National Vaccine Injury Compensation Program Revision of the Vaccine Injury Table

SUMMARY: This final rule amends the existing regulations governing the

National Vaccine Injury Compensation Program (VICP) by adding a new

section regarding the Vaccine Injury Table (Table) to the regulations,

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).

The VICP provides a system of no-fault compensation for certain

individuals who have been injured by specific childhood vaccines. The

Vaccine Injury Table included in the Act establishes presumptions about

causation of certain illnesses and conditions, which are used by the

Court to adjudicate petitions. The amendments to the Vaccine Injury

Table will affect only those petitions filed for compensation under the

VICP after the effective date of this rule.

EFFECTIVE DATE: This regulation is effective March 10, 1995.

FOR FURTHER INFORMATION CONTACT:

Geoffrey Evans, M.D., Chief Medical Officer and Deputy Director,

Division of Vaccine Injury Compensation, Bureau of Health Professions,

(301) 443-4198, or David Benor, Senior Attorney, Office of the General

Counsel, (301) 443-2006.

SUPPLEMENTARY INFORMATION:

Introduction and Procedural History

On August 14, 1992, the Assistant Secretary for Health, with the

approval of the Secretary of Health and Human Services (the Secretary),

published in the Federal Register (57 FR 36878) a Notice of Proposed

Rulemaking (NPRM) to amend the Vaccine Injury Table (the Table). (A

correction notice to the NPRM was also published on September 11, 1992,

57 FR 41809). The NPRM was issued pursuant to section 2114(c) of the

Act, which authorizes the Secretary to promulgate regulations to modify

the Table.

As stated in the preamble to the proposed rule, under section 312

of the National Childhood Vaccine Injury Act of 1986 (Pub. L. 99-660),

Congress mandated that the Secretary review the scientific literature

and other information on specific adverse consequences of pertussis and

rubella vaccines. The Secretary entered into a contract with the

Institute of Medicine (IOM), as recommended by Congress, to perform

this review. The IOM published a report of its review entitled,

``Adverse Effects of Pertussis and Rubella Vaccines,'' on August 27,

1991 (hereinafter ``IOM Report''). The Public Health Service Task Force

on the VICP evaluated the IOM report and made the initial

recommendations regarding possible revision of the Table.

These recommendations were reviewed by a special subcommittee of

the National Vaccine Advisory Committee (NVAC) (a committee authorized

under section 2105 of the Act). The subcommittee overwhelmingly

endorsed all of the proposed revisions except for the addition of

chronic arthritis to the Table. The full NVAC endorsed the

subcommittee's recommendations for revising the Table.

The Advisory Commission on Childhood Vaccines (ACCV), whose

membership by statutory directive reflects a variety of views relating

to childhood immunizations (authorized under section 2119 of the Act),

considered the NVAC report as well as the PHS Task Force

recommendations. 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 ACCV voted approval of all of the

PHS Task Force recommendations except for the removal of the condition

of Encephalopathy. The ACCV voted unanimously to retain Encephalopathy

on the Table provided the existing definition in the Aids to

Interpretation was clarified. The Secretary proposed changes to the

Table after reviewing the recommendations of these three entities.

As provided by section 2114(c) of the Act, the Department provided

for a 6-month comment period, which closed on February 11, 1993. On

December 3, 1992, the Department held a public hearing for the purpose

of receiving oral testimony on the proposed rule.

During the process of analyzing the comments received in response

to the NPRM, the Agency became aware of the imminent publication of a

10-year follow-up study to the National Childhood Encephalopathy Study

(NCES) (Madge N., Diamond J., Miller D., Ross E., McManus C., Wadsworth

J., Yule W. The National Childhood Encephalopathy Study: A 10-year

follow-up. A report of the medical, social, behavioural and educational

outcomes after serious, acute, neurologic illness in early childhood.

Developmental Medicine and Child Neurology 1993; Supplement No.

68;35(7):1-118; Miller D.L., Madge N., Diamond J., Wadsworth J., Ross

E. Pertussis immunization and serious acute neurological illness in

children. British Medical Journal 1993; 307:1171-1176, hereinafter

``Miller study.''). Because the Miller study looked specifically at the

relationship between vaccine administration and subsequent neurological

damage, the Department determined that it should not proceed with

publication of the final rule until there had been a sufficient

opportunity to consider the conclusions of the new Miller study.

Accordingly, the Department asked the IOM to convene a Committee for

purposes of evaluating the Miller study in light of the conclusions of

its initial report. On March 2, 1994, the Institute of Medicine issued

a report entitled ``DPT Vaccine and Chronic Nervous System Dysfunction:

A New Analysis.'' On March 24, 1994, the Department published a notice

in the Federal Register affording members of the public and additional

30 days to comment on the Miller study and the IOM report. See Federal

Register March 24, 1994, (59 FR 13916).

The Agency also asked a subcommittee of the NVAC to review the

IOM's conclusions regarding the implications of the Miller study. On

March 15, the NVAC subcommittee met to review (among other things) the

Miller study. The subcommittee was composed of members of the NVAC, and

received input from outside experts from the fields of epidemiology,

pediatric infectious disease, and pediatric neurology. The views of the

NVAC are discussed below where relevant.

The ACCV reviewed the IOM report on the Miller study at its

meetings in March and June, 1994. In addition, the ACCV was asked to

provide comments during the additional public comment period. Comments

received from two individual Commission members will be discussed

below. At the June meeting, the Commission discussed in detail the

Miller study and the IOM report. The consensus of the Commission was

that the original table in the statute requires modification to make it

consistent with current medical and scientific knowledge regarding

adverse events associated with certain vaccines. The Commission was

split, however, on the appropriate frame of reference for modifying the

Table. Some [[Page 7679]] Commission members expressed the view that

the starting point for revisions to the Table should be the original

Table in the statute. The other commissioners agreed that the Secretary

should further refine the Table, but that the starting point for

additional revisions should be the modified Table as published in the

NPRM on August 14, 1992.

The Department has listened carefully to the Commissioners'

concerns. After weighing all the varied opinions expressed at the June

meeting, as well as the written comments received from two commission

members, the Department has decided that a final rule which is a

revised and refined version of the proposed rule published in 1992 will

reflect best the scientific evidence. However, in drafting the final

rule, the Department made many of the changes suggested by members of

the Commission. These changes will be explained below. In this regard,

the Department recognizes that one of the objectives of the National

Vaccine Plan, which was released recently by the National Vaccine

Program Office/OASH, is to ensure that the Vaccine Injury Table is

updated periodicall to reflect the latest scientific knowledge. The

final rule is consistent with this goal, as well as the statutory

directive that the Secretary revise the Table.

Although by law the regulation will only affect those petitions

filed after the effective date specified above, the Department

encourages the Special Masters of the U.S. Court of Federal Claims to

apply the scientific findings which form the basis of the revised Table

where appropriate. For instance, in cases where petitioners are

intending to prove causation in fact, the IOM's conclusions regarding

causation may be relevant for consideration by the Special Master. In

addition, the Special Master could find, based on the conclusions of

the IOM, that a particular injury was due to a factor unrelated to

vaccine administration. Prior to promulgation of this rule, several

Special Masters viewed the IOM report as instructive regarding certain

illnesses and conditions and their relationship to vaccine

administration. The Department hopes that the use of the IOM report

continues, and that the findings and conclusions made by the Secretary

in promulgating this rule will be applied by the Masters where the

facts of the case make it appropriate to do so. In some cases, as

explained below, the Secretary's findings as set forth in the NPRM at

57 FR 36879 were not incorporated into the final rule. This decision

does not affect the Secretary's findings and should not deter the

Special Masters from applying the findings where appropriate.

The Department received 41 written comments and five oral comments

on the NPRM, and five comments in response to the Federal Register

Notice to Extend the Public Comment Period (March 24, 1994). Comments

were received from health professional organizations, parent

organizations, medical professionals, attorneys, and the general

public. All comments were carefully considered. The Department's

responses to the comments are discussed below in two separate sections.

Section I discusses the comments addressing legal issues, and Section

II discusses those comments addressing medical issues. The discussion

does not address comments that either generally supported or generally

criticized the proposed Table changes without making a specific point.

In preparing this final rule, the Department also made a number of

changes, both editorial and substantive in nature. The substantive

changes are discussed where appropriate as follows:

I. Legal Issues

The Secretary's Authority To Promulgate the Regulation

Several commenters suggested that the Department had exceeded its

authority in promulgating the regulation. First, commenters argued that

this is a function which belongs to the legislative branch and which

cannot be delegated to the Department based on the Separation of Powers

doctrine. The Department disagrees with this legal argument for several

reasons. In enacting a particular statutory scheme, Congress will often

leave particular gaps with instructions to the Department charged with

executing the statute to promulgate regulations to fill the gaps and

interpret the statutory language. See Chevron v. Natural Resources

Defense Council, Inc., 467 U.S. 837 (1984). In promulgating

regulations, the Department is limited to the authority delegated by

Congress, and is obligated to act consistent with Congressional intent.

See Bowen v. Georgetown University Hospital, 488 U.S. 204 (1988).

Pursuant to these basic principles of administrative law, the Secretary

is promulgating this regulation to amend the Vaccine Injury Table.

The statute explicitly authorizes the Secretary in section 2114(c)

of the Act to modify the Table and states that the ``Secretary may

promulgate regulations to modify * * * the Vaccine Injury Table.'' See

42 U.S.C. 300aa-14(c)(1). The statute further provides that ``a

modification of the Vaccine Injury Table under paragraph (1) may add

to, or delete from, the list of injuries, disabilities, illnesses,

conditions, and deaths for which compensation may be provided, or may

change the time periods for the first symptom or manifestation of the

onset of the significant aggravation of any such injury, disability,

illness, condition, or death.'' See 42 U.S.C. 300aa-14(c)(3). Under

section 312 of Pub. L. 99-660, Congress mandated that the Secretary

review the scientific literature and other information on specific

adverse consequences of pertussis and rubella vaccines. As mandated by

the statute, after completion of this study (undertaken by the

Institute of Medicine), and the consultation required by section

2114(c) of the Act, the Department proposed the revisions to the Table.

In so doing, the Department was acting exactly within the authority

delegated to it by the Congress.

Further, as stated in the preamble to the Notice of Proposed

Rulemaking, the legislative history explains that Congress intended the

Secretary to modify the Table. The Conference Report states as follows:

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.

See H.R. Rept. 99-908, Part 1, September 26, 1986, page 18 (reprinted

in 1986 U.S. Code Cong. and Admin. News, Vol. 6, page 6359). This

passage indicates that the Department is acting consistent with

Congressional intent.

At least two commenters argued that the Department exceeded its

authority in modifying the ``Qualifications and Aids to

Interpretation'' (Qualifications) found in section 2114(b) of the Act.

This argument, too, is misplaced. First, section 312 requires that the

Secretary make findings regarding which illnesses [[Page 7680]] and

conditions can reasonably be determined to be caused by certain

vaccines. It further requires the Secretary to make findings regarding

``the circumstances under which such causation or aggravation can

reasonably be determined to occur.'' 42 U.S.C. 300aa-1 note. The

purpose of the Qualifications and Aids to Interpretation is to describe

those circumstances under which certain conditions occur. Congress

stated that the Qualifications provide ``various descriptions and

definitions that the Committee intends be used in interpreting the

meaning of the Table.'' See H.R. Rept. 99-908, Part 1, September 26,

1986, page 19 (reprinted in 1986 U.S. Code Cong. and Admin. News, Vol.

6, page 6360). Given that Congress required the Secretary to make

findings regarding the circumstances under which causation can occur,

and that she was then required to promulgate regulations as a result of

such findings, she could not have fulfilled her obligations under

section 312 without modifying the Qualifications as well as the Table

itself.

Moreover, the statutory language and the legislative history quoted

above indicate that the Qualifications must be viewed as part of the

Table. The statute states that ``the following qualifications and aids

to interpretation shall apply to the Vaccine Injury Table in subsection

(a).'' See 42 U.S.C. 300aa-14(b). Thus, Congress intended the Table and

the Qualifications to be viewed as one unit because the Qualifications

explain and clarify the terms of the Table. It stands to reason,

therefore, that if the Table is changed, the Qualifications must be

changed accordingly.

In fact, Congress anticipated that changes to the Table would

require similar changes to the Qualifications and Aids to

Interpretation in order to guarantee that the two sections are

consistent. The statute states that ``if a provision of the table to

which paragraph (1), (2), (3), or (4) [the paragraphs of the

Qualifications and Aids to Interpretation] applies is revised under

subsection (c) or (d), such paragraph shall not apply to such provision

after the effective date of the revision unless the revision specifies

that such paragraph is to continue to apply.'' (42 U.S.C. 300aa-

14(b)(4)). Thus, the Qualifications contained in the original statute

become null and void once that initial Table is changed, unless the

Secretary specifies that they are to apply. Implicit in this authority

is the authority to promulgate by regulation Qualifications applicable

to the revised Table.

