[Federal Register Volume 80, Number 145 (Wednesday, July 29, 2015)]
[Proposed Rules]
[Pages 45132-45154]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-17503]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

42 CFR Part 100

RIN 0906-AB01


National Vaccine Injury Compensation Program: Revisions to the 
Vaccine Injury Table

AGENCY: Health Resources and Services Administration (HRSA), HHS.

ACTION: Notice of proposed rulemaking (NPRM).

-----------------------------------------------------------------------

SUMMARY: The Secretary proposes to amend the Vaccine Injury Table 
(Table) by regulation. These proposed regulations will have effect only 
for petitions for compensation under the National Vaccine Injury 
Compensation Program (VICP) filed after the final regulations become 
effective. The Secretary is seeking public comment on the proposed 
revisions to the Table.

DATES: Written comments must be submitted on or before January 25, 
2016.

ADDRESSES: You may submit comments, identified by the Regulatory 
Information Number (RIN) 0906-AB01 in one of three ways, as listed 
below. The first is the preferred method. Please submit your comments 
in only one of these ways to minimize the receipt of duplicate 
submissions.
    1. Federal eRulemaking Portal. You may submit comments 
electronically to http://www.regulations.gov. Click on the link 
``Submit electronic comments on HRSA regulations with an open comment 
period.'' Submit your comments as an attachment to your message or 
cover letter. (Attachments should be in Microsoft Word or WordPerfect; 
however, Microsoft Word is preferred).
    2. By regular, express or overnight mail. You may mail written 
comments to the following address only: Health Resources and Services 
Administration, Department of Health and Human Services, Attention: 
HRSA Regulations Officer, Parklawn Building, Room 14-101, 5600 Fishers 
Lane, Rockville, MD 20857. Please allow sufficient time for mailed 
comments to be received before the close of the comment period.
    3. Delivery by hand (in person or by courier). If you prefer, you 
may deliver your written comments before the close of the comment 
period to the same address: Parklawn Building Room 14-101, 5600 Fishers 
Lane, Rockville, MD 20857. Please call in advance to schedule your 
arrival with one of our HRSA Regulations Office staff members at 
telephone number (301) 443-1785. This is not a toll-free number.
    Because of staffing and resource limitations, and to ensure that no 
comments are misplaced, Program cannot accept comments by facsimile 
(FAX) transmission. In commenting, by any of the above methods, please 
refer to file code (#HRSA-0906-AB01). All comments received on a timely 
basis will be available for public inspection without change, including 
any personal information provided, in Room 14-101 of the Health 
Resources and Services Administration's offices at 5600 Fishers Lane, 
Rockville, MD, on Monday through Friday of each week from 8:30 a.m. to 
5:00 p.m. (excluding Federal holidays). Phone: (301) 443-1785. This is 
not a toll-free number.

FOR FURTHER INFORMATION CONTACT: Please visit the National Vaccine 
Injury Compensation Program's Web site, http://www.hrsa.gov/vaccinecompensation/, or contact Dr. Avril Melissa Houston, Director, 
Division of Injury Compensation Programs, Healthcare Systems Bureau, 
Health Resources and Services Administration, Parklawn Building, Room 
11C-26, 5600 Fishers Lane, Rockville, MD 20857. Phone calls can be 
directed to (301) 443-6593.

SUPPLEMENTARY INFORMATION: The President encourages Federal agencies 
through Executive Order 13563 to develop balanced regulations by 
encouraging broad public participation in the regulatory process and an 
open exchange of ideas. The Department of Health and Human Services 
(HHS) accordingly urges all interested parties to examine this 
regulatory proposal carefully and to share your views with us, 
including any data to support your positions. If you have questions 
before submitting comments, please see the ``For Further Information'' 
box below for the name and contact information of the subject-matter 
expert involved in this proposal's development. We must consider all 
written comments received

[[Page 45133]]

during the comment period before issuing a final rule.
    If you are a person with a disability and/or a user of assistive 
technology who has difficulty accessing this document, please contact 
HRSA's Regulations Officer at Parklawn Building, Room 14-101, 5600 
Fishers Lane, Rockville, MD 20857; or by telephone at 301-443-1785, to 
obtain this information in an accessible format. This is not a toll 
free telephone number. Please visit http://www.HHS.gov/regulations for 
more information on HHS rulemaking and opportunities to comment on 
proposed and existing rules.
    A public hearing on this proposed rule will be held before the end 
of the public comment period. A separate notice will be published in 
the Federal Register providing details of this hearing. Subject to 
consideration of the comments received, the Secretary intends to 
publish a final regulation.

Background

    The National Childhood Vaccine Injury Act of 1986, title III of 
Public Law 99-660 (42 U.S.C. 300aa-10 et seq.), established a Federal 
compensation program for persons thought to be injured by vaccines. The 
statute governing the program has been amended several times since 1986 
and is hereinafter referred to as ``the Act.'' Petitions for 
compensation under this Program are filed in the United States Court of 
Federal Claims, with a copy served on the Secretary, who is denominated 
the ``Respondent.'' The Court, acting through judicial officers called 
Special Masters, makes findings as to eligibility for, and amount of, 
compensation.
    In order to receive an award under this Program, a petitioner must 
establish a vaccine-related injury or death, either by proving that a 
vaccine actually caused or significantly aggravated an injury 
(causation-in-fact) or by demonstrating the occurrence of what has been 
referred to as a ``Table Injury.'' That is, a petitioner may show that 
the vaccine recipient suffered an injury of the type enumerated in the 
regulations at 42 CFR 100.3--the ``Vaccine Injury Table''--
corresponding to the vaccination in question, and that the onset of 
such injury took place within a time period also specified in the 
Table. If so, the injury is presumed to have been caused by the 
vaccination, and the petitioner is entitled to compensation (assuming 
that other requirements are satisfied), unless the respondent 
affirmatively shows that the injury was caused by some factor other 
than the vaccination (see sections 300aa-11(c)(1)(C)(i), 300aa-
13(a)(1)(B)), and 300aa-14(a) of the Act). Currently, cases are often 
resolved by settlements reached by both parties and approved by the 
Court.
    When Congress first enacted the Act, it mandated reviews by the 
Institute of Medicine (IOM) of the National Academy of Sciences with 
the express purpose of providing a better scientific rationale for any 
presumptions of vaccine causation. Under sections 312 and 313 of Public 
Law 99-660, Congress mandated that the IOM review the scientific 
literature and other information on specific adverse consequences of 
vaccines covered by the Program. Congress enacted a mechanism for 
modification of the statutory Table, through the promulgation of 
regulatory changes by the Secretary, after consultation with the 
Advisory Commission on Childhood Vaccines (ACCV). By statutory 
directive, the membership of the ACCV reflects a variety of 
stakeholders with different perspectives (42 U.S.C. 300aa-19).
    Efforts by the Secretary to modify the initial statutory Table, and 
its definitional counterpart, the Qualifications and Aids to 
Interpretation (QAI) began with publication of the two congressionally 
mandated IOM reviews in 1991 and 1994, respectively. With a few 
exceptions, the approach by the Secretary was straightforward: If the 
IOM concluded that there was evidence that a condition was ``causally 
related,'' it was added to or left on the Table. However, if there was 
no proven scientific evidence of an association, it was not added to 
the Table or it was removed. The entire process, from publication of 
the IOM reports, to promulgation of final rules in 1995 and 1997 took 
approximately 3 to 4 years.
    The IOM has analyzed numerous possible vaccine injury connections 
over the years and after conducting a third comprehensive review of the 
scientific literature on vaccines and adverse events, released a report 
entitled, Adverse Effects of Vaccines: Evidence and Causality (2012). 
This third IOM report was conducted under the Department's initiative 
and was not statutorily mandated. The committee charged with 
undertaking this review consisted of 16 members with expertise in the 
following fields: Pediatrics, internal medicine, neurology, immunology, 
immunotoxicology, neurobiology, rheumatology, epidemiology, 
biostatistics, and law (http://www.iom.edu/reports/2011/Adverse-Effects-of-Vaccines-Evidence-and-Causality.aspx). The members of the 
review committee are subject to the stringent conflict of interest 
criteria imposed by the IOM. The committee met eight times over the 
course of 35 months, surveying more than 11,000 abstracts and reviewing 
in-depth 1,487 scientific and medical studies. The committee did not 
perform any original research.
    The IOM Committee undertook the task of judging whether, based on 
available scientific evidence, a causal relationship exists between 
each adverse event examined and exposure to the following eight 
vaccines: Measles-mumps-rubella vaccine, varicella virus vaccine, 
seasonal influenza vaccines (which did not include the H1N1 influenza 
vaccine distributed in 2009), hepatitis A vaccine, hepatitis B vaccine, 
human papillomavirus vaccine, diphtheria tetanus toxoid and acellular 
pertussis-containing vaccines, and meningococcal vaccine. The charge to 
the Committee involved these eight vaccines because they are the 
vaccines with the vast majority of alleged adverse events in the claims 
for compensation filed under the Program. In addition, some of these 
vaccines had not been reviewed previously by the IOM.
    Two types of evidence were utilized by the IOM in determining the 
strength of a causal association: Epidemiologic evidence from studies 
of populations and mechanistic evidence derived primarily from 
biological and clinical studies in animals and humans such as case 
reports. To determine the weight of the evidence, the IOM used a 
summary classification scheme that incorporated both the quality and 
quantity of the individual articles and the consistency of the group of 
articles in terms of direction of effect. Four weight-of-evidence 
categories were utilized, with epidemiologic evidence assessed to be 
high, moderate, limited or insufficient, and mechanistic evidence 
assessments of strong, intermediate, weak or lacking.
    The IOM started each adverse event assessment from a position of 
neutrality, moving in either direction (i.e., evidence favoring or 
rejecting causation) only when the epidemiologic and/or mechanistic 
evidence suggested a more definitive assessment. As with the previous 
IOM studies, a classification system was used to categorize the IOM's 
conclusions about the strength of a causal association. These 
categories are as follows:
    1. Evidence convincingly supports a causal relationship;
    2. Evidence favors acceptance of a causal relationship;
    3. Evidence favors rejection of a causal relationship; or
    4. Evidence is inadequate to accept or reject a causal 
relationship.

[[Page 45134]]

    The IOM Committee concluded in certain circumstances that the 
evidence convincingly supports, or favors acceptance of, a causal 
relationship based only on a mechanistic assessment, even when the 
epidemiological evidence was inconclusive or absent. The 2012 IOM 
Report, on pages 17-18 explains that strong mechanistic evidence 
``always carries sufficient weight for the committee to conclude the 
evidence convincingly supports a causal relationship. . .This 
conclusion [attributing the disease to the vaccine and not to other 
etiologies] can be reached even if the epidemiologic evidence is rated 
high in the direction of no increased risk or even decreased risk.''
    The IOM concluded the evidence convincingly supports 14 specific 
vaccine-adverse event relationships, with all but one based on strong 
mechanistic evidence, and the epidemiologic evidence rated as either 
having limited confidence or being insufficient. Four vaccine adverse 
events judged to have either epidemiologic evidence of moderate 
certainty or mechanistic evidence of intermediate weight were placed in 
the ``evidence favors acceptance of a causal relationship'' category, 
while five other vaccine adverse events were placed in the ``evidence 
favors rejection'' category. A finding against a causal relationship 
required high or moderate epidemiologic evidence in the direction of no 
effect or decreased risk along with the absence of strong or 
intermediate mechanistic evidence supporting a causal relationship. The 
vast majority (135 vaccine-adverse event combinations) were placed in 
the ``evidence is inadequate to accept or reject a causal 
relationship'' category.
    After release of the report, nine HHS workgroups including HRSA and 
the Centers for Disease Control and Prevention (CDC) medical staff 
reviewed the IOM conclusions on 158 vaccine-adverse events, as well as 
any newly published scientific literature not contained in the IOM 
report, and developed a set of proposed changes to the Table and QAI. 
The work of the HHS workgroups ended and HRSA continued to monitor the 
literature.
    In 2006, the ACCV established ``Guiding Principles for Recommending 
Changes to the Vaccine Injury Table'' (Guiding Principles) to assist 
the ACCV in evaluating proposed Table revisions and determining whether 
to recommend changes to the Table to the Secretary. The Guiding 
Principles consist of two overarching principles: (1) The Table should 
be scientifically and medically credible; and (2) where there is 
credible scientific and medical evidence both to support and to reject 
a proposed change (addition or deletion) to the Table, the change 
should, whenever possible, be made to the benefit of petitioners. The 
Guiding Principles also state, among other factors, that ``[t]o the 
extent that the [IOM] has studied the possible association between a 
vaccine and an adverse effect, the conclusions of the IOM should be 
considered by the ACCV and deemed credible but those conclusions should 
not limit the deliberations of the ACCV.'' Although not binding on the 
Secretary, the ACCV Guiding Principles were utilized by the nine HHS 
workgroups in the development of the proposed changes to the Table. In 
particular, recommendations regarding appropriate time intervals for 
the onset of a Table injury, or diagnostic criteria in the QAI were 
influenced by the Guiding Principles. As part of its mandate under the 
Act, the ACCV considered the proposed changes set forth in this NPRM in 
its quarterly meetings on March 8, 2012, September 5, 2013, December 5, 
2013, June 5, 2014, and September 4, 2014. The ACCV deliberations 
included scientific and public policy considerations, and were also 
influenced by the 2006 Guiding Principles. For each proposed change by 
the Secretary, the ACCV voted for one of three options:
    1. ACCV concurs with the proposed change(s) to the Table (and QAI) 
and would like the Secretary to move forward (with or without 
comments);
    2. ACCV does not concur with the proposed change(s) to the Table 
(and QAI) and would not like the Secretary to move forward; or
    3. ACCV would like to defer a recommendation on the proposed 
change(s) to the Table (and QAI) pending further review at a future 
ACCV meeting.

Findings

    In prior Table revisions, the Secretary determined that the 
appropriate framework for making changes to the Table is to make 
specific findings as to the illnesses or conditions that can reasonably 
be determined in some circumstances to be caused or significantly 
aggravated by the vaccines under review and the circumstances under 
which such causation or aggravation can reasonably be determined to 
occur. The Secretary continues this approach based on the 2012 IOM 
report, the work of the nine workgroups that reviewed the IOM findings, 
and after giving due consideration to the ACCV's recommendations.
    For the vast majority of the vaccine adverse event pairs that were 
reviewed by the IOM (135), the IOM determined that the evidence is 
inadequate to accept or reject a causal relationship. With the 
exception of seasonal influenza vaccine and Guillain-Barr[eacute] 
Syndrome (GBS), unless the IOM findings addressed a condition that was 
already on the Table, the Secretary makes no additional findings and 
proposes no change to the Table with regard to the vaccine adverse 
event pairs in this category. For seasonal influenza vaccines, the 
Secretary proposes to add the injury of GBS to the Table for the policy 
reasons discussed in this NPRM. For any vaccine adverse event pairs for 
which future scientific evidence develops to support a finding of a 
causal relationship, the Secretary will consider future rulemaking to 
revise the Table accordingly.
    Applying the remaining IOM conclusions, with the Guiding 
Principles, the Secretary intends to make certain changes to the Table, 
and also intends to leave certain items already on the Table unchanged. 
In so doing, the Secretary makes the following findings:

Findings That Result in Additions or Changes to the Table

    1. The scientific evidence convincingly supports a causal 
relationship between measles-mumps-rubella (MMR) vaccine and measles 
inclusion body encephalitis.
    2. The scientific evidence convincingly supports a causal 
relationship between varicella vaccine and vaccine disseminated 
varicella infection (widespread chickenpox rash shortly after 
vaccination).
    3. The scientific evidence convincingly supports a causal 
relationship between varicella vaccine and disseminated varicella 
infection with subsequent infection resulting in pneumonia, meningitis, 
or hepatitis in individuals with demonstrated immunodeficiencies.
    4. The scientific evidence convincingly supports a causal 
relationship between varicella vaccine and vaccine strain viral 
reactivation.
    5. The scientific evidence convincingly supports a causal 
relationship between varicella vaccine and vaccine strain viral 
reactivation with subsequent infection resulting in meningitis or 
encephalitis.
    6. The scientific evidence convincingly supports a causal 
relationship between varicella vaccine and anaphylaxis.
    7. The scientific evidence convincingly supports a causal

[[Page 45135]]

relationship between influenza vaccines and anaphylaxis.
    8. The scientific evidence convincingly supports a causal 
relationship between meningococcal vaccines and anaphylaxis.
    9. The scientific evidence favors acceptance of a causal 
relationship between human papillomavirus vaccines and anaphylaxis.
    10. The scientific evidence convincingly supports a causal 
relationship between an injection-related event and deltoid bursitis. 
For reasons detailed below, the Secretary proposed adding a more 
expansive injury of Shoulder Injury Related to Vaccine Administration 
(SIRVA) to the Table.
    11. The scientific evidence convincingly supports a causal 
relationship between an injection-related event and syncope.
    12. The scientific evidence is inadequate to accept or reject a 
causal relationship between seasonal influenza vaccines and GBS. 
However, the Secretary proposes a Table change for the reasons 
discussed in this NPRM.

