[Federal Register Volume 60, Number 216 (Wednesday, November 8, 1995)]
[Proposed Rules]
[Pages 56289-56300]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-27562]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
42 CFR Part 100
RIN 0905-AE52
National Vaccine Injury Compensation Program: Revisions and
Additions to the Vaccine Injury Table--II
AGENCY: Health Resources and Services Administration, PHS, HHS.
ACTION: Notice of proposed rulemaking; findings.
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SUMMARY: The Secretary has made findings as to certain illnesses and
conditions that can reasonably be determined in some circumstances to
be caused or significantly aggravated by certain vaccines. Based on
these findings, the Secretary proposes to amend the Vaccine Injury
Table (Table) by regulation under section 313 of the National Childhood
Vaccine Injury Act of 1986 and section 2114 (c) and (e) of the Public
Health Service Act (the Act).
These proposed regulations would have effect only for petitions for
compensation under the National Vaccine Injury Compensation Program
(VICP) filed after the new regulations become effective.
DATES: Comments must be submitted on or before May 6, 1996. A public
hearing on this proposed rule will be held before the end of the public
comment period. A separate notice will be published in the Federal
Register to provide the details of this hearing.
ADDRESSES: Written comments should be addressed to Fitzhugh Mullan,
M.D., Director, Bureau of Health Professions (BHPr), Health Resources
and Services Administration (HRSA), Room 8-05, Parklawn Building, 5600
Fishers Lane, Rockville, Maryland 20857. All comments received will be
available for public inspection and copying at the Office of Research
and Planning, BHPr, Room 8-67, Parklawn Building, at the above address
weekdays (Federal holidays excepted) between the hours of 8:30 a.m. and
5:00 p.m.
FOR FURTHER INFORMATION CONTACT: Geoffrey Evans, M.D., Chief Medical
Officer, Division of Vaccine Injury Compensation, BHPr, (301) 443-4198
or David Benor, Senior Attorney, Office of the General Counsel, (301)
443-2006.
SUPPLEMENTARY INFORMATION: On August 14, 1992, the Secretary published
in the Federal Register (57 FR 36878) findings as to the illnesses and
conditions that can reasonably be determined in some circumstances to
be caused or significantly aggravated by certain vaccines. Based on
these findings, the Secretary proposed to amend the Vaccine Injury
Table (Table) by regulation pursuant to section 312 of the National
Childhood Vaccine Injury Act of 1986 and section 2114(c) of the Public
Health Service Act (the Act). After consideration of comments on the
proposed rule, the Secretary published a final rule in the Federal
Register on February 8, 1995 (60 FR 7678). The Secretary indicated in
the preamble to that rule that further modifications to
[[Page 56290]]
the Vaccine Injury Table would be made as new scientific evidence
became available regarding the causal relationship between certain
vaccines and various adverse events. Pursuant to section 313 of the
National Childhood Vaccine Injury Act of 1986 and section 2114(c) of
the Act, the Secretary arranged for a second study, again to be
conducted by the Institute of Medicine (IOM) of the National Academy of
Sciences. This study, entitled Adverse Events Associated with Childhood
Vaccines: Evidence Bearing on Causality, covers those vaccines not
addressed in the IOM's section 312 Report. (Institute of Medicine.
Stratton KR, Howe CJ, Johnston RB, eds. Adverse Events Associated with
Childhood Vaccines: Evidence Bearing on Causality. Washington, D.C.
National Academy Press; 1994) This Notice of Proposed Rulemaking (NPRM)
addresses modifications to the Vaccine Injury Table as a result of this
latest IOM report.
The National Childhood Vaccine Injury Act of 1986, title III of
Pub. L. 99-660 (42 U.S.C. 300aa-10 et seq.), established a Federal
compensation program for persons thought to be injured by vaccines.
Petitions for compensation under this Program are filed with the United
States Court of Federal Claims, with a copy served on the Secretary,
who is denominated the ``Respondent.'' The Court, acting through
Special Master, makes findings as to eligibility for, and amount of,
compensation.
In order to gain an award under this program, the petitioner must
establish a vaccine-related injury or death, either by showing an event
which is presumed to be caused by a vaccine or by proving causation in
fact. In some cases, the petitioner may simply demonstrate the
occurrence of what has been referred to as a ``Table injury.'' That is,
it may be shown that the vaccine recipient suffered an injury of the
type enumerated in section 2114(a) of the Act (42 U.S.C. 300aa-14(a))--
the ``Vaccine Injury Table''--corresponding to the vaccination in
question, and that the onset of such injury took place within a time
period from the vaccination also specified in the Table. If so, the
Table injury was in effect presumed to have been caused by the
vaccination, and the petitioner was automatically entitled to
compensation (assuming that various jurisdictional requirements were
satisfied), unless it was affirmatively shown that the injury was
caused by some factor other than the vaccination (see secs.
2111(c)(1)(C)(i), 2113(a)(1)(B)), and 2114(a) of the Act). Congress
recognized that the Table initially set forth in the statute inevitably
would compensate some individuals whose injuries were not actually
caused by the vaccine. Congress was willing to accept some such
inaccuracy for simplicity's sake, and in order to ensure compensation
of most persons actually injured by the enumerated vaccines.
The legislative history states:
``The Committee recognizes that there is public debate over the
incidence of illnesses that coincidentally occur within a short time
of vaccination. The Committee further recognizes that the deeming of
vaccine-relatedness adopted here may provide compensation to some
children whose illness is not, in fact, vaccine-related. The
Committee anticipates that the research on vaccine injury and
vaccine safety now ongoing and mandated by this legislation will
soon provide more definitive information about the incidence of
vaccine injury and that, when such information is available, the
Secretary or the Advisory Commission on Childhood Vaccines * * * may
propose to revise the Table, as provided below in Section 2114
[Initial Table]. Until such time, however, the Committee has chosen
to provide compensation to all persons whose injuries meet the
requirements of the petition and the Table and whose injuries cannot
be demonstrated to be caused by other factors.'' [H.R. Rept. 99-908,
Part 1, September 26, 1986, page 18 (or as found in 1986 U.S. Code
Cong. and Admin. News, Vol. 6, page 6359)].
Since the enactment of the statute, there have been serious
concerns about the degree to which the assumptions underlying the
Vaccine Injury Table were founded in science, and concerns that
substantial numbers of petitions were being compensated inappropriately
because they are being compensated for non-vaccine-related injuries.
Indeed, when it first enacted the statute creating this Program,
Congress mandated reviews to be undertaken by the IOM with the express
purpose of providing a better scientific rationale for any presumptions
of vaccine causation. Under section 312 of Pub. L. 99-660, Congress
mandated that the IOM review the scientific literature and other
information on specific adverse consequences of pertussis and rubella
vaccines. The 312 Report is discussed extensively in the Final Rule
published on February 8, 1995 (60 FR 7678). Under section 313 of Pub.
L. 99-660, Congress mandated that the IOM conduct a similar review
regarding the risks associated with those pediatric vaccines not
covered by the 312 Report.
Section 313 Report
The Institute of Medicine conducted this second review, and
released its report in late 1993 (hereinafter ``313 Report''). The
committee charged with undertaking this review consisted of fourteen
members with expertise in the following fields: immunology, pediatrics,
internal medicine, infectious diseases, neurology, virology,
microbiology, epidemiology, and public health. The committee met six
times over the course of 18 months, and reviewed more than 7,000
abstracts of scientific and medical studies. They read over 2,000
published books and articles, analyzed information from the U.S. Public
Health Service Vaccine Adverse Events Reporting System, and considered
additional material submitted by interested parties. The committee did
not perform any original research. See 313 Report, Executive summary,
pp. 3-4.
The IOM Committee undertook the task of judging whether, based on
available evidence, a causal relationship exists between each adverse
event examined and exposure to vaccines against the following diseases:
diphthteria, measles, mumps, poliomyelitis, tetanus, hepatitis B, and
hemophilus influenzae type b (Hib). Vaccines for hepatitis B and
hemophilus influenzae type b (Hib) were not mandated by Congress to be
part of the section 313 study; however, because these vaccines are now
mandated for inclusion in the Vaccine Injury Compensation Program, the
Secretary asked the IOM to address these vaccines as well. See section
2114(e) of the Act, as added by section 13632(a)(2) of the Omnibus
Budget Reconciliation Act (OBRA) of 1993, Pub. L. 103-66, which is
discussed fully below.)
As with the 312 Report, the IOM used a classification system to
categorize their conclusions about the strength of a causal
association. These categories are as follows:
1. No evidence bearing on a causal relation.
2. The evidence is inadequate to accept or reject a causal
relation.