Two commenters stated that the regulation exceeded the Department's

authority by attempting to prescribe elements of proof necessary to

prevail in a petition for vaccine compensation. They argued that this

function is reserved to the United States Court of Federal Claims. As

explained above, the Secretary is authorized to revise the

Qualifications as well as the Table. The statute states that the

Secretary may ``add to, or delete from, the list of injuries,

conditions, and deaths for which compensation may be provided or may

change the time periods for the first symptom or manifestation of the

onset or the significant aggravation of any such injury, disability,

illness, condition or death.'' The original Table and Qualifications

delineate those elements which must be proven in order to take

advantage of a presumption of causation.

In this regard, the commenters should understand the function of

the Table. The purpose is not to set forth standards of proof for

establishing causation-in-fact. Rather, the purpose is to set out a

standard for establishing presumed causation, which, absent a finding

of a factor unrelated to the vaccine, will allow a petitioner to

receive compensation without the burden of proving causation for those

conditions included on the Table. Accordingly, the Qualifications

properly set out standards for defining those conditions on the Table.

Petitioners remain free to establish causation in fact by producing

credible scientific information peculiar to their conditions.

Although the commenters assert that the Department is impermissibly

creating elements of proof, the Qualifications as drafted originally

contain numerous requirements that are, in essence, elements of proof.

For example, the paragraph describing the requirements for a `residual

seizure disorder' states the number of seizures which must have

occurred in the year after the vaccine was administered for the

petitioner to be found to have suffered a residual seizure disorder. In

addition, section 2114(b)(3)(A) of the Act describing the definition of

encephalopathy states that ``Encephalopathy usually can be documented

by slow wave activity on an electroencephalogram.'' Similarly, the

revised Qualifications indicate the elements which must be proven to

establish a presumption of causation for those injuries and conditions

listed in the modified Table.

In objecting to this aspect of the Qualifications, the commenters

assume erroneously that the revised Qualifications alter the Special

Master's role in determining whether a Table Injury has been proven.

The Special Master's role is to consider the information contained in

the record, including oral testimony, medical records and medical

opinion. The Master must weigh the evidence, examine the credibility of

the witnesses, reconcile the points of disagreement between the parties

and issue a final decision. The revised Qualifications do not alter

this role. As did the former Qualifications, they require the

petitioner to demonstrate a Table condition by proving that various

events occurred. The Special Master must still analyze the evidentiary

issues which arise in the context of attempting to prove a Table

injury.

The Effect of the Regulation on Other Statutory Sections

One commenter stated that the Qualifications and Aids to

Interpretation are inconsistent with section 2113(b) of the Act, which

permits the Special Master to find that the injury occurred within the

Table period even if the symptoms were not recorded or were incorrectly

recorded in the medical records. The commenter specifically took issue

with the section of the revised Qualifications which states that an

``an acute encephalopathy should be sufficiently severe to require

health care intervention and hospitalization.'' In addition, during the

June 1994 meeting of the ACCV, at least one member of the Commission

objected to this requirement as being overly restrictive because

hospitalization is required. The Commission member voicing this concern

felt that the rule should recognize that not all parents would respond

to a possible encephalopathic event by taking the child to the

hospital.

The revised Qualifications and Aids to Interpretation are not

inconsistent with section 2113(b) of the Act, because the Special

Master may still find that a preponderance of the evidence indicates

that the encephalopathy was severe enough to require medical

intervention or hospitalization, but that because of error or omission

the event was either not recorded or was incorrectly recorded. In

addition, under the revised Qualifications, although medical records

should be provided in most cases, the language ``sufficiently severe''

is meant to be consistent with section 2113(b)(2) of the Act and would

permit a finding in favor of petitioner if the Special Master found

that a preponderance of the evidence indicated that the injury was

sufficiently severe such that medical intervention should have been

sought. [[Page 7681]]

In the Department's view, the original statute does not intend the

Special Master to find that the injury occurred within the Table period

in the absence of any records recording the injury, unless the

petitioner is able to produce clear, cogent, and consistent testimony

to explain the absence of records. The Court has found in favor of

petitioners in the absence of corroborating medical records where the

preponderance of evidence, including oral testimony, demonstrates that

the adverse event occurred within the Table timeframe. The requirement

contained within the revised Aids to Interpretation is meant to include

only those events which are so serious that they require medical

intervention (whether or not medical intervention was actually sought),

and are, therefore, properly referred to as encephalopathies. The

requirement is simply meant to exclude those conditions which are not

serious enough to warrant medical attention. These types of minor

symptoms (e.g., excessive crying, sleepiness) were specifically

excluded from the definition of encephalopathy contained within the

original statute, but have been alleged by some petitioners to be signs

and symptoms of an encephalopathy. The revised Qualifications and Aids

to Interpretation simply seek to make clear the intent of Congress.

The Department recognizes, however, that the language ``should be

sufficiently severe,'' is somewhat confusing. In addition, the

Department recognizes that the phase ``medical intervention and

hospitalization'' is redundant, and open to various interpretations.

Accordingly, the regulatory language in Sec. 100.3(b)(2)(i) as proposed

has been revised to read ``An acute encephalopathy is one that is

sufficiently severe so as to require hospitalization.'' The Department

is making this change in the interests of clarity, consistent with the

explanation articulated above. In order to demonstrate a Table

encephalopathy, the petitioner must prove that the injury was indeed

serious enough to warrant hospitalization, whether or not records of

such hospitalization exist. Certainly, however, contemporaneous medical

records are of extreme importance in proving that a Table injury

occurred.

The Sufficiency of the IOM Report as the Basis for the Changes to the

Vaccine Injury Table

Several commenters stated that the Department relied on

insufficient data in proposing modifications to the Table. These

commenters argued that Congress intended that more definitive

information be available before the Table is revised. The commenters

took issue with both the conclusions of the Institute of Medicine and

the Department's interpretation of those conclusions. Section 312 of

Pub. L. 99-660 (42 U.S.C. 300aa-1, note) required the Secretary to

complete a review of ``all relevant medical and scientific information

regarding the connection between various vaccines and specified adverse

events.'' The Secretary was then required to publish in the Federal

Register findings regarding ``whether each of the illnesses or

conditions set forth in subsection (a) can reasonably be determined in

some circumstances to be caused or significantly aggravated by

pertussis containing vaccines.'' See 42 U.S.C. 300aa-1, note.

Simultaneously, the statute required that the Secretary propose changes

to the Table as a result of the findings.

This language indicates that Congress intended that the Secretary

modify the Table consistent with the conclusions of the review

undertaken by the Institute of Medicine. Nowhere is there a

requirement, however, that the causal connection between the

administration of vaccines and certain adverse events be definite and

conclusive before any changes are made. The IOM concluded that ``the

evidence is insufficient to indicate a causal relation between vaccines

containing pertussis'' and certain adverse events. Because the evidence

was determined as ``insufficient,'' the Department concluded that it

could not ``reasonably determine'' that a causal connection exists, and

the Table is being revised accordingly.

The section of the legislative history cited by the commenter in

support of the objection states that ``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 (discussed below in section 2119) may propose to

revise the Table as provided below in section 2114.'' This statement

merely indicates a recognition by Congress that the original Vaccine

Injury Table was overinclusive, and that more research would yield more

definitive information. As described in the preamble to the proposed

regulation, and consistent with the statutory requirements, the

findings of the Institute of Medicine represented a comprehensive

review of the existing evidence as well as numerous opportunities for

comment from various experts and members of the public. The systematic

process undertaken by the Department to evaluate the findings of the

IOM demonstrates that the Department reviewed sufficiently the findings

of the IOM and their applicability to the Table. These findings clearly

indicated that the original Table was out of step with the state of

medical knowledge. Accordingly, the Secretary was obliged to propose

revisions. Although the IOM's original conclusion was modified somewhat

in the 1994 report regarding pertussis vaccine and chronic nervous

system damage, the Department has determined that the major changes to

the Table published in the NPRM reflect the IOM's latest conclusions

regarding this difficult issue. Nevertheless, as discussed below, the

final rule reflects some minor changes made to the proposed rule in

light of the Miller study and comments provided to the Department in

connection with this study.

Two commenters felt that the Department had ignored relevant

information in revising the Table. Specifically, they believed that the

Department should have viewed the claims that have either been

compensated or conceded by the Department as proof that the

presumptions conferred by the Table are accurate. However, the fact

that a particular case has either been adjudicated compensable or

conceded by HHS does not imply that a medical conclusion regarding

vaccine-relatedness has been made. The process of deciding claims is

based on whether the claim fits the parameters of the Table, or whether

causation has been proven. Most claims have been adjudicated ``table

cases,'' meaning that the petitioners were afforded the presumption of

causation conferred by the statute. This determination involves an

analysis of various evidentiary and other legal issues, but does not

prove or disprove whether a causal relationship exists in fact between

certain vaccines and adverse events. The outcome of these cases does

not have any bearing on whether the Table should be revised to reflect

the findings of the Institute of Medicine.

One commenter referred to a letter written by the organization

Dissatisfied Parents Together on May 8, 1991, to then Secretary

Sullivan regarding concerns that members of the Immunization Practices

Advisory Committee (ACIP) who have advised pharmaceutical companies, or

conducted research funded by such companies may have a conflict of

interest which precludes their serving [[Page 7682]] on the ACIP. The

Department has determined that this comment is irrelevant as far as the

modification of the Table is concerned. In undertaking its review, the

IOM did not rely on the views of members of the ACIP or the work-

product of that Committee.

The Effect of the Proposed Changes on the Vaccine Injury Compensation

Program

Two commenters suggested that the result of the proposed revisions

would be an increase in the transaction costs of the Program because

many petitioners will pursue their cases by attempting to prove

causation-in-fact. The Department has taken this concern into

consideration and has concluded that the benefits of the proposed

regulation outweigh the possibility of more protracted and complex

hearings. The intent of the regulation is to make the Table consistent

with medical knowledge regarding the relationship between vaccines and

certain adverse events. The Department notes that Congress recognized

that the original Vaccine Injury Table would permit individuals whose

conditions were not related to vaccine administration to be adjudicated

eligible for compensation. If the Table is revised to permit

compensation only in those cases where vaccine relatedness is more

accurately proven, greater resources will be available to compensate

those truly deserving of compensation.

In a similar vein, several commenters expressed concern that the

Department was seeking to prevent children deserving of compensation

from receiving assistance under the Program. In fact, exactly the

opposite is true. The revised Table merely affects the presumption of

causation available to certain petitioners. Petitioners will, of

course, continue to have the option of proving causation by a

preponderance of evidence if they are unable to prove a Table injury.

Moreover, the Department recognizes that there is a desperate need for

parents to obtain resources to cover the significant medical costs of

caring for a sick child. However, the intent of the VICP was to

compensate only those individuals whose injuries are vaccine-related.

The proposed regulation is simply an attempt to come closer to

realizing this goal than was possible with the language of the original

Vaccine Injury Table.

Three commenters suggested that the proposed regulation would

result in an increased number of civil actions filed against vaccine

manufacturers and administrators. In enacting the National Childhood

Vaccine Injury Act, Congress determined that one of the goals of the

Act was to reduce the number of civil actions filed against vaccine

administrators and manufacturers. The other major goal was to provide

compensation to those individuals whose conditions were caused by

vaccines. See H.R. Rept. 99-908, Part 1, September 26, 1986, page 6

(reprinted in 1986 U.S. Code Cong. & Admin News, Vol. 6, page 6347).

The Committee recognized, however, that the Table would possibly

provide compensation to some children whose illnesses are not vaccine-

related, but that further research and modifications to the Table would

result in a more equitable distribution of funds. In balancing these

two Congressional goals, the Department has determined that the

benefits of fulfilling the latter requirement outweigh the risk that an

increased number of civil actions will be filed against vaccine

administrators or manufacturers.

Furthermore, the Department believes that the combined effect of

the IOM's review and this regulatory action may reduce the extent of

tort litigation by giving the courts (and potential plaintiffs weighing

the wisdom of filing suit) definitive guidance as to the state of

scientific knowledge regarding vaccine-related injuries. As causation

must typically be proven in tort actions, the Department believes that

the findings on these issues may well reduce the amount of tort

litigation and may allow easier resolution of any such claims that are

litigated.

II. Medical Issues

The Department's Interpretation of the IOM Report

Six commenters suggested that the Department's findings are a

misinterpretation of the IOM Report. In the Department's view, however,

the proposed changes do reflect accurately the conclusions of the IOM

report.

Both the NPRM and the final rule (with some revisions are discussed

below), reflect most closely the package of recommendations as

developed by the PHS Task Force, reviewed by the NVAC, and endorsed by

the ACCV. The proposed changes are in accordance with the scientific

findings of the IOM Committee. In instances where the IOM found

information suggesting a causal relation and continued effects, the

Department acted to ensure coverage under the Program (e.g., adding

chronic arthritis to the Table). However, where the IOM found that the

evidence did not support a causal relation and continued effects, the

Department removed the legal presumption of causation by removing or

redefining the current injury listed on the Table. The fact that the

proposed revisions received overwhelming approval from three

independent science and health policy committees, and the endorsement

of two national health professionals associations (American Academy of

Pediatrics and American Medical Association), confirms the basic

soundness of the initial proposed revisions.

