Advisory
Commission on Childhood Vaccines Meeting
October
30, 2007
Minutes
Members Present
- Jeffrey
M. Sconyers, J.D, Chair
- Jaime G. Deville, M.D., Vice Chair
- Tawny
Buck
- Magdalena
Castro-Lewis
- Margaret Fisher, M.D.
- Charlene Gallagher, J.D.
-
William Paul Glass, Jr., J.D.
-
Tamara Tempfer
Ex-Officio
Members Present
-
Marion Gruber, Ph.D.
-
Barbara Mulach, Ph.D.
- Dan Salmon, Ph.D.
Executive Secretary
- Geoffrey Evans, M.D., Director, Division
of Vaccine Injury Compensation (DVIC),
Healthcare Systems Bureau (HSB), Health
Resources and Services Administration
(HRSA)
Staff
Liaison
Welcome and Report of the Chair
Mr. Sconyers called the meeting to order,
welcomed those present and introduced
new Commission members:
Ms. Magdalena Castro-Lewis, National
Alliance for Hispanic Health, representing
the general public.
Dr. Margaret Fisher, a pediatric and
infectious disease physician and Medical
Director at Children’s Hospital,
Monmouth (NJ) Medical Center.
Ms. Charlene Gallagher, an attorney,
Senior Division Counsel, Vaccine Business
Unit, Wyeth Laboratories, representing
industry on the Commission.
Dr. Daniel Salmon, ex-officio member,
a vaccine safety specialist at the National
Vaccine Program Office.
Approval of June 2007 Meeting Minutes
Mr. Sconyers invited approval of the
minutes of the June 7, 2007 ACCV meeting,
which was held by teleconference.
(On motion duly made by Mr. Glass and
seconded by Ms. Castro-Lewis, the minutes
were unanimously approved.)
Mr. Sconyers invited the report of the
Director, DVIC.
Report from the Division of Vaccine
Injury Compensation - Geoffrey Evans,
M.D., Director
Dr. Evans reviewed the agenda for the
meeting and described the informational
material provided to ACCV members including
an autism update from the Office of Special
Masters, and a report on Thimerosal
and Autism Spectrum Disorders by
the Senate Committee on Health, Education,
Labor and Pensions.
Noting that the average number of non-autism
claims received annually has been between
140 and 150, the claims for 2007 spiked
to 235 mainly because the two-year filing
deadline for influenza vaccine injury
claims (dating eight years prior to the
announcement of eligibility) was July
1, 2007. The 184 claims related to that
deadline were lower than expected. There
has also been a slight decline in the
number of autism-involving-thimerosol
claims during past three years, although
the rate may increase as the current autism
hearings progress.
The annual awards during 2007 were the
highest in the history of the program,
about $91.4 million, largely because of
the increased number of hepatitis B claims
filed in the late 90’s being adjudicated
and reaching judgment. The average annual
awards stand at about $564 million for
the past five years, with attorney’s
fees and costs at about $2 million. The
Vaccine Injury Compensation Trust Fund,
which had recently been receiving about
$200 million, took in $300 million in
2007, mainly because influenza vaccines
are now covered by the VICP. About a third
of the annual Trust income is derived
from interest earnings.
Dr. Evans listed a number of significant
activities that have occurred since the
last meeting:
Dr. India Jevaji represented DVIC in
an ex-officio capacity at the Advisory
Committee on Immunization Practices in
Atlanta on June 27-28. The Committee revised
guidelines for the use of hepatitis A
vaccine in children 12 months to 4 years
of age. On July 25, Dr. Jevaji and Dr.
Evans participated in a workgroup concerned
with maternal immunization of women during
pregnancy and breastfeeding. Dr. Evans
stated that he had participated as an
ex-officio member at the meeting of the
National Vaccine Advisory Committee in
Washington on October 22-23, and had attended
the Advisory Committee on Immunization
Practice in Atlanta on October 24-25.
Finally, Dr. Jevaji participated in a
telephonic meeting of the Brighton Collaboration
Working Group on July 16 (a CDC project
to harmonize definitions related to vaccine
safety).
On July 5, DVIC published a Federal
Register Notice that outlined the
new formula for calculating average costs
of a health insurance policy. It is a
key factor in determining lost earnings
when an injured individual reaches 18
years of age and, as part of an award,
is entitled to lost earnings compensation.
The previous method overestimated average
health insurance costs, which are deducted
from the lost earnings award amount. The
new average cost of health insurance is
approaching $400 per month.