Findings That Do Not Result in Changes to the Table Because the Injury 
Is Already on the Table

    1. The scientific evidence convincingly supports a causal 
relationship between MMR vaccine and anaphylaxis.
    2. The scientific evidence convincingly supports a causal 
relationship between Hepatitis B vaccine and anaphylaxis.
    3. The scientific evidence convincingly supports a causal 
relationship between tetanus toxoid vaccine and anaphylaxis.
    4. The scientific evidence is inadequate to accept or reject a 
causal relationship between tetanus toxoid-containing vaccines 
(including those containing the acellular pertussis component but not 
the whole cell pertussis component) and encephalopathy and 
encephalitis.
    5. The scientific evidence is inadequate to accept or reject a 
causal relationship between MMR vaccine and chronic arthritis in women.
    6. The scientific evidence is inadequate to accept or reject a 
causal relationship between MMR vaccine and chronic arthritis in 
children.
    7. The scientific evidence is inadequate to accept or reject a 
causal relationship between MMR vaccine and encephalopathy or 
encephalitis.

Findings That Do Not Result in Changes to the Table Because the Injury 
Is Transient in Nature

    1. The scientific evidence convincingly supports a causal 
relationship between MMR vaccine and febrile seizures.
    2. The scientific evidence favors acceptance of a causal 
relationship between MMR vaccine and transient arthralgia in women.
    3. The scientific evidence favors acceptance of a causal 
relationship between MMR vaccine and transient arthralgia in children.

Findings That Do Not Result in Changes to the Table Because the 
Evidence Favors Rejection of a Causal Relationship

    1. The scientific evidence favors a rejection of a causal 
relationship between MMR vaccine and autism.
    2. The scientific evidence favors a rejection of a causal 
relationship between MMR vaccine and type 1diabetes.
    3. The scientific evidence favors a rejection of a causal 
relationship between DTaP (tetanus) vaccine and type 1diabetes.
    4. The scientific evidence favors a rejection of a causal 
relationship between inactivated (as opposed to the live intranasal) 
influenza vaccine and Bell's palsy.
    5. The scientific evidence favors a rejection of a causal 
relationship between inactivated influenza vaccine and exacerbation of 
asthma or reactive airway disease episodes in children and adults.

Discussion of Proposed Table Changes

    The Secretary has examined the recommendations of the ACCV and 
proposes that the Table set forth at 42 CFR 100.3 be revised as 
described below. Following each vaccine and adverse event there is a 
discussion of the IOM conclusion and, where applicable, other relevant 
conclusions, as well as the Department's proposal. It should be noted 
that the ACCV concurred with all of the proposals regarding the Table 
and QAI. Each of the changes proposed by the Department and the 
rationale for the proposal is described in detail. An important 
consideration in proposing changes to the Table is the need to make the 
Table as easy to understand and as clear as possible. With this goal in 
mind, the Secretary has proposed new language and clarified certain 
sections of the QAI which must be used by the Special Masters and the 
parties in understanding when a particular set of symptoms is 
consistent with a particular Table injury.
    As provided in 42 U.S.C. 300aa-14(c)(4), the modified Table will 
apply only to petitions filed under the Program after the effective 
date of the final regulation. Petitions must also be filed within the 
applicable statute of limitations. The general statute of limitations 
applicable to petitions filed with the VICP, set forth in 42 U.S.C. 
300aa-16(a), continues to apply. In addition, the statute identifies a 
specific exception to this statute of limitations that applies when the 
effect of a revision to the Table makes a previously ineligible person 
eligible to receive compensation or when an eligible person's 
likelihood of obtaining compensation significantly increases. Under 
this section, an individual who may be eligible to file a petition 
based on the revised Table may file the petition for compensation not 
later than 2 years after the effective date of the revision if the 
injury or death occurred not more than 8 years before the effective 
date of the revision of the Table (42 U.S.C. 300aa-16(b)). This is true 
even if such individual previously filed a petition for compensation, 
and is thus an exception to the ``one petition per injury'' limitation 
of 42 U.S.C. 300aa-11(b)(2).
    Based on the requirements of the Administrative Procedure Act, the 
Department publishes a Notice of Proposed Rulemaking in the Federal 
Register before a regulation is promulgated. The public is invited to 
submit comments on the proposed rule. In addition, a public hearing 
will be held for this proposed rule. After the public comment period 
has expired, the comments received and the Department's responses to 
the comments will be addressed in the preamble to the final regulation. 
The Department will publish the final rule in the Federal Register.
    In the following sections, background information on different 
categories of vaccines as well as the Secretary's rationale for any 
proposed Table change is provided. It should also be noted that the 
proposed QAIs are designed to define the conditions covered on the 
Table and to rule out other conditions that are not covered on the 
Table (and for which there has been no finding of a causal relation to 
the vaccines). In addition, the QAIs make clear that if certain other 
circumstances exist that do not, in the Secretary's view, warrant a 
presumption of causation, the Table presumption will not be apply.

[[Page 45136]]

I. Vaccines Containing Tetanus Toxoid

    Currently there are four tetanus-diptheria (Td) vaccines licensed 
in the United States, two of which also contain acellular pertussis 
vaccines (Tdap and DTap); a diphtheria-tetanus (DT) vaccine for 
children younger than age 7 years; and one tetanus toxoid vaccine (TT). 
In addition, there are three combination vaccines approved for use in 
children, including (DTaP-IPV-HepB), (DTaP-IPV-Hib), and (DTaP-IPV). 
Immunity to tetanus wanes over time, so booster doses are needed. 
According to the CDC recommended schedule of immunizations for 
children, an infant and child should receive four doses of DTaP in the 
first 18 months of life and a booster dose between 4 to 6 years. Tdap 
is recommended at age 11 to 12 years.
    Since 2005, the Advisory Committee on Immunization Practices (ACIP) 
and the CDC have recommended a Tdap vaccine booster dose for all 
adolescents aged 11 through 18 years of age and for adults aged 19 
through 64 years who have not received a dose. A Td booster is 
recommended every 10 years thereafter. As part of wound management care 
to prevent tetanus, a tetanus toxoid-containing vaccine is recommended 
for wound management in anyone who has not received a tetanus-
containing vaccine for 5 years or more. The CDC recommends that one 
dose of Tdap be administered to pregnant women during each pregnancy 
regardless of the interval since the prior Td or Tdap vaccination.
A. Shoulder Injury Related to Vaccination
    Shoulder Injury Related to Vaccine Administration (SIRVA) is an 
adverse event following vaccination thought to be related to the 
technique of intramuscular percutaneous injection (the procedure where 
access to a muscle is obtained by using a needle to puncture the skin) 
into an arm resulting in trauma from the needle and/or the 
unintentional injection of a vaccine into tissues and structures lying 
underneath the deltoid muscle of the shoulder. As the proposed 
definition indicates, SIRVA is an injury related to the intramuscular 
injection of a vaccine. Consequently, by definition, a Table injury of 
SIRVA will not result for those vaccines that are not administered by 
intramuscular injection, including oral polio and rotavirus; 
subcutaneous MMR, MMRV, varicella, and meningococcal-polysaccharide; 
intranasal influenza; and intradermal influenza. In addition, a Table 
injury of SIRVA will not result for those vaccines that are 
administered via a needleless jet device. Jet injectors are needleless 
systems for vaccine or medication administration that utilize a high-
pressure jet of liquid to penetrate the skin. During administration, 
the needleless syringe is placed against the injection site and as the 
medication or vaccine passes through the injector under high pressure 
it forms a jet of fluid that penetrates the skin. These devices do not 
penetrate the skin to a degree that would result in SIRVA. Current 
information regarding routes of administration for various vaccine 
formulations is available on the Centers for Disease Control and 
Prevention's Web site: http://www.cdc.gov/vaccines/recs/vac-admin/default.htm?s_cid=.
    Clinical signs of shoulder pain and restricted motion in the 
affected shoulder appear shortly after vaccination. Medical review of 
VICP claims shows more than 30 cases of severe, persistent shoulder 
pain beginning shortly after vaccination and resulting in prolonged 
restriction of function. Often these cases were diagnosed as deltoid 
bursitis. [Atanasoff S, Ryan T, Lightfoot R, and Johann-Liang R, 2010, 
Shoulder injury related to vaccine administration (SIRVA), Vaccine 
28(51):8049-8052.]
    The IOM reviewed the scientific and medical literature finding 
evidence that convincingly supports a causal relationship between 
vaccine injection (with a needle) into an arm and deltoid bursitis. The 
report noted that the published VICP case series (Atanasoff et al.), as 
described, were clinically consistent with deltoid bursitis. The VICP 
case series found that 93 percent of patients had the onset of shoulder 
pain within 24 hours of vaccine administration and 54 percent had 
immediate pain following vaccine injection. The VICP case series found 
several diagnoses, beyond deltoid bursitis, that resulted in shoulder 
pain following vaccination, including tendonitis, impingement syndrome, 
frozen shoulder syndrome, and adhesive capsulitis. Another case series 
reported two cases of shoulder pain, weakness and reduced range of 
motion following vaccination with onset of symptoms within 48 hours of 
vaccination. [Bodor M, Montalvo E, Vaccination related shoulder 
dysfunction, Vaccine 25(2007) 585-587.]
    In order to capture the broader array of potential injuries, the 
Secretary proposes to add SIRVA for all tetanus toxoid-containing 
vaccines that are administered intramuscularly through percutaneous 
injection into the upper arm. The interval of onset will be less than 
or equal to 48 hours.
    While the Secretary proposes adding SIRVA to the Table for the MMR 
and Varicella vaccines, to meet the proposed QAI for SIRVA, the vaccine 
must be one intended for intramuscular administration in the upper arm. 
The Secretary acknowledges that currently there are no MMR or Varicella 
vaccines that are administered by intramuscular injection. However, the 
Secretary proposes that the Table include SIRVA as an injury for those 
vaccines, recognizing that, presently, the absence of an intramuscular 
formulation of the vaccines will prevent petitioners from meeting the 
Table QAI for SIRVA with respect to those vaccines. The advantage of 
such proposal is that the Table would not require modification should 
an intramuscular formulation of those vaccines develop. The 
disadvantage of this proposal could be confusion about whether a Table 
injury for SIRVA may be satisfied for those vaccines, despite the QAI's 
requirement that the associated vaccine be intended for intramuscular 
administration. Accordingly, the Secretary specifically seeks the 
public's views on her proposal to include SIRVA as a Table injury for 
the MMR and varicella vaccines notwithstanding the fact that there 
currently is not an intramuscular formulation. Consequently, by 
definition, a Table injury of SIRVA will not result for those vaccines 
that are not administered by intramuscular injection, including oral 
polio and rotavirus; subcutaneous MMR, MMRV, varicella, and 
meningococcal-polysaccharide; intranasal influenza; and intradermal 
influenza.
B. Vasovagal Syncope
    Vasovagal syncope is the loss of consciousness (fainting) caused by 
a transient decrease in blood flow to the brain. Vasovagal syncope is 
usually a benign condition but may result in falling and injury. 
Vaccination is known to be one cause of vasovagal syncope. Both serious 
and non-serious injuries can occur as a result of syncope. The types of 
serious injuries that may occur following a syncopal episode include, 
but are not limited to, skin lacerations, bone fractures, dental 
injuries, traumatic brain injuries, and death. Other injuries include 
traumatic injuries sustained from automobile accidents that occurred 
due to a vaccinee experiencing syncope while driving within a short 
time period after vaccine receipt.
    The IOM reviewed the literature concerning a possible link between 
the injection of a vaccine and syncope. Although the Committee found 
the epidemiologic evidence was insufficient or absent to assess an 
association

[[Page 45137]]

between the injection of a vaccine (with a needle) and syncope, the 
Committee concluded the mechanistic evidence was strong based on 35 
cases presenting definitive clinical evidence. In addition, the HHS's 
Division of Injury Compensation Programs (DICP) has identified eight 
cases from its database alleging syncope as a vaccine injury 
(unpublished data). All had six months of residual symptoms as a result 
of syncope. In all eight cases, DICP found that syncope was directly 
related to vaccine administration.
    The IOM concluded that the evidence convincingly supports a causal 
relationship between the injection of a vaccine (with a needle) and 
syncope. It did not limit this conclusion to a particular vaccine and 
explained that the evidence from one case report it examined as part of 
the mechanistic evidence it reviewed suggested ``that the injection, 
and not the contents of the vaccine, contributed to the development of 
syncope.''
    In order to be eligible for compensation, the Act requires that the 
residual effects of the alleged vaccine injury must have continued for 
a period of at least 6 months (unless the injury results in in-patient 
hospitalization and surgery, or death). The Secretary recognizes that 
in many instances cases involving syncope will not meet the statutory 
severity criteria, as the reaction can be short-lived and treated 
effectively. However, there is a known risk of serious residual injury 
or of death from syncope.
    Although syncope typically has no long term consequences, the 
Program has found that not infrequently, syncope is associated with 
residual effects lasting more than 6 months. Therefore, the Secretary 
proposes to add vasovagal syncope to the Table for all tetanus toxoid 
containing vaccines that are administered through percutaneous 
injection to permit an award of compensation in serious cases meeting 
the severity criteria. The proposed time interval of onset is less than 
or equal to 1 hour following vaccination. Syncope is an injury related 
to the injection of a vaccine. Consequently, the Secretary does not 
propose adding syncope as a Table injury for those vaccines that are 
not administered by injection, including oral polio and rotavirus 
vaccine. With respect to other vaccines, such as the intranasal 
influenza vaccine, while syncope is proposed as an injury for the 
general category of vaccines (i.e., seasonal influenza vaccines), the 
specific formulation will not result in a Table injury of syncope by 
definition because it is not administered by injection. The Secretary 
is not aware of any reliable and persuasive evidence demonstrating that 
syncope occurs following administration of a vaccine via a needleless 
jet device; however, it may be plausible for syncope to occur with this 
route of administration. Therefore, the Secretary seeks the public's 
views as to whether the Secretary should include syncope as a Table 
injury for those vaccines that are administered via a needleless jet 
device. The Secretary also seeks the public's views as to whether 
syncope should be a Table injury for other categories of vaccines 
(e.g., rotavirus) notwithstanding the fact that there currently is not 
a formulation that is administered by injection in order to encompass 
future formulations that may be administered by injection.

II. Vaccines Containing Extracted or Partial Cell Pertussis Bacteria, 
or Specific Pertussis Antigen(s)

    Diphtheria, tetanus, and whole cell pertussis (DTwP) vaccines were 
used for much of the 20th century to control pertussis (whooping cough) 
disease. Concerns about the safety of DTwP (also referred to as DTP) 
vaccine prompted development of vaccines with an acellular pertussis 
component. With data showing fewer local, systemic, and more serious 
adverse events after acellular (DTaP) vaccine when compared to whole 
cell DTwP vaccine, the FDA licensed diphtheria and tetanus toxoids and 
acellular pertussis (DTaP) vaccines in 1991 for use in children aged 15 
months to 6 years, and in 1996 for use in infants and children aged 6 
weeks to 6 years. By 2000, DTaP had replaced DTwP and, like the whole 
cell pertussis vaccine, was subsequently licensed in combination with 
other vaccines for routine use in children. Further, in 2005, FDA 
licensed tetanus and diphtheria toxoid (Td) and, acellular pertussis 
(Tdap) vaccine, for use in persons 10 years of age and older, as this 
vaccine is thought to decrease the number of pertussis carriers in the 
population, which would lead to a decrease in the number of pertussis 
outbreaks.
    The Secretary notes that there are significant differences between 
whole cell and acellular pertussis vaccines. Although both vaccine 
types were developed for the same purpose (i.e., immunization against 
pertussis), they have significantly different compositions, and 
different effects on biological systems (e.g., the immune and nervous 
systems). DTwP is distinct from DTaP because the former contains many 
bacterial proteins, including endotoxins (some of which are known 
neurotoxins) and the latter does not. These neurotoxins are thought to 
possibly act synergistically to cause adverse neurologic events in 
susceptible DTwP vaccine recipients. To date, no adequate study has 
been published that demonstrates a causal relationship between 
acellular pertussis vaccines and encephalopathy/encephalitis. 
Furthermore, studies have demonstrated a significant reduction in the 
number of common adverse events with acellular pertussis, such as 
crying and fevers, and less common ones, such as febrile seizures. 
[Pertussis vaccination: use of acellular pertussis vaccines among 
infants and young children recommendations of the advisory committee on 
immunization practices (ACIP), MMWR, 1997; 46(RR-7):1-25.] [Le Saux N, 
et al. Health Canada Immunization Monitoring Program-Active (IMPACT)] 
[Decrease in hospital admissions for febrile seizures and reports of 
hypotonic-hyporesponsive episodes presenting to hospital emergency 
departments since switching to acellular pertussis vaccine in Canada: A 
report from IMPACT. Pediatrics. 2003; 112(5):e348.] Pertussis antigen-
containing vaccines were included in the original statutory Table.
A. Encephalopathy/Encephalitis
    The initial Table and QAI set forth in the 1986 statute reflected 
Congress' initial legislative determinations on vaccine-related 
injuries for DTwP vaccine. Further, modifications to the Table and QAI 
promulgated by the Secretary in 1995 were based on the scientific 
findings related to DTwP vaccine, the key study being the British 
National Childhood Encephalopathy Study (NCES), which found some 
evidence of acute neurologic illness (encephalopathy) 1 to 7 days after 
vaccination with the whole cell pertussis vaccine. Similarly, a 10 year 
NCES follow-up found evidence of chronic nervous system effects. 
However, the evidence from this follow-up study remained insufficient 
to indicate the presence or absence of a causal relation between DTP 
and chronic nervous system dysfunction. On the other hand, a more 
recent epidemiologic study of whole cell pertussis-containing vaccines 
did not show a relationship with encephalopathy or encephalitis (Ray et 
al). The IOM conclusions in 1991 and 1994 were mixed regarding the 
statistically significant findings of encephalopathy in both the 
original NCES and its 10 year follow-up. [IOM, Adverse Effects of 
Pertussis and Rubella Vaccines, 1991. IOM, Adverse Events Associated 
with Childhood Vaccines, 1994.] In the end, the Secretary, with

