![](media/image1.png){width="1.05625in" height="0.8368055555555556in"}

![](media/image2.png){width="6.249305555555556in"
height="7.013888888888889e-2in"}

**National Vaccine Advisory Committee (NVAC)**

**June 1-2, 2004 meeting**

[Meeting Overview]{.underline}

The major focus of this meeting was influenza. Presentations included
those the NVAC Influenza Working Group as well as senior personnel of
the National Vaccine Program Office, the Centers for Disease Control and
Prevention, the Food and Drug Agency, and Health Canada. The three
subcommittees in their respective meetings also discussed influenza from
their perspectives of immunization coverage, communication and future
vaccines. Additional topics of discussion included: vaccine safety,
vaccine financing, public participation in vaccine policy, the IOM's
report regarding vaccines and autism, and smallpox vaccine.

[Committee Members in Attendance]{.underline}

Dr. Charles M. Helms---*Chair*

Dr. Jeffrey P. Davis

Dr. Fernando A. Guerra

Dr. Alan Richard Hinman

Dr. David Johnson

Ruth Katz

Dr. Jerome O. Klein

Mary Beth Koslap-Petraco

Dr. Georges Peter

Dr. Richard Raymond

Dr. Patricia N. Whitley-Williams

Dr. Adele Young

## [Executive Secretary]{.underline}

Dr. Bruce Gellin

## [Liaison Representatives]{.underline}

Dr. Steven Black, American Association of Health Plans -- (6/2 only)

Jackie Noyes, Advisory Commission on Childhood Vaccines

Dr. Gary D. Overturf, Vaccines and Related Biologics Products Advisory
Committee

Dr. Myron Levin, Advisory Committee on Immunization Practices

Ms. Jackie Noyes, Advisory Commission on Childhood Vaccines -- (6/2
only)

## [Ex Officio Members]{.underline}

Dr. Steve Cochi, Acting Director, National Immunization Program (NIP),
Centers for Disease Control and Prevention (CDC)

Dr. George Curlin, National Institutes of Health (NIH)

Dr. Bill Egan, Food and Drug Administration (FDA)

Dr. Geoffrey Evans, Medical Director, Division of Vaccine Injury
Compensation Program, Health Resources and Services Administration
(HRSA)

Dr. James Randolph Farris, Regional Administrator, Region VI, Centers
for Medicare and Medicaid Services (CMS)

Emily Marcus Levine, Senior Attorney, Office of the General Counsel,
DHHS

Col. Renata J. M. Engler, Chief, Allergy/Immunology Department, Walter
Reed Medical Center, Department of Defense (DoD) -- (6/2 only)

# [Committee Members Absent]{.underline}

Dr. Norman Baylor, Microbiologist, Center for Biologics Evaluation and
Research (CBER), Food and Drug Administration (FDA)

Dr. Ann Margaret Arvin, Director, Stanford-LPCH Vaccine Program,
Stanford University School of Medicine

Dr. Neal Brandes, U.S. Agency for International Development (USAID)

Dr. Gary Freed, Director of Pediatric Health Services Research and
Fellowship Program at the University of Michigan at Ann Arbor

Dr. William Schaffner, Professor and Chair, Department of Preventive
Medicine, Vanderbilt School of Medicine

Dr. Donald E. Williamson, State Health Officer, Alabama Department of
Public Health

# [Invited Speakers]{.underline}

Dr. Cristina Beato, Acting Assistant Secretary of Health

Dr. Jerome Donlon, DHHS, OS, ASPHEP

Dr. John D. Grabenstein, Department of Defense Smallpox Vaccination
Clinical Evaluation Team

Dr. Arlene King, Director, Immunization and Respiratory Infections
Division, Health Canada

Dr. Marie McCormick, Chair, Immunization Safety Review Committee

Dr. Barbara Mulach, DHHS, NIH, NIAID

Dr. Lance E. Rodewald, Director, Immunization Services Division, NIP,
CDC

Dr. Jeanne Santoli, Associate Director of Science, NIP, CDC

Dr. Benjamin Schwartz, National Vaccine Program Office (NVPO)

Dr. Greg Wallace, Acting Chief, Program Support Branch, Immunization
Services Division, NIP, CDC

**Welcome from the National Vaccine Advisory Committee Chair -- Dr.
Charles Helms**

Dr. Charles Helms welcomed the meeting attendees and asked National
Vaccine Advisory Committee (NVAC) members to introduce themselves. Dr.
Helms asked NVAC members to declare conflicts of interest as they arise,
noting that they rarely occur given the general issues they discuss. Dr.
Guerra noted that his department receives some support from a number of
vaccine companies for clinical and field trials, including Merck,
AventisPasteur, and GSK. Dr. Helms then asked all of the guests in the
audience to introduce themselves.

ACTION: The February 2004 NVAC meeting minutes were approved by the full
Committee.

Dr. Helms then noted four new members of the committee, three of whom
were able to attend the meeting: Dr. Gary Freed of the University of
Michigan, Dr. David Johnson of AventisPasteur, Dr. Richard Raymond of
the Nebraska Health and Human Services System, and Dr. Adele Young of
George Mason University. Dr. Helms then announced that Dr. Ann Arvin has
agreed to assume the role of Chair of the Future Vaccine Subcommittee
following Dr. Patricia Fast's departure. Additionally, Drs. Jerome Klein
and Patricia Whitley-Williams have both agreed to continue as Chairs of
the Subcommittee on Vaccine Safety and the Subcommittee on Immunization
Coverage respectively.

Dr. Helms noted that this meeting was again going to concentrate on
influenza, largely in response to Acting Assistant Secretary for Health
Dr. Beato's request of the previous meeting for the development of a
working group in that area.

**Report of the National Vaccine Program Office -- Dr. Bruce Gellin**

Dr. Bruce Gellin, Director of the National Vaccine Program Office
(NVPO), gave a brief status report regarding the Pandemic Influenza
Preparedness and Response Plan. He noted that the Plan was in final
review, having been passed from the Department to other agencies. The
Plan's release will be announced in the *Federal Register* and will be
followed by a 60-day public comment period, during which the Committee
is hoping to be able to provide comment as well. During this time, the
Plan will be posted on the DHHS website
([www.hhs.gov](http://www.hhs.gov/)). Dr. Gellin commented that the plan
is large and complicated and will involve many parts of DHHS, as well as
other agencies and international governments as well. The Plan is a
complex "living" document and periodic reviews and updates are expected.

Department international activities regarding influenza: Dr. Gellin
noted that Secretary Tommy G. Thompson recently met with Minsters of
Health from over 12 Asian countries that had been hit with avian
influenza outbreaks last year, reinforcing the importance of pandemic
influenza preparedness and particularly surveillance and international
collaboration.

Dr. Gellin noted two RFPs currently being reviewed by the Department
addressing vaccine production as an integral part of pandemic
preparedness. One is intended to ensure adequate egg supply to permit
year-round production and the second is intended for cell culture
vaccines.

The CDC's Blue Ribbon Panel on Vaccine Safety is scheduled to meet later
in the week. Anticipated topics include: CDC's current vaccine safety
program, the program's intramural and extramural collaborative
activities, and the optimal organizational location for vaccine safety
activities within the CDC. NVAC will hear back from CDC at a subsequent
meeting on this panel's consultation.

**NVAC Influenza Vaccine Working Group -- Dr. Charles Helms (Chair)**

Dr. Charles Helms noted that the February NVAC meeting was built, in
large part, around the National Influenza Immunization Program. During
that meeting, Acting Assistant Secretary for Health, Dr. Christina Beato
charged the Committee to step back and look at the National Influenza
Immunization Program as a whole. Specifically, she asked NVAC to consult
with NVPO, DHHS agencies, and their advisory committees, as appropriate,
to thoroughly review the program and to report back insights and
recommendations. In response to this charge, Dr. Georges Peter put
together a NVAC Influenza Vaccine Working Group and asked Dr. Helms to
chair it. The purpose of the working group is to evaluate strategies and
capabilities to reduce the impact of influenza disease in the U.S. and
make recommendations on how to substantially improve prevention and
reduce disease burden. The working group was asked to present a
preliminary report at this NVAC meeting.

The working group was divided into the following three Subgroups:

-   Influenza Vaccine Research, Development, and Production Subgroup
    chaired by Dr. Ann Arvin with Dr. Gellin as the NVPO staff.

-   Influenza Vaccine Recommendations and Strategies Subgroup chaired by
    Dr. Jerome Klein with Dr. Ben Schwartz from NVPO. This subgroup
    includes issues related to adult immunization, measuring the burden
    of disease and vaccine efficacy.

