison, NVPO    [[Kbart@hhs.gov]{.underline}](mailto:Kbart@hhs.gov)                                         1.202.205.0076 -Office
                                                       Office (NVPO), HHS, Washington DC     Representative                                                                                                       1.202.260.1165 -Fax

                                                                                                                                                                                                                  

  BROOME, Claire            MD MPH                     Adjunct Professor Rollins School of   Invited Independent      [[cvbroome@gmail.com]{.underline}](mailto:cvbroome@gmail.com)                               1.510.248.4095 -Home
                                                       Public Health, Emory University       Consultant for                                                                                                       1.510.219.9629 -Cell
                                                       (retired CDC, Berkeley, CA)           Epidemiology                                                                                                         

                                                                                                                                                                                                                  

  DEKKER, Cornelia          MD                         Associate Professor, Pediatrics,      Invited Liaison, CISA    [[cdekker@stanford.edu]{.underline}](mailto:cdekker@stanford.edu)                           1.650.724.4437 -Office
                                                       Medical Director, Stanford-LPCH       Network Principal                                                                                                    1.650.724.3088 -Fax
                                                       Vaccine Program, Stanford University  Investigator                                                                                                         
                                                       School of Medicine, Stanford, CA      Representative                                                                                                       

                                                                                                                                                                                                                  

  DENNEHY, Penelope         MD                         Professor of Pediatrics, The Warren   Invited Independent      [[Pdennehy@lifespan.org]{.underline}](mailto:Pdennehy@lifespan.org)                         1.401.444.8360 -Office
                                                       Alpert Medical School of Brown        Consultant for                                                                                                       1.401.444.5650 -Fax
                                                       University, Director of Pediatric     Pediatrics/Pediatric                                                                                                 
                                                       Infectious Diseases, Hasbro           Infectious Diseases                                                                                                  
                                                       Children\'s Hospital, Providence, RI                                                                                                                       

  DEVILLE, Jaimie           MD                         Associate Clinical Professor of       Invited Liaison,         [[jdeville@mednet.ucla.edu]{.underline}](mailto:jdeville@mednet.ucla.edu)                   1.310.825.9660 -Office
                                                       Infectious Disease, Department of     Advisory Commission on                                                                                               1.310.825.9175 -Fax
                                                       Pediatrics, David Geffen School of    Childhood Vaccines                                                                                                   
                                                       Medicine, University of CA, Los       (ACCV) Representative                                                                                                
                                                       Angeles                                                                                                                                                    

                                                                                                                                                                                                                  

  EVANS, Geoffrey           MD                         Director, National Vaccine Injury     Invited Liaison, VICP    [GEvans@HRSA.GOV]{.underline}                                                               301-443-6593 -Office
                                                       Compensation Program (VICP), Health   Representative                                                                                                       301-443-4198 -Fax
                                                       Resources and Services Administration                                                                                                                      
                                                       (HRSA) , Rockville, MD                                                                                                                                     

                                                                                                                                                                                                                  

  JACKSON, Lisa             MD MPH                     Senior Investigator, Group Health     Invited Liaison, VSD     [[Jackson.L@ghc.org]{.underline}](mailto:Jackson.L@ghc.org)                                 1.206.442.5216 -Office
                                                       Cooperative, Seattle, WA              Project Principal                                                                                                    1.206.287.4677 -Fax
                                                                                             Investigator                                                                                                         
                                                                                             Representative                                                                                                       

                                                                                                                                                                                                                  

  **[Name]{.underline}**    **[Degree]{.underline}**   **[Title/Affiliation]{.underline}**   **[Role]{.underline}**   **[Email Address]{.underline}**                                                             **[Phone
                                                                                                                                                                                                                  Number]{.underline}**

  PAVIA, Andrew             MD                         George and Ester Gross Presidential   Invited Liaison,         [[Andy.pavia@hsc.utah.edu]{.underline}](mailto:Andy.pavia@hsc.utah.edu)                     1.801.581.6791 -Office
                                                       Professor and Chief, Division of      National Vaccine                                                                                                     1.801.560.4607 -Cell
                                                       Pediatric Infectious Diseases,        Advisory Committee                                                                                                   
                                                       University of Utah, Salt Lake City,   Representative, Chair                                                                                                
                                                       UT                                    Subcommittee on Vaccine                                                                                              
                                                                                             Safety                                                                                                               

                                                                                                                                                                                                                  