[[Page 45138]]

unanimous support of the ACCV, retained encephalopathy on the Table, 
but clarified the definition of encephalopathy in the QAI to make it 
more clinically precise. [Miller D, Wadsworth J, Ross E, Severe 
neurological illness: Further analysis of the British National 
Childhood Encephalopathy Study. Tokai J Exp Clin Med. 1988; 
13(suppl):145-155; Miller D, Madge N, Diamond J, Wadsworth J, and Ross 
E, Pertussis Immunization and Serious Acute Neurological Illnesses in 
Children, BMJ, 1993;307:1171-6; Ray P, Hayward J, Michelson D, Lewis E, 
Schwalbe J, Black S, Shinefield H, Marcy M, Huff K, Ward J, Mullooly J, 
Chen R, Davis R, and the Vaccine Safety Datalink Group, Encephalopathy 
After Whole-Cell Pertussis or Measles Vaccination: Lack of Evidence for 
a Causal Association in a Retrospective Case-Control Study. Ped Infec 
Dis J. 2006; 25(9):768-773.]
    Acellular pertussis-containing vaccines were developed because of 
concerns about events due to whole cell pertussis. Toxicologists argue 
that components in these two types of pertussis vaccines differ greatly 
and should be treated as separate entities. Animal models have 
demonstrated that whole cell pertussis constituents have different 
effects than those with acellular pertussis. In one study, only whole 
cell pertussis vaccines caused seizure activity in mice. Levels of 
inflammatory markers were elevated in the whole cell pertussis group 
but not the acellular pertussis group. In another study, mice that 
received whole cell pertussis intravenously succumbed while those that 
received acellular pertussis did not. [Sato Y, Sato H, Comparison of 
Toxicities of Acellular Pertussis Vaccine with Whole Cell Pertussis 
Vaccine in Experimental Animals, Dev Biol Stand, 1991; 73:251-62; 
Donnelly S, Loscher CE, Lynch MA, Mills KH, Whole-cell but not 
Acellular Pertussis Vaccines Induce Convulsive Activity in Mice: 
evidence of a role for toxin-induced interleukin-1beta in a new murine 
model for analysis of neuronal side effects of vaccination. Infect 
Immun. 2001 July; 69(7):4217-4223.]
    The 2012 IOM report on adverse events found that the evidence was 
inadequate to accept or reject a causal association between acellular 
pertussis-containing vaccines and encephalopathy and encephalitis. As 
previously stated, there is no credible evidence of a causal 
relationship between acellular pertussis vaccines and encephalopathy/
encephalitis. Clinical studies have demonstrated a significant 
reduction in the number of common adverse events with acellular 
pertussis vaccine, as compared to whole cell pertussis vaccine, such as 
crying and fevers, and less common ones, such as febrile seizures. 
Although there have been large-scale surveillance studies conducted on 
the effects of acellular pertussis vaccines in infants and young 
children, such as those done in Canada and Australia, the study design 
used passive surveillance and therefore, the evidence is not as 
definitive as a controlled, well-designed epidemiologic study using a 
case control or cohort design [Le Saux N, et al. e348] [Lawrence G., 
Menzies R., Burgess M., McIntyre P., Wood N., Boyd I., Purcell P., 
Isaacs D. Surveillance of adverse events following immunization: 
Australia, 2000-2002. Commun Dis Intell. 2003; 27(3):307-23]. With 
regard to adolescents and adults, the Committee included a study by Yih 
(2009) which found that the number of encephalitis, encephalopathy or 
meningitis cases within 42 days of Tdap vaccination were less than a 
historical Td cohort with a relative risk of 0.84. [Yih W. K., Nordin 
J.D., Kulldorff M., Lewis E., Lieu T.A., Shi P., and Weintraub E. S., 
2009, An assessment of the safety of adolescent and adult tetanus-
diphtheria-acellular pertussis (Tdap) vaccine, using active 
surveillance for adverse events in the vaccine safety datalink, Vaccine 
27(32):4257-4262]
    In view of the limited epidemiological data, and as influenced by 
the Guiding Principles, the Secretary does not propose to make any 
changes to the Table, leaving intact the Table injury of 
encephalopathy/encephalitis for vaccines containing pertussis antigens, 
with an onset less than 72 hours from vaccination. However, the 
Secretary proposes to re-organize, clarify, and update the QAI for 
acute and chronic encephalopathy, and to include a new definition for 
acute encephalitis based on the Brighton Collaboration criteria and 
several other references. The Brighton Collaboration is an 
international voluntary collaboration that develops globally accepted 
and standardized case definitions of adverse events following 
immunizations. More information can be found at: https://brightoncollaboration.org/public.
B. Shoulder Injury Related to Vaccination
    The Secretary proposes to add SIRVA for pertussis antigen-
containing vaccines. [See I.A.] The interval of onset will be less than 
or equal to 48 hours.
C. Vasovagal Syncope
    The Secretary proposes to add vasovagal syncope to the Table for 
pertussis antigen-containing vaccines. [See I.B.] The proposed time 
interval of onset is less than or equal to 1 hour following 
vaccination.

III. Vaccines Containing Measles, Mumps, and Rubella Vaccine or Any of 
Its Components

    Since the 1960s, measles, mumps, and rubella (MMR), a live, 
attenuated virus vaccine, has been routinely administered to children 
in the U.S. In 2005, the tetravalent measles, mumps, rubella, and 
varicella (MMRV) vaccine was added to the immunization schedule. MMR 
vaccine was included in the original statutory Table.
A. Vaccine Strain Measles Viral Disease Including Measles Inclusion 
Body Encephalitis (MIBE)
    Severe complications associated with the measles virus or a mutated 
form of the virus, such as measles inclusion body encephalitis (MIBE), 
can be broadly categorized as measles viral diseases. The Table 
currently lists ``vaccine-strain measles viral infection in an 
immunodeficient recipient'' as a Table injury for vaccines containing 
measles virus, with an onset of 6 months. This condition is defined in 
the QAI as ``a disease caused by the vaccine-strain that should be 
determined by vaccine-specific monoclonal antibody or polymerase chain 
reaction tests.''
    MIBE is a rare, slow encephalitis caused by chronic with the 
measles virus, and is thus a subset of the condition already listed on 
the Table. MIBE is confined to immunodeficient individuals and is 
frequently fatal. MIBE occurs primarily in children and young adults, 
and typically occurs within 1 year of the initial infection or 
vaccination. A gradual decline in intellectual abilities and behavioral 
alterations are followed by progressive myoclonus; muscle spasticity; 
seizures; dementia; autonomic dysfunction; and ataxia. Death usually 
occurs 1 to 3 years after disease onset. Pathologic features include 
perivascular cuffing, eosinophilic cytoplasmic inclusions, neurophagia, 
and fibrous gliosis.
    The IOM concluded that the evidence convincingly supports a causal 
relationship between MMR vaccine and MIBE in individuals with 
demonstrated immunodeficiencies. Out of the five case reports the IOM 
found, two had wild-type measles infection and these did not contribute 
to the weight of evidence. Only one out of the three

[[Page 45139]]

contributing case reports had vaccine-strain measles virus isolated. 
Because of limitations due to testing and viral properties, in most 
cases it is difficult to characterize wild-type versus vaccine-strain 
measles. [Bitnun A., Shannon P., Durward A., Rota P.A., Bellini W.J., 
Graham C., Wang E., Ford-Jones E.L., Cox P., Becker L., Fearon M., 
Petric M., and Tellier R.,. 1999. Measles inclusion-body encephalitis 
caused by the vaccine strain of measles virus. Clinical Infectious 
Diseases 29(4):855-861.] The current Table lists ``Vaccine-strain 
measles viral infection in an immunodeficient recipient'' for measles 
virus-containing vaccines with a time interval of onset of 6 months. 
Case reports of MIBE cited by the IOM showed a time interval of onset 
that varied from 8 days to 11 months.
    For the reasons discussed above and in keeping with the spirit of 
the Guiding Principles, the Secretary proposes to change the injury of 
``vaccine-strain measles viral infection in an immunodeficient 
recipient'' to ``vaccine-strain measles viral disease in an 
immunodeficient recipient.'' Because MIBE is a type of measles virus-
associated disease occurring in immunodeficient individuals, the 
Secretary proposes a new time interval of onset of up to 12 months from 
the date of vaccination for those cases in which the typing of vaccine 
strain was not performed, because most cases of vaccine-strain disease 
occur within 1 year of vaccination. There is no time interval for onset 
proposed if the vaccine strain of the virus is identified, as it can be 
concluded that the vaccine was a contributing cause of the injury. 
Cases in which wild-type measles strain is isolated will be excluded. 
Revisions to the Table will distinguish between cases in which the 
measles vaccine strain is identified versus those cases in which 
laboratory testing was not done or the results were inconclusive. In 
addition, the Secretary proposes adding diagnostic criteria to the QAI.
B. Encephalopathy and Encephalitis
    The IOM concluded that the evidence is inadequate to accept or 
reject a causal relationship between MMR vaccine and encephalopathy or 
encephalitis. Not only is there limited epidemiologic evidence on a 
possible causal association, the mechanistic evidence is weak, based on 
current knowledge about natural infection and few case reports. Natural 
(wild-type) infection (measles, mumps, and/or rubella virus) is thought 
to cause neurologic illness through damage to the neurons by direct 
viral invasion. This is thought to be either from direct viral 
infection and/or viral reactivation (particularly in immunocompromised 
patients). These same mechanisms may be responsible for vaccine-
associated encephalopathy/encephalitis, but evidence linking these 
mechanisms directly to MMR vaccine strains (detection of viral antigens 
or antibodies) has not been shown. [Makela A., J. P. Nuorti, and H. 
Peltola. 2002. Neurologic disorders after measles-mumps-rubella 
vaccination. Pediatrics 110(5):957-963.] [Ray, P., J. Hayward, D. 
Michelson, E. Lewis, J. Schwalbe, S. Black, H. Shinefield, M. Marcy, K. 
Huff, J. Ward, J. Mullooly, R. Chen, and R. Davis. 2006. Encephalopathy 
after whole-cell pertussis or measles vaccination: Lack of evidence for 
a causal association in a retrospective case-control study. Pediatric 
Infectious Disease Journal 25(9):768-773.]
    In view of the limited mechanistic data, and as influenced by the 
Guiding Principles, the Secretary does not propose to make any changes 
to the Table, leaving intact the Table injury of encephalopathy/
encephalitis for MMR vaccines, with an onset not less than 5 days and 
no more than 15 days from vaccination. However, the Secretary proposes 
to re-organize, clarify, and update the QAI for acute and chronic 
encephalopathy and include a new definition for acute encephalitis 
based on the Brighton Collaboration criteria and several other 
references. [Ford-Jones L., MacGregor D., Richardson S., et al. Acute 
childhood encephalitis and meningoencephalitis: Diagnosis and 
management. Paediatr Child Health (1988). Jan-Feb;3(1):33-40] [Ball R., 
Halsey N., Braun M., et al. Development of case definitions for acute 
encephalopathy, encephalitis, and multiple sclerosis reports to the 
Vaccine Adverse Event Reporting System. Journal of Clinical 
Epidemiology (2002). 55:819-824.]
C. Febrile Seizures
    Febrile seizures are a common cause of convulsions in young 
children. Generally viewed as benign and not indicative of brain 
disease, they occur in two to four percent of children up to age 5 
years. Febrile seizures are often seen as the body temperature 
increases rapidly; but, may develop as the fever is declining. Most 
events last a minute or two, although some can be as brief as a few 
seconds. A family history of febrile seizures increases the child's 
risk of occurrence. Anything that causes fever, such as viral or 
bacterial infections, can bring on a febrile seizure.
    The IOM Committee concluded that the evidence convincingly supports 
a causal relationship between MMR vaccine and febrile seizures. Based 
on seven epidemiologic studies, the Committee had a high degree of 
confidence that there is an increased risk of febrile seizures after 
receipt of MMR vaccine. The Committee assessed the mechanistic evidence 
regarding an association between MMR vaccine and febrile seizures as 
intermediate based on 12 cases presenting clinical evidence. 
[Farrington, P., S. Pugh, A. Colville, A. Flower, J. Nash, P. Morgan-
Capner, M. Rush, and E. Miller. 1995. A new method for active 
surveillance of adverse events from diphtheria/tetanus/pertussis and 
measles/mumps/rubella vaccines. Lancet 345(8949):567-569.] [Miller, E., 
N. Andrews, J. Stowe, A. Grant, P. Waight, and B. Taylor. 2007. Risks 
of convulsion and aseptic meningitis following measles-mumps-rubella 
vaccination in the United Kingdom. American Journal of Epidemiology 
165(6):704-709.] [Barlow, W. E., R. L. Davis, J. W. Glasser, P. H. 
Rhodes, R. S. Thompson, J. P. Mullooly, S. B. Black, H. R. Shinefield, 
J. I. Ward, S. M. Marcy, F. DeStefano, and R. T. Chen. 2001. The risk 
of seizures after receipt of whole-cell pertussis or measles, mumps, 
and rubella vaccine. New England Journal of Medicine 345(9):656-661.]
    Patients who had post-MMR vaccination febrile seizures had no 
higher risk of subsequent seizure or neurodevelopmental disability than 
other children with febrile seizures in the absence of vaccine 
administration. The long-term rate of epilepsy was not increased in 
children who had febrile seizures following MMR vaccination compared 
with children who had febrile seizures of a different etiology 
[Vestergaard, M., A. Hviid, K. M. Madsen, J. Wohlfahrt, P. Thorsen, D. 
Schendel, M. Melbye, and J. Olsen. 2004. MMR vaccination and febrile 
seizures: Evaluation of susceptible subgroups and long-term prognosis. 
Journal of the American Medical Association 292(3):351-357.] [Barlow, 
W. E., R. L. Davis, J. W. Glasser, P. H. Rhodes, R. S. Thompson, J. P. 
Mullooly, S. B. Black, H. R. Shinefield, J. I. Ward, S. M. Marcy, F. 
DeStefano, and R. T. Chen. 2001. The risk of seizures after receipt of 
whole-cell pertussis or measles, mumps, and rubella vaccine. New 
England Journal of Medicine 345(9):656-661.]
    Although febrile seizures can be alarming to parents and other 
family members, the overwhelming majority of children who have febrile 
seizures recover quickly and have no lasting effects. Only very rarely 
can febrile seizures lead to serious injury or disability.

[[Page 45140]]