-   The Influenza Vaccine Delivery, Financing, and Demand Subgroup
    chaired by Dr. Fernando Guerra with Sarah Landry from NVPO. Key
    issues include: private and public delivery systems, communications
    issues, and demand.

The draft report should be prepared in September and be suitable to
present to NVAC in October.

Drs. Klein and Schwartz then provided a summary of the Influenza
Vaccines Subgroup activities. The objectives of the subgroup are to: 1)
examine the data on influenza disease burden; 2) assess the
effectiveness of current surveillance systems; 3) suggest strategies to
improve current influenza surveillance systems; and 4) consider
alternative vaccination strategies to decrease disease burden.

Dr. Schwartz then reviewed the subgroup recommendations based on its
evaluations. The subgroup recommends: 1) the expansion of active,
prospective surveillance with etiological diagnosis in sentinel
populations of children and adult, such as the New Vaccine Surveillance
Network; 2) collaboration with health care organizations to obtain rapid
turn-around data on influenza-like illness and documented influenza
disease that can be used in annual vaccination effectiveness studies; 3)
meetings should be held to evaluate the different methods of estimating
program impacts, reconcile the differences between different
epidemiological approaches, and to propose studies that will help
resolve those differences; and, 4) recognizing that surveillance is
expensive, support should be provided to expand surveillance activities.
With respect to new influenza vaccination strategies, recognizing that
ACIP is the primary Federal advisory committee with a mandate to make
immunization recommendations to CDC, the subgroup would like to support
and contribute to the ACIP evaluation process as they consider expanded
or universal influenza vaccination.

Dr. Schwartz closed by identifying several potential NVAC roles, which
reflect the Committee's position in addressing crosscutting issues.
These include:

1.  Assessment of the vaccine supply issues: The current supply of
    vaccines manufactured for the U.S. market is not adequate to
    vaccinate the entire population. Supply issues will be a key factor
    related to the ability to implement a universal vaccination
    recommendation.

2.  Assessment of vaccine delivery strategies and delivery technologies
    that could make universal immunization more feasible.

3.  Assessment of vaccine financing options: While the Vaccines for
    Children (VFC) program provides publicly funded vaccinations for
    children under the age of 18 and Medicare covers immunization of
    adults over 65 years of age, there will be a large gap in coverage
    should recommendations become universal.

Dr. Guerra, chair of the Vaccine Finance, Delivery and Acceptance
Subgroup provided a review of their work thus far. The questions guiding
the subgroup's work are: What changes should be made to enhance
acceptance and promote demand for influenza vaccine by the public and
health officials? Are the current private/public programs for adult
immunization adequate? What changes can be made to strengthen this
programmatic infrastructure?

Research conducted by the subgroup supported the following conclusions:
many unvaccinated patients appear unwilling to spend the time and money
required to finance their own vaccination; third party coverage for
immunizations is a fig leaf; and as stated in "Unequal Treatment" from
the Institute of Medicine (2002) - "Priorities should shift from
documenting disparities to assessing interventions strategies ... that
separate the contribution of the patient, provider, and institution."
This led the subgroup to ask: Can we increase demand and delivery
without putting additional burden on the patient or provider? Literature
suggests this can be accomplished by: reorganizing the delivery of
preventive services; instituting provider/patient reminder-recall;
giving the patient a salient reason to be vaccinated; and reducing
out-of-pocket costs. Dr. Guerra referred to one of the conclusions of
*Calling the Shots* (IOM, 2000), which found that the improvement of
adult immunization rates will require more than increased vaccine
purchases: a comprehensive and coordinated adult immunization program
needs to be initiated within each state, with leadership at the
national, state, and local levels.

Short-term priorities are to investigate alternative delivery
strategies, enhance outreach to other preventive care strategies and
minimize "missed opportunities," and reinforce the importance of the flu
vaccine for health care workers. The long-term priorities are to find
opportunities to enhance/create comprehensive vaccination programs for
adults, and to address financing issues and make influenza vaccination a
more cost-effective prevention strategy.

Dr. Guerra noted that there are opportunities where adults find
themselves in a variety of settings that could be incorporated into the
concept of a medical home for maintaining good levels of adult
immunization coverage beyond influenza and pneumococcal vaccines. They
also need to seriously look at the alternative vaccination sites that do
not always connect themselves to a traditional medical home, such as
pharmacies with delegated standing orders. There are many alternative
sites including large employers who provide a variety of adult
immunizations for their workers. He also noted the need for a "Vaccines
for Adults" program, the adult equivalent of the Vaccines for Children
(VFC) program. Such a program would allow more coverage of the front-end
costs and make adult vaccine availability more comprehensive.

Dr. Gellin gave the final subgroup presentation on behalf of Dr. Arvin.
The Vaccine Research Subgroup looked at a list of important research
issues, many of which NIAID was already considering in their research
portfolio. Areas requiring further/ongoing research include:

-   Understanding the limits of existing vaccines in vulnerable
    populations, particularly with the elderly.

-   Influenza immunity and immune evasion.

-   The potential role of adjuvants in enhancing immune response to
    influenza vaccines. While adjuvants might enhance the vaccine
    performance in the elderly, they may, at the same time, have a role
    in expanding the antigen supply for pandemics and, therefore,
    increase the number of doses of available vaccine.

-   New technology for vaccine production: some new technologies were
    discussed at the February 2004 NVAC meeting.

-   Better understanding of the virulence and transition dynamics,
    particularly the veterinary/human interface.

-   Infrastructure and resource needs. As outbreaks have resulted from a
    lack of containment in some laboratories, there may be a need to
    increase the number of bio-safety laboratories to allow necessary
    work.

-   The importance of public/private partnerships and input from
    stakeholders in developing a national research strategy.

-   Global harmonization and the possibility of using influenza as a
    model for vaccine harmonization between the FDA and EMEA and others.

Dr. Gellin highlighted a section from a WHO meeting report from March of
this year that discussed future vaccines. The report highlights the
importance of cross-subtype vaccines that confer long-lasting protection
as a possible approach. This approach may even allow future stockpiling
of vaccines for pandemics. In summary, Dr. Gellin reviewed the
subgroup's preliminary conclusions: 1) DHHS should consider conducting a
comprehensive cross-agency overview of all ongoing and planned research
with the goal of developing a coherent national influenza research
agenda, recognizing that there is a broad range of overlapping research
needs among the agencies; and 2) innovation for developing improved
vaccines (i.e. vaccines that are more effective, have broad protection,
and better production technologies) needs to be encouraged and enhanced.

Dr. Helms thanked the subgroups and noted that a substantial amount of
work had been done. He then opened the floor to Dr. Beato before
allowing questions.

**Welcome from the Acting Assistant Secretary for Health - Dr. Cristina
Beato**

*[Welcome to Dr. Charles Helms, NVAC Chair]{.underline}*\
Dr. Beato welcomed and thanked meeting attendees. She formally welcomed
Dr. Helms as the Chair of NVAC. He is a professor of internal medicine
at the University of Iowa (UI) at the Roy J. and Lucille A. Carver
College of Medicine and Chief of Staff at UI Hospitals and Clinics. He
also served as Medical Director at the Office of Clinical Outcomes and
Research Management at the UI Hospitals and Clinics. He was elected
Chief of Staff of UI Hospitals and Clinics in 1998. He received his B.A.
at Cornell University, and his Ph.D. and M.D. degrees at the University
of Rochester, School of Medicine. He was a resident physician of
internal medicine at Massachusetts General Hospital and a research
associate and medical officer at the Laboratory of Infectious Diseases
at NIH before joining the faculty back at UI in 1976. He has been
involved in hospital and patient safety issues, quality improvement, and
health policy issues throughout his career. In 1985, he was awarded the
Robert Wood Johnson health policy fellowship. He has worked with the
Majority Staff of the Committee on Labor and Human Resources of the U.S.
Senate and is very familiar with the workings of Congress. He was
involved in negotiating and drafting legislation establishing the
National Vaccine Program and the National Vaccine Injury Compensation
Program. He chaired the Public Policy Committee of the Infectious
Diseases Society of America. He was appointed as a member to NVAC and
chaired ACIP's Working Group on Bioterrorism. Dr. Beato expressed that
she is much honored to have Dr. Helms as Chair of the Committee. He will
be invaluable in guiding information to the Secretary and herself.