One of the commenters addressing the Miller study suggested that in

light of the 1994 IOM Report, the Department should rescind certain

findings made after release of the 1991 Report and published in the

preamble to the NPRM. In the NPRM, published on August 14, 1992, the

Department made certain findings as required by section 312(b) of Pub.

L. 99-660 (42 U.S.C. 300aa-1 note). The Department has reviewed these

findings again in light of the commenter's concerns, and has determined

that the findings remain valid. In fact, the conclusions of the IOM and

the NVAC subcommittee (discussed below) with respect to pertussis

vaccine and chronic neurological damage confirm the soundness of

findings three and four as listed in the NPRM. These findings read, in

pertinent part, as follows:

3. The evidence is insufficient to indicate a causal relation

between vaccines containing pertussis and: Epilepsy * * * chronic

neurologic damage, * * * learning disabilities and attention-

deficient disorder, * * * or permanent neurologic damage or death

following hypotonic-hyporesponsive episodes.

4. The evidence is consistent with a causal relation between

vaccines containing pertussis and? Acute encephalopathy and shock

and ``unusual shock-like state.''

The recent IOM report was confined to a review of the Miller study, and

is, therefore, limited to the circumstances of that particular study.

Given the conclusions articulated by the IOM and the accompanying

caveats, and the discussion and conclusions of the NVAC subcommittee,

the Department concludes that the findings published with the NPRM

reflect best the state of scientific knowledge. It should be noted

again that in drafting the revised Qualifications and Aids to

Interpretation, the Department decided not to eliminate the presumption

of causation for encephalopathy despite the conclusions of the 1991 IOM

study. Rather, consistent with the recommendation of the ACCV, the

Department included a presumption of vaccine causation for those

individuals who experience an acute encephalopathy within 3 days after

vaccination, who go on to suffer 6 [[Page 7683]] months of residual

effects, and who experience chronic neurological dysfunction. This

presumption is consistent with the IOM's conclusions articulated in its

1994 report.

Four commenters suggested that the IOM's causation category of

``insufficient evidence'' should not be interpreted to mean that DTP

vaccine does not cause the condition. Furthermore, they suggest that

both the IOM and the Department present no data which support the

proposition that acute encephalopathy, subsequent to the receipt of a

pertussis vaccine, has a more benign neurological outcome than acute

encephalopathies from other agents. The Department has considered these

comments but maintains that the IOM report provides a foundational

basis for the proposed changes.

The 1991 IOM report concluded the evidence was insufficient to

indicate a causal relationship between vaccines containing pertussis

and chronic neurological damage for a variety of conditions including

encephalopthy, shock collapse or Hypotonic-Hyporesponsive Episode

(HHE), epilepsy, and other neurologic and non-neurologic disorders.

Comments that expressed concern over this classification focused for

the most part on acute encephalopathy and chronic neurologic damage,

while a few discussed shock-collapse (HHE) or recurrent seizures

(epilepsy). The issue of encephalopathy following pertussis vaccination

is a difficult one. On one hand, in its 1991 Report, the TOM found

evidence ``consistent with a familiar evidence ``consistent with a

causal relation'' for acute encephalopathy, yet on the other hand, it

decided there was ``insufficient evidence'' regarding chronic

nuerologic damage. Due to limitations in the data, the IOM could not

conclude with any certainty whether there is any causal relationship

between pertussis vaccine and shock-collapse (HHE), epilepsy, or any of

the other disorders under this classification category. In its 1994

report addressing the Miller study, the IOM concluded that ``evidence

is insufficient to indicate whether or not DTP increases the overall

risk in shildren of chronic nervous system dysfunction.'' They

concluded further, that the ``balance of evidence is consistent with a

causal relation between DTP and the forms of chronic nervous system

dysfunction described in the NCES in those children who experienced a

serious acute neurological illness within 7 days after vaccine

administration.'' The IOM also concluded, however, that ``the evidence

remains insufficient to indicate the presence or absence of a causal

relation between DTP and chronic nervous system dysfunction under any

other circumstances.'' See 1994 IOM Report, Executive Summary.

Because section 2111(c) of the Act requires that a Petitioner must

show 6 months of residentual effects of a Table injury, a finding of a

relation pertussis-containing vaccines and acute, but not chronically,

does not justify the presumption of causation for long-term neurologic

damage. However, should the evidence show that abnormal neurologic

signs continued beyond the acute state, and therefore the injured

indidivual never returned to a ``normal neurological state,'' than

title may be granted. This conclusion is consistent with the 1994 IOM

report.

The language of section 312 of Pub. L. 99-660 (42 U.S.C. 300aa-1,

note) also supports the Department's conclusion. The IOM determined in

its 1991 report that the evidence is insufficient to support a

conclusion that a causal relationship between DTP vaccine and chronic

neurologic damage exists. The 1994 IOM finding was limited to the

conditions described in the NCES and to those children who experienced

an acute event following vaccination. Therefore, the Department

concluded that it could not ``reasonably determine'' that as a general

rule a causal relationship exists, and the Table is being modified

accordingly. Because section 312 requires such a determination in order

to sustain the presumption of causation, the Department was obligated

to revise the Table consistent with the conclusions of the IOM.

The removal of the legal presumption of causation has been applied

to other conditions in the ``insufficient evidence'' category (i.e.,

HHE and residual seizure disorder). The Department notes, however, 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 have previously been awarded. Petitioners

may still prevail by providing proof that the vaccine actually caused

the specific injury alleged to have occurred.

Three commenters suggested that the IOM's burden of proof standard

was too high. They suggested that the IOM should develop a confidence

level that is more lenient than 95 percent, particularly when it is

applied to the ``preponderance of the evidence'' burden of proof

standards present in the VICP. After consideration of the process used

by the IOM in developing its report, it is the Department's view that

the IOM's standard was appropriate.

Congress mandated that the IOM review the scientific literature and

other information on specific adverse consequences of pertussis and

rubella vaccines. The Committee was composed entirely of physicians and

scientists, whose task it was to evaluate the literature on adverse

events following these vaccines. Any ``burden of proof'' standard had

to be consistent with the standard applied throughout the science of

epidemiology, policy considerations notwithstanding. It is the

Secretary's responsibility under section 312 of Pub. L. 99-660 (42

U.S.C. 300aa-1, note) to utilize the IOM's conclusions to provide a

better scientific rationale for any presumptions of vaccine causation

under the Program.

Moreover, although the statute requires merely a ``preponderance of

the evidence'' standard in evaluating compensation claims, there is no

requirement that anything other than the standard commonly used among

scientific and medical professionals be applied in re-defining those

conditions which will receive a presumption of causation by use of the

Table. The preponderance of evidence standard is only relevant when a

Master is evaluating a particular case.

One commenter suggested that the IOM conclusions were incorrect

regarding DTP's pathological effects in animals or children. The

commenter stated that the IOM erred in diminishing the importance of,

or incorrectly judged, the conclusions of controlled epidemiologic

studies. Furthermore, the commenter suggested that the IOM Committee

was remiss in its examination of the evidence concerning long-term

sequelae for HHE. Finally, two commenters criticized the IOM because no

original research was done in putting together its conclusions. As

stated above, the Department has considered these comments, but has

determined that the process used by the IOM was appropriate.

The 1991 IOM Committee was made up of 11 experts in infectious

disease, pediatrics, internal medicine, neurology, epidemiology,

biostatistics, decision analysis, immunology and public health. During

the 20 months of their work, approximately 1,400 citations were

reviewed and 5 public meetings were held. No new research was

conducted. Committee members considered new or controversial data and

various points of view and sought to identify gaps in knowledge. The

IOM cited many gaps and limitations of knowledge. Its conclusions were

reached, however, after an exhaustive analysis of the best

epidemiologic data available, and other information.

[[Page 7684]] Congress did not mandate any specific research, but

rather, an extensive review of all the available information on adverse

events.

One commenter suggested the IOM incorrectly judged the conclusions

of the British National Childhood Encephalopathy Study (NCES). Another

commenter stated that the NCES is the only ``suitable'' study that has

been done, and that it concluded that there was a causal relationship

between the DTP vaccine and permanent neurologic injuries. One

commenter also suggested that the NCES proved the onset of a neurologic

disorder, including seizures, within 7 days of a DTP vaccination is

vaccine-related. The Department has reviewed the conclusions of the

NCES in light of these comments, but disagrees for the following

reasons.

The 1991 IOM Report considered carefully the results of the NCES,

which concluded there is an increased risk of acute neurologic illness

(encephalopathy and seizures) within 7 days following DTP immunization,

and that in some instances, this may lead to permanent neurologic

illness. The methods and results of the NCES have been thoroughly

analyzed since publication of the study, which has led to continued

controversy about the study's findings and a reassessment of the role

of pertussis vaccine as a cause of permanent neurologic damage. (IOM

Report, page 99-107)

In its 1991 report, the IOM described potential areas of error and

bias regarding the study's conclusions on acute neurologic illness and

chronic neurologic damage. Regarding acute neurologic illness, the

Committee cited three areas of potential study weakness: case

ascertainment, determination of the onset of illness, and the lack of

control for potential confounding factors. Despite these limiting

factors, the IOM believed that the NCES demonstrated statistical

significance for acute neurologic illness where onset is within 7 days

of DTP vaccination. Their conclusion was based on the fact that only

controlled epidemiological studies can address the relationship between

neurologic illness and vaccine causation. Of the four controlled

studies reviewed (including the NCES), only the NCES demonstrated a

statistically significant risk following DTP vaccine. However, the IOM

noted that the ``total number of cases reported in the other three

studies was consistent with attributable risk found in the NCES,'' and

on this basis concluded the evidence was consistent with a causal

relation between DTP vaccine and acute encephalopathy. (IOM Report,

page 117)

The NCES' conclusion regarding permanent neurologic damage was

viewed differently by the 1991 IOM Committee. The Committee described

concerns over (1) the number and composition of cases on which the

estimates were based and (2) the nature of the relationship between an

episode of acute neurologic illness and subsequent demonstration of

neurologic or developmental abnormalities. Both concerns cast doubt

upon the NCES' conclusion that DTP vaccine causes residual neurologic

injury.

The conclusion regarding permanent injury was based on seven

children who were found to have residual neurologic illness on follow-

up. Since the NCES was published, some of these seven children have

been diagnosed with non-vaccine related conditions. Thus, the risk

estimates are ``very fragile'' at best, since the number of children

with new unexplained neurologic illness was very small. (IOM Report,

page 106).

Similarly, the NCES' conclusions on residual effects begs the

central question of causation. All seven children found to have

``permanent neurologic illness'' on follow-up were presumed to be

normal prior to vaccination. However, no baseline neurologic

examination was performed on any of these children. Additionally, two

of the seven had seizures as their manifestation of acute neurologic

illness within 7 days of DTP vaccination. As the IOM noted, many

experts question whether seizures alone cause neurologic illness, or

rather are the ``markers'' of those children with pre-existing

neurologic disease. (IOM Report, page 107).

As explained above, a follow-up study to the NCES was published by

Miller, et al. in the fall of 1993. The Department asked the IOM to

look at the Miller study's conclusions regarding DTP vaccine and

subsequent neurological damage. The Department then asked a

subcommittee of the National Vaccine Advisory Committee (NVAC) to

review this later IOM report, as well as the Miller study. The NVAC

Subcommittee acknowledged the original NCES (and Miller follow-up) as

the most comprehensive long-term study on this subject to date, yet

noted there are limitations in the data. These include the lack of

neuropathologic studies on case children, the fact that young infants

with pre-existing neurologic disorders (damage) can be normal on

physical examination at the time of immunization, the failure to

exclude alternative etiologic diagnoses, and the non-specific range of

disorders classified by NCES authors under the rubric ``chronic nervous

system dysfunction.'' The subcommittee noted also that the working

definition of ``acute neurologic illness'' used in the NCES is not

consistent with the current medical understanding of acute

encephalopathy as an acute, generalized disorder of the brain. Children

were placed in the NCES case definition who experienced only febrile

seizures, a benign condition known to be triggered by DTP vaccine, yet

never proven to have lasting effects, absent signs of acute

encephalopathy. These limitations disallow definitive causal

conclusions that would necessitate changes to the Secretary's

definition of encephalopathy in the NPRM.

In reviewing the Miller study, the IOM Committee reached three

conclusions:

(a) The evidence is insufficient to indicate whether or not DTP

increases the overall risk in children of chronic nervous system

dysfunction.

(b) The balance of evidence is consistent with a causal relation

between DTP and the forms of chronic nervous system dysfunction

described in the NCES in those children who experienced a serious acute

neurologic illness within 7 days after vaccine.