Mr. Sconyers expressed appreciation for
the report and invited questions. Hearing
none, he invited Mr. Rogers to present
a report from the Department of Justice.
Report from the Department of Justice
- Mark Rogers, J.D., Deputy Director,
Torts Branch, Civil Division
Mr. Rogers reported that three attorneys
had left his office and the process to
replace them had begun. He added that
he might again be assigned in a temporary
duty status to a military command for
an indefinite period of time. If so, Vince
Matanoski would assume the duties of Acting
Deputy Director. Mr. Rogers provided copies
of his remarks to the ACCV prior to the
meeting.
Providing a brief update on cases filed
since the last Commission meeting, Mr.
Rogers noted that 204 cases had been filed,
120 non-autism (86 influenza vaccine cases)
and 94 autism cases. Anticipating the
deadline mentioned in Dr. Evans' report,
Mr. Rogers stated that with millions of
influenza vaccinations it was difficult
to estimate how many claims might be filed
before the July 1, 2007 deadline. There
were only 86 influenza claims filed. There
were 94 autism claims filed; of those,
he anticipated that many would be dismissed
as untimely.
In terms of cases resolved, there were
123 claims resolved in total. Of those,
47 claims were compensated. Within that,
28 were settled mainly by mutual agreement
to terms. Mr. Rogers emphasized the benefits
of amicable settlement. Seven cases were
compensated as a result of proffer, which
is a similar agreement by the parties
that must be approved by the Special Master.
There were seven entitlement decisions
against the Government. There were five
death claims in which the Government conceded
compensation based on the evidence.
Mr. Rogers stated that there were 76
dismissals. Of those, 47 were non-autism.
Within that group, seven were voluntary
dismissals in which the petitioner simply
withdrew; and 16 were summary judgments
in which a proposal is made by either
party and the Special Master rules on
the evidence existing in the record. In
addition, there were four trials resulting
in dismissal of petitioner's case. There
were six dismissals for failure to produce
necessary evidence or documentation (usually
by the petitioner). Those dismissals typically
occur after the Special Master has provided
ample time for a petitioner to develop
the case but there is insufficient documentation
to prosecute the claim. There were eight
motions to dismiss usually for jurisdictional
reasons (mainly statute of limitations
problems), and six dismissals for other
reasons. Of the 28 autism cases dismissed,
those claims were dismissed either because
the original petition was untimely, because
there was a lack of documentation, or
the petitioner simply asked that the case
be dismissed. Finally, there was one voluntary
withdrawal pursuant to Section 21(b) of
the Vaccine Act., which reflects petitioner's
statutory right to leave the Program if
after a certain amount of time they do
not want to continue with the proceedings.
Turning to developments in the autism
area, Mr. Rogers explained that one key
case had been tried. The case, Cedillo
v. HHS, was based on the theory
that the combination of MMR and vaccines
containing thimerosal create a synergism
to cause autism spectrum disorder. One
Special Master served as the lead while
two additional Special Masters also heard
evidence simultaneously. The decision
has not been rendered in that case yet.
There are two follow-up trials under
that same theory. The case, Hazelhurst
v. HHS, was completed in Charlotte,
North Carolina, and the case Snyder
v. HHS, is still on target for
trial, November 5, 2007 in Orlando, Florida.
A series of three cases based on a second
theory, that vaccines containing thimerosal
alone cause autism, will be heard in Washington,
DC from May 12-30, 2008. The specific
petitioners have not yet been identified,
however, the Government has received three
expert reports from petitioners. The parties
are operating under scheduling deadlines
to file expert reports with the Government's
expert reports due February 23, 2008.
Finally, there is a third theory of causation
that MMR alone causes autism. That theory
will be tested in the summer of 2008,
and the Special Masters expect that all
of the proceedings in all of the theories
will be completed by September 2008.
In the area of appeals, Mr. Rogers noted
that two cases were presented to the Supreme
Court for review by petitioners. In Markovich
v. HHS, the Government maintained
that the 36-month statute of limitations
to file a claim begins with a symptom
that is determined by an objective medical
standard. The petitioner claimed that
the standard was subjective and could
not be relied on to identify the first
symptom that would start the statute of
limitations clock. The Supreme Court denied
the petitioner's writ of certiorari.
The second case, Pafford v. HHS,
involved a ruling by the Federal Circuit
that it was the petitioner's burden (and
not the respondent, as the petitioner
claimed) to show a medically acceptable
time frame linking the onset of the illness
to the vaccination. The Supreme Court
denied petitioner's writ of certiorari.