*[Pandemic Preparedness Response Plan]{.underline}*\
Dr. Beato announced that the Pandemic Preparedness Response Plan will be
going on the Department website soon, asking everyone in the room to
take a look at it and to provide their questions, concerns, and
constructive criticism. She noted that the original draft of this plan
was completed 17 years ago. It is critical that the plan be shared with
stakeholders and the public for feedback so that the best plan for the
country can be created. State groups will also be asked provide
feedback.

*[Comments for the Influenza Vaccine Working Group]{.underline}*

-   The surveillance of emerging new strains overseas was not addressed
    in the Influenza Vaccine Working Group briefings, is the working
    group comfortable with how it is currently working?

> *Dr. Schwartz:* Additional investments are important as is
> coordinating the investments with the WHO and existing surveillance
> structures.

-   This is the first year they will see this happen, could an update be
    given in mid-December?

> *Dr. Schwartz:* An update might even be possible for the October NVAC
> meeting.

-   What could be done to incorporate influenza surveillance in what the
    states are doing with regard to bioterrorism?

> *Dr. Schwartz:* What stood out to the working group and what would
> make this very difficult to cover in a multi-component surveillance
> system is directly defining the amount of influenza through diagnostic
> testing and determining who has influenza versus other respiratory
> diseases.

-   Would the Vaccine Finance, Delivery, and Acceptance Sub-group
    consider thinking outside of the science and examining the influenza
    vaccine as a product for which we want to increase demand and start
    with a reachable population, such as health care providers? How do
    the various populations learn from this and how can we get adults to
    realize that influenza vaccination is a benefit to them and become
    willing to make an effort, in terms of time and money, to acquire
    the vaccine?

> *Dr. Guerra:* This issue has been addressed in preliminary
> discussions. Health care workers, as a group, need to be targeted to
> increase immunization coverage. Information from lessons learned over
> the last few years---whether through large group practices, hospitals
> where they serve on staff, medical societies, or professional
> organizations---to try to increase demand using local campaigns.
> Another issue is communication and how to convey the message that the
> many different health care workers need to set the example. This needs
> to be done in a way to benefit a much larger community. On the
> financing side, this continues to be an issue because it is a very
> uneven playing field, but there are ways to increase coverage with
> minimal costs.

-   Has the subgroup considered how offering an over-the-counter vaccine
    might affect delivery and costs if research were successful in
    producing a vaccine that could be offered this way?

> *Dr. Guerra:* This would be ideal and has been part of past
> discussions about the intranasal vaccination. This could be possible
> if costs decreased to a reasonable level and safety issues could be
> dealt with. There are existing models from which they can learn: using
> pharmacists as public health extenders has been very successful; or,
> delegating standing orders linked to public health systems with good
> accountability where targeted populations can be maintained.

-   Technology continues to improve for financing and tracking systems
    if, for example, the vaccine were available over the counter (e.g.,
    bar coding). If this becomes possible in 5 years, has the subgroup
    looked at what steps NVAC could recommend to the Secretary and DHHS
    to improve technology and access?

> *Dr. Guerra:* There have been ongoing discussions on trying to achieve
> a national system for immunization registries and tracking systems.
> There have been good models for children's programs that need to be
> applied to adults, but they need to be accurate to ensure they are
> working. Additional resources are needed to develop this type of
> program at the local and state levels. This can be done through
> technologies such as bar coding and scanning, which allow the
> efficient handling of large data sets. Furthermore, studies have shown
> that reminder-recall systems linked to registries or tracking systems
> are highly effective.

-   Was there anything outstanding about the California and New York
    programs that NVAC should more deeply examine as a possible national
    best practice model?

> *Dr. Guerra:* The states have been generous with resources for
> eligible target populations, particularly Medicaid-eligible young
> adults and populations with disabilities. This moves them in the
> direction of needing an adult equivalent to the VFC program, where
> upfront costs would be covered and vaccines would be available,
> particularly for the uninsured.

-   Is reaching out to both insured and uninsured 18 to 21 year olds who
    do not see the value in vaccination an area where NVAC should elicit
    partners to do an Ad Council campaign or use some other new and
    creative means to educate the public about the benefits of
    vaccination? In particular, it is difficult to relate the value of
    influenza vaccinations if health care providers do not see the
    value. How could the Department utilize creative means or social
    marketing approaches to increase awareness or get health care
    providers to lead by example?

> *Glen Nowak* (Director of Communications, NIP): Part of the problem is
> that there are no recommendations for annual vaccinations for young
> adult populations or even populations 18 to 49 years of age. There are
> three groups that need to be targeted in such a campaign: one group
> values the vaccination and only want to know when the vaccine is
> available; the second group is waiting to see how bad the season is
> expected to be before deciding to be vaccinated; and the third group
> is unconvinced of the value of the influenza vaccine.

Dr. Helms thanked Dr. Beato for her questions and for following the
activities so closely.

Dr. Beato closed in noting that an overview of comprehensive,
cross-agency research (as mentioned in Dr. Gellin's Sub-group report),
is something that really needs to be done.

**Ottawa's "Universal" Influenza Immunization Program -- Dr. Arlene King
(Health Canada)**

Dr. Arlene King explained that she would give some background on
Ottawa's universal influenza immunization program, briefly discuss
surveillance, how they generate scientific recommendations, the program
and process development processes in Canada, vaccine supply, public
education, vaccine safety, and influenza research. Canada has 13
provinces and territories, and the responsibility for delivery of health
care services lies with the provinces and territories. The only
jurisdiction with a universal approach to influenza immunization is
Ontario, Canada's largest province with about 12 million people,
accounting for about 30 percent of the Canadian population.

Dr. King stated that they have been working hard over the past few years
to develop a National Immunization Strategy (NIS), a comprehensive,
collaborative (among governments), progressive strategy to meet the
current and future immunization needs of all Canadians. It is also a
means for governments and other key stakeholders to work in partnership
to address national immunization issues. The five key components of NIS
are: national goals and objectives; equitable access through
collaborative immunization program planning; vaccine supply;
immunization registries; and immunization safety. There are five
supporting activities: immunization research, public education,
professional education, approaches to special populations (e.g.,
travelers and first generation immigrants), and vaccine preventable
disease surveillance.

The mainstay of the influenza surveillance program in Canada is
FluWatch, a partnership with all jurisdictions producing weekly reports
that are posted on the Health Canada website. FluWatch has four major
activities: 1) early detection and monitoring of national and provincial
influenza activity through real time surveillance of influenza-like
illnesses; 2) international monitoring of influenza activity; 3)
information sharing through vast networks; and, 4) rapid, real-time
information dissemination. In addition, a pilot project collects real
time data on influenza hospitalizations in children through the IMPAct
program, a major contributor to Canada's pediatric surveillance program.
Finally, national vital statistics and hospital data are used in
estimating the impact of influenza on morbidity and mortality, including
modeling. She added that last year, they requested that all provinces
and territories report influenza-related mortality from all
jurisdictions. This was well received and implemented by all
jurisdictions. Scientific recommendations are provided by: the National
Advisory Committee for Immunization (NACI); and the Pandemic Influenza
Committee.

Through the newly formed Canadian Immunization Committee (CIC), all
jurisdictions will have recommendations and will be responsible for
developing: national goals and objectives that will ensure they move
towards harmonization of programs across the country; effective and
cost-effective immunization programs; frameworks and practices; and
guidelines and best practices. Since 2000, Ontario has had a publicly
funded program for all residents aged 6 months and older. Most other
provinces use a "targeted approach" in which publicly funded programs
provide for vaccines and program delivery for seniors, high-risk people
under 65 years of age, household contacts of high-risk people, and
health care workers.

Canada has established very innovative arrangements that protect them,
for the most part, from vaccine shortages. They have a Vaccine Supply
Working Group that reports directly to CIC and involves all
jurisdictions that purchase vaccines. It is involved in reviewing and
assessing Canadian vaccine supply issues and making recommendations to
vaccine manufacturers and Health Canada. They also have a bulk
purchasing program in place through the Public Works and Government
Services of Canada. This process enables the purchase of virtually the
entire supply of publicly funded vaccines.

The Annual Influenza Awareness campaign is designed to raise awareness
of the need for annual influenza immunization. The campaign provides
credible sources of information for the public, health professionals,
and the media. Ontario has a very well funded, very strong public
education program to promote its universal program. There is a lot of
investment with several well-recognized key stakeholders participating
in things such as television advertisements.

The influenza vaccine-associated adverse event surveillance system
(VAESS) is the cornerstone of vaccine safety. It includes a passive
surveillance system that enables rapid risk assessment and response to
reported events. Generally, vaccine providers report vaccine-associated
adverse events to their local health authorities or local medical
officers of health. Reports are subsequently forwarded to provincial and
territorial health ministries and then sent to Health Canada.

