[Federal Register Volume 79, Number 61 (Monday, March 31, 2014)]
[Proposed Rules]
[Pages 17973-17993]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-06102]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

42 CFR Part 110

RIN 0906-AA79


Countermeasures Injury Compensation Program: Pandemic Influenza 
Countermeasures Injury Table

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

ACTION: Notice of proposed rulemaking.

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SUMMARY: The Public Readiness and Emergency Preparedness Act (PREP Act) 
directs the Secretary of Health and Human Services (the Secretary), to 
establish a Countermeasures Injury Compensation Program (the Program) 
to provide ``timely, uniform, and adequate compensation'' to eligible 
individuals who sustain serious physical injuries or to certain 
survivors of individuals who die as a direct result of the use or 
administration of covered countermeasures identified by the Secretary 
in declarations issued under the PREP Act. The Secretary has delegated 
authority to administer the Program to the Health Resources and 
Services Administration (HRSA). Through this regulation, the Secretary 
proposes a Table for pandemic influenza covered countermeasures 
identified by the Secretary in several PREP Act declarations. This 
regulation also includes proposed Table time intervals for the first 
symptom or manifestation of onset of injury, Table injury definitions, 
and requirements which define the terms and conditions included on the 
Table. These are considered part of the proposed Table.

DATES: Written comments must be submitted on or before May 30, 2014. 
Subject to consideration of the comments received, the Secretary 
intends to publish a final regulation.

ADDRESSES: You may submit comments in one of three ways, as listed 
below.

[[Page 17974]]

Please submit your comments in only one of these ways to minimize the 
receipt of duplicate submissions. The first is the preferred method.
    1. Federal eRulemaking Portal. You may submit comments 
electronically to www.regulations.gov. Click on the link ``[S]ubmit 
electronic comments on HRSA regulations with an open comment period.'' 
You may submit attachments to your comments in any file format accepted 
by Regulations.gov.
    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, the Program cannot accept comments by facsimile 
(FAX) transmission. When commenting by any of the above methods, please 
refer to file code: 0906-AA79. Comments received on a timely 
basis will be available for public inspection as they are received, 
beginning approximately three weeks after publication of this notice, 
online at www.regulations.gov or in person at: Parklawn Building, 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 p.m. (excluding Federal holidays). Phone: (301) 
443-1785. This is not a toll-free number.

FOR FURTHER INFORMATION CONTACT: Please visit the Countermeasures 
Injury Compensation Program's Web site, http://www.hrsa.gov/cicp/, or 
contact Dr. Vito Caserta, Director, Countermeasures Injury Compensation 
Program, Healthcare Systems Bureau, HRSA, Parklawn Building, Room 11C-
06, 5600 Fishers Lane, Rockville, MD 20857. Phone calls can be directed 
to (855) 266-2427. This is a toll-free number.

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 
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 
names and contact information of subject matter experts involved in 
this proposal's development. We must consider all written comments 
received 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 see the 
``For Further Information'' box below for the names and contact 
information to obtain this information in an accessible format. Please 
visit http://www.HHS.gov/regulations for more information on HHS 
rulemaking and opportunities to comment on proposed and existing rules.
    The PREP Act (Pub. L. 109-148) directs the Secretary to establish, 
through regulations, a Covered Countermeasures Injury Table (Table) 
identifying serious physical injuries that are presumed to be directly 
caused by the administration or use of covered countermeasures 
identified in PREP Act declarations issued by the Secretary. The 
Secretary may only add injuries to a Table if it is determined based on 
``compelling, reliable, valid, medical and scientific evidence'' that 
the administration or use of the covered countermeasure directly causes 
such covered injuries.\1\ Such a Table informs the public about serious 
physical injuries supported by medical and scientific evidence known to 
be directly caused by covered countermeasures. In addition, such a 
Table creates a rebuttable presumption of causation, for compensation 
purposes, for eligible individuals whose injuries are listed on a Table 
and meet the requirements of a Table.
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    \1\ Section 319F-4(b)(5)(A) of the Public Health Service Act, as 
amended (42 U.S.C. 247d-6e(b)(5)(A)).
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Background

    The Public Readiness and Emergency Preparedness Act of 2005 (PREP 
Act), part of the ``Department of Defense, Emergency Supplemental 
Appropriations to Address Hurricanes in the Gulf of Mexico, and 
Pandemic Influenza Act, 2006,'' Public Law 109-148, establishes 
liability protections for certain covered persons and authorizes the 
payment of benefits to eligible individuals injured by covered 
countermeasures. Both liability protections and compensation are 
available under the PREP Act based on the terms of the PREP Act 
declarations (hereafter declarations or Secretarial declarations) 
issued by the Secretary of Health and Human Services (the Secretary).
    The purpose of a Secretarial declaration is to identify a disease, 
health condition, or a threat to health that is currently, or may in 
the future constitute, a public health emergency. In addition, the 
Secretary, through a declaration, may recommend and encourage the 
development, manufacturing, distribution, dispensing, and 
administration or use of one or more covered countermeasures to treat, 
prevent, or diagnose the disease, condition, or threat specified in the 
declaration.\2\
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    \2\ Section 319F-3(b) of the PHS Act (42 U.S.C 247d-6d(b)).
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    This notice of proposed rulemaking (NPRM) concerns only the 
compensation program authorized by the PREP Act, not the liability 
protections set forth therein. Specifically, the PREP Act authorizes 
the Secretary to establish and administer this program to provide 
timely, uniform, and adequate compensation to certain individuals who 
develop serious physical injuries or to certain survivors of 
individuals who die as a direct result of the use or administration of 
a covered countermeasure identified in a Secretarial declaration.\3\ 
The Secretary delegated responsibility for establishing and 
administering the Program to HRSA, within the Department of Health and 
Human Services (HHS).
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    \3\ Section 319F-4(a) of the PHS Act (42 U.S.C. 247d-6e(a)).
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    The PREP Act authorizes the Secretary to publish regulations to 
establish and administratively implement the Program. Specifically, the 
PREP Act authorizes the Secretary to determine Program eligibility, the 
process to apply for benefits, the methods of payments and amounts of 
compensation, and the process for further review of Requests for 
Benefits submitted by, or on behalf of, requesters. To be considered 
for compensation for any serious physical injury or death, an 
individual must

[[Page 17975]]

submit a Request for Benefits with the required information.
    The Secretary published the interim final rule implementing the 
Program on October 15, 2010.\4\ This rule, which was published as a 
final rule on October 7, 2011, explains the Program's policies, 
procedures, and requirements. Title 42 of the Code of Federal 
Regulations (CFR) Sec.  110.20(a) states that individuals must 
establish that a covered injury occurred in order to be eligible for 
benefits under the Program. A covered injury is death or a serious 
injury determined by the Secretary to be: (1) An injury meeting the 
requirements of a Covered Countermeasures Injury Table, which is 
presumed to be the direct result of the administration or use of a 
covered countermeasure unless the Secretary determines there is another 
more likely cause; or (2) an injury (or its health complications) that 
is the direct result of the administration or use of a covered 
countermeasure. This includes serious aggravation caused by a covered 
countermeasure of a pre-existing condition. 42 CFR 110.3(g).
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    \4\ 42 CFR part 110.
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    Serious injury means serious physical injury. Physical biochemical 
alterations leading to physical changes and serious functional 
abnormalities at the cellular or tissue level in any bodily function 
may, in certain circumstances, be considered serious injuries. As a 
general matter, only injuries that warranted hospitalization (whether 
or not the person was actually hospitalized) or injuries that led to a 
significant loss of function or disability (whether or not 
hospitalization was warranted) will be considered serious injuries. 42 
CFR 110.3(z).
    Through this NPRM, the Secretary proposes adding subpart K to 42 
CFR part 110, which had been reserved for the purpose of creating an 
Injury Table for covered countermeasures. These countermeasures are 
identified in Secretarial declarations relating to pandemic influenza, 
including influenza caused by the 2009 H1N1 pandemic influenza virus 
(hereafter referred to as the 2009 H1N1 virus), and other potential 
pandemic strains, such as H5N1 avian influenza.
    The Table proposed in this notice is limited to pandemic influenza 
covered countermeasures. Future Countermeasure Injury Tables (Tables) 
may be created for other countermeasures relating to threats to health 
that pose or constitute public health emergencies, since the PREP Act 
mandates the establishment of a Program Table identifying covered 
injuries that may be presumed to be directly caused by the 
administration or use of a covered countermeasure. To date, 
declarations have been issued with respect to countermeasures against 
pandemic influenza A viruses, anthrax, botulism, smallpox, and acute 
radiation syndrome. The Secretary may publish Tables in the Federal 
Register through separate amendments to 42 CFR part 110 in the future.
    The 2009 H1N1 virus outbreak quickly emerged into an influenza 
pandemic in the spring of 2009. An influenza pandemic is a worldwide 
epidemic of the disease and occurs when: (1) A new influenza virus 
appears against which the human population has no or very limited 
immunity; and (2) the virus can spread easily from person-to-person in 
a sustained manner.
    The 2009 H1N1 virus was a new recombinant influenza A virus of 
swine origin that was first recognized as causing human illness with 
transmission from person to person in Mexico and the United States in 
the early spring of 2009. The first documented case in the United 
States was confirmed by laboratory testing at the Centers for Disease 
Control and Prevention (CDC) on April 15, 2009. The virus then spread 
rapidly throughout the world and it was determined that the human 
population had very limited immunity to this novel influenza A virus.
    The virus has been reported to cause a wide range of influenza-like 
symptoms, including fever, cough, sore throat, body aches, headaches, 
chills, fatigue, nausea, vomiting, and/or diarrhea. Most infections 
have been mild and self-limiting; however, serious illnesses including 
pneumonia and death have occurred.
    Due to the novel nature of the 2009 H1N1 virus and the increasing 
number of CDC-confirmed cases indicating rapid spread, the Acting 
Secretary of HHS issued a public health emergency determination, under 
section 319 of the Public Health Service (PHS) Act \5\ on April 26, 
2009, titled ``Determination that a Public Health Emergency Exists.'' 
This determination stated that a public health emergency was in 
existence nationwide involving the pandemic 2009 H1N1 influenza virus 
because it affected, or had significant potential to affect, national 
security. More information is available at http://www.flu.gov/planning-preparedness/federal/h1n1emergency042609.html#. This declaration was 
renewed by the Secretary on July 24, 2009; October 1, 2009; December 
28, 2009; and March 23, 2010. Each renewal, titled ``Renewal of 
Determination that a Public Health Emergency Exists,'' focused 
specifically on the 2009 H1N1 influenza pandemic. HHS did not further 
renew this determination, which resulted in the expiration of the 
Secretary's 2009 H1N1 influenza public health emergency determination 
on June 23, 2010, under section 319 of the PHS Act.\6\ However, HHS 
still encourages individuals to continue to practice flu prevention 
techniques (http://www.flu.gov/prevention-vaccination/index.html#).
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    \5\ 42 U.S.C. 247d.
    \6\ 42 U.S.C. 247d.
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Definition of Covered Countermeasure

