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**National Vaccine Advisory Committee (NVAC)**

**June 6--7, 2006, Meeting Minutes**

[Meeting Overview]{.underline}

The Committee heard presentations on a variety of issues during this
2-day meeting. CDC officials presented information on human
papillomavirus (HPV) vaccines, the upcoming influenza season,
meningococcal conjugate vaccine (MCV) supply, and the recent mumps
outbreaks in the Midwest. The Committee received an update on pandemic
vaccines, discussed current procedural terminology (CPT) coding for new
vaccines, and heard reports from the National Vaccine Program Office
(NVPO) on its Unmet Needs Program and from the NVAC Adolescent
Immunization Working Group.

[Committee Members in Attendance]{.underline}

> Gary L. Freed, M.D., M.P.H.---*Chairperson*
>
> Jon R. Almquist, M.D.
>
> Guthrie S. Birkhead, M.D., M.P.H.
>
> Cornelia Dekker, M.D.
>
> Jaime Fergie, M.D., F.A.A.P.
>
> Lance K. Gordon, Ph.D.
>
> Alan R. Hinman, M.D.
>
> Sharon G. Humiston, M.D., M.P.H.
>
> David R. Johnson, M.D., M.P.H.
>
> Jerome O. Klein, M.D.
>
> Mary Beth Koslap-Petraco, M.S., C.P.N.P.
>
> Charles Lovell, Jr., M.D., F.A.C.P.
>
> Trish Parnell
>
> Andrew T. Pavia, M.D.
>
> Adele E. Young, Ph.D.

[Outgoing Chairman (Honored Guest)]{.underline}

> Charles M. Helms, M.D., Ph.D.

[Executive Secretary]{.underline}

> Bruce G. Gellin, M.D., M.P.H., Director, NVPO

[Assistant Secretary for Health]{.underline}

> Admiral John O. Agwunobi, M.D., M.B.A., M.P.H., United States Public
> Health Service
>
> (USPHS)

[NVAC Ex Officio Members]{.underline}

> Norman W. Baylor, Ph.D., Food and Drug Administration (FDA)
>
> Neal Brandes, Agency for International Development (USAID)
>
> George Curlin, M.D., National Institutes of Health (NIH)
>
> Lawrence R. Deyton, M.D., M.P.H., Department of Veterans Affairs (VA)
>
> Geoffrey Evans, M.D., Health Resources and Services Administration
> (HRSA)
>
> James Randolph Farris, M.D., Centers for Medicare and Medicaid
> Services (CMS)
>
> Captain (USPHS) Anne Schuchat, M.D., Centers for Disease Control and
> Prevention (CDC)

[Liaison Representatives]{.underline}

> Jon S. Abramson, M.D., Advisory Committee on Immunization Practice
> (ACIP)
>
> Marguerite Evans Willner, Advisory Commission on Childhood Vaccines
> (ACCV)
>
> Mahnaz Farhang-Mehr, Nova Scotia Department of Health
>
> Ruth Karron, M.D., Vaccines and Related Biological Products Advisory
> Committee
>
> (VRBPAC)
>
> David Salisbury, C.B., F.R.C.P., F.R.C.P.C.H., F.F.P.H.M., United
> Kingdom (UK)
>
> Department of Health

[Committee Members Absent]{.underline}

> Calvin Johnson, M.D., M.P.H.
>
> Laura E. Riley, M.D.

[Invited Speakers]{.underline}

> Dr. Larry J. Anderson, CDC
>
> Dr. Joel F. Bradley, Vanderbilt University
>
> Dr. Daniel B. Fishbein, CDC
>
> Dr. Suchita Lorick, CDC
>
> Dr. Lauri Markowitz, CDC
>
> Dr. Mary McCauley, CDC
>
> Dr. Glen Nowak, CDC
>
> Ms. Ellyn Ogden, USAID
>
> Dr. Cynthia M. Rand, University of Rochester
>
> Dr. Robin Robinson, Office of Public Health Emergency Preparedness
> (OPHEP)
>
> Dr. Jeanne M. Santoli, CDC
>
> Dr. Benjamin Schwartz, NVPO
>
> Dr. Gregory Wallace, CDC

**Welcome from the National Advisory Committee Chairperson---Dr. Gary
Freed**

Dr. Freed called the meeting to order at 9:00 a.m. on Tuesday, June 6,
2006. As his first act, he introduced three new Committee members---Dr.
Jon R. Almquist, Clinical Professor of Pediatrics at the University of
Washington; Dr. Guthrie S. Birkhead, Director of the Center for
Community Health of the New York State Department of Health; and Ms.
Trish Parnell, Founder and Executive Director of Parents of Kids with
Infectious Diseases.

Dr. Freed asked all the Committee members to introduce themselves in
turn, following which he requested a vote on the previous meeting's
minutes.

**Action Item**: The Committee voted unanimously to accept the corrected
minutes of the November 29--30, 2005, meeting.

**Welcome from the Executive Secretary---Dr. Bruce Gellin**

Dr. Gellin welcomed the Committee members and observers. He thanked the
members for having been willing to take on extra work and said that new
NVPO staff should soon be able to assume that burden.

**Welcome from the Department of Health and Human Services (HHS)---Dr.
John O. Agwunobi**

Dr. Agwunobi observed that many of the items on the Committee's agenda
are of vital importance to the health of the nation and stated that
there is an urgent need for advice from this Committee in the setting of
policies that affect all citizens. He mentioned particularly the issue
of the role of government in relation to rising vaccine costs and the
fostering of discussions at the community level.

Dr. Agwunobi welcomed the new NVAC Chairman, Dr. Gary Freed, and spoke
of the productive relationship that has already begun. He then
recognized the past Chairman, Dr. Charles Helms.

**Presentation of Certificate of Appreciation to the Outgoing Chair**

Dr. Agwunobi presented a plaque to Dr. Helms in appreciation of
outstanding contributions to HHS and to the Nation during his long
tenure as an NVAC member and two terms as Chairman. The Assistant
Secretary stated that Dr. Helms' exceptional expertise and capable
leadership have contributed significantly to the Nation's vaccine
readiness. Dr. Helms thanked the Committee for having made his service a
unique and rewarding experience.

**Oath of Office to New NVAC Members**

Dr. Agwunobi administered the oath to Dr. Birkhead. Dr. Almquist and Ms.
Parnell were sworn in on June 5.

**HPV Vaccine---Dr. Lauri Markowitz, CDC**

Dr. Markowitz reported that two candidate prophylactic HPV vaccines are
in development. Merck's quadrivalent vaccine is effective against HPV
types 6, 11, 16, and 18 and should receive an FDA decision in June,
2006. The other is a bivalent vaccine from GlaxoSmithKline (GSK) aimed
at preventing HPV types 16 and 18. The FDA is expected to reach a
decision on it in 2007.

Dr. Markowitz began by providing some background on HPV and cervical
cancer.

-   HPV is an enveloped DNA virus with more than 100 types, of which
    approximately 40 are sexually transmitted. Types 6 and 11 are low
    risk, causing genital warts and respiratory papillomas; types 16 and
    18 are high risk and are responsible for anogenital cancers.

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-   HPV is the most common sexually transmitted infection (STI) in the
    United States. The first infection is usually acquired soon after
    sexual debut. Infection with multiple types is common. Infection is
    usually transient and not associated with symptoms---90 percent of
    infections clear within 2 years. Persistent HPV infection is the
    cause of cervical and other anogenital cancers; e.g., anal, penile,
    vaginal, vulvar.

-   Cervical cancer mortality rates have declined steadily since the
    introduction of the Pap test. Seventy percent of cases are caused by
    HPV types 16 and 18. Ninety percent of genital warts and of
    recurrent respiratory papillomatosis are caused by HPV types 6 and
    11.

Dr. Markowitz next addressed the issue of adolescent sexual activity.
She noted that, by age 15, approximately 25 percent of adolescents of
both genders have had vaginal sex, the number increasing, by age 19, to
77 percent for girls and 69 percent for boys. She noted that high risk
HPV is more prevalent among adolescents aged 14 to 19 than in any other
age group and that there is a great increase in HPV infection after the
onset of sexual activity. There are an estimated 20 million people
infected with HPV in the United States, 15 percent of persons aged 15 to
49 are currently infected, and there are 6.2 million new infections
every year.

Dr. Markowitz then turned to the particulars of the vaccines in
development. The antigen used for immunization is HPV L1, a major capsid
protein of the virus. The expression of the L1 protein uses recombinant
technology. L1 proteins self-assemble into virus-like particles (VLP).
Both candidates are HPV VLP vaccines.

Both vaccines have a three-dose schedule. While Merk's product uses an
alum adjuvant, GSK's contains an adjuvant referred to as ASO4, which
contains 3-deacylated monophosphoryl A. Clinical efficacy trials have
been conducted on young women. Merck's quadrivalent vaccine has been
tested for safety in both women and men. Phase III trials have shown its
efficacy to be 100 percent in preventing HPV-related cervical cancer
precursors and external genital lesions.

Dr. Markowitz summarized the trial results relating to the quadrivalent
vaccine. The vaccine has high efficacy in 16 to 26 year old females who
are naive to HPV. The duration of protection and the need for a booster
are unknown, although there is no evidence of waning immunity. No
therapeutic efficacy has been demonstrated. The vaccine is safe; side
effects are mainly local reactions. Seroconversion rates in 9 to 26 year
olds are greater than 99 percent. Antibody titers are substantially
higher than after natural infection and highest in those vaccinated at
younger ages. However, these decline over time after the third dose and
plateau by 18 months.

She said that even with 100 percent coverage, which she considers
unlikely, the current generation of HPV vaccines will not eliminate the
need for cervical cancer screening, as 30 percent of cervical cancers
have causes other than HPV 16 or 18 infection.