3. The evidence favors rejection of a causal relation.
4. The evidence favors acceptance of a causal relation.
5. The evidence establishes a causal relation.
After release of the IOM 313 Report in December 1993, the Advisory
Commission on Childhood Vaccines (ACCV) recommended that the Secretary
convene a task force of experts to review the conclusions of the IOM
committee and to consider appropriate changes to the Vaccine Injury
Table. Accordingly, on March 15, 1994, an ad hoc subcommittee of the
National Vaccine Advisory Committee (NVAC) (see section 2105 of the
Act) met to review the 313 Report. This subcommittee meeting included
members of the NVAC, representatives from the
[[Page 56291]]
Advisory Committee on Immunization (ACIP), the ACCV, the Food and Drug
Administration's Vaccine Related Biological Products Advisory
Committee, the Academy of Pediatrics Committee on Infectious Diseases
(the ``Redbook'' committee), and appropriate Public Health Services
(PHS) staff. Where appropriate, the subcommittee also solicited the
views of experts in the area of childhood vaccines. The subcommittee
concurred with the IOM's conclusions in almost all cases. The
subcommittee did not agree with the IOM's conclusions in six specific
areas which will be discussed, as appropriate, in the individual
vaccine sections below.
Following the NVAC Subcommittee's review, the ACCV, whose
membership, by statutory directive, reflects a variety of views
relating to childhood immunizations (section 2119 of the Act),
considered the proposed changes to the Vaccine Injury Table at its
September and December 1994 meetings. The ACCV deliberations included
public policy considerations, whereas the NVAC charge was to consider
only the scientific issues raised by the existing Table, the recent IOM
report, and other scientific information.
The Secretary has examined the recommendations of the NVAC
Subcommittee, and of the ACCV, and proposes that the Table set forth at
42 CFR 100.3 be revised as described below. As described above, the
process for developing proposals for changing the Table in response to
the 313 report is very similar to that undertaken with respect to the
312 Report. In both cases, the Department solicited the views of the
two key advisory committees that are charged with making
recommendations to the Department regarding vaccine safety and the
vaccine compensation program. Making recommendations to change the
Table involves the difficult task of balancing scientific concerns and
public policy concerns. The Department's overall goal, consistent with
Congress' intent in enacting the VICP, is to provide just and fair
compensation to those individuals who experience adverse events that
can reasonably be determined to have been caused by the covered
vaccines. The Department views its role as requiring consideration of
public policy concerns, as well as the purely scientific data, in
translating these determinations into decisions to change the Table.
Another important consideration in proposing changes to the Table is
the need to make the Table as easy to understand and as clear as
possible. With this goal in mind, the Department is proposing to revise
the Qualifications and Aids to Interpretation which may be used by the
Special Masters in understanding when a particular set of symptoms is
consistent with a particular Table injury. The Department welcomes
comments regarding the clarity of the proposed Qualifications and Aids
to Interpretation. As provided in section 2114(c)(4), the new table
will apply only to petitions filed under the Program after the
effective date of the final regulation.
In addition, this NPRM includes changes to the Table based on the
requirements of the Omnibus Budget Reconciliation Act of 1993, Pub. L.
103-66, which required, in part, that the Secretary amend the Table to
include additional vaccines which have been recommended for routine
administration to children. Specifically, this Act added a new section
2114(e) to the National Childhood Vaccine Injury Act of 1986. This
section now reads as follows:
(e) ADDITIONAL VACCINES--
(1) VACCINES RECOMMENDED BEFORE AUGUST 1, 1993--
By August 1, 1995, the Secretary shall revise the Vaccine Injury
Table included in subsection (a) to include--
(A) vaccines which are recommended to the Secretary by the
Centers for Disease Control and Prevention (CDC) before August 1,
1993, for routine administration to children,
(B) the injuries, disabilities, illnesses, conditions and deaths
associated with such vaccines, and
(C) the time period in which the first symptoms or
manifestations of onset or other significant aggravation of such
injuries, disabilities, illnesses, conditions, and deaths associated
with such vaccines may occur.
(2) VACCINES RECOMMENDED AFTER AUGUST 1, 1993--When after August
1, 1993, the Centers for Disease Control and Prevention (CDC)
recommends a vaccine to the Secretary for routine administration to
children, the Secretary shall, within 2 years of such
recommendation, amend the Vaccine Injury Table included in
subsection (a) to include--
(A) vaccines which were recommended for routine administration
to children,
(B) the injuries, disabilities, illnesses, conditions, and
deaths associated with such vaccines, and
(C) the time period in which the first symptoms or
manifestations of onset or other significant aggravation of such
injuries, disabilities, illnesses, conditions, and deaths associated
with such vaccines may occur.
Based on the requirements of this section, the Department proposes
to add to the Table hepatitis B and Hib vaccines. In addition, in order
to create an efficient and streamlined method of adding additional
vaccines to the Table, as required by section 2114(e)(2) above, the
Department proposes to add to the Table now a general category for any
new vaccine that in the future is recommended by CDC for routine
administration to children, upon indication to the Secretary that a
particular vaccine has been recommended. Accordingly, once Congress
enacts an excise tax to cover that vaccine, the vaccine will be covered
under the VICP. Until specified injuries are added to the Table through
the rulemaking process, individuals who receive newly recommended
vaccines will not receive a presumption of causation, but will instead
be eligible to receive compensation upon proving causation in fact.
Consistent with the general process for amending the Table, once the
Department determines that specific adverse events have been associated
with newly recommended vaccines, the Department will propose further
changes to the Vaccine Injury Table in order to confer the appropriate
presumption of causation.
Based on the requirements of the Administrative Procedure Act, the
Department publishes a Notice of Proposed Rulemaking in the Federal
Register before a regulation is promulgated. The public is invited to
submit comments on this proposed rule. In addition, a public hearing
will be held for this proposed rule. After the public comment period
has expired, the Department will publish the final rule in the Federal
Register. The Comments received on the proposed rule and the
Department's responses to the comments will be addressed in the
preamble to the final regulation.
Guidelines
Section 313 requires that the Secretary establish guidelines based
on the results of the 313 Report ``respecting the administration'' of
the vaccines that were reviewed, which guidelines shall include:
``(i) the circumstances under which any such vaccine should not
be administered,
(ii) the circumstances under which administration of any such
vaccine should be delayed beyond its usual time of administration,
and
(iii) the groups, categories, or characteristics of potential
recipients of such vaccine who may be at significantly higher risk
of major adverse reactions to such vaccine than the general
population of potential recipients.''
The establishment of these guidelines will be undertaken as a separate
activity from this rulemaking.
Findings
Section 313, unlike section 312, does not require that the
Secretary make specific findings as to the ``illnesses or conditions *
* * that can reasonably
[[Page 56292]]
be determined in some circumstances to be caused or significantly
aggravated'' by the vaccines under review, or ``the circumstances under
which such causation or aggravation can reasonably be determined to
occur.'' Nevertheless, the Department has concluded that these
determinations are the appropriate framework for making changes to the
Table as a result of the 313 Report. Accordingly, the findings below
and the proposed Table that follows are based on these determinations.
For some Table changes, the ``circumstances under which * * * causation
or aggravation can reasonably be determined to occur'' are reflected in
the terms of the Table itself (e.g., vaccine strain polio infection in
immunodeficient individuals); for others, the circumstances are
reflected in the Qualifications and Aids to Interpretation that
accompany the Table (e.g., thrombocytopenic purpura for vaccines to
prevent measles).
The Secretary makes the following findings:
1. The scientific evidence favors acceptance of a causal
relationship between vaccines containing tetanus toxoid and brachial
neuritis.
2. The scientific evidence is insufficient to accept or reject a
causal relationship between vaccines containing tetanus toxoid and
Guillain Barre Syndrome (GBS). While there may be a causal relationship
in extremely rare cases, the Secretary is unable to identify the
circumstances in which the vaccine causes the condition.
3. The scientific evidence favors rejection of a causal
relationship between vaccines containing tetanus toxoid and
encephalopathy.
4. The scientific evidence is insufficient to accept or reject a
causal relationship between vaccines containing tetanus toxoid and
residual seizure disorder.
5. The scientific evidence indicates a causal relationship between
vaccines to prevent measles and (a) thrombocytopenic purpura and (b)
measles vaccine-strain viral infection in immunodeficient individuals.
6. The scientific evidence is insufficient to accept or reject a
causal relationship between vaccines to prevent measles and residual
seizure disorder.
7. The scientific evidence is insufficient to accept or reject a
causal relationship between polio live virus (OPV) and Guillain-Barre
Syndrome (GBS).
8. The scientific evidence indicates a causal relationship between
OPV and vaccine-strain polio viral infection.