  PETER, Georges            MD                         Professor Emeritus of Pediatrics, The Invited Independent      [[gpeter@lifespan.org]{.underline}](mailto:gpeter@lifespan.org)                             1.617.277.1090 -Office
                                                       Warren Alpert Medical School of Brown Consultant, External                                                                                                 1.617.277.1129 -Fax
                                                       University, Providence, RI            Leader                                                                                                               
                                                       (Brookline, MA)                                                                                                                                            

                                                                                                                                                                                                                  

  RELMAN, David             MD                         Associate Professor of Microbiology & Invited Independent      [[relman@stanford.edu]{.underline}](mailto:relman@stanford.edu)                             1.650.852.3308 -Office
                                                       Immunology and of Medicine, Stanford  Consultant for Genomics                                                                                              1.650.852.3291 -Fax
                                                       University School of Medicine, Palo                                                                                                                        
                                                       Alto, CA                                                                                                                                                   

                                                                                                                                                                                                                  

  SCHAFFNER, William        MD                         Professor and Chair, Department of    Invited Independent      [[william.schaffner@vanderbilt.edu]{.underline}](mailto:william.schaffner@vanderbilt.edu)   1.615.322.2037 -Office
                                                       Preventive Medicine, Vanderbilt       Consultant for Internal                                                                                              1.615.343.8722 -Fax
                                                       University School of Medicine,        Medicine/Adult                                                                                                       
                                                       Nashville, TN                         Infectious Diseases                                                                                                  

  SMITH, Jean Claire        MD                         Assistant to the Director for         Invited Liaison,         [jis6@CDC.GOV]{.underline}                                                                  1.404.639.6227 -Office
                                                       Immunization Policy, Immunization     Advisory Committee on                                                                                                1.404.639.8905 -Fax
                                                       Services Division, National Center    Immunization Practices,                                                                                              
                                                       for Immunization and Respiratory      Executive Secretary                                                                                                  
                                                       Diseases, CDC                         Representative                                                                                                       

                                                                                                                                                                                                                  

  WILSON, Christopher       MD                         Professor and Chairman, Department of Invited Independent      [[cbwilson@u.washington.edu]{.underline}](mailto:cbwilson@u.washington.edu)                 1.206.685.3956 -Office
                                                       Immunology, University of Washington  Consultant for                                                                                                       1.206.616.4561 -Fax
                                                       School of Medicine, Seattle, WA       Immunology                                                                                                           
  ------------------------- -------------------------- ------------------------------------- ------------------------ ------------------------------------------------------------------------------------------- -----------------------

**[Appendix D-1:]{.underline}**

**Table of Contents**

**Scientific Consultancy Briefing Materials**

[Tab 1 -- Scientific Consultancy]{.underline}

Meeting Agenda (draft)

Scientific Consultancy Overview

Scientific Consultancy Participant List

Scientific Consultancy Organizers and Leaders

Research Agenda Development Presentation

[Tab 2 -- Immunization Safety Office (ISO)]{.underline}

Overview Presentation

Fact Sheet

Strategic Plan (draft)

[Tab 3 -- Institute of Medicine (IOM)]{.underline}

Summary of Reports on Vaccine Safety

Summary of Vaccine Safety Research, Data Access and Public Trust

[Tab 4 -- Vaccine Safety Datalink Project (VSD)]{.underline}

Overview Presentation

Current Research

Publications

Journal Articles on VSD Research Methodology

-   Pediatrics 1997 (Chen)

-   NEJM 2001 (Davis)

-   Pediatrics 2001 (DeStefano)

-   Pediatrics 2006 (Goodman and Nordin)

[Tab 5 -- Clinical Immunization Safety Assessment Network
(CISA)]{.underline}

Overview Presentation

Current Research

[Tab 6 -- Vaccine Adverse Event Reporting System (VAERS)
and]{.underline}

Overview Presentation

Publications

VAERS Reporting Form

Journal Articles on VAERS Research Methodology

-   Pediatrics 2001 (Zanardi and Haber)

-   Pediatric Infectious Disease Journal 2004 (Varrichio and Iskander)

-   JAMA 2005 (Wise and Iskander)

[Tab 7 -- The Brighton Collaboration]{.underline}

Overview Presentation

Publications

Journal Article on Brighton Research Methodology

-   Advances in Patient Safety (Kohl)