Dr. Markowitz concluded by reporting that the ACIP HPV Vaccine Workgroup
will recommend routine vaccination of females 11 to 12 years of age with
three doses of quadrivalent HPV vaccine and that the vaccination series
may be started as early as 9 years (depending on FDA indication) at the
discretion of the physician. Vaccination also will be recommended for
females 13 to 26 years of age who have not previously been vaccinated.
Older females, not yet sexually active, can expect to have the full
benefit of vaccination and even those women who are sexually active may
derive benefit from vaccination since infection with one HPV type does
not appear to adversely affect the protection afforded by the vaccine
against other types.

Dr. Markowitz expects that the quadrivalent vaccine may be licensed for
use in males at a later date.

**Discussion**

Dr. Freed asked Dr. Abramson, as Chair of the ACIP, whether he had any
additional comments. Dr. Abramson said that Dr. Markowitz did an
admirable job of presenting information on what appears to be a very
efficacious vaccine. He further observed that, while it is not ACIP's
job to determine the budgetary implications of this, he would be remiss
if he did not say that they are major and that NVAC needs to take on
that issue. ACIP will vote, at its meeting on June 29--30, on the
safety, efficacy, and cost effectiveness of Merck's quadrivalent
vaccine, but not on issues pertaining to its financial aspects.

Dr. Abramson inquired about the plateau in antibody response and whether
there might be boosting from natural infection. Dr. Markowitz said that
there was no indication of such boosting.

Several additional questions were raised by the Committee:

-   Dr. Pavia asked whether ACIP will make a recommendation as to
    Vaccines for Children (VFC) coverage. Dr. Markowitz said that ACIP
    is planning for a VFC vote.

-   Dr. Dekker asked whether there are data on concomitant vaccine
    administration. Dr. Markowitz responded that, currently, there are
    only data on concomitant administration of hepatitis B vaccine.
    Because the new HPV vaccine is not a live vaccine, ACIP is planning
    to recommend that it be administered with other adolescent vaccines.

-   Dr. Klein asked whether Dr. Markowitz could provide any insight as
    to manufacturing capability. Dr. Markowitz answered that Merck says
    they will have enough vaccine and have geared up for worldwide
    distribution.

-   Dr. Birkhead asked what the advantage would be of also vaccinating
    males. Dr. Markowitz indicated that, with very high coverage in
    females, there would be little benefit in vaccinating males, but
    with lower coverage in females, there would be a benefit to
    vaccinating males.

-   Dr. Fergie asked whether a change would be recommended in the
    frequency of Pap smears for vaccinated women. Dr. Markowitz said
    that no recommendation is anticipated at present but that it may
    make sense. She emphasized, however, that the efficacy of the
    vaccine for women vaccinated after the start of sexual activity is
    not well known.

-   Dr. Pavia inquired about the efficacy of fewer than three doses. Dr.
    Markowitz said that neither company has data on that issue.

-   A representative from Merck reported that the company will extend
    eligibility for free vaccine to uninsured adults. In response to Dr.
    Klein's question as to why adults were targeted, the representative
    said that it is anticipated that funding for children will be
    covered.

**NVAC Adolescent Immunization Working Group**

Three presentations were made prior to discussion by the Committee.

***Data from the National Health Interview Survey (NHIS)---Dr. Mary
McCauley, CDC***

Dr. McCauley reported on NHIS data collected on children vaccinated at
the ages 11 or 12. The data were collected from face-to-face interviews.
The analysis Dr. McCauley reported was limited to respondents who
reported information from a vaccination record rather than from memory.
The investigators examined coverage attained for hepatitis B (Hep B),
measles, mumps, and rubella (MMR), and tetanus-diphtheria (Td).

Dr. McCauley addressed the issue of the study's limitations: The records
were not validated by the providers; only visits at which a vaccine was
administered were evaluated; data were not weighted to represent the
entire adolescent population; and the sampling strategy was not devised
with this type of analysis in mind.

Nonetheless, several conclusions were noted. The number of adolescents
who received Hep B, MMR, and Td vaccines at ages birth to 10 years
increased steadily, and few adolescents who needed a vaccine received it
at ages 11 or 12.

Dr. McCauley noted that, until 2005, Td was the only vaccine universally
recommended for adolescents. She observed that new adolescent vaccines
have become permanent additions to a growing adolescent schedule. The
need for recommendations for catchup vaccines is coming to an end as
children born later receive the vaccines at younger ages.

Current challenges suggested by Dr. McCauley include reaching
adolescents with the recommended physician visit at ages 11 and 12;
assuring vaccine financing and equity; assuring the system's capacity to
deliver an ever increasing number of vaccines; and educating providers,
parents, and adolescents about vaccine-preventable diseases and the
efficacy of the vaccines.

***Menactra Coverage Among Adolescents---Dr. Suchita Lorick, CDC***

Dr. Lorick discussed the ACIP recommendations for Menactra, a
tetravalent meningococcal polysaccharide-protein conjugate vaccine
(MCV4), and the degree to which the recommendations for vaccination were
met. ACIP recommended administering the vaccine to U. S. military
recruits, college freshmen living in dormitories, adolescents about to
enter high school (e.g., at approximately 15 years of age), groups
judged to be at increased risk, and 11 and 12 year olds at the
preadolescent healthcare visit.

The study reported by Dr. Lorick focused on the latter group; i.e.,
preadolescents at a healthcare visit. Using data from the Vaccine Safety
Datalink (total number of subjects, 619,000), she reported that the
percentage of 11 to 16 year old managed care organization (MCO) members
who were vaccinated with Menactra in 2005 at five sites was low in the
nontarget groups (ages 13 and 16) and slightly higher in the groups
targeted (ages 11 to 12 and 14 to 15). There was a sharp peak in
vaccinations during the summer months (June through August).

***Adolescent Utilization of Preventive Services---Dr. Cynthia Rand,
University of Rochester***

Dr. Rand presented an analysis of the preventive healthcare visit
patterns of adolescents, when immunizations are typically administered,
using data from the 1994--2003 National Ambulatory Medical Care Survey
(NAMCS), the National Hospital Ambulatory Medical Care Survey (NHAMCS),
and the Medical Expenditure Panel Survey (MEPS).

According to the study, 30 percent of adolescents did not receive
healthcare. More than 50 percent participated in primary care visits,
though these declined with age. Pediatricians and family practitioners
were the major care providers until age 16. Females continued to receive
care (more from gynecologists) as they grew older. Male adolescents
dropped off from care after age 16. Few adolescents received sufficient
visits for three administrations of a vaccine.

Dr. Rand reported the following conclusions from her analysis: We should
immunize preferably in early to mid adolescence; gynecologists should
reach older adolescent females with vaccines if they were missed
earlier; physicians should not miss opportunities for vaccination; and
consideration should be given to delivering vaccine series at wider
intervals.

**Discussion**

The Committee members discussed Dr. McCauley's reference to the
reliability of vaccination records versus reports from memory and noted
the large differences observed between the two reporting methods.

Addressing Dr. Lorick's study, Dr. Hinman observed that some States
(e.g., Oregon) have long histories of recording immunizations.

Dr. Lovell asked about disparities in coverage. He said that he would
like to see the data broken out in more detail. Dr. McCauley replied
that there were not enough cases in the study to stratify meaningfully
by race or ethnicity. An observer suggested that the National
Immunization Survey should have information on race.

Dr. Dekker asked about the recent CDC announcement of the investigation
of a link between Guillain-Barre Syndrome and MCV4. Dr. Lorick replied
that she did not think the announcement would have a great impact on
adolescent vaccination. Dr. Dekker also inquired about availability of
the MCV4 vaccine during peak administration periods. Dr. Lorick said
that three of the five MCOs reported that they did not experience
shortages.

Discussion again turned to the discrepancy between using vaccination
records versus self-reports for research purposes. It was suggested that
preventive services are often billed as another type of visit and
records of preventive visits alone may not reflect the true situation of
vaccinations administered.

Dr. Fishbein, referring to the earlier presentations, observed that
uptake of vaccines by adolescents is "slow and low." In his opinion,
there were many opportunities for research applications in the area of
adolescent vaccination; as he put it, "Good ideas abound. The problem is
that we need to anticipate which are the great ideas." In his view, only
two types of intervention will be effective in increasing adolescent
vaccine coverage above 15 percent: (1) School-based vaccination and (2)
school mandates.

***Adolescent Immunization Working Group: Next Steps---Dr. Gary Freed,
NVAC***

Dr. Freed said that one important step for this Working Group is to
define and publish the problems and imperatives for adolescent
immunization. The focus of such an effort should be on presenting the
rationale and importance of adolescent immunization. It will be
important, he said, to provide a framework for the public discussion and
any actions that may result from that discussion.

In order to frame the public debate, Dr. Freed suggested three "hot
button" issues on which the Working Group will focus:

(1) Schools and other nontraditional venues for adolescent immunization;

(2) School mandates; and

(3) Informed consent.

To do this, he suggested that the Working Group build on previous work,
gather expert opinion (to the extent that they have not already done
so), and determine the areas of need for more information. He indicated
that it will not be necessary for the Working Group to take a position
on all of the hot button issues, but that the issues should be well
defined and the Working Group should be fully informed in order to frame
the public discussion.

Dr. Freed said that the Working Group will use the measles white paper
as a guide. It is highly regarded and does not provide answers to the
issues it raises, but rather, frames them.

**Discussion**

Dr. Abramson raised an issue concerning use of tools that are now
available for information dissemination, such as direct-to-consumer
advertising. Dr. Freed replied that this is one of the questions
addressed by the measles white paper---what would be the most effective
means of information dissemination? He further stated that he hoped to
draw on the expertise of the various NVAC Subcommittees.

The question was raised of a timeframe for the white paper. Dr. Freed
said that a draft of the paper should be ready within 4 months.

In response to a question about what other nontraditional locales might
be considered in reaching adolescents with immunizations, Dr. Freed
suggested that places like Walmart might be likely venues.

Related to the topic of how best to reach adolescents, Dr. Salisbury
commented on his experience with an immunization campaign in the UK
targeting children ages 5 through 18. In response to a question about
the ages at which the highest coverage was attained, Dr. Salisbury
replied that it was probably ages 11 through 13. He observed, too, that
in the UK, young people are not required to have parental consent but
can consent themselves, provided they understand the consequences. Based
on his experience, he commented that school programs work in reaching
large numbers of adolescents.

