[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