9. The scientific evidence indicates a causal relationship between
hepatitis B vaccine and anaphylaxis.
10. The scientific evidence favors acceptance of a causal
relationship between Hib vaccine (unconjugated, polyribosylribitol
phosphate (PRP) vaccine only) and early-onset Hib disease.
Discussion of Proposed Table Changes
The following proposed revision of the Table and the related
Qualifications and Aids to Interpretation takes into account the
recommendations of the ACCV and the NVAC Subcommittee. These two
outside reviewing bodies have based their recommendations primarily on
the IOM Report as well as other relevant scientific information. Set
forth below is a discussion of each proposed change to the Table,
including an explanation of the rationale for the change. Where the
Department proposes to amend the Table in a manner inconsistent with
the recommendations of the ACCV, there is specific discussion of the
basis for such proposal; for all other proposed changes, the ACCV
concurred with the proposals.
The Department notes that the removal of a condition from the
Table, or the inclusion of a revised definition thereof, will not
necessarily result in compensation being denied where it would
previously have been awarded. Rather, the result will be that a
presumption of causation will no longer apply. Petitioners may still
prevail by providing proof of causation in fact.
The Department is proposing to use different categories for the
Table itself from those set forth in the initial statutory Table or in
the revised Table set forth in the regulations at 42 CFR 100.3. Rather
than combine different vaccines, such as DTP and DT in the same
category, the Department is proposing to identify groups of vaccines by
a primary antigen. Thus, one category will be vaccines to prevent
pertussis, which would include P, DTP, DTaP, and other combination
vaccines one of whose components is pertussis. Similarly, vaccines to
prevent rubella would include MMR, MR, and R.
I. Tetanus Toxoid-Containing Vaccines
A. Guillain-Barre Syndrome
Guillain-Barre syndrome, or acute inflammatory demyelinating
polyneuropathy, is a well-described neurologic disorder marked by an
initially progressive motor paralysis. While the illness may be life-
threatening, recovery is usually complete after weeks or months. Based
on a great deal of data gathered since the entity was clearly
delineated 75 years ago, it is thought that this disorder is immune-
mediated and targets peripheral nerves.
Over half of all patients with GBS have a history of a preceding
acute infectious illness, either respiratory or gastrointestinal, in
the 1 to 4 weeks prior to the onset of neuropathic symptoms. Several
infectious agents, including both bacterial (e.g., Campylobacter jejuni
and Mycoplasma pneumoniae) and viral [e.g., Epstein-Barr virus, human
immunodeficiency virus (HIV), and cytomegalovirus] ones, are associated
with GBS.
Vaccinations in general are infrequent antecedent events in
patients with GBS, probably occurring in less than 1 to 5 percent of
all cases. GBS is known to occur following the administration of rabies
vaccine produced from the nervous tissue of infected animals, and there
were more than expected GBS cases in this country following the massive
effort in 1976-77 to immunize the populace against a threatened
pandemic of swine influenza. While the experience with rabies and swine
influenza vaccines is well-documented, a causal relation, if one
exists, between tetanus toxoid and GBS is not so self-evident. The
Institute of Medicine did conclude that the evidence favors a causal
relation between tetanus toxoid and GBS, and by extension that it
favors a causal relation between vaccines containing tetanus toxoid,
DT, Td, DTP and DTaP. A subcommittee of the National Vaccine Advisory
Committee was divided on the question of causality, voting by only a 6
to 5 margin to concur with the IOM's conclusion as to causality between
tetanus toxoid-containing vaccines and GBS; the subcommittee
recommended unanimously that GBS not be added to the Vaccine Injury
Table.
The IOM based its Category 4 conclusion (``The Evidence Favors
Acceptance of a Causal Relation'') on an assessment of biologic
plausibility and on case reports. One case in particular, that of a 42-
year-old man who experienced three separate bouts of a GBS-like illness
after tetanus immunizations and later had further relapses without
antecedent immunizations of any sort, was relied on very heavily as
evidence that there was more than a theoretical possibility of GBS
brought on by tetanus immunizations (Pollard JD, Selby G. Relapsing
neuropathy due to tetanus toxoid: report of a case. Journal of
Neurological Science 1978;37:113-125). The significance of this case
and other evidence was debated by the NVAC
[[Page 56293]]
Subcommittee before it made its recommendations.
CDC presented data to the NVAC Subcommittee from epidemiologic
studies on this issue available since the IOM review. These large
population studies showed that there was no increased risk of GBS after
tetanus toxoid-containing vaccines in either adults or children. These
findings suggest that while certain individuals may have a predilection
for GBS after various triggers (including vaccination), such
individuals are extremely rare.
The ACCV recommended by a 5 to 4 vote to add GBS to the Table as a
recognized Table injury for tetanus toxoid-containing vaccines and that
the Aids to Interpretation be designed to exclude from the presumption
of causation cases which are not vaccine-related. There are no biologic
markers or other means, however, to distinguish the very rare cases of
vaccine-related GBS from the far more common cases of GBS due to other
causes. As noted above, the one case primarily relied upon by the IOM
was one which, due to the multiple occurrences of GBS following
vaccination, could be found compensable under the causation in fact
standard. Indeed, the VICP has compensated one individual for GBS
following receipt of tetanus toxoid vaccine based on this causation in
fact approach.
The Department has evaluated the comments of the NVAC Subcommittee
and of the ACCV and has determined not to propose the addition of GBS
to the Table. While the isolated cases of GBS following tetanus toxoid-
containing vaccines do indicate biologic plausibility for causation,
the results of CDC studies demonstrate that there is no measurable
increase in risk of this condition following vaccination. (Chen R, Kent
J, Rhodes P, Simon P, Schonberger L. Investigation of a possible
association between influenza vaccination and Guillain-Barre syndrome
in the United States, 1990-1991 (abstract); Post Marketing Surveillance
1992; 6:5-6.) Indeed, the IOM noted that ``no estimate of incidence or
relative risk is available. It would seem to be low.'' (IOM Report, p.
89.) Thus, to add this condition to the Table would almost certainly
result in compensating an inordinate number of non-vaccine-related
cases for the extremely rate vaccine-related case. The Department has
concluded that the condition should not be given a presumption of
causation but should be addressed instead under the causation in fact
standard.
B. Brachial Neuritis
Brachial neuritis, alternatively known as brachial plexus
neuropathy and by other names, such as neuralgic amyotrophy, was first
linked to vaccination or administration of antiserum a half century
ago. It has also been reported after various infections and concurrent
with other diseases, as well as after trauma, but in the majority of
cases there is no history of antecedent illness or immunization. This
acute onset peripheral nerve disorder usually begins with a deep, often
severe aching pain in the shoulder and upper arm. The pain is followed
in days or weeks by weakness and atrophy in upper extremity muscle
groups. Sensory loss may accompany the motor deficits, but is generally
a less notable clinical feature. Recovery is complete in most cases,
though it may require more than a year for full return of function. The
IOM concluded that while the evidence is inadequate to accept or reject
a causal relation between tetanus toxoid, DT, or Td and peripheral
neuropathy (other than those caused by direct intraneural injection),
there is biologic plausibility that vaccines could cause brachial
neuritis. Taking into account biologic plausibility along with
published case reports and uncontrolled observational studies (Tsairis
P, Dyck PJ, Mulder DW. Natural history of brachial plexus neuropathy:
report on 99 patients. Archives of Neurology 1972; 27:109-117) (Beghi
E, Kurland LT, Mulder DW, Nicolosi A. Brachial plexus neuropathy in the
population of Rochester, Minnesota, 1970-1981. Annals of Neurology
1985; 18:320-323) of brachial neuritis after receipt of tetanus toxoid,
from which a relative risk on the order of 5 to 10 was estimated, the
IOM viewed the evidence as favoring acceptance of a causal relation
between all tetanus toxoid-containing vaccines and brachial neuritis.
A subcommittee of the National Vaccine Advisory Committee concurred
with the IOM conclusion as to causality and recommended the addition of
this condition to the Vaccine Injury Table. Citing the rarity of
brachial neuritis in children, this panel left open the possibility of
including an age-range qualifier to its recommendation that the
condition be added to the Table.
The series reported in 1972 by Tsairis and colleagues included a
case of brachial neuritis in a 3-month-old infant 3 days after a DTP
immunization; and in 1973, Martin and Weintraub reported a case of
brachial neuritis in a 5-month-old boy 2 days after he received in the
thigh his first does of DTP, with resolution of the neuritis within 48
hours. (Martin GI, Weintraub MI. Brachial neuritis and seventh nerve
palsy: a rare hazard of DPT vaccination. Clinical Pediatrics 1973;
12:506-507.) In view of these reported cases of brachial plexopathy in
infants after receipt of tetanus toxoid-containing vaccines (DTP), and
a paucity of data about incidence according to age, the Department has
decided to add brachial plexopathy to the Vaccine Injury Table without
any age-range qualifier.