Dr. Almquist raised a question about whether the administration of HPV
vaccine is a sexual issue, which, in many States, may mean that an
adolescent can give consent earlier than on other medical issues. Dr.
Hinman replied that that would require State-specific interpretation.

Dr. Hinman inquired about Canada's experience. Dr. Farhang-Mehr said
that results are similar to those reported by Dr. Salisbury, except that
parents in Canada must give consent. It was mentioned that, in British
Columbia, Hep B coverage went from 3 percent to 95 percent in 1 year
because of the efforts of Dr. Simon Dobson and others.

Dr. Freed was asked whether the Working Group had considered private
sector involvement. He responded that utilizing the private sector is
one of the nontraditional approaches that will be considered.

The point was made that school mandates may mean that parents would be
asked to spend hundreds of dollars in order to keep their children in
school or States may be forced to raise millions to pay for vaccinations
administered in the schools. Dr. Freed agreed that the issue can not be
disentangled from issues of finance.

An observer pointed out that the Department of Justice has programs for
incarcerated youth, "an already disenfranchised group," and encouraged
Dr. Freed to consider reaching out, beyond the schools, to such a group.
Dr. Freed replied that this, too, will be considered.

Dr. Gellin brought the discussion to a close by commenting that there
will be many solutions to consider and that the purpose at this juncture
is to raise the issues and to foster effective discussion.

**The NVPO Unmet Needs Program---Dr. Benjamin Schwartz, NVPO**

Dr. Schwartz provided a description of the Unmet Needs Program. The
program provides support to Federal Government organizations for vaccine
and immunization projects originating from the National Vaccine Plan and
current HHS, NVPO, and NVAC priorities.

Although projects are funded for a maximum of 2 years, such support can
provide "seed money" and "a catalyst" for long-term projects. The Unmet
Needs Program also allows NVPO to address new and emerging issues that
fall outside the regular funding cycle. Applicants include scientists
and project officers from Federal agencies that participate in the
Interagency Vaccine Group; e.g., HHS agencies, the Department of
Defense, and USAID.

The Unmet Needs Program sponsors both intramural and extramural projects
and domestic and international new research or conferences. It provides
between \$4 and 5 million annually for new and continuing projects.

Funding decisions are based on a defined review process. That process
includes three steps: (1) An initial agency review and ranking; (2)
scoring by reviewers from two agencies, two NVAC reviewers, and one NVPO
reviewer; and (3) a technical review panel meeting comprised of NVAC and
NVPO representatives. Evaluation criteria include methodology,
importance, feasibility, personnel, agency priority, and interagency
collaboration. Projects with budgets that fall below \$180,000 receive
an additional five points. The highest scoring proposals are generally
funded.

Dr. Schwartz compared the Unmet Needs Program priority categories from
2004 to 2006. Adolescent vaccination, new and future vaccines, pandemic
influenza, and vaccine safety have been priorities throughout that
period. Other priorities for 2006 include adult vaccination, annual
influenza vaccine supply, financing, and economic analysis. He noted
that, despite vaccine financing being a priority for 2006, only one
application was received. Furthermore, he spoke of the need to work more
closely with the agencies to solicit more proposals on priority
categories.

The presentation outlined specific projects funded under each of the
categories and provided more detail about certain projects (e.g.,
cytomegalovirus surveillance, polio vaccine, emerging lyssaviruses),
showing the relationship between recommendations arising from NVAC
Subcommittees and Working Groups and funded projects. Dr. Schwartz noted
that over 60 percent of the projects funded engendered publications in
peer-reviewed journals. One-third involved interagency cooperation.

**Discussion**

Dr. Young asked whether mechanisms would be put into place to report the
completion, the success, and the fiscal responsibility of funded
projects. Dr. Schwartz acknowledged that a better way is needed to make
those data known. Dr. Curlin also suggested that plans be put in place
to identify and continue funding for successful startup projects.

Dr. Humiston addressed the fact that few good proposals were received in
some priority areas. She suggested linking with health communication
scientists at the agencies in order to make NVPO's research needs clear
to a larger audience.

The Committee's discussion turned to issues involving reviewer workload
and the focusing of funding priorities.

-   Dr. Hinman observed that the Unmet Needs funding has been remarkably
    successful but pointed out the large amount of work involved in
    evaluating proposals and suggested narrowing the focus of the
    funding priorities to better focus proposals on priority topics. Dr.
    Schwartz acknowledged that one of the challenges is to keep the
    proposals brief.

-   Dr. Schuchat remarked that many important issues needing funding
    might be missed with a narrower focus. Dr. Salisbury indicated that,
    if the solicitation is more focused, the review process will need to
    come under more scrutiny.

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-   Dr. Freed commented that applicants have taken quite a broad view of
    what types of projects can be proposed within the priorities. This
    comment was followed by Dr. Hinman commenting on whether the weeding
    of unsuitable applications should happen at review or whether there
    should be a triage process. Dr. Schwartz said that he would welcome
    a short-lived task force composed of NVAC members, agency
    representatives, and NVPO staff to address the issue. Dr. Gellin
    suggested that this issue should be reviewed within the year.

**Development of CPT Codes for New Vaccines---Dr. Joel Bradley,
Vanderbilt University**

Dr. Bradley began by commenting that the reimbursement system for
vaccine delivery needs to be simplified. Acknowledging that physicians
must work within the coding and contracting systems to fund services, he
noted that vaccine administration is undervalued by payers, new vaccine
coverage often lags behind reimbursement, and the increasing number of
new vaccines exacerbates payment problems.

Vaccine administration is often undervalued and physician reimbursement
does not adequately cover the cost of administration. He shared the
opinion that problems exist in the reimbursement methodology for
vaccines, including delays in coverage for new vaccines and the use of
average sales price of the vaccines themselves to determine
reimbursement, which does not take into consideration the cost of the
office visit. Dr. Bradley indicated that the number of new vaccines has
increased these problems.

CPT codes describe services performed. The codes are maintained by the
American Medical Association and are revised yearly. There are
approximately 100 evaluation and management codes and over 8,000
procedure codes. Physician reimbursement depends on selecting the
correct CPT code and correctly linking it to the diagnostic codes
developed by the World Health Organization (WHO) published as *The
International Classification of Diseases, 9th Revision, Clinical
Modification* (ICD-9-CM).

Physician reimbursement is determined by the Resource-Based Relative
Value Scale (RBRVS), the physician-payment schedule for Medicare---but
used by most payers. Most CPT codes are assigned a "relative value";
i.e., services are ranked relative to the costs of the resources used to
perform them. The three major RBRVS components are physician services
(accounting, on average, for 53 percent of the total relative value),
practice expense (approximately 44 percent), and malpractice insurance
costs (about 3 percent). Dr. Bradley broke each of these components into
more specific subcomponents. For example, "physician work" will include
physician time, physical effort, judgment required, and other factors.
Practice expense and liability coverage can be broken down in a similar
manner.

Payments are determined by multiplying the relative value units (RVUs)
resulting from this process by a conversion factor in dollars per RVU.
The conversion factor used by CMS is based on a formula that is
legislated and may rise or fall as directed by Congress. Payers who
adopt RBRVS as their physician fee schedule may use other conversion
factors and may omit some codes and their associated values; e.g.,
preventive care or vaccines may not be covered.

Dr. Bradley next addressed possible solutions for reimbursement
problems. He stressed that new vaccine codes should be active when the
vaccines come on the market. He pointed out that the Vaccine Coding
Caucus was established to improve the timing of new vaccine codes. He
also discussed recent changes to vaccine coding.

-   In 2005, new immunization administration codes were created because
    CMS (and other payers) had undervalued the codes for vaccine
    administration by omitting the "work" value. A new code has been
    created for face-to-face vaccine risk-benefit counseling done by
    physicians, nurse practitioners, or physician assistants. New codes
    also allow physicians to report reasons for nonadministration of
    routine vaccines.

-   As of 2006, all codes have been fully valued. These relative values
    are resource based and validated through a rigorous process that
    should serve as the basis (i.e., the floor) for valuing the services
    by private payers and State Medicaid programs.

Dr. Bradley noted that the use of "average sales price" for medication
reimbursement may push reimbursement of vaccine products below the
actual costs of purchase, storage, and inventory maintenance.

In addition, Dr. Bradley stated that the coding for multiple-component
vaccines is not yet right. The paradox is that, as the number of
components in one vaccine increases, the physician work of counseling
increases, but the practice expenses decrease. The American Academy of
Pediatrics (AAP)---part of the American Medical Association's CPT
Advisory Committee---is working on this problem. The AAP now has a
private payer advocacy program that includes meetings with National,
regional, State, and local payers, and vaccines are a top priority of
this group.

Finally, Dr. Bradley discussed the pay-for-performance (P4P) programs
that some payers are implementing. These programs provide incentives for
physicians to improve performance on selected measures. He indicated
that it is likely that pediatric programs will use immunization rates as
a measure. In his opinion, correct coding, both CPT and ICD, will become
even more important as pediatric P4P programs increase.

**Discussion**

Dr. Klein commented that the reimbursement process is very complicated
and is best done by offices large enough to afford dedicated personnel.
He expressed concern that, as the number of vaccines increase,
completing the paperwork involved in reimbursement for vaccine
administration will become more difficult for small practices. Dr.
Almquist agreed and added that billing data do not reflect what happens
in small offices; physicians lose money because it is too complicated to
report everything. Dr. Hinman added that a number of registries that use
billing data to monitor service delivery examined physician records and
found that children were better immunized than the billing records
showed---also suggesting lost physician income.

Dr. Birkhead raised the issue of the feasibility of implementing
electronic records vs. traditional paper records for some providers. Dr.
Farris reported that financial help is sometimes available to physicians
to help implement an electronic medical record system. Dr.
Koslap-Petraco commented that, in her experience, electronic filing
improves reimbursement, though initially it can be very difficult.