    The Secretary has issued several PREP Act declarations concerning 
pandemic influenza covered countermeasures, pursuant to section 319F-
3(b) of the PHS Act.\7\ ``Covered countermeasure'' is defined in the 
PREP Act and includes three categories.\8\ The first category, 
consisting of ``qualified pandemic or epidemic product[s],'' is defined 
in section 319F-3(i)(7) of the PHS Act.\9\ This category includes 
products (drugs, biologics, and devices) manufactured, used, designed, 
developed, modified, licensed, or procured to diagnose, mitigate, 
prevent, treat, or cure a pandemic or epidemic or to limit the harm 
such pandemic or epidemic might otherwise cause. The category also 
extends to products used to diagnose, mitigate, prevent, treat, or cure 
a serious or life-threatening disease or condition caused by a 
``qualified pandemic or epidemic product.'' \10\ To qualify, a drug, 
biologic, or device must be: (1) Approved or cleared under the Federal 
Food, Drug, and Cosmetic Act (FD&C Act) or licensed under the PHS Act; 
(2) the subject of research for possible use and subject to an 
exemption under sections 505(i) or 520(g) of the FD&C Act; or (3) 
authorized for emergency use in accordance with section 564, 564A, or 
564B of the FD&C Act.
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    \7\ 42 U.S.C. 247d-6d(b).
    \8\ Section 319F-3(i)(1) of the PHS Act (42 U.S.C. 247d-
6d(i)(1)).
    \9\ 42 U.S.C. 247d-6d(i)(7).
    \10\ Section 319F-3(i)(7)(A)(ii) of the PHS Act (42 U.S.C. 247d-
6d(i)(7)(A)(ii)).
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    The second category includes ``security countermeasure[s].'' A 
security countermeasure, defined in section 319F-2(c)(1)(B) of the PHS 
Act,\11\ is a drug, biologic, or device that the Secretary determines: 
(1) Is a priority to diagnose, mitigate, prevent, or treat harm either 
from an agent identified as a material threat or from a condition that 
may result in injuries or deaths, and may be caused by administering a 
drug, biologic, or device against such an agent; (2) is a necessary

[[Page 17976]]

countermeasure; and (3) is approved or cleared under the FD&C Act or 
licensed under the PHS Act or will likely be approved, cleared, or 
licensed within ten years or is authorized for emergency use under 
section 564 of the FD&C Act.
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    \11\ 42 U.S.C. 247d-6b(c)(1)(B).
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    The final category consists of drugs,\12\ biologics,\13\ or devices 
\14\ that are authorized for emergency use in accordance with section 
564, 564A, or 564B of the FD&C Act.
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    \12\ As defined in section 201(g)(1) of the FD&C Act (21 U.S.C. 
321(g)(1)).
    \13\ As defined in section 351(i) of the PHS Act (42 U.S.C. 
262(i)).
    \14\ As defined in section 201(h) of the FD&C Act (21 U.S.C. 
321(h)).
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    To be eligible for the liability protections of the PREP Act or to 
receive benefits under the compensation provisions of the PREP Act, a 
covered countermeasure must meet one of these three categories and must 
also be described by the Secretary in a declaration.

Covered Countermeasures

    In this section, we provide an overview of the covered 
countermeasures subject to Secretarial declarations that will be 
included on the proposed Table.

Pandemic Influenza Vaccine Declarations

    The Secretary published a declaration covering pandemic influenza A 
H5N1 vaccines on January 26, 2007.\15\ This declaration was amended on 
November 21, 2007, with the effective date of November 30, 2007, adding 
influenza vaccines caused by subtypes H7 and H9.\16\ The January 26, 
2007, declaration was further amended on October 10, 2008, to add 
influenza caused by subtypes H2 and H6 and covering vaccines to prevent 
these diseases.\17\ A fourth amendment was signed by the Secretary on 
June 15, 2009, which specified that pandemic H1N1 influenza and 
vaccines are covered.\18\ The June 15, 2009, declaration also 
republished the amended January 26, 2007, declaration in its entirety 
and stated that the 2009 H1N1 virus and resulting disease constituted a 
public health emergency. The June 15, 2009, republished declaration was 
amended on September 28, 2009, adding provisions regarding the H5N1, 
H2, H6, H7, H9 subtypes and 2009 H1N1 vaccines.\19\ The declaration was 
amended on February 26, 2010, which republished the June 15, 2009, 
declaration with amendments.\20\
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    \15\ 72 FR 4710 (Feb. 1, 2007)); http://www.gpo.gov/fdsys/pkg/FR-2007-02-01/pdf/E7-1635.pdf.
    \16\ 72 FR 67731 (Nov. 30, 2007); http://www.gpo.gov/fdsys/pkg/FR-2007-11-30/pdf/07-5884.pdf.
    \17\ 73 FR 61871 (Oct. 17, 2008); http://www.gpo.gov/fdsys/pkg/FR-2008-10-17/pdf/E8-24736.pdf.
    \18\ 74 FR 30294 (June 25, 2009); http://www.gpo.gov/fdsys/pkg/FR-2009-06-25/pdf/E9-14948.pdf.
    \19\ 74 FR 51153 (Oct. 5, 2009); http://www.gpo.gov/fdsys/pkg/FR-2009-10-05/pdf/E9-23844.pdf.
    \20\ 75 FR 10268 (March 5, 2010); http://www.gpo.gov/fdsys/pkg/FR-2010-03-05/pdf/2010-4644.pdf.
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    This February 26, 2010, amended declaration widened the scope of 
the previous declarations to extend to vaccines against pandemic 
influenza A viruses with pandemic potential and to associated 
adjuvants.\21\
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    \21\ 75 FR 10268.
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    The declaration was further amended on February 29, 2012. This 
amendment extended the effective time period, reformatted the 
declaration, modified or clarified terms, and republished the February 
26, 2010, declaration with amendments.\22\
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    \22\ 77 FR 13329 (March 6, 2012); http://www.gpo.gov/fdsys/pkg/FR-2012-03-06/pdf/2012-5312.pdf.
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    Although the ``determination that a public health emergency 
exists'' under section 319 of the PHS Act \23\ expired, the PREP Act 
declarations remain effective as described above.
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    \23\ 42 U.S.C. 247d.
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Diagnostics, Personal Respiratory Protection Devices, and Respiratory 
Support Devices Declarations

    On December 17, 2008, the Secretary signed a PREP Act declaration 
concerning pandemic influenza diagnostics, personal respiratory 
protection devices, and respiratory support devices.\24\
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    \24\ 73 FR 78362 (Dec. 22, 2008)); http://edocket.access.gpo.gov/2008/pdf/E8-30510.pdf.
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    Pandemic influenza diagnostics are defined in section IX of the 
declaration as ``diagnostics to identify avian or other animal 
influenza A viruses that pose a pandemic threat, or to otherwise aid in 
the diagnosis of pandemic influenza, when (1) [l]icensed under section 
351 of the Public Health Service Act; (2) approved under section 505 or 
section 515 of the FD&C Act; (3) cleared under section 510(k) of the 
FD&C Act; (4) authorized for emergency use under section 564 of the 
FD&C Act; (5) used under section 505(i) of the FD&C Act or section 
351(a)(3) of the PHS Act and 21 CFR part 312; or (6) used under section 
520(g) of the FD&C Act and 21 CFR part 812.'' \25\
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    \25\ 73 FR 78362.
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    Pandemic influenza personal respiratory protection devices are 
defined in section IX of the declaration as being ``for use by the 
general public to reduce wearer exposure to pathogenic biological 
airborne particulates during public health medical emergencies, such as 
an influenza pandemic, when (1) [l]icensed under section 351 of the 
Public Health Service Act; (2) approved under section 505 or section 
515 of the FD&C Act; (3) cleared under section 510(k) of the FD&C Act; 
(4) authorized for emergency use under section 564 of the FD&C Act; (5) 
used under section 505(i) of the FD&C Act or section 351(a)(3) of the 
PHS Act and 21 CFR part 312; or (6) used under section 520(g) of the 
FD&C Act and 21 CFR part 812.'' \26\
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    \26\ 73 FR 78362.
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    Pandemic influenza respiratory support devices are defined in 
section IX of the declaration as, ``devices to support respiratory 
function for patients infected with highly pathogenic influenza A H5N1 
viruses or other influenza viruses that pose a pandemic threat when (1) 
[l]icensed under section 351 of the Public Health Service Act; (2) 
approved under section 505 or section 515 of the FD&C Act; (3) cleared 
under section 510(k) of the FD&C Act; (4) authorized for emergency use 
under section 564 of the FD&C Act; (5) used under section 505(i) of the 
FD&C Act or section 351(a)(3) of the PHS Act and 21 CFR part 312; or 
(6) used under section 520(g) of the FD&C Act and 21 CFR part 
812.''\27\
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    \27\ 73 FR 78362.
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Antiviral Medication Declarations

    The Secretary signed a PREP Act declaration on October 10, 2008, 
adding the influenza antiviral drugs Tamiflu and Relenza as pandemic 
influenza covered countermeasures.\28\ This declaration was amended on 
April 26, 2009, to expand the category of covered diseases to all 
animal influenza A viruses that are or may be capable of developing 
into a pandemic strain.\29\
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    \28\ 73 FR 61861 (Oct. 17, 2008)); http://www.gpo.gov/fdsys/pkg/FR-2008-10-17/pdf/E8-24733.pdf.
    \29\ 74 FR 29213 (June 19, 2009)); http://www.gpo.gov/fdsys/pkg/FR-2009-06-19/pdf/E9-14412.pdf.
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    In addition, the Secretary signed a September 28, 2009, PREP Act 
declaration for the antiviral drug, peramivir, when used to treat 
influenza caused by the pandemic 2009 H1N1 virus.\30\
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    \30\ 74 FR 50968 (Oct. 2, 2009)); http://www.gpo.gov/fdsys/pkg/FR-2009-10-02/pdf/E9-23761.pdf.
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General Information

    The effective dates for the above-referenced declarations vary, and 
the Secretary has the authority to amend the declarations at any time. 
The declarations, including amendments to

[[Page 17977]]

the declarations, are published in the Federal Register.
    In addition to the above-referenced declarations, the Secretary 
also has issued declarations for countermeasures to the security 
threats of anthrax, smallpox, botulism, and acute radiation syndrome. 
Injury Tables for these covered countermeasures may be published at a 
later date.
    As noted above, the PREP Act authorized the Secretary to create 
Tables for each covered countermeasure identified in a declaration if 
there is compelling, reliable, valid, medical and scientific evidence 
that the countermeasure directly causes a covered injury. In this NPRM, 
the Secretary proposes a Table for injuries directly resulting from the 
use or administration of pandemic influenza covered countermeasures 
identified in the above-referenced declarations. The proposed Table 
lists serious physical injuries that have been demonstrated by 
compelling, reliable, valid, medical and scientific evidence to be 
directly caused by the administration or use of the covered 
countermeasures.\31\ Only injuries supported by this type of evidence 
are proposed for inclusion on the Table.
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    \31\ Section 319F-4(b)(5)(A) of the PHS Act (42 U.S.C. 247d-
6e(b)(5)(A)).
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    For each countermeasure, the proposed Table will include the 
covered injuries and/or conditions directly caused by such 
countermeasure and the applicable time intervals for the first symptom 
or manifestation of onset of injuries. The Program's statute directs 
that covered injuries presumed to be caused by the administration or 
use of a covered countermeasure must be included on a Table.\32\ The 
Secretary proposes also to note on the Table if no injuries or 
conditions qualify for a Table presumption for a particular 
countermeasure at this time. This is done to reflect that she 
considered the possibility of Table injuries for these covered 
countermeasures. Claims related to any injuries alleged to be caused by 
these countermeasures will be considered on a case-by-case basis.
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    \32\ Section 319F-4(b)(5)(A) of the PHS Act (42 U.S.C. 247d-
6e(b)(5)(A)).
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    General information about applying for compensation/benefits under 
the Program is outside the scope of this NPRM, but is available in 42 
CFR part 110.40 or on the Program's Web site, www.hrsa.gov/gethealthcare/conditions/countermeasurescomp/howtofile.html. The 
implementing regulations for this Program can also be found at: 
www.gpo.gov/fdsys/pkg/FR-2011-10-07/pdf/2011-25858.pdf.

