Advisory
Commission on Childhood Vaccines Meeting
March
6-7, 2008
Minutes
Members
Present
- Jeffrey
M. Sconyers, J.D, Chair
- Jaime G. Deville, M.D., Vice Chair
- Tawny
Buck (Via Phone)
- Tamara Tempfer, RN-C, MSN, PNP
- Margaret Fisher, M.D., FAAP
- Charlene Gallagher, J.D.
-
Magdalena Castro-Lewis
Ex-Officio
Members Present
-
Marion Gruber, Ph.D.
- John Iskander, M.D., M.P.H.
-
Barbara Mulach, Ph.D.
- Dan Salmon, Ph.D.
Executive Secretary
- Geoffrey Evans, M.D., Director, DVIC
Staff
Liaison
- Michelle Herzog, DVIC, HSB, HRSA
Office of General Counsel
March 6, 2008
Introduction
Mr. Sconyers convened the 68th quarterly
meeting of the Advisory Commission of
Childhood Vaccines (ACCV) at 1:05 p.m.
and welcomed all participants. On motion
duly made and seconded, the minutes of
the October 2007 meeting were unanimously
approved.
Report from the Division of Vaccine
Injury Compensation (DVIC)
Geoffrey S. Evans, M.D., Director
Dr. Evans welcomed members and guests
in attendance and reviewed the agenda
for the two-day meeting.
Financial Report
Dr. Evans reviewed the 2007 filings for
non-autism claims (239) and autism claims
(167), a total of 406 claims. It was slightly
higher than 2006, partly because of the
Omnibus hearings in June 2007. During
the first four months of fiscal year 2008,
there have been 81 claims, 44 non-autism,
37 autism, which is slightly lower than
the average number of filings for the
same period in past years. The 2007 awards,
however, were the highest in the history
of the program -- $91 million versus an
average of about $59 million for the past
six years. Attorneys’ fees were
similar to past years, about $4 million.
The Trust Fund stands at $2.7 billion,
having increased significantly because
of the addition of flu vaccine which is
distributed to a very large population,
about 120 million doses annually. It is
anticipated that the fund will increase
by about $340 million in 2008, a little
over a third of which will come from interest.
DVIC Activities
Dr. Evans updated the Commission on significant
DVIC activities since the last meeting.
Dr. Rosemary Johann-Liang attended the
“Understanding the Genomic Basis
of Vaccine Safety Workshop” in Atlanta
(January 30-31). The workshop was intended
to begin addressing whether there is a
genetic factor in individuals that is
involved in adverse reactions to vaccination.
From February 5-6, Dr. Evans represented
HRSA as an ex officio member of the National
Vaccine Advisory Committee. Tammy Tempfer
also attended the meeting in her new role
as ACCV liaison to NVAC.
On February 21, Dr. Indira Jevaji attended
the FDA Vaccines and Related Biological
Products Advisory Committee meeting, which
considered the GlaxoSmithKline’s
license application for a new oral rotavirus
vaccine, trade name, Rotarix. Finally,
both Drs. Johann-Liang and Evans attended
the February 27-28 Advisory Committee
on Immunization Practices meeting in Atlanta.
As reported in the media, the ACIP recommended
extending the routine use recommendation
for influenza vaccine from 59 months up
to age 18 years, effective no later than
the 2009-2010 flu season.
Autism
Dr. Evans commented that, despite reports
and commentary in the media to the contrary,
DVIC has reviewed data concerning the
allegation that vaccines cause autism
and has discovered no credible evidence
for support. He added that the 6-year
anniversary of the Omnibus Autism Proceeding
is in July and that the substantial amount
of scientific data accumulated during
this time has not shown any association
between autism and vaccines.
Report from the Department of Justice
to ACCV Commission
Vince Matanoski, J.D
Acting Deputy Director, Torts Branch
Civil Division, Department of Justice
Mr. Matanoski reported that he is serving
as Acting Deputy Director for the Torts
Branch, vaccine section while Mr. Rogers
was deployed to Iraq.
Personnel
Since the last ACCV meeting, the Department
of Justice (DOJ) has hired three new attorneys,
but lost two. The office was in the process
of hiring replacement attorneys and staff.
Statistics
Regarding cases filed, Mr. Matanoski
noted that the DOJ’s numbers were
consistent with Dr. Evans’s numbers,
however, according to the DOJ statistics,
there were 90 cases filed since October,
2007, the beginning of the fiscal year.
Of those, 52 were non-autism and 38 were
autism proceedings. Of the autism claims
filed, most were “short form”
filings and cases filed without the records.
Eventually, more information will be needed
in all of these cases before they can
proceed. Since October, 2007, there were
122 cases resolved. Mr. Matanoski noted
that there were about 1,000 non-autism
and about 4,800 autism cases pending in
the Program. Of the 122 cases resolved,
43 were compensated and of those, 38 were
settled. The settlements highlight the
cooperation between the Government’s
counsel and petitioners’ attorneys.
There were 79 cases dismissed (49 non-autism,
30 autism). Most dismissals were non-autism
and initiated by the petitioners while
a few were time-barred.
Autism
In the area of litigation, Mr. Matanoski
reported that three trials involving the
first theory of causation presented by
the Petitioners’ Steering Committee
(PSC) were completed. The theory in each
trial was whether the MMR vaccine causes
autism and was tried in the cases of Cedillo
v. HHS, Hazelhurst v. HHS and Snyder v.