Based on the published literature and case reports, the Department
is proposing a time of onset between 2 and 28 days. The proposed
Qualifications and Aids to Interpretation are designed to define this
condition under new paragraph (b)(7) and to rule out other conditions
for which there has been no finding of a causal relation to the
vaccine.
C. Encephalopathy
The IOM concluded that the evidence favors rejection of a causal
relation between DT, Td, or tetanus toxoid and either acute or chronic
encephalopathy. A subcommittee of the National Vaccine Advisory
Committee concurred with the IOM conclusion as to causality and
recommended the removal of this condition from the Vaccine Injury
Table. The ACCV concurred. Accordingly, the Department proposes to
delete this condition from the Table.
D. Residual Seizure Disorder
The Department has already taken regulatory action, based on the
section 312 review, to delete the condition of residual seizure
disorder (RSD) from the Table for vaccines containing tetanus toxoid.
See 42 CFR 100.3, as amended at 60 FR 7694. The additional findings
from the section 313 Report provide further support for this action.
Accordingly, the Department is setting forth a discussion of the
additional findings from the IOM that are relevant to this decision.
The Institute of Medicine concluded that the evidence favors
rejection of a causal relation between DT and infantile spasms, and is
inadequate to accept or reject a causal relation between DT and
residual seizure disorder other than infantile spasms. The IOM also
viewed the evidence as inadequate to accept or reject a causal relation
between tetanus toxoid or Td and residual seizure disorder. These
conclusions paralleled its earlier conclusions about infantile spasms
(``favors rejection of a causal relation'') and residual seizure
disorder (``inadequate to accept or reject a causal relation'') for
DTP.
While the IOM may not have felt that it had adequate evidence to
reject a
[[Page 56294]]
causal relationship between tetanus toxoid, DT, or Td and residual
seizure disorder, except in the special case of infantile spasms, it
cited no evidence suggestive of a causal relationship. Indeed, the
evidence adduced, which included data from three uncontrolled
observational studies, could reasonably be interpreted as favoring
rejection of a causal relationship. (Pollock TM, Morris J. A 7-year
survey of disorders attributed to vaccination in North West Thames
region. Lancet 1983; 1:753-757) (Pollock TM, Miller E, Mortimer, JY,
Smith G. Symptoms after primary immunization with DTP and with DT
vaccine. Lancet 1984; 2:146-149) (Pollock TM, Miller E, Mortimer JY,
Smith G. Post-vaccination symptoms following DTP and DT vaccination.
Developments in biological standardization. 1985; 61:407-410) (Hirtz
DG, Nelson KB, Ellenberg JH. Seizures following childhood
immunizations. Journal of Pediatrics 1983; 102:14-18)
All three studies reported on relatively large numbers of children
(>200,000 in all) and did identify some who did experience seizures
sometime after primary or booster DT immunizations. Of those who
experienced seizures, almost all their seizures either: (1) Were
isolated events (i.e., did not experience further seizures before
observational period ended); (2) occurred in the face of fever or
intercurrent illness and were without manifest neurologic residua; (3)
occurred well after the receipt of vaccine (e.g., two individuals with
convulsions at 22- and 24-days post-immunization, respectively); (4)
happened in the face of a significant prior neurologic history (e.g.,
``several months earlier he had sustained a skull fracture in a car
accident and had been in a coma but had apparently recovered''); or (5)
took place under some combination of these special circumstances. Of
the Hertfordshire experience reported by Pollock et al. (1984 and
1985), the IOM said, ``That study did not show any evidence for
residual seizure disorder de novo following receipt of DT.''
Clearly, whether the evidence is interpreted as inadequate to
decide for or against a causal relation between these tetanus toxoid-
containing vaccines (i.e., T, DT, and Td) and residual seizure
disorders, or as sufficient to favor rejection, there is no support for
a claim that there is a causal relationship, or that one is at all
likely. The Department has therefore determined that residual seizure
disorder cannot reasonably be determined in some circumstances to be
caused or significantly aggravated by tetanus toxoid-containing
vaccines.
II. Vaccines to Prevent Rubella
In the final rule recently issued after consideration of the
section 312 IOM report, the Department added chronic arthritis as a
Table injury for vaccines against rubella. (60 FR 7694-7695.) The
Department also promulgated in the Qualifications and Aids to
Interpretation criteria for determining when chronic arthritis would be
given a presumption that the vaccine caused the condition.
Faced with petitions filed under the Program alleging that
arthritis was caused in fact by the rubella vaccine, the Court of
Federal Claims developed criteria for determining when to compensate
such petitions. In an order dated January 11, 1993, a Special Master of
the Court set forth criteria for such a determination. The Special
Master did so after hearing expert testimony from witnesses
representing the fields of rheumatology, virology and infectious
disease.
The Department concludes that it is appropriate to reconcile the
Special Master's criteria with the criteria in the final rule, to the
extent possible. Accordingly, the Department has undertaken to evaluate
the Special Master's criteria for possible use in revised
Qualifications and Aids to Interpretation, as well as in the time
period for onset of the symptoms of arthritis set forth in the Table of
Injuries.
The Special Master's criteria are quoted below:
``1. The petitioner in fact had a rubella vaccination, at a time
when the petitioner was 18 years or older.
``2. The petitioner had a history, over a period of at least three
years prior to the vaccination, of freedom from any sort of persistent
or recurring polyarticular joint symptoms.
``3. The petitioner has developed an antibody response to the
rubella virus.
``4. The petitioner experienced the onset of polyarticular
arthropathic symptoms during the period between one and six weeks after
the vaccination.
``5. Polyarticular arthropathic symptoms continued for at least six
months after the onset; or, if symptoms remitted after the acute stage,
polyarticular arthropathic symptoms recurred within one year of such
remission.
``6. There is an absence of another good explanation for the
arthropathy; the petitioner has not received a confirmed diagnosis of
rheumatoid arthritis, nor a diagnosis of any of a number of other
specified conditions.''
The Department has decided to propose incorporating into the Table
and Aids to Interpretation elements of criteria 2, 3, and 4. That
portion of criterion 2 that refers to a 3-year period without symptoms
prior to vaccination is accepted and is proposed to be added in
introductory paragraph (b)(6)(i); the portion of criteria 2 and 4
referring to polyarticular joint symptoms is not accepted, as the
Department believes that objective signs of arthropathy (joint disease)
are necessary. The Department does not agree with criterion 1, the age
qualifier, as it would establish an arbitrary age of onset which is not
supported by the current medical literature. Criterion 4 specifies a
time of onset after vaccination from between 1 and 6 weeks. The final
rule pursuant to the section 312 report specified a time of onset from
0-42 days. On review of the relevant medical literature and expert
testimony, the Department believes that the evidence would not support
a finding of causation with onset before the seventh day after rubella
vaccination. Accordingly, the Department proposes to change the period
for the first symptom or manifestation of onset of chronic arthritis in
the Table itself to be between 7-42 days as reflected in revised
paragraph (b)(6)(i)(A).
For the most part, criteria 5 and 6 are already part of the rule
adopted pursuant to the section 312 report. No further changes are
proposed in this regard.
The Department does not agree, however, with the Court's inclusion
of arthralgia (joint pain) as evidence of arthropathic symptoms. Based
on medical expert testimony and other related scientific information,
the Department continues to believe that arthralgia alone, in the
absence of objective signs of arthritis, should not be viewed as
evidence of rubella vaccine-related chronic arthritis. Furthermore, the
Department is proposing to add paragraph (b)(6)(i)(C) that ``medical
documentation of an antibody response to the rubella virus'' is
required.
Although criterion 6 does not list fibromyalgia as an alternative
diagnosis for purposes of determining eligibility for compensation, a
recent Court decision (Johnson v. Secretary, HHS, No. 92-478V),
concluded that fibromyalgia is a condition unrelated to rubella
vaccination. Accordingly, the Department proposes to add fibromyalgia
in paragraph (b)(6)(ii) to the list of conditions which will not be
given a presumption of vaccine causation.