Dr. Freed commented that vaccine financing transcends many
Subcommittees' agendas and that a Working Group may be required to deal
specifically with this issue. He is working with Dr. Gellin on a charge
for such a group. Dr. Klein suggested that an NVAC Working Group should
coordinate activities with other organizations that are looking into
financing issues. Dr. Abramson supported the formation of such a Working
Group, expressing the view that the current, complicated system may
itself be wasting money. Dr. Lovell pointed out the need to look at both
sides of the equation---not only the costs of immunization, but the
costs of not immunizing.

Dr. Pavia suggested that it will be difficult to form a short-term
working group for this ongoing problem and recommended that the audience
needs to be identified. Dr. Freed clarified his previous statement;
indicating that the proposed Working Group should be ongoing and also
should provide output periodically. Once formed, the Working Group, will
decide on its audience.

**Day 2---June 7, 2006**

**Agency, Department, and Advisory Committee Reports**

Reports on the vaccine-related activities of several Federal agencies
were reported as summarized below.

***USAID---Ms. Ellyn Ogden***

Mr. Neal Brandes introduced his colleague, Ms. Ogden, who spoke about
USAID's role in the Polio Eradication Initiative. She reported that
there has been a dramatic decrease in the number of reported cases,
falling from the 350,000 cases in 125 countries reported in 1988 to only
784 cases in 6 countries in 2003. There is still persistent polio in
southern Asia and parts of Africa. A recent outbreak in Nigeria resulted
in 21 additional countries importing the virus. The intensity of
transmission is much higher in Nigeria than elsewhere in the world.
There are still high numbers of zero-dose (unvaccinated) children in
northern Nigeria. Surveillance seems to be working in Afghanistan and
Pakistan, though some areas are inaccessible to researchers. Epidemics
are slowing in Ethiopia and Indonesia. Type 3 polio appears to be on the
verge of eradication in Asia. The last reported case of Type 2 was in
India in 1999.

Ms. Ogden indicated that the new international standard for outbreak
response includes beginning planning within 72 hours and implementation
within 4 weeks. USAID is endeavoring to increase effective partnerships
with local organizations, to strengthen selected systems, and to improve
surveillance and communication to improve response. In addition, USAID
has developed a transit program for mobile populations who often to have
been missed in immunization programs.

***ACCV/Vaccine Injury Compensation Program (VICP)---Dr. Geoff Evans***

More than 5,000 claims have been filed for adjudication as part of the
Omnibus Autism Proceeding. The U.S. Court of Federal Claims is
overseeing a 2-step process which will ultimately lead to a hearing on
entitlement to compensation. The first step, discovery, is coming to an
end. Submission of expert medical reports is next with the entitlement
hearing likely to take place sometime in 2007. In other news, at its
March meeting the Advisory Commission on Childhood Vaccines (ACCV)
recommended that the Secretary convene a scientific panel to review the
injuries and conditions on the Vaccine Injury Table to ensure that it
reflects current science. Dr. Evans also reported on two recent
decisions by the United States Court of Appeals for the Federal Circuit
that appear to relax the standards by which vaccine causation is
determined in "off-Table" VICP claims. The Court found that proof of
causation could be met by establishing the following:

(1) A medical theory connecting the vaccination and injury;

(2) A logical sequence of cause and effect; and

(3) A proximate temporal relationship between vaccination and injury.

The Court also found that treating physicians are in the best position
to determine whether such a logical sequence demonstrates a connection
between vaccination and injury.

***VRBPAC/FDA---Dr. Norman Baylor***

Dr. Baylor reported that, in May, the FDA approved Merck's Zostavax
vaccine for the prevention of herpes zoster in individuals aged 60 and
older. There also was a unanimous vote supporting the safety and
efficacy of Merck's new HPV vaccine for cervical cancer. The FDA will
participate in a WHO meeting on pandemic influenza. Dr. Baylor indicated
that influenza vaccine is on track. In March, the FDA issued two
guidance documents on the licensure pathway for pandemic flu vaccines.

***NIH---Dr. George Curlin***

Speaking of the enthusiasm surrounding the new HPV vaccine, Dr. Curlin
reminded the Committee of the vital role played by fundamental research
in the development of this successful vaccine.

***CMS---Dr. J. Randolph Farris***

Dr. Farris reported on CMS's launch of its Physician Voluntary Reporting
Program in January to improve quality of care. Additionally, Dr. Farris
addressed the issue of how the structure of the Medicare system affects
coverage for Zostavax. Zostavax will not be covered under Medicare Part
B but will be covered under Part D (prescription drug coverage) at 75
percent of cost (or less, depending on the circumstances of the
individual). Administration costs will not be covered under Part D.

***VA---Dr. Lawrence Deyton***

In March, the VA finalized its plan for prepandemic flu response. The VA
plan is available on the VA Web site at
**www.publichealth.va.gov/flu/pandemicflu.htm**. The VA is implementing
that plan. The seasonal influenza vaccination campaign is starting for
the upcoming flu season. The VA has ordered 2.5 million doses of
vaccine. Dr. Deyton reported that last year's season is the first for
which the VA has data on the rate of vaccination of VA health system
workers. Fifty-three percent were vaccinated---a baseline from which to
judge future improvement.

The VA also has been monitoring the outbreak of mumps in the Midwest.
MMR vaccine has been provided to all healthcare facility staff who need
it. The VA's Occupational Health Group is updating the policy on
preemployment disease screening and vaccination.

**Subcommittee on Vaccine Development and Supply---Dr. Cornelia Dekker
and Dr. Jerome Klein**

Dr. Dekker summarized the presentations on vaccine adjuvants made to the
Subcommittee by Dr. Charles J. Hackett of the National Institute of
Allergy and Infectious Diseases (NIAID) and Dr. Elizabeth M. Sutkowski
of the Center for Biologics Evaluation and Research (CBER).

Adjuvants mimic infection in a controlled manner. The functions of
adjuvants in vaccines include the following:

-   Triggering antigen-presenting cells;

-   Promoting T- and B-cell activation;

-   Reducing the amount of antigen needed;

-   Promoting earlier, stronger, more durable responses, including
    memory; and

-   Enhancing cross-protective responses.

Unless a vaccine triggers the innate immune system, a good immune
response will not be produced.

In the United States today, the primary added adjuvant in approved
vaccines is alum. New adjuvants are being developed based on innate
immune receptors. These adjuvants include CpG, lipid A mimics,
RNA-based, peptide-based, carbohydrate-based, and small-molecule
activators of toll-like receptor (TLR) signaling.

The science of adjuvants is growing rapidly and, in addition to
immunogen planning, adjuvant planning also is required.

Dr. Sutkowski presented regulatory considerations in the nonclinical
safety assessment of adjuvanted preventive vaccines. She discussed
safety concerns associated with vaccines and adjuvants. Because vaccines
are administered to healthy individuals, including small children,
extensive nonclinical safety of adjuvants, including local
reactogenicity and systemic toxicity testing, is required. In addition,
she offered general considerations for choosing a relevant animal model
for toxicology studies and discussed toxicology study design
considerations. She noted, in summary, that nonclinical safety
assessment is a key component in vaccine development and that toxicology
testing is requested as part of the nonclinical safety assessment of
certain products, including novel adjuvants and adjuvanted vaccines.

Dr. Klein addressed the issue of vaccine supply, noting that it would be
unwise for recommendations for vaccine coverage to get too far ahead of
the available vaccine.

**Subcommittee on Immunization Coverage---Dr. Alan Hinman**

The Subcommittee considered the growing numbers of new vaccines and the
escalation of the associated costs. Dr. Hinman reported that it was
generally agreed during the Subcommittee's discussion of these issues
that there is need for more information. The subject of the
underinsured, for instance, was often touched on. Having no standard
definition of the term "underinsured" makes the formulation of solutions
problematic.

The Subcommittee will take the following actions:

(1) Formulate a definition of "underinsured" suitable for its discussion
    of vaccine coverage;

(2) Ascertain the prevalence of underinsured individuals and its
    probable increase or decrease. Two likely sources for this
    information are the National Immunization Survey (NIS), which is now
    looking at the underinsured, and a member survey conducted by
    America's Health Insurance Plans (AHIP);

(3) Determine the attitudes and practices of employers, benefits
    managers, and providers. This will be done by engaging the National
    Business Group on Health (NBGH) and suitable organizations
    representing benefits managers and providers;

(4) Address the issue of reimbursement for providers; and

(5) Seek ways to engage all major stakeholders, including the public, in
    the discussion.

The goal of the Subcommittee is the development of recommendations to
ensure that all persons targeted to receive new vaccines will have
access to those vaccines without financial impediment to themselves or
to their providers.

**Subcommittee on Communication and Public Engagement---Dr. Sharon
Humiston**

Dr. Humiston began by stating that new types of health education
materials for adolescents and their parents will need to be developed.
Therefore the Subcommittee will develop proposals for such materials &
describe the needed components in an adolescent white paper. She then
presented results from the CDC-funded study by the Rochester Center for
Adolescent Immunization Research on of the development of health
education materials for adolescents and their parents. The research
showed that the desirable characteristics of communication are that it
be factually accurate, easily understood, relevant to concerns, and
quick to read. Unlike adolescents and parents, providers look to
organizations such as AAP, ACIP, or the American Academy of Family
Physicians for information on immunization. To be most effective for
healthcare personnel, information should be stratified by specialty and
certification. Parents want information from physicians. Adolescents
look to parents and physicians and also turn to the Internet and the
popular media. Dr. Humiston commented that entertainment is a key
component of Web sites constructed to reach teenagers. She stressed the
Subcommittee's consensus that it is important to test messages that are
developed with the target audiences.