HHS. All of those cases are in various
stages of post-trial briefing. The Cedillo
case is the closest to completion, while
Hazelhurst and Snyder are undergoing further
briefing. In the Snyder trial, the PSC
sought to obtain information from MMR
trials in the United Kingdom on the presumption
that the information might assist the
special master in determining whether
the US labs involved in testing produced
valid results. The Government presented
evidence from experts that appeared at
the UK proceedings regarding the validity
of the lab tests. The status of the PSC’s
efforts to obtain the information is unclear.
If they are successful in obtaining that
information, a decision in Snyder may
take a little longer while the special
master considers that evidence. Overall,
Mr. Matanoski did not anticipate any of
the decisions in the first round of test
cases to be issued before the second theory
of causation begins. The second theory,
which is whether Thimerosal in vaccines
causes autism, is scheduled to start on
May 12, 2008 in Washington, DC. That trial
is expected to last three weeks. Both
sides have filed their expert reports.
Currently, the parties are in the rebuttal
stages meaning that they have an opportunity
to file rebuttal expert reports. Petitioners
have the opportunity to file first, and
then the Government will determine whether
or not rebuttal evidence is warranted.
Mr. Matanoski anticipates that the May
12, 2008 trial will start on time.
Regarding whether or not vaccines cause
autism, there has been no change in the
litigation position of the Secretary.
Mr. Matanoski addressed what appears to
be confusion surrounding a document that
was recently put out in the media. First,
DOJ policy is not to comment on cases
that are pending in litigation. Because
the document involves an active case,
Mr. Matanoski could not discuss the contents
of that document. Instead, Mr. Matanoski
spoke generally about the type of document
that was circulated in the media. The
document is called a Rule 4(c) report,
and is prepared by DOJ in litigation.
In regular civil actions, a complaint
is filed by a plaintiff and the defendant
files an answer, which is a legal document.
The Rule 4(c) Report is not a statement
of scientific position or research. It
is specific to the facts of a particular
case filed under the Vaccine Act. The
Rule 4(c) Report is used in every case
that is filed in the Program. It is not
specific to any class of cases. It represents
communication from one party to another
about a legal position taken on a case
and conveys the Government’s legal
position on compensation in a particular
case under the Vaccine Act. These documents
are used by the presiding special master
to understand the Government’s legal
position on compensation. The special
master typically asks questions about
the document and investigates further
during the course of the proceedings,
particularly when the Government takes
the position that compensation is not
appropriate. Mr. Matanoski emphasized
that the position taken in the Rule 4(c)
Report is investigated by a special master
as the case progresses. In the autism
cases, the Government filed a Rule 4(c)
Report in every filed case even when there
were no records to review. In those instances,
the Government’s Rule 4(c) Report
noted that DOJ cannot take a position
on compensation because there are not
filed documents.
Regarding the course of the autism litigation,
the PSC may allege new claims for compensation.
The legal theories will continue to unfold
during the autism proceedings. Mr. Matanoski
reiterated Dr. Evans’s view that
there is no scientific evidence that would
change the Government’s position
on whether or not vaccines cause autism.
In fact, there is voluminous scientific
evidence directly addressing that question
and the scientific evidence has overwhelmingly
shown that there is no connection between
vaccines and autism.
Recognizing that the Chief Special Master
will also address the ACCV members about
the volume of cases pending in the Program,
Mr. Matanoski noted that there are about
4,800 autism cases pending. Most of those
cases lack documentation and/or were filed
without supporting records. Within the
next two years, however, those cases will
be activated. That means that records
will be ordered to be filed in each case
so that an initial evaluation can be made
on jurisdiction, as well as whether they
are properly considered part of the omnibus
proceeding. With the autism litigation,
which is a large part of the volume, there
will be about 6,000 total cases to be
evaluated. So far, 200 of the autism cases
have been activated. DOJ has taken steps
to ensure the availability of sufficient
resources to evaluate the claims, including
hiring contract individuals. The case
review will pose significant staffing
issues for DOJ, but Mr. Matanoski believed
that it will be within the present budget.
Considering the increased caseload from
1,000 cases to 6,000 cases, DOJ will be
reviewing future budget requests. Overall,
the review process will present a huge
change in DOJ’s operations given
the six-fold workload increase.
Appeals
In the appellate area, Mr. Matanoski
discussed two decisions from the U.S.
Court of Appeals for the Federal Circuit
(Federal Circuit). The case, Avera v.
HHS, involved attorneys’ fees. Petitioners’
attorney, who was located in Cheyenne,
Wyoming, sought compensation of his hourly
rates consistent with hourly rates paid
to attorneys who prevail against the Government
in certain fee-shifting statutes litigated
in Washington, D.C. The rates that petitioners
sought for their Cheyenne based attorney
are known as Laffey Matrix rates. Mr.
Matanoski explained that the Laffey Matrix
is used by the U.S. Attorneys’ Office
in Washington, DC in certain fee-shifting
statutory cases when a plaintiff prevails
against the Government, and is based on
Washington, DC hourly rates. The Laffey
Matrix hourly rates are significantly
higher than the hourly rates that petitioners’
Cheyenne-based attorney would receive
in Cheyenne, Wyoming. Petitioners’
attorney is located in Cheyenne and performed
all of his work there. In seeking Washington,
DC rates, petitioners’ attorney
sought to apply a forum rule analysis.
Counsel asserted that because all of the
vaccine cases are filed in the Court of
Federal Claims, which is physically located
in Washington, DC, and a decision issues
from the Office Special Masters, also
located in Washington, DC, petitioners’
counsel should be entitled to the Laffey
Matrix rates. The Laffey Matrix rates
represented a three-fold increase from
petitioners’ counsel’s Cheyenne,
Wyoming. A panel of three judges from
the Federal Circuit heard oral argument
and decided that under the facts of this
case, petitioners’ attorney was
not entitled to the hourly rates of the
forum, which it deemed to be Washington,
DC. Petitioners’ attorney was entitled
to hourly rates consistent with Cheyenne,
Wyoming, where he performed all of the
work in that case. The Court did not opine
upon whether or not the Laffey Matrix
constituted the appropriate forum rate.