(c) The evidence remains insufficient to indicate the presence or

absence of a causal relation between DTP and chronic nervous system

dysfunction under any other circumstances.

After extensive review and discussion, the NVAC subcommittee agreed

with the IOM's conclusion that children who experience serious, acute

neurological events after DTP vaccination can go on to exhibit

``chronic nervous system dysfunction.'' The NVAC subcommittee concluded

that despite the conclusions of the Miller study, the information

remains insufficient to accept or reject whether DTP administration

prior to the acute, serious neurologic event influenced the likelihood

of neurologic dysfunction. In order to avoid any confusion on this

point, the Subcommittee approved the following summary statement:

Children immunized with whole-cell DTP vaccines rarely

experience acute, serious neurologic events that require

hospitalization. An important question pertains to the long-term

complications of these events. Among all children hospitalized with

serious neurologic events, irrespective of their etiology or

relationship to DTP, there is a potential for the presence of

neurologic dysfunction when they are evaluated 10 years later.

However, the data are insufficient to accept or reject whether DTP

administration prior to the acute, serious neurologic event

influenced the potential for neurologic dysfunction. See National

Vaccine Advisory Committee (NVAC), Report of the Ad Hoc Subcommittee

on Childhood Vaccines, p.7.

[[Page 7685]] The Agency has reviewed carefully the IOM's

conclusions and the NVAC subcommittee's evaluation of the IOM report,

recognizing that questions will continue regarding DTP vaccine and

chronic nervous system dysfunction. In addition, the Agency has

considered comments provided by three individuals in response to the

March 24, 1994 Federal Register Notice. These commenters suggested that

the Department should retract some of the changes to the Vaccine Injury

Table proposed in 1992, arguing that those changes are not inconsistent

with the 1994 IOM report. The Agency has determined that despite the

uncertainty regarding causation, the final rule is consistent with both

the IOM report and the NVAC subcommittee's conclusions regarding the

Miller study. The final rule permits an individual to receive a

presumption of causation if the DTP vaccine recipient ``manifests,

within the applicable period, an injury meeting the description * * *

of an acute encephalopathy, and then a chronic encephalopathy persists

in such person for more than six months beyond the date of

vaccination.'' See Sec. 100.3(b)(2). Thus, the final rule is consistent

with the IOM's conclusion that some children have been shown to have

experienced an acute encephalopathy following vaccine administration

and then have gone on to develop chronic neurologic dysfunction. See

1994 IOM Report, Executive Summary.

The only circumstances under which a presumption of causation would

not be available to an individual with chronic neurological dysfunction

would be (1) where the child had not experienced an acute

encephalopathy within several days after DTP vaccination, or (2) where

the child experienced an acute encephalopathy within several days of

DTP vaccination, but returned to a normal neurological state, and did

not suffer 6 months of residual effects after the administration of the

vaccine.

The denial of a presumption of causation for the former is

consistent with the IOM's conclusions as articulated in both its 1991

and 1994 reports. The IOM did not conclude that chronic neurological

dysfunction should be presumed to be caused by DTP vaccine in the

absence of an acute encephalopathy that occurs within several days

following vaccination. See 1994 IOM Report at page 10. The IOM stated

the following:

The evidence remains insufficient to indicate the presence or

absence of a causal relation between DTP and chronic nervous system

dysfunction under any other circumstances. That is, because the NCES

is the only systematic study of chronic nervous system dysfunctions

after DTP, the committee can only comment on the causal relation

between DPT and those chronic nervous system dysfunctions under the

conditions studied by the NCES. In particular, it should be noted

that the chronic nervous system dysfunctions associated with DTP

followed a serious acute neurologic illness that occurred in

children within 7 days after receiving DPT. 1994 IOM Report at page

11.

Neither the IOM report nor the Miller study addressed the scenario

where a child would experience an acute encephalopathy within several

days following vaccine administration, would return to a normal

neurological state, but at some point in the future would exhibit signs

of chronic neurological dysfunction. The most recent report by the IOM

does not present any information which warrants a modification of the

presumptions in the final rule. Therefore, the final rule is consistent

with the IOM's conclusions and the NVAC subcommittee's assessment of

those conclusions.

The NVAC subcommittee was also asked to look at whether the

evidence as described in the IOM report would support a conclusion that

the time period in the vaccine injury table for acute encephalopathy

following DTP vaccine should be changed from 3 to 7 days. The

subcommittee concluded that there is presently insufficient information

to justify such a change. The Department has reviewed the conclusions

of the IOM report as well as those of the NVAC subcommittee and has

determined that the rule should not be modified. In this regard, the

Department recognizes that it is accepting the analysis of the NVAC

subcommittee, rather than acting solely on the basis of this particular

statement from the 1994 IOM report. However, it is important to note

that the 1991 IOM report, which included a review of numerous

scientific studies and other medical literature, did not draw any

conclusions regarding the appropriate time period.

In preparing the latest report, the IOM confined its analysis to

the Miller study, which was a follow-up to the original NCES. Given the

limitations of the IOM's conclusions, including the lack of primary

data analysis, as well as the methodologic limitations that have been

noted with regard to the NCES, the NVAC subcommittee determined that

the conclusions of the Miller study with respect to the appropriate

timeframe could not be extended beyond the parameters of this one

particular study. After careful consideration, and recognizing the

extensive expertise of the NVAC subcommittee, the Department has

decided to accept the conclusions of the NVAC subcommittee.

Accordingly, the 3 day timeframe, as originally determined by Congress,

will not be changed. Petitioners may seek to prove causation in fact

for conditions arising between 3 and 7 days after vaccination and may,

of course, introduce the Miller study and the IOM report as evidence

bearing on such an argument.

One commenter suggested that the 1991 IOM report contradicts an

earlier 1985 IOM report which gave risk estimates for reactions

following whole cell pertussis vaccination, and stated that pertussis

vaccine causes permanent neurologic damage.

The 1985 IOM Report focused on building a model to help evaluate

the risks and benefits for existing and new vaccines to allow informed

judgments on priorities for developing new vaccines. In drafting their

conclusions, the 1985 group used informed judgments on vaccine risks,

and the financial benefits of reducing disease. Because of the larger

number of vaccines studied in the 1985 report, the review of the

scientific literature on specific adverse events in this report was far

less extensive than that in the 1991 report.

Analysis of Other Data

Before any changes should be made to the Table, four commenters

suggested that the Vaccine Adverse Events Reporting System (VAERS) data

and/or Vaccine Injury Compensation Program records should be examined

and analyzed. VAERS is a passive reporting system which relies in large

part on reports of events temporally related to vaccine administration.

Therefore, no reliable conclusions about causation could be drawn from

the reported VAERS data without its undergoing substantial analysis.

While the Department recognizes the importance of VAERS, it is

unwilling to overstate its importance by using temporal relationships

to define a new Table.

Further, the IOM's section 312 study involved a thorough review of

scientific and medical information contained in peer reviewed journals.

However, information based on anecdotal reports (e.g., VAERS), or a

series of case reports, such as claims filed under the VICP, has less

certain scientific reliability, and therefore should also not be used

as a basis for revising the Table. Because of the limitations of these

types of evidence, the Department does not concur with this suggested

approach.

The ACCV's Scientific Review Subcommittee reviews cumulative data

[[Page 7686]] collected through the VAERS system at each quarterly

meeting. In December 1992, the Subcommittee wrote the following

concerning: ``VAERS as a means of surveillance of temporally-related

adverse events, has definite limitations and does not allow the

evaluation of possible causal relationships between vaccine

administration and adverse events.'' VAERS's data potentially serve as

a ``signal'' of possible causal relationships, which can then be

investigated through what are termed Large Linked Data Bases (LLDB's).

The Subcommittee encouraged increased utilization of LLDB data because

of its potential for surveillance of adverse events and their possible

causal relationship to vaccine administration.

The Department will monitor future analysis of VAERS and LLDB data.

Should information suggest modifications to the Table, the Department

will publish a new NPRM reflecting this new information with proposals

for change.

One commenter suggested that the Department ignored cases in the

medical literature (and VICP case files) that show a pattern of

increasingly severe reactions after succeeding DTP shots in the same

child. The commenter argued that the IOM Report indicated it would tend

to support the hypothesis of a causal link between pertussis vaccine

and permanent neurologic damage if case histories show such a pattern.

In its analysis, the IOM reviewed case reports and case series

along with controlled epidemiologic studies. It is true that the IOM

suggested that the increasing severity of a reaction following

immunization in the same individual might indicate a causal link to the

vaccine. The Department did not view this hypothesis as strong enough

to warrant a presumption of causation. The results of the 1994 IOM

Report have not changed this conclusion. However, any petitioner who

can demonstrate evidence of progressive or repetitive adverse effects

following vaccination may be eligible for compensation by proving

causation in fact.

Three commenters suggested there should be no changes to the Table

before the section 313 study (of other vaccine risks) is completed. One

commenter suggested specifically that changes to the timeframe under

Residual Seizure Disorder are not appropriate before results of the

section 313 study have been published.

In publishing the final rule, the Department has considered the

effect of the section 313 study. Section 313 of The National Childhood

Vaccine Injury Act of 1986, Pub. L. 99-660, mandated that the Secretary

arrange with the IOM for an additional broad study of the risks

associated with each vaccine set forth in the Table, other than the

vaccines (pertussis and rubella) previously identified in the section

312 study discussed above. The IOM section 313 study, entitled

``Adverse Events Associated with Childhood Vaccines: Evidence Bearing

on Causality,'' was released on September 14, 1993. The study covers

adverse events following these commonly-administered vaccines: measles,

mumps, diphtheria, tetanus, polio, Hemophilus influenza type b, and

Hepatitis B.

On March 15, 1994, a subcommittee of the NVAC met to consider the

section 313 report. The subcommittee was composed of members of the

NVAC and received testimony from outside experts in the fields of

epidemiology, pediatric infectious disease, and pediatric neurology.

The Department determined that the conclusions of the subcommittee

regarding the section 313 report do not provide a basis for changing

the final rule at this time. However, the Department is presently

reviewing the conclusions of the NVAC subcommittee regarding the

section 313 report. It is likely that after this review the Department

will initiate further rulemaking proceedings. The Department has

concluded, however, that there are no compelling reasons which would

justify delaying the promulgation of the final rule pending completion

of that review.

Anaphylaxis

One commenter suggested that the examples of anaphylaxis given by

the IOM do not provide a basis for the proposed revisions.

The IOM examined case reports and epidemiologic studies concerning

anaphylaxis and anaphylactic shock. There was considerable variability

in the onset and clinical signs of what was defined as ``anaphylaxis.''

One ``suspected association'' with pertussis vaccine was a case report

of twins from 1946, both of whom died within 24 hours of pertussis

vaccination (IOM Report, page 146). Forensic examination confirmed

tissue evidence of anaphylaxis. However, both exhibited clinical signs

within 4 hours of vaccination. Other than the 1946 case reports, none

of the other examples of ``anaphylaxis'' cited by the IOM, that began

after 4 hours of vaccination, was associated with permanent injury.

Again, Petitioners may receive compensation under the Program if they

prove their injury was caused by the vaccination, even if the onset was

after the 4 hours specified in the Table.

One commenter noted that the IOM Committee did not address the

timeframe within which to expect anaphylaxis. The commenter suggested

further that the Department should have taken into account the fact

that infants react differently than children and adults.

Although it is true that infants may react differently to illness

or medications, the pediatric literature is clear in stating that

severe anaphylactic reactions occur immediately with antigen exposure

and rarely show their first manifestation after 4 hours.

One commenter suggested that the proposed revision for DTP, MMR and

Polio fail to allow for delayed hypersensitivity.

The medical literature supports the conclusion that the more severe

anaphylactic reactions occur closer in time to the antigen exposure. An

anaphylactic reaction that shows its first manifestation greater than 4

hours after antigen exposure is likely to be a mild reaction and thus

very unlikely to lead to any permanent injury or sequelae. If a

petitioner is injured by a delayed hypersensitivity reaction,

compensation still can be awarded if causation in fact is proven.

One commenter suggested that the changes do not allow for hypoxia,

ischemia, or hypoxia/ischemia, which are common complications of

anaphylaxis and anaphylactoid shock. However, the proposed Table allows

for any sequela whose first sign or clinical manifestation falls within

Table guidelines, as long as the sequela is caused by the Table injury.

Encephalopathy

Much of the discussion of comments related to ``encephalopathy'' is

set forth above under the heading ``The Department's Interpretation of

the IOM Report.'' Set forth below are the remaining issues regarding

encephalopathy.

One commenter suggested that the initial sentence under the

definition of ``encephalopathy'' which states, ``[t]he term

encephalopathy means any acute or chronic significant acquired

abnormality of, or injury to, or impairment of function of the brain,''

is too vague and seems to contradict the more specific definitions

which follow the proposed subparagraphs (i) and (ii).