Adolescents are interested in knowing the side effects of vaccines, the
natural history of the disease the vaccine is designed to protect
against, how long immunization will last, and the need (if any) for a
booster. Dr. Humiston noted that although vaccination of adolescents
during acute care visits is an option, physicians often face parental
resistance

**Subcommittee on Vaccine Safety---Dr. Andrew Pavia**

Dr. Pavia reported that the Subcommittee recommends the formation of a
new Working Group to implement the Institute of Medicine (IOM)
recommendations that NVAC review the data distribution protocols of the
Vaccine Safety Datalink (VSD). The Working Group membership should
include representatives of the public and private sectors, the academic
community, and the recipients of vaccines and their families. The
Working Group should review the research agenda of the CDC's
Immunization Safety Office and should establish one or more town hall
meetings to enable the broadest possible input and participation in
discussion.

NVAC members discussed whether a Working Group or an extension of the
existing Subcommittee will be most effective and whether NVAC has the
resources to undertake an effort involving an ongoing process of review
and oversight. A decision on the creation of the Working Group and town
hall meeting was not reached, but, following extensive discussion,
Chairman Gary Freed concluded that it is clear that NVAC should address
the ideas behind the proposed Working Group.

**2006--07 Influenza Season Update---Dr. Jeanne Santoli and Dr. Glen
Nowak, CDC**

***Influenza Vaccination---Dr. Santoli***

Dr. Santoli addressed four issues: (1) Expanded recommendations for
annual vaccination, (2) vaccine supply projections, (3) challenges, and
(4) key strategies for administration planned or considered.

Beginning with the 2006--07 season, ACIP recommendations for annual
influenza vaccination are expanded to include children 2 through 4 years
of age and includes other household contacts (i.e., parents and
siblings) and out-of-home caregivers. The rationale for the expansion is
based on an increased risk of clinic and emergency department visits.

As of June 2006, approximately 100 million doses of vaccines are
available. There is potential for an increase of up to 120 million
doses. This has been made possible because there are now four
manufacturers in this market due to HHS efforts to enhance production
capacity by securing contracts to ensure a year-round egg supply,
negotiating contracts to increase cell-culture capacity, and improving
guidance from the FDA to influenza vaccine manufacturers.

CDC expects that providers will be unable to obtain sufficient vaccine
for 3-year-old patients since there is a single supplier of vaccine for
that age group. However, at present there is no information to suggest
that production problems will result in a delay of the vaccine that has
already been ordered. October is the time when vaccination is fully
underway and shortages become apparent.

However, contingency plans are needed in the event that vaccine is
delayed or the supply is insufficient to meet demand. At present there
is no plan to implement tiered vaccination; this strategy is being held
in reserve. There will be increased communication with distributors and
with State and local public health officials to prevent the spread of
rumors.

As many adults do not make regular visits to their doctors, workplaces
will be targeted as a key venue for vaccine administration. Colleges and
universities also will be targeted, as the recent mumps outbreak has
shown the potential for widespread transmission in this setting.

***Communications and Media Planning for the Flu Season---Dr. Nowak***

Dr. Nowak pointed out that influenza is a year-round story. Cases peak
in January and February. The next season's vaccine development begins in
March and April. In subsequent months, recommendations are updated and
disseminated, distribution begins, and vaccination campaigns get under
way.

There is evidence that media attention can encourage people to get
vaccinated. Media attention is shaped by many factors, including the
severity of initial cases, the population groups affected, and competing
news stories. Media interest requires "news"---significant new
developments or findings---and is difficult to achieve and sustain. One
solution is to design press conferences and press releases around
*Morbidity and Mortality Weekly Report* (MMWR) articles and updates or
around other journal articles and new findings from sponsored research.

Expanded recommendations for who should be vaccinated mean more people
need to be reached, necessitating more media coverage. The CDC influenza
immunization communication/media budget is far smaller than similar
budgets for commercial products, yet the objectives are ambitious---to
increase awareness of recommendations among members of recommended
groups, to foster provider awareness and adoption of recommendations,
and to support community education and communication efforts.

**Discussion**

Dr. Klein asked about whether vaccine stockpiles will be created. Dr.
Santoli responded that vaccine will be purchased for stockpile this
year. Dr. Klein also asked about late-onset flu and how possible it is
to communicate to the public that later in the season is not too late to
be vaccinated. Dr. Nowak replied that CDC has made the effort to
communicate this message in the past but that news coverage is often
uncertain as it is "old news" by that time.

Dr. Santoli stated that as soon as new recommendations are disseminated,
there should be guidelines in the event that vaccine supply runs short.
She said that, when there is a supply of unsold vaccine, physicians need
to be informed that the supply exists and how to get it. Mr. Phil
Hosbach (sanofi pasteur) added that there is now a greater supply of
vaccine because of better physician reimbursement and fairer vaccine
pricing.

Ms. Koslap-Petraco commented that physicians are reporting to her that
they are being told by drug companies that they have reached the limits
on the number of doses they can have, even when a reserve of unsold
vaccine exists. A general discussion on this point ensued, and some
suggestions were offered.

**Menactra Supply Update---Dr. Gregory Wallace, CDC**

Dr. Wallace reviewed the introduction of the vaccine and the initial
recommendations, addressed issues of supply and demand, and spoke of the
lessons learned in the past year.

Menactra was licensed by the FDA in January 2005. In February, ACIP
recommended routine vaccination for 11- and 12-year-olds, for previously
unvaccinated adolescents at high school entry, and for populations at
increased risk (such as college freshmen living in dormitories), and VCF
added the vaccine to its program.

A high demand for the vaccine began in June, with order limits and back
orders. Demand for Menactra far outstripped that for Menomune, an
earlier meningococcal vaccine. Despite discrete recommendations, there
was a heavy demand across all adolescent age groups.

Approximately 4.2 million doses of Menactra were distributed in 2005.
Approximately 6 million doses are projected for 2006, with demand
expected to be highest in the summer. A notice appeared in the MMWR for
May 19, 2006, advising readers that a limited supply of MCV4 exists and
to defer vaccination of 11- and 12-year-olds. Priority will be given to
those entering high school and to college freshmen living in
dormitories.

The lessons learned from the 2005 shortfall in Menactra supply include
the following:

-   Open communication with stakeholders markedly improves
    interventions.

-   Implementing new vaccines and new recommendations is increasingly
    complicated (citing such factors as supply versus demand, financing,
    and distribution).

-   Supply and demand are often unpredictable, necessitating a "dynamic
    transparency."

**Discussion**

A question was asked concerning Menomune availability and the relative
number of doses needed of Menactra and Menomune. Dr. Wallace replied
that Menomune is being held in reserve and that Menactra requires
significantly fewer doses. Mr. Hosbach was asked whether sanofi pasteur
will phase out Menomune. He replied that it will be maintained through
the summer of 2006. Some will be shipped to the Sahara and elsewhere.

**Mumps Outbreak---Dr. Larry Anderson**

Dr. Anderson presented the clinical and epidemiologic features of mumps,
noting that up to 20 percent of infections are asymptomatic. One of the
characteristics of the virus is that there is 1 serotype, but 12
genotypes. Common and uncommon complications, communicability, mode of
transmission, and seasonality also were presented.

More than 50 percent of reported cases are in children age 5 to 9 but
that there is a shift to younger ages due to children being placed in
childcare.

Mumps vaccination started in 1968. The greatest effectiveness was seen
after recommendation of the vaccine for routine administration. There
was a brief resurgence in the late 1980s, and from this it was learned
that one dose is insufficient to control transmission.

Healthy People 2010 set a goal of the elimination of indigenous mumps
transmission in the United States. Prior to the recent outbreak, there
have been fewer than 300 cases per year since 2001. (There were
approximately 160,000 in 1968.)

The recent mumps outbreak was initially reported in Iowa in 2005 and
reached a peak in March 2006. The CDC response included national
surveillance and epidemiological investigations of vaccine efficacy and
transmission and risk factors, laboratory studies, vaccination, and
public communications efforts.

As of the end of May 2006, there have been 4,283 reported cases. Iowa
had the highest number of cases (1,889), followed primarily by States
immediately adjoining it. The disease was most prominent among 18- to
24-year-olds, indicating that college campuses were probably a
significant source of transmission.

In reports from Iowa, 6 percent of those infected were unvaccinated, 12
percent had received one dose of vaccine, and 51 percent had received
two doses. The vaccination status of the remaining 31 percent is
unknown. According to another study among college students, the vaccine
failure rate was 10 percent for those who had received one dose and 8
percent among those who had had two doses. Historically, one-dose
failure rates have been between 6 and 18 percent.

Reported complications included orchitis (27), meningitis (11),
encephalitis (4), and deafness (4). There were no deaths. Many
physicians have little experience with mumps and the diagnostic tools
are not optimal.

Mumps has now been eliminated in Finland with high and sustained
two-dose MMR administration. In contrast, in the 2004--05 UK outbreak,
over 72,000 cases were reported, the majority among 15- to 24-year-olds.
Sixty-seven percent were unvaccinated, 30 percent had received one dose
of MMR, and only 3 percent had received two doses.

As a result of recent experience, ACIP has updated its recommendations
for children and health facility workers.

**Discussion**

Dr. Pavia asked whether there was an association between the year of
vaccination and attack rates. Dr. Anderson replied that the issue was
not investigated.

Dr. Abramson questioned whether the elimination of mumps is a realistic
possibility. Dr. Hinman noted that, initially, there was not the same
enthusiasm for mumps elimination that there was for the elimination of
measles or rubella and noted that the recent outbreak is not
incompatible with the goal of elimination.

**Pandemic Vaccines Update---Dr. Robin Robinson, OPHEP**

Dr. Robinson reported that HHS has established the following goals:

-   Building and maintaining a pandemic influenza (H5N1) vaccine
    stockpile adequate to cover 20 million people; and

-   Creating the ability to provide H5N1 vaccine to all U. S. citizens
    within 6 months of the declaration of a pandemic.

HHS will expand and diversify influenza vaccine types, increase the
number of domestic manufacturers, and enlarge surge capacity. To that
end, HHS awarded five new contracts in May 2006---one contract was
already in place from 2005---for commercial-scale production.