Summary of Proposed Regulation

    This NPRM proposes to amend the Program's implementing regulations 
\33\ and, if adopted, would establish a table of injuries resulting 
from the administration or use of pandemic influenza covered 
countermeasures. Certain conditions of interest that are currently not 
being proposed for inclusion on the Table also are discussed in this 
NPRM.
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    \33\ 42 CFR part 110.
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General Requirement of Serious Physical Injuries or Deaths

    By statute, only serious physical injuries or deaths directly 
resulting from the use or administration of a covered countermeasure 
may be compensable under the Program.\34\ The serious physical injury 
or death may be compensable regardless of whether the injury is a Table 
injury or a non-Table injury. Because this requirement of a serious 
physical injury applies to all Requests for Benefits filed with the 
Program, the Secretary considered this requirement while drafting the 
proposed Table included in this NPRM.
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    \34\ Section 319F-4(a), (e)(3) of the PHS Act (42 U.S.C. 247d-
6e(a), (e)(3)).
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    In general, only injuries or significant aggravation of injuries 
that warranted hospitalization (whether or not the person was actually 
hospitalized) or that led to a significant loss of function or 
disability will be considered serious physical injuries.\35\ It is 
recognized that the term ``disability'' can be defined in many ways, 
and there are several definitions used by the Federal government 
specific to various programs and services. To provide further clarity 
as to the type of disability that would qualify as a serious injury for 
the Program, under this proposed rule, the term ``disability'' is 
defined as ``a physical or mental impairment that substantially limits 
one or more major life activities of an individual.'' This definition 
corresponds with the first listed definition of disability in the 
Americans with Disabilities Act, 42 U.S.C. 12102(1)(A). This definition 
was chosen because it is consistent with the Program's existing 
authorities and adds further guidance by using a widely accepted 
definition familiar to the general public.
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    \35\ 42 CFR 110.3(z).
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    In addition, pursuant to 42 CFR 110.3(z), ``physical biochemical 
alterations leading to physical changes and serious functional 
abnormalities at the cellular or tissue level in any bodily function 
may, in certain circumstances, be considered serious physical 
injuries.'' According to the preamble to the interim final rule, 
serious physical injuries also include ``instances in which there may 
be no measurable anatomic or structural change in the affected tissue 
or organ, but there is an abnormal functional change. For example, many 
psychiatric conditions are caused by abnormal neurotransmitter levels 
in key portions of the central nervous system. Thus, it is possible 
that certain serious psychiatric conditions may qualify as serious 
physical injuries if the psychiatric conditions are a manifestation of 
a physical biochemical abnormality in neurotransmitter level or type 
caused by a covered countermeasure. One way of determining that an 
abnormal physical change in neurotransmitter level is causing the 
injury would be a clinical challenge that demonstrates a positive 
clinical response to a medication that is designed to restore the 
balance of appropriate neurotransmitters necessary for normal function 
in an injured countermeasure recipient.'' \36\
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    \36\ 75 FR 63661.
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    Only serious physical injuries believed to have a direct causal 
relationship with the use or administration of a covered countermeasure 
based on compelling, reliable, valid, medical and scientific evidence 
may be included on the Table.
    Minor injuries do not meet the definition of a serious physical 
injury. For example, covered injuries do not include common and 
expected skin reactions (such as localized swelling or warmth that is 
not of sufficient severity to warrant hospitalization and does not lead 
to significant loss of function or disability). Expected minor 
reactions, such as headaches and body aches, commonly occur with 
influenza vaccinations. However, if a minor injury leads to a serious 
physical injury, and the minor injury was directly caused by a covered 
countermeasure, the Program may compensate the individual for the 
serious physical injury. The injury's causal link to the countermeasure 
must be based on compelling, reliable, valid, medical and scientific 
evidence. The Program will consider such claims on a case-by-case 
basis.

Serious Aggravation of Pre-Existing Conditions

    Injuries covered under the Program may include serious aggravations 
of pre-existing conditions if such aggravations were caused by a 
covered countermeasure (i.e., any disorder that is proven to the 
satisfaction of the Secretary to have been made significantly more 
severe as the direct

[[Page 17978]]

result of the administration or use of the covered countermeasure). The 
serious aggravation of the pre-existing condition must be supported by 
compelling, reliable, valid, medical and scientific evidence and show a 
direct causal link between the aggravation or worsening of the pre-
existing condition and the countermeasure. The Program will consider 
claims involving serious aggravations of pre-existing conditions on a 
case-by-case basis.

Table Time Intervals

    The proposed Table includes time intervals, per covered injury, 
describing the time interval between the administration or use of the 
covered countermeasure and the first symptom or manifestation of onset 
of injury after the administration or use of the countermeasure. In 
addition to meeting the requirements of the Table injury, the symptom 
or manifestation of onset of injury must be evident within the time 
period described on the Table. The time intervals are biologically 
sound time intervals based on medical and scientific evidence in which 
nearly all of the cases of injury are known to appear when the injury 
is actually caused by the covered countermeasure. As is the case for 
non-Table injuries, Table injuries not meeting the Table time intervals 
may be compensated based on adequate demonstration of compelling, 
reliable, valid, medical and scientific evidence supporting that the 
countermeasure had a causal role.

Table Definitions and Requirements

    The proposed Table also includes definitions of the terms and 
conditions included on the Table which sets forth the requirements 
necessary to establish the Table injuries. For this reason, the Table 
definitions and requirements are considered part of the Table. To 
receive compensation for a Table injury, the individual must meet the 
time interval, Table definition, and any other Table requirements, in 
addition to the other Program requirements.

Presumption Created for Table Injuries

    For purposes of this Program, a rebuttable presumption exists that 
a Table injury was directly caused by the administration or use of a 
covered countermeasure if the first symptom or manifestation of onset 
of an injury listed on the Table occurred within the time period 
indicated, and the Table's definitions and requirements are satisfied. 
By statute, this presumption only applies to Table injuries.\37\ An 
individual may obtain this presumption of causation by submitting 
medical documents demonstrating that the covered injury occurred, that 
it began within the time interval specified on the Table after 
administration or use of a covered countermeasure, that there was not 
another more likely cause, and that all other applicable Table 
requirements and Table definitions are met.
---------------------------------------------------------------------------

    \37\ Section 319F-4(b)(5)(A) of the PHS Act (42 U.S.C. 247d-
6e(b)(5)(A)).
---------------------------------------------------------------------------

    Nevertheless, the presumption is not conclusive. It may be rebutted 
if, based on review of the relevant medical and scientific evidence, 
the Secretary determines that the Table injury was more likely caused 
by other factors and not directly caused by the countermeasure.

Non-Table Injuries

    Compensation may be available for individuals who develop an injury 
not included on the Table, or an injury that is included on the Table 
but where the injury begins outside the allotted time interval provided 
by the Table, or the injury does not satisfy the definition or 
requirements included on the Table with respect to such injury. In 
these cases, the requester does not receive the presumption of 
causation for a Table injury and must demonstrate that the use or 
administration of the covered countermeasure directly caused the 
injury. The regulation administratively implementing the Program 
includes more information about the requirements for such an 
injury.\38\ For example, a temporal association between the 
administration or use of a covered countermeasure and onset of the 
injury (i.e., the injury occurs a certain time after the administration 
or use of the countermeasure) alone is not sufficient to show that an 
injury is the direct result of a covered countermeasure.\39\ Proof of a 
causal association for the non-Table injury must still be based on 
compelling, reliable, valid, medical and scientific evidence.
---------------------------------------------------------------------------

    \38\ 42 CFR 110.20(c).
    \39\ 42 CFR 110.20(c).
---------------------------------------------------------------------------

Sequelae (Health Complications) of Table and Non-Table Injuries

    A requester who demonstrates a Table injury may be entitled to 
benefits related to sequelae (health complications), including death, 
if the Program determines that the sequelae resulted from the Table 
injury. This is also applicable to a requester who develops sequelae 
from a non-Table injury, but only if the non-Table injury is shown to 
be directly caused by a covered countermeasure, and the evidence shows 
a causal relationship based on compelling, reliable, valid, medical and 
scientific evidence. The Program will consider compensation for 
sequelae that develop from Table and non-Table injuries on a case-by-
case basis.

Injuries Sustained as a Result of a Pandemic Influenza Virus

    An individual will not have suffered a covered injury if a covered 
countermeasure is ineffective in diagnosing, preventing, or treating 
the underlying disease for which the countermeasure was administered or 
used, and the individual sustains an injury caused by the disease and 
not by the covered countermeasure. An injury sustained as the direct 
result of a disease (or health condition or threat to health), e.g., 
2009 H1N1 influenza infection, for which the Secretary recommended the 
administration or use of a covered countermeasure in a declaration, is 
not a covered injury. This is because the injury results from the 
disease itself and not from the administration or use of a covered 
countermeasure. For more information, see 42 CFR 110.20(d).

Amendments to the Proposed Table of Injuries

    The Secretary has the discretion to modify the Table in the future. 
For example, the Secretary may amend the Table by adding or removing 
injuries, modifying the governing time intervals, and/or revising the 
Table definitions and requirements. The Secretary will monitor new 
studies and evolving medical and scientific evidence concerning any 
causal relationships between covered countermeasures and injuries or 
death. The Secretary may amend the Table at any time while the Program 
remains operational. Changes to the Table will be accomplished as 
amendments to 42 CFR part 110 and will be published in the Federal 
Register.