The Department had proposed to retain the language of the original

Aids to Interpretation to serve as an introduction to the definition of

encephalopathy. The Department agrees that it is imprecise, and that it

tends to differ from the guidance provided in the definitions for acute

and chronic [[Page 7687]] encephalopathy which immediately follow.

Accordingly, the proposed language in Sec. 100.3(b)(2) has been revised

to clarify the definitions for acute and chronic encephalopathy.

Comments concerning the criteria for the diagnosis of acute

encephalopathy (paragraphs (b)(2)(i) (A) and (B)) were offered by three

individuals. One commenter suggested that the criteria for the

diagnosis in the less than 24-month-old age group were too narrow and

restrictive. All three commenters felt there were clinical

inconsistencies in the specific criteria. One commenter felt it was an

unwarranted burden to require two out of three criteria in order to

satisfy the definition of acute encephalopathy (for children 24 months

of age or older). Some members of the ACCV felt that the definition of

acute encephalopathy for children over 24 months implies that a seizure

must last 24 hours to be within the definition. One commenter suggested

the definition was unlike any other employed in medicine or science.

The Department has considered carefully the concerns regarding the

definition of encephalopathy and offers the following responses.

The current Qualifications and Aids to Interpretation do not

reflect precisely medical knowledge of the condition

``encephalopathy.'' Many medical experts testifying in proceedings

under the VICP have stated the definition is too vague and needs

clarification. The term ``encephalopathy'' refers generally to a

disturbance of brain function. Clinical definitions vary, as do

opinions on the relationship between encephalopathy and seizures. After

several pages of discussion, the IOM finally defined it as

``encephalopathy, encephalitis, or encephalomyelitis.'' Unfortunately,

this definition is clinically imprecise, and in part circular. While it

may serve to evaluate studies on neurologic disease, it does not impart

guidance to physicians or attorneys on the specific clinical signs of a

child or adult with encephalopathy.

In an effort to define encephalopathy better, the Department used

the definition approved by the ACCV in 1991. The basic criteria were

taken from a peer-reviewed multi-center study assessing adverse events

following immunization in all age groups. (Fenichel GM., Lane DA,

Livengood JR, Horwitz SJ, Menkes JH, Schwartz JF. Adverse events

following immunization: Assessing probability of causation. Pediat

Neurol 1989; 5:287-290) One of its authors, a pediatric neurologist and

former ACCV Chairman, proposed that the Commission use the criteria as

the basic framework to define encephalopathy for purposes of making

changes to the Aids to Interpretation. Following its approval by the

ACCV, additional clarifications were needed to define better clinical

signs in the pre-verbal (less than 24-month) age group, and identify

correctly infants or children who may be experiencing temporary

medication effects, rather than true signs of encephalopathy. The

Department appreciates that the criteria are viewed by some as overly

burdensome. Any clarifications to the definition were for the sole

purpose of allowing non-physicians to identify correctly infants or

children with clinical signs of encephalopathy. However, the ACCV

during its June 1994 meeting suggested that some modifications be made

to the age criteria to reflect the fact that some children under 24

months have more advanced verbal skills. The Department agrees with

this suggestion and has, therefore, changed the age marker from 24 to

18 months for purposes of distinguishing between preverbal and verbal

children. Sec. 100.3(b)(2)(i).

Additionally, the Department agrees that the term ``stupor'' is

imprecise and somewhat restrictive, and has therefore decided to

specify the clinical signs reflective of an acute encephalopathy and

delete the terms ``stupor and coma.'' Acknowledging the difficulty of

defining ``encephalopathy,'' the Department has focused on clinical

criteria that clearly distinguish infants and children with brain

dysfunction from those with transient ``lethargy.'' The diminished

alertness and motor activity, which characterize the lethargic infant

or child, are frequently observed as the physiological response to

fever, infection or other acute illness. The severity and duration of

the behavioral changes differentiate mere lethargy from the more

serious impairment of consciousness that is the hallmark of

encephalopathy (i.e., obtundation, stupor and coma). To provide the

clearest guidance to petitioners' attorneys and the Court, the

Department has added a new paragraph (b)(2)(i)(D) to the section to

identify specific clinical signs constituting ``a significantly

decreased level of consciousness.''

As to concerns articulated by members of the ACCV during the June

1-2, 1994 meeting, the Department did not intend, in listing the signs

for identifying acute encephalopathy in children older than 24 months,

that a ``seizure associated with loss of consciousness'' persist for 24

hours. Rather, the Department intends that in order to be experiencing

an acute encephalopathy a child must experience a significantly altered

mental state or decreased level of consciousness. It is the child's

overall condition which must persist for 24 hours, rather than any one

particular seizure.

One of the ACCV members questioned the Department's decision to use

24 hours, rather than some other period, as the appropriate time period

under the definition of acute encephalopathy. The Department decided to

use 24 hours because this was the marker used in the multi-center study

cited above which established the criteria used by the Department in

drafting the definition of encephalopathy. See Fenichel, et al. The

choice of this time period is also consistent with the way in which

medical professionals gauge and document clinical changes over time.

One commenter suggested there is not a clear distinction between

acute and chronic encephalopathy. In response to this comment, the

Department has added additional language in the final rule for

clarification. For example, the Department revised the introductory

language of Sec. 100.3(b)(2) to make clear that an individual may be

found to have suffered an encephalopathy only if ``such recipient

manifests, within the applicable time period, an injury meeting the

description below of an acute encephalopathy, and then a change in

mental or neurological status persists in such person for more than 6

months beyond the date of vaccination.'' In addition, the Department

added similar language to Sec. 100.3(b)(2)(ii) to clarify the meaning

of chronic encephalopathy.

Two commenters suggested that the term ``neurologically normal''

may be inappropriate because children ``who return to a normal

neurological state after an acute encephalopathy,'' but later develop

signs of a chronic encephalopathy, may easily be misdiagnosed as normal

during this time period. Two commenters questioned whether the

definition ``neurologically normal'' should be based on various testing

criteria (e.g., CT or MRI scans, electroencephalogram (EEG), or lumbar

puncture). The Department has considered these comments and has revised

the first sentence in paragraph (b)(2)(ii) for clarification.

It is expected that any child or adult with a chronic

encephalopathy as a result of a vaccine-related acute encephalopathy

would show evidence of abnormalities in mental or neurological status

in the days to weeks following the vaccination. In the case of an

infant or child, these would be seen as a loss or slowing of

developmental milestones during this time period

[[Page 7688]] following the acute event. Because testing criteria and

the interpretation of results may vary with age group and medical

condition, no additional criteria are suggested for the diagnosis of

chronic encephalopathy. The Department agrees, however, that the Aids

to Interpretation should contain a clear distinction between acute and

chronic encephalopathy. As explained above, additional language has

been added in the final rule for clarification.

Members of the ACCV suggested the phrase ``return to a normal

neurological state'' was too vague, and failed to specify the methods

to be used for gauging a ``normal neurological state.'' These members

also suggested that there might not be any evidence in the medical

records to document this fact. The Department has considered this

suggestion, but has determined that the language in the definition of

chronic encephalopathy need not be changed. It is the Department's

intent that if all other parts of the definition are satisfied, the

presumption remains intact unless there is affirmative evidence that

the child returned to a normal neurological state; such evidence could

consist of documented subjective descriptions of the child's behavior

and development and/or objective findings on physical examinations

performed by physicians in the post-immunization period. Thus, in those

cases where this issue is unclear, or not documented, the presumption

would be that a child whose acute encephalopathy was followed by signs

of a persistent neurologic deficit did not return to a normal

neurological state.

During the June 1-2, 1994 meeting, members of the ACCV also

suggested that parts of the definition of encephalopathy in the

Qualifications and Aids to Interpretation as published in the NPRM were

too restrictive. Specifically, they took issue with the underlined

phrase of the introductory language of Sec. 100.3(b)(2)(i)(D), which

states that ``[t]he following clinical features alone, or in

combination, do not qualify as evidence of an acute encephalopathy or a

significant change in either mental status or level of consciousness as

described above * * *.'' The Department agrees with the commenters and

notes that this language did not reflect accurately the Department's

intent. The point of this language as written in the NPRM was further

to clarify the language as written in the NPRM was further to clarify

the language in the statute, which states that certain signs and

symptoms are compatible with an encephalopathy but ``in and of

themselves are not conclusive evidence of encephalopathy.'' 42 U.S.C.

300aa-14(b)(3)(A). The language in the statute has been interpreted in

many different ways by the Special Masters and has led to results in

some cases which the Department believes are inconsistent with the

medical and scientific literature on this topic. The medical evidence

indicates that certain symptoms do not conclusively establish an

encephalopathy, but instead are merely symptoms that are compatible

with an encephalopathy. Nevertheless, in order to take account of the

concerns of the ACCV, the Department has changed the underlined

language above to ``do not demonstrate.''

One commenter suggested that DTP may aggravate pre-existing genetic

or congenital conditions, and for that matter, other acquired

conditions.

The Department is aware that, in rare instances, a vaccine may

alter the clinical course of a pre-existing condition. Under section

2111(c)(1)(C) of the Act, ``significant aggravation'' of a pre-existing

condition may establish eligibility for compensation provided the

Petitioner is able to demonstrate that a Table injury occurred and that

the prior condition was significantly aggravated during the Table

timeframe, or is able to demonstrate proof of causation in fact.

In considering the comment, the Department realized that there

could be confusion regarding the issue of significant aggravation of

pre-existing conditions. Accordingly, the Department decided to

eliminate the proposed Sec. 100.3(b)(2)(v). Because the statute

includes a definition of ``significant aggravation,'' it is unnecessary

for this term to be defined in the final rule. See 42 U.S.C. 300aa-33;

section 2133 of Act.

As noted above, the Department received five comments in response

to the March 24, 1994, Federal Register notice soliciting comments

regarding the 1994 IOM report. Two comments, one submitted by the

American Academy of Pediatrics, and the other by a vaccine

manufacturer, expressed support for the revised Vaccine Injury Table as

presented in the NPRM. The commenters stated that further revisions to

the proposed Vaccine Injury Table are not warranted based on the

conclusions of the latest IOM review. The Academy of Pediatrics did

suggest, however, that the Table should reflect the ``possibility that

in some children with acute encephalopathy, chronic dysfunction may

subsequently exist, but this is a rare event and the data do not allow

confirmation or rejection of whether this is a direct association.''

The final rule reflects the concern articulated by the Academy. The

revised Table confers a presumption of causation on those individuals

who suffer an acute encephalopathy within 3 days after vaccine

administration, and who then go on to exhibit 6 months of residual

effects, followed by chronic neurological dysfunction.

The other three comments are discussed, where relevant, under the

heading ``The Department's Interpretation of the IOM Report.''

Hypotonic-Hyporesponsive Episode (HHE)

One commenter supported the removal of hypotonic-hyporesponsive

episode (HHE) from the original Table as proposed by stating that HHE

has no long-term effects and does not lead to death; the remaining

commenters were critical of the change. One commenter pointed out that

HHE is a heterogeneous term, which includes features of HHE and

anaphylaxis. It also includes a subset of children with ``unusual

shock-like states'' who have a ``lot-dependent, bimodal, or other form

of onset.'' It was suggested that the Department should give the

benefit of doubt in terms of causation to this group. One commenter

suggested features of collapse are life-threatening. The Department

responds as follows.

Although HHE is not well understood, there are consistent, albeit

rare, clinical signs reported to occur transiently following DTP

immunization. The onset in young infants is usually within 12 hours

following pertussis immunization. Clinical features include pallor,

fever, and decreased activity and responsiveness. Although these

infants may have a significantly decreased activity level and ``shock-

like'' appearance, actual loss of consciousness and hypotension (shock)

have not been demonstrated to occur. Disorders such as anaphylaxis

should easily be distinguishable from shock-collapse or HHE because of

the clearly defined physiologic changes known to occur with

anaphylaxis, which do not occur in HHE. See 1991 IOM Report, 171-186;

Cody CL, Baraff LJ, Cherry JD, March SM, Manclark CR. 1981. Nature and

rates of adverse reactions associated with DTP and DT immunizations in

infants and children. Pediatrics 68:650-660.

The 1991 IOM report found evidence ``consistent with a causal

relation'' between the pertussis vaccine and HHE (shock collapse), but

concluded there was insufficient evidence concerning chronic neurologic

damage. Because there is no proven relationship between HHE and

residual neurologic damage, [[Page 7689]] no purpose is served by

retaining HHE on the Table. Removing HHE as a Table injury places the

burden of proof on the petitioner that an HHE was caused by a vaccine

and that it resulted in death or residual effects lasting at least 6

months.

Additional comments were received in response to the Notice

published on March 24, 1994, requesting comments on the Miller study

and 1994 IOM report. Two commenters argued that the conclusions of this

IOM report are inconsistent with the Department's proposal to remove

HHE from the Vaccine Injury Table. The commenters suggested that

because the Qualifications and Aids to Interpretation include ``loss of

consciousness'' as one of the symptoms of HHE, and because the NCES

would have included a severe shock-collapse resulting in

hospitalization as a serious, acute neurologic illness, it is

appropriate for HHE to continue to receive the presumption of causation

conferred by the Table.