A contract was awarded in September 2004 to sanofi pasteur to ensure the
establishment of secure, year-round embryonated hen's eggs and other
essential supplies for 5 years. Six formulations of H5N1 vaccine (with
or without alum) were completed in November 2005. NIAID began clinical
safety and immunogenicity studies in March 2006. Final safety and
immunogenicity testing of pilot investigational lots of H7N7 + alum
adjuvant vaccine is in progress in NIAID clinical trials. Vaccine and
treatment evaluation units will be available later in 2006. Several H5N1
clade 2 virus reference strains will be studied for production and
antigenicity to produce clinical lots for safety and immunogenicity
evaluation.

Dr. Robinson briefly discussed issues involved in egg- versus cell-based
influenza vaccines.

Currently, there are three main cell lines used in the production of
vaccines: Vero cells (DynPort), MDCK cells (GSK, MedImmune, Novartis,
Solvay), and PER C6 cells (sanofi pasteur).

A contract was awarded to sanofi pasteur in April 2005 to develop a PER
C6-based influenza vaccine with a surge capacity of 300 million
monovalent doses. Manufacturing of pilot investigational lots was
completed in France for safety and immunogenicity clinical evaluation in
the United States. Phase I studies are scheduled for later in 2006.

A solicitation for cell-based and recombinant influenza vaccines was
issued in April 2005, with awards issued in May 2006. The proposals were
required to address clinical manufacturing, product assay development,
clinical evaluation, clinical assay development, product-related
equipment, process validation, and manufacturing facility design.
Required deliverables included a product development plan, a clinical
and regulatory plan, a facility plan, a feasibility plan, and pandemic
and seasonal vaccine development milestones. Contracts were awarded to
DynPort, GSK, MedImmune, Novartis, and Solvay.

An increase in egg capacity will result in 77 million treatment courses
of pandemic flu vaccine by 2008. Cell-based vaccines will become a
larger part of the output in later years. By 2011, the total vaccine
courses, egg- and cell-based, will exceed 300 million.

**Discussion**

Dr. Abramson questioned the status of trials in children. Dr. Robinson
responded that he believes trials are underway. Dr. Abramson then asked
whether any thought has been given to administering clade 1 and clade 2
to "prime" the country. Dr. Robinson reported that there have been talks
with the Department of Defense about that strategy; a panel of experts
will be brought together to discuss the approach. Dr. Gellin raised a
question about the amount of data that will be necessary to establish a
level of comfort regarding priming with a novel vaccine. He indicated
that decision makers also need data on the degree of impact of
adjuvanted vaccine relative to unadjuvanted vaccine.

Dr. Gordon asked about recombinant vaccines. Dr. Robinson said that in
fiscal year 2007, HHS will issue a solicitation specifically for
recombinant vaccines.

Dr. Pavia commented that it was difficult to see the big picture
regarding the timelines of the vaccines. He asked that, as data are
collected, NVAC be kept informed about the process for reviewing the
data and making decisions. Dr. Robinson responded that CDC, and panels
such as NVAC, will likely be called upon to help in the analysis of data
and that these analyses will have an effect on stockpiling. Dr. Curlin
commented that the research process has established ways of reviewing
the data. He does not believe the public will be well-served by
involving more people in that process. He added that progress has been
carefully documented and is going well.

Dr. Freed opened the floor to additional public comment. There were no
comments and the meeting was adjourned as scheduled.

**List of Appendixes**

Appendix A Subcommittee Minutes

**Invited Speakers**

Appendix 1 Human Papillomavirus (HPV) Vaccine---Markowitz (PPT)

Appendix 2a Immunization: What Happens at Ages 11--12? National Health
Interview Survey,

1997--2003---McCauley (PPT)

Appendix 2b Menactra's Uptake Patterns Among Adolescents: United States,
2005---Lorick

(PPT)

Appendix 2c Adolescent Healthcare Utilization in the U.S.---Rand (PPT)

Appendix 2d Adolescent Working Group---Freed (PPT)

Appendix 3 The NVPO Unmet Needs Program: FY2006 Update---Schwartz (PPT)

Appendix 4 CPT Coding and Reimbursement Update, 2006---Bradley (PPT)

Appendix 5a Influenza Vaccination Update for 2006--07---Santoli (PPT)

Appendix 5b The 2006--07 Influenza Immunization Season: An Early Look at

Communications and Media Planning---Nowak (PPT)

Appendix 6 Menactra (MCV4) Supply Update---Wallace (PPT)

Appendix 7 Mumps Outbreak: United States, 2006---Anderson (PPT)

Appendix 8 HHS Influenza Vaccine Projects---Robinson (PPT)

**Agency, Department, and Advisory Committee Reports**

Appendix 9a USAID's Polio Eradication Initiative---Ogden (PPT)

Appendix 9b USAID Issue Brief (PDF)

Appendix 10a VICP Summary (Word)

Appendix 10b ACCV Resolution (Word)

Appendix 10c ACCV Guiding Principles (Word)

Appendix 11 VA Update (Word)

**Subcommittee Reports**

Appendix 12a Vaccine Adjuvants: Science and Practicalities---Hackett
(PPT)

Appendix 12b Regulatory Considerations in the Nonclinical Safety
Assessment of

Adjuvanted Preventive Vaccines---Sutkowski (PPT)

Appendix 13 Assessing Coverage With Newly Introduced Vaccines:
Perception,

Program, and Financing---Hinman (PPT)

Appendix 14 NVAC Subcommittee on Communications and Public Engagement---

Humiston (PPT)

**Appendix A---Subcommittee Minutes**

**Subcommittee on Immunization Coverage---Chair: Dr. Alan R. Hinman**

**Attendees**: Jon R. Almquist, NVAC; J. Randolph Farris, NVAC; Daniel
B. Fishbein, CDC; Gary L. Freed, NVAC; Lance K. Gordon, NVAC; Claire
Hannon, Association of Immunization Managers; Phil Hosbach, sanofi
pasteur; Charles Lovell, NVAC; Mary McCauley, CDC; Lance Rodewald, CDC;
Jeanne M. Santoli, CDC; Mark Whitaker, New Mexico Immunization
Coalition; Adele E. Young, NVAC; Jennifer Zavolinsky, Every Child by
Two; Bruce Campbell, notetaker.

***Assuring Coverage With Newly Introduced Vaccines***

The meeting consisted of a general discussion centered on finding the
best means to ensure that all persons, particularly children and
adolescents, for whom immunization is recommended would not be kept from
it for want of a mechanism to defray the costs.

The Subcommittee considered the fact that several new vaccines have
recently been introduced, or are about to be introduced, into the
routine schedule for children and adolescents. These include
pneumococcal conjugate, meningococcal conjugate, rotavirus, and human
papillomavirus (HPV) vaccines.

The Subcommittee discussed the rise in vaccine costs in the last 10
years. It was observed that the costs to fully immunize a child in 1995
were approximately \$150; in 2006, with rotavirus but without HPV
vaccine, the cost has risen to approximately \$850; and the cost is
expected to climb to over \$1,000 by 2008.

Also discussed were the various sources of financing for vaccines, both
public and private. Among the former are the Vaccines for Children
Program, State and local governments, and the provisions made in section
317 of the Public Health Services Act. Private sources include insurance
and out-of-pocket expenditure.

It was generally agreed that meeting the increasing costs is becoming
more difficult. The Subcommittee discussed the varying lengths of delay
between approval or recommendation of a vaccine and coverage. Insurance
plans, if they include vaccine coverage, may have a delay of up to 6
months. Section 317 covers only after a significant delay. State and
local governments may or may not cover after a delay that is often as
long as 2 years.

The Subcommittee also noted that vaccine price was not the only cost to
be considered. Reimbursement to physicians for vaccine administration
also was considered important and might, it was observed, help to ensure
adherence to recommendations.

In addition to increased costs, the Subcommittee noted that there has
been a recent increase in the number of vaccines. There was some
discussion regarding whether this was a general trend or whether it
marked a temporary "bubble" in vaccine development. Those inclined to
the latter opinion pointed out that, after HPV, there will be a gap
before any more vaccines are introduced for universal use.

The Subcommittee discussed the issue of rebates. The suggestion was made
that coverage for immunization costs be mandated for those who would
thereby be relieved of the necessity to cover the cost of treatments for
the diseases prevented. Others responded that the more recent vaccines
are associated with less common or less mortal diseases and, while a
good investment, may not necessarily be cost-saving in any easily
calculable way. Another response was that, unless there is one payer,
consensus will be needed as to the pocket from which the rebates should
be drawn.

It was noted that it has become standard to have a dollar limit on
preventive services generally and that there is a move away from
universal coverage by insurance companies.

The issue was raised as to whether the United States can really afford
to immunize everyone. This led to discussion of whether there was a need
to prioritize vaccines. There was general agreement that, at present,
the societal consensus is that we can and should be able to provide a
vaccine to everyone for whom it has been recommended.

During discussion of these issues, the need for more information was
expressed on a number of topics. For example, the subject of the
underinsured often was touched on. It was noted that there is no
standard definition of the term, which made the formulation of solutions
problematic.

A number of proposals were agreed upon.

(1) The Subcommittee will formulate a definition of "underinsured"
    suitable for its discussion of vaccine coverage.

(2) The Subcommittee will ascertain the prevalence of underinsured
    status and its probable increase or decrease. Two likely sources for
    this information are the National Immunization Survey (NIS), which
    is now looking at the underinsured, and a member survey conducted by
    America's Health Insurance Plans (AHIP).

(3) The Subcommittee will determine the attitudes and practices of
    employers, benefits managers, and providers. This will be done by
    engaging with the National Business Group on Health (NBGH) and with
    suitable organizations representing benefits managers and providers.

(4) The Subcommittee will address the issue of reimbursement for
    providers.

(5) The Subcommittee will seek ways to engage all major stakeholders,
    including the public, in the discussion.

The goal of the above proposals is the development of recommendations to
ensure that all persons targeted to receive new vaccines will have
access to those vaccines without financial impediment to themselves or
to their providers.