[[Page 56295]]
III. Vaccines to Prevent Measles
A. Thrombocytopenic Purpura
In children, most cases of immune (idiopathic) thrombocytopenia
purpura (ITP) are self-limited disorders that follow a viral infection,
most commonly a nonspecific respiratory infection. Viral antigen is
thought to trigger synthesis of antibody that reacts with virus
antigen, and then the antibody-antigen complex is bound to receptors on
the platelet surface. Immune thrombocytopenic purpura often produces
petechiae, purpura, and mucosal bleeding. The associated symptoms of
petechiae, purpura and mucosal bleeding are generally only seen when
the platelet counts are less than 50,000/mm 3 (thrombocytopenia is
defined as a platelet count less than 150,000/mm 3). Red and white
blood cells are normal in ITP. Acute thrombocytopenia in children
rarely becomes chronic, that is, lasting more than 6 months. Chronic
thrombocytopenic purpura is thought to be related to an underlying
autoimmune disorder and not to be the result of a viral vaccination or
viral infection.
The Institute of Medicine (IOM) concluded that the evidence
establishes a causal relation between MMR and immune thrombocytopenia
and a causal relation between MMR and death from complications
associated with severe thrombocytopenia. The conclusions of the IOM
were based on biologic plausibility, case series, uncontrolled
observational studies (e.g., Nieminen U, Peltola H, Syrjala MT,
Makipernaa A, Kekomaki R. Acute thrombocytopenic purpura following
measles, mumps and rubella vaccination: a report on 23 patients. Acta
Paediatrica 1993; 82:267-270) and the controlled observational study by
Oski and Naiman (Oski FA, Naiman JL. Effect of live measles vaccine on
the platelet count. New England Journal of Medicine 1996; 275:352-356).
The study by Oski and Naiman reported on the occurrence of immune
thrombocytopenia after the administration of the Edmonston B measles
vaccine, a vaccine which is no longer used in the United States. In
this controlled observational study, the maximum depression of the
platelet count was noted at 1 week post-immunization (although a
decrease in platelet count could be seen by 3 days post-immunization),
and platelet counts return to preimmunization levels generally by 3
weeks post-immunization. In the study by Nieminen and colleagues, 23 of
approximately 700,000 children immunized over an 8-year period were
found to have thrombocytopenia after immunization with MMR vaccine. The
platelet count reached its nadir at 21 days (median) post-immunization,
with purpura appearing at 17 days (median) post-immunization. The IOM
thought that it was biologically plausible that the MMR vaccine could
cause immune thrombocytopenia. The NVAC Subcommittee concurred with the
IOM conclusion, but because the ITP that was observed after vaccination
with MMR was relatively benign with complete recovery in less than 6
months, recommended against the addition of this disease to the Vaccine
Injury Table. While cases with full recovery is less than 6 months will
not be eligible for compensation (see section 2111(c)(1)(D)(i) of the
Act), the rare case with continuing complications should be eligible
for a presumption of causation. Thus, the Department proposes that
thrombocytopenic purpura be added to the Vaccine Injury Table.
The Department's proposal is based on the IOM conclusion of
biologic plausibility of immune thrombocytopenia occurring after MMR
vaccination, the possible risk to injury from that thrombocytopenia,
and the necessity to clarify the clinical aspects of thrombocytopenia
that should be compensable. Conditions that can cause thrombocytopenia
or are associated with thrombocytopenia, but are not related to immune
thrombocytopenia associated with MMR vaccination, are listed in the
Qualifications and Aids to Interpretation as noncompensable conditions.
This list of conditions is not exhaustive. A 7- to 30-day timeframe of
onset is proposed as the period for a Table injury. This timeframe is
largely based on the 1993 uncontrolled study by Nieminen and
colleagues.
The ACCV voted to concur with the proposal to add thrombocytopenic
purpura to the Table but requested some clarification and changes to
the proposed Qualifications and Aids to Interpretation. The reference
to a bone marrow examination now includes the phrase ``if performed''
in response to concerns from ACCV members that this test may not have
been used in rare cases. Some ACCV members were concerned about the
reference to ``viral infections'' and suggested that examples of
viruses that cause immune thrombocytopenia be listed. The Department
has accepted this suggestion but notes that while some examples are
listed, it would not be practical to list all viral etiologies of
immune thrombocytopenia. Thrombocytopenic purpura is proposed to be
added under paragraph (b)(8).
B. Residual Seizure Disorder
The IOM placed Residual Seizure Disorder (RSD) in Category #2
(``insufficient evidence'') for monovalent measles, and multivalent
measles and mumps vaccines, and Category #1 (``no evidence'') for mumps
vaccine alone. Information from case reports, case series, and
uncontrolled observational studies, seems to indicate that most
seizures following measles immunization are ``febrile seizures'' and,
therefore, are not expected to lead to recurrent seizures or epilepsy.
There were no controlled studies identified by the IOM. Unlike
encephalopathy following measles immunization, there is no apparent
biologic plausibility for RSD. Furthermore, there is no apparent
biologic plausibility for RSD. Furthermore, there is little evidence
that seizures, in the absence of acute encephalopathy, can lead to
chronic encephalopathy or any clinical manifestation such as RSD.
Both the 1991 and 1994 NVAC Ad Hoc Subcommittees commented on this
issue. The former endorsed the removal of RSD, noting the lack of
research or clinical data supporting this as a Table condition. Since
its removal went significantly beyond the scope of the changes proposed
by the PHS Task Force on the Vaccine Injury Compensation Program based
on the section 312 IOM Report, the Secretary decided to defer removal
awaiting publication of the section 313 IOM Report. Three years later,
similar viewpoints were expressed by the NVAC Subcommittee. The
Subcommittee unanimously recommended removal of any condition now
present on the Table that was placed in Category #2 by the section 313
IOM. Residual Seizure Disorder fits this criterion, and therefore, the
legal presumption of causation is proposed to be removed from the
Table.
The ACCV voted 5 to 4 to retain RSD as a Table injury for MMR (and
components thereof) vaccines. Some members felt that the IOM did not
cite evidence strong enough to delete from the Table an injury that
Congress had placed thereon. Some felt that there would be potential
disruption of the Program if new data emerge showing that there is a
causal relation for this condition. One member raised a concern about
the number of cases now pending under the Program citing this Table
injury. Furthermore, a member expressed concern that the U.S. Court of
Federal Claims would make it more difficult for a petitioner to prove
causation in fact for this condition if it is removed from the Table.
Another
[[Page 56296]]
member felt it would be unwise to remove the condition prior to
publication of the final Qualifications and Aids to Interpretation for
``encephalopathy'' under the section 312 rule.
The Department has given careful consideration to the issues raised
by the ACCV. As indicated above, the evidence is insufficient for the
Secretary to conclude that the condition can reasonably be determined
in some cases to be caused or aggravated by the MMR vaccine. This is
true regardless of the inclusion of the condition on the initial
statutory Table of Injuries and regardless of the number of cases filed
under the initial Table.
As to the possibility of having to include this condition again on
the Table should new scientific data support such an action, the
Department would of course be willing to consider such action should
there be reliable data for doing so. Under section 2116(b) of the Act,
should the condition be reintroduced to the Table, petitioners would
have 2 years to file a petition based on injuries occurring at any time
during the 8-year period prior to such reintroduction.
As to the increased difficulty of proving causation in fact, it is
of course the case that this burden was not imposed on petitioners
while there was a Table injury of this sort. The Court of Federal
Claims will be faced with determining causation in fact under the
statutory preponderance of the evidence standard. The IOM's conclusions
and the data underlying it will be, in the Department's opinion,
relevant to that inquiry.
Finally, with regard to the definition of ``encephalopathy'' in the
section 312 rule, the Department notes that seizures alone are not
defined as constituting an encephalopathy, but that certain serious
seizure events with demonstrated sequelae can do so. (See 42 CFR
Sec. 100.3(b)(2), as added at 60 FR 7694).
For the foregoing reasons, the Department is proposing the removal
of the condition RSD for MMR (or components thereof) vaccines from the
Table.
C. Vaccine Strain Measles Viral Infection in an Immunodeficient
Recipient
The Institute of Medicine study concluded that the evidence
establishes a causal relation between vaccine-strain measles virus
infection in immunocompromised individuals and death. This conclusion
is based on a few case reports of death following the administration of
live attenuated measles virus vaccine in children with severe combined
immunodeficiency syndrome, leukemia, or dysgammaglobulinemia (Monafo
WJ, Haslam DB, Roberts RL, Zaki SR, Bellini WJ, and Coffin CM.
Disseminated measles infection after vaccination in a child with a
congenital immunodeficiency. J of Pediatrics 1994; 124(2):273-276)
(Hong R, Gilbert EF, Opitz JM. Omenn disease: termination in lymphoma.