The Federal Circuit affirmed the Special
Master's dismissal in the Marks
v. HHS case. In Marks,
the Special Master dismissed petitioner's
claims because they were not supported
by medical records or expert medical opinion.
In a second case, Walther v. HHS,
the Federal Circuit agreed with the petitioner
that the Special Master applied an incorrect
legal standard by requiring the petitioner
to eliminate other possible causes of
injury. That was remanded for further
hearing and is in litigation.
In the Court of Federal Claims there
were five new cases, four of which were
decided. In Anderson v. HHS,
the Court affirmed the Special Master's
dismissal of petitioner's claim because
petitioner failed to provide objective
evidence that petitioner's alleged vaccine
-related injuries lasted more than six
months, which is a requirement for compensation
under the Act. In a similar case, Ruiz
v. HHS, the Court affirmed the
Special Master's decision to dismiss petitioner's
case based on petitioner's failure to
establish that the alleged vaccine-related
injuries lasted for more than six months.
In Ianuzzi v. HHS, the
Court reversed the Special Master's award
of attorneys' fees to petitioners' counsel.
The Government argued, in this affirmative
appeal, that some of the attorneys' fees
had been incurred prior to the filing
of petitioner's claim, before petitioner
had retained counsel, and after judgment
was issued in the case. Finally, in Hocraffer
v. HHS, the Court agreed with
the petitioner on appeal that the Special
Master had improperly excluded certain
evidence submitted by the petitioner's
attorney in the damages phase of the trial
and failed to properly calculate pain
and suffering. That case was remanded
to the Special Master for further review.
Mr. Rogers turned to the issue of the
time it takes to complete a case. Mr.
Rogers explained that his office reviewed
every case filed during calendar year
2002 to determine whether or not each
had been resolved and, if not, why. Referring
to a Power Point presentation, Mr. Rogers
explained that there were 772 cases filed
in 2002 that were still open on October
1, 2007. Of those, 746 were autism cases
that have mainly been delayed because
of the process related to the current
series of test cases being processed.
Of the 26 non-autism cases still pending,
seven were waiting for petitioner to provide
an expert opinion report, 10 were in the
damages phase (settling on attorney's
fees, pending settlement negotiations,
or rulings on entitlement), six were related
to scheduling, and three were pending
decisions on motions made by petitioner
(to transfer case to the Omnibus Autism
Proceedings) or respondent (motion to
dismiss). In terms of unresolved cases,
the following (broken down into areas
of responsibility) represent the percent
attributed to the entity that has the
power to affect the delay. The Court controls
6% of the instances that require resolution
to move the case forward; the respondent
controls 7%, and the petitioner controls
87%.
In the 7% that falls under the purview
of the respondent, about 27% is spent
in developing and processing expert witness
reports; about 40% is spent fulfilling
the statutory requirements after receiving
a petition (which must be completed within
90 days unless an extension of time is
granted by the Court); and 33% is Aother,@
working on briefings assigned by the Special
Masters, on settlement negotiations, or
on other administrative matters.
In the 6% that falls under the purview
of the Court, about 65% of the time is
attributed to scheduling; and 35% of the
time is attributable to the Court issuing
a decision.
For the 87% that falls under the purview
of the petitioner, about 44% is spent
obtaining medical records (which constitutes
a significant portion of petitioner's
time inasmuch as the Special Masters issue
orders requiring petitioner to document
the case before proceeding) and 22% in
obtaining expert medical/technical reports.
The balance is allocated to stayed proceedings,
which are ordered by the Special Master
who typically issues a stay at the petitioner's
request.
In summary, Mr. Rogers explained that
his office and the Court had a very small
opportunity to affect the speed with which
cases move through the system. Primarily,
the petitioner holds the key to reducing
the length of time a case requires for
completion.
Review of Vaccine Information Statements
- Charles Skip Wolfe, National Center
for Information and Respiratory Diseases
(NCIRD), CDC
Mr. Wolfe expressed appreciation for
the Commission’s valuable counsel
in reviewing the Vaccine Information Statements
(VIS) as they are revised from time to
time. He explained that the VIS program
appears to be an important informational
tool as evidenced in part by the 13 million
hits on the VIS/childhood vaccination
schedule on the NCIRD web site. He invited
comments on the five Vaccine Information
Statements submitted to the ACCV for review.
He noted that all of the VISs were in
circulation and that they would be updated
based on NCIRD requirements and comments
of the ACCV.