Health Canada is currently looking at developing an overall national
research agenda. In addition, they have been asked by the province of
Ontario to coordinate the evaluation of their Universal Influenza
Immunization Program and plan to have further discussions with
stakeholders and other jurisdictions to participate in this evaluation.
The other key area is mock-up vaccine production and clinical trials
with novel influenza vaccine strains to test pandemic vaccine production
capacity. They are also proceeding to collaborate on the development of
new vaccine technologies. A major vaccine coverage survey is planned,
which includes flu utilization, and they are conducting annual vaccine
effectiveness studies.

The country's overall influenza immunization rates were a bit lower than
those for Ontario, and it is uncertain whether this is the result of
promotion or their universal program. The coverage rate for people 65
and older was 77 percent in Ontario and 70 percent to 75 percent for the
rest of the country. Coverage for people under 65 years of age with
chronic medical conditions was 48 percent, while coverage among
individuals in this age group with no risk factors was only 26 percent.
The greatest success story was coverage among long-term care facility
residents and staff. Among residents, coverage was about 95 percent, and
80 percent to 85 percent for staff and volunteers. Among hospital
workers in Ontario, coverage was about 50 percent. The impact on
morbidity and mortality and affirmation of coverage rates are still
uncertain.

**READII Update -- Dr. Lance Rodewald (CDC/NIP)**

The Racial and Ethnic Adult Disparities in Immunization Initiative
(READII) was a department-initiated project where DHHS asked CDC for an
important set of demonstration projects that could reduce racial and
ethnic disparities. CDC (in collaboration with CMS, HRSA, AoA, and AHRQ)
aimed to reduce the dramatic plus 20 percentage gap in coverage between
elderly African Americans and Hispanic Americans and whites. The five
project sites are: Chicago, Milwaukee, Mississippi's Delta region,
Rochester, and San Antonio.

In March 2004, there was a mid-course review meeting to review and
discuss the successes and challenges in the project. Major observations
made during this meeting included: 1) significant barriers to greater
private provider participation exist; 2) lack of financial incentives to
implement interventions; 3) provider concern regarding financial risk
and sustainability. Recommendations made by invited panelists
included: 1) to establish relationships with public health providers,
targeted communities, and others to foster a prevention mindset for
adults, i.e. using CMS's "Welcome to Medicare" visit as a way to put the
idea of prevention in the minds of people over 65; 2) to adopt an
"intergenerational approach" to messages and vaccination so that one
generation can protect another generation; 3) to develop a "menu" of
approaches to flu vaccination; and, 4) to provide vaccine in a
replacement model to avoid upfront provider costs.

Outcome evaluation using the CMS telephone survey of Medicare
beneficiaries residing in the project areas was done in three waves the
first wave of which is currently being evaluated. The topics of the
outcome evaluation intended to measure change over time and to
understand the relationship between racial and ethnic disparities and
various factors predictive of vaccination included vaccination coverage
levels, provider recommendations, and knowledge and attitudes of
patients. Baseline data presented from the first wave of evaluation
showed noticeable gaps in coverage between the white, African-American,
and Hispanic populations in each site, with the exception of Chicago,
where coverage among whites and Hispanics was very close.

Data on the relationship between provider recommendation and actual
influenza vaccination indicate that provider recommendations influence
patient vaccination. The data also show that only about 50 percent of
patients received a recommendation from their provider. Rates were lower
among people who believed that they had become ill from the influenza
vaccination.

Dr. Rodewald also presented data on coverage for pneumococcal
vaccination by READII site and race. Again, baseline data showed racial
and ethnic disparities. Data on the relationship between provider
recommendation and pneumococcal vaccination compared to influenza
vaccination showed that noticeably fewer African-Americans received
provider recommendations for pneumococcal vaccination (40 percent) than
whites (60 percent). For influenza vaccination, about half of each
racial/ethnic group reported receiving a provider's recommendation. The
data for pneumococcal vaccination showed that vaccine coverage was
extremely low among patients who did not receive provider
recommendation. The data indicate that provider recommendation has a
profound effect on coverage, which is an area that needs work.

Evaluation of specific interventions covered: standing orders in health
department clinics; practices targeted for assessment and feedback;
practices providing free vaccine; pharmacist vaccination;
reminder/recall; and, community immunization clinics. For each
intervention, they looked at coverage before and after implementation of
the intervention. In addition, they are examining the percent
implementing these changes. For pharmacist vaccination and community
immunization clinics, they are examining the proportion of persons
presenting for a flu shot who are eligible to receive pneumococcal
vaccine. In addition, for community immunization clinics, they are
looking at the proportion of people presenting for a flu shot who are
not "regulars."

There will be a final wave of evaluation activities in January 2005 with
the hope of disseminating the findings.

**Preview of the 2004-2005 Influenza Season -- Dr. Jeanne Santoli
(CDC/NIP)**

Dr. Jeanne Santoli reviewed the timeline for the upcoming season, which
included vaccine contracts, purchases, and administration. Pre-booking
for influenza vaccine for non-CDC orders began in December 2003, which
is earlier than usual because of last season's experience. Between March
and May, Federal influenza vaccine contracts (including both
preservative-free and preservative--containing formulas) were
negotiated, immediately after which Federal immunization grantees began
placing orders. In August, ACIP will assess the need for tiered
vaccination. In September, vaccine delivery and vaccination typically
begins, and in March 2005, the vaccination season ends. Dr. Santoli
discussed changes and updates to influenza recommendations, highlighting
the change from an encouragement to a recommendation for the annual
vaccination of healthy children aged 6 to 23 months and close contacts
of those aged 0 to 23 months.

Dr. Santoli noted that it is critical to evaluate what is currently
being done to expand pediatric influenza vaccination. CDC is either
involved in, collaborating on, or sponsoring about a dozen studies that
will assess: vaccine effectiveness and impact; vaccination coverage;
location and timing of vaccination; prevalence of provider
recommendation to parents; barriers faced by providers during the
2003--2004 influenza season; parental reasons for declining vaccination;
and the burden of hospital-acquired influenza infections among children.

Assuring an adequate vaccine supply is important, but hampered by the
fact that we do not know how providers' and parents' past season
experiences will affect this season's demand. This is further
complicated by the variation in vaccine formulation preferences. Another
factor is that preservative-free vaccines have a reduced production
yield.

Dr. Santoli presented data on influenza vaccine doses produced for the
U.S. market from 1999 to 2003. Data show that vaccine production has
increased over the past 5 years, with approximately 87 million doses
produced last year. The vaccine production projections for the upcoming
year are estimated to range from 90 to 100 million doses, including 7 to
8 million doses of preservative-free inactivated influenza vaccine and 1
to 2 million doses of live attenuated vaccine.

CDC's pre-season actions have included developing estimates of grantee
need and monitoring vaccine orders from grantees. In response to the
emerging difference between demand from the Federal grantee orders and
the amount of vaccines available from Federal contracts, they have put a
hold on Federal contract purchases for preservative-containing influenza
vaccine with state dollars so that 317 dollars and VFC funds can be used
first. They are also working with manufacturers on increasing contract
maximums. They expect to be able to increase contract maximums by about
1.2 million doses in both contracts, and this will likely meet the
demand from grantee orders. They are also working on developing an
allocation plan to ensure an equitable vaccine distribution across the
states. Although there is an encouragingly high level of demand from the
states, it is uncertain how that will translate into provider and family
demand for vaccination. CDC will also work with manufacturers and
distributors during the season to track vaccine supply weekly.

Another method to ensure an adequate vaccine supply is to stockpile
influenza vaccine. This will be supported this year by the VFC program,
with \$40 million dollars from the FY 2004 budget and \$40 million from
the FY 2005 budget. The contracting process is underway and the
stockpile will contain a mix of inactivated vaccine products. NIP/NCID
at CDC is working to develop release models (possible influenza season
scenarios) and mechanisms for vaccine distribution for each scenario.

This season's expanded recommendations provide an opportunity for
growing the influenza vaccine market and culture, which will likely have
long-term influenza vaccination benefits. She noted that the
recommendations call for an increase in the target population of 20
million people. The target population for the 2004--2005 season is
estimated at about 186 million, while the previous season had a target
population of about 165 million. The increase is primarily in the 6 to
23 month age group along with household contacts. Additionally,
pediatric vaccination may change public perception of influenza
vaccination by linking it with routine childhood immunization,
demonstrating the safety of the vaccine in very young infants, and
increasing awareness of the importance of parental vaccination to
protect young children.