The Table in Effect at the Time a Claim Is Filed

    The version of the Table that applies to a requester is the one 
that is in effect on the filing date of his/her Request for Benefits 
unless a subsequent one is published that may provide greater benefit 
to the requester. If a new Table or an amendment to an existing Table 
would benefit a requester, as described in the following section, the 
requester may have an additional opportunity to file a Request for 
Benefits.

Filing Deadlines and Table Additions or Amendments

    In accordance with 42 CFR 110.42(f), in the event that the 
Secretary issues a

[[Page 17979]]

new Covered Countermeasure Injury Table or amends a previously 
published Table, requesters may have an extended filing deadline based 
on the effective date of the Table amendment. This extended filing 
deadline will apply only if the Table amendment enables a requester who 
could not establish a Table injury before the amendment to establish 
such an injury. For example, if the Table proposed in this NPRM is 
adopted, any person who meets the Table requirements for an injury of 
anaphylaxis after receiving the monovalent 2009 H1N1 vaccine (2009 H1N1 
vaccine) would have one year from the effective date of the Table's 
adoption to file a Request for Benefits. This filing deadline applies 
regardless of whether the requester previously filed a request form 
with the Program.
    Individuals may seek compensation for one or more injuries stemming 
from a single administration of a covered countermeasure. However, if 
individuals have previously received compensation for an injury through 
the Program, they may not re-file a claim for compensation if the same 
injury is later added to a Table. The inability for individuals to re-
file their claim avoids such individuals having the opportunity to 
receive additional compensation for the same serious physical injury. 
However, this does not preclude filing a Request for Benefits for an 
injury or aggravation of an injury, resulting from the subsequent 
administration or use of the same type of covered countermeasure. It 
also does not preclude subsequent Requests for Benefits for an injury, 
or an aggravation of an injury, resulting from the administration or 
use of a different covered countermeasure or a different injury from 
the same countermeasure.
    The filing deadline provided under 42 CFR 110.42(f) is an 
additional filing period to the one afforded to all potential 
requesters under 42 CFR 110.42(a). Therefore, persons who would be 
eligible to use the filing deadline described in Sec.  110.42(f) could 
rely on the deadline provided under Sec.  110.42(a) or Sec.  110.42(f).
    It is important to note that the additional filing deadline 
described in 42 CFR 110.42(f) is only available to persons who meet the 
requirements of: (1) A new Table or an amendment(s) to a Table; (2) the 
Table time interval(s); (3) Table definitions; and (4) any other Table 
requirements. In this case, such persons may be eligible for the 
presumption of causation. Persons who sustained injuries not included 
on the Table, or those who do not meet all of the requirements for such 
a Table injury but may prove causation of the injury through other 
means, will not be afforded an additional one-year filing deadline 
based on the Table change. Because the Table change would not enable 
such individuals to establish a Table injury, they would be subject to 
the standard filing deadline described in 42 CFR 110.42(a) (i.e., one 
year from the date of administration or use of the covered 
countermeasure).

Overview of the Proposed Table

    Through this NPRM, as authorized by statute, the Secretary is 
proposing a Table for several covered countermeasures listing serious 
physical injuries (i.e., illnesses, disabilities, conditions, etc.). 
The serious physical injuries included on the Table are injuries that 
are supported by compelling, reliable, valid, medical and scientific 
evidence showing that the administration or use of the covered 
countermeasures directly causes such covered injuries. The Table lists 
the serious injuries directly caused by a specific countermeasure, if 
any, the time interval within which the first symptom or manifestation 
of onset of adverse effects must appear, and the definition of the 
injury. Table definitions are included to further explain each covered 
injury and the level of severity necessary to qualify as a Table 
injury. However, as discussed above, individuals with injuries not 
meeting these requirements of the Table injury may still pursue their 
claims as non-Table injuries under the Program.
    The injuries included on the proposed Table and the time intervals, 
Table definitions, and Table requirements reflect the Secretary's best 
efforts to identify those serious physical injuries causally related to 
the covered countermeasures. The causal linkages between the covered 
countermeasures and these associated Table injuries are based on 
compelling, reliable, valid, medical and scientific evidence. The 
Secretary will stay informed of updates in the scientific and medical 
field concerning new information about causal association between 
injuries and covered countermeasures.

Pandemic Influenza Countermeasures Injury Table

    In response to the 2009 H1N1 pandemic, the 2009 H1N1 vaccine was 
licensed by the Food and Drug Administration (FDA) as a strain change 
from the seasonal influenza vaccine. The vaccine was developed using 
the same FDA-approved manufacturing processes used to produce the 
seasonal influenza vaccine.
    The United States has a long record of safety regarding seasonal 
influenza vaccines. Because the 2009 H1N1 vaccine was produced using 
the same processes as the annual seasonal influenza vaccine, its safety 
profile was expected to be similar to that of any strain change of the 
seasonal influenza vaccine.
    The Federal response to the 2009 H1N1 influenza pandemic centered 
on a mass vaccination program unprecedented in its size and scope in 
the United States. Because of this response, the Federal government 
significantly increased its vaccine safety monitoring efforts.\40\ 
After the 2009 H1N1 vaccination program began in the fall of 2009, HHS 
and its Agencies worked in close partnership with the Department of 
Defense and others in the areas of research, surveillance, and 
programmatic activities to determine if vaccine safety signals or 
adverse events following immunization were related to the 2009 H1N1 
vaccine by chance or were truly adverse reactions to the vaccine. In 
addition, the National Vaccine Advisory Committee (NVAC), which 
provides advice to the HHS Assistant Secretary for Health (ASH), 
established the H1N1 Vaccine Safety Risk Assessment Working Group (the 
Working Group), with the charge to conduct independent, rapid reviews 
of available safety monitoring data for the 2009 H1N1 vaccine. The 
Working Group met regularly to review available data from Federal 
vaccine safety monitoring systems. The NVAC deliberated on the Working 
Group's findings and shared information with the ASH. HHS also worked 
with other countries to share vaccine data and safety information on 
the 2009 H1N1 vaccine. At the local level, public health departments 
and public and private medical health entities collaborated in Federal 
vaccine safety monitoring efforts as well.
---------------------------------------------------------------------------

    \40\ Daniel A. Salmon, ``Immunization-Safety Monitoring Systems 
for the 2009 H1N1 Monovalent Influenza Vaccination Program,'' 
Pediatrics: Supplement 1; May 2011, S79.
---------------------------------------------------------------------------

    The Secretary is aware of minor adverse events associated with the 
2009 H1N1 vaccine and other pandemic influenza vaccines. Specifically, 
for the 2009 H1N1 injectable vaccine, common minor adverse events 
included temporary tenderness, pain, redness, and swelling at the 
injection site, and acute systemic reactions such as headache, malaise, 
and muscle aches in people of all ages, and fever in children. For the 
2009 H1N1 intranasal vaccine, common minor temporary adverse events 
include runny nose, cough, nasal congestion, and headache in all age 
groups; sore throat and tiredness or weakness in adults; and abdominal

[[Page 17980]]

pain, vomiting, diarrhea, and fever in children. Cases involving 
unusually severe forms of minor adverse events that meet the serious 
physical injury standard may qualify as non-Table injuries and will be 
reviewed on a case-by-case basis by the Program. As described above, 
minor injuries are excluded from the Table.
    The proposed Table not only includes the covered injuries listed, 
but also the necessary time intervals between the administration of the 
vaccine and the first symptom or manifestation of onset of the Table 
injury required for a Table presumption of causation. In addition, the 
Table lists Table definitions and Table requirements for each covered 
injury.
    The proposed Table lists the injuries of anaphylaxis, syncope, and 
deltoid bursitis for pandemic influenza vaccines, including the 2009 
H1N1 vaccine, and Guillain-Barre Syndrome (GBS) for only the 2009 H1N1 
vaccine.

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. In an anaphylactic reaction, an immediate 
reaction generally occurs within minutes after exposure, and in most 
cases, the individual develops signs and symptoms within four hours 
after exposure to the antigen. The immediate reaction 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 sequelae. 
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.\41\ The Institute of Medicine (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.\42\ It also has found that the evidence 
convincingly supports a causal relationship between influenza vaccine 
and anaphylaxis.\43\
---------------------------------------------------------------------------

    \41\ 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.
    \42\ Institute of Medicine (IOM), Immunization Safety Review 
Vaccination and Sudden Unexpected Death in Infancy, (Washington, DC: 
The National Academies Press, 2003) 55.
    \43\ IOM, Adverse Effects of Vaccines: Evidence and Causality 
(Washington, DC: The National Academies Press, 2012) 288.
---------------------------------------------------------------------------

    Because influenza vaccines are currently prepared from influenza 
viruses propagated in embryonated chicken eggs, the final vaccine 
product contains a limited quantity of egg protein that can induce 
immediate hypersensitivity reactions in some persons with severe egg 
allergies. The inactivated injectable vaccine (prepared from 
inactivated or killed influenza virus) may also contain gelatin 
proteins, which can be a source of allergic reactions in sensitized 
individuals. The live attenuated intranasal vaccine (containing living 
weakened virus) contains egg proteins, gentamicin, and gelatin, which 
may cause allergic reactions in sensitized individuals.
    The 1994 IOM Report noted in support of a causal association that 
there exists an observation of a spectrum of host responses to the 
influenza vaccine that follow a logical biological gradient from true 
anaphylaxis to milder hypersensitivity reactions. Biological gradient 
refers to the observation of a spectrum of responses from mild to 
severe, and in the case of hypersensitivity reactions the reported 
spectrum after the vaccine runs from mild skin manifestations to chest 
and throat tightness and cardiovascular events to full blown 
anaphylaxis.\44\ The CDC adopted the Advisory Committee on Immunization 
Practice's findings, concluding that ``[i]mmediate--presumably 
allergic--reactions (e.g., hives, angioedema, allergic asthma, and 
systemic anaphylaxis) rarely occur after influenza vaccination. These 
reactions probably result from hypersensitivity to certain vaccine 
components.'' \45\
---------------------------------------------------------------------------

    \44\ IOM, Adverse Events Associated With Childhood Vaccines 
Evidence Bearing on Causality, (Washington, DC: The National 
Academies Press, 1994) 60.
    \45\ Scott A. Harper, MD, et al., ``Prevention and Control of 
Influenza,'' Morbidity and Mortality Weekly; July 29, 2005; 16.
---------------------------------------------------------------------------

    For its 2012 report, the IOM reviewed certain adverse events for 
their association with seasonal influenza vaccine. The 2009 H1N1 
vaccine contains many of the same anaphylaxis-causing components as the 
seasonal influenza vaccine (e.g., egg protein). Although the IOM 
reported limited confidence in the epidemiologic evidence, they 
assessed the mechanistic evidence regarding an association between 
influenza vaccine and anaphylaxis as strong. This assessment was based 
on 22 cases in the medical literature that present a strong temporal 
relationship, the finding of antigelatin IgE in two cases, the finding 
of two cases with positive skin prick tests to gelatin, and one case 
with positive rechallenge (where the same acute adverse event occurs 
after more than one administration of the vaccine). The IOM concluded 
that ``the evidence convincingly supports a causal