    The National Childhood Vaccine Injury Act of 1986 requires the 
effects of the alleged vaccine injury must have continued for at least 
6 months (unless the injury results in in-patient hospitalization and 
surgery, or death). Because the current medical literature supports 
febrile seizures only very rarely have long term consequences this 
condition is not being proposed for inclusion on the Table. However, 
the Program will consider causation-in-fact claims for febrile seizures 
leading to serious injury or death on a case-by-case basis.
D. Transient Arthralgia in Women and Children
    Arthralgia means joint pain without signs of inflammation (e.g. 
erythema, warmth, pallor, edema, or decreased range of movement). 
Arthritis is arthralgia with signs of inflammation. Arthropathy 
encompasses arthralgia or arthritis and refers to any joint disease. 
Unlike arthritis, arthralgia is a symptom and there may be no objective 
measures for confirmation. The IOM concluded that the evidence favors 
acceptance of a causal relationship between MMR vaccine (attributable 
to the rubella component) and transient arthralgia in women and 
children. The IOM had a moderate degree of confidence in the 
epidemiologic evidence for women (based on four studies) that 
consistently reported an increased risk of transient arthralgia after 
MMR vaccination. Similarly, the mechanistic evidence regarding an 
association between rubella vaccine and transient arthralgia in women 
was intermediate based on 13 case reports. Two-thirds of the studies 
involved post-partum women. [Slater, P. E., T. Ben-Zvi, A. Fogel, M. 
Ehrenfeld, and S. Ever-Hadani. 1995. Absence of an association between 
rubella vaccination and arthritis in underimmune postpartum women. 
Vaccine 13(16):1529-1532.] [Ray, P., S. Black, H. Shinefield, A. 
Dillon, J. Schwalbe, S. Holmes, S. Hadler, R. Chen, S. Cochi, and S. 
Wassilak. 1997. Risk of chronic arthropathy among women after rubella 
vaccination. Journal of the American Medical Association 278(7):551-
556] [Tingle, A. J., L. A. Mitchell, M. Grace, P. Middleton, R. 
Mathias, L. MacWilliam, and A. Chalmers. 1997. Randomised double-blind 
placebo-controlled study on adverse effects of rubella immunisation in 
seronegative women. Lancet 349(9061):1277-1281.] [Mitchell, L. A., A. 
J. Tingle, L. MacWilliam, C. Home, P. Keown, L. K. Gaur, and G. T. 
Nepom. 1998. HLA-DR class II associations with rubella vaccine-induced 
joint manifestations. Journal of Infectious Diseases 177(1):5-12.]
    There were seven epidemiologic studies of children that 
consistently reported an increased risk of arthralgia after MMR 
vaccination. The IOM had a moderate degree of confidence in the 
epidemiologic evidence based on the seven studies with sufficient 
validity and precision to assess an association between MMR vaccine and 
transient arthralgia in children. The mechanistic evidence was weak 
based on knowledge about natural rubella infection. [Peltola, H., and 
O. P. Heinonen. 1986. Frequency of true adverse reactions to measles-
mumps-rubella vaccine. Lancet 327(8487):939-942.] [Virtanen, M., H. 
Peltola, M. Paunio, and O. P. Heinonen. 2000. Day-to-day reactogenicity 
and the healthy vaccinee effect of measles-mumps-rubella vaccination. 
Pediatrics 106(5):E62.] [Benjamin, C. M., G. C. Chew, and A. J. Silman. 
1992. Joint and limb symptoms in children after immunization with 
measles, mumps, and rubella vaccine. BMJ 304(6834):1075-1078.] [Davis, 
R. L., E. Marcuse, S. Black, H. Shinefield, et al. 1997. MMR2 
immunization at 4 to 5 years and 10 to 12 years of age: A comparison of 
adverse clinical events after immunization in the vaccine safety 
datalink project. Pediatrics 100(5):767-771] [dos Santos, B. A., T. S. 
Ranieri, M. Bercini, M. T. Schermann, S. Famer, R. Mohrdieck, T. 
Maraskin, and M. B. Wagner. 2002. An evaluation of the adverse reaction 
potential of three measles-mumps-rubella combination vaccines. Revista 
Panamericana de Salud Publica/Pan American Journal of Public Health 
12(4):240-246.] [LeBaron, C. W., D. Bi, B. J. Sullivan, C. Beck, and P. 
Gargiullo. 2006. Evaluation of potentially common adverse events 
associated with the first and second doses of measles-mumps-rubella 
vaccine. Pediatrics 118(4):1422-143] [Heijstek, M. W., G. C. S. 
Pileggi, E. Zonneveld-Huijssoon, et al. 2007. Safety of measles, mumps 
and rubella vaccination in juvenile idiopathic arthritis. Annals of the 
Rheumatic Diseases 66(10):1384-1387.]
    Because transient arthralgia is a subjective symptom that 
frequently lacks objective evidence for confirmation and has no long-
term effects or consequences, this condition is not being proposed for 
inclusion on the Table.
E. Chronic Arthropathy in Women and Children and Arthropathy in Men
    The IOM concluded that the evidence was inadequate to accept or 
reject a causal relationship between MMR vaccine and chronic 
arthropathy in women and children, as well as arthropathy in men. The 
committee had limited confidence in the epidemiologic evidence for 
rubella vaccine and chronic arthralgia or arthritis. The epidemiologic 
evidence was insufficient or absent to assess an association between 
measles or mumps vaccine and chronic arthralgia or chronic arthritis in 
women. The IOM assessed the mechanistic evidence regarding rubella 
vaccine and chronic arthralgia or chronic arthritis in women as low-
intermediate; and as lacking between measles or mumps vaccine and 
chronic arthralgia or chronic arthritis in women. In children, the IOM 
found the epidemiologic evidence to be insufficient or absent for the 
association between MMR and chronic arthropathy. The IOM found the 
mechanistic evidence between rubella vaccine and chronic arthropathy to 
be weak and they found the evidence to be lacking for measles and mumps 
vaccines. The IOM had limited confidence in the epidemiologic evidence 
for an association between MMR vaccine and arthropathy in men. The IOM 
found the mechanistic evidence regarding the association between 
rubella vaccine and arthropathy in men to be weak. The IOM found the 
mechanistic evidence between measles or mumps vaccine and arthropathy 
in men as lacking. [Ray, P., S. Black, H. Shinefield, A. Dillon, J. 
Schwalbe, S. Holmes, S. Hadler, R. Chen, S. Cochi, and S. Wassilak. 
1997. Risk of chronic arthropathy among women after rubella 
vaccination. Journal of the American Medical Association 278(7):551-
556.] [Tingle, A. J., L. A. Mitchell, M. Grace, P. Middleton, R. 
Mathias, L. MacWilliam, and A. Chalmers. 1997. Randomised double-blind 
placebo-controlled study on adverse effects of rubella immunization in 
seronegative women. Lancet 349(9061):1277-1281.] Peters, M. E., and S. 
Horowitz. 1984. Bone changes after rubella vaccination. American 
Journal of Roentgenology 143(1):27-28. Geiger, R., F. M. Fink, B. 
Solder, M. Sailer, and G. Enders. 1995. Persistent rubella infection 
after erroneous vaccination in an immunocompromised patient with acute 
lymphoblastic-leukemia in remission. Journal of Medical Virology 
47(4):442-444.]
    In spite of the limited epidemiological and mechanistic data, based 
on the Guiding Principles, the Secretary does not propose to make any 
changes to the Table, leaving intact the Table injury of chronic 
arthritis for MMR vaccines, with an onset not less than 7 days and no 
more than 42 days from vaccination. However, the Secretary proposes to

[[Page 45141]]

provide a definition for chronic arthritis in the QAI, based on the 
Brighton Collaboration criteria and several other references.
F. Shoulder Injury Related to Vaccination
    The Secretary proposes to add SIRVA to the Table for vaccines 
containing measles, mumps and/or rubella virus. [See section I.A 
above.] The interval of onset will be less than or equal to 48 hours. 
However, the Secretary recognizes that there currently is no 
intramuscular formulation of this vaccine available and therefore, 
petitioners alleging an injury of SIRVA associated with this vaccine 
presently cannot meet the QAI for SIRVA. Please see section I.A., 
above, for additional discussion on this point.
G. Vasovagal Syncope
    The Secretary proposes to add vasovagal syncope to the Table for 
vaccines containing measles, mumps and/or rubella virus. [See section 
I.B above.] The proposed time interval of onset is less than or equal 
to 1 hour following vaccination.

IV. Vaccines Containing Polio Inactivated Virus

    Since 2000, inactivated polio vaccine (IPV) has been the only polio 
vaccine used in the United States, although live virus oral polio 
vaccine (OPV) is still used in many parts of the world. The Secretary 
proposes changes to the Table related only to IPV, as an injected 
vaccine. OPV was included in the original statutory Table and remains 
on the regulatory Table.
A. Shoulder Injury Related to Vaccination
    The Secretary proposes to add SIRVA as a Table injury for vaccines 
containing polio inactivated virus. [See Section I.A above.] The 
interval of onset will be less than or equal to 48 hours.
B. Vasovagal Syncope
    The Secretary proposes to add vasovagal syncope to the Table for 
vaccines containing polio inactivated virus. [See Section I.B above.] 
The proposed time interval of onset is less than or equal to 1 hour 
following vaccination.

V. Hepatitis B Vaccines

    The recombinant hepatitis B vaccine was first licensed by the FDA 
in 1986. Produced from cultured and purified yeast cells, it is the 
current form of vaccine used in the United States. Prior to 1991, the 
vaccine was recommended only for high risk individuals. However, the 
recommendation was extended to include all infants, since infected 
infants and children are at higher risk for developing chronic liver 
disease with subsequent liver cancer, and approximately one-third of 
those who acquire hepatitis B infection do not have any identified risk 
factors, and, therefore, were frequently not immunized. The effective 
date of coverage for hepatitis B vaccine is August 6, 1997.
A. Shoulder Injury Related to Vaccination
    The Secretary proposes to add SIRVA as a Table injury for hepatitis 
B vaccines. [See section I.A above.] The interval of onset will be less 
than or equal to 48 hours.
B. Vasovagal Syncope
    The Secretary proposes to add vasovagal syncope to the Table for 
hepatitis B vaccines. [See section I.B above.] The proposed time 
interval of onset is less than or equal to 1 hour following 
vaccination.

VI. Haemophilus Influenzae Type B Vaccines

    Haemophilus influenzae type b (Hib) conjugate vaccines were first 
licensed by the FDA in 1987 and have been recommended by the CDC for 
routine use since 1991. The vaccine is given to infants and children up 
to the age of school entry. The effective date of coverage for Hib 
vaccines is August 6, 1997, with no injuries or conditions specified.
    In order for a category of vaccines to be covered under the VICP, 
the category of vaccine must be recommended for routine administration 
to children by the Centers for Disease Control and Prevention (for 
example, vaccines that protect against seasonal influenza), subject to 
an excise tax by Federal law, and added to the Program by the Secretary 
of Health and Human Services. The Internal Revenue Code defines a 
``taxable vaccine'' as including ``[a]ny HIB vaccine''. See 26 U.S.C. 
4132(a)(1)(H). Thus, the Secretary proposes to modify category IX on 
the Table from ``Haemophilus influenzae type b polysaccharide conjugate 
vaccines'' to ``Haemophilus influenza type b vaccines,'' as a technical 
change in order to be most inclusive.
A. Shoulder Injury Related to Vaccination
    The Secretary proposes to add SIRVA as a Table injury for Hib 
vaccines. [See section I.A above.] The interval of onset will be less 
than or equal to 48 hours.
B. Vasovagal Syncope
    The Secretary proposes to add vasovagal syncope to the Table for 
Hib vaccines. [See I.B.] The proposed time interval of onset is less 
than or equal to 1 hour following vaccination.

VII. Varicella Vaccines

    The varicella (chickenpox) virus vaccine, which was first licensed 
by the Food and Drug Administration in 1995, contains a live, 
attenuated strain of the varicella virus. Chickenpox is a highly 
contagious disease and although usually mild, infants, adolescents, 
adults, pregnant women, and immunocompromised individuals are at higher 
risk for serious complications. Since the introduction of the vaccine 
there has been a significant decrease in the number of cases of the 
disease with the greatest effect in states with the highest vaccination 
coverage. Varicella vaccine is listed on the Table, effective August 6, 
1997, with no injuries or conditions specified.
A. Disseminated Vaccine-Strain Viral Disease
    Disseminated varicella vaccine-strain viral disease is a condition 
in which the affected individual develops the varicella rash caused by 
the vaccine strain that spreads beyond the dermatome (an area of skin 
supplied by the nerve fibers of a single spinal root) involved in the 
vaccination and/or there is involvement of other organs such as the 
brain, lungs, and liver. For organs other than the skin, disease, not 
just mildly abnormal laboratory values, must be demonstrated in the 
involved organ. In this section, the word ``disseminated'' is defined 
by the IOM as the spreading of the rash (or the virus) beyond the 
dermatome involved in the vaccination.
    The IOM reviewed the evidence for vaccine causation of disseminated 
varicella disease with and without involvement of organs beyond the 
skin. They found three case reports in which vaccinated individuals 
developed lesions confined to the skin after immunization, and in whose 
lesions the vaccine strain of the varicella virus was identified. In 
addition, the IOM identified 550 cases reported to passive surveillance 
systems in which an attempt was made to identify the virus from skin 
lesions in individuals who developed disseminated varicella disease 
after vaccination without involvement of another organ. The wild-type 
virus was identified in 210 cases; the vaccine-strain virus was 
identified in 125 cases; and in the remaining cases either the sample 
was inadequate, the virus could not be identified, or there

[[Page 45142]]

was no virus present. The committee also identified nine cases in which 
the vaccine strain of the virus was identified in individuals who had 
meningitis, pneumonia or hepatitis in addition to skin lesions. Cases 
of disseminated disease, which were reviewed by the IOM in individuals 
who were thought to be immunocompetent, all occurred within 42 days of 
immunization. The time of onset was not further specified. In many 
cases the timeframe from vaccination to onset of disseminated illness, 
without other organ involvement, was not provided for immunocompromised 
individuals, but in the cases for which there was data, there was a 
broad range of onset, spanning from 1 week in one case to ``up to 87 
days'' in another. For four cases, in which onset was reported, the 
interval following vaccination was 18 days to 6 weeks. For disseminated 
disease with other organ involvement, onset was 13 days after 
vaccination in the only immunocompetent patient for whom data was 
available, and onset was between 10 and 35 days in eight 
immunocompromised individuals. [Wise, R. P., M. E. Salive, M. M. Braun, 
G. T. Mootrey, J. F. Seward, L. G. Rider, and P. R. Krause. 2000. 
Postlicensure safety surveillance for varicella vaccine. Journal of the 
American Medical Association 284(10):1271-1279.] [Goulleret, N., E. 
Mauvisseau, M. Essevaz-Roulet, M. Quinlivan, and J. Breuer. 2010. 
Safety profile of live varicella virus vaccine (Oka/Merck): Five-year 
results of the European varicella zoster virus identification program 
(EU VZVIP). Vaccine 28 (36):5878-5882.]
    The IOM found the evidence convincingly supports a causal 
relationship between varicella vaccine and disseminated varicella 
disease, both for cases confined to the skin and for cases where the 
spread involves other organs. However, the IOM limited their finding of 
causation in cases in which organs beyond the skin were involved to 
those with demonstrated immunodeficiencies. The Secretary notes that 
there is a significant overlap in the time-frames involved in the onset 
of disseminated disease in both immunocompetent and immunocompromised 
individuals. The Secretary further notes that although the IOM found 
convincing support for disseminated disease with other organ 
involvement only in immunocompromised individuals, the Secretary 
proposes, in accordance with the ACCV Guiding Principles, that the 
Table injury apply to all individuals, regardless of the status of 
their immune system, because it is possible that an individual so 
affected may not have been completely evaluated for an existing 
immunodeficiency, or suffered from an immunodeficiency that is subtle 
and beyond our current ability to test.
    The Secretary proposes to add disseminated vaccine-strain 
infection, both with and without other organ involvement, as a Table 
injury for varicella-containing vaccines. There is no time interval for 
onset if the vaccine strain of the virus is identified. However, if 
testing is not done or does not identify the virus, it is proposed that 
the injury qualify as a Table injury if the onset is 7 to 42 days 
following vaccination. If the wild-type virus or another non-vaccine-
strain virus is identified, there will be no presumption of causation 
and it will not meet the Table criteria. If there is involvement of an 
organ beyond the skin, and no virus was identified in that organ, the 
involvement of all organs must occur as part of the same discrete 
illness.
B. Varicella Vaccine-Strain Viral Reactivation
    Varicella vaccine-strain viral reactivation disease is defined as 
the presence of the rash of herpes zoster (shingles) with or without 
concurrent disease in another organ. Shingles is a painful, blistering 
skin rash due to the reactivation of varicella (chickenpox) virus that 
involves one or more sensory dermatomes. After natural varicella 
infection, the virus lies dormant in the spinal dorsal root ganglia. 
Shingles occurs after the virus becomes active again.
    There is a significant body of literature showing that the vaccine-
strain of the virus can cause shingles without other organ involvement. 
However, the wild-type chickenpox virus has been identified in many of 
the cases occurring after vaccination. The Committee reviewed 111 cases 
in which individuals who received a varicella-containing vaccine 
developed reactivated varicella disease without other organ involvement 
and in whom the vaccine-strain of the virus was identified. The IOM 
found six cases in which individuals who had received varicella vaccine 
developed reactivated disease in another organ, and in all the cases, 
the vaccine-strain of the virus was identified in the other organ. In 
four of those cases, the vaccine-strain of the virus was also 
identified in the skin. The findings for other organ involvement in 
these case reports were limited to the meninges and brain. The IOM 
concluded that the evidence convincingly supports a causal relationship 
between varicella vaccine and vaccine-strain viral reactivation, with 
or without involvement of an organ other than the skin. [Chaves, S. S., 
P. Haber, K. Walton, R. P. Wise, H. S. Izurieta, D. S. Schmid, and J. 
F. Seward. 2008. Safety of varicella vaccine after licensure in the 
United States: Experience from reports to the vaccine adverse event 
reporting system, 1995-2005. Journal of Infectious Diseases 197(SUPPL. 
2):S170-S177.] [Iyer, S., M. K. Mittal, and R. L. Hodinka. 2009. Herpes 
zoster and meningitis resulting from reactivation of varicella vaccine 
virus in an immunocompetent child. Annals of Emergency Medicine 
53(6):792-795.] [Levin, M. J., R. L. DeBiasi, V. Bostik, and D. S. 
Schmid. 2008. Herpes zoster with skin lesions and meningitis caused by 
two different genotypes of the Oka varicella-zoster virus vaccine. 
Journal of Infectious Diseases 198(10):1444-1447.]
    The Secretary proposes to add vaccine-strain viral reactivation, 
both with and without other organ involvement, as a Table injury for 
varicella-containing vaccines. Although the IOM specified whether they 
considered immunocompetent or immunocompromised individuals, their 
causality conclusions for vaccine-strain reactivation, with and without 
other organ involvement, did not differentiate between these two 
groups. Because disease caused by varicella virus reactivation can 
occur many years, or even decades, after the initial disease or 
vaccination, the Secretary proposes that the QAI require laboratory 
confirmation of the presence of the vaccine-strain of the virus. With 
such confirmation, the status of the affected individual's immune 
system is not relevant. In addition, there is no proposed time interval 
for this injury, as laboratory confirmation of vaccine-strain virus 
obviates the need for such a proposal. Since petitioners must 
demonstrate the presence of vaccine-strain varicella infection, the 
presumption includes the involvement of skin and other organs.
C. Anaphylaxis
    Anaphylaxis is a single discrete event that presents as a severe 
and potentially life threatening multi-organ reaction, particularly 
affecting the skin, respiratory tract, cardiovascular system, and the 
gastrointestinal tract. The diagnosis of anaphylaxis requires the 
simultaneous involvement of two or more organ systems. In an 
anaphylactic reaction, an immediate reaction generally occurs within 
minutes after exposure, and in most cases, the individual develops 
signs and symptoms within 4 hours after exposure to the antigen. The 
immediate reaction