[Additional Resources Located in Back Pocket]{.underline}

ACIP Immunization Schedules

Red Book Vaccine Status Table

**[Appendix D-2:]{.underline}**

**[Immunization Safety Office External Scientific Consultancy
Meeting]{.underline}**

**[Atlanta, Georgia, May 10 and 11, 2007]{.underline}**

**Late-breaking Materials**

+----+--------------------------+-------------------------------------+
| It | Category                 | Document                            |
| em |                          |                                     |
+----+--------------------------+-------------------------------------+
| 1  | Administrative           |                                     |
+----+--------------------------+-------------------------------------+
| 1  |                          | Final Meeting Agenda                |
| -A |                          |                                     |
+----+--------------------------+-------------------------------------+
| 1  |                          | Updated Meeting Participant List    |
| -B |                          |                                     |
+----+--------------------------+-------------------------------------+
| 1  |                          | Hotel and Meal Information          |
| -C |                          |                                     |
+----+--------------------------+-------------------------------------+
|    |                          |                                     |
+----+--------------------------+-------------------------------------+
| 2  | Updated Presentation for |                                     |
|    | Opening Session on the   |                                     |
|    | Immunization (ISO), CDC  |                                     |
+----+--------------------------+-------------------------------------+
| 2  |                          | Immunization Safety Office Overview |
| -A |                          | Presentation (Dr. Iskander)         |
+----+--------------------------+-------------------------------------+
| 3  | Additional Presentations |                                     |
|    | for Opening Session on   |                                     |
|    | ISO, CDC                 |                                     |
+----+--------------------------+-------------------------------------+
| 3  |                          | Vaccine Safety Monitoring --        |
| -A |                          |                                     |
|    |                          | Perspectives from a Former          |
|    |                          |                                     |
|    |                          | Immunization Program Director (Dr.  |
|    |                          | Orenstein)                          |
+----+--------------------------+-------------------------------------+
| 3  |                          | Summary of the Institute of         |
| -B |                          | Medicine Immunization Safety        |
|    |                          | Reviews, 2001−2004 (Dr. Broder)     |
+----+--------------------------+-------------------------------------+
| 3  |                          | Updates from the Clinical           |
| -C |                          | Immunization Safety Assessment      |
|    |                          | Network Annual Meeting (Drs. Dekker |
|    |                          | and Vellozzi)                       |
+----+--------------------------+-------------------------------------+
| 3  |                          | Updates from the Vaccine Safety     |
| -D |                          | Datalink Project Annual Meeting     |
|    |                          | (Drs. Jackson and Gargiullo)        |
+----+--------------------------+-------------------------------------+
| 4  | Materials for            |                                     |
|    | Brainstorming Sessions   |                                     |
+----+--------------------------+-------------------------------------+
| 4  |                          | Immunization Safety Office External |
| -A |                          | Scientific Consultancy Meeting:     |
|    |                          | Brainstorming Session Procedures    |
|    |                          | (Drs. Broder and Peter)             |
+----+--------------------------+-------------------------------------+
| 4  |                          | Immunization Safety Office External |
| -B |                          | Scientific Consultancy Meeting:     |
|    |                          | Brainstorming Session Background    |
|    |                          | (Dr. Broder)                        |
+----+--------------------------+-------------------------------------+
| 4  |                          | Vaccines by Life Stage Table (Dr.   |
| -C |                          | Broder)                             |
+----+--------------------------+-------------------------------------+
| 4  |                          | Consultant Feedback Worksheets      |
| -D |                          |                                     |
+----+--------------------------+-------------------------------------+

**[Appendix E: Sample Brainstorming Worksheet]{.underline}**

Date:

Name of consultant:

**[Life stage 1: Infant \<12 months of age]{.underline}**

For this session, please list what you believe to be the 5 most
important research topics?

For each topic, please address 3 specific questions, using the codes
below.

Question 1: Why is the topic important (note all that apply)

⁭1. Burden of health risk associated with vaccine preventable disease in
the absence of vaccination?

⁭2. Burden of health risk associated with the adverse event following
vaccination?

⁭3. Perceived intensity of public or professional concern? ⁭4. Other
(specify)

Question 2: Using a scale of 1--5 (highest), what is the overall
priority score for the topic?