**Subcommittee on Vaccine Development and Supply Report---Co-Chairs: Dr.
Cornelia Dekker and Dr. Jerome Klein**

Attendees: John Abrahamson, CDC; George Curlin, NIH; Cornelia Dekker,
NVAC; Charles J. Hackett, NIAID; Jerome Klein, NVAC; Benjamin Schwartz,
NVPO; Elizabeth M. Sutkowski, CBER/FDA; Greg Wallace, CDC; Bruce G.
Weginer, CDC; Laura York, Wyeth Vaccines Research; GlaxoSmithKline (GSK)
Vaccines Representative; Andrea Savoye, notetaker.

Dr. Dekker welcomed members and introduced two speakers who delivered
presentations on the "development" side of the Subcommittee's scope of
responsibilities.

***Vaccine Adjuvants---Science and Practicalities---Dr. Charles J.
Hackett, NIAID***

Dr. Hackett discussed key points related to using and planning for
exogenous adjuvants in vaccine research and production. The function of
adjuvants in vaccine responses includes triggering antigen-presenting
cells; promoting T- and B-cell activation; reducing the amount of
antigen needed; promoting earlier, stronger, more durable responses,
including memory; and (perhaps) enhancing crossprotective responses.
Unless a vaccine triggers the innate immune system a good immune
response will not be produced. Adjuvants mimic infection in a controlled
manner. He noted that many vaccines produce adjuvant activity in an
intrinsic manner. Intrinsic adjuvants such as single- or double-stranded
RNA are used in live attenuated viral vaccines; bacterial DNA (CpG) is
used in whole cell vaccines.

The primary added adjuvant in approved vaccines in the United States
today is alum. In discussing why it is necessary to look beyond current
adjuvants, Dr. Hackett noted the following:

-   While alum stimulates antibody responses, it is a poor producer of
    cellular immunity. (It has tested weak when compared to known innate
    immune ligands.)

-   Mechanisms of alum and other adjuvants are not well understood.

-   Efficacy of current adjuvants may be lacking for mucosal, skin, and
    other routes.

New adjuvants are being developed based on innate immune receptors.
These adjuvants include CpG, Lipid A mimics, RNA-based, Peptide-based,
carbohydrate-based, and small molecule activators of TLR signaling. Dr.
Hackett discussed differences between study subject responses to
hepatitis B vaccines---one with alum as the adjuvant and one with CpG.
The vaccine with CpG led to more rapid development of protective
antibodies in a larger number of people.

In considering adjuvant use in vaccine planning, Dr. Hackett indicated a
need to determine immune response enhancement (e.g., cell-mediated
immunity), formulation and delivery, stability and storage, and
quantities required (a high ratio of adjuvant to immunogen is often
required). In summary, he stressed that the science of adjuvants is
growing rapidly; a pipeline of new adjuvants is being developed; an
unprecedented capability to manipulate immunity now exists; and, in
addition to immunogen planning, adjuvant planning also is required.

***Regulatory Considerations in the Nonclinical Safety Assessment of
Adjuvanted Preventive Vaccines---Dr. Elizabeth M. Sutkowski, CBER/FDA***

Dr. Sutkowski's presentation focused on indications for adjuvanted
vaccines for infectious disease prevention. She noted that there
currently are numerous clinical studies of vaccines with adjuvants in
progress. The adjuvants included mineral salts, oil-emulsion and
surfactant-based particulates, microbial derivatives, endogenous human
immunomodulators, and combinations of these. Although adjuvants alone
are not licensed, vaccines in the United States are currently limited to
aluminum-derived adjuvants. Promising vaccine adjuvant combinations
(e.g., *AS04*-MPL+alum) included in formulations for hepatitis B, HPV,
and malaria vaccines have been approved in Europe. She referenced
guidance from the FDA regarding adjuvants for production, testing, and
clinical studies (included under 21 CFR 610.15, Constituent Materials).

Two broad safety concerns associated with vaccines/adjuvants were
presented:

\(1\) Potential local reactions such as pain, redness, swelling; or

\(2\) Potential systemic reactions such as anaphylaxis, pyrogenicity, or
organ-specific toxicity.

Because vaccines are administered to healthy individuals, including
small children, extensive nonclinical safety of adjuvants, including
local reactogenicity and systemic toxicity testing, is required. The
World Health Organization (WHO) issued guidance on nonclinical
evaluation of vaccines and safety data required for the Investigational
New Drug (IND) application process. The IND process requires sufficient
chemistry, manufacturing, and controls (CMC) and biological activity
information with regard to antigen(s), adjuvant(s), and antigen/adjuvant
formulation, as well as full study reports with results from toxicology
testing of novel adjuvant(s) and antigen/adjuvant formulation intended
for clinical use.

Dr. Sutkowski offered the following general considerations for choosing
a relevant animal model for toxicology studies:

-   One species is adequate for the studies---nonhuman primates are not
    usually necessary;

-   Choose species in which the antigen is immunogenic and the adjuvant
    augments the immune response;

-   Include sufficient numbers of animals per sex, per group; and

-   Evaluate the quality of the immune response if necessary.

She then made a few general remarks about good laboratory practices and
what is needed to move from animal to human studies.

In terms of toxicology study design considerations, including dose level
and frequency of administration and the specific parameters that need to
be monitored, the following was noted:

-   When toxicity studies have been completed, full toxicity study
    reports should be submitted with the IND or the master file. The
    reports should include a narrative summary and a study summary
    table, tabular summary data and statistics, individual animal data,
    and certificates of analysis for test article(s) and supporting
    stability data.

-   As clinical studies proceed, researchers may be asked to provide
    additional assessments (e.g., safety pharmacology, repeat dose
    toxicity study in a second species, pharmacokinetic studies,
    genotoxicity, and carcinogenicity studies) for products such as
    certain adjuvants or adjuvanted vaccines. At an early stage of
    development, the safety and added value of the adjuvant in the
    adjuvanted vaccine formulation should be demonstrated with a
    head-to-head comparison of adjuvanted and nonadjuvanted forms of the
    vaccine.

In summary, Dr. Sutkowski noted that nonclinical safety assessment is a
key component in vaccine development and that toxicology testing is
requested as part of nonclinical safety assessment of certain products,
including novel adjuvants and adjuvanted vaccines. She concluded by
providing participants with a list of select publications on safety
evaluation of vaccines/adjuvants and contact information for guidance
from CBER.

**Comments and Questions**

Dr. Dekker asked Dr. Sutkowski if CBER had looked at adjuvants in terms
of combinations for new pandemic vaccines. Dr. Sutkowski responded that
there are not special programs for this purpose, but as things develop
they will be created.

The Subcommittee was asked why progress on new adjuvant formulation and
use has been so slow. Members noted that potential toxicity, development
time, and cost may all be factors. A representative from GSK noted that
there are some drugs in Phase III development that have been formulated
with new adjuvants.

Dr. Sutkowski was asked to comment on her confidence in the ability of
the current approval process to evaluate potential toxicities. She
responded that there are checks and balances built into the system to
screen for toxicities; e.g., careful clinical monitoring and evaluation
of adverse effects.

The members discussed whether the FDA required any changes in the
development process given the new adjuvants being used. It was noted
that there are no special changes required for testing and approval of
vaccines with new adjuvants and that adjuvants are the next step in
improving vaccines. It also was noted that adjuvants are considered
intellectual property, which is a barrier to "mixing and matching"
results. A member noted that everyone wants to be careful in preparing
vaccines for approval, starting with establishing appropriate doses and
keeping in mind that not every adjuvant works the same with every
antigen. The Subcommittee discussed whether existing vaccinations would
ever be reformulated using new adjuvants and noted that the amount of
time necessary to test and gain approval for the reformulated vaccine
makes this unlikely because drug companies prefer developing products to
meet new medical needs.

The Subcommittee asked Dr. Weniger to give a presentation on
dose-sparing strategies at the NVAC meeting in September. Dr. Weniger
offered to invite staff to present on interesting work being done in
Cuba through WHO.

The Subcommittee also considered whether to develop a paper, meeting, or
presentation on dose optimization strategies or a broader application
such as dose optimization targeting vaccine efficacy, targeting special
populations. Interest was voiced in continuing to look at adjuvants and
alternative routes of administration, noting that the NVPO Unmet Needs
Program has funded some adjuvant projects and should be considered as a
way to stimulate movement. Members interested in developing the idea
further agreed to contact Dr. Dekker.

Discussion turned to the related subject of whether it is cost-effective
to run clinical trials to determine if fewer doses of a vaccine are just
as effective, noting that countries outside of the United States use
smaller doses of vaccine than are administered in the United States.
Further thinking on this subject is needed.

On the topic of supply, the Subcommittee noted that the availability of
vaccine affects recommendations for coverage. As an example, the DTaP
and HPV vaccine manufacturers are trying to build platforms for their
releases. On the subject of vaccine supply and distribution, the
Subcommittee presented the following for consideration by NVAC:

-   Picking one age group to be vaccinated does not work.

-   Physicians should not be the guardians of vaccine supply.

-   Vaccine recommendations should not run ahead of the probable supply.

-   There may not be a global answer for every vaccine.

-   It is difficult to predict peripheral demand.

-   The annual influenza vaccination should be recommended for everyone.

-   Make a narrow initial recommendation and broaden it (e.g., expand
    age groups) in the future.

-   Drive demand by getting information out.

-   Be smarter next time.

**Subcommittee Communication and Public Engagement---Chair: Dr. Sharon
Humiston**

**Attendees:** Trish Parnell, NVAC; Karen Nielsen, GlaxoSmithKline; Mary
Beth Koslap-Petraco, NVAC; Melissa McPheeters, University of Michigan;
David R. Johnson, NVAC; Cynthia Rand, University of Rochester; David
Salisbury, NVAC; Kathleen Stratton, IOM; Jaime Fergie, NVAC; Glen Nowak,
CDC; Curtis Allen, CDC; Dianne Welsh and Linda Gough, notetakers.