[[Page 45143]]

leads to a combination of skin rash, mucus membrane swelling, leakage 
of fluid from the blood into surrounding tissues, tightening of the air 
passages in the lungs with tissue swelling, and gastrointestinal 
symptoms that can lead to shock, organ damage, and death if not 
promptly treated.
    Symptoms may include swelling, itching, rash, trouble breathing, 
chest tightness, and/or dizziness. Death, if it occurs, usually results 
from airway obstruction caused by laryngeal edema (throat swelling) or 
bronchospasm and may be associated with cardiovascular collapse.
    Other significant clinical signs and symptoms may include the 
following: cyanosis (bluish coloration in the skin due to low blood 
oxygen levels), hypotension (low blood pressure), bradycardia (slow 
heart rate), tachycardia (fast heart rate), arrhythmia (irregular heart 
rhythm), edema (swelling) of the pharynx and/or larynx (throat or upper 
airway) with stridor (noisy breathing on inspiration), dyspnea 
(shortness of breath), diarrhea, vomiting, and abdominal pain. Autopsy 
findings may include acute emphysema (a type of lung abnormality), 
which results from lower respiratory tract obstruction, edema 
(swelling) of the upper airway, and minimal findings of eosinophilia 
(an excess of a type of white blood cell associated with allergy) in 
the liver. When death occurs within minutes of exposure without signs 
of respiratory distress, lack of significant pathologic findings would 
not exclude a diagnosis of anaphylaxis.
    Anaphylaxis may occur following exposure to allergens from a 
variety of sources including food, aeroallergens, insect venom, drugs, 
and immunizations. Most treated cases resolve without sequela. 
Anaphylaxis can be due to an exaggerated acute systemic 
hypersensitivity reaction, especially involving immunoglobulin E 
antibodies, as in allergic anaphylaxis, or it could be a non-
immunologically mediated reaction leading to similar clinical 
symptomatology as in non-immune anaphylaxis. Non-immune anaphylaxis 
cannot be detected by skin tests or in vitro allergy diagnostic 
procedures. As stated, anaphylaxis is a single discrete event. It is 
not an initial episode of a chronic condition such as chronic urticaria 
(hives).
    Anaphylaxis following immunization is a rare occurrence with 
estimates in the range of 1-10 per 1 million doses distributed, 
depending on the vaccine studied. [The Brighton Collaboration 
Anaphylaxis Working Group, ``Anaphylaxis: Case Definition and 
Guidelines for Data Collection, Analysis, and Presentation of 
Immunization Safety Data, Vaccine, Aug. 2007; 5676.] The IOM has 
reported that the evidence favors acceptance of a causal relationship 
between certain vaccines and anaphylaxis based on case reports and case 
series. The IOM has reported that causality could be inferred with 
reasonable certainty based on one or more case reports because of the 
unique nature and timing of anaphylaxis following vaccine 
administration and provided there is an absence of likely alternative 
causes. [Institute of Medicine (IOM), Immunization Safety Review 
Vaccination and Sudden Unexpected Death in Infancy, Washington, DC: The 
National Academies Press, 2003) 55.] The IOM concluded that the 
scientific evidence convincingly supports a causal relationship between 
varicella vaccine and anaphylaxis. There are multiple, well-documented 
reports in the literature that anaphylaxis occurs after receipt of the 
varicella vaccine. One case series reported 16 cases of anaphylaxis 
after vaccination against varicella, with nearly all demonstrating 
anti-gelatin immunoglobulin E (IgE) antibodies. [Sakaguchi, M., T. 
Nakayama, H. Fujita, M. Toda, and S. Inouye. 2000b. Minimum estimated 
incidence in Japan of anaphylaxis to live virus vaccines including 
gelatin. Vaccine 19(4-5):431-436.]
    There is a long history of including anaphylaxis as a known adverse 
effect of vaccines, including in the initial Table contained in the 
Act. The time-frame for the first symptom or manifestation of onset 
contained in the original statutory Table was shortened from 24 hours 
to 4 hours in the Table changes promulgated in 1995. Since that time, 
anaphylaxis has been added as an injury for the Hepatitis B vaccine.
    The statute requires that injuries eligible for compensation under 
the Program be of sufficient seriousness to cause continued effects for 
more than 6 months, result in death, or result in inpatient 
hospitalization and surgical intervention. The Secretary continues to 
recognize that in many instances, cases involving anaphylaxis will not 
meet the statutory severity criteria, as the reaction can be short-
lived and treated effectively. However, because there is a known risk 
of serious residual injury or death from anaphylaxis, the Secretary 
continues to recommend that anaphylaxis be included on the Table for 
other vaccines, and be added for varicella virus vaccines.
    The Secretary proposes to add anaphylaxis as a Table injury for 
varicella virus-containing vaccines, with an onset less than or equal 
to 4 hours from the administration of the vaccine. In addition, the 
Secretary proposes to update the definition of anaphylaxis in the QAI. 
(see proposed regulation text at proposed paragraph (c)(1)).
D. Shoulder Injury Related to Vaccination
    The Secretary proposes to add SIRVA as a Table injury for varicella 
virus-containing vaccines. [See section I.A above.] The interval of 
onset will be less than or equal to 48 hours. However, the Secretary 
recognizes that there currently is no intramuscular formulation of this 
vaccine available, and therefore petitioners alleging an injury of 
SIRVA associated with this vaccine presently cannot meet the QAI for 
SIRVA. Please see section I.A., above, for additional discussion on 
this point.
E. Vasovagal Syncope
    The Secretary proposes to add vasovagal syncope to the Table for 
varicella virus-containing vaccines. [See section I.B above.] The 
proposed time interval of onset is less than or equal to 1 hour 
following vaccination.

VIII. Pneumococcal Conjugate Vaccines

    Pneumococcal conjugate vaccines were first licensed by FDA in 2000. 
Over the next decade, the heptavalent (seven serotypes) vaccine 
dramatically reduced the rate of invasive pneumococcal disease in young 
infants and nasal carriage of the vaccine serotypes among all age 
groups, including the immunocompromised and older individuals. A 13-
valent pneumococcal conjugate vaccine licensed in 2010 has replaced the 
7-valent product in the infant schedule. Pneumococcal conjugate 
vaccines are included on the Table, with an effective date of coverage 
of December 19, 1999, with no injuries or conditions specified.
A. Shoulder Injury Related to Vaccination
    The Secretary proposes to add SIRVA as a Table injury for 
pneumococcal conjugate vaccines. [See section I.A above.] The interval 
of onset will be less than or equal to 48 hours.
B. Vasovagal Syncope
    The Secretary proposes to add vasovagal syncope to the Table for 
pneumococcal conjugate vaccines. [See section I.B above.] The proposed 
time interval of onset is less than or equal to 1 hour following 
vaccination.

IX. Hepatitis A Vaccines

    Hepatitis A vaccine was first licensed by FDA in 1996 and 
introduced incrementally, first for children living in

[[Page 45144]]

communities with the highest rates of disease and then in 1999 for 
children living in States/communities with consistently elevated rates 
of infection. The impact of immunization with hepatitis A vaccine has 
been a dramatic decline in the rates of disease and a sharp reduction 
in the groups with the highest risk of infection: Native Americans and 
Alaskan natives. Rates of hepatitis A infection are now similar in most 
areas of the United States. As a consequence, hepatitis A vaccine has 
now been recommended for all children in the United States who are 12-
23 months of age. Hepatitis A vaccine is included on the Table, with an 
effective date of December 1, 2004.
A. Shoulder Injury Related to Vaccination
    The Secretary proposes to add SIRVA as a Table injury for hepatitis 
A vaccines. [See section I.A above.] The interval of onset will be less 
than or equal to 48 hours.
B. Vasovagal Syncope
    The Secretary proposes to add vasovagal syncope to the Table for 
hepatitis A vaccines. [See section I.B above.] The proposed time 
interval of onset is less than or equal to 1 hour following 
vaccination.

X. Seasonal Influenza Vaccines

    All seasonal trivalent influenza vaccines have been covered under 
the VICP since July 1, 2005. At that time, all seasonal influenza 
vaccines were trivalent. Quadrivalent vaccines for seasonal influenza 
became available for general use for the 2013-14 influenza season. On 
June 25, 2013, Public Law 113-15 was enacted, extending the applicable 
excise tax on trivalent influenza vaccines to also include any other 
vaccines against seasonal influenza. See Public Law 113-15 (amending 26 
U.S.C. 4132(a)(1)(N)). The amendment included in Public Law 113-15 
ensured that seasonal influenza vaccines are covered under the Program. 
Seasonal influenza vaccines (other than trivalent influenza vaccines) 
were added to the Table under the final catch-all category (42 CFR 
100.3(c)(8)) with an effective date of November 12, 2013. The Secretary 
proposes to modify category XIV on the Table from ``Trivalent influenza 
vaccines'' to ``Seasonal influenza vaccines.''
    There are currently six types of seasonal influenza vaccines 
distributed during flu season. The standard dose trivalent inactivated 
influenza vaccine (IIV3) contains three killed virus strains and is 
injected. IIV3 is indicated in individuals 6 months of age or older, 
including healthy people and those with chronic medical conditions 
(such as asthma, diabetes, or heart disease). High dose trivalent 
inactivated influenza vaccine (IIV3 High dose) is indicated in 
individuals who are 65 years of age or older. Trivalent recombinant 
influenza vaccine (RIV3) is indicated for individuals between the ages 
of 18 and 49 years. The standard dose quadrivalent inactivated 
influenza vaccine (IIV4) has the same indications as IIV3. The 
quadrivalent live attenuated influenza vaccine (LAIV4) is indicated for 
healthy, non-pregnant persons aged 2-49 years. The cell-culture based 
inactivated influenza vaccine (ccIIV3) is indicated for individuals who 
are 18 years of age and older.
    The covered injuries proposed for seasonal influenza vaccines are 
the same as those proposed for trivalent influenza vaccines. The 
trivalent influenza vaccine and the quadrivalent influenza vaccine, 
distributed each year during flu season, are types of seasonal 
influenza vaccines.
A. Anaphylaxis
    The Secretary proposes to add anaphylaxis as a Table injury for 
seasonal influenza vaccines. [See section VII.C above.] The IOM 
concluded that the scientific evidence convincingly supports a causal 
relationship between trivalent influenza vaccines and anaphylaxis. 
Sensitivity to eggs has long been known to cause allergic reactions to 
influenza vaccination in some individuals. The IOM assessed the 
mechanistic evidence as strong, including the following: 21 case 
reports of potential anaphylaxis following influenza vaccine; a strong 
temporal relationship between vaccine administration and anaphylactic 
reaction; isolation of anti-gelatin IgE in two cases; positive skin 
testing as a positive re-challenge in two cases; and repeated symptoms 
to vaccination against influenza on two occasions. Their conclusion 
made no distinction between the intranasal live attenuated vaccine and 
the injected vaccine. [Coop, C.A., S.K. Balanon, K.M. White, B. A. 
Whisman, and M.M. Rathkopf. 2008. Anaphylaxis from the influenza virus 
vaccine. International Archives of Allergy and Immunology 146(1):85-
88.] [Chung, E.Y., L. Huang, and L. Schneider. 2010. Safety of 
influenza vaccine administration in egg-allergic patients. Pediatrics 
125(5):e1024-e1030.] [Lasley, M.V. 2007. Anaphylaxis after booster 
influenza vaccine due to gelatin allergy. Pediatric Asthma, Allergy and 
Immunology 20(3):201-205.]
    The Secretary proposes to add anaphylaxis as a Table injury for 
seasonal influenza vaccines, with an onset of less than or equal to 4 
hours from the administration of the vaccine. In addition, the 
Secretary proposes to update the definition of anaphylaxis in the QAI.
B. Shoulder Injury Related to Vaccination
    The Secretary proposes to add SIRVA only for seasonal influenza 
vaccines that are injected intramuscularly (as detailed in the proposed 
QAI). As proposed, this injury would not apply to formulations of the 
live attenuated influenza vaccine (LAIV), as LAIV is not administered 
intramuscularly with a needle. [See section I.A above.] In addition, 
this injury would not apply to the formulations of influenza vaccine 
where the route of administration is intradermal, such as the 
formulation that delivers 0.1 milliliters of vaccine through a 
prefilled microinjection system that contains a needle that is only 1.5 
millimeters long. This needle is not long enough to enter the deltoid 
bursa or any other structure in the shoulder related to the development 
of SIRVA. SIRVA would apply only to formulations of the seasonal 
influenza vaccine that are administered through intramuscular 
injection. The interval of onset will be less than or equal to 48 
hours.
C. Vasovagal Syncope
    The Secretary proposes to add vasovagal syncope to the Table for 
injected vaccines only (as detailed in the proposed QAI). As proposed, 
this injury would apply to the seasonal inactivated influenza vaccine 
that is injected intramuscularly but not to the LAIV, as LAIV is not 
administered with a needle, and the syncopal reaction appears to be 
related to the act of injection. [See section I.B above.] The proposed 
time interval of onset is less than or equal to 1 hour following 
vaccination.
D. Guillain-Barr[eacute] Syndrome (GBS)
    GBS is an acute paralysis caused by dysfunction in the peripheral 
nervous system (i.e., the nervous system outside the brain and spinal 
cord). GBS may manifest with weakness, abnormal sensations, and/or 
abnormality in the autonomic (involuntary) nervous system. In the 
United States, each year approximately 3,000 to 4,000 cases of GBS are 
reported, and the incidence of GBS increases in older individuals. 
Senior citizens tend to have a poorer prognosis. Most people fully 
recover from GBS, but some people can either

[[Page 45145]]

develop permanent disability or die due to respiratory difficulties. It 
is not fully understood why some people develop GBS, but it is believed 
that stimulation of the body's immune system, as occurs with 
infections, can lead to the formation of autoimmune antibodies and 
cell-mediated immunity that play a role in its development.
    GBS may present as one of several clinicopathological subtypes. The 
most common type in North America and Europe, comprising more than 90 
percent of cases, is acute inflammatory demyelinating polyneuropathy 
(AIDP), which has the pathologic and electrodiagnostic features of 
focal demyelination of motor and sensory peripheral nerves and roots. 
Demyelination refers to a loss or disruption of the myelin sheath, 
which wraps around the axons of some nerve cells and which is necessary 
for the normal conduction of nerve impulses in those nerves that 
contain myelin. Polyneuropathy refers to the involvement of multiple 
peripheral nerves. Motor nerves affect muscles or glands. Sensory 
nerves transmit sensations. The axon is a portion of the nerve cell 
that transmits nerve impulses away from the nerve cell body. Another 
subtype of GBS, called acute motor axonal neuropathy (AMAN), is 
generally seen in other parts of the world and is predominated by 
axonal damage that primarily affects motor nerves. AMAN lacks features 
of demyelination. Another less common subtype of GBS includes acute 
motor and sensory neuropathy (AMSAN), which is an axonal form of GBS 
that is similar to AMAN, but also affects the axons of sensory nerves 
and roots.
    The diagnosis of the AIDP, AMAN, and AMSAN subtypes of GBS requires 
bilateral flaccid (relaxed with decreased muscle tone) limb weakness 
and decreased or absent deep tendon reflexes in weak limbs, and a 
monophasic illness pattern with the interval between onset and nadir of 
weakness between 12 hours and 28 days with a subsequent clinical 
plateau. The clinical plateau leads to either stabilization at the 
nadir of symptoms, or subsequent improvement without significant 
relapse. Death may occur without clinical plateau. Treatment-related 
fluctuations in all subtypes of GBS can occur within 9 weeks of GBS 
symptom onset and recurrence of symptoms after this time-frame would 
not be consistent with GBS. In addition, there must not be a more 
likely alternative diagnosis for the weakness.
    Other factors in all subtypes of GBS that add to diagnostic 
certainty, but are not required for diagnosis, include 
electrophysiologic findings consistent with GBS or cytoalbuminologic 
dissociation (i.e., elevation of cerebral spinal fluid (CSF) protein 
and a total white cell count in the CSF less than 50 cells per 
microliter).
    The weakness in the AIDP, AMAN, and AMSAN subtypes of GBS is 
usually, but not always, symmetric and usually has an ascending pattern 
of progression from legs to arms. However, other patterns of 
progression may occur. The cranial nerves can be involved. Respiratory 
failure can occur due to respiratory involvement. Fluctuations in the 
degree of weakness prior to reaching the point of greatest weakness or 
during the plateau or improvement phase may occur, especially in 
response to treatment. These fluctuations occur in the first 9 weeks 
after onset and are generally followed by eventual improvement.
    According to the Brighton Collaboration, Fisher Syndrome (FS), also 
known as Miller Fisher Syndrome, is a subtype of GBS characterized by 
ataxia, areflexia, and ophthalmoplegia, and overlap between FS and GBS 
may be seen with limb weakness. [James J. Sejvar et. al. Guillain-Barre 
Syndrome and Fisher Syndrome: Case definitions and guidelines for 
collection, analysis, and presentation of immunization safety data 
Vaccine 29(3):599-612]. The diagnosis of FS requires bilateral 
ophthalmoparesis; bilateral reduced or absent tendon reflexes; ataxia; 
the absence of limb weakness (the presence of limb weakness suggests a 
diagnosis of AIDP, AMAN, or AMSAN); a monophasic illness pattern; an 
interval between onset and nadir of weakness between 12 hours and 28 
days; subsequent clinical plateau (the clinical plateau leads to either 
stabilization at the nadir of symptoms or subsequent improvement 
without significant relapse); no alteration in consciousness; no 
corticospinal track signs; and the absence of an identified, more 
likely, alternative diagnosis. Death may occur without a clinical 
plateau.
    Exclusionary criteria for the diagnosis of GBS include the ultimate 
diagnosis of any of the following conditions: Chronic inflammatory 
demyelinating polyneuropathy (CIDP), carcinomatous meningitis, brain 
stem encephalitis (other than Bickerstaff brainstem encephalitis), 
myelitis, spinal cord infarct, spinal cord compression, anterior horn 
cell diseases such as polio or West Nile virus infection, subacute 
inflammatory demyelinating polyradiculoneuropathy, multiple sclerosis, 
cauda equina compression, metabolic conditions such as hypermagnesemia 
or hypophosphatemia, tick paralysis, heavy metal toxicity (such as 
arsenic, gold, or thallium), drug-induced neuropathy (such as 
vincristine, platinum compounds, or nitrofurantoin), porphyria, 
critical illness neuropathy, vasculitis, diphtheria, myasthenia gravis, 
organophosphate poisoning, botulism, critical illness myopathy, 
polymyositis, dermatomyositis, hypokalemia, or hyperkalemia. The above 
list is not exhaustive. [Sejvar 599-612].
    For all subtypes of GBS (AIDP, AMAN, AMSAN, and FS), the onset of 
symptoms less than 3 days (72 hours) after exposure excludes that 
exposure as a cause because the immunologic steps necessary to create 
symptomatic disease require a minimum of 3 days.
    CIDP is clinically and pathologically distinct from GBS. The onset 
phase of CIDP is generally greater than 8 weeks and the weakness may 
remit and relapse. CIDP is also not monophasic. [Sejvar 599-612.]
    In the past, GBS has been causally associated with certain 
vaccines. For example, the 1976 influenza A (swine flu) vaccine was 
found by the IOM to be causally associated with GBS. The risk of 
developing GBS in the 6 week period after receiving the 1976 swine flu 
vaccine was 9.2 times higher than the risk for those who were not 
vaccinated. [Lawrence B. Schonberger, et al., ``Guillain-Barre Syndrome 
Following Vaccination in the National Influenza Immunization Program, 
United States, 1976-1977,'' American Journal of Epidemiology, 25 Apr. 
1979; 118 and IOM, ``Immunization Safety Review: Influenza Vaccines and 
Neurological Complications,'' (Washington, DC: The National Academies 
Press, 2004) 25]. Since the 1976 influenza season, numerous studies 
have been conducted to evaluate whether other influenza vaccines were 
associated with GBS. In most published studies, no association was 
found, but one large study published in the New England Journal of 
Medicine evaluated the 1992-93 and 1993-94 influenza seasons and 
suggested approximately one additional case of GBS out of 1 million 
persons vaccinated, in the 6 weeks following vaccination, may be 
attributable to the vaccine formulation used in those years. The 
background incidence of GBS not associated with a vaccine among adults 
was documented in the study to be 0.87 cases per million persons for 
any 6 week period. [Tamar Lasky, et al., ``The Guillain-Barr[eacute] 
Syndrome and the 1992-1993 and 1993-1994 Influenza Vaccines,'' The New 
England Journal of Medicine, Dec. 17, 1998; 1797.]