In closing, Dr. Santoli reviewed the themes from the 2004 Influenza
Summit that took place in April in Atlanta, GA: develop a crisis plan,
including monitoring vaccine supply at levels lower than the
manufacturer; create a year-long, coordinated approach to influenza
communications; continue efforts to improve influenza vaccine uptake for
current risk groups and extend the vaccination season when appropriate;
improve health care worker vaccination rates; advocate for
public/private funding for influenza vaccination, particularly for
underinsured and uninsured adults; consider a broader concept of
influenza prevention as a part of Summit activities; and explore
universal vaccination.

**[Pandemic Influenza]{.underline}**

**The Influenza Pandemic Preparedness and Response Plan -- Dr. Ben
Schwartz (NVPO)**

The plan has been cleared by DHHS and its agencies and is being reviewed
by other departments. After clearance, it will be released to the public
in the *Federal Register* and online for an anticipated 60-day comment
period. The plan will then be revised to incorporate comments and a
"final" plan will be posted. The "final" plan will be a working document
that will be reviewed and revised periodically.

Key issues where decisions need to be made and where public comment will
be particularly important include: 1) public and private sector vaccine
purchase and distribution; 2) selection of priority groups for early
vaccination and antiviral chemoprophylaxis and therapy is another issue;
3) the approach to indemnification, liability protection, and
compensation.

Possible public and private sector roles in pandemic vaccine purchase
options:

-   All vaccine purchased by the public - This approach would provide
    the best opportunity to target priority groups and would require
    planning for mass distribution to both the public and private
    sectors.

-   An increased public role where about 85 percent would be purchased
    by the public sector - The public sector focus could be on priority
    groups and underserved populations that are not as well covered
    given the current predominantly private system. (Coordination
    between the public and private sector would be required.)

-   The current predominantly private approach - The public sector must
    focus on limited priority groups and children via the VFC program.

-   Rather than having a static approach to those distributing the
    vaccine, which would change over the course of a pandemic and where
    different waves of disease may occur seasonally, when vaccine is
    most limited, the public sector could distribute vaccines to
    targeted groups in greatest need -- ex: as vaccine becomes more
    available, they could move to the increased public role approach.
    When vaccine is most available, they could return to the current
    system that is predominantly private.

Identification of priority groups could be defined based on pandemic
response goals. These goals are to: reduce health impacts by maintaining
quality health care systems, which suggests that health care workers can
be a target group for vaccination, protecting those at highest risk;
and, reduce social and economic impacts, indicating the importance of
maintaining essential community services, which in turn makes essential
community service providers a target group. Would it be beneficial to
have national guidance as opposed to having states decide who the
priority groups should be? Once priority groups are defined, specific
definitions of these groups at state and local levels need to be
determined.

Dr. Schwartz explained that NVPO would like NVAC to provide input on key
issues with the pandemic plan, particularly on the "decision" issues
that he highlighted. They also welcome comment on any other issues where
NVAC's broad stakeholder perspective or NVPO priorities (e.g., vaccine
supply, financing, and safety) are relevant. They thought NVAC might
help by providing a forum for public discussion and input through the
Public Participation Working Group.

**Canadian Pandemic Plan -- Dr. Arlene King (Health Canada)**

Dr. Arlene King discussed the Canadian Pandemic Plan, including an
overview of the plan's evolution; how the plan was used in response to
H5N1 (2003) and SARS; how the plan has been modified, including key
challenges, successes, and general lessons learned from SARS; and the
current status of the plan and next steps.

The pandemic planning in Canada has been happening for some time. The
impetus for the current state of affairs was avian flu in Hong Kong in
1997. Federal-provincial-territorial (F/P/T) planning took place from
1998 to 2000. Planning continued in 2000 to 2001 with two national
planning meetings, and working groups were established in 2000 to 2001.
This resulted in the F/P/T Working Agreement being accepted by all
provinces and territories on roles and responsibilities during a
pandemic. A multiyear vaccine contract and a pandemic contract were
signed for the annual provision of vaccine as well as for a pandemic
infrastructure, ensuring a constant state of pandemic vaccine readiness.
They then established the Pandemic Influenza Committee (PIC). Lessons
learned from SARS were incorporated between July 2003 and January 2004.
On December 12, 2003, the Canadian Pandemic Influenza Plan was approved
by the Deputy Ministers of Health. The plan was released to the public
on February 12, 2004 and is available online at
www.hc-sc.gc.ca/pphb-dgspsp/cpip-pclcpi/.

The PIC was established under the F/P/T working group. It has federal
and provincial co-chairs and 18 voting members representing all
jurisdictions. The PIC's role is to provide technical advice for annual
and pandemic influenza prevention and control. They would report
directly to the Ministers of Health during the pandemic, providing
advice on any issues that may come up. The PIC also provides ongoing
overall guidance on the plan.

Dr. King noted the biggest challenge was the public health
infrastructure with regard to human resources, data management capacity,
policies, procedures, and legislation. Other key problems were
information gathering and sharing and evidence-based decision making.

In terms of general lessons learned, Dr. King noted that team work is
essential, and there needs to be dedicated leadership that will not be
pulled away to deal with other issues--- leading a crisis like this is a
full-time job. It is critical to plan staffing, have shifts to allow
time off, and achieve continuity of response activities. It is important
to support the staff/responders, for example, by providing meals,
off-hours transportation, childcare, etc. A "think tank" team that is
not directly involved in the response is also needed. PIC has done this
effectively by having a team that was thinking beforehand about issues
that may come up. The response team components should include a
coordination and operations team (with international liaison), a
technical team, a logistics team, a communications team, and a think
tank team.

Another lesson, related to H5N1 and H7N3, is that zoonotic diseases can
and will cross the species barrier and cause illness in humans. Ties
must be forged with those responsible for non-human animal disease
surveillance and response. Those managing epizootics may be the index
cases of the next emerging infectious disease. This was the case in
British Columbia where the people doing the culling were the ones who
became infected through direct contact with infected chickens.
Therefore, occupational health and safety personnel will be important
allies in public health response.

The Canadian Pandemic Influenza Plan is based on nationally agreed upon
goals and is organized into components. The plan uses WHO Pandemic
Phases. She noted that wherever possible, one should adopt common
terminology and surveillance definitions to avoid confusion. The
Canadian phases are completely consistent with the global pandemic
phases. The plan is national and outlines the roles and responsibilities
of all levels of government. It is a model for national emergency
response plans that contains checklists and technical annexes. The plan
is a dynamic or "evergreen" document that will be continually worked on.

Dr. King then discussed current activities with respect to the plan.
They are using their pandemic influenza structures and processes to
define Canada's response to Avian Influenza. They are working on a new
annex related to the management of human health issues related to
domestic avian influenza outbreaks. They are finalizing and posting new
annexes on first nations, public health measures, and surveillance. They
are working on completing their antiviral drug strategy. There is a
finalized scientific recommendation on what should be done with regard
to antiviral drug stockpiling. This is currently under consideration at
the policy level. They are testing domestic vaccine production
infrastructure, regulatory processes, and clinical trial protocols. They
are also working on developing an influenza research agenda, further
"exercising" the plan, and completing the recovery section.

Dr. King closed by noting that, "The only thing more difficult than
planning for an emergency has to explain why you didn't."

**[Subcommittee Updates and Reports]{.underline}**

**Immunization Coverage Subcommittee -- Dr. Patricia Whitley-Williams
(NVAC)**

Dr. Patricia Whitley-Williams noted that they had an interesting
discussion on the immunization of adolescents, and Dr. Ben Fishbein gave
a presentation on the status of adolescent immunization coverage. NHIS
2002 data revealed that little has been done in the area of adolescent
immunization. Less than 20 percent of adolescents had an immunization
record available. Coverage in the 13 to 15 year old age group based on
shot record information was 50 percent for hepatitis B, 30 percent for
the tetanus booster, and 70 percent for the second dose of measles. The
rate for the second dose of measles is much higher because most children
receive their second dose when they are 4 to 6 years old.

In 1996, the Committee published a paper in the MMWR on adolescent
immunization with both vaccine-specific recommendations, as well as
general recommendations. At the time, there were seven vaccines, four of
which were recommended for adolescents (tetanus booster, hepatitis B,
2^nd^ dose of measles and varicella). Three were designated for
high-risk individuals---influenza, pneumococcal, and hepatitis A. The
general recommendations were that scheduled visits would be at 11 to 12
years of age, as opposed to 14 to 16, and that all immunizations be
assessed at each medical visit. Several changes have taken place since
the publication of that report including: the introduction of the child
health insurance program; introduction of registries; and incorporation
of the adolescent immunization schedule into the routine childhood
immunization schedule, which is published annually.