Mr. Matanoski explained that while the
Court in Avera, adopted a forum rule,
it applied an exception to the forum rule.
Under the exception, if the “bulk
of the work” is not performed in
the forum (Washington, DC) and the forum
rates are substantially higher than the
locality where petitioner’s counsel
is located, then the forum rates (Washington,
DC) do not apply. In the Vaccine Program,
Mr. Matanoski noted that nearly every
case will fall under the exception to
the forum rule as most of the cases that
go to hearing are not tried in Washington,
DC. Most vaccine cases are tried over
the phone or in locations convenient to
the petitioners rather than holding any
court proceedings in Washington, DC. Most
of the petitioners and their lawyers live
and work outside Washington, DC. For example,
a petitioners’ counsel’s bill
might reflect that for the vast majority
of time, eighty hours was spent working
at the petitioners’ attorney’s
office in Cheyenne, Wyoming, with six
hours of time spent in Washington, DC
for a hearing. So, under a strict or common
sense interpretation of the Avera “bulk
of the work” exception to the forum
rule, one would say that most fees will
be paid consistent with the market rates
for where the petitioner’s attorney’s
office is located and where the bulk of
the work was performed. Nevertheless,
Mr. Matanoski predicted that there will
be a great deal of litigation to test
the contours of the Avera decision and
its exception to forum rule in the context
of the Vaccine Act. Mr. Matanoski expects
that a forum rule analysis and its exceptions
will be done on a case-by-case basis and
be fact specific. Notably, even if the
forum of Washington, DC applied, Avera
does not discuss an appropriate rate.
He predicted further litigation in this
area.
Also in the Avera case, petitioners’
attorney also requested payment of interim
fees, that is, payment of fees before
the case was completed pending appeal.
The Federal Circuit panel further ruled
that an award of interim fees and costs
was available under the Vaccine Act, however,
petitioners did not demonstrate that interim
fees were necessary in their case. The
Court in Avera found that the Vaccine
Act does not prevent an award of interim
fees, however, it offered little guidance
on when fees would be appropriate. Thus,
Mr. Matanoski expects further litigation
as petitioners and the Government attempt
to determine the contours of the Court’s
decision. DOJ has already contacted some
of petitioners’ counsel, who also
expressed an interest in discussing some
possible parameters for seeking payment
of interim fees. There was a meeting with
some petitioner’s attorneys to try
and reach an understanding of when it
would make sense for petitioners to seek
interim fees without having a huge impact
on the proceedings and where the Government
would have an opportunity to review the
request. In Avera, petitioners’
counsel sought interim fees after a decision
on entitlement issued and the case was
on appeal. A few scenarios were discussed,
including limits on the number of applications
for interim fees. The goal is to keep
the cases moving. Mr. Matanoski emphasized
the impact on the Program, however, if
there are multiple applications for payment
of interim fees and costs during the course
of a proceeding. From DOJ’s view,
instead of moving the case forward to
entitlement, the parties would be involved
in trying to resolve the interim fee requests.
Mr. Matanoski acknowledged that he understands
the views of petitioners’ counsel
that payment of interim fees could be
very helpful to them. Mr. Matanoski emphasized
that seeking interim fees on a biweekly
or monthly basis could result in longer
processing time for decisions. Mr. Matanoski
expressed that DOJ and some petitioners
attorneys were expected to continue discussions
on the parameters of interim fees to try
and cooperatively find common ground,
however, he predicted that continued litigation
would be inevitable.
Another case decided by the Federal Circuit
that will impact the Program is Zatuchni/Snyder
v. HHS. Originally, it was filed as Snyder
but Mrs. Snyder unfortunately died during
the pendency of the proceedings, and the
case is currently Zatuchni, which reflects
the name of the estate. In the underlying
case, petitioner was awarded compensation
for her death. The Government contended
that petitioner should be awarded $250,000.00,
which is the cap available if petitioner’s
death was found to be related to her vaccine-injury.
Petitioner contended that because Mrs.
Snyder was alive while her claim was pending
under the Vaccine Act, she should also
receive compensation for her pain and
suffering, as well as lost wages and past
unreimbursed expenses. The special master
found against petitioner and awarded $250,000.00
but issued findings on how much those
damages would be if the Court of Federal
Claims reversed. On appeal to the Court
of Federal Claims, the judge reversed
the special master, and awarded the additional
damages.
After hearing oral argument, the Federal
Circuit in Zatuchni/Snyder also disagreed
with the special master and found that
petitioner’s estate would be entitled
to the additional damages above the $250,000.00
available for vaccine injuries resulting
in death. The Government had maintained
throughout the appellate proceedings that
its waiver of sovereign immunity to be
sued limited the amount of damages available
to $250,000.00. The Federal Circuit did
not address that argument other than to
note, in a footnote, that they found the
terms of the Vaccine Act to be clear in
awarding additional damages. The holding
by the Federal Circuit in Zatuchni/Snyder
is fairly limited to the facts inasmuch
as it would apply where a person filed
a claim for vaccine-related injuries,
received a favorable ruling that the injuries
were vaccine-related, and then died before
receiving compensation for those injuries.
That fact pattern is rare in the Program.
Also, the opinion was a split decision
meaning two judges in the majority and
one who concurred with the result but
not the reasoning. The concurring judge
agreed that petitioner was entitled to
the additional injury-related damages
but for different reasons and disagreed
with the entire majority opinion. Mr.