It is important to understand that the Miller study did not purport

to set forth a definition of ``encephalopathy'' for purposes of the

VICP or the Vaccine Injury Table. Rather, it simply defined a set of

conditions which fell under the rubric of ``acute neurologic illness''

that could be studied in relation to the administration of DTP vaccine.

Loss of consciousness is not a recognized sign of HHE (see Cody et

al.), notwithstanding its inclusion in the original statutory

Qualifications and Aids to Interpretation. The Department recognizes

that the 1991 IOM Report included among the symptoms of HHE a loss of

consciousness. However, the Department believes that this simply

reflected some of the case reports in the literature that were reviewed

by the IOM. Given the IOM's statement that the cases reported may

include other conditions, such as anaphylaxis, the Department does not

view the IOM's discussion as a sufficient basis to expand its view of

what properly constitutes HHE. See 1991 IOM Report, p. 171-177. Rather,

children experiencing a loss of consciousness should properly be

considered under the rubric of encephalopathy. Furthermore, there is no

clear evidence that HHE (1) represents acute neurologic dysfunction,

(2) requires medical intervention (although medical consultation is

frequently sought), or (3) leads to any permanent sequelae or death. It

is unlikely that nay of the cases described in the NCES were those of

infants experiencing HHE. In light of these considerations, the

Department concludes that there is an insufficient basis to retain HHE

as a separate category on the Table.

Residual Seizure Disorder

One commenter suggested that some of the seizure classifications

under Residual Seizure Disorder are out of date. They cited the example

of ``grand mal'' seizures which has been dropped from the International

Classification of Diseases. The commenter also questioned the use of

the word ``signs'' in this section. The Department agrees with the

commenter that some of the original seizure terminology has changed

over time. Section 100.3(b)(4) has been revised and the word ``signs''

has been deleted from the text.

One commenter objected to proposed paragraph (b)(3)(ii) regarding

the 24-hour requirement for separation of seizures under Residual

Seizure Disorder. The commenter disagreed that a 24-hour separation in

seizures makes the diagnosis of recurrent seizures (epilepsy) more

likely, and that seizures occurring on the same day are generally

regarded as part of the same event.

The Department intends that the 24-hour requirement for the

separation of seizures will make it more likely that a Petitioner who

qualifies under Residual Seizure Disorder has a recurring seizure

disorder (epilepsy). The study cited in the NPRM, (Reference: Hauser

WA. et al: Seizure recurrence after a first unprovoked seizure. NEJM

1982; 307(9):522-528), shows that seizures separated by more that 24

hours make a recurrent disorder more likely. Its importance is

underscored by the fact that seizures commonly occur in clusters. For

purposes of predicting recurrence of seizures, those occurring within a

24-hour period are generally viewed as a single event (with the same

cause). It is likely that any petitioner who experiences a vaccine-

related epileptic disorder will still qualify by having further

seizures over the 12-month period specified under the statute. See

section 2114(b)(2)(A) of the Act.

Recognizing the commenter's concerns, and in the interest of

clarity, the Department has modified slightly the definition of a

distinct seizure episode for purposes of this section. The last

sentence of Sec. 100.3(b)(3)(i) now reads, ``A distinct seizure or

convulsion episode is ordinarily defined as including all seizure or

convulsive activity occurring within a 24-hour period, unless competent

and qualified expert neurologic testimony is presented to the contrary

in a particular case.''

Two commenters did not agree with the language in paragraph (b)(4)

that absence (petit mal) epilepsy is not associated with acute

encephalopathy secondary to DTP immunization. Both suggested that the

diagnosis be determined by requiring such a child to have an EEG with

3-per-second spike-and-wave, since it is known that children who have

such minor seizures with different EEG's are often the victims of

severe brain damage and should not be excluded. Finally, it was

suggested that the phrase ``if properly diagnosed'' be used under these

conditions. The Department's response to these comments is as follows.

There is little credible evidence to support the conclusion that

absence (petit mal) epilepsy is associated with acute encephalopathy

following vaccination. It is true, however, that atypical absence and

other forms of spike-and-wave epilepsy may be the sequelae of an acute

encephalophathy, but are not in themselves the features of such.

Following acute encephalopathy, features of atypical absence seizures

may develop months to years later as part of the sequelae to the acute

injury. Other types of staring behavior may constitute seizure activity

associated with an acute encephalopathy, such as an individual with

Herpes simplex type 1 encephalitis. However, these patients typically

present with other clinical signs of acute encephalopathy. (Generalized

Seizures: Absence. In Dreifuss F. (ed): Pediatric Epileptology. Boston,

J. Wright/PSG, 1983, p. 65-91.) It also should be noted that seizures

alone do not constitute an encephalopathy. (1991 IOM Report, page 87).

Requiring EEG confirmation of 3-per-second spike-and-wave to make

the diagnosis of absence (petit) epilepsy may be excessively

restrictive. While patients may have these characteristic EEG findings,

it is neither practical nor advisable to require that the EEG

constitute the basis for diagnosis. Frequently, absence (petit mal)

epilepsy is diagnosed on clinical criteria alone, (i.e., expected age

group, seizure behavior, relationship to hyperventilation and/or

response to ethosuximide therapy). It is therefore impractical to

require EEG confirmation. Furthermore, inserting the phrase ``if

properly diagnosed'' would create confusion as to whether EEG

confirmation is necessary for the diagnosis of this condition.

One commenter suggested it is incorrect to state that petit mal and

absence seizures are the only types of seizure activity with which

staring can be associated. The Department agrees, and did not intend to

imply such in the Preamble to the NPRM. Other [[Page 7690]] conditions

associated with staring, such as atypical absence epilepsy, or various

sequelae to central nervous system injury are noted above in the

Department's response under absence (petit mal) epilepsy.

One commenter suggested that the Department has shown no evidence

that pertussis-related febrile seizures have more benign outcomes than

those induced by other agents. The commenter states that because the

literature shows that a small percentage of children who experience

febrile seizures go on to have permanent problems, the Department's

findings that there is insufficient evidence are erroneous. One

commenter suggested febrile seizures produce brain damage. Another

commenter suggested that not every seizure which is contemporaneous

with a fever is a febrile seizure. The Department agrees in part, and

disagrees in part with these comments for the following reasons.

The term ``febrile seizure'' refers to seizures in infancy or

childhood (between 3 months to 5 years of age) associated with fever,

but without evidence of intracranial infection or other defined cause.

Infants or children who have a pre-existing history of an afebrile

seizure, or recurrent afebrile seizures (epilepsy) are not included in

this category.

While it is true that children with a history of ``febrile

seizures'' may eventually show neurologic deficits, there is no

persuasive experimental or epidemiologic evidence that these deficits

are a result of neurologic injury occurring at the time of the febrile

seizure. Furthermore, there is no evidence that febrile seizures affect

intellectual performance as judged by comparison of affected children

to their siblings. (Consensus Statement. 1980. Febrile seizures: long

term management of children with fever-associated seizures. Pediatrics

66:1009-1012) (Ellenberg JH, Nelson KB. Febrile seizures and later

intellectual performance. Arch Neurol 1978;35:17-21)

Although the IOM concluded ``febrile seizures'' are causally

related to DTP vaccine, most experts believer that febrile seizures do

not cause permanent damage. The clinical courses of children

experiencing febrile seizures following DTP vaccination are

indistinguishable from the clinical courses of children who experience

febrile seizures from other causes. (Hirtz DG, et al. Seizures

following childhood immunizations. J. Pediatr. 1983;314:1085-1088)

While febrile seizures are by their very nature benign, and

therefore not associated with permanent damage, not all seizures

contemporaneous with fever are ``febrile seizures.'' This latter group

of seizures may be the result of pre-existing neurologic disease or

injury, which produces a predisposition to seizure activity with

elevated temperature. Alternatively, one can have an acute

encephalopathy which presents itself as fever and seizures (e.g.,

meningitis). In such a case, the other requisite clinical

manifestations of clinical encephalopathy should be present (i.e.,

diminished consciousness and/or focal or generalized neurologic signs).

One commenter disagreed with the exclusion of infantile spasms. One

commenter noted that the diagnosis for infantile spasms has no

etiological significance. It was suggested there is no medical support

to eliminate this type of seizure disorder from those potentially

compensated. One commenter suggested that it is inappropriate to

exclude infantile spasms, as the U.S. Court of Federal Claims has ruled

that DTP causes infantile spasms. The Department has considered these

comments and offers the following clarification.

The IOM concluded infantile spasms is not casually related to DTP

vaccination. Therefore, there is no basis for a legal presumption of

causation for this condition when it follows DTP vaccination.

Petitioners have the right to prove causation in fact in instances in

which infantile spasms has its onset following immunization.

The U.S. Court of Federal Claims has held that seizures diagnosed

as infantile spasms can be considered a Table injury if the requisite

timeframes are met. The Court has held that the respondent cannot claim

that infantile spasms is a factor unrelated to vaccine administration

unless the precise cause of the infantile spasms can be identified. The

Court's reasoning was based on a technical interpretation of the

statute, and does not purport to be an analysis of the medical issues

involved. Furthermore, the Court's analysis relied, of course, on the

initial Table. It cannot be viewed as relevant to the actual causation

issue which is the basis for revising the Table. See Johnston v.

Secretary of HHS, 22 Cl. Ct. 75 (1990).

Nevertheless, the Department has decided to remove all references

to infantile spasms from the final rule. This decision was made based

purely on procedural grounds. The Department concluded that this issue

is more appropriately addressed in the ``factor unrelated'' section of

the statute (42 U.S.C. 300aa-13(b)), rather than as part of the Vaccine

Injury Table. The decision to revise the rule in this manner does not

affect the Department's findings regarding infantile spasms (based on

the IOM report), nor should it be viewed as inconsistent with the

Department's response to the commenters' concerns. The Department

continues to believe that deciding cases involving infantile spasms,

the Court of Federal Claims should rely heavily on the IOM's conclusion

that the evidence does not indicate a causal relationship between

pertussis vaccine and infantile spasms.

One commenter claims to have concluded ``within medical certainty''

that chronic neurologic damage occurred in children who had acute

afebrile seizures within the timeframes of the current Table of

injuries, and as manifestations of acute encephalopathies. The

commenter does not, however, provide sufficient evidence to justify a

revision of the proposed language.

The IOM concluded that afebrile seizures are not causally related

to DTP vaccine. They considered many studies, including one which

showed that short-lived convulsions, with or without fever, have not

been demonstrated to cause permanent sequelae, regardless of whether

the seizures occur in association with receipt of DTP. vaccine. (IOM

Report p. 118) (Hirtz DG. et al. Seizures following childhood

immunizations. J. Pediatr. 1983; 102:14-18. and Ellenberg JH, Hirtz DG,

Nelson KB. Do seizures in children cause intellectual deterioration?

NEJM 1986; 314:1085-1088) (Ad Hoc Committee for the Child Neurology

Society. Consensus Statement: Pertussis immunization and the central

nervous system. Ann. of Neuro. 1991; 29 (4): 458-460).

The Department also reversed the order of Sec. 100.3(b)(3)(i) and

Sec. 100.3(b)(3)(ii). This change was made to make the order of these

two subparagraphs more logical.

In response to the March 24, 1994, Federal Register Notice

requesting comments on the 1994 IOM Report, two commenters argued that

because seizures were included in the definition of encephalopathy and

chronic nervous system dysfunction used by the NCES, the Department

should not remove residual seizure disorder from the Table.

The Department disagrees with the commenters on this point. As

discussed above, the 1991 IOM report concluded that no causal

relationship can be proven between DTP and afebrile seizures. In its

1994 report, the IOM did not retract any of its 1991 conclusions

regarding DTP and seizure disorders. It merely recognized that the NCES

included seizures as one of those conditions to be monitored or

purposes [[Page 7691]] of tracking long-term dysfunction. This

recognition does not provide any information one way or the other

regarding causation.

Crucial to understanding the Department's response is the knowledge

that the working definition of ``acute neurologic illness'' used in the

NCES is not consistent with the current medical understanding of acute

encephalopathy as an acute, generalized disorder of the brain. Children

were placed in the NCES case definition who experienced only febrile

seizures, a benign condition know to be triggered by DTP vaccine, yet

never proven to have lasting effects absent signs of acute

encephalopathy. Thus, placing seizures in the NCES case definition of

encephalopathy is inconsistent with the current medical understanding

of acute encephalopathy. Moreover, both the IOM and the NVAC

subcommittee agreed that there is no evidence that chronic

encephalopathy in the absence of acute post-immunization encephalopathy

is causally related to the vaccine. Therefore, there is no basis for

providing a legal presumption of vaccine causation for chronic effects

based solely on the occurrence of a seizure following DTP immunization.

There is simply no need for, nor is there medical evidence to support,

a separate presumption for residual seizure disorder in connection with

DTP vaccine.