Mr. Wolfe explained that the varicella
VIS revision was required because the
ACIP had recommended a two-dose schedule
for children. Dr. Fisher suggested that
the word “catch up” used to
describe the change might not be clear
to parents, and suggested that describing
it as a “new recommendation”
would be appropriate. Noting that the
VIS might be in existence for some time,
and the term “new recommendation”
might become confusing, there was also
a suggestion that it include a revision
date and perhaps a brief explanation for
the change, including a comment that the
two-dose schedule would also be appropriate
for adults.
The next VIS to be reviewed was for meningococcal
vaccines. This will be the first review
of this particular VIS since it was just
added to the injury table. There has been
a change recommending use in children
2 to 11 years old. Dr. Fisher questioned
why the wording has not been changed.
Mr. Wolfe indicated the wording would
be changed based upon the recommendation
published by the ACIP.
The meeting was interrupted by an emergency
egress exercise and upon resuming the
meeting, Mr. Wolfe stated that, during
that interruption, members of the ACCV
had suggested that, under the section
describing who should not be inoculated,
individuals who have previously had the
disease should be included. In addition,
there was a recommendation that the National
Vaccine Injury Compensation Program be
described in some way on the VIS. Mr.
Wolfe stated that the description is usually
included, but can be absent when the VIS
is published before the vaccine is included
in the program. The next revision would
include that information.
Concerning the hepatitis B VIS, Mr. Wolfe
commented that the revision was similar
to the varicella VIS in that the ACIP
had published a recommendation that there
should be a birth dose administered. In
addition, there were a number of vaccination
schedules in previous VISs that had been
deleted, which subsequently resulted in
a number of inquiries as to the reason
for the deletion. Mr. Wolfe commented
that the three-dose schedule would be
described, but there would be an additional
comment that there were other schedules
that could be discussed with health care
providers. He stated that the deletion
of a specific reference to Baker’s
yeast was also deleted and that a more
generic “yeast allergy” had
been inserted in the contraindications
section.
Mr. Wolfe stated that the human papillomavirus
(HPV) vaccine VIS was the first of its
kind since the vaccine had only recently
been added to the injury table. He added
that, because of federal legislation,
even though it is not specifically relevant,
a statement about the use of condoms in
the prevention of sexually transmitted
disease would have to be included.
Finally, Mr. Wolfe noted that rotavirus
vaccine is a newly licensed vaccine, immediately
covered by the program because as earlier
version had been covered. He urged ACCV
members who might have subsequent thoughts
and recommendations concerning the VISs
reviewed, to submit them at any time.
Ms. Castro-Lewis recommended that it
would be appropriate to include an announcement
on the standard VIS that a translation
was available for Spanish-speaking individuals,
and that announcement should be in Spanish.
Mr. Wolfe agreed that a statement could
be included at the bottom of each of the
vaccine information statements.
Update on the National Institute of
Allergy and Infectious Diseases (NIAID),
Naitonal Institutes of Health (NIH) Vaccine
Activities - Barbara Mulach, NIAID, NIH
Dr. Mulach announced that NIAID recently
awarded a $50 million contract for modeling
immune response, mainly in the mouse model.
The research will look at the whole immune
system instead of individual immune responses.
The NIAID immunology group is also studying
immune response in various groups of individuals
(e.g., the elderly, pregnant women) to
determine whether there are differences
in how immune systems respond to threat
and whether there are methods for improving
that response in these specific groups.
Dr. Mulach announced that the Jordan
Report had been publicly released
and made available to members of the ACCV.
In addition to information on specific
vaccines, it includes updates on other
areas of research -- influenza vaccine
research, tuberculosis, malaria, vaccine
supplies, adolescent vaccine schedule
strategies, et cetera.
Although not specific to vaccines, the
Department of Health and Human Services
has released a new biodefense strategic
plan that, in addition to dealing with
potential biological attack threats, includes
discussion of emerging infectious diseases,
strategies for therapeutic vaccines, vaccine
delivery strategies (e.g., patch versus
intradermal), and the potential enhancing
effects of adjuvants.
Discussion of Petitioners’ Satisfaction
Survey - Tamara Overby, Chief, Policy
Analysis Branch, DVIC
Ms. Overby explained that the Program
will conduct a retrospective survey evaluation
of the claims process from the perspective
of the petitioner. The study is being
developed in response to ACCV recommendations
and the results of an OMB evaluation in
2005 that found that the Program had never
conducted an evaluation, a process that
should be undertaken on a regular basis.
