National Vaccine Injury Compensation Program: Revisions and Additions to the Vaccine Injury TableII

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

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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

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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

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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