Barriers to the improvement of adolescent immunization coverage include:
the lack of a medical home; the lack of routine medical visits for
adolescents; problems with accessing hard to reach or high-risk
adolescents; and, vaccine financing for adolescents. Additionally, there
is a need for a tremendous amount of public education. There are missed
opportunities to immunize adolescents when they show up in emergency
departments, SCI clinics, gynecologist offices, etc. Schools were
discussed as a possible site for administering immunization, but
resources would be a barrier. While school-based clinics played a role
in increasing coverage in terms of hepatitis B in adolescents, there are
only about 2,200 school-based clinics in the country, most of which
exist at the high school level rather than the more appropriate middle
school level. State laws regarding middle school entry have assisted in
improving hepatitis B coverage.

Registries were considered as a source of documentation in lieu of shot
records and the issue of how long to keep data in the registries was
raised. Dr. Alan Hinman noted that it would depend on state law. In some
states, data can only be kept in registries until children reach 18 or
20 years of age, while in other states, data can be kept for life.

NVAC's role and the next steps: a panel discussion to gather and review
data, and hear testimony on barriers to adolescent immunization, health
care delivery patterns of adolescents, and potential creative solutions
to improve coverage in an effort to develop specific recommendations on
how to improve coverage among adolescents. NIP staff volunteered to
develop an agenda.

The issue of the CDC RFP to look at attitudes of parents, patients, and
providers on adolescent immunization was raised. Unmet needs funding was
considered as a possible source for additional studies.

**Future Vaccines Subcommittee -- Dr. Barbara Mulach (NIH)**

Dr. Barbara Mulach took the lead for the Future Vaccines Subcommittee in
Dr. Ann Arvin's absence. The Future Vaccines Subcommittee received
summaries about two workshops that were funded by NVPO Unmet Needs
funding.

The first was an enteric vaccine for pediatric youths workshop sponsored
by NVPO, NIH, NIAID, FDA, the Bill and Melinda Gates Foundation, the
Institute for OneWorld Health, and WHO. It brought together many
different groups to discuss the status of current enteric diseases, the
need for different vaccines, and the status of vaccines in the pipeline.
It showed that in some cases, such as rotavirus, the world is in very
good shape. With other vaccines, they are much further behind (e.g., E
coli) and they need more basic research. With respect to vaccines in the
pipeline, there were many questions about getting things past the
development stage to late stage testing, development, and actual use.
Another issue that came up was the importance of finding out more about
the populations that are getting the disease. The results of the
workshop will be written up, and they are deciding whether to publish it
or post it on a website.

The second workshop was the first International Neonatal Vaccination
Workshop that took place in March, which was funded by NVPO Unmet Needs
funding, with help from CDC and NIH. They discussed different issues
with respect to neonatal vaccination, such as what is known about this
population, hurdles to vaccinating such young children, possibilities
for vaccinating pregnant women, regulatory perspectives, and liability
perspectives. Dr. Mulach noted that Dr. Arvin was actively involved in
developing the agenda and will be involved in developing the publication
for a peer-reviewed journal.

They then discussed: the subcommittee role in a possible update of the
National Immunization Plan; immunity, when boosters are needed; and, how
to reach adolescents; where they would like to focus some of the Unmet
Needs funds; biodefense as an example of how things can move forward
when you get the right kind of attention; therapeutic vaccines; and,
novel delivery systems.

**Vaccine Safety and Communication Subcommittee -- Dr. Jerome Klein
(CDC)**

Dr. Klein noted that the subcommittee discussed the upcoming meeting at
CDC, which will review U.S. vaccine safety programs, and discussed the
role of NVAC in the subsequent report. This meeting of the Blue Ribbon
Panel on Vaccine Safety is also charged with looking at the intramural
and extramural collaborative activities of the vaccine safety program.

Dr. Evans noted that an article by Dr. Halsey, Dr. Salmon, and Dr.
Moulton proposes a model for a vaccine safety board. They begin with the
premise that since the Federal government purchases more than 50 percent
of the vaccines and is responsible for promotion, as well as vaccine
safety assessment, there are real and perceived conflicts of interests.
The public must know that vaccine safety is taken seriously and is
investigated by people whose primary goal is vaccine safety, without any
connection to program goals or financial gain. Based on reports by the
National Research Council, the article proposes that separating risk
assessment from risk management would eliminate many of these conflicts;
a problem resulting from the conflicts of interest is loss of public
confidence. The authors proposed using the National Transportation
Safety Board (NTSB) as a model for a new vaccine safety board.

There was a commentary provided by Roger Bernier and Karen Midthun,
which highlight the activities of various agencies. They believe that
the current system in the FDA and CDC is set up to perform vaccine
safety evaluations. It facilitates interactions between risk management
and risk assessment, and provides safeguards against conflicts of
interest. CDC recognizes that because of its large role, there may be
perceived conflicts.

To build public trust, CDC is conducting the Blue Ribbon Panel, and both
CDC and FDA are taking steps to improve transparency. Dr. Klein noted
that the anticipated timetable for the Blue Ribbon Panel report is early
summer, followed by a period of public comment. NVAC's role is to review
the report and make recommendations to the Assistant Secretary of
Health.

**[Working Group Updates & Reports]{.underline}**

**Public Participation in Vaccine Decision-Making -- Ruth Katz, JD, MPH
(NVAC)**

Dr. Katz explained that the working group grew out of the work of the
Wingspread Group, named after their first meeting place. The group is
comprised of representatives from health professional organizations,
government agencies, academia, industry, NGOs, and private consultants
to look at ways to enhance the public's engagement in decision-making
about national vaccine policy.

The group developed a proposal known as Vaccine Policy Analysis
Collaborative (VPACE). NVAC was asked to review the proposal and comment
on whether the recommendations were appropriate. The working group was
formed several months ago with members including herself, Ms.
Koslap-Petraco, Dr. Klein, Dr. Schaffner, and Dr. Gellin, with Dr. Helms
serving in an ex-officio capacity. The working group was asked to review
the VPACE recommendations and other models to develop mechanisms for the
public to better engage in vaccine policy. They have had conference
calls, and have put together a proposed agenda for a meeting that will
take place in the fall. The meeting would be a 2-day meeting in
Washington, D.C., with the Wingspread Group and others. They will look
at the VPACE recommendations and other models to engage the public in
vaccine policy-making. In meeting with different groups and discussing
the various models, they will possibly have enough examples with which
to report to NVAC. They share a common goal of finding a better way to
engage the public because perception becomes reality, and often the
perception is that vaccines are unsafe and the government is not doing
its job. Dr. Katz noted that they welcome comments on additions or
potential changes to the proposed participants list.

**Vaccine Financing -- Dr. Alan Hinman (NVAC) & Dr. Nicole Smith
(CDC/NIP)**

Dr. Alan Hinman noted that a NVAC working group has been formed to
develop a response to the IOM report "Financing Vaccines in the 21^st^
Century." One of the recommendations of that report was that the NVPO
convene meetings with stakeholders to discuss the implications of the
IOM's recommendations. The members from NVAC include Dr. Arvin, Dr.
Black, Dr. Klein, Dr. Peter, and Dr. Williamson. Other members include
David Neumann from the National Partnership for Immunization (NPI),
industry representatives, Dr. Rodewald and Dr. Smith from the NIP, and
Dr. Gellin and Ms. Landry from the NVPO.

The primary activities included a series of telephone calls and
interviews conducted last winter. A public meeting is planned in
Washington, D.C., on June 28--29, 2004. Invitations to participate in
the meeting have been sent out to representatives of vaccine
manufacturers and professional associations. The general theme of the
meeting is to get feedback from participants on the seven options to
vaccine financing included in the IOM report. The working group will
take the information and develop a report to present to NVAC at the
October meeting.

**[Other Activities]{.underline}**

**IOM Report on Vaccines and Autism -- Dr. Marie McCormick (IOM)**

Dr. McCormick noted that she would be discussing the hypothesized
association between vaccines and autism. Specifically, the committee
narrowed its tasks to associations between MMR vaccine and autism, and
thimerosal-containing vaccines and autism. She noted that the committee
did not focus on other neurodevelopmental disorders. The committee
focused on this topic at the request of the Inter-Agency Vaccine Group
to re-examine this issue in its eighth and final report. The issue was
re-examined because of significant new data that have emerged and
because the topic remains considerably controversial.