Ms. Overby stated that the evaluation
questionnaire was developed and previously
distributed to ACCV members as a draft.
Comments received from ACCV members have
been incorporated in the revised draft
distributed at this meeting.
The survey will be sent to a target group
of about a thousand individuals who filed
claims during the past five years that
were either dismissed or were compensated.
The purpose is to determine what the petitioners
thought of the overall process. She conceded
that the survey was long (about 40 questions)
and would take some time to complete,
and that there was no way to estimate
a response rate.
The Program does not have personal information
about the petitioners, so the survey will
be sent to the petitioner’s attorney
to be forwarded for completion. After
speaking to several petitioners’
attorneys there is reason to believe that
the attorneys will cooperate in requesting
their clients to complete the survey.
A private contractor has been hired to
conduct the survey and tabulate results.
A small pilot survey will precede submission
of the survey to OMB for approval, a legal
requirement for all surveys originated
by federal agencies. She added that the
survey will be available in Spanish on
request.
Mr. Sconyers acknowledged the leadership
of ACCV members Dr. Deville and Ms. Buck
in supporting the process of moving the
survey forward. During discussion, Ms.
Overby affirmed that the survey would
be available on the DVIC web site. It
will be mailed to petitioners and a prepaid
return envelope will be included in the
survey package.
Report from ACCV Futures II Workgroup
- Jaime Deville, M.D.
Dr. Deville discussed the full-day meeting
of the ACCV’s Futures II Workgroup,
which first considered the safety provisions
of the National Childhood Vaccine Injury
Act of 1986, for which sustained funding
has not been provided. Dr. Salmon was
present and provided a thorough review
of NVPO activities, a description of the
Investigational New Drug process from
early clinical studies through the Phase
I, II and III clinical trials, to licensing.
He covered the FDA’s inspection
and control process, and the various surveillance
networks that exist to track adverse events
related to drugs. He discussed the interrelated
activities of various federal agencies
interested in drug safety, and the new
effort to develop a vaccine safety plan
that would be reviewed by the Institute
of Medicine.
Dr. Deville stated that the Workgroup
looked at the Petitioners’ Satisfaction
Survey, deciding that it was too long,
a characteristic that might adversely
affect response rate. There was discussion
on how make the survey more user-friendly.
A discussion of structured settlements
was postponed until a later meeting because
the invited expert on the subject was
unable to attend. Finally, the Workgroup
discussed the administrative requirements
of VICP, reaching an agreement that the
flat funding for the program over the
past years (of about $3 million since
1994) along with the increased financial
requirements due primarily to expert witness
program costs, staffing needs and the
autism caseload is not sufficient. This
has resulted in a detriment to some activities,
such as outreach and the conduct of meetings
and conferences. The issue will be on
a future agenda.
Dr. Deville listed several agenda items
for future meetings -- the petitioner’s
structured settlement issue, a review
of the vaccine injury table, using the
Trust Fund to fund HHS vaccine safety
activities, the VICP administrative budget
and program needs, and a review of the
final results of the Petitioners’
Satisfaction Survey.
Report on Autism Hearing from Petitioner’s
Attorney - Tom Powers, J.D., Williams,
Love, O’Leary, Crain & Powers
PC
Mr. Powers provided an update on the
process by which the Office of the Special
Masters will sort out how to handle over
4,800 claims alleging vaccine-related
autism. Three Special Masters (Hastings,
Campbell-Smith and Vowell) have been selected
to hear three test cases in each of three
categories based on theories of damage.
It is anticipated that once the nine test
cases have been heard, and decisions handed
down, those decisions will provide a reasonable
framework for expediting the handling
of the 4,800 pending cases and any others
that may be filed. Each of the Special
Masters will preside over one of the three
cases for each theory and write the opinion
on that case; although all three Special
Masters will sit en banc during each of
the hearings.
The first causation theory maintains
that exposure to thimerosal-containing
vaccines in combination with MMR is a
cause of autism (called the combined thimerosal/MMR
theory of causation). The first test case,
Cedillo v. HHS, was completed
in June and took 12 hearing days, producing
hundreds of scientific papers and thousands
of pages of transcript. The second test
case, Hazelhurst v. HHS,
was heard in North Carolina in early October
and took only four hearing days, in part
because some of the product of the Cedillo
v. HHS case could be applied
to the case. The third case, Snyder
v. HHS, will be heard in Florida
in early November.