Sudden Infant Death Syndrome

Two commenters suggested there is not a clear distinction between a

death characterized as Sudden Infant Death Syndrome (SIDS) and one that

is vaccine-related (paragraph (b)(2)(iii) of the NPRM).

The IOM concluded that SIDS is not causally related to DTP vaccine.

This conclusion was based on several controlled epidemiologic studies

involving hundreds of thousands of vaccinations. Although the diagnosis

of SIDS is one of exclusion of other causes, there are specific

guidelines as to the history preceding death, findings on forensic

examination, and the ruling out of other causes by death scene

examination (when possible). Moreover, the possibility that DTP-related

deaths are commonly misclassified as SIDS was also considered by the

IOM Committee. Since there was no evidence of an increased risk of SIDS

following DTP immunization, or of any observable ``pertussis death

syndrome,'' the committee considered that such effects were not

supported by the medical literature. In addition, those studies that

examined infant deaths other than SIDS in relation to DTP vaccine also

demonstrated no excess risk in the post-immunization interval. This

observation argues against the possibility that DTP-related deaths were

missed as a result of their being misclassified as deaths other than

SIDS. (Correspondence from Christopher P. Howson, Ph.D., Project

Director, Committee to Review the Adverse Consequences of Pertussis and

Rubella Vaccines to Dr. George Curlin, Deputy Director, Division of

Microbiology and Infectious Diseases, National Institute of Allergy and

Infectious Diseases: 9/18/91)

Nevertheless, as with infantile spasms, the Department has decided

to remove all references to Sudden Infant Death Syndrome from the final

rule. This decision, too, was made based purely on procedural grounds.

The Department concluded (as with infantile spasms) that this issue is

more appropriately addressed in the ``factor unrelated'' section of the

statute (42 U.S.C. Sec. 300aa-13(b)), rather than as part of the

Vaccine Injury Table. The decision to make this change does not affect

the Department's findings regarding SIDS (based on the IOM report), nor

should it be viewed as inconsistent with the above analysis regarding

the Department's response to the commenters' concerns. The Department

continues to believe that in deciding cases involving SIDS, the Court

of Federal Claims should rely heavily on the IOM's conclusion that the

evidence does not indicate a causal relationship between pertussis

vaccine and SIDS.

Tuberous Sclerosis Complex

One commenter suggested that the proposed revisions do not take

into account the condition of tuberous sclerosis complex (TSC), which

some believe can be aggravated by DTP vaccine. Since DTP vaccine can

cause fevers which trigger seizures, there remains a question whether

someone with TSC would have a worse outcome as a result of a seizure

following a DTP shot. One commenter suggested that infantile spasms is

frequently associated with TSC and the U.S. Court of Federal Claims has

found compensable infantile spasms cases that manifested after DTP

vaccine. The Department provides the following clarification regarding

the effect the new Table will have on individuals with TSC.

TSC is a genetic disorder manifested chiefly as mental deficiency,

epilepsy and skin lesions. Seizures occur in 80-90 percent of

individuals with tuberous sclerosis. This disorder frequently presents

in infancy, commonly in the form of infantile spasms. Some petitioners

have argued that administration of a DTP vaccine can significantly

aggravate a case of TSC.

The Act provides two avenues of proof in order to establish

eligibility for compensation. A petitioner is afforded a presumption of

causation if he/she can establish that an injury listed in the Table

occurred within the specified time period. Otherwise, the petitioner

may argue that an injury occurred which is not listed in the Table, but

which was nonetheless caused by the vaccine. The TSC cases presented to

the Court, some petitioners who sought to establish a Table case argued

that the child experienced seizures within 3 days of receipt of a

vaccine and that this event significantly aggravated the pre-existing

TSC. Some petitioners who were unable to establish Table cases argued

that although the child did not sustain an injury listed in the Vaccine

Injury Table, the vaccine nonetheless was the cause-in-fact of the

aggravation of the underlying Tuberous Sclerosis. In either case, the

petitioner had the burden of proving that the clinical course of the

pre-existing condition had been significantly aggravated. Typically,

petitioners presented expert testimony to support this theory.

The revisions to the Vaccine Injury Table do not, by and large,

change the petitioner's burden of proof in TSC cases. The only

difference is that there is not a presumption of causation for residual

seizure disorders for DTP vaccine. As explained in the preamble to the

NPRM, and reiterated here, the IOM concluded that there is no causal

relation between pertussis vaccine and afebrile seizures. However, to

receive a presumption of causation, petitioners may still argue that an

encephalopathy (as defined in the revised Qualifications) occurred

within 3 days of vaccine administration and that this encephalopathy

significantly aggravated the pre-existing Tuberous Sclerosis. In

addition, petitioners may continue to argue that the vaccine was the

cause-in-fact of the aggravation of the TSC. As far as infantile spasms

is concerned, the Department has removed all references to this

condition from the final rule as explained above. Therefore,

petitioners have available to them the same avenues of proof open to

individuals with other types of seizures.

One commenter noted that MMR frequently triggers epilepsy in

children with TSC. The same analysis as above applies. Here, the

petitioner may take advantage of the presumption of causation if he or

she is able to prove either a Table encephalopathy, or a Table residual

seizure disorder, and that that injury significantly aggravated the

underlying TSC. If the evidence does [[Page 7692]] not demonstrate that

the case meets the requirements of the Table, the case will be

evaluated based on a causation theory.

Diphtheria/Tetanus Vaccines (DT, TD, TT)

One commenter suggested that making changes to non-pertussis

components based on studies of pertussis vaccine is inappropriate.

Although the section 312 study (``IOM Report'') did not

specifically study the non-pertussis antigens of DTP vaccine (i.e.,

diphtheria, tetanus), most individuals receiving pertussis antigen,

also were given these antigens. Therefore, some inferential data is

present. Moreover, studies reveal little evidence that these antigens

are causally related to the injuries currently listed in the Table

under DTP, other than Anaphylaxis. In the section 313 study, the IOM

concluded that the evidence favored rejection of a causal relation

between DT/Td/TT and encephalopathy. After review of the section 313

Report, the Department may promulgate additional changes to the Table.

MMR Vaccines

One commenter suggested that the requirement for at least 5 days of

viral replication is inappropriate. One commenter suggested that the

changes for encephalopathy are wrong because there is a broad spectrum

of severity. Sequelae may occur after less serious acute

encephalopathy. The proposed changes would exclude all but the most

severe acute encephalopathies from the Table. The Department has

considered these comments, but has concluded that the medical evidence

supports the proposed changes.

Since viral replication is required for a viral vaccine-associated

encephalopathy, a window for the expected time of onset is appropriate.

The onset of vaccine-related illness following MMR (or any of its

components) is generally from 7 to 14 days, thus a time interval of 5

to 15 days would be all-inclusive. Any acute encephalopathy of unknown

cause, regardless of severity or duration, that occurs during the 5 to

15 day time frame would be eligible for the Table presumption, provided

the child or adult has continued evidence of ``chronic

encephalopathy.'' The 1991 NVAC Subcommittee felt there was strong

support in the literature to narrow the timeframe as above. Some felt

Residual Seizure Disorder should be removed from the Table based on the

lack of evidence for causation in the current medical literature. This

was not done because it went significantly beyond the scope of changes

proposed by the PHS Task Force. However, at that time, the Subcommittee

recognized additional changes may be forthcoming once the section 313

study results are published and have been reviewed. Since the

Subcommittee's original discussion on this issue, the IOM issued its

section 313 report. The IOM concluded for both encephalopathy and

residual seizure disorder that the evidence is inadequate to accept or

reject a causal relation. After review of the 313 Report, the

Department may promulgate additional changes to the Table based on this

conclusion.

One commenter suggested that the evidence for an association

between rubella vaccine and chronic arthritis is inconclusive. The

section 312 IOM Committee concluded that the evidence is ``consistent

with a causal relation'' between the currently used rubella vaccine (RA

27/3) and chronic arthritis in adult women, although the evidence is

limited in scope and confined to reports from one institution. To

establish this biologically plausible relation more firmly, the

Committee expressed the need for prospective, double-blind, controlled

trials in which individuals are followed for at least 12 months after

vaccination with attempts to isolate and identify rubella virus. At

least one medical research center is pursuing this research to try and

obtain better data on causation.

Many investigators still view the evidence as inconclusive with

regard to chronic arthritis. However, the IOM's finding justifies the

inclusion of chronic arthritis on the Vaccine Injury Table since there

is biologic plausibility of causation, and the term ``chronic

arthritis'' is defined as effects lasting greater than 6 months. In

this instance, the IOM is stating there is ``consistent'' evidence for

both acute onset and residual effects lasting greater than 6 months.

Previously described changes for Table injuries under DTP involved

conditions (i.e., HHE and Residual Seizure Disorder) that the IOM did

not view as having strong evidence for both acute and chronic effects.

Although the Department added chronic arthritis to the Table,

guidelines written into the Aids to Interpretation will preclude

patients with pre-existing conditions or other non-vaccine related

musculoskeletal disorders from being legally presumed to have a

vaccine-related injury. As information from prospective studies becomes

available, modifications may be made to the Table or Aids to

Interpretation based on this data.

Polio Vaccines

Two commenters suggested that Inactivated Polio Vaccine (IPV),

known as the Salk vaccine, may be proven to be causally related to

poliomyelitis. The IOM evaluated the relationship between polio

vaccines and adverse events in its section 313 study. Except for the

1955 incident with inadequate inactivation of live polio virus in the

Cutter Company supply of IPV, there have been no serious adverse events

causally tied to this vaccine. Since the ``Cutter Incident,'' when

manufacturing and testing difficulties were identified and corrected,

the safety of released inactivated Poliovirus vaccine has been assured.

(See IOM Section 313 Report at 188,; see also Bodian, D., et al.

Interim Report, Public Health Service Technical Committee on

Poliomyelitis Vaccine. JAMA:1444-7, 1955) Furthermore, no serious side

effects of currently available inactivated poliovirus vaccines have

been documented. (Report of the Committee on Infectious Diseases,

American Academy of Pediatrics 1991:389) Because these earlier problems

have been cured, and there is no current evidence bearing on a causal

relationship, the section 313 study does not discuss specifically the

connection between IPV and poliomyelitis. Therefore, there is no

evidence of a causal relationship which would justify adding

poliomyelitis to the Table for IPV.

Other Changes

At the meeting on June 1-2, 1994, members of the ACCV suggested

that the definition of ``sequela'' imposes a higher burden of proof

than that required by the statute. The Department disagrees that the

definition affects the burden of proof, but agrees that the definition

as written should be simplified. Accordingly, the definition in

Sec. 100.3(b)(5) has been modified to read as follows: ``The term

sequela means a condition or event which was actually caused by a

condition listed in the Vaccine Injury Table.'' This definition is

consistent with current scientific understanding that in order for a

subsequent event to be considered a sequela of an initial event, there

must be a causal relationship between the two.

Technical Changes

First, in publishing the NPRM, the Department inadvertently

misquoted the statutory introduction to the Vaccine Injury Table.

Accordingly, the introductory paragraph of Sec. 100.3(a) now reads as

follows: ``In accordance with section 312(b) of the National Childhood

Vaccine Injury Act of 1986, [[Page 7693]] title III of Pub. L. 99-660

(42 U.S.C. 300aa-note) and section 2114(c) of the Public Health Service

Act (42 U.S.C. 300aa-14(c)), the following is a table of vaccines, the

injuries, disabilities, illnesses, conditions, and deaths resulting

from the administration of such vaccines, and the time period in which

the first symptom or manifestation of onset or of the significant

aggravation of such injuries, disabilities, illnesses, conditions, and

deaths is to occur after vaccine administration for purposes of

receiving compensation under the Program:''

Second, we are revising Sec. 100.3(c), entitled ``Effective date

provisions.'', to change the term ``United States Claims Court''

wherever it appears to read ``United States Court of Federal Claims'',

in accordance with section 902(b) of title IX, Pub. L. 102-572, the

Federal Courts Administration Act of 1992 (See 106 Stat. 4516).

In addition, the Department is making a technical change to the

existing regulations (42 CFR part 100) by revising the currently

codified acronym used to refer to the National Vaccine Injury

Compensation Program from ``NVIC'' to ``VICP'' wherever it appears

under part 100. ``VICP'' has been used for the entire history of the

program to avoid confusion with the parents' advocacy group known as

the National Vaccine Information Center (NVIC), Dissatisfied Parents

Together (DPT).

Since these changes are of a technical nature, the Secretary has

determined pursuant to 5 U.S.C. 553 and departmental policy that it is

unnecessary and impractical to follow proposed rulemaking procedures.

Economic Impact

The NPRM preamble erred in not explaining that this 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. Attorneys, while small entities within the meaning of the

Act, will still be awarded costs and fees for cases they bring on a

reasonable basis. The reduced number of vaccine cases brought will be

negligible measured against overall business opportunities for lawyers.