[[Page 45146]]

    The IOM published a thorough scientific review of the peer-reviewed 
literature in 2004 and concluded that people who received the 1976 
swine influenza vaccine had an increased risk for developing GBS [IOM, 
Immunization Safety Review: Influenza Vaccines and Neurological 
Complications, 25]. Based on its review of the published literature, 
the IOM also decided that the evidence linking GBS and influenza 
vaccines in influenza seasons other than 1976 was not clear. This led 
to the IOM's conclusion that the evidence was inadequate to accept or 
reject a causal relationship between influenza immunization and GBS for 
years other than 1976.
    In 2012, the IOM published another report that evaluated the 
association of seasonal influenza vaccine and GBS. Pandemic vaccines, 
such as the influenza vaccine used in 1976 and the monovalent 2009 H1N1 
influenza vaccine, were specifically excluded and not evaluated. The 
IOM concluded that the evidence is inadequate to accept or reject a 
causal relationship between seasonal influenza vaccine and GBS. (IOM, 
Adverse Effects of Vaccines 334). It is important to note that 
monovalent vaccines are usually only given in response to an actual or 
potential pandemic, while seasonal influenza vaccines are offered 
annually. The monovalent 2009 H1N1 vaccine, a type of pandemic vaccine, 
is covered under the Countermeasures Injury Compensation Program. The 
VICP does not cover pandemic influenza vaccines, such as the 2009 H1N1 
Influenza vaccine.
    A meta-analysis of the VSD, EIP (Emerging Infections Program--an 
active population-based surveillance program), and PRISM (Post-
Licensure- Rapid Immunization Safety Monitoring--a cohort-based active 
surveillance network) data was performed and published, together with 
additional data from safety surveillance studies performed by Medicare, 
the Department of Defense, and the Department of Veterans Affairs, 
which, in total, analyzed data from 23 million people who were 
vaccinated with the influenza A (H1N1) 2009 monovalent vaccine. [Daniel 
A. Salmon et al., ``Association between Guillain-Barr[eacute] syndrome 
and influenza A (H1N1) 2009 monovalent inactivated vaccines in the USA: 
a meta-analysis,'' Lancet, electronically published March 13, 2013, 
http://dx.doi.org/10.1016/S0140-6736(12)62189-8.] The meta-analysis 
provides the benefit of additional statistical power. Additional power 
allows for the analyses of certain hypotheses which were not possible 
to analyze individually in the six studies that made up the meta-
analysis. The meta-analysis found that the 2009 H1N1 inactivated 
vaccine was associated with a small increased risk of GBS within 6 
weeks of vaccination. This excess risk is equivalent to 1.6 excess 
cases in the 6 weeks after vaccination per million people vaccinated. 
This increased risk found in the meta-analysis was consistent: (1) 
Across studies looking at different groups of people; (2) using 
different definitions of illness; (3) in people who received or did not 
receive a concurrent seasonal influenza vaccine or had influenza-like 
symptoms; (4) across various time windows; and (5) in different age 
categories. This suggests that these five factors did not affect the 
risk of developing GBS.
    Considering the totality of the evidence with the enhanced 
surveillance studies and meta-analysis performed to monitor the safety 
of the monovalent 2009 H1N1 vaccine, scientific evidence demonstrates a 
small increased risk of GBS in the 6 weeks following administration of 
the monovalent 2009 H1N1 vaccines.
    Presently, there is no scientific evidence demonstrating that 
current formulations of the seasonal influenza vaccine, which contain 
the H1N1 virus, can cause GBS. However, the degree of surveillance 
needed to detect an increased risk of one case per million 
vaccinations, as was seen with the monovalent 2009 H1N1 vaccine, is 
unlikely to be routinely performed as the strains in the flu vaccines 
change from year to year. Nonetheless, numerous studies have been 
conducted in order to determine whether a possible association between 
seasonal influenza vaccines and GBS exists, and almost all have not 
shown any causal relationship. The IOM reviewed literature concerning 
such studies and concluded that the evidence was inadequate to accept 
or reject a causal association for all versions of seasonal influenza 
vaccines since 1976.
    Using studies demonstrating a causal association between the 2009 
H1N1 and 1976 swine flu vaccines and GBS as background, the Secretary 
proposes to add the injury of GBS to the Table for seasonal influenza 
vaccines. Although the scientific evidence does not show a causal 
association for current formulations of seasonal flu vaccines and GBS, 
the Secretary proposes including the injury of GBS for seasonal 
influenza vaccines on the Table in accordance with the ACCV Guiding 
Principles, acknowledging the fact that seasonal influenza vaccine 
formulations, unlike other vaccines, change from year-to-year and that 
enhanced surveillance activities may not occur with each virus strain 
change. This is done even though it appears that any instances of GBS 
caused by seasonal influenza vaccines, if they exist at all, are very 
rare. The Secretary proposes adding GBS to the Table for seasonal 
influenza vaccines and recognizes that this will create a presumption 
of causation that will result in compensation for numerous instances of 
GBS that are not vaccine-related.
    While there is no evidence demonstrating that current formulations 
of the seasonal influenza vaccine can cause GBS, the totality of the 
evidence, particularly the enhanced surveillance studies and meta-
analysis performed to monitor the safety of the 2009 H1N1 vaccine, 
provides compelling evidence of a small increased risk of GBS in the 6 
weeks following the administration of the 2009 H1N1 vaccine. Utilizing 
this scientific data as background, the Secretary proposes an onset 
interval of 3-42 days for GBS presumed to be caused by the seasonal 
influenza vaccine to be covered under the proposed Table. Day 3 begins 
72 hours after administration of the vaccination and takes into account 
the time interval needed to show first signs or symptoms after 
exposure. [Peripheral Neuropathy (Philadelphia, PA: Elsevier Saunders, 
2005, 626].

XI. Meningococcal Vaccines

    There are two types of meningococcal vaccines administered in the 
United States. The polysaccharide vaccine was licensed by the FDA in 
1978, and is indicated for persons 2 years of age and older; the 
meningococcal conjugate vaccines were licensed starting in 2005. The 
conjugate vaccines were developed with the expectation that they would 
provide more long-lasting immunity, a more rapid immune response upon 
exposure to Neisseria meningitidis, and the development of ``herd 
immunity'' through reduction of the asymptomatic carrier state. The 
meningococcal polysaccharide and conjugate vaccines were added to the 
Table with an effective date of February 1, 2007.
A. Anaphylaxis
    The Secretary proposes to add anaphylaxis as a Table injury for 
meningococcal vaccines. [See section VII.C above.] The IOM Committee, 
following an extensive review of the scientific and medical literature, 
concluded that the evidence convincingly supported a causal 
relationship between meningococcal vaccines and anaphylaxis. The 
Institute of Medicine based their conclusion on a case report of 
anaphylaxis with onset

[[Page 45147]]

30 minutes following vaccination. [Yergeau, A., L. Alain, R. Pless, and 
Y. Robert. 1996. Adverse events temporally associated with 
meningococcal vaccines. Canadian Medical Association Journal 
154(4):503-507.]
    The Secretary proposes to add anaphylaxis as a Table injury for 
meningococcal vaccines, with an onset less than or equal to 4 hours 
from the administration of the vaccine. In addition, the Secretary 
proposes to update the definition of anaphylaxis in the QAI.
B. Shoulder Injury Related to Vaccination
    The Secretary proposes to add SIRVA as a Table injury for 
meningococcal vaccines. [See section I.A above.] The interval of onset 
will be less than or equal to 48 hours.
C. Vasovagal Syncope
    The Secretary proposes to add vasovagal syncope to the Table for 
meningococcal vaccines. [See section I.B above.] The proposed time 
interval of onset is less than or equal to 1 hour following 
vaccination.

XII. Human Papillomavirus Vaccines

    The first human papillomavirus (HPV) vaccine was licensed by the 
FDA in June 2006 for females between the ages of 9-26 years. In 2011, 
one of the two licensed HPV vaccines was given a permissive use 
recommendation in males by the CDC and other recommending bodies (i.e., 
the American Academy of Pediatrics and the American Academy of Family 
Physicians). HPV vaccine was added to the Table with an effective date 
of February 1, 2007.
A. Anaphylaxis
    The Secretary proposes to add anaphylaxis as a Table injury for HPV 
vaccines. [See VII.C] The IOM Committee concluded that the evidence 
favors acceptance of a causal relationship between human papillomavirus 
vaccines and anaphylaxis. They based their conclusion on temporality 
and clinical symptoms consistent with anaphylaxis in 9 reports from 
VAERS over 31 months of surveillance. [Slade, B.A., L. Leidel, C. 
Vellozzi E.J. et al. Post licensure safety surveillance for 
quadrivalent human papillomavirus recombinant vaccine. Journal of the 
American Medical Association 2009. 302(7):750-757.]
    The Secretary notes that there are limitations to the VAERS passive 
reporting system. First, there is underreporting; not all adverse 
events following vaccines are reported to the system. The rates of 
underreporting have been examined for different disorders and are 
greatest for adverse events of mild severity. Second, many reports are 
filed before a complete clinical evaluation has been conducted. 
Therefore, the presumptive diagnosis that has been provided at the time 
of the report may not be the correct diagnosis. Third, investigations 
conducted after the initial report sometimes reveal alternative causes 
for the adverse event. In many instances, incomplete information is 
provided in the initial report. Follow-up of the reports by the CDC and 
FDA may be conducted to collect additional information from the 
healthcare providers. The primary purpose of VAERS is to look for 
signals for evidence of unexpected adverse events that would require 
other investigations to try to determine causal relationships. Although 
conclusions about causation are not possible for most adverse events 
reported to VAERS, the IOM found likely causality based on the 
distinctive nature of anaphylactic reactions and the temporal 
relationship between the HPV vaccine administration and the event. The 
Secretary proposes to add anaphylaxis as a Table injury for HPV 
vaccines, with an onset of less than or equal to 4 hours from the 
administration of the vaccine. In addition, the Secretary proposes to 
update the definition of anaphylaxis in the QAI.
B. Shoulder Injury Related to Vaccination
    The Secretary proposes to add SIRVA as a Table injury for HPV 
vaccines. [See section I.A above.] The proposed time interval of onset 
is less than or equal to 48 hours.
C. Vasovagal Syncope
    The Secretary proposes to add vasovagal syncope to the Table for 
HPV vaccines. [See section I.B above.] The proposed time interval of 
onset is less than or equal to 1 hour following vaccination.

XIII. Category for Any New Vaccine Recommended by the Centers for 
Disease Control and Prevention for Routine Administration to Children 
After Publication by the Secretary of a Notice of Coverage

    Category XVII of the current Table pertains to any new vaccine 
recommended by the CDC for routine administration to children, after 
publication by the Secretary of a notice of coverage. This category 
pertains to vaccines that are covered under the Program, but with 
respect to which the Secretary has not yet finalized actions adding the 
vaccines as separate categories to the Table. Through this rule, the 
Secretary proposes retaining this category and adding two associated 
injuries for vaccines covered by this category.
A. Shoulder Injury Related to Vaccination
    The Secretary proposes to add SIRVA for the category of vaccines 
captured under Category XVII of the Table. [See section I.A above.] As 
detailed in the proposed QAI, this injury would only apply to 
intramuscular vaccines injected into the upper arm. The interval of 
onset will less than or equal to 48 hours.
B. Vasovagal Syncope
    The Secretary proposes to add vasovagal syncope to the Table for 
this category of vaccines. As detailed in the proposed QAI, this injury 
would apply only to injected vaccines as the syncopal reaction appears 
to be related to the act of injection. [See section I.B above.] The 
proposed time interval of onset is less than or equal to 1 hour 
following vaccination.

XIV. Additional Table Changes

    The Secretary is proposing a number of organizational and 
structural changes to the Table and QAI designed to increase clarity 
and scientific accuracy, including the addition of a glossary of terms 
used within the Table and the QAI.
Organizational Changes
     To streamline the Table, the Secretary proposes a new 
paragraph (b), Provision that applies to all vaccines listed. This 
section includes any acute complication or sequela, including death, of 
the illness, disability, injury, or condition listed, rather than 
adding this provision to every line of the Table.
     To further streamline the Table, the Secretary proposes 
the deletion of redundant wording in the various definitions, 
particularly with regard to any references to the presumption of 
causation, and the importance of the entire medical record. These 
elements have been included in paragraph (b). In addition, complicated 
language previously included in the definition of encephalopathy, which 
indicated that idiopathic injuries do not rebut the Table presumption, 
has been simplified and made generally applicable to all injuries. This 
has also been included in paragraph (b).
     The QAI (proposed paragraph (c)) contain definitions for 
those terms that are used in the Table (paragraphs (a) and (b)).

[[Page 45148]]

     The newly added glossary (proposed paragraphs (d)) defines 
terms used in multiple places in the QAI (proposed paragraph (c)). Most 
of these terms were formerly contained in the QAI, and have been moved 
to the glossary so that each reference is consistent. These definitions 
include: chronic encephalopathy, significantly decreased level of 
consciousness, injected, and seizure.
     The proposed Table and QAI include some changes made by 
the Final Rule adding Intussusception as an Injury for Rotavirus 
Vaccines to the Vaccine Injury Table (80 FR 35848, June 23, 2015).
Expansion
     The Secretary proposes to add definitions for new Table 
injuries, including SIRVA, disseminated varicella-strain virus disease, 
varicella vaccine-strain viral reactivation disease, GBS, and vasovagal 
syncope.
     The Secretary proposes to add definitions of terms that 
had been on the Table or in the QAI, but that previously were 
undefined, including encephalitis, injected, and immunodeficient 
recipient.
Harmonization
     The Secretary proposes additional changes to the QAI to 
address certain changes in scientific nomenclature. Definitions, such 
as acute encephalopathy and acute encephalitis, both of which lead to 
chronic encephalopathy, have been harmonized. Definitions for brachial 
neuritis and SIRVA have also been harmonized.
     The Secretary proposes modification of category XIV on the 
Table from ``Trivalent influenza vaccines'' to ``Seasonal influenza 
vaccines''.
     The Secretary proposes modification of category IX on the 
Table from ``Haemophilus influenzae type b polysaccharide conjugate 
vaccines'' to ``Haemophilus influenzae type b vaccines''.
     Minor technical changes resulting from updated medical 
information have been included in the definitions of anaphylaxis, 
encephalopathy, chronic arthritis, brachial neuritis, thrombocytopenic 
purpura, and seizure.
    All of the proposed changes were discussed and approved by the 
ACCV, although the ACCV expressed some reservations regarding the 
definition of ``immunodeficient recipient''. The discussion was 
reviewed, and the Secretary has modified the definition to address the 
concerns raised by the ACCV.