Matanoski remarked that essentially there
are two diametrically opposed decisions
within one opinion that reach the same
result. It is unclear whether or not DOJ
will seek further review by the Federal
Circuit en banc or rehearing; the Solicitor
General of the United States makes that
determination. A rehearing en banc means
that all of the judges sitting on the
panel would hear the case along with the
original panel.
Mr. Matanoski also discussed another
case decided by the U.S. Supreme Court
that impacts vaccine cases, J.R. Sand
& Gravel v. U.S., involving a question
of jurisdiction. The Supreme Court reaffirmed
the established rule on jurisdiction.
Under the Vaccine Act, a case that is
untimely filed lacks jurisdiction at the
inception of the filing and should not
have been filed. Pending before the Federal
Circuit but not yet decided is Mojica
v. HHS, which was brought by petitioner.
In Mojica, the petition was filed one
day late because of an error entirely
attributed to Federal Express delivery.
There, the judge, Court of Federal Claims,
held that the special master correctly
dismissed petitioner’s case for
lack of jurisdiction. Even under those
circumstances, the Court of Federal Claims
found that equitable tolling did not apply
afford jurisdiction.
Another jurisdictional issue was decided
by the Court of Federal Claims, in Kay
v. HHS. There, the judge, Court of Federal
Claims, found that the special master
correctly denied petitioners’ request
for fees and costs after dismissing their
claim for lack of jurisdiction because
the petition was time-barred. Petitioners
have not yet filed an appeal to the Federal
Circuit. Mr. Matanoski generally noted
that there were several other fact specific
appeals pending and decided by the Court
of Federal Claims.
Questions
In response to a question from Ms. Tempfer
regarding a newspaper article, Mr. Matanoski
clarified that no autism rulings have
been issued. Ms. Buck observed that the
ACCV had unanimously recommended the payments
of interim attorneys’ fees and appreciated
the Government’s efforts to work
with petitioners’ attorneys on implementing
that process. She further observed that
the ACCV recommended paying both death
benefits and lost wage damages should
a petitioner die before the case is decided.
Mr. Matanoski predicted that the result
of Zatuchni/Snyder will be more litigation
and offered a few different scenarios
of what areas will be litigated in terms
of compensation for death benefits and
lost wages.
Omnibus Autism Proceedings Update
& Implications of the Causation Standard
in the Program
Chief Special Master Gary Golkiewicz
Chief Special Master Golkiewicz presented
information on the following topics:
- Causation Standard
- Policy-based versus traditional
tort-based
- Recent Federal Circuit opinion
– leans heavily towards setting
a standard whereby more cases are
compensated
- HHS policy – recommendations
to change table a balancing act
between basing changes on science
versus public policy
- Federal Circuit – “Althen”
three-part test for establishing
causation.
- Workload
- Two goals of Act – reduce
liability of those manufacturing
and administering vaccines; and
to provide compensation to those
individuals who were injured as
a result of a vaccine.
- Major issues with current process
is the time it takes to complete
a claim
- Building of cases including
obtaining medical records
- Scheduling – coordination
of activities among all key
players
- Damages phase – disagreements
can result in additional litigation
and negotitation
- Possible solutions
- Alternative Dispute Resolution
- Program to identify similar
cases
- Autism
- 4,800 cases pending
- Petitioners advised to hold off
filing medical records
- Timeliness review – 200
month
- Unknown – what Federal
Circuit will do with the recommendations
from the test cases.
Meeting
transcript for Chief Special Master Golkiewicz’s
full presentation.
Discussion of Newly-Added Vaccines
to the Vaccine Injury Table
Rosemary Johann-Liang, M.D.
Dr. Johann-Liang reported that four new
vaccines had been added to the Vaccine
Injury Table: hepatitis A (2004), influenza
(2005,), human papillomavirus (2007) and
two meningococcal vaccines, conjugate
and polysaccharide (2007).
Since licensure of hepatitis A vaccine,
there has been a 70 percent decline in
disease, with the largest declines among
children. The adverse events reported
were minor. There was one report of Guillain
Barré syndrome (GBS) in 2005. There
have been no recent claims filed for this
vaccine.
Influenza vaccine reports have been mostly
minor adverse reactions -- soreness at
the injection site, various systemic events
that occur within a few hours that may
persist for a few days (fever, malaise,
myalgia, etc.). In the very young, less
than 5 years of age, the reported rate
is about 11%, falling to 4-5% in children
6 to 10, and in adult studies there has
not been a significant difference between
placebo controls and subjects who received
the vaccine.
An Institute of Medicine study released
in 2006 concluded that there was no causal
relationship between the influenza vaccine
and neurological disorders, such as incident
and relapsing multiple sclerosis, nor
any proven evidence of causation for GBS.
Two Canadian studies reported conflicting
results for GBS, so a definitive epidemiological
answer has been elusive.
The live attenuated influenza vaccine,
which contains the same three antigens
and other components (except thimerosol)
that are in the trivalent inactivated
vaccine has seen a few serious adverse
events reported, including GBS, anaphylactic
shock and some asthmatic exacerbations,
particularly in younger children. When
the flu vaccine was added to the Vaccine
Injury Table there was a sharp increase
in claims filed, which continued until
the deadline for filing in 2007. It is
of note that, of 195 claims filed, only
20 were for children under age 20. The
injuries for those claims were mainly
neurologic complications and pain.