[[Page 17981]]

relationship between influenza vaccine and anaphylaxis.'' \46\
---------------------------------------------------------------------------

    \46\ IOM, Adverse Effects of Vaccines, 345.
---------------------------------------------------------------------------

    The IOM also stated that the onset of anaphylaxis generally occurs 
within a few hours of exposure.\47\ Consistent with the time interval 
for the first manifestation of anaphylaxis after vaccines covered by 
the National Vaccine Injury Compensation Program (VICP), the Program 
proposes an onset interval of 0-4 hours for anaphylaxis to be covered 
under the proposed Table.
---------------------------------------------------------------------------

    \47\ IOM, Immunization Safety Review Vaccination, 5.
---------------------------------------------------------------------------

    Based on the nature and timing of anaphylaxis and the medical 
literature (including the fact that it is a very rare event with 
significant symptomatology), compelling, reliable, valid, medical and 
scientific evidence shows a direct link between influenza vaccines, 
including pandemic influenza vaccines (e.g., the 2009 H1N1 vaccine) and 
anaphylaxis.\48\ Anaphylaxis is proposed for inclusion on the Table 
because it is a serious physical injury that may be directly caused by 
the use of the pandemic influenza vaccine, as supported by compelling, 
reliable, valid, medical and scientific evidence.
---------------------------------------------------------------------------

    \48\ Hector S. Izurieta, et al., ``Adverse Events Reported 
Following Live, Cold-Adapted, Intranasal Influenza Vaccine,'' 
Journal of the American Medical Association, Dec. 7, 2005; 2721 and 
Stanley A. Plotkin, et al., Vaccines, 5th Edition, (United Kingdom: 
Elsevier, 2008) 97, 982.
---------------------------------------------------------------------------

    In a very small minority of cases of acute anaphylaxis, initial 
symptoms of the immediate reaction may present up to 12 hours after 
exposure. A more slowly evolving late phase hypersensitivity reaction 
is also possible, with an onset that usually begins 4-8 hours after the 
immediate reaction ends. The medical literature contains reports of 
late phase onset up to 72 hours later.\49\ The late phase reaction 
results from a different immunologic mechanism of action. The late 
phase reaction is part of a biphasic reaction. It is possible for the 
first immediate hypersensitivity reaction to be relatively mild, 
unrecognized, or not observed.
---------------------------------------------------------------------------

    \49\ The Brighton Collaboration, 5678.
---------------------------------------------------------------------------

    There may be unusual cases in which the immediate reaction is 
delayed and/or cases in which the immediate reaction is not recognized, 
with the first apparent manifestation occurring in the late phase. 
These unusual cases will be evaluated on a case-by-case basis, and the 
Secretary will determine causation based on the presence of compelling, 
reliable, valid, medical and scientific evidence.

Vasovagal Syncope

    Vasovagal syncope is a temporary loss of consciousness (fainting) 
and postural tone that includes a reflex drop in blood pressure and may 
be triggered by an event associated with pain or anxiety. This reaction 
is known to occur as a result of any injection, including the injection 
of a vaccine. Some people may experience jerking movements after losing 
consciousness which generally are not seizures.
    In its 2012 report, the IOM concluded, based on mechanistic 
evidence, that the evidence convincingly supports a causal relationship 
between the injection of a vaccine and syncope. Included in the 
evidence was one case of positive re-challenge involving influenza 
vaccine.\50\ As a rule, syncope after vaccination is not associated 
with serious injuries; however, in approximately 10 percent of reported 
cases it can cause serious injury related to physical trauma from an 
associated fall or other related accidents. Only serious injuries are 
eligible for compensation.
---------------------------------------------------------------------------

    \50\ IOM, Adverse Effects of Vaccines, 343.
---------------------------------------------------------------------------

    Most cases of syncope occur within one hour of vaccination. The 
Program will therefore propose an onset interval of 0-1 hour for 
vasovagal syncope caused by injected pandemic influenza vaccine to be 
covered under the proposed Table. Vasovagal syncope is proposed for 
inclusion on the Table because it may result in serious physical injury 
that is directly caused by the use of the vaccine, as supported by 
compelling, reliable, valid, medical and scientific evidence.

Subdeltoid Bursitis

    Subdeltoid bursitis (i.e., deltoid bursitis, subacromial bursitis) 
is an inflammation of the bursa located between the deltoid muscle and 
the capsule of the shoulder joint. A bursa is a closed fluid-containing 
sac. Bursae serve to reduce friction between bones and tendons, or 
bones and skin. The pain from subacromial or subdeltoid bursitis is 
usually located in the lateral aspect of the shoulder. There is 
frequently tenderness to direct palpation (the process of using your 
hands to examine the body, especially while perceiving/diagnosing a 
disease or illness) below the acromion process (part of the shoulder). 
A shoulder with isolated bursitis should have full passive range of 
motion with more tenderness on actively resisted abduction than on 
passive abduction. This bursa extends below the deltoid muscle, and it 
is possible for a deep injection given high in the shoulder to 
inadvertently enter the bursa causing an inflammatory bursitis. 
Subdeltoid bursitis can result in debilitating pain or immobility. Only 
serious injuries are eligible for compensation.
    The IOM evaluated three cases of positive re-challenge associated 
with influenza vaccine from the Vaccine Adverse Event Reporting System 
(VAERS) in addition to a published report of 13 claims in the VICP. 
Most of the cases had onset of symptoms within 48 hours of vaccination. 
The IOM concluded that the evidence convincingly supports a causal 
relationship between the injection of a vaccine and deltoid 
bursitis.\51\ The Program will therefore propose an onset interval of 
0-48 hours for subdeltoid bursitis caused by injected pandemic 
influenza vaccine to be covered under the proposed Table.
---------------------------------------------------------------------------

    \51\ IOM, Adverse Effects of Vaccines, 18.
---------------------------------------------------------------------------

    Injury to other musculoskeletal structures in the shoulder or upper 
arm (e.g., tendons, ligaments, bone, muscle, nerves) due to direct 
injection of the vaccine into these structures, or injuries resulting 
from the localized inflammation caused by the vaccine in close 
proximity to these structures, will be reviewed on a case-by-case 
basis.
    Subdeltoid bursitis is proposed for inclusion on the Table because 
it may be a serious physical injury that may be directly caused by the 
use of the pandemic influenza vaccine, as supported by compelling, 
reliable, valid, medical and scientific evidence.

Guillain-Barr[egrave] Syndrome (GBS)

    Multiple studies performed to monitor the safety of 2009 H1N1 
vaccine provide evidence that demonstrates a small, statistically 
significant increased risk of GBS in the six weeks following 
administration of the 2009 H1N1 vaccine, as outlined below.
    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 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

[[Page 17982]]

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. 
Demyelinating 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. Another subtype called acute motor axonal 
neuropathy (AMAN) is generally seen in other parts of the world and is 
predominated by axonal damage that primary affects motor nerves. AMAN 
lacks features of demyelination. The axon is a portion of the nerve 
cell that transmits nerve impulses away from the nerve cell body. 
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 nine 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 nine weeks 
after onset and are generally followed by eventual improvement.
    According to the Brighton Collaboration,\52\ 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. 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.
---------------------------------------------------------------------------

    \52\ Sejvar, 599-612.
---------------------------------------------------------------------------

    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.\53\
---------------------------------------------------------------------------

    \53\ Sejvar, 599-612.
---------------------------------------------------------------------------

    For all subtypes of GBS (AIDP, AMAN, AMSAN, and FS), the onset of 
symptoms less than three days (72 hours) after exposure essentially 
excludes that exposure as a cause because the immunologic steps 
necessary to create symptomatic disease require a minimum of three 
days.
    CIDP is clinically and pathologically distinct from GBS. The onset 
phase of CIDP is generally greater than eight weeks and the weakness 
may remit and relapse. CIDP is also not monophasic.\54\
---------------------------------------------------------------------------

    \54\ Sejvar, 599-612.
---------------------------------------------------------------------------

    In the past, GBS has been causally associated with certain 
vaccines. For example, rabies vaccines produced in nervous system 
tissue such as goat, sheep, or suckling mouse brain have been tied to 
an increased risk of GBS in people vaccinated with this vaccine. 
However, this method of vaccine production is no longer used in the 
United States.
    Another example is the 1976 influenza A (swine flu) vaccine, which 
was found by the IOM to be causally associated with GBS. The risk of 
developing GBS in the six-week period after receiving the 1976 swine 
flu vaccine was 9.2 times higher than the risk for those who were not 
vaccinated.\55\ 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 one million 
persons vaccinated, in the six weeks following vaccination, may be 
attributable to the vaccine formulation used in those years. The 
background incidence of GBS not associated with vaccine among adults 
was documented in the study to be 0.87 cases per million persons for 
any 6-week period.\56\
---------------------------------------------------------------------------

    \55\ 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.
    \56\ Tamar Lasky, et al., ``The Guillain-Barr[egrave] Syndrome 
and the 1992-1993 and 1993-1994 Influenza Vaccines,'' The New 
England Journal of Medicine, Dec. 17, 1998; 1797.