Pediatric Pathology 1985; 3:143-154) (Mihartsch MJ, Ohnacker H, Just M,
Nars PW. Lethal measles giant cell pneumonia after live measles
vaccination in a case of thymic alymphophasia Gitlin. Helvetica
Paediatrica Acta 1972; 27(2):143-146) (Mawhinney H, Allen IV, Beare JM,
Bridges JM, Connolly HH, Haire, et al. Dysgammaglobulinaemia
complicated by disseminated measles. British Medical Journal 1971;
2:380-381) (Mitus A, Holloway A, Evans AE, Enders JF. Attenuated
measles vaccine in children with acute leukemia. American Journal of
Disease of Children 1962; 103:243-248). Measles and, to a much lesser
extent, measles vaccine infection in severely immunocompromised
individuals may result in an overwhelming infection and death. The NVAC
Subcommittee concurred with the IOM conclusion, but recommended that
compensation for this condition be provided under the causation in fact
standard of the statute, rather than through the presumption given by
the Vaccine Injury Table.
The Department has decided to propose adding disseminated vaccine-
strain measles virus infection in immunocompromised recipients to the
Table. This decision is based on the recently published report by
Monafo et al. of a 15-month-old immunodeficient male who received
measles vaccine and died 3 months later of a molecularly-confirmed
vaccine-strain measles virus infection (Monafo WJ, Haslam DB, Roberts
RL, Zaki SR, Bellini WJ, and Coffin CM. Disseminated measles infection
after vaccination in a child with a congenital immunodeficiency.
Journal of Pediatrics 1994; 124(2):273-276). The time for onset is
proposed to be 6 months, as is the case in the statutory Table for
immunocompromised individuals and polio vaccines. Death as a sequela to
this condition would also be covered by the Table. The Qualifications
and Aids to Interpretation, under proposed paragraph (b)(9), provides
that the measles virus should be determined to be the vaccine-strain by
vaccine-specific monoclonal antibody or polymerase chain reaction
sequencing, in order to eliminate cases of injury based on endemic
measles.
IV. Oral Polio Vaccine
A. Guillain-Barre Syndrome (GBS)
The Institute of Medicine study concluded that the evidence favored
the acceptance of a causal relation between oral poliovirus vaccine
(OPV) and Guillain-Barre syndrome (GBS). The conclusion was based on an
increased incidence of GBS in a 6-year surveillance study for GBS in a
southern province of Finland (Uusimaa) reported by Kinnunen et al. in
1989 (Kinnunen E, Farkkila M, Hovi T, Juntunen J, Weckstrom P.
Incidence of Guillain-Barre syndrome during a nationwide oral
poliovirus vaccine campaign. Neurology 1989; 39:1034-1036). Ten cases
of poliomyelitis due to wild poliovirus occurred between August 1984
and January 1985 at a time when inactivated polio vaccine (IPV) was
generally used, and a mass immunization program with OPV immunized 94
percent of the Finnish population between 2/10/85 and 3/15/85. Ten
cases of GBS occurred in OPV recipients within 10 weeks after
immunization, and the relative risk calculated by the IOM committee
among adult OPV recipients in a population previously immunized with
IPV was statistically significant when calculated on calendar quarters.
However, the discussion of the report by Kinnunen et al. states that
``if we add the 4 cases in the 4th quarter of 1985 (sic--data actually
refer to 1984), there are 7 cases before OPV and 7 cases after OPV in
this 6-month period.'' Thus, OPV in this population could not be the
only explanation for the GBS cases, since the analysis by calendar
quarters was inconsistent with the analysis of GBS cases based on the
periods before and after the administration of OPV or if the quarters
were constructed in another way.
Since the publication of the IOM report in 1993, Rantala et al.
failed to show a temporal association between GBS and OPV after
studying 93 cases of GBS identified in children less than 15 years of
age from 22 hospitals over 6 years (Rantala H, Cherry JD, Shields WD,
Uhari M. Journal of Pediatrics 1994; 124(2):220-3). On the basis of the
available information, the presumption that OPV causes GBS within any
time period should not be granted. Based on the most recent data, which
had not been available to the IOM committee, the NVAC Subcommittee
unanimously concurred with this proposal. The ACCV voted to concur with
the proposal not to add GBS to the Table. Those not
[[Page 56297]]
voting in favor voiced reservations over their unfamiliarity with the
Rantala study, and the fact that its conclusions differed from the
IOM's findings.
The Department has evaluated the comments of the NVAC Subcommittee
and of the ACCV and has decided not to propose the addition to GBS to
the Table. While it is true that the IOM felt the evidence was
sufficient to determine that GBS was casually related to OPV, new data
published since the IOM study and the NVAC Subcommittee conclusions
have persuaded the Department that a presumption of causation should
not be provided. Petitioners, however, may use the IOM report to pursue
a causation in fact theory before the U.S. Court of Federal Claims.
B. Vaccine-Strain Poliovirus Infection and Death
The Institute of Medicine study concluded that the evidence
establishes a causal relation between oral poliovirus vaccine (OPV) and
vaccine-strain infection and death, including infection that results in
paralytic poliomyelitis. This conclusion is based on case reports of
deaths with poliovirus infections among non-immunodeficient and
immunodeficient vaccine recipients. (IOM Report, pages 296-299) Since
September 1994, the eradication of indigenous wild type poliovirus in
the United States has been certified.
Death and vaccine-associated paralytic poliomyelitis within 30 days
in non-immunodeficient individuals, and within 6 months in
immunodeficient individuals, are already covered in the Vaccine Injury
Table, and poliovirus myocarditis and death in a 3-month-old non-
immunodeficient male has been compensated by a preponderance of the
medical evidence. Based on case reports, the Department has concluded
that vaccine-strain poliovirus infection determined by the isolation of
poliovirus from the affected tissue that occurs within 30 days after
administration or contact in non-immunodeficient individuals, and
within 6 months after administration or contact in immunodeficient
individuals, should be added to the Table.
A subcommittee of the National Vaccine Advisory Committee concurred
with the IOM conclusions and accepted the original Department proposal
not to add it to the Table. Since the NVAC meeting, the Department has
decided to provide a legal presumption of causation for vaccine-strain
polioviral infection within 30 days in non-immunodeficient individuals,
and within 6 months in immunodeficient individuals. The ACCV voted
unanimously in favor of this proposal.
The Qualifications and Aids to Interpretation, under proposed
paragraph (b)(10), contains standards for determining whether a case is
due to the vaccine strain of the virus. The identification of
poliovirus is necessary to eliminate an enterovirus other than vaccine-
strain poliovirus that can cause similar overwhelming infection and
death. Isolation of poliovirus from the stool is not sufficient to
establish a specific tissue infection or disease caused by vaccine-
strain poliovirus, because viral shedding from the gastrointestinal
tract occurs in the absence of other tissue infection or disease. The
poliovirus should be determined to be vaccine-strain by oligonucleotide
or polymerase chain reaction tests.
V. Hepatitis B Vaccine
A. Anaphylaxis or Anaphylactic Shock
In 1981, a plasma-derived hepatitis B vaccine was licensed for the
first time in the United States. In 1986, the first recombinant
hepatitis B vaccine produced by genetic engineering was licensed and is
the form currently used in the United States. In 1991, the Advisory
Committee on Immunization Practices recommended that hepatitis B
vaccine be administered to all infants in the United States.
The Institute of Medicine concluded that the evidence establishes a
causal relation between hepatitis B vaccine and anaphylaxis (313
Report, p. 230). The conclusion was based on biologic plausibility, the
temporal sequence of observed events following vaccination, and the
observation of a spectrum of clinical reactions from mild
hypersensitivity to anaphylaxis in the host after exposure to hepatitis
B vaccine.
The Department proposes to add hepatitis B vaccine to the Table.
Anaphylaxis and anaphylactic shock with onset within 4 hours following
the administration of the vaccine is proposed as a Table injury. Both
the NVAC Subcommittee and ACCV voted unanimously in favor of this
proposal.
VI. Hemophilus influenzae type b (Hib) Vaccine [polyribosylribitol
phosphate (PRP) only]
A. Early Onset Invasive Hib Disease
The unconjugated Hemophilus influenzae type b polysaccharide or PRP
vaccine was first licensed in April 1985. Since December 1987, when the
first polysaccaharide-protein conjugate vaccine was licensed, the PRP
has not been routinely administered. It is no longer available for
general use.
Surveillance, serologic, and experimental data have demonstrated a
transient decrease in protective antibody levels following immunization
with the unconjugated PRP vaccine. Analysis of the data suggests that
children over 18 months of age who received their first Hib
immunization with the unconjugated PRP vaccine had an increased risk of
Hemophilus disease in the 7-day interval following the immunization.