Economic and Regulatory Impact

    Executive Order 12866 directs agencies to assess all costs and 
benefits of available regulatory alternatives and, when rulemaking is 
necessary, to select regulatory approaches that provide the greatest 
net benefits (including potential economic, environmental, public 
health, safety, distributive, and equity effects). In addition, under 
the Regulatory Flexibility Act, if a rule has a significant economic 
effect on a substantial number of small entities the Secretary must 
specifically consider the economic effect of a rule on small entities 
and analyze regulatory options that could lessen the impact of the 
rule.
    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 an unnecessary burden. Regulations that 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.
    The Secretary has determined that no resources are required to 
implement the requirements in this rule. Compensation will be made in 
the same manner. This proposed rule only lessens the burden of proof 
for potential petitioners. Therefore, in accordance with the Regulatory 
Flexibility Act of 1980 (RFA), and the Small Business Regulatory 
Enforcement Act of 1996, which amended the RFA, the Secretary certifies 
that this rule will not have a significant impact on a substantial 
number of small entities.
    The Secretary has also determined that this proposed rule does not 
meet the criteria for a major rule as defined by Executive Order 12866 
and would have no major effect on the economy or Federal expenditures. 
We have determined that the proposed rule is not a ``major rule'' 
within the meaning of the statute providing for Congressional Review of 
Agency Rulemaking, 5 U.S.C. 801. Similarly, it will not have effects on 
State, local, and tribal governments and on the private sector such as 
to require consultation under the Unfunded Mandates Reform Act of 1995.
    Nor on the basis of family well-being will the provisions of this 
rule affect the following family elements: family safety; family 
stability; marital commitment; parental rights in the education, 
nurture and supervision of their children; family functioning; 
disposable income or poverty; or the behavior and personal 
responsibility of youth, as determined under section 654(c) of the 
Treasury and General Government Appropriations Act of 1999.
    This rule is not being treated as a ``significant regulatory 
action'' under section 3(f) of Executive Order 12866. Accordingly, the 
rule has not been reviewed by the Office of Management and Budget.
    As stated above, this proposed rule would modify the Vaccine Injury 
Table based on legal authority.

Impact of the New Rule

    This proposed rule will have the effect of making it easier for 
future petitioners alleging injuries that meet the criteria in the 
Vaccine Injury Table to receive the Table's presumption of causation 
(which relieves them of having to prove that the vaccine actually 
caused or significantly aggravated the injury).

Paperwork Reduction Act of 1995

    This proposed rule has no information collection requirements.

List of Subjects in 42 CFR Part 100

    Biologics, Health insurance, Immunization.

    Dated: June 24, 2015.
James Macrae,
Acting Administrator, Health Resources and Services Administration.
    Approved: July 10, 2015.
Sylvia M. Burwell,
Secretary.

    Accordingly, 42 CFR part 100 is proposed to be amended as set forth 
below:

PART 100--VACCINE INJURY COMPENSATION

0
1. The authority citation for 42 CFR part 100 continues to read as 
follows:

    Authority:  Secs. 312 and 313 of Public Law 99-660 (42 U.S.C. 
300aa-1 note); 42 U.S.C. 300aa-10 to 300aa-34; 26 U.S.C. 4132(a); 
and sec. 13632(a)(3) of Public Law 103-66.

0
2. Revise Sec.  100.3 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 Public Law 99-660, 100 Stat. 
3779 (42 U.S.C. 300aa-1 note) and section 2114(c) of the Public Health 
Service Act, as amended (PHS 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

[[Page 45149]]

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. Paragraph (b) of this section sets 
forth additional provisions that are not separately listed in this 
Table but that constitute part of it. Paragraph (c) of this section 
sets forth the Qualifications and Aids to Interpretation for the terms 
used in the Table. Conditions and injuries that do not meet the terms 
of the Qualifications and Aids to Interpretation are not within the 
Table. Paragraph (d) of this section sets forth a glossary of terms 
used in paragraph (c).

                          Vaccine Injury Table
------------------------------------------------------------------------
                                                        Time period for
                                                       first symptom or
                                       Illness,        manifestation of
                                  disability, injury      onset or of
             Vaccine                 or condition         significant
                                        covered        aggravation after
                                                            vaccine
                                                        administration
------------------------------------------------------------------------
I. Vaccines containing tetanus    A. Anaphylaxis....  <=4 hours.
 toxoid (e.g., DTaP, DTP, DT,     B. Brachial         2-28 days (not
 Td, or TT).                       Neuritis.           less than 2 days
                                  C. Shoulder Injury   and not more than
                                   Related to          28 days)
                                   Vaccine            <=48 hours.
                                   Administration.
                                  D. Vasovagal        <=1 hour.
                                   syncope.
II. Vaccines containing whole     A. Anaphylaxis....  <=4 hours.
 cell pertussis bacteria,         B. Encephalopathy   <=72 hours
 extracted or partial cell         or encephalitis.   <=48 hours.
 pertussis bacteria, or specific  C. Shoulder Injury
 pertussis antigen(s) (e.g.,       Related to
 DTP, DTaP, P, DTP-Hib).           Vaccine
                                   Administration.
                                  D. Vasovagal        <=1 hour.
                                   syncope.
III. Vaccines containing          A. Anaphylaxis....  <=4 hours.
 measles, mumps, and rubella      B. Encephalopathy   5-15 days (not
 virus or any of its components    or encephalitis.    less than 5 days
 (e.g., MMR, MM, MMRV).           C. Shoulder Injury   and not more than
                                   Related to          15 days)
                                   Vaccine            <=48 hours.
                                   Administration.
                                  D. Vasovagal        <=1 hour.
                                   syncope.
IV. Vaccines containing rubella   A. Chronic          7-42 days (not
 virus (e.g., MMR, MMRV).          arthritis.          less than 7 days
                                                       and not more than
                                                       42 days).
V. Vaccines containing measles    A.                  7-30 days (not
 virus (e.g., MMR, MM, MMRV).      Thrombocytopenic    less than 7 days
                                   purpura.            and not more than
                                  B. Vaccine-Strain    30 days).
                                   Measles Viral
                                   Disease in an
                                   immunodeficient
                                   recipient.
                                  --Vaccine-strain    Not applicable.
                                   virus identified.
                                  --If strain         <=12 months.
                                   determination is
                                   not done or if
                                   laboratory
                                   testing is
                                   inconclusive.
VI. Vaccines containing polio     A. Paralytic Polio  ..................
 live virus (OPV).
                                  --in a non-         <=30 days.
                                   immunodeficient
                                   recipient.
                                  --in an             <=6 months.
                                   immunodeficient
                                   recipient.
                                  --in a vaccine      Not applicable.
                                   associated
                                   community case.
                                  B. Vaccine-Strain   ..................
                                   Polio Viral
                                   Infection.
                                  --in a non-         <=30 days.
                                   immunodeficient
                                   recipient.
                                  --in an             <=6 months.
                                   immunodeficient
                                   recipient.
                                  --in a vaccine      Not applicable.
                                   associated
                                   community case.
VII. Vaccines containing polio    A. Anaphylaxis....  <=4 hours.
 inactivated virus (e.g., IPV).
                                  B. Shoulder Injury  <=48 hours.
                                   Related to
                                   Vaccine
                                   Administration.
                                  C. Vasovagal        <=1 hour.
                                   syncope.
VIII. Hepatitis B vaccines......  A. Anaphylaxis....  <=4 hours.
                                  B. Shoulder Injury  <=48 hours.
                                   Related to
                                   Vaccine
                                   Administration.
                                  C. Vasovagal        <=1 hour.
                                   syncope.
IX. Haemophilus influenzae type   A. Shoulder Injury  <=48 hours.
 b (Hib) vaccines.                 Related to
                                   Vaccine
                                   Administration.
                                  B. Vasovagal        <=1 hour.
                                   syncope.
X. Varicella vaccines...........  A. Anaphylaxis....  <=4 hours.
                                  B. Disseminated     ..................
                                   varicella vaccine-
                                   strain viral
                                   disease.
                                  --Vaccine-strain    Not applicable.
                                   virus identified.
                                  --If strain         7-42 days (not
                                   determination is    less than 7 days
                                   not done or if      and not more than
                                   laboratory          42 days).
                                   testing is
                                   inconclusive.
                                  C. Varicella        Not applicable.
                                   vaccine-strain
                                   viral
                                   reactivation.
                                  D. Shoulder Injury  <=48 hours.
                                   Related to
                                   Vaccine
                                   Administration.
                                  E. Vasovagal        <=1 hour.
                                   syncope.

[[Page 45150]]

 
XI. Rotavirus vaccines..........  A. Intussusception  1-21 days (not
                                                       less than 1 day
                                                       and not more than
                                                       21 days).
XII. Pneumococcal conjugate       A. Shoulder Injury  <=48 hours.
 vaccines.                         Related to
                                   Vaccine
                                   Administration.
                                  B. Vasovagal        <=1 hour.
                                   syncope.
XIII. Hepatitis A vaccines......  A. Shoulder Injury  <=48 hours.
                                   Related to
                                   Vaccine
                                   Administration.
                                  B. Vasovagal        <=1 hour.
                                   syncope.
XIV. Seasonal influenza vaccines  A. Anaphylaxis....  <=4 hours.
                                  B. Shoulder Injury  <=48 hours.
                                   Related to
                                   Vaccine
                                   Administration.
                                  C. Vasovagal        <=1 hour.
                                   syncope.
                                  D. Guillain-        3-42 days (not
                                   Barr[eacute]        less than 3 days
                                   Syndrome.           and not more than
                                                       42 days).
XV. Meningococcal vaccines......  A. Anaphylaxis....  <=4 hours.
                                  B. Shoulder Injury  <=48 hours.
                                   Related to
                                   Vaccine
                                   Administration.
                                  C. Vasovagal        <=1 hour.
                                   syncope.
XVI. Human papillomavirus (HPV)   A. Anaphylaxis....  <=4 hours.
 vaccines.
                                  B. Shoulder Injury  <=48 hours.
                                   Related to
                                   Vaccine
                                   Administration.
                                  C. Vasovagal        <=1 hour.
                                   syncope.
XVII. Any new vaccine             A. Shoulder Injury  <=48 hours.
 recommended by the Centers for    Related to         <=1hour.
 Disease Control and Prevention    Vaccine
 for routine administration to     Administration.
 children, after publication by   B. Vasovagal
 the Secretary of a notice of      syncope.
 coverage.
------------------------------------------------------------------------

    (b) Provisions that apply to all conditions listed. (1) Any acute 
complication or sequela, including death, of the illness, disability, 
injury, or condition listed in paragraph (a) of this section (and 
defined in paragraphs (c) and (d) of this section) qualifies as a Table 
injury under paragraph (a) except when the definition in paragraph (c) 
requires exclusion.
    (2) In determining whether or not an injury is a condition set 
forth in paragraph (a) of this section, the Court shall consider the 
entire medical record.
    (3) An idiopathic condition that meets the definition of an 
illness, disability, injury, or condition set forth in paragraph (c) of 
this section shall be considered to be a condition set forth in 
paragraph (a) of this section.
    (c) Qualifications and aids to interpretation. The following 
qualifications and aids to interpretation shall apply to, define and 
describe the scope of, and be read in conjunction with paragraphs (a), 
(b), and (d) of this section:
    (1) Anaphylaxis. Anaphylaxis is an acute, severe, and potentially 
lethal systemic reaction that occurs as a single discrete event with 
simultaneous involvement of two or more organ systems. Most cases 
resolve without sequela. 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. There are no specific 
pathological findings to confirm a diagnosis of anaphylaxis.
    (2) Encephalopathy. A vaccine recipient shall be considered to have 
suffered an encephalopathy if an injury meeting the description below 
of an acute encephalopathy occurs within the applicable time period and 
results in a chronic encephalopathy, as described in paragraph (d) of 
this section.
    (i) Acute encephalopathy. (A) For children less than 18 months of 
age who present:
    (1) Without a seizure, an acute encephalopathy is indicated by a 
significantly decreased level of consciousness that lasts at least 24 
hours,
    (2) Following a seizure, an acute encephalopathy is demonstrated by 
a significantly decreased level of consciousness that lasts at least 24 
hours and cannot be attributed to a postictal state--from a seizure or 
a medication.
    (B) For adults and children 18 months of age or older, an acute 
encephalopathy is one that persists at least 24 hours and is 
characterized by at least two of the following:
    (1) A significant change in mental status that is not medication 
related (such as a confusional state, delirium, or 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) The following clinical features in themselves do not 
demonstrate an acute encephalopathy or a significant change in either 
mental status or level of consciousness: sleepiness, irritability 
(fussiness), high-pitched and unusual screaming, poor feeding, 
persistent inconsolable crying, bulging fontanelle, or symptoms of 
dementia.
    (D) Seizures in themselves are not sufficient to constitute a 
diagnosis of encephalopathy and in the absence of other evidence of an 
acute encephalopathy seizures shall not be viewed as the first symptom 
or manifestation of an acute encephalopathy.
    (ii) Regardless of whether or not the specific cause of the 
underlying condition, systemic disease, or acute event (including an 
infectious organism) is known, an encephalopathy shall not be 
considered to be a condition set forth in the Table if it is shown that 
the encephalopathy was caused by:

[[Page 45151]]

    (A) An underlying condition or systemic disease shown to be 
unrelated to the vaccine (such as malignancy, structural lesion, 
psychiatric illness, dementia, genetic disorder, prenatal or perinatal 
central nervous system (CNS) injury); or
    (B) An acute event shown to be unrelated to the vaccine such as a 
head trauma, stroke, transient ischemic attack, complicated migraine, 
drug use (illicit or prescribed) or an infectious disease.
    (3) Encephalitis. A vaccine recipient shall be considered to have 
suffered encephalitis if an injury meeting the description below of an 
acute encephalitis occurs within the applicable time period and results 
in a chronic encephalopathy, as described in paragraph (d) of this 
section.
    (i) Acute encephalitis. Encephalitis is indicated by evidence of 
neurologic dysfunction, as described in paragraph (c)(3)(i)(A) of this 
section, plus evidence of an inflammatory process in the brain, as 
described in paragraph (c)(3)(i)(B) of this section.
    (A) Evidence of neurologic dysfunction consists of either:
    (1) One of the following neurologic findings referable to the CNS: 
Focal cortical signs (such as aphasia, alexia, agraphia, cortical 
blindness); cranial nerve abnormalities; visual field defects; abnormal 
presence of primitive reflexes (such as Babinski's sign or sucking 
reflex); or cerebellar dysfunction (such as ataxia, dysmetria, or 
nystagmus); or
    (2) An acute encephalopathy as set forth in paragraph (c)(2)(i) of 
this section.
    (B) Evidence of an inflammatory process in the brain (central 
nervous system or CNS inflammation) must include cerebrospinal fluid 
(CSF) pleocytosis (>5 white blood cells (WBC)/mm\3\ in children >2 
months of age and adults; >15 WBC/mm3 in children <2 months of age); or 
at least two of the following:
    (1) Fever (temperature >= 100.4 degrees Fahrenheit);
    (2) Electroencephalogram findings consistent with encephalitis, 
such as diffuse or multifocal nonspecific background slowing and 
periodic discharges; or
    (3) Neuroimaging findings consistent with encephalitis, which 
include, but are not limited to brain/spine magnetic resonance imaging 
(MRI) displaying diffuse or multifocal areas of hyperintense signal on 
T2-weighted, diffusion-weighted image, or fluid-attenuation inversion 
recovery sequences.
    (ii) Regardless of whether or not the specific cause of the 
underlying condition, systemic disease, or acute event (including an 
infectious organism) is known, encephalitis shall not be considered to 
be a condition set forth in the Table if it is shown that the 
encephalitis was caused by:
    (A) An underlying malignancy that led to a paraneoplastic 
encephalitis;
    (B) An infectious disease associated with encephalitis, including a 
bacterial, parasitic, fungal or viral illness (such as herpes viruses, 
adenovirus, enterovirus, West Nile Virus, or human immunodeficiency 
virus), which may be demonstrated by clinical signs and symptoms and 
need not be confirmed by culture or serologic testing; or
    (C) Acute disseminated encephalomyelitis (ADEM). Although early 
ADEM may have laboratory and clinical characteristics similar to acute 
encephalitis, findings on MRI are distinct with ADEM displaying 
evidence of acute demyelination (scattered, focal, or multifocal areas 
of inflammation and demyelination within cerebral subcortical and deep 
cortical white matter; gray matter involvement may also be seen but is 
a minor component); or other conditions or abnormalities that would 
explain the vaccine recipient's symptoms.
    (4) Intussusception. (i) For purposes of paragraph (a) of this 
section, intussusception means the invagination of a segment of 
intestine into the next segment of intestine, resulting in bowel 
obstruction, diminished arterial blood supply, and blockage of the 
venous blood flow. This is characterized by a sudden onset of abdominal 
pain that may be manifested by anguished crying, irritability, 
vomiting, abdominal swelling, and/or passing of stools mixed with blood 
and mucus.
    (ii) For purposes of paragraph (a) of this section, the following 
shall not be considered to be a Table intussusception:
    (A) Onset that occurs with or after the third dose of a vaccine 
containing rotavirus;
    (B) Onset within 14 days after an infectious disease associated 
with intussusception, including viral disease (such as those secondary 
to non-enteric or enteric adenovirus, or other enteric viruses such as 
Enterovirus), enteric bacteria (such as Campylobacter jejuni), or 
enteric parasites (such as Ascaris lumbricoides), which may be 
demonstrated by clinical signs and symptoms and need not be confirmed 
by culture or serologic testing;
    (C) Onset in a person with a preexisting condition identified as 
the lead point for intussusception such as intestinal masses and cystic 
structures (such as polyps, tumors, Meckel's diverticulum, lymphoma, or 
duplication cysts);
    (D) Onset in a person with abnormalities of the bowel, including 
congenital anatomic abnormalities, anatomic changes after abdominal 
surgery, and other anatomic bowel abnormalities caused by mucosal 
hemorrhage, trauma, or abnormal intestinal blood vessels (such as 
Henoch Scholein purpura, hematoma, or hemangioma); or
    (E) Onset in a person with underlying conditions or systemic 
diseases associated with intussusception (such as cystic fibrosis, 
celiac disease, or Kawasaki disease).
    (5) Chronic arthritis. Chronic arthritis is defined as persistent 
joint swelling with at least two additional manifestations of warmth, 
tenderness, pain with movement, or limited range of motion, lasting for 
at least 6 months.
    (i) Chronic arthritis may be found in a person with no history in 
the 3 years prior to vaccination of arthropathy (joint disease) on the 
basis of:
    (A) Medical documentation recorded within 30 days after the onset 
of objective signs of acute arthritis (joint swelling) that occurred 
between 7 and 42 days after a rubella vaccination; 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; and
    (C) Medical documentation of an antibody response to the rubella 
virus.
    (ii) 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 idiopathic 
arthritis, systemic lupus erythematosus, systemic sclerosis, mixed 
connective tissue disease, polymyositis/determatomyositis, 
fibromyalgia, necrotizing vasculitis and vasculopathies and Sjogren's 
Syndrome), degenerative joint disease, infectious agents other than 
rubella (whether by direct invasion or as an immune reaction), 
metabolic and endocrine diseases, trauma, neoplasms, neuropathic 
disorders, bone and cartilage disorders, and arthritis associated with 
ankylosing spondylitis, psoriasis, inflammatory bowel disease, Reiter's 
Syndrome, blood disorders, or arthralgia (joint pain), or joint 
stiffness without swelling.
    (6) Brachial neuritis. This term is defined as dysfunction limited 
to the upper extremity nerve plexus (i.e., its trunks, divisions, or 
cords). A deep, steady, often severe aching pain in the