The second causation theory is that mercury-containing
vaccines, whether or not accompanied by
MMR vaccination, caused autism (called
the thimerosal-only theory). Three test
cases will be selected in November and
various petitioners are beginning to develop
and submit the necessary documentation
to proceed. The cases will be heard in
May of 2008.
The third causation theory states that
the MMR vaccine, notwithstanding whether
there is thimerosal present or not in
the vaccine, can cause autism (MMR-only
theory). Three cases will be heard by
the end of September 2008.
During discussion, Mr. Powers stated
that it will take at least two or three
months before the briefs are available
to close the Cedillo v. HHS
case. Asked about whether the first three
cases will affect the outcome of the other
two causation theory cases, Mr. Powers
suggested that there is more overlap in
the MMR-only cases than in the thimerosol-only
cases, and the thimerosal-only case will
probably not help in the MMR-only case.
Mr. Powers noted that the Office of Special
Masters has been working to develop a
process to handle the thousands of claims
filed once the test cases have been decided
and the framework for processing cases
has been defined. It appears that the
Office will create groups of 50 or so
cases and allow petitioners’ attorneys
to submit enough supporting documentation
to make decisions on eligibility, mainly
on the basis of timeliness of filing the
original claim. The management process
will be challenging, sorting out those
clearly eligible, those clearly ineligible,
and those in the middle which will require
some effort to resolve.
Update from the National Vaccine Program
Office (NVPO) - Dan Salmon, Ph.D., NVPO
Dr. Salmon briefly discussed activities
at NVPO. The National Vaccine Advisory
Committee (NVAC) met the week before the
ACCV meeting and discussed the National
Vaccine Plan, an overall strategic plan
for federal vaccine activities, which
includes vaccine safety and the injury
compensation program. The plan development
process includes public comment and review
by the Institute of Medicine.
The NVAC also approved the adolescent
criteria for state-mandated school vaccination
schedules and intends to develop the criteria
in an article for journal publication.
It is one of several other recently published
articles that look at the issue of compulsory
vaccination.
The NVAC Safety Subcommittee has merged
with the NVAC Communications Subcommittee
and expanded its membership to include
consultants in immunology, toxicology,
neurology, epidemiology, biostatistics
and pharmacology. The Immunization Safety
Office of CDC is developing a research
agenda that will deal with very specific
hypothesis-driven research issues. The
agenda will be reviewed by the Subcommittee.
Another task that NVPO will ask the Subcommittee
to take on is a broad review of the current
federal system for vaccine safety. NVPO
is developing a comprehensive report of
the federal system that will serve as
a basis for the review.
Dr. Salmon commented that the ACCV might
be interested in an NVPO assessment of
maternal immunization -- whether or not
pregnant women should be routinely vaccinated
with vaccines normally made available
to the public, and whether or not pregnant
women should be specifically vaccinated
against certain high-risk diseases that
should be prevented in pregnant women.
Update on the Center for Biologics and
Evaluation Research (CBER), Food and Drug
Administration (FDA) Vaccine Activities
- Marion Gruber, Ph.D., CBER, FDA
Dr. Gruber commented on a series of FDA
drug approvals:
A Sanofi Pasteur vaccine for H5N1 avian
flu was approved for persons 18 to 63
years of age, but the company will not
make the vaccine available to the commercial
market. The Federal Government will purchase
the drug for its Strategic National Stockpile
for distribution by public health officers
in the event of a pandemic flu outbreak.
On August 31st, FDA approved smallpox
(vaccinia) vaccine only for persons at
high risk of smallpox infection. Clinical
trials revealed that the vaccine is effective
but there is a relatively high rate of
serious adverse events, such as myocarditis,
and the sponsor was required to develop
a “RiskMAP” program to fully
inform recipients of its potential risks.
On September 19th, FDA approved FluMist,
an intranasal live attenuated vaccine
for influenza for children beginning at
2 years of age. It had previously been
approved for individuals 5 to 49 years
of age. Since the vaccine is known to
induce wheezing in some recipients, the
manufacturer was required to develop a
RiskMAP. It was contraindicated for children
with asthma or active airway disease.
Further the manufacturer, MedImmune, was
required to launch a large post-marketing
trial to evaluate safety signals and safety
outcomes such as asthma and wheezing.
On September 28 the FDA licensed an inactivated
influenza vaccine, made by an Australian
company, for individuals 18 years and
older. The vaccine was shown to increase
immune response against the influenza
subtypes present in the vaccine.