The Institute of Medicine found that the evidence favored acceptance of
a causal relation between unconjugated PRP vaccine and early onset
(i.e. onset within 7 days) invasive Hib disease in children over 18
months of age who received their first Hib immunization with the
unconjugated PRP vaccine (IOM report, p. 260). However, ``the evidence
favors rejection of a causal relation between immunization with Hib
conjugate vaccines and early-onset Hib disease'' (IOM report, p. 261).
The NVAC Subcommittee concurred with these conclusions. Thus, the
statutory presumption of causation should be extended to cases of
invasive Hib disease that meet the standards proposed in the
Qualifications and Aids to Interpretation. Early-onset Hib disease is
proposed to be added under paragraph (b)(11).
VII. Hib Vaccine (Conjugate)
The Hib conjugate vaccines are proposed to be added to the Table
with no condition specified. While the Hib conjugate vaccines appear to
be capable of causing a transient decline in serum antibody levels
following immunization, prospective observational studies have not
demonstrated that immunization with the conjugate vaccines increases
the risk of early-onset Hib disease. The Institute of Medicine found
``the evidence favors rejection of a causal relation between
immunization with Hib conjugate vaccines and early-onset Hib disease''
(IOM report, p. 261). The NVAC Subcommittee concurred with this
conclusion. One member of the ACCV expressed the view that the
information upon which the IOM based its conclusion was unreliable. A
motion to include early onset Hib disease as a Table injury for Hib
conjugate vaccines did not pass. The ACCV voted to accept the
Department's recommendation by an 8 to 1 vote.
VIII. New Vaccines Recommended for Routine Administration by CDC
The Department proposes to add to the Table any new vaccine that is
[[Page 56298]]
recommended by the Centers for Disease Control and Prevention (CDC) for
routine administration to children, upon indication to the Secretary
that the vaccine has been so recommended. Accordingly, once Congress
enacts an excise tax to cover that vaccine, the vaccine will be covered
under the VICP. Until specified injuries are added to the Table through
the rulemaking process, individuals who receive newly recommended
vaccines will not receive a presumption of causation, but will instead
be required to prove causation in fact. Of course, consistent with the
general process for amending the Table, once the Department determines
that specific adverse events have been associated with newly
recommended vaccines, the Department will propose further changes to
the Vaccine Injury Table in order to confer the appropriate presumption
of causation.
The Food and Drug Administration licensed hepatitis A virus vaccine
on February 22, 1995, and licensed varicella virus vaccine on March 17,
1995. Vaccines licensed after August 10, 1993, and recommended by the
CDC for ``routine administration'' to children are mandated by OBRA of
1993 to be included in the National Vaccine Injury Compensation
Program. Recommendations on hepatitis A and varicella vaccine usage by
CDC are pending. Furthermore, based on information from clinical
trials, there are no specific injuries for either vaccine identified by
the Secretary at this time that would warrant inclusion on the Vaccine
Injury Table. Further guidance in these areas will be forthcoming
during the NPRM's publication and public comment period.
Economic Impact
The Secretary certifies that this proposed rule will not have a
significant impact on a substantial number of small businesses, because
it will have only small effects, and those primarily on individuals.
The effects will be primarily on the ability of certain individuals to
obtain compensation without having a burden of proving causation in
fact. Attorneys who represent such individuals will be affected only to
the extent that they may have a harder or easier burden of proof with
respect to the petitions filed. However, under section 2115(e) of the
Act, in almost all cases, attorneys' reasonable fees and costs are
reimbursed from the Vaccine Injury Compensation Trust Fund.
Executive Order 12866 requires that all regulations reflect
consideration of alternatives, of costs, of benefits, of incentives, of
equity, and of available information. Regulations must meet certain
standards, such as avoiding unnecessary burden. Regulations which are
``significant'' because of cost, adverse effects on the economy,
inconsistency with other agency actions, effects on the budget, or
novel legal or policy issues, require special analysis.
As stated above, this proposed rule would modify the Vaccine Injury
Table based on legal authority, and under that authority the Court will
award such fees and costs as appropriate under the law. As such, the
regulation would have little direct effect on the economy or on Federal
or State expenditures.
Effect of the New Rule
The proposed rule will have an effect for individuals who were not
eligible to file petitions based on the earlier versions of the Vaccine
Injury Table, but who may be eligible to file petitions based on the
revised Table. The Act permits such individuals to file a petition for
such compensation not later than 2 years after the effective date of
the revision if the injury or death occurred no more than 8 years
before the effective date of the revision of the Table. See 42 U.S.C.
300aa-16(b). As part of the Omnibus Budget Reconciliation Act of 1993,
Congress amended this section to permit individuals to file claims
within this 2-year period, even if they had already filed a claim
involving a particular vaccine, but only if the Table revision will
``significantly increase the likelihood of obtaining compensation.''
See Pub. L. 103-66, sec. 13632(a)(1), August 10, 1993. For example,
this amendment would permit an individual whose claim alleging MMR
vaccine-related thrombocytopenic purpura had been dismissed by the
Claims Court to file a new claim for the same vaccine-related injury,
if the individual can show that the addition of thrombocytopenic
purpura to the Table as a MMR vaccine-related condition has
significantly increased the likelihood of obtaining compensation. This
rule will also affect potential claims for individuals whose conditions
are proposed to be removed from the Table. Although these individuals
will be able to pursue their claims under the ``causation in fact''
standard, they will not be entitled to a presumption of causation that
is granted by having a condition on the Vaccine Injury Table.
Possible Effect on Other Legislation
This rule will not have an effect on the Vaccines for Children
program, implemented by the Centers for Disease Control and Prevention
under section 1928 of the Social Security Act, as enacted by section
13631 of the Omnibus Budget Reconciliation Act of 1993 (Pub. L. 103-66,
August 10, 1993). This section provides for the establishment of a
program to distribute free vaccines to all vaccine-eligible children,
as defined by this section. The proposed rule would modify the existing
Vaccine Injury Table, a mechanism by which compensation is awarded to
individuals who have been found to have suffered from vaccine-related
injuries. Because the two authorities are not related, the publication
of this rule should not have any impact on the Vaccines for Children
Program.
Paperwork Reduction Act of 1980
This proposed rule has no information collection requirements.
List of Subjects in 42 CFR Part 100
Biologics, Health insurance, Immunization.
Dated: June 2, 1995.
Philip R. Lee,
Assistant Secretary for Health.
Approved: August 22, 1995.
Donna E. Shalala,
Secretary.
Accordingly, 42 CFR Part 100 is proposed to be amended as set forth
below.
PART 100--VACCINE INJURY COMPENSATION
1. The authority citation for part 100 is revised to read as
follows:
Authority: Sec. 215 of the Public Health Service Act (42 U.S.C.
216); sec. 2115 of the PHS Act, 100 Stat. 3767, as amended (42
U.S.C. 300aa-15); Sec. 100.3, Vaccine Injury Table, issued under
secs. 312 and 313 of Pub. L. 99-660, 100 Stat. 3779-3782 (42 U.S.C.
300aa-1 note) and sec. 2114 (c) and (e) of the PHS Act, 100 Stat.
3766 and 107 Stat. 645 (42 U.S.C. 300aa-14 (c) and (e)).
2. Section 100.3 is amended by revising the Vaccine Injury Table in
paragraph (a); by setting out the introductory text in paragraph (b);
by revising paragraph (b)(6); by adding paragraphs (b)(7), (b)(8),
(b)(9), (b)(10), and (b)(11); and by revising paragraph (c) to read as
follows:
Sec. 100.3 Vaccine injury table.
(a) * * *
[[Page 56299]]
------------------------------------------------------------------------
Time period for first symptom or
Illness, disability, injury or manifestation of onset or of
condition covered significant aggravation after vaccine
administration
------------------------------------------------------------------------
I. Vaccines containing tetanus
toxoid (e.g., DTaP, DTP, DT, Td,
or TT):
A. Anaphylaxis or 4 hours.
anaphylactic shock.
B. Brachial Neuritis......... 2-28 days.
C. Any sequela (including Not applicable.
death) of an illness,
disability, injury, or
condition referred to above
which illness, disability,
injury, or condition arose
within the time period
prescribed.
II. Vaccines containing whole
cell pertussis bacteria,
extracted or partial cell
pertussis bacteria, or specific
pertussis antigen(s) (e.g., DTP,
DTaP, P, DTP-Hib):
A. Anaphylaxis or 4 hours.
anaphylactic shock.
B. Encephalopathy (or 72 hours.
encephalitis).
C. Any sequela (including Not applicable.
death) of an illness,
disability, injury, or
condition referred to above
which illness, disability,
injury, or condition arose
within the time period
prescribed.
III. Measles, mumps, and rubella
vaccine or any of its components
(e.g., MMR, MR, M, R):
A. Anaphylaxis or 4 hours.
anaphylactic shock.