Therefore, SBA is incorrect in saying that a regulatory flexibility

analysis is required. Therefore, the Secretary certifies that this

final rule will not have a significant economic impact on a substantial

number of small entities.

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 final regulation modifies 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. For the same reasons, the Secretary has also

determined that this is not a ``significant'' rule under Executive

Order 12866.

Effect of the New Rule

The NPRM failed to explain the effect of the rule for individuals

who were not eligible to file petitions based on the original 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 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 vaccine-

related arthritis 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 arthritis to the Table as a rubella vaccine-

related condition has significantly increased the likelihood of

obtaining compensation. The Department believes that the amendment

would not permit someone who had had a claim for an alleged vaccine-

related encephalopathy subsequent to DTP vaccine to refile a claim that

had been dismissed by the Claims Court, as the changes in the Table

related to DTP and encephalopathy do not appear to significantly

increase the likelihood of obtaining compensation.

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 final rule modifies 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 final rule has no information collection requirements.

List of Subjects in 42 CFR Part 100

Biologics, Health insurance, Immunization.

Dated: November 16, 1993.

Philip R. Lee,

Assistant Secretary for Health.

Approved: November 9, 1994.

Donna E. Shalala,

Secretary.

Accordingly, 42 CFR part 100 is 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, the Vaccine Injury Table, issued under

sec. 312 of Pub. L. 99-660, 100 Stat. 3779 (42 U.S.C. 300aa-1 note)

and sec. 2114(c) of the PHS Act (42 U.S.C. 300aa-14(c)).

2. Section 100.1 is revised to read as follows:

Sec. 100.1 Applicability.

This part applies to the National Vaccine Injury Compensation

Program (VICP) under subtitle 2 of title XXI of the Public Health

Service (PHS) Act.

3. The first sentence in Sec. 100.2 is revised to read as follows:

Sec. 100.2 Average cost of a health insurance policy.

For purposes of determining the amount of compensation under the

VICP, section 2115(a)(3)(B) of the PHS Act, 42 U.S.C.

300aa.15(a)(3)(B), provides that certain individuals are entitled to

receive an amount reflecting [[Page 7694]] lost earnings, less certain

deductions. * * *

4. Section 100.3 is added to read as follows:

Sec. 100.3 Vaccine injury table.

(a) In accordance with section 312(b) of the National Childhood

Vaccine Injury Act of 1986, title III of Pub. L. 99-660, 100 Stat. 3779

(42 U.S.C. 300aa-1 note) and section 2114(c) of the Public Health

Service Act (42 U.S.C. 300aa-14(c)), the following is a table of

vaccines, the injuries, disabilities, illnesses, conditions, and deaths

resulting from the administration of such vaccines, and the time period

in which the first symptom or manifestation of onset or of the

significant aggravation of such injuries, disabilities, illnesses,

conditions, and deaths is to occur after vaccine administration for

purposes of receiving compensation under the Program:

Vaccine Injury Table

----------------------------------------------------------------------------------------------------------------

Time period for first symptom or

manifestation of onset or of

Illness, disability, injury or condition covered significant aggravation after

vaccine administration

----------------------------------------------------------------------------------------------------------------

I. DTP; P; DT; Td; or Tetanus Toxoid; or in any combination with Polio; or

any Other Vaccine Containing Whole Cell Pertussis Bacteria, Extracted or

Partial Cell Pertussis Bacteria, or Specific Pertussis Antigen(s):

A. Anaphylaxis or anaphylactic shock..................................... 4 hours.

B. Encephalopathy (or encephalitis)...................................... 72 hours.

C. Any sequela (including death) of an illness, disability, injury, or Not applicable.

condition referred to above which illness, disability, injury, or

condition arose within the time period prescribed.

II. (a). Measles, mumps, rubella, or any vaccine containing any of the

foregoing as a component:

A. Anaphylaxis or anaphylactic shock..................................... 4 hours.

B. Encephalopathy (or encephalitis)...................................... 5-15 days (not less than 5 days

and not more than 15 days) for

measles, mumps, rubella, or any

vaccine containing any of the

foregoing as a component.

C. Residual seizure disorder in accordance with subsection (b)(3)........ 5-15 days (not less than 5 days

and not more than 15 days) for

measles, mumps, rubella, or any

vaccine containing any of the

foregoing as a component.

D. Any sequela (including death) of an illness, disability, injury, or Not applicable.

condition referred to above which illness, disability, injury, or

condition arose within the time period prescribed.

II. (b). In the case of measles, mumps, rubella (MMR), measles, rubella (MR)

or rubella vaccines only:

A. Chronic arthritis..................................................... 42 days.

B. Any sequela (including death) of an illness, disability, injury, or Not applicable.

condition referred to above which illness, disability, injury, or

condition arose within the time period prescribed.

III. Polio Vaccine (other than Inactivated Polio Vaccine):

A. Paralytic Polio

In a non-immunodeficient recipient................................... 30 days.

In an immunodeficient recipient...................................... 6 months.

In a vaccine associated community case............................... Not applicable.

B. Any acute complication or sequela (including death) of an illness, Not applicable.

disability, injury, or condition referred to above which illness,

disability, injury, or condition arose within the time period prescribed.

IV. Inactivated Polio Vaccine:

A. Anaphylaxis or anaphylactic shock..................................... 4 hours.

B. Any acute complication or sequela (including death) of an illness, Not applicable.

disability, injury, or condition referred to above which illness,

disability, injury, or condition arose within the time period prescribed.

----------------------------------------------------------------------------------------------------------------

(b) Qualifications and aids to interpretation. The following

qualifications and aids to interpretation shall apply to the Vaccine

Injury Table in paragraph (a) of this section:

(1) Anaphylaxis and anaphylactic shock. For purposes of paragraph

(a) of this section, Anaphylaxis and anaphylactic shock mean an acute,

severe, and potentially lethal systemic allergic reaction. Most cases

resolve without sequelae. Signs and symptoms begin minutes to a few

hours after exposure. Death, if it occurs, usually results from airway

obstruction caused by laryngeal edema or bronchospasm and may be

associated with cardiovascular collapse. Other significant clinical

signs and symptoms may include the following: Cyanosis, hypotension,

bradycardia, tachycardia, arrhythmia, edema of the pharynx and/or

trachea and/or larynx with stridor and dyspnea. Autopsy findings may

include acute emphysema which results from lower respiratory tract

obstruction, edema of the hypopharynx, epiglottis, larynx, or trchea

and minimal findings of eosinophilia in the liver, spleen and lungs.

When death occurs within minutes of exposure and without signs of

respiratory distress, there may not be significant pathologic findings.

(2) Encephalopathy. For purposes of paragraph (a) of this section,

a vaccine recipient shall be considered to have suffered an

encephalopathy only if such recipient manifests, within the applicable

period, an injury meeting the description below of an acute

encephalopathy, and then a chronic encephalopathy persists in such

person for more than 6 months beyond the date of

vaccination. [[Page 7695]]

(i) An acute encephalopathy is one that is sufficiently severe so

as to require hospitalization.

(A) For children less than 18 months of age who present without an

associated seizure event, an acute encephalopathy is indicated by a

significantly decreased level of consciousness lasting for at least 24

hours. Those children less than 18 months of age who present following

a seizure shall be viewed as having an acute encephalopathy if their

significantly decreased level of consciousness persists beyond 24 hours

and cannot be attributed to a postictal state (seizure) or medication.

(B) For adults and children 18 months of age or older, an acute

encephalopathy is one that persists for at least 24 hours and

characterized by at least two of the following:

(1) A significant change in mental status that is not medication

related; specifically a confusional state, or a delirium, or a

psychosis;

(2) A significantly decreased level of consciousness, which is

independent of a seizure and cannot be attributed to the effects of

medication; and

(3) A seizure associated with loss of consciousness.

(C) Increased intracranial pressure may be a clinical feature of

acute encephalopathy in any age group.

(D) A ``significantly decreased level of consciousness'' is

indicated by the presence of at least one of the following clinical

signs for at least 24 hours or greater (see paragraphs (b)(2)(i)(A) and

(b)(2)(i)(B) of this section for applicable timeframes):

(1) Decreased or absent response to environment (responds, if at

all, only to loud voice or painful stimuli);

(2) Decreased or absent eye contact (does not fix gaze upon family

members or other individuals); or

(3) Inconsistent or absent responses to external stimuli (does not

recognize familiar people or things).

(E) The following clinical features alone, or in combination, do

not demonstrate an acute encephalopathy or a significant change in

either mental status or level of consciousness as described above:

Sleepiness, irritability (fussiness), high-pitched and unusual

screaming, persistent inconsolable crying, and bulging fontanelle.

Seizures in themselves are not sufficient to constitute a diagnosis of

encephalopathy. In the absence of other evidence of an acute

encephalopathy, seizures shall not be viewed as the first symptom or

manifestation of the onset of an acute encephalopathy.

(ii) Chronic Encephalopathy occurs when a change in mental or

neurologic status, first manifested during the applicable time period,

persists for a period of at least 6 months from the date of

vaccination. Individuals who return to a normal neurologic state after

the acute encephalopathy shall not be presumed to have suffered

residual neurologic damage from that event; any subsequent chronic

encephalopathy shall not be presumed to be a sequela of the acute

encephalopathy. If a preponderance of the evidence indicates that a

child's chronic encephalopathy is secondary to genetic, prenatal or

perinatal factors, that chronic encephalopathy shall not be considered

to be a condition set forth in the Table.

(iii) An encephalopathy shall not be considered to be a condition

set forth in the Table if in a proceeding on a petition, it is shown by

a preponderance of the evidence that the encephalopathy was caused by

an infection, a toxin, a metabolic disturbance, a structural lesion, a

genetic disorder or trauma (without regard to whether the cause of the

infection, toxin, trauma, metabolic disturbance, structural lesion or

genetic disorder is known). If at the time a decision is made on a

petition filed under section 2111(b) of the Act for a vaccine-related

injury or death, it is not possible to determine the cause by a

preponderance of the evidence of an encephalopathy, the encephalopathy

shall be considered to be a condition set forth in the Table.

(iv) In determining whether or not an encephalopathy is a condition

set forth in the Table, the Court shall consider the entire medical

record.

(3) Residual Seizure Disorder. (i) A petitioner may be considered

to have suffered a residual seizure disorder for purposes of paragraph

(a) of this section, if the first seizure or convulsion occurred 5-15

days (not less than 5 days and not more than 15 days) after

administration of the vaccine and 2 or more additional distinct seizure

or convulsion episodes occurred within 1 year after the administration

of the vaccine which were unaccompanied by fever (defined as a rectal

temperature equal to or greater than 101.0 degrees Fahrenheit or an

oral temperature equal to or greater than 100.0 degrees Fahrenheit). A

distinct seizure or convulsion episode is ordinarily defined as

including all seizure or convulsive activity occurring within a 24-hour

period, unless competent and qualified expert neurological testimony is

presented to the contrary in a particular case.

(ii) For purposes of paragraph (a) of this section, a petitioner

shall not be considered to have suffered a residual seizure disorder,

if the petitioner suffered a seizure or convulsion unaccompanied by

fever (defined as a rectal temperature equal to or greater than 101.0

degrees Fahrenheit or an oral temperature equal to or greater than

100.0 degrees Fahrenheit) before the fifth day after the administration

of the vaccine involved.

(4) Seizure and convulsion. For purposes of paragraphs (b) (2) and

(3) of this section, the terms, ``seizure'' and ``convulsion'' include

myoclonic, generalized tonic-clonic (grand mal), and simple and complex

partial seizures. Absence (petit mal) seizures shall not be considered

to be a condition set forth in the Table. Jerking movements or staring

episodes alone are not necessarily an indication of seizure activity.

(5) Sequela. The term ``sequela'' means a condition or event which

was actually caused by a condition listed in the Vaccine Injury Table.

(6) Chronic Arthritis. (i) For purposes of paragraph (a) of this

section, chronic arthritis may be found in a person with no prior

history 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

within 42 days after a rubella vaccination; and

(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.

(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 rheumatoid arthritis, systemic lupus

erythematosus, systemic sclerosis, mixed connective tissue disease,

polymyositis/dermatomyositis, 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, Reiter'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.

(c) Effective date provisions. The Table of Injuries set forth in

paragraph [[Page 7696]] (a) of this section applies to petitions for

compensation under the Program filed with the United States Court of

Federal Claims on or after March 10, 1995. The Qualifications and Aids

to Interpretation set forth in paragraph (b) of this section apply to

petitions filed with the United States Court of Federal Claims on or

after March 10, 1995. The petitions for compensation filed with the

United States Court of Federal Claims before March 10, 1995 shall be

governed by section 2114(a) (initial ``Table'') and section 2114(b)

(initial ``Qualification and Aids to Interpretation'') of the Public

Health Service Act as in effect on February 8, 1995.

[FR Doc. 95-2945 Filed 2-7-95; 8:45 am]

BILLING CODE 4160-15-M