Dr. Gruber noted that there are now six
manufacturers of influenza vaccines licensed
in the U.S.
Finally, Menactra, which has been approved
for individuals 11 to 55 years of age,
was recently approved for children 2 to
10 years of age. Menactra protects against
invasive meningococcal disease. Dr. Evans
commented that ACIP had recommended limited
use in high-risk children in the younger
age group of 2 to 10 years. Routine use
is not recommended.
On October 4th, FDA published a Federal
Register Notice about development
of effectiveness and safety assessments
related to vaccines developed for use
in pandemic situations. The question is
how to conduct a safety assessment for
a vaccine that is reserved for a unique
disaster situation? The Federal Register
Notice seeks interested parties who are
able to develop programs that can monitor
adverse events and assess efficacy following
the administration of the pandemic influenza
vaccine.
During discussion Ms. Tempfer asked about
differences in the six influenza vaccines
available and how a consumer would decide
which to rely on. Dr. Gruber stated that,
except for FluMist which is a live attenuated
vaccine, there was little difference in
the six in terms of influenza virus subtypes
in the vaccine. All six have slightly
different manufacturing processes and
formulations. All contain thimerosal but
some are available in thimerosal-free
formulations, and the vaccines are approved
for different age ranges.
Dr. Gruber discussed the recently passed
FDA Amendments Acts of 2007 (HR 3580),
which was signed into law on September
27th. It is a major law that reauthorizes
the Prescription Drug User Fee Act, the
Medical Device User Fee Act, the Pediatric
Research Equity Act and the Best Pharmaceuticals
for Children Act. Although FDA has not
yet fully analyzed the law requirements
and time lines, Dr. Gruber offered a number
of observations.
Title IX authorizes FDA to require post-marketing
epidemiological and clinical trials of
already-approved drugs and to require
safety-related label changes. Manufacturers
may also be required to develop formal
Risk Evaluation and Mitigation Strategies
(REMS) for specified drugs. The FDA must
have a scientific rationale to make these
requirements and the studies must have
a specific primary outcome -- to assess
a known risk or signal of risk of drug
use. And the studies may only be required
if existing surveillance systems (like
VAERS) are not able to assess a known
serious risk or signals of serious risk.
When the requirement is made, the sponsor
must submit a time table for the study
and describe any obstacles that may exist
in conducting the study.
The FDA may determine that a REMS is
required to assess whether the benefits
of a drug outweigh the risks before or
after the drug has been licensed. The
REMS would consider the size of the drug
use population, the seriousness of the
disease being treated, the benefits of
the drug, and what mitigation strategies
would be appropriate (e.g., package inserts,
letters to health care providers). The
mitigation must not be a burden to the
patient or inhibit reasonable access to
the drug.
Dr. Gruber noted that Section 905 of
the Act requires that FDA set up a surveillance
system to monitor adverse events, the
establishment of a “risk identification
and analysis system” that would
eventually involve monitoring up to 100
million individuals by 2012 from multiple
sources. It will involve significant collaborating
with public and private entities to provide
analysis of drug safety data.
Finally, the law requires establishment
of an expert committee to look at data
privacy and security and to develop recommendations
for the ethical use of post-marketing
data.
There was a brief discussion about whether
the funding provided in the law would
be sufficient for the mandates.
Update on Vaccine Safety Datalink (VSD),
Vaccine Adverse Event Reporting System
(VAERS), and the Immunization Safety Office
(ISO), CDC - Karen Broder, M.D., ISO,
CDC
Dr. Broder reported on several issues
discussed at the recent Advisory Committee
on Immunization Practices (ACIP) meeting
in Atlanta. ACIP provides guidance on
immunization issues to the HHS Secretary
and Assistant Secretary for Health and
to the Director of CDC, particularly focusing
on how to best use licensed vaccines to
prevent communicable disease. It establishes
a list of vaccines for distribution through
the Vaccines for Children Program.
Dr. Broder briefly described the Vaccine
Adverse Event Reporting System (VAERS),
operated jointly by CDC and FDA, the largest
passive surveillance system that derives
its data from voluntary reports by physicians
and private individuals, and mandatory
reports from manufacturers.
The Vaccine Safety Datalink Project is
a collaboration between CDC and eight
large managed care organization that provide
medical and immunization histories on
about 5.5 million people annually. VSP
also conducts research on hypotheses that
are proposed internally and by outside
sources.