There was media coverage in 2007 for
the human papillomavirus vaccine (HPV)
which resulted in a tripling of VAERS
reported adverse events, but relatively
few serious outcomes were reported. No
adverse event related to death could be
causally linked to HPV. There have, however,
been a significant number of reports of
syncope that are temporally related to
HPV mainly among adolescent girls, but
a causal relationship is still under investigation.
Older women, up to 45 years of age, are
beginning to receive HPV and the adverse
events reports appear to be similar to
those among the adolescents.
Finally, the meningococcal conjugate
vaccine, Menactra, was approved in June
2005 for those 11 to 55 years of age.
In 2007, vaccine use was lowered to 2
years of age, although because of a number
of reasons not related to safety, (economic
considerations, the fact that new vaccines
specifically for infants are close to
approval) there was a recommendation to
administer the vaccine only to high risk
children 2 to 10 years of age. It was
observed that meningococcal disease is
rarely seen in children age 2 to 5, and
really does not appear in any significant
way until the middle teens.
During discussion, Dr. Johann-Liang clarified
that only the vaccines had been added
to the Vaccine Injury Table, and not any
specific adverse events. Potential injuries,
if any, must await further post-licensure
experience.
Vaccine Safety Datalink (VSD)
John Iskander, M.D., M.P.H.
Associate Director for Science, ISO, CDC
Dr. Iskander explained that the Vaccine
Safety Datalink (VSD) is the national
active national surveillance program for
vaccine safety, located at eight HMO’s
around the US and capable of conducting
vaccines studies on both adults and children.
A new development is the Rapid Cycle Analysis
(RCA) process. Previously retrospective
studies were updated every 6 to 12 months;
the RCA conducts targeted studies that
can be updated weekly. Target adverse
events are selected based on VAERS reports,
the biologic characteristics of the vaccine,
and issues that may have arisen during
pre-licensure testing.
For example, pre-licensure testing revealed
that a combination of MMR and varicella
vaccine (known as MMRV) may cause an increased
incidence of fever. A preliminary look
at MMRV given alone versus MMR and V given
separately did show 2 times the likelihood
of causing fever 7 to 10 days after vaccination.
Based on this rapid cycle analysis, the
ACIP changed its position from preferring
administration of the MMRV to a neutral
position on either form of administration,
in combination or separately. Another
recent study published in Pediatrics indicated
a possible low risk (1 in 40,000) of thrombocytopenia
following MMR administration. However,
the study revealed no other acute or long-term
complications..
Finally, RCA was applied to the incidence
of intussusception related to Merck’s
rotavirus vaccine, RotaTeq, and the result
was that intussusception was no more likely
to occur after vaccination than by chance
alone.
During discussion, Dr. Iskander commented
that the live, attenuated MMR vaccine
might have similar adverse effects to
mumps, which could include loss of hearing.
There were some VAERS reports of loss
of hearing, but the data was insufficient
to conclude that the vaccine as a causal
factor. Therefore, it would be appropriate
to consider a controlled study to look
at the issue.
Vaccine Adverse Event Reporting
System (VAERS) Update
Jane Woo, M.D.
Dr. Woo stated that the National Childhood
Vaccine Injury Act mandated the establishment
of a reporting system, which became the
Vaccine Adverse Event Reporting System
(VAERS), a passive surveillance system
to collect data on adverse events after
vaccination. . Reports are submitted by
health care providers, vaccine recipients,
vaccine manufacturers, and other interested
parties. Between 15,000 to 20,000 such
reports are received each year.
FDA medical officers review the reports,
looking for patterns for vaccines in general
and specific vaccine products, as well.
Strength of VAERS include timeliness of
the data, the ability to determine rare
adverse events, lot-specific safety assessment,
hypothesis generation, and national and
international coverage. Weaknesses of
VAERS include under-reporting (some doctors,
for example, do not submit reports), over-reporting
(e.g., by a media blitz), uncertain number
of vaccine doses administered, incomplete
reports, and the absence of an unvaccinated
control group. .
Concerning specific adverse events, Dr.
Woo mentioned that 28 cases of Guillain
Barré syndrome have been confirmed
among adolescents who received Menactra®.
The number of reports is consistent with
the number that would be anticipated in
the general population. A large study
sponsored by the manufacturer will include
10 million people and may help to estimate
the risk.
Dr. Woo discussed VAERS reports of syncope
after adolescent vaccines, including a
phenomenon known as convulsive syncope
(fainting accompanied by seizure activity
(although it is not a specific seizure
disorder). The risk appears to be higher
after the simultaneous administration
of multiple vaccines. The recommendation
that patients be observed for about 20
minutes, in case of an allergic reaction,
could also prevent falls and injuries
due to syncope.
Finally, FluMist® is now licensed
for influenza prevention in health people
2-49 years old. A large post-marketing
study will be used to evaluate the safety
of the vaccine in children 24-59 months
old, with particular emphasis on asthma,
allergic reactions, and neurological disorders.
During the discussion, Dr. Woo commented
that, although individuals in foreign
countries may report adverse events to
VAERS, they typically do not. The FDA
can encourage, but not enforce, reporting
in the medical community. It was noted,
however, that the Act mandates physician
reporting for certain adverse events.
Through web alerts, the FDA and CDC can
inform the community of specific concerns
and ask people to send reports. Dr. Salmon
noted that even the legal requirement
to distribute Vaccine Information Statements
is admittedly ignored by 40% of those
who administer vaccines.
The number of reports to VAERS for individual
vaccine lots varies, but lots with a large
number of reports do not necessarily have
an increased risk of adverse events. Lots
vary in size, so variation in the number
of reports per lot based on coincidental
events occurring after vaccination is
to be expected. FDA looks not only at
the number of events per lot and the lot
size, but also the type of events and
any unusual or unexpected patterns in
clinical or demographic characteristics.