Question 3: What are some feasible approaches to study the topic (check
all that apply)

⁭1. Large-linked database study ⁭2. Other epidemiological study

⁭3. Epidemiological study involving collection of biological specimens ⁭4.
Clinical trial ⁭ 5. Other approach (specify)

+---+-------------------+----------------+---------+------------------+
|   | Vaccine Safety    | 1\) Why is the | 2\)     | 3\) Approaches   |
|   |                   | topic          | P       | to study the     |
|   | Research Topic    | important?     | riority | topic? (choices  |
|   |                   | (choices 1−5;  | score   | 1−5; list all    |
|   |                   | list all that  | 1−5 (5  | that apply)      |
|   |                   | apply)         | is      |                  |
|   |                   |                | hi      |                  |
|   |                   |                | ghest)? |                  |
+---+-------------------+----------------+---------+------------------+
| 1 |                   |                |         |                  |
+---+-------------------+----------------+---------+------------------+
| 2 |                   |                |         |                  |
+---+-------------------+----------------+---------+------------------+
| 3 |                   |                |         |                  |
+---+-------------------+----------------+---------+------------------+
| 4 |                   |                |         |                  |
+---+-------------------+----------------+---------+------------------+
| 5 |                   |                |         |                  |
+---+-------------------+----------------+---------+------------------+

Comments:

**[Appendix F:]{.underline}**

**[Endorsement from Consultants that Report Represents Individual
Input]{.underline}**

Each consultant was asked to respond to the following statement:

I have reviewed the 10/21/2007 Draft "Report from an Individual
Simultaneous Consultation on the Centers for Disease Control and
Prevention's Immunization Safety Office Research Agenda: May 10 and 11,
2007, Atlanta, GA."

This document accurately reflects my individual comments and the events
as they transpired on May 10 and 11, 2007 during the portions of the
meeting that I attended.

1\. I agree with this statement and have [no]{.underline} additional
comments related to content (exclude minor comments related to grammar,
spelling and writing style) \_\_\_

2\. I agree with this statement but have additional comments related to
content (describe below) \_\_\_

3\. I do [not]{.underline} agree with this statement (describe below)
\_\_\_

Of the seven consultants, four checked box 1 and three checked box 2.
Comments from the individuals who checked box 2 have been incorporated
into the final document.

**[Appendix G]{.underline}**

**[Independent Consultant Presentations]{.underline}**

1.  Immunization Safety Office Scientific Consultancy: the Pediatric
    Infectious Disease Perspective, presented by Penelope H. Dennehy, MD

2.  Immunization Safety Issues: Results of a Mini-Survey of Colleagues,
    presented by William Schaffner, MD

3.  Vaccines and Women's Health, presented by Kevin A. Ault, MD

4.  Immunologic Mechanisms of Vaccine Adverse Events, presented by
    Christopher Wilson, MD

5.  Genetics and Emerging Vaccine Safety Issues, presented by David
    Relman, MD

6.  Immunization Safety Office: Epidemiology and the Research Agenda,
    presented by Claire Broome, MD, MPH

[^1]: Vaccine Safety Research, Data Access, and Public Trust**,**
    available at <http://www.nap.edu/catalog/11234.html>, accessed
    1/16/08.

[^2]: The 2007 ACIP immunization schedule for persons aged 0-18 years is
    available at
    <http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5551a7.htm?s_cid=mm5551a7_e>;

    the 2006 ACIP adult immunization schedule is available at
    <http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5540a10.htm?s_cid=mm5540a10_e>.,
    accessed 10-20-07.

[^3]: Redbook Online: Status of Licensure and Recommendations for New
    Vaccines.
    <http://aapredbook.aappublications.org/news/vaccstatus.shtml>,
    accessed 10/20/07.

[^4]: "Off label" use occurs when a vaccine is used for a purpose
    different from one of the indications for which the product is
    approved by the Food and Drug Administration (FDA).

[^5]: Information available at <http://clinicaltrials.gov/>, accessed on
    December 8, 2007; at time of access no trials for preventive
    vaccination with HSV vaccine were enrolling pregnant women.

[^6]: Information from these two brainstorming sessions overlapped and
    has been consolidated for this report.

[^7]: In May 2004, the IOM published a report titled, "Immunization
    Safety Review: Vaccines and Autism." The IOM Immunization Safety
    Review Committee concluded that "the evidence favors rejection of a
    causal relationship between thimerosal-containing vaccines and
    autism " and that "the evidence favors rejection of a causal
    relationship between MMR vaccine and autism." Executive summary
    available at <http://www.iom.edu/?ID=4705>, accessed on December 8,
    2007.

[^8]: Information about the National Children's Study is available at
    <http://www.nationalchildrensstudy.gov/about/mission/index.cfm>,
    accessed on December 8, 2007.

[^9]: Some minor modifications in the order of events occurred to
    accommodate consultant schedules (10/13/07)