Dr. Broder briefly discussed three areas
of interest presented at the ACIP meeting
-- use of FluMist in children ages 24
to 59 months; early thimerosal exposure
and neuropsychological outcomes in children
7 to 10 years; and episodes of syncope
reported after vaccination.
In September the FDA approved the use
of FluMist in younger children 2 to 5
years of age, who were shown in pre-licensure
tests to be vulnerable to an increased
risk for development of wheezing after
vaccination. Even with the approval, it
is not recommended for children who have
recurrent wheezing. The ACIP discussion
pointed out that physicians might have
difficulty defining recurrent wheezing
in a busy clinic. ACIP voted to recommend
use of FluMist in the approved age group,
but to encourage providers to make an
effort to determine whether a younger
child had recurrent wheezing by asking
the parents a proactive question about
previous diagnosis or comment by a healthcare
provider that the child had had that condition.
In that case, the child would receive
an inactivated influenza vaccine injection.
Dr. Broder referred to a September paper
in the New England Journal of Medicine
that described a study of children 7 to
10 years of age exposed to thimerosal
at an early age to determine if there
were negative effects on neuropsychological
functioning -- specifically speech and
language, attention span, fine motor functioning,
perception, motor and phonic tics, academic
performance, and ADHD. Among 42 outcomes
there were minimal significant associations
with thimerosal exposure parentally or
within seven months of birth. The study
showed that the few negative effects were
mainly in males and were mainly manifested
in behavior and tics. The evidence did
not support a causal relationship between
thimerosol exposure and psychological
functioning at 7 to 10 years of age.
The third study looked at syncope (fainting)
after vaccination because it could lead
to injury. Although uncommon, one form,
vasovagal syncope, can be caused by the
pain and/or anxiety that sometimes accompany
a vaccination experience. The ACIP approved
a recommendation that providers should
observe those vaccinated for 15 minutes
and if evidence of syncope appears, continue
observation until the symptoms abate.
Dr. Broder presented a graph (2004 to
2007) of syncopal events after vaccination
in individuals 5 years of age and over.
The graph clearly demonstrated an increase
in syncopal events (mainly in females)
within one day of vaccination after the
approval and introduction of HPV vaccine
(which is a three-dose series) in June
2006.
Dr. Broder commented that the Institute
of Medicine, in a 2005 report, recommended
that NVAC provide advice on the Vaccine
Safety Datalink’s research plan.
A three-phase process was established.
Currently, in the first phase the ISO
is developing a draft research agenda
with input from outside multidisciplinary
consultants, including representatives
of pharmaceutical companies, the Interagency
Vaccine Group, and others. There have
also been brainstorming sessions related
to life stages (infants, children, adolescents,
elderly, pregnant women) and a number
of specific areas have been considered
-- non-antigen vaccine components including
adjuvants, new vaccine technology, public
perception, host factors, vaccination
practices, clinical outcomes including
adverse events, and other areas. After
the draft ISO Scientific Agenda is complete,
the National Vaccine Advisory Committee
will undertake a scientific review of
this Agenda and advise CDC on the content
and priorities. CDC will respond to the
NVAC feedback and finalize the Agenda.
Public Comment
Mr. Sconyers noted that there were no
requests from individuals wishing to make
a public comment during the meeting.
Future Agenda Items
Dr. Evans suggested that an occasional
agenda item might be entitled “noteworthy
quotes by ACCV members.” He proposed
that the first one be a quote by Dr. Margaret
Fisher:
“School children are among the
group most responsible for transmission
of contagious respiratory viruses, including
influenza. Children are inherently more
at risk because they congregate in groups.
They like to share their secretions. They
won’t share their toys, but are
happy to share their germs.”
Ms. Gallagher suggested that a review
of the VICP 2008 budget be included in
a future agenda, especially with regard
to whether there is any ACCV action that
would be appropriate.
Concluding Remarks and Adjournment
Mr. Sconyers pointed out the copy of
the letter in the meeting book materials
that was sent to HHS Secretary Leavitt
by the ACCV chair pursuant to actions
taken during the March meeting. There
being no further business, the meeting
was concluded.
(Whereupon at 3:00 p.m., the meeting
was adjourned.)
| This
information reflects the current thinking of the United States Department
of Health and Human Services on the topics addressed. This information is
not legal advice and does not create or confer any rights for or on any
person and does not operate to bind the Department or the public. The ultimate
decision about the scope of the statutes authorizing the VICP is within
the authority of the United States Court of Federal Claims, which is responsible
for resolving claims for compensation under the VICP.
|
|