Dr. Woo stated that, since she has been
at the FDA, no vaccine lot has been definitely
proven to cause specific adverse events.
In addition, while manufacturers report
the number of vaccines doses that have
been distributed, the number of doses
that are administered is not always known.
Finally, Dr. Woo noted that VAERS does
not conduct clinical trials, but works
with CDC and the manufacturers to help
design studies that will address potential
safety concerns.
Update from the National Vaccine
Program Office (NVPO)
Dan Salmon, Ph.D.
Dr. Salmon explained that the National
Vaccine Advisory Committee had changed
its structure to rely on working groups
rather than subcommittees to develop recommendations.
The Safety Working group will be composed
of appointed NVAC members who have expertise
in the field, plus a number of consultants
from different disciplines, including
child and maternal health, epidemiology,
genomics, toxicology, neurology and others.
There are five members who were also involved
in the recent IOM Immunization Safety
Review Committee. Finally, he noted that
ACCV member, Tawny Buck, was on the working
group, as one of two representatives of
parents of affected children.
The working group has two main objectives.
The first, which came out of the IOM report,
is to develop the framework of a research
agenda for the Immunization Safety Office
project. The second is to look at the
entire federal vaccine safety system as
to how it could optimize vaccine safety,
reduce adverse events, and improve the
confidence of the American public in the
safety of vaccines.
The first objective will require the
CDC to conduct an information-gathering
process from which the CDC will develop
a draft research agenda. Then, that draft
will be reviewed by the NVAC working group,
which will make recommendations for prioritization.
Then the CDC will develop the final agenda.
The second charge, to review the national
system, has resulted in a relatively large
review report prepared by the NVPO of
what the national vaccine system looks
like today. That report will be submitted
to the NVAC Working Group on Vaccine Safety
and Communications, which will develop
a plan for what the system ought to be.
The entire process should be competed
within about 18 months. Dr. Salmon mentioned
that the NVPO working group will have
an open meeting on April 11 as part of
the information-gathering process.
Finally, Dr. Salmon mentioned that the
NVPO is beginning to work on maternal
immunization with the objective of developing
a report on future activities.
Update on the Immunization Safety
Office (ISO/CDC)
John Iskander, M.D.
Dr. Iskander explained that the ISO (which
includes VSD and affiliation with the
Brighton Collaboration) is responsible
for scientific surveillance and research
related to vaccine safety. He added that
the NVPO was more of a policy office,
charged with coordinating federal vaccine
activities.
He described an example of research,
a study of the varicella vaccine involving
more than 50 million distributed doses.
The study revealed four confirmed cases
of neurological illness which occurred
more than six months after vaccination,
and all the children involved recovered.
A second study involved vaccines which
contained thimerosol versus vaccines that
did not. The study showed no evidence
of local infection or hypersensitivity
in either vaccine. He added that new data
shows that ethyl mercury, a byproduct
of thimerosol metabolism, is rapidly excreted
after vaccination.
Concerning GBS, he stated that the results
of the Harvard Pilgrim study, previously
mentioned by Dr. Woo, should be available
in 2009. Also, an NVPO-sponsored animal
study at the University of Pennsylvania
showed that swine flu vaccine does induce
antibodies that may be related to GBS,
and further studies are planned. Non-federal
scientists, looking at VAERS data, have
suggested that vaccines other than influenza
vaccine could be associated with GBS.
The ISO pointed out some weaknesses in
the study design in a published letter
to the editor. Finally, there were over
2,500 VAERS reports on Gardasil, the quadrivalent
HPV, including some that reported serious
adverse events of death, GBS and deep
vein thrombosis. Analysis of the VAERS
data showed no evidence of causation.
Nonetheless, the reports generated some
media response.
Concerning a Hib vaccine recall, the
recall was based on contamination of the
vaccine manufacturing equipment; there
was no contamination of the vaccines,
nor were there any reported infections.
Finally, Dr. Iskander stated that the
ISO was beginning to look at stage-of-life
factors related to vaccines -- infants,
children, adolescents, adults. A number
of independent scientists and consultants
providing input into a 5 year scientific
agenda have suggested a wide range of
issue that could be examined.
Update on National Institute of
Allergy and Infectious Diseases (NIAID)
Vaccine Activities
Barbara Mulach, Ph.D.
Dr. Mulach briefly referred to the thimerosal-containing
vaccine study mentioned by Dr. Iskander,
adding that it was conducted in Argentina
and that there was evidence that the thimerosal
was rapidly excreted in the children’s
urine and feces. These results were published
in the February 2008 issue of Pediatrics
(1). In addition, recently NIH-supported
researchers at UC-Davis conducted a study
to try to replicate the results of a toxicological
study of mice exposed to thimerosal. The
initial study by Horning et al indicated
that the mice exposed to thimerosal exhibit
altered behavior and neurological changes.
In contrast, the results of the UC-Davis
study do not indicate pervasive developmental
neurotoxicity following vaccine-level
thimerosal injections in this strain of
mice (2).
References:
- Pichichero ME, Gentile A, Giglio
N, Umido V, Clarkson T, Cernichiari
E,
Zareba G, Gotelli C, Gotelli M, Yan
L, Treanor J. Mercury levels in
newborns and infants after receipt of
thimerosal-containing vaccines.
Pediatrics 121(2):e208-214 (2008).
- Berman RF, Pessah IN, Mouton PR,
Mav D, Harry J. Low-level neonatal
thimerosal exposure: Further evaluation
of altered neurotoxic potential in
SJL mice. Toxicol. Sci. (2008) 101:294-309.