Dr. Cynthia Rand presented the Rochester Center for Adolescent
Immunization Research's CDC-funded project on communicating with
adolescents and parents to improve adolescent healthcare. The results of
the study are intended to provide solutions to the problem of getting
adolescents in for care and should provide insight into providers' views
on the barriers to adolescent care. She noted that a bias of the study
is that participants were chosen to be interviewed based on their
presence at the doctors office. The challenge is that, while adolescents
reported the doctor's office as the best place to receive health
information, teens are least likely to frequent doctor offices. However,
she stressed that this initial qualitative study should help to develop
a larger quantitative survey. A second round of interviews is planned
for the summer 2006.

Adolescents were asked three questions: (1) Where would be a good place
to receive information about vaccines, (2) What information would they
want to receive about the vaccine, and (3) Is it appropriate for doctors
to talk to young adolescents about cancer and sexually transmitted
infections (STIs)?

The majority of participants responded to the first question by stating
that the doctor's office is an appropriate place to receive such
information (Dr. Rand noted that this could be a bias of the study's
having been conducted at the doctor's office). Areas frequented by their
peer group, including McDonald's and Wegman's (a local grocery store)
also were considered appropriate. The participants also noted that
written information is helpful; Subcommittee attendees suggested a
vaccine information statement.

In response to the second question, adolescents stated that they wanted
to have information on side effects, what the vaccine would protect
against, whether it would be given in other countries, and whether a
booster would be needed. One study participant asked to receive
information on the consequence of not receiving the vaccine.

In response to the third question, most adolescents thought it scary to
hear information on cancer. Many 15-year-olds stated that they would not
have understood information about STIs at 11 years of age.

Subcommittee members then discussed some experiences related to
communicating with adolescents and parents about vaccines.

In the United Kingdom (UK), a message about HPV vaccine was focused on
cervical cancer screening rather than vaccination for STIs. As a result,
if a doctor or reputable agency recommended and endorsed a vaccine, then
parents were more likely to support vaccination at school. However,
parents wanting more information about long-term consequences and safety
of vaccines were less likely to support vaccination in school. Members
stressed that one message does not work for all and that values differ
among groups---emphasizing the importance of developing and testing
messages that have a strong communication component with informed
consent. It was noted that in the UK there are variations in the age
parents thought it was appropriate for adolescents to receive the
vaccine but that, overall, teens stated a younger age than did their
parents.

Research conducted by Parents of Kids with Infectious Diseases (PKIDs)
indicated that both parents and children thought that doctors were a
trusted source of information. Considering doctors' time constraints, it
was suggested that "viral marketing"---a strategy that encourages
individuals to pass on a marketing message to others---creates a
potential for exponential growth in a message's influence and may be a
way to transmit the message of vaccination to adolescents.

The Measles White Paper was discussed as a template to develop new
health education materials for adolescents.

The Subcommittee formulated recommendations to NVAC for adolescent human
papillomavirus (HPV) vaccine communication and public engagement to
reach providers, parents or guardians, and adolescents.

(1) Physicians and healthcare workers must understand the value and
    importance of the new immunization for adolescents and advocate for
    the vaccine.

(2) Parents and guardians also should be made aware of the value and
    health benefits of the adolescent immunization recommendations and
    be motivated to have their children vaccinated.

(3) Adolescents should be informed as to the value, benefits, and
    reasons for recommended vaccinations.

The steps recommended to achieve success are as follows:

-   Identify the barriers to adolescent HPV vaccine communication and
    public engagement;

-   Develop messages that reach and impact target audiences;

-   Identify message delivery channels and messengers that are visible,
    credible, and persuasive; and

-   Ensure vaccine recommendations and resources are grounded in
    operational realities.

The Subcommittee noted the time limitations and costs versus benefits of
having physicians educate their patients as well as administering the
vaccine, which is not always feasible. The Subcommittee agreed that, if
reputable organizations---such as the Advisory Committee on Immunization
Practices (ACIP), public health officials, and manufacturers---endorsed
the message of adolescent vaccination, this may encourage the support of
physicians, parents, and guardians in the promotion of adolescent
vaccination.

The Subcommittee also discussed how to better structure the Unmet Needs
Program so that collaboration between scientists and communicators,
including engaging public comment, can influence vaccine research. It
was suggested that NVAC prioritize this type of collaboration within the
proposal review system by awarding five points to grant applications
that include communication initiatives.

In conclusion, agenda items for the September Subcommittee meeting were
formulated.

-   Emma English (NVPO), will discuss how the NVPO website could act as
    a central site, with links to current events.

-   Ms. Joanne Yarwood, Head of Immunization Information of the UK
    Department of Health, will be invited to attend to inform members
    about experience in the UK.

-   The Subcommittee will discuss the draft of the NVAC Adolescent
    Working Group white paper at the September meeting.

**Subcommittee on Vaccine Safety---Chair: Dr. Andrew Pavia**

**Attendees:** Andrew Pavia, NVAC; Kenneth Bart, NVPO; Robert Davis,
ISO/CDC; Emma English, NVPO; Geoffrey Evans, HRSA; Ann McMahon, FDA;
Mike McNeil, CDC; Riyadh Muhammad, FDA; Margaret Williams, APCO
Worldwide; Marguerite Evans Willner, NVAC; Lois Goodstein, notetaker.

***Review of IOM Report and Blue Ribbon Panel---Dr. Andrew Pavia,
NVAC***

Dr. Pavia presented a review of the Blue Ribbon Panel and the IOM report
that focused on the Vaccine Safety Datalink (VSD) and asked what the
Subcommittee might do with the charges that came out of those reports.
Was the release of data handled well? Was there a need for some form of
external review? A key recommendation was that a Committee should be
formed for oversight of VSD and for review of protocols and data
distribution. In order to avoid a conflict of interest, a reorganization
of immunization safety and other processes into two separate areas was
suggested. This was accomplished with the creation of the Immunization
Safety Office at CDC within the Office of the Director.

There is also a need for a group of stakeholders with a wide range of
expertise to review the overall mission, scope, coordination, and
science of the CDC vaccine safety effort. Dr. Pavia stressed the
importance of ensuring that both NVPO and CDC were hearing from everyone
concerned about vaccine safety---parents, manufacturers, and others.

According to Dr. Bart, the IOM was contracted by the CDC to respond to a
series of criticisms and provide feedback to the CDC. NVAC should
empower its Safety Subcommittee to review the VSD agenda by a process
that incorporates unbiased people. They would gain benefit from the
public's input, and the public should be encouraged to express their
opinions. The question of which IOM recommendations should be
implemented was raised as was whether people's opinions could help VSD's
agenda emerge.

Dr. Davis noted that it must be specified how analyses should be done.
Everyone needs to be assured that things are done with great
transparency. The Safety Working Group's first charge---to review,
discuss, and deliberate on the safety research agenda of the ISO---is
huge, and help is needed to create a well-founded research plan for the
ISO.

***Review of Proposed Plan for a Safety Research Working Group and Town
Hall Meeting***

Dr. Pavia reviewed the objectives for the Vaccine Safety Working Group
as follow:

The membership would comprise experts and interested parties
representative of the public and private sectors, the academic
community, and the community of families and recipients of vaccines;
e.g., CDC, FDA, NIH, manufacturers, Department of Defense, VA, parents,
AAP, and vaccine researchers. Its charges follow:

-   Review, discuss, and deliberate on the safety research agenda of the
    ISO/CDC.

-   Following the town hall meeting, summarize and assemble the comments
    and recommendations of the Working Group of the Safety Subcommittee
    of the NVAC for presentation and review by the NVAC.

-   Consider the merits of making this process an annual event.

-   Consider broadening the charge to extend beyond the reaches of the
    VSD research agenda to include review of the overall vaccine safety
    enterprise of the CDC and/or the entire Department's vaccine safety
    research agenda with the following goals in mind:

    -   Bringing the best possible science to bear;

    -   Ensuring that the scope and breadth of efforts is designed to
        detect issues in vaccine safety;

    -   Ensuring transparency and communication among scientists, public
        health officials, and the public; and

    -   Ensuring/improving public confidence in the safety system.

-   Evaluate the adequacy of resources directed at vaccine safety.

Dr. Pavia also reviewed the proposed goals of the town hall meeting on
the VSD research priorities as follow:

-   Enable the broadest possible input and participation in the
    discussion.

-   Review the past, present, and proposed future research agenda of the
    ISO through the VSD mechanisms and obtain input from all interested
    stakeholders in vaccine safety, including parent groups, public
    health officials, insurers, vaccine manufacturers, FDA, CDC, and
    lawmakers.

-   Specifically solicit speakers from the community/public ahead of
    time to present their points of view.

**Discussion**

The Subcommittee discussed the question of opening up the discussion of
the town hall meeting to areas other than VSD and talking about
different ways HHS is looking at vaccine safety. Members agreed that the
Working Group must have a reference point and that the town hall meeting
serves that purpose well. The public should be informed of expected
outcomes just as researchers are. Discussion ensued about the goals and
objectives of the town hall meeting. It is important to show people the
complexity of bringing a vaccine to the public and to find out what
people think---it is essential that people know they are being heard. It
was suggested that Kathleen Stratton's (IOM) participation in this
discussion would be useful.

Discussion followed about the need for a facilitator and the appropriate
level of structure at the town hall meeting. Subcommittee members
emphasized the need to give everyone a chance to talk, the need for the
meeting to be structured (but not overly so), and the need to emphasize
interactivity. The issues of the number and selection process for
invitees were raised, with Dr. Pavia suggesting choosing organizations
that represent the public and letting them pick their representatives.
Members discussed the logistics of the meeting, the purpose of which is
to engage the public to inform the vaccine safety agenda. Some
logistical concerns include the length of the meeting, the balance of
group and breakout sessions, and the balance of scientists'
presentations and public input. The issues of privacy and of the amount
of data that should be available to outside researchers in order to
benefit everybody were raised; During the discussion, it was noted that
conflict of interest means different things to different people.

After reiterating the importance of engaging people and making them feel
comfortable at the town hall meeting, the Subcommittee agreed to follow
up by teleconference to discuss next steps.