[[Page 45152]]

shoulder and upper arm usually heralds onset of the condition. The pain 
is typically followed in days or weeks by weakness in the affected 
upper extremity muscle groups. Sensory loss may accompany the motor 
deficits, but is generally a less notable clinical feature. Atrophy of 
the affected muscles may occur. The neuritis, or plexopathy, may be 
present on the same side or on the side opposite the injection. It is 
sometimes bilateral, affecting both upper extremities. A vaccine 
recipient shall be considered to have suffered brachial neuritis as a 
Table injury if such recipient manifests all of the following:
    (i) Pain in the affected arm and shoulder is a presenting symptom 
and occurs within the specified time-frame;
    (ii) Weakness:
    (A) Clinical diagnosis in the absence of nerve conduction and 
electromyographic studies requires weakness in muscles supplied by more 
than one peripheral nerve.
    (B) Nerve conduction studies (NCS) and electromyographic (EMG) 
studies localizing the injury to the brachial plexus are required 
before the diagnosis can be made if weakness is limited to muscles 
supplied by a single peripheral nerve.
    (iii) Motor, sensory, and reflex findings on physical examination 
and the results of NCS and EMG studies, if performed, must be 
consistent in confirming that dysfunction is attributable to the 
brachial plexus; and
    (iv) No other condition or abnormality is present that would 
explain the vaccine recipient's symptoms.
    (7) Thrombocytopenic purpura. This term is defined by the presence 
of clinical manifestations, such as petechiae, significant bruising, or 
spontaneous bleeding, and by a serum platelet count less than 50,000/
mm\3\ with normal red and white blood cell indices. Thrombocytopenic 
purpura does not include cases of thrombocytopenia associated with 
other causes such as hypersplenism, autoimmune disorders (including 
alloantibodies from previous transfusions) myelodysplasias, 
lymphoproliferative disorders, congenital thrombocytopenia or hemolytic 
uremic syndrome. Thrombocytopenic purpura does not include cases of 
immune (formerly called idiopathic) thrombocytopenic purpura that are 
mediated, for example, by viral or fungal infections, toxins or drugs. 
Thrombocytopenic purpura does not include cases of thrombocytopenia 
associated with disseminated intravascular coagulation, as observed 
with bacterial and viral infections. Viral infections include, for 
example, those infections secondary to Epstein Barr virus, 
cytomegalovirus, hepatitis A and B, human immunodeficiency virus, 
adenovirus, and dengue virus. An antecedent viral infection may be 
demonstrated by clinical signs and symptoms and need not be confirmed 
by culture or serologic testing. However, if culture or serologic 
testing is performed, and the viral illness is attributed to the 
vaccine-strain measles virus, the presumption of causation will remain 
in effect. Bone marrow examination, if performed, must reveal a normal 
or an increased number of megakaryocytes in an otherwise normal marrow.
    (8) Vaccine-strain measles viral disease. This term is defined as a 
measles illness that involves the skin and/or another organ (such as 
the brain or lungs). Measles virus must be isolated from the affected 
organ or histopathologic findings characteristic for the disease must 
be present. Measles viral strain determination may be performed by 
methods such as polymerase chain reaction test and vaccine-specific 
monoclonal antibody. If strain determination reveals wild-type measles 
virus or another, non-vaccine-strain virus, the disease shall not be 
considered to be a condition set forth in the Table. If strain 
determination is not done or if the strain cannot be identified, onset 
of illness in any organ must occur within 12 months after vaccination.
    (9) Vaccine-strain polio viral infection. This term is defined as a 
disease caused by poliovirus that is isolated from the affected tissue 
and should be determined to be the vaccine-strain by oligonucleotide or 
polymerase chain reaction. Isolation of poliovirus from the stool is 
not sufficient to establish a tissue specific infection or disease 
caused by vaccine-strain poliovirus.
    (10) Shoulder injury related to vaccine administration (SIRVA). 
SIRVA manifests as shoulder pain and limited range of motion occurring 
after the administration of a vaccine intended for intramuscular 
administration in the upper arm. These symptoms are thought to occur as 
a result of unintended injection of vaccine antigen or trauma from the 
needle into and around the underlying bursa of the shoulder resulting 
in an inflammatory reaction. SIRVA is caused by an injury to the 
musculoskeletal structures of the shoulder (e.g. tendons, ligaments, 
bursae, etc.). SIRVA is not a neurological injury and abnormalities on 
neurological examination or nerve conduction studies (NCS) and/or 
electromyographic (EMG) studies would not support SIRVA as a diagnosis 
(even if the condition causing the neurological abnormality is not 
known). A vaccine recipient shall be considered to have suffered SIRVA 
if such recipient manifests all of the following:
    (i) No history of pain, inflammation or dysfunction of the affected 
shoulder prior to intramuscular vaccine administration that would 
explain the alleged signs, symptoms, examination findings, and/or 
diagnostic studies occurring after vaccine injection;
    (ii) Pain occurs within the specified time-frame;
    (iii) Pain and reduced range of motion are limited to the shoulder 
in which the intramuscular vaccine was administered; and
    (iv) No other condition or abnormality is present that would 
explain the patient's symptoms (e.g. NCS/EMG or clinical evidence of 
radiculopathy, brachial neuritis, mononeuropathies, or any other 
neuropathy).
    (11) Disseminated varicella vaccine-strain viral disease. 
Disseminated varicella vaccine-strain viral disease is defined as a 
varicella illness that involves the skin beyond the dermatome in which 
the vaccination was given and/or disease caused by vaccine-strain 
varicella in another organ. For organs other than the skin, disease, 
not just mildly abnormal laboratory values, must be demonstrated in the 
involved organ. If there is involvement of an organ beyond the skin, 
and no virus was identified in that organ, the involvement of all 
organs must occur as part of the same, discrete illness. If strain 
determination reveals wild-type varicella virus or another, non-
vaccine-strain virus, the viral disease shall not be considered to be a 
condition set forth in the Table. If strain determination is not done 
or if the strain cannot be identified, onset of illness in any organ 
must occur 7- 42 days after vaccination.
    (12) Varicella vaccine-strain viral reactivation disease. Varicella 
vaccine-strain viral reactivation disease is defined as the presence of 
the rash of herpes zoster with or without concurrent disease in an 
organ other than the skin. Zoster, or shingles, is a painful, 
unilateral, pruritic rash appearing in one or more sensory dermatomes. 
For organs other than the skin, disease, not just mildly abnormal 
laboratory values, must be demonstrated in the involved organ. There 
must be laboratory confirmation that the vaccine-strain of the 
varicella virus is present in the skin or in any other involved organ, 
for example by oligonucleotide or polymerase chain reaction. If strain 
determination reveals

[[Page 45153]]

wild-type varicella virus or another, non-vaccine-strain virus, the 
viral disease shall not be considered to be a condition set forth in 
the Table.
    (13) Vasovagal syncope. Vasovagal syncope (also sometimes called 
neurocardiogenic syncope) means loss of consciousness (fainting) and 
postural tone caused by a transient decrease in blood flow to the brain 
occurring after the administration of an injected vaccine. Vasovagal 
syncope is usually a benign condition but may result in falling and 
injury with significant sequela. Vasovagal syncope may be preceded by 
symptoms such as nausea, lightheadedness, diaphoresis, and/or pallor. 
Vasovagal syncope may be associated with transient seizure-like 
activity, but recovery of orientation and consciousness generally 
occurs simultaneously with vasovagal syncope. Loss of consciousness 
resulting from the following conditions will not be considered 
vasovagal syncope: organic heart disease, cardiac arrhythmias, 
transient ischemic attacks, hyperventilation, metabolic conditions, 
neurological conditions, and seizures. Episodes of recurrent syncope 
occurring after the applicable time period are not considered to be 
sequela of an episode of syncope meeting the Table requirements.
    (14) Immunodeficient recipient. Immunodeficient recipient is 
defined as an individual with an identified defect in the immunological 
system which impairs the body's ability to fight infections. The 
identified defect may be due to an inherited disorder (such as severe 
combined immunodeficiency resulting in absent T lymphocytes), or an 
acquired disorder (such as acquired immunodeficiency syndrome resulting 
from decreased CD4 cell counts). The identified defect must be 
demonstrated in the medical records, either preceding or postdating 
vaccination.
    (15) Guillain-Barr[eacute] Syndrome (GBS). (i) GBS is an acute 
monophasic peripheral neuropathy that encompasses a spectrum of four 
clinicopathological subtypes described below. For each subtype of GBS, 
the interval between the first appearance of symptoms and the nadir of 
weakness is between 12 hours and 28 days. This is followed in all 
subtypes by a clinical plateau with stabilization at the nadir of 
symptoms, or subsequent improvement without significant relapse. Death 
may occur without a clinical plateau. Treatment related fluctuations in 
all subtypes of GBS can occur within nine weeks of GBS symptom onset 
and recurrence of symptoms after this time-frame would not be 
consistent with GBS.
    (ii) The most common subtype in North America and Europe, 
comprising more than 90 percent of cases, is acute inflammatory 
demyelinating polyneuropathy (AIDP), which has the pathologic and 
electrodiagnostic features of focal demyelination of motor and sensory 
peripheral nerves and nerve roots. Another subtype called acute motor 
axonal neuropathy (AMAN) is generally seen in other parts of the world 
and is predominated by axonal damage that primarily affects motor 
nerves. AMAN lacks features of demyelination. Another less common 
subtype of GBS includes acute motor and sensory neuropathy (AMSAN), 
which is an axonal form of GBS that is similar to AMAN, but also 
affects the sensory nerves and roots. AIDP, AMAN, and AMSAN are 
typically characterized by symmetric motor flaccid weakness, sensory 
abnormalities, and/or autonomic dysfunction caused by autoimmune damage 
to peripheral nerves and nerve roots. The diagnosis of AIDP, AMAN, and 
AMSAN requires:
    (A) Bilateral flaccid limb weakness and decreased or absent deep 
tendon reflexes in weak limbs;
    (B) A monophasic illness pattern;
    (C) An interval between onset and nadir of weakness between 12 
hours and 28 days;
    (D) Subsequent clinical plateau (the clinical plateau leads to 
either stabilization at the nadir of symptoms, or subsequent 
improvement without significant relapse; however, death may occur 
without a clinical plateau); and,
    (E) The absence of an identified more likely alternative diagnosis.
    (iii) Fisher Syndrome (FS), also known as Miller Fisher Syndrome, 
is a subtype of GBS characterized by ataxia, areflexia, and 
ophthalmoplegia, and overlap between FS and AIDP may be seen with limb 
weakness. The diagnosis of FS requires:
    (A) Bilateral ophthalmoparesis;
    (B) Bilateral reduced or absent tendon reflexes;
    (C) Ataxia;
    (D) The absence of limb weakness (the presence of limb weakness 
suggests a diagnosis of AIDP, AMAN, or AMSAN);
    (E) A monophasic illness pattern;
    (F) An interval between onset and nadir of weakness between 12 
hours and 28 days;
    (G) Subsequent clinical plateau (the clinical plateau leads to 
either stabilization at the nadir of symptoms, or subsequent 
improvement without significant relapse; however, death may occur 
without a clinical plateau);
    (H) No alteration in consciousness;
    (I) No corticospinal track signs; and
    (J) The absence of an identified more likely alternative diagnosis.
    (iv) Evidence that is supportive, but not required, of a diagnosis 
of all subtypes of GBS includes electrophysiologic findings consistent 
with GBS or an elevation of cerebral spinal fluid (CSF) protein with a 
total CSF white blood cell count below 50 cells per microliter. Both 
CSF and electrophysiologic studies are frequently normal in the first 
week of illness in otherwise typical cases of GBS.
    (v) To qualify as any subtype of GBS, there must not be a more 
likely alternative diagnosis for the weakness.
    (vi) Exclusionary criteria for the diagnosis of all subtypes of GBS 
include the ultimate diagnosis of any of the following conditions: 
chronic immune demyelinating polyradiculopathy (``CIDP''), 
carcinomatous meningitis, brain stem encephalitis (other than 
Bickerstaff brainstem encephalitis), myelitis, spinal cord infarct, 
spinal cord compression, anterior horn cell diseases such as polio or 
West Nile virus infection, subacute inflammatory demyelinating 
polyradiculoneuropathy, multiple sclerosis, cauda equina compression, 
metabolic conditions such as hypermagnesemia or hypophosphatemia, tick 
paralysis, heavy metal toxicity (such as arsenic, gold, or thallium), 
drug-induced neuropathy (such as vincristine, platinum compounds, or 
nitrofurantoin), porphyria, critical illness neuropathy, vasculitis, 
diphtheria, myasthenia gravis, organophosphate poisoning, botulism, 
critical illness myopathy, polymyositis, dermatomyositis, hypokalemia, 
or hyperkalemia. The above list is not exhaustive.
    (d) Glossary for purposes of paragraph (c) of this section--(1) 
Chronic encephalopathy--(i) A chronic encephalopathy occurs when a 
change in mental or neurologic status, first manifested during the 
applicable Table time period as an acute encephalopathy or 
encephalitis, persists for at least 6 months from the first symptom or 
manifestation of onset or of significant aggravation of an acute 
encephalopathy or encephalitis.
    (ii) Individuals who return to their baseline neurologic state, as 
confirmed by clinical findings, within less than 6 months from the 
first symptom or manifestation of onset or of significant aggravation 
of an acute encephalopathy or encephalitis 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 or encephalitis.
    (2) Injected refers to the intramuscular, intradermal, or

[[Page 45154]]

subcutaneous needle administration of a vaccine.
    (3) Sequela means a condition or event which was actually caused by 
a condition listed in the Vaccine Injury Table.
    (4) Significantly decreased level of consciousness is indicated by 
the presence of one or more of the following clinical signs:
    (i) Decreased or absent response to environment (responds, if at 
all, only to loud voice or painful stimuli);
    (ii) Decreased or absent eye contact (does not fix gaze upon family 
members or other individuals); or
    (iii) Inconsistent or absent responses to external stimuli (does 
not recognize familiar people or things).
    (5) Seizure includes myoclonic, generalized tonic-clonic (grand 
mal), and simple and complex partial seizures, but not absence (petit 
mal), or pseudo seizures. Jerking movements or staring episodes alone 
are not necessarily an indication of seizure activity.
    (e) Coverage provisions. (1) Except as provided in paragraph 
(e)(2), (3), (4), (5), (6), (7), or (8) of this section, this section 
applies to petitions for compensation under the Program filed with the 
United States Court of Federal Claims on or after [EFFECTIVE DATE OF 
THE FINAL REGULATION.]
    (2) Hepatitis B, Hib, and varicella vaccines (Items VIII, IX, and X 
of the Table) are included in the Table as of August 6, 1997.
    (3) Rotavirus vaccines (Item XI of the Table) are included in the 
Table as of October 22, 1998.
    (4) Pneumococcal conjugate vaccines (Item XII of the Table) are 
included in the Table as of December 18, 1999.
    (5) Hepatitis A vaccines (Item XIII of the Table) are included on 
the Table as of December 1, 2004.
    (6) Trivalent influenza vaccines (Included in item XIV of the 
Table) are included on the Table as of July 1, 2005. All other seasonal 
influenza vaccines (Item XIV of the Table) are included on the Table as 
of November 12, 2013.
    (7) Meningococcal vaccines and human papillomavirus vaccines (Items 
XV and XVI of the Table) are included on the Table as of February 1, 
2007.
    (8) Other new vaccines (Item XVII of the Table) will be included in 
the Table as of the effective date of a tax enacted to provide funds 
for compensation paid with respect to such vaccines. An amendment to 
this section will be published in the Federal Register to announce the 
effective date of such a tax.

[FR Doc. 2015-17503 Filed 7-28-15; 8:45 am]
 BILLING CODE 4160-15-P