Update from the Center for Biologics,
Evaluation and Research (CBER/FDA)
Marion Gruber, Ph.D.
Dr Gruber reported that, since the last
ACCV meeting in October 2007, there were
no new vaccine approvals. Biologics license
applications for the following vaccines
are currently under review by FDA: human
papillomavirus vaccine, a Diphtheria and
Tetanus Toxoids Adsorbed combined with
Inactivated Poliomyelitis Vaccine (Pentacel)
as well as a rotavirus vaccine (Rotarix)
manufactured by GlaxoSmithKline Biologicals.
The proposed indication for Rotarix is
for the prevention of rotavirus gastroenteritis
caused by G1 and non-G1 types (including
G2, G3, G4, and G9) when administered
as a 2-dose series to infants 6 to 24
weeks of age. For this vaccine safety
and efficacy data were presented to the
FDA Vaccines and Related Biological Products
Advisory Committee on February 20, 2008.
On February 21, 2006, the FDA Vaccines
and Related Biological Products Advisory
Committee met to consider which influenza
viruses should be included in vaccines
for use in the 2008-2009 influenza season
in the US. Based on surveillance data,
responses to current vaccines and availability
of strains and reagents, the committee
recommended that influenza vaccines for
2008-2009 should be trivalent and also
recommended three strain changes compared
to the influenza vaccine used in the 2007-2008
season:
Influenza A (H1N1) |
|
– Replace current
vaccine strain with alternative H1N1
isolate |
|
|
• A/Brisbane/59/2007
(H1N1)-like virus |
Influenza A (H3N2) |
|
– Replace current
vaccine strain with alternative H3N2
isolate |
|
|
• A/Brisbane/10/2007 (H3N2)-like
virus |
Influenza B |
|
– Replace current
vaccine strain with alternative |
|
|
• B/Florida/4/2006-like virus
|
The influenza vaccine compositions to
be used in the 2008-2009 season in the
US are identical to those recommended
by WHO February 13, 2008. FDA is currently
discussing licensure pathways for quadrivalent
influenza vaccines. ACCV participants
remarked that the influenza vaccine distributed
in the 2007-2008 season was less effective.
Dr. Gruber noted that during the 2007-2008
influenza season new influenza strains
began to emerge that did not fully match
the vaccine strains. The challenges in
making decisions regarding what strains
to include in the annual vaccines were
briefly discussed. Decisions makers need
as much time as possible to gather relevant
data but that time may impinge on the
manufacturing timelines and requirements.
The final decision on what influenza strains
to include in the annual influenza vaccine
is often based on an educated guess.
Public Comment
Mr. Sconyers invited public
participation in the meeting. There were
no requests by members of the public to
comment.
March 7, 2008
Unfinished Business from Day One
Mr. Sconyers opened the meeting and invited
members to bring up issues related to
the preceding day’s proceedings.
Mr. Glass referred to an article in the
reference materials handout (reference
9.3, Schecter) that stated that thimerosol-containing
influenza vaccine from multi-dose vials
had been recommended for children age
6 to 23 months. Dr. Iskander confirmed
that the recommendation from ACIP was
that infants 6 to 23 months of age should
receive flu vaccine, but the recommendation
did not specify the type of vaccine. Dr.
Evans noted that only Sanofi-Pasteur manufactures
a thimerosol-free flu vaccine (about 6
million doses a year), but had had difficulty
in effectively distributing the vaccine
such that a portion of each year’s
production remain unused.
Dr. Iskander suggested that most pediatricians
would order thimerosol-free vaccine (although
only about half of the children receive
vaccinations from their physicians). The
distribution system is complicated --
it involves the need to order right after
the flu season and the doctor’s
distributor may not know who the manufacturer
will be months later. Availability can
be uneven geographically and even the
CDC’s FluFinder program may not
be able to help move thimerosol-free vaccine
efficiently.
There was a brief discussion about the
premise that, with the removal of thimerosol
from children’s vaccines, incidence
of autism should decline. But it was noted
that the diagnostic parameters are expanding
and the sophistication of diagnosis is
increasing so that the rate could well
continue to increase. Mr. Glass commented
that thimerosol in flu vaccine could confound
the premise. He added that the diagnosis
of autism is an evolutionary phenomenon
and that parents have often experienced
significant delays in finally receiving
a definitive diagnosis. He expressed concern
that statements from the government and
in the press that claim children’s
vaccines are thimerosol-free are misleading,
and the words “except for influenza
vaccine” should be added as a caveat.
Ms. Buck agreed, noting that parents should
have the option of choosing a thimerosol-free
vaccine and that there should be sufficient
education to allow an informed decision
in that matter. Ms. Buck requested information
be provided on the price to practitioners
who requested thimerosal-free vaccines
and how it differed from regular vaccines.
On another matter, there was a request
that a legislative update be provided.
Dr. Evans stated that there had been little
activity on the Hill since the last ACCV
meeting. Two bills have been introduced
in Congress -- the Mercury-Free Vaccines
Act (H.R. 881) and the Comprehensive Comparative
Study of Vaccinated and Unvaccinated Populations
Act (H.R. 2832). There has been no further
action.
Report from the ACCV Future II Workshop
Jaime Deville, M.D.
Dr. Deville reported that the working
group had been interested in four issues.
The first is how the VICP is responding
to the needs of minority populations in
terms of how they access the program benefits.
This is being addressed through the administration
of the Petitioners’ Satisfaction
Survey.