In terms of the causality assessment, it was concluded that the evidence
favors rejection of a causal relation between both MMR vaccine and
thimerosal-containing vaccines and autism. The rationale for the MMR and
autism finding is that 14 large, well-designed epidemiological studies
consistently showed no association between the MMR vaccine and autism.
This is consistent the committee's findings in its 2001 report, which
rejected a causal relationship between MMR and autism.

They also looked at potential biological mechanisms as possible
explanations for a relationship between vaccines and autism. These
included: the release of chemicals into the brain due to a disruption of
intestinal functions by the MMR vaccine; the triggering of abnormalities
in the immune system that are indicative of vaccine-induced damage to
the central nervous system; the increased accumulation and decreased
excretion of mercury from the brains of a subgroup of children; and the
effects of thimerosal on a variety of biochemical pathways.

In terms of the significance assessment, the committee concludes that
because autism can be such a devastating condition, any speculation that
links vaccine and autism means that this is and will remain a
significant issue. The committee recommends a public health response
that fully supports an array of vaccine safety activities. It also
recommends that available funding for autism research be channeled to
the most promising areas, and association with vaccine does not appear
to be a promising area. The committee does not recommend a policy review
of the licensure of the MMR vaccine or thimerosal-containing vaccines or
of the current recommendations for administration of those vaccines.

She presented five recommendations for surveillance and epidemiological
research. The recommendations included using standard and accepted case
definitions and assessment protocols for autistic spectrum disorder
(ASD), as well as conducting clinical and epidemiological studies of
sufficient rigor to identify risk factors and biological markers of ASD.
The third recommendation was to strengthen surveillance of adverse
events (e.g., standardize case definitions of adverse events, establish
guidelines for use of VAERS, continue the use of linked databases and
other tools, and further develop CISA). The committee also recommended
conducting surveillance of ASD as exposure to thimerosal declines, and
increasing efforts to quantify levels of prenatal and postnatal exposure
to thimerosal and other forms of mercury in infants, children, and
pregnant women.

With respect to clinical studies, the committee recommends that because
chelation therapy has potentially serious risks, it be used only in
carefully controlled research settings with appropriate oversight by the
Institutional Review Board to protect the interests of children who
participate. In terms of communications, the committee recommends
developing programs to increase public participation in vaccine safety
research and policy decisions, and enhancing the skills and willingness
of scientists and government officials to engage in constructive
dialogue with the public about research findings and their implications
for policy development.

**Smallpox Vaccine Updates -- Dr. Jerome Donlon (HHS/ASPHEP) & Dr. John
Grabenstein (DoD)**

Dr. Jerome Donlon noted that the strategic national stockpile has 8
million doses of the Wyeth DryVax. There are 425 million doses of the
AventisPasteur, which would be used as an IND and is not licensed.
ACAM2000 has a delivery of 170 million doses and the projected final
delivery is estimated to be 210 million. This is under an IND as they
progress with their Phase 3 trial and will eventually submit an
application for licensure. In addition, relative to the smallpox
preparedness program, there are about 27,400 Vaccinia Immune Globulin
(VIG) treatments consisting of about eight vials per treatment,
depending on weight. The target for VIG is 30,000 and is expected to be
completed in the next couple of months. He commented that they are
comfortable with the amount and types of smallpox vaccines available.
There is a next generation smallpox vaccine program in development,
primarily looking at vaccines that would be available for
immunocompromised individuals.

Dr. Donlon discussed the ACAM2000 Phase 3 trial. There were two
trials---one for naïve subjects (1,163 subjects) and the other for
previously vaccinated subjects (1,792 subjects). In late March, they
began to note the occurrence of three possible myocarditis cases.
Looking at the records and indications, six possible myocarditis cases
(five males and one female) surfaced, of which four were asymptomatic.
Looking at EKGs and records, four more asymptomatic myocarditis cases
surfaced. All of these cases occurred among the naïve subjects. The
study program had a DryVax arm and an Acambis arm, and there was at
least one myocarditis case in each arm. The study was placed on clinical
hold on April 6, 2004, and is currently under review by the Data and
Safety Monitoring Board (DSMB) and the Center for Biologics Evaluation
and Research (CBER). When these reviews are complete, they will
determine the status of the Phase 3 trial. Studies for children are
planned once the adult trials are complete.

Dr. John Grabenstein then gave his presentation on the "Incidence and
Follow-Up of Inflammatory Cardiac Complications after Smallpox
Vaccination in a Large Cohort of Healthy Vaccines." He noted that the
Department of Defense has vaccinated over 626,000 people against
smallpox in the past 18 months. They have been publishing their
experiences in peer-reviewed publications. Their experience with ten
HIV-positive people was in the May 1 issue of *Clinical Infectious
Diseases*. He noted that his charge at this meeting is to discuss his
experiences with myocarditis and pericarditis.

Among the 626,000 vaccines, there were no cases of progressive vaccinia,
eczema vaccinatum, fetal vaccinia, and no cases of contact transfer in
the work place. There were 71 cases of myocarditis, pericarditis, or
both. Of these, 69 have had more than 60 days since diagnosis, which
allows the opportunity to follow them up.

Most of the cases are in their 20s, approximately 71 percent are primary
vaccines and 29 percent are re-vaccines. The cases of
myocarditis/pericarditis are disproportionately Caucasian and
disproportionately male, and very highly clustered in the second week
post-vaccination. Of the 66 cases for which they have follow-up data,
they identified an abnormality of the ECG in 46 (70 percent) of the
cases. They were principally ST-segment elevations, normal-variant early
repolarizations, and T-wave abnormalities.

Dr. Grabenstein summarized the conclusions of the study. Post-vaccinial
myopericarditis should be considered in patients with chest pain 30 days
following smallpox vaccination. ECG, echocardiography, and functional
status were shown to return to normal within a few months after the
onset of illness. Approximately 24 percent of patients had persisting
subjective complaints and of patients reporting persistent chest
discomfort, none had objective functional limitations and all had normal
myocardial function.

**Prevnar -- Dr. Greg Wallace (FDA)**

Dr. Greg Wallace noted that he would be giving a brief update of the
Prevnar vaccine supply. The national mean distribution, since its
licensure in February 2000, is estimated at 1.15 million to about 1.3
million doses per month. The first public vaccine was purchased in July
2000 and the recommendations for Prevnar were published in MMWR soon
afterward. The first episode of delayed delivery was in August 2000,
followed by recommendations to give vaccine priority to children under 1
year of age and high-risk children from 1 to 5 years of age. Afterwards,
the updated recommendations were published in the MMWR based on
individual provider supply. Problems occurred after that with the
Prevnar shortage ending in May 2003. The announcement of a limited
supply of Prevnar was released in December 2003, after which they went
from a three-dose schedule to a two-dose schedule. The preliminary
numbers for May 2004 showed some improvement in distribution.

Dr. Wallace then discussed the projections for future Prevnar supply.
The current projections suggest that supply will be adequate for
three-dose coverage in the summer and four-dose coverage in the fall.
The exact timing of the recommendations has yet to be determined, and
will be based on actual supply in the upcoming months. NIP meets weekly
with manufacturers, FDA representatives, ACIP, AAP, and AAFP to track
supply and make the appropriate recommendations. The manufacturer has
implemented significant investment to prevent future shortages. They
have a second filling site up and running, and have plans for additional
production and filling sites.

Lessons learned: 1) improved communication results in improved responses
to shortages; 2) routine vaccine supply continues to be vulnerable, and
production redundancy is needed to help prevent supply issues.

**[HHS Agencies/Committees Reports]{.underline}**

**ACIP/NIP Report -- Dr. Steven Cochi (CDC/NIP)**

Dr. Steven Cochi reviewed two success stories in the immunization field.
Both stories are examples of when there is an effective vaccine, a good
understanding of the epidemiology of a disease, and recommendations were
implemented despite a variety of challenges.

[Hepatitis A Vaccine Program:]{.underline}

This program was implemented in increments. In 1996, they targeted
high-risk groups/children living in high-rate communities. In 1999, they
went through a geographic targeting, which included children living in
communities with consistently elevated incidences between 1987 and 1997.
Next steps for this program will be discussed at the June ACIP meeting.

High-risk counties are concentrated in the West and Southwest. This
pattern closely follows the ACIP recommendation made in 1999 for routine
hepatitis A vaccination of children. The most recent NIS data show the
11 states with the recommended vaccination had 44 percent coverage from
January to June 2003. The intermediate states had 26 percent coverage,
while the lowest rate had 3 percent coverage.