B. Encephalopathy (or 5-15 days (not less than 5 days and
encephalitis). not more than 15 days).
C. Any sequela (including Not applicable.
death) of an illness,
disability, injury, or
condition referred to above
which illness, disability,
injury, or condition arose
within the time period
prescribed.
IV. Vaccines containing rubella
virus (e.g., MMR, MR, R):
A. Chronic arthritis......... 7-42 days.
B. Any sequela (including Not applicable.
death) of an illness,
disability, injury, or
condition referred to above
which illness, disability,
injury, or condition arose
within the time period
prescribed.
V. Vaccines containing measles
virus (e.g., MMR, MR, M):
A. Thrombocytopenic purpura.. 7-30 days.
B. Vaccine-Strain Measles 6 months.
Viral Infection in an
immunodeficient recipient.
C. Any sequela (including Not applicable.
death) of an illness,
disability, injury, or
condition referred to above
which illness, disability,
injury, or condition arose
within the time period
prescribed.
VI. Vaccines containing polio
live virus (OPV):
A. Paralytic Polio
--in a non- 30 days.
immunodeficient
recipient.
--in an immunodeficient 6 months.
recipient.
--in a vaccine associated Not applicable.
community case.
B. Vaccine-Strain Polio Viral
Infection
--in a non- 30 days.
immunodeficient
recipient.
--in an immunodeficient 6 months.
recipient.
--in a vaccine associated Not applicable.
community case.
C. Any acute complication or Not applicable.
sequela (including death) of
an illness, disability,
injury, or condition
referred to above which
illness, disability, injury,
or condition arose within
the time period prescribed.
VII. Vaccines containing polio
inactivated virus (e.g., IPV):
A. Anaphylaxis or 4 hours.
anaphylactic shock.
B. Any acute complication or Not applicable.
sequela (including death) of
an illness, disability,
injury, or condition
referred to above which
illness, disability, injury,
or condition arose within
the time period prescribed.
VIII. Hepatitis B. vaccines:
A. Anaphylaxis or 4 hours.
anaphylactic shock.
B. Any acute complication or Not applicable.
sequela (including death) of
an illness, disability,
injury, or condition
referred to above which
illness, disability, injury,
or condition arose within
the time period prescribed.
IX. Hemophilus influenzae type b
polysaccharide vaccines
(unconjugated, PRP vaccines):
A. Early-onset Hib disease... 7 days.
B. Any acute complication or Not applicable.
sequela (including death) of
an illness, disability,
injury, or condition
referred to above which
illness, disability, injury,
or condition arose within
the time period prescribed.
X. Hemophilus influenzae type b
polysaccharide conjugate
vaccines:
No Condition Specified
XI. Any new vaccine recommended
by the Centers for Disease
Control and Prevention for
routine administration to
children, after publication by
the Secretary of a notice of
coverage:
No Condition Specified
------------------------------------------------------------------------
(b) Qualifications and aids to interpretation. The following
qualifications and aids to interpretation shall apply to the Vaccine
Injury Table to paragraph (a) of this section:
* * * * *
(6) Chronic Arthritis. (i) For purposes of paragraph (a) of this
section, chronic arthritis may be found in a person with no history in
the 3 years prior to vaccination of arthropathy (joint disease) on the
basis of:
(A) Medical documentation, recorded within 30 days after the onset,
of objective signs of acute arthritis (joint swelling) that occurred
between 7 and 42 days after a rubella vaccination;
(B) Medical documentation (recorded within 3 years after the onset
of acute arthritis) of the persistence of objective signs of
intermittent or continuous arthritis for more than 6 months following
vaccination; and
(C) Medical documentation of an antibody response to the rubella
virus.
(ii) For purposes of paragraph (a) of this section, the following
shall not be considered as chronic arthritis: Musculoskeletal disorders
such as diffuse connective tissue diseases (including but not limited
to rheumatoid arthritis, juvenile
[[Page 56300]]
rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis,
mixed connective tissue disease, polymyositis/dermatomyositis,
fibromyalgia, necrotizing vasculitis and vasculopathies and Sjogren's
Syndrome), degenerative joint disease, infectious agents other than
rubella (whether by direct invasion or as an immune reaction),
metabolic and endocrine diseases, trauma, neoplasms, neuropathic
disorders, bone and cartilage disorders and arthritis associated with
ankylosing spondylitis, psoriasis, inflammatory bowel disease,
Reither's syndrome, or blood disorders.
(iii) Arthralgia (joint pain) or stiffness without joint swelling
shall not be viewed as chronic arthritis for purposes of paragraph (a)
of this section.
(7) Brachial neuritis. (i) This term is defined as dysfunction
limited to the upper extremity nerve plexus (i.e., its trunks,
divisions, or cords) without involvement of other peripheral (e.g.,
nerve roots or a single peripheral nerve) or central (e.g., spinal
cord) nervous system structures. A deep, steady, often severe aching
pain in the shoulder and upper arm usually heralds onset of the
condition. The pain is followed in days or weeks by weakness and
atrophy in upper extremity muscle groups. Sensory loss may accompany
the motor deficits, but is generally a less notable clinical feature.
The neuritis, or plexopathy, may be present on the same side as or the
opposite side of the injection; it is sometimes bilateral, affecting
both upper extremities.
(ii) Weakness is required before the diagnosis can be made. Motor,
sensory, and reflex findings on physical examination and the results of
nerve conduction and electromyographic studies must be consistent in
confirming that dysfunction is attributable to the brachial plexus. The
condition should thereby be distinguishable from conditions that may
give rise to dysfunction of nerve roots (i.e., radiculopathies) and
peripheral nerves (i.e., including multiple mononeuropathies), as well
as other peripheral and central nervous system structures (e.g.,
cranial neuropathies and myelopathies).
(8) Thrombocytopenic purpura. This term is defined by a serum
platelet count less than 50,000/mm3. Thrombocytopenic purpura does
not include cases of thrombocytopenia associated with other causes such
as hypersplenism, autoimmune disorders (including alloantibodies from
previous transfusions) myelodysplasias, lymphoproliferative disorders,
congenital thrombocytopenia or hemolytic uremic syndrome. This does not
include cases of immune (formerly called idiopathic) thrombocytopenic
purpura (ITP) that are mediated, for example, by viral or fungal
infections, toxins or drugs. Thrombocytopenic purpura does not include
cases of thrombocytopenia associated with disseminated intravascular
coagulation, as observed with bacterial and viral infections. Viral
infections include, for example, those infections secondary to Epstein
Barr virus, cytomegalovirus, hepatitis A and B, rhinovirus, human
immunodeficiency virus (HIV), adenovirus, and dengue virus. An
antecedent viral infection may be demonstrated by clinical signs and
symptoms and need not be confirmed by culture or serologic testing.
Bone marrow examination, if performed, must reveal a normal or an
increased number of megakaryocytes in an otherwise normal marrow.
(9) Vaccine-strain measles viral infection. This term is defined as
a disease caused by the vaccine-strain that should be determined by
vaccine-specific monoclonal antibody or polymerase chain reaction
tests.
(10) Vaccine-strain polio viral infection. This term is defined as
a disease caused by poliovirus that is isolated from the affected
tissue and should be determined to be the vaccine-strain by
oligonucleotide or polymerase chain reaction. Isolation of poliovirus
from the stool is not sufficient to establish a tissue specific
infection or disease caused by vaccine-strain poliovirus.
(11) Early-onset Hib disease. This term is defined as invasive
bacterial illness associated with the presence of Hib organism on
culture of normally sterile body fluids or tissue, or clinical findings
consistent with the diagnosis of epiglottitis. Hib pneumonia qualifies
as invasive Hib disease when radiographic findings consistent with the
diagnosis of pneumonitis are accompanied by a blood culture positive
for the Hib organism. Otitis media, in the absence of the above
findings, does not qualify as invasive bacterial disease. A child is
considered to have suffered this injury only if the vaccine was the
first Hib immunization received by the child.
(c) Effective data provisions. The revised Table of Injuries set
forth in paragraph (a) of this section and the Qualifications and Aids
to Interpretation set forth in paragraph (b) of this section apply to
petitions for compensation under the Program filed with the United
States Court of Federal Claims on or after [the effective date of the
Federal Register document which adopts these revisions as a final
rule]. Petitions for compensation filed before [such effective date]
shall be governed by section 2114 (a) and (b) of the Public Health
Service Act as in effect on January 1, 1995, or by Sec. 100.3 as in
effect on March 10, 1995 (see 60 FR 7678, et seq., February 8, 1995) as
applicable.
[FR Doc. 95-27562 Filed 11-7-95; 8:45 am]
BILLING CODE 4160-15-M