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

[[Page 17983]]

    The IOM published a thorough scientific review of the peer reviewed 
literature in 2004 \57\ and concluded that people who received the 1976 
swine influenza vaccine had an increased risk for developing GBS. 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.
---------------------------------------------------------------------------

    \57\ IOM, Immunization Safety Review: Influenza Vaccines and 
Neurological Complications, 25.
---------------------------------------------------------------------------

    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 2009 H1N1 influenza 
vaccine, were specifically not evaluated. The IOM concluded that the 
evidence is inadequate to accept or reject a causal relationship 
between seasonal influenza vaccine and GBS.\58\
---------------------------------------------------------------------------

    \58\ IOM, Adverse Effects of Vaccines, 334.
---------------------------------------------------------------------------

    The Working Group, in its February 7, 2012, final report to the 
NVAC regarding 2009 H1N1 safety surveillance, reported that a meta-
analysis combining the results from each study group participating in 
the 2009 H1N1 enhanced safety surveillance revealed a small, 
statistically significant increased risk of GBS in the six weeks after 
receiving the 2009 H1N1 vaccine. The meta-analysis was predominantly 
based on enhanced safety surveillance studies performed by different 
investigators with different populations in the Emerging Infections 
Program (EIP), the Vaccine Safety Datalink (VSD), and the Post-
Licensure Rapid Immunization Safety Monitoring (PRISM) System.
    The VSD enhanced safety surveillance includes active surveillance 
and medical record review in a well-defined population of nine million 
people. The self-controlled risk interval study design showed a 
statistically significant relative risk of 4.4 of GBS after monovalent 
inactivated 2009 H1N1 influenza vaccine. The corresponding risk 
difference or attributable risk was 5.0 per million vaccine doses in 
the six weeks following vaccination. The authors concluded that there 
was a relatively small elevated risk (a quadrupling of the risk) of GBS 
following monovalent inactivated 2009 H1N1 vaccine, but that there was 
no increased risk following the trivalent seasonal vaccine (when 
administered without 2009 H1N1) in the 2009-2010 influenza season.\59\
---------------------------------------------------------------------------

    \59\ Sharon K. Greene, et al., ``Risk of Confirmed Guillain-
Barr[egrave] Syndrome Following Receipt of Monovalent Inactivated 
Influenza A (H1N1) and Seasonal Influenza Vaccines in the Vaccine 
Safety Datalink Project, 2009-2010,'' American Journal of 
Epidemiology, Jun. 1, 2012; 1100.
---------------------------------------------------------------------------

    The EIP implemented active population-based surveillance for GBS 
following H1N1 vaccine in 10 different areas of the country, capturing 
a population of approximately 45 million people. Analyses using self-
controlled methods found a statistically significant increased relative 
risk of GBS after 2009 H1N1 influenza vaccine of between 2.1 and 3.0, 
depending on the exact methods used. The corresponding attributable 
risks per million doses administered in the six weeks after vaccination 
were 1.5 and 2.8. The authors concluded that the results suggest a low 
increased risk (a doubling or tripling of the risk) of GBS following 
the monovalent 2009 H1N1 influenza vaccine.\60\
---------------------------------------------------------------------------

    \60\ Jerome I. Tokars, et al., ``The Risk of Guillain-
Barr[egrave] Syndrome Associated with Influenza A (H1N1) 2009 
Monovalent Vaccine and 2009-2010 Seasonal Influenza Vaccines: 
Results from a Self-Controlled Analysis,'' Pharmacoepidemiology and 
Drug Safety, May 2012; 546.
---------------------------------------------------------------------------

    Another analysis using EIP data found a statistically significant 
adjusted rate ratio of 1.57 with a corresponding attributable risk of 
0.74 excess GBS cases per one million vaccine doses in the six weeks 
following monovalent 2009 H1N1 influenza vaccination. The findings for 
seasonal vaccine demonstrated a rate ratio similar to that for 2009 
H1N1 vaccine, but the association was not statistically significant. 
Although the authors conclude that the relationship between monovalent 
2009 H1N1 influenza vaccine and GBS during the 2009-2010 influenza 
season was likely weak (the study found a 57 percent increased risk of 
GBS in the six weeks after vaccination compared to controls) and that 
the excess risk of GBS was small, these data support a causal 
connection due to the results showing a statistically significant 
increased risk.\61\ The consistent trend across studies of an increased 
risk provides support that the measured association of a 57 percent 
increase in risk after the vaccination is real and that it reflects a 
causal association even if this one analysis demonstrates a modest or 
small increase in relative risk.
---------------------------------------------------------------------------

    \61\ Matthew E. Wise, et al., ``Guillain-Barre Syndrome During 
the 2009-2010 H1N1 Influenza Vaccination Campaign: Population-based 
Surveillance Among 45 Million Americans,'' American Journal of 
Epidemiology, Jun. 1, 2012; 1110.
---------------------------------------------------------------------------

    The EIP combined the data obtained from doses of the monovalent 
live attenuated 2009 H1N1 vaccine and the monovalent inactivated 2009 
H1N1 vaccine and therefore the conclusions provide compelling evidence 
related to the administration of both vaccines and GBS.
    The PRISM system is a cohort-based active surveillance network that 
conducted a retrospective analysis to determine if the 2009 H1N1 
vaccine was associated with an increased risk of any of 14 pre-
specified outcomes. Five health insurance and associated companies with 
38 million members, together with nine immunization registries, 
contributed records related to approximately 2.6 million doses of 2009 
H1N1 vaccine. The self-controlled risk interval analysis of chart-
confirmed GBS cases found an elevated but not statistically significant 
incident rate ratio for GBS after inactivated 2009 H1N1 vaccine. The 
incident rate ratio was 2.5 with a confidence interval of 0.42 to 
15.\62\ Although this study does not reach statistical significance, 
the results trend in the same direction of an increased risk of GBS 
after receiving the 2009 H1N1 vaccine as outlined in, and consistent 
with, the studies above. The wide confidence interval suggests this 
analysis did not have sufficient power to reach statistical 
significance.
---------------------------------------------------------------------------

    \62\ W. Katherine Yih, et al., ``Surveillance for Adverse Events 
Following Receipt of Pandemic 2009 H1N1 Vaccine in the Post-
Licensure Rapid Immunization Safety Monitoring (PRISM) System, 2009-
2010,'' American Journal of Epidemiology, Jun. 1, 2012; 1120.
---------------------------------------------------------------------------

    A meta-analysis was performed of the VSD, EIP, and PRISM data 
mentioned above, together with additional data from safety surveillance 
studies performed by Medicare, the Department of Defense, and the 
Department of Veterans Affairs, which analyzed data from 23 million 
vaccinated people. The meta-analysis found that the 2009 H1N1 
inactivated vaccine was associated with a small increased risk of GBS 
within six weeks of vaccination. This excess risk is equivalent to 1.6 
excess cases in the six weeks after vaccination per million people 
vaccinated.
    The meta-analysis provides the benefit of additional statistical 
power. Statistical power reflects the ability of a study to detect a 
true effect from the exposure being studied. Additional statistical 
power allows for the analyses of certain hypotheses, not possible to 
analyze individually in the six studies that made up the meta-analysis. 
This increased risk found in the meta-analysis was consistent: (1) 
Across studies looking at different groups of people; (2) using 
different definitions of

[[Page 17984]]

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.\63\
---------------------------------------------------------------------------

    \63\ Daniel A. Salmon et al., ``Association Between Guillain-
Barre 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.
---------------------------------------------------------------------------

    Considering the totality of the evidence, and particularly the 
enhanced surveillance studies and meta-analysis performed to monitor 
the safety of the 2009 H1N1 vaccine, compelling evidence demonstrates a 
small increased risk of GBS in the six weeks following administration 
of the 2009 H1N1 vaccine. The Program will therefore propose an onset 
interval of 3-42 days for GBS caused by the 2009 H1N1 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.\64\ GBS 
is proposed for inclusion on the Table because it is a serious physical 
injury, and the fact that it may be directly caused by the use of the 
2009 H1N1 vaccine is supported by compelling, reliable, valid, medical 
and scientific evidence.
---------------------------------------------------------------------------

    \64\ Peripheral Neuropathy (Philadelphia, PA: Elsevier Saunders, 
2005), 626.
---------------------------------------------------------------------------

Pandemic Influenza Countermeasure Conditions of Special Interest

    Although the conditions listed below are of special interest to the 
public and are being monitored by HHS, the Secretary does not propose 
including them on the Table at this time because compelling, reliable, 
valid, medical and scientific evidence of causation does not currently 
exist. The conditions include the following:

(1) Spontaneous Miscarriage

    The Secretary has a special interest in spontaneous miscarriages 
with respect to the 2009 H1N1 vaccine because pregnant women were a 
priority group targeted for this vaccination. Spontaneous miscarriages 
commonly occur regardless of the use or administration of any vaccines. 
There are about six million clinically recognized pregnancies in the 
United States each year, and approximately 15 percent of those 
pregnancies will end in clinically recognized miscarriages with no 
known cause (spontaneous miscarriages). This calculates to 
approximately 900,000 miscarriages per year, or an average of 2,466 per 
day in the United States regardless of vaccination status. Given the 
large number of women who experience spontaneous miscarriages with no 
known cause and the large number of pregnant women who received the 
2009 H1N1 vaccine, it is expected that a significant number of pregnant 
women would demonstrate a coincidental temporal association between the 
vaccine and miscarriages with no other evidence of a causative role.
    The H1N1 Working Group, in its February 7, 2012, final report to 
the NVAC regarding 2009 H1N1 safety surveillance, reported on pregnancy 
outcomes. Some studies showed weak statistical signals for an increased 
risk of pre-eclampsia and miscarriage after 2009 H1N1 vaccine 
administration. These results were not consistent across different 
studies, and there were several important methodological limitations to 
these analyses, suggesting that it was not a real association with the 
vaccine. The H1N1 Working Group concluded that surveillance associated 
with the 2009 H1N1 vaccine was adequate to detect serious pregnancy 
complications that occurred with a high incidence. However, a high 
incidence of serious pregnancy complications was not seen. To discern 
smaller effects, the Working Group recommended the performance of 
methodological work to enhance surveillance of vaccine adverse events 
in pregnant women.
    There is, therefore, no compelling evidence to date supporting a 
causal relationship between the 2009 H1N1 vaccine and spontaneous 
miscarriage. For this reason, the Secretary does not propose including 
spontaneous miscarriage as a Table injury. Should compelling, reliable, 
valid, medical and scientific evidence demonstrate such a link, the 
Secretary may add this injury to the Table. Unless such an amendment is 
made, the Program will consider any claims for spontaneous miscarriage 
on a case-by-case basis as non-Table claims.

(2) Febrile Seizures

    Influenza vaccinations are known to occasionally cause fever in 
some children. Seizures secondary to fever (febrile seizures) from any 
cause have been observed in 2-5 percent of children between the ages of 
three months and five years, with the peak age being 14 to 18 months.
    For its 2012 report, the IOM reviewed the medical evidence for non-
pandemic influenza vaccine causing seizures. The IOM had a moderate 
degree of confidence in the epidemiologic evidence. The studies 
reviewed had sufficient validity and precision to assess an association 
between influenza vaccine and seizures. These studies consistently 
reported a null association. The IOM concluded that the evidence is 
inadequate to accept or reject a causal relationship between seasonal 
influenza vaccine and seizures.\65\ In addition, enhanced surveillance 
to assess the safety of the 2009 H1N1 vaccine provided evidence that 
this vaccine did not cause seizures.\66\
---------------------------------------------------------------------------

    \65\ IOM, Adverse Effects of Vaccines, 304.
    \66\ Yih, 1123.
---------------------------------------------------------------------------

    In 2011, enhanced surveillance for febrile seizures in the United 
States was conducted through the VSD. More than 200,000 children 
between the ages of six months and four years were studied. The 
analyses showed that febrile seizures following trivalent seasonal 
influenza vaccine and pneumococcal vaccine (PCV 13) given at different 
visits rarely occurred. The seizures were most common in children age 
12 to 23 months when the two vaccines were given in the same health 
care visit. The analyses demonstrated one additional febrile seizure 
among every 2,000 to 3,000 children vaccinated. However, these analyses 
do not apply to the 2009 H1N1 vaccine.
    Compelling, reliable, valid, medical and scientific evidence does 
not currently exist causally linking seizures, including febrile 
seizures, with the 2009 monovalent H1N1 influenza vaccine. The Program 
will consider a claim for febrile seizure leading to serious injury or 
death on a case-by-case basis as a non-Table claim.