The overall disease incidence has plummeted with the vaccine licensing
in 1995 and the ACIP geographic recommendations in 1999. They have
complete data for 2002, which show the incidence rate down to 2.9 per
100,000. Looking at the 2002 incidence rates data by county, there has
also been a dramatic decrease, making it hard to distinguish the
high-risk states. Rates have also converged for racial/ethnic minorities
as the Hepatitis A incidence among American Indians/Alaskan Natives and
Hispanics have decreased. This is a good example of how an effective
vaccine, good recommendations, and equitable vaccine distribution can
eliminate racial/ethnic disparities with disease incidence.

David Johnson asked if the schedule and expansion of the program to all
children is open for further discussion at ACIP. Dr. Cochi explained
that Hepatitis A is on the June ACIP agenda and that these and other
slides will likely be presented; he believes this will lead to an
informal discussion of future directions for the program
recommendations.

[Pneumococcal Conjugate Vaccine]{.underline}:

The pneumococcal conjugate vaccine (PCV7) implementation and Active
Bacterial Core surveillance (ABCs) is run by the Division of Bacterial
and Mycotic Diseases, NCID. The pneumococcal conjugate vaccine was
licensed February 2000, and by fall 2000, a program was in place for
public sector purchase of vaccine for rapid use. There was a vaccine
shortage from August 2001 to May 2003, and a second shortage occurred in
February 2004.

U.S. vaccination recommendations are for all children under age 2 and
for high-risk children aged 2 to 4 years with chronic illness or
immunocompromising conditions. It should also be considered for all
children aged 2 to 4 years with priority for children who are aged 24 to
35 months, Alaskan Native/American Indian, African American, or
attending daycare.

According to the most recent NIS coverage data, 59 percent show full
coverage with three or more doses of PCV7 among aged children 19 to 35
months. Since program implementation, there has been a decrease in
disease incidence when compared with the pre-vaccine baseline by year of
age.

Before the vaccine was available, the disparity in relative risk for
African American children was 2.9 times higher than for white children.
With licensure of the vaccine, the gap has decreased to 2 times in the
most recent provisional data for 2003. Both groups are below the target
2010 incidence rate objectives.

A herd effect has also been seen. For children under 2 years old and
children aged 5 to 17 years, there was approximately a 50 percent
decrease in incidence when compared with the pre-vaccine baseline. Even
in the adult population, the trend data show an incidence rate decline
in the elderly and those aged 40 to 64 and 20 to 39 years.

[2004 Challenges:]{.underline}

The greatest challenge is the tremendous increase in cost to fully
vaccinate a child. Based on public sector data, from 1985 to 2004,
vaccination costs went from \$45 to an estimated \$472. Trend data for
the most recent 6-year period show costs more than doubled from \$186 to
\$472, which vaccine purchase appropriation (317 discretionary funding)
has been flat with a recent slight decrease. Additionally, influenza
vaccination has been added as an unfunded program mandate. It is a great
challenge for state immunization programs to maintain the same high
level of service they have provided. They went from being able to fully
vaccinate an estimated 747,000 children in 1999 to only 467,000 children
in 2004, creating risk of disparities among states, particularly with
implementation of PCV. There are 19 states that have a three-tiered
policy. This policy paradoxically offers the vaccine to public clinics
for VFC-eligible children, but for non-VFC-eligible underinsured
children (those with high copays or premiums or no immunization
coverage), the public clinics do not offer PCV. The near poor are turned
away, and states are having a great deal of difficulty trying to rectify
this situation.

**ACCV/DVIC Report -- Ms. Jackie Noyes (ACCV) & Dr. Geoffrey Evans
(HRSA)**

Ms. Jackie Noyes explained that the Advisory Committee on Childhood
Vaccines (ACCV) gained three new members at the time of the conference
call in December, and then, after the March meeting, three others were
appointed. They have six brand new members and three remaining. An
excellent orientation session for new members was given by Division of
Vaccine Injury Compensation Program staff and the Department of Justice
(DOJ) to explain how this program is supposed to work and current
challenges.

About 3,600 alleged autism cases are in the Vaccine Compensation System
and are being held for disposition for one special master. There are
approximately 24 cases that have been voluntarily dismissed and are
going back into the tort system. There is bipartisan legislation in the
House containing many process improvements and language to close legal
loopholes in the original act, but they cannot seem to get the momentum
to move forward. There is also legislation, by Senator Bill Frist, that
would address many of the issues that they hope will move soon. They
seem to be back at the question at the beginning of the Vaccine
Compensation Program, which is how they keep this a viable program. Dr.
Geoffrey Evans added that it is his understanding the class action suits
are moving in the direction of being dismissed, according to Randy Moss.

Only one pre-1988 claim remains to be adjudicated, and it is expected to
be paid this fiscal year. Within the non-autism program, they are
receiving 110 to 120 claims per year. In a rough breakdown, it comes to
25 percent DTP, 25 percent MMR, and 20 percent Hepatitis B. They still
have just over 400 Hepatitis B cases waiting to be adjudicated. Only 27
of the autism-thimerosal claims have been adjudicated; most, if not all,
have voluntarily withdrawn to go on to the tort system. There have been
no decisions on the merits of causation for these cases. It will likely
take more than a year to complete the discovery, which is unique to the
program. Then, there will be a hearing followed by a decision on
causation.

The Advisory Commission on Childhood Vaccines will be meeting in a few
weeks, and there will be further discussion of adding influenza to the
compensation program. On April 30, MMWR published CDC's recommendation
for the routine use of the influenza vaccine for the 6 to 23 month age
group, which started their process for putting together a notice of
proposed rule making after consultation with the advisory commission.
There will also be presentations on reports on the live attenuated and
the inactivated influenza vaccines. Kathleen Stratton will also present
on the autism report. The meeting will be in Rockville, Maryland, and
teleconferencing will be available.

**VRPBAC/FDA Report -- Dr. Gary Overturf & Dr. Norman Baylor (FDA)**

Dr. Gary Overturf explained that they have had two major meetings since
NVAC's previous meeting this year. Strains were selected. There was one
delay with the B strain because there were so few isolates this year.
There was some concern that they were not receiving the data, so there
was a 2-week delay. Most of the data were from Canadian strains, which
confirmed that the B strain of the Shanghai lineage constituted about 80
percent of the few strains they had. It was also put in the 2004--2005
PIV vaccines.

A 2-day meeting was also held to review and discuss the processing of
influenza vaccine, along with yearly production methods. Substantial
time was taken to discuss the science with different cell cultures and
genetically engineered vaccines. Dr. Overturf came away from the meeting
convinced that cell culture vaccines will be difficult to achieve. One
of the problems with influenza vaccine is that we are very dependent on
underdeveloped countries, and those diagnostic cultures are almost all
done in cell culture because it is much cheaper and available. There are
continuing and increased concerns about tissue agents. There is no model
for an annual vaccine produced in a cell culture. Part of problem is the
diagnostic cultures that are the initial isolates, which also are
transferred in cell cultures. Long-term solutions are not forthcoming
and a tremendous amount of research is required.

One laboratory review of interest this year is the review of the viral
DNA laboratory, which includes a FDA group that was recently formed to
examine advantageous agents in cell cultures. This laboratory includes
all the work on possible herpes vaccines, and they also received money
for small pox through bioterrorism funding. All labs fund 85 percent of
their research with dollars outside of FDA, so VRPBAC has little impact.
The purpose of the reviews is to try to direct the FDA response into
various research activities, to examine what is being done and to
determine if it is productive in terms of FDA's regulatory and research
activities. At least 50 percent of labs' time is spent on regulatory
affairs, not research. A review of the Laboratory of Biophysics will
take place later this year. On average, they review two or three labs
per year.

**NIH -- Dr. George Curlin (NIH)**

Dr. George Curlin raised the issue of the avian flu vaccine
hemagglutinins. USDA considers all H5 and H7 strain isolates as class A
agents. Discussions need to happen with USDA and DHHS to propagate the
strains to get them in the hands of researchers and vaccine
manufacturers quickly. NIH is heavily involved with the H5 vaccine
prototypes in addition to cell substrate vaccines.

In biodefense, NIH is very active with the clinical trials and clinical
development plans for protective anthrax and second-generation small pox
vaccines. They are finishing the healthy adults and beginning to move
into the high-risk populations with children and the elderly as planned.

They have reached the end of enrollment and are completing a large-scale
nonvalent pneumococcal vaccine project. The number of cases by protocol
will provide protection to the lowest 25 percent of pneumococcal
pneumonia in infants in Gambia. Those data will be available this time
next year.

**Adjournment -- Dr. Charles Helms (Chair)**

Dr. Helms thanked the NVPO staff for their work and adjourned the
meeting.