The second issue is structured settlements,
how monies are paid, and how the Department
of Justice appoints brokers to arrange
the payments. The working group became
aware that a significant proportion of
the structured payments are handled by
a single broker. It was reported that
petitioners are concerned about their
rights in deciding who makes arrangements
for the settlements. There was an observation
that, although the Department of Justice
had previously provided a briefing on
this issue, it was not possible to obtain
a petitioners’ attorney perspective.
The individual who had brought this issue
to the workgroup’s attention declined
an invitation to present.
The third issue was the fact that the
administrative budget of the VICP had
not increased in a number of years. That
issue became moot when a sizeable increase
in that budget was approved.
Finally, the working group was concerned
that sufficient funding was not provided
for research related to vaccine safety.
Four alternatives were discussed. First,
for the ACCV to request that the Secretary
devote a portion of the HHS budget to
vaccine safety research; second, that
a small portion of the Trust Fund be diverted
for vaccine safety research; third that
interest on the Trust Fund be used for
vaccine safety research; and fourth, that
a new excise tax on vaccines be established,
the income from which would be devoted
to vaccine safety research. There was
a brief discussion of the various proposals,
which made it clear that there was a lack
of consensus as to how the issue should
be approached. Limitations on direct partnerships
between the government and private sector
were discussed, although it was conceded
that there has been significant public-private
partnership under which information has
been shared, an approach that could be
helpful.
There was a suggestion that the issue
should be brought to the full Commission
as a future agenda item, and there was
some concern expressed that the proposal
could be outside the charter of the Commission.
Mr. Sconyers suggested that one approach
would be to develop a series of alternative
proposals for the full Commission to consider,
rather than focus on the narrow issue
of increased vaccine safety research.
He expressed appreciation to Dr. Deville
and Ms. Buck and the working group members
for their contributions to the process
Petitioners Satisfaction Survey
Rebecca Ledsky
Altarum Institute
Ms. Ledsky briefly described the process
by which a petitioner’s satisfaction
survey was developed. The Office of Management
and Budget requires a periodic evaluation
of every federal program, and Altarum
was hired to facilitate that evaluation
for the DVIC. The first step was to develop
an evaluation feasibility study that would
be followed by a specific evaluation.
The product of that effort was to assess
whether petitioners who completed the
claims process were satisfied with the
outcome. Survey questions included how
the individual learned about the program,
how the claims process worked, the outcomes
of the process (award and payment, the
role of the life care planners), and how
the claimants felt about the various players
in the process (the DVIC, the Department
of Justice attorneys, and the special
masters).
The survey will go to anyone who completed
the process, with or without a positive
award outcome, in the last five years,
a total of about 700 individuals. The
survey would be self-administered, either
in writing or online, and would be anonymous.
Although not required, space is provided
in the questionnaire for individual to
expand responses with written comments.
A Spanish language version would be available.
After four months, the anonymous data
would be analyzed and a report would be
prepared for the DVIC.
The survey will be distributed in the
spring and summer so that the report can
be written by October. Its purpose is
to provide baseline data to reflect what
the DVIC is accomplishing currently.
During discussion, there was a comment
that some individuals might prefer to
respond in person, perhaps in a telephone
conversation and there was a recommendation
that the Spanish language version be included
in the original transmission of the survey,
and not just “made available.”
In addition, the Spanish language versions
should be reviewed by an individual familiar
with the issues related to vaccine safety
and the DVIC, and not just a professional
translator. Mr. Sconyers requested that
the report be available for the December
Commission meeting.
Election of Chair and Vice Chair
Mr. Sconyers invited nominations for
Vice Chair and Chair for the next annual
term of office.
(On motion duly made by Mr. Glass and
seconded by Dr. Fisher, Ms. Tawny Buck
was elected Vice Chair by unanimous acclamation.)
(On motion duly made by Ms. Tempfer
and seconded by Dr. Fisher, Mr. Sconyers
was elected Chair for a second consecutive
term by unanimous acclamation.)
Public Comment
Ms. Tempfer suggested that the fall Commission
meeting be scheduled to coincide with
the November 19th Judicial Conference.
Mr. Sconyers noted that there were no
requests for public comment.
Future Agenda Items
Mr. Sconyers stated that several suggestions
for future agenda items had been made
during the course of the meeting. There
was a request that the CDC provide an
orientation presentation to familiarize
Commission members with the CDC web site.
He added that a discussion of the structured
settlement issue and the appointment of
brokers would be considered for the agenda,
and that the minutes of the working group
concerning those issues would be provided
in advance. Similarly the working group
minutes related to future vaccine safety
research, as well as a copy of the Commission’s
charter would be sent to members so that
a discussion of that issue could be included
on the next agenda. Finally, he noted
that a speaker would be invited to discuss
the issues related to thimerosol-free
and thimerosol-containing influenza vaccine
and its use in the pediatric population.
Ms. Castro-Lewis requested that an agenda
item be considered that would update the
Commission on the state of vaccine safety
research and its future direction.
Mr. Sconyers requested that the Commission
establish an agenda committee to work
with Dr. Evans’ office to develop
appropriate agendas for future meetings.
Adjournment
Dr. Evans announced that Tamara Overby
would be leaving the DVIC after six years,
to serve as Division Director for the
Division of Applications and Awards in
HRSA’s Bureau of Clinician Recruitment
and Service. He congratulated Tamara on
her promotion.
On motion duly made and seconded, there
was unanimous agreement to adjourn. The
meeting adjourned at 12.20 p.m.
__________________________
Jeffrey Sconyers, J.D.
ACCV Chair |
________________________
Jaime Deville. M.D
ACCV Vice-Chair
|
__________________________
Geoffrey Evans, M.D.
Executive Secretary, ACCV |
__________________________
Date |
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.
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