(3) Bronchospasm

    Bronchospasm is a constriction of the muscles in the walls of the 
smaller breathing tubes (bronchioles) in the lungs. It is facilitated 
by cells in the immune system under the influence of various stimuli. 
The resulting constriction and inflammation causes a narrowing of the 
airways and an increase in mucus production, which reduces air 
exchange. This causes breathlessness, coughing, and wheezing. Some 
common causes of bronchospasm in a susceptible person are allergic 
reactions to certain foods and medications, chemical irritation, and 
infections.
    Evidence indicates that the 2009 H1N1 intranasal vaccine may be 
associated with bronchospasm in children younger than two years of age; 
however, this has not been observed consistently in older individuals. 
For this reason, the intranasal vaccine is not recommended for children 
younger than two years of age. To date, no direct link

[[Page 17985]]

has been shown between bronchospasm and the 2009 H1N1 vaccination 
through surveillance when given to recommended populations. Therefore, 
the Secretary does not propose including bronchospasm on the Table for 
the 2009 H1N1 vaccine at this time.
    In its 2012 report, the IOM concluded that the evidence is 
inadequate to accept or reject a causal relationship between seasonal 
Live Attenuated Influenza Vaccine (LAIV) and asthma exacerbation or 
reactive airway disease episodes in both children younger than five 
years of age and persons who are five years of age or older. In 
addition, this same IOM committee concluded that the evidence favors 
rejection of a causal relationship between inactivated influenza 
vaccine and asthma exacerbation or reactive airway disease episodes in 
children and adults.\67\
---------------------------------------------------------------------------

    \67\ IOM, Adverse Effects of Vaccines, 356.
---------------------------------------------------------------------------

    Should compelling, reliable, valid, medical and scientific evidence 
arise to demonstrate a direct link between bronchospasm and the 2009 
H1N1 vaccine with respect to populations for which the vaccine is 
indicated, the Secretary may add this injury to the Table. Unless such 
an amendment is made, the Program will consider any claims for 
bronchospasm leading to serious injury or death on a case-by-case basis 
as a non-Table claim.

Pandemic Influenza Antiviral Medications

    Influenza antiviral medications including Tamiflu and Relenza have 
been reported in controlled trials to shorten the time to symptom 
improvement in acute uncomplicated influenza caused by circulating 
viral strains; based on retrospective observational studies and pooled 
analyses, many experts believe they can reduce the severity and 
duration of influenza and can reduce the risk of influenza-related 
complications, severe illness, and death. Tamiflu, Relenza, and 
peramivir have been used to combat influenza A and B viruses by 
inhibiting the viral neuraminidase enzyme involved in releasing viral 
particles from the infected cell. These antivirals were used to treat 
and protect against illness due to the 2009 H1N1 virus in the 2009-2010 
pandemic influenza season. Tamiflu and Relenza are covered when used to 
treat or protect against a current or potential pandemic influenza. 
Peramivir is covered when used to treat 2009 H1N1 influenza during the 
2009 pandemic season. The use of these drugs for the treatment or 
prevention of seasonal influenza is not covered.
    Tamiflu is a prescription medicine taken by mouth for the 
prevention and treatment of influenza. Similarly, Relenza is an inhaled 
prescription drug used for the prevention and treatment of influenza. 
Peramivir is an intravenous investigational antiviral drug currently 
limited in use in the United States. For example, it has been used in 
clinical trials and for a time was available under an emergency use 
authorization (EUA) in response to the 2009 H1N1 pandemic. However, 
this EUA is currently not in effect.
    The proposed Table currently includes anaphylaxis for Tamiflu, 
Relenza and peramivir because compelling, reliable, valid, medical and 
scientific evidence establishes a causal relationship between these 
drugs and anaphylaxis. A discussion of anaphylaxis can be found in the 
pandemic influenza vaccines section of this preamble to this NPRM. 
Further support for causation is based on the well-established 
biological mechanism that anaphylaxis, according to the IOM reports of 
1994 and 2003 on vaccine adverse events, can occur after exposure to a 
foreign antigen or drug and by the temporal sequence of observed events 
following exposure. In addition, the spectrum of host responses that 
follows a logical biologic gradient, as described by the IOM, from mild 
hypersensitivity reactions to true anaphylaxis have been observed and 
are known to occur in post marketing surveillance for Tamiflu and 
Relenza. During the pandemic there was only limited use of peramivir 
under IND or EUA in the United States, and postmarketing experience 
comparable to Tamiflu and Relenza is not available, but peramivir is 
included here on the basis of experience with similar drugs.
    Compelling, reliable, valid, scientific and medical evidence 
supports that antiviral drugs can cause anaphylaxis if the onset of the 
condition occurs within four hours after the administration or use of 
the antiviral.\68\ According to the American College of Allergy, 
Asthma, and Immunology, any person can develop an allergic drug 
reaction to any drug (http://www.acaai.org/allergist/allergies/Types/drug-allergy/Pages/default.aspx).
---------------------------------------------------------------------------

    \68\ Werner J. Pichler, et al., ``Drug Hypersensitivity 
Reactions: Pathomechanisms and Clinical Symptoms,'' Medical Clinics 
North America, July 2010; 651-654.
---------------------------------------------------------------------------

    Tamiflu capsules contain gelatin, which is a protein known to cause 
allergic reactions and anaphylaxis in sensitized individuals. With 
Relenza, each dose inhaled contains lactose powder that also contains 
milk proteins, which may cause the spectrum of allergic reactions in 
sensitized individuals. Based on the unique nature of the presentation 
and timing of anaphylaxis together with consensus in the medical 
community regarding causation and the existing medical literature, the 
Secretary proposes including anaphylaxis on the Table for Tamiflu, 
Relenza, and peramivir. For the reasons discussed for anaphylaxis, the 
Secretary proposes including an onset interval of 0-4 hours on the 
Table after the administration or use of Tamiflu, Relenza, or 
peramivir. Anaphylaxis is proposed for inclusion on the Table because 
it is a serious physical injury that may be directly caused by the use 
of these antiviral medications, as supported by compelling, reliable, 
valid, medical and scientific evidence.
    Since only serious physical injuries qualify as covered injuries, 
the Secretary does not propose including minor adverse events for 
Tamiflu, Relenza and peramivir on the Table. Minor side effects 
associated with Tamiflu include nausea and vomiting, which usually 
occur in the first two days of treatment. Minor side effects associated 
with Relenza include cough, nasal irritation, nausea, vomiting, 
headache, and ear, nose, and throat infections. The more commonly 
reported side effects of peramivir, which may or may not be related 
causally, are diarrhea, nausea, vomiting, and a decrease in white blood 
cell count. These side effects were reported from clinical trials. 
Possible side effects of receiving any medication (including peramivir) 
by vein are brief pain, bleeding, bruising of the skin where the needle 
entered, soreness and swelling, and inflammation or infection at the 
needle entry point. These reactions are usually minor and resolve 
without complication. However, in cases in which these symptoms worsen 
and lead to serious physical injury or death, the Program will consider 
these claims on a case-by-case basis as non-Table claims.

Pandemic Influenza Antivirals Conditions of Special Interest

    The Secretary does not propose to include the following conditions 
associated with the antiviral drugs on the Table at this time, although 
they are of special interest to the public. These conditions may be 
added in the future if compelling, reliable, valid, medical and 
scientific evidence becomes available showing a direct link between the 
antiviral drug(s) and these conditions. Such conditions include:

[[Page 17986]]

(1) Bronchospasm

    Bronchospasm is a constriction of the muscles in the walls of 
smaller breathing tubes (bronchioles) in the lungs. It is facilitated 
by cells in the immune system under the influence of various stimuli. 
The resulting constriction, inflammation, and increased mucus 
production causes a narrowing of the airways which reduces air exchange 
and may lead to breathlessness, coughing, and/or wheezing.
    Serious cases of bronchospasm, including fatalities, have been 
reported to FDA and manufacturers during treatment with Relenza in 
patients with and without underlying airway disease.\69\ Many of these 
cases were reported during post-marketing surveillance and causality 
was difficult to assess because, for example, some patients without 
prior pulmonary disease may also have respiratory abnormalities from 
acute respiratory infection that could resemble this adverse drug 
reaction.
---------------------------------------------------------------------------

    \69\ Relenza (zanamivir) Inhalation Powder, for oral inhalation 
[package insert]. Research Triangle Park, NC: GlaxoSmithKine: 
December 2011. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021036s027lbl.pdf. Accessed March 22, 2013.
---------------------------------------------------------------------------

    Should compelling, reliable, valid, medical and scientific evidence 
become available and demonstrate a direct link between bronchospasm and 
Relenza the Program may add this injury to the Table. Unless such an 
amendment is made, the Program will consider any claims for 
bronchospasm leading to serious injury or death on a case-by-case basis 
as non-Table claims.

(2) Neuropsychiatric Events

    Rarely, transient neuropsychiatric events such as self-injury or 
delirium have been reported in post-market monitoring among persons 
taking Tamiflu and Relenza. The majority of reports were among children 
and adolescents living in Japan. Because influenza infection itself may 
be associated with a variety of neurologic and behavioral symptoms 
(e.g., seizures, delirium and hallucinations), it is unclear whether 
the antiviral drugs are responsible for these neuropsychiatric effects. 
To date, retrospective analyses conducted by the manufacturers of 
Tamiflu and Relenza and the Vaccine Safety Datalink have not found 
evidence for an increased risk of neuropsychiatric events after Tamiflu 
or Relenza use.\70\
---------------------------------------------------------------------------

    \70\ Toovey, Stephen, et al., ``Post-Marketing Assessment of 
Neuropsychiatric Adverse Events in Influenza Patients Treated with 
Oseltamivir: An Updated Review,'' Adv Ther, October 2012; 826-48; 
and Greene, Sharon, et al., ``Risk of adverse events following 
oseltamivir treatment in influenza outpatients, Vaccine Safety 
Datalink Project, 2007-2010,'' Pharmacoepidemiology and Drug Safety, 
October 2012; published online (no page numbers).
---------------------------------------------------------------------------

    Should compelling, reliable, valid, medical and scientific evidence 
become available and demonstrate a direct link between neuropsychiatric 
effects and Tamiflu and/or Relenza, the Program may add these injuries 
to the Table. Unless such an amendment is made, the Program will 
consider any claims for neuropsychiatric effects leading to serious 
injury or death on a case-by-case basis as non-Table claims.

Pandemic Influenza Personal Respiratory Protection Devices

    To reduce the risk of infection in certain populations and areas 
with confirmed cases of 2009 H1N1 influenza, the CDC has put forward 
recommendations for the use of personal respiratory protection devices. 
Personal respiratory protection devices are for use by individuals to 
reduce wearer exposure to pathogenic biological airborne particulates 
according to the Secretarial declaration of December 17, 2008.\71\ Such 
devices also can be used to reduce transmission of infection from the 
person wearing the device to another. Examples of personal respiratory 
protection devices are ``facemasks'' and respirators. The term 
``facemask'' refers to disposable facemasks approved by FDA for use as 
medical devices, including facemasks labeled as surgical, dental, 
medical procedure, isolation, or laser masks. These facemasks loosely 
fit the face. They have specific levels of protection from penetration 
of blood and body fluids and help stop droplets from being spread by 
the individuals wearing them. Furthermore, a facemask acts to prevent 
splashes or sprays from reaching the mouth and nose of the person 
wearing the facemask. A facemask generally does not protect against 
breathing in very small aerosolized particles that may contain viruses.
---------------------------------------------------------------------------

    \71\ 73 FR 78362.
---------------------------------------------------------------------------

    A respirator refers to an N95 or higher filtering face piece 
respirator. A respirator that fits properly on the face can filter out 
virus-containing small particles in the aerosol that can be generated 
by an infected person. Compared to a facemask, it is harder to breathe 
through a respirator for long periods of time. Although some 
respirators may cause latex or contact allergies, these reactions are 
generally self-limited and do not usually rise to the level of serious 
injury.
    The Secretary considered potential injuries due to the use or 
administration of personal respiratory protection devices. The use of 
personal respiratory protection devices may cause injury in some 
wearers. However, the Secretary finds that use or administration of 
personal respiratory protection devices generally are not known to 
cause serious physical injuries. Therefore, the proposed Table 
indicates that there presently is ``[N]o condition covered'' for this 
countermeasure. Injuries may be added in the future if compelling, 
reliable, valid, medical and scientific evidence develops revealing a 
causal relationship between a personal respiratory protection device 
and a serious adverse event. The Program will consider a claim leading 
to serious injury or death from the use or administration of a personal 
respiratory protection device on a case-by-case basis as a non-Table 
claim.

Pandemic Influenza Respiratory Support Devices

    Infection with the 2009 H1N1 virus and other pandemic strains of 
influenza can lead to serious respiratory tract disease, including 
pneumonia. Additionally, influenza infection can make people more 
susceptible to bacterial pneumonia and other serious complications. 
Individuals infected with covered influenza A viruses may require 
respiratory support with respiratory devices, such as mechanical 
ventilators, lung expansion devices, and extracorporeal membrane 
oxygenation (ECMO). Mechanical ventilators assist or control 
respiration continuously. Lung expansion devices include products such 
as intermittent positive-pressure breathing, nasal positive end-
expiratory pressure, and continuous nasal positive airway pressure. 
ECMO mechanically provides for essential lung functions outside the 
body.
    Generally, patients requiring respiratory support devices already 
have a significant degree of injury or compromise to their lungs. 
Notwithstanding any prior lung injuries, it is possible to sustain 
serious respiratory tract damage directly from these devices. 
Complications from the underlying influenza infection may have a great 
deal of overlap with effects or adverse events secondary to the use of 
respiratory support devices.
    The proposed Table includes post-intubation tracheal stenosis, 
ventilator-induced lung injury (VILI), ventilator-associated pneumonia 
(VAP), and ventilator-associated tracheobronchitis (VAT) as injuries 
caused by mechanical ventilators. Bleeding events also are listed as 
Table injuries associated with receiving anticoagulation medication for 
ECMO. These are proposed for inclusion on the Table because they are 
serious

[[Page 17987]]

physical injuries that may be directly caused by the use of respiratory 
support devices, as supported by compelling, reliable, valid, medical 
and scientific evidence.

Tracheal Stenosis

    The proposed Table includes tracheal stenosis, which is an abnormal 
narrowing in the windpipe that can increase the work of breathing. Oral 
or nasal endotracheal tubes or tracheostomy tubes (tubes placed in the 
throat to assist with breathing) are most commonly used to deliver 
mechanical ventilatory support in respiratory failure. Despite 
technological improvements, tracheal stenoses still constitute an 
important group of complications after intubation and tracheostomy. 
Early endotracheal tubes were not designed to minimize pressure from 
the tube's cuff, leading to a much higher incidence of tracheal 
stenosis than is seen with more modern endotracheal tubes with more 
compliant cuffs. These newer cuffs have been shown to greatly reduce, 
but not eliminate, the incidence of tracheal stenosis. Endotracheal 
intubation is used to secure a patient's airway, to act as a means to 
deliver oxygen gas from the ventilator to the patient, to prevent 
aspiration, and/or to help to clear secretions. Pressure from the 
endotracheal tube itself or from the cuff of the endotracheal tube, 
which achieves a pneumatic seal between the tube and trachea, can lead 
to regions of tracheal ischemia (a restriction in blood supply) that 
may eventually cause tracheal stenosis.
    The reported incidence of symptomatic or clinically significant 
tracheal stenosis following tracheostomy and laryngotracheal intubation 
currently is less than one percent. When stenosis occurs, the process 
leading to airway narrowing can begin at any time after intubation or 
placement of a tracheostomy tube. Tracheal stenosis due to endotracheal 
intubation mostly occurs at the cuff of the tube due to decreased blood 
flow to the trachea caused by the cuff. The most important reason for 
stenosis at the tracheal stoma site (the opening of a tracheostomy) is 
damaged cartilage and wound infection. In addition, previous cervical 
or tracheal trauma can negatively affect healing of the stoma leading 
to stenosis.
    The usual presenting symptoms of tracheal stenosis may include 
shortness of breath, stridor (an abnormal, high-pitched, inspiratory 
sound produced by turbulent airflow through a partially obstructed 
airway), and/or wheezing. A slow resumption of physical activity after 
being on a ventilator can mask or delay the first symptom or 
manifestation of the onset of injury of tracheal stenosis. These 
obstructive symptoms appearing in a person who is at rest indicate the 
diameter of the trachea has decreased to 30 percent or less of its 
normal size at the point of narrowing. Less stenosis can become 
symptomatic with exertion, and shortness of breath on exertion is the 
most common presenting symptom. Symptoms usually develop within 2 to 42 
days after removal of the tube in people who develop symptoms.
    The length and severity of a tracheal stenosis lesion is ideally 
determined by bronchoscopic evaluation including laryngoscopy to assess 
vocal cord function and the presence and location of stenosis in the 
windpipe. Computerized axial tomography (CT) scans can serve as a rough 
guide to the location of the stenosis. Other causes of tracheal 
stenosis include malignant and benign tumors, infections of the trachea 
(such as tuberculosis and fungal diseases), radiotherapy, tracheal 
surgery, trauma, congenital abnormality, inflammatory diseases, and 
autoimmune diseases.
    Compelling, reliable, valid, medical and scientific literature 
support a direct link between tracheal stenosis and ventilators due to 
the placement of an endotracheal or a tracheostomy tube.\72\ Therefore, 
this injury is proposed for inclusion on the Table.
---------------------------------------------------------------------------

    \72\ John C. Wain, Jr., ``Postintubation Tracheal Stenosis,'' 
Seminars in Thoracic and Cardiovascular Surgery, Fall 2009; 284-286; 
and Mitlu M. Gokhan and Fhillip Factor, ``Complications of 
Mechanical Ventilation,'' Respiratory Care Clinics of North America; 
Jun. 2, 2000; 230.
---------------------------------------------------------------------------

Ventilator-Associated Pneumonia (VAP) and Ventilator-Associated 
Tracheobronchitis (VAT)

    VAP and VAT are other potential conditions that can be caused by 
ventilator use. VAP and VAT are defined as occurring in patients who 
manifest pneumonia or tracheobronchitis more than 48 hours after being 
intubated. There is no minimum period of time of ventilator use for the 
pneumonia or tracheobronchitis to be considered ventilator-associated. 
Bacteria growing in the mouth and on the breathing tube can easily 
enter the normally bacteria-free trachea and lungs, and this is 
generally the source of the bacteria for VAP and VAT. Most of the 
diagnostic criteria for VAP and VAT include clinical symptoms and signs 
of infection, including the signs of a lung infection, new onset of 
fever, purulent sputum (upper respiratory secretions containing pus), 
leukocytosis (increased white blood cell count), leukopenia (decreased 
white blood cell count), wheezing, cough, bradycardia (diminished heart 
rate), chest pain, coughing blood, abnormal breath sounds, altered 
mental status, laboratory evidence of infection, and a decline in the 
ability to oxygenate and remove carbon dioxide from the blood.\73\ An 
individual with these symptoms and signs and no abnormalities on chest 
x-ray may have VAT because the infection in the trachea may not be seen 
on a chest x-ray. Patients with chest x-ray findings consistent with 
pneumonia may have VAP. VAT can be related to VAP with regard to cause, 
but is different because the location of the infection is in the 
trachea instead of the lungs.
---------------------------------------------------------------------------

    \73\ Centers for Disease Control and Prevention (CDC), 
Ventilator-Associated Event; January 2013; http://www.cdc.gov/nhsn/PDFs/pscManual/10-VAE_FINAL.pdf.
---------------------------------------------------------------------------

    VAP is the most common infection acquired in intensive care units. 
Recent publications report that the rate of VAP ranges from 0.0 to 5.8 
cases per 1,000 ventilator days.\74\ Patients with VAP require more 
days of mechanical ventilation and hospitalization, and more 
medications. The mortality rate may exceed 10 percent.
---------------------------------------------------------------------------

    \74\ CDC, 6-1.
---------------------------------------------------------------------------

    There is compelling reliable, valid, medical and scientific 
evidence indicating that VAP and VAT are injuries that may be caused by 
mechanical ventilator use.\75\ Thus, VAP and VAT are proposed Table 
injuries for respiratory support devices that are used to mechanically 
ventilate covered patients.
---------------------------------------------------------------------------

    \75\ Dennis L. Kasper, MD, Harrison's ``Principles of Internal 
Medicine, 16th edition''; (United States of America: McGraw-Hill, 
2005); 777; and Susan E Coffin, et al., ``Strategies to Prevent 
Ventilator Associated Pneumonia in Acute Care Hospitals,'' Infection 
Control and Hospital Epidemiology, Oct. 2008; S31-S40.
---------------------------------------------------------------------------

    There may be cases where an individual has VAP or VAT but does not 
meet the proposed definition of VAP or VAT. Such cases will be 
evaluated on a case-by-case basis, and the Secretary will determine 
medical eligibility based on the presence of compelling, reliable, 
valid, medical and scientific evidence.

Ventilator-Induced Lung Injury (VILI)

    The medical literature demonstrates that mechanical ventilation can 
harm the lung and result in VILI.\76\ VILI occurs as a result of 
mechanical trauma to lung structures induced by the positive pressure 
delivered to the lungs

[[Page 17988]]

by the ventilator. The positive pressure produces alveolar (air sac) 
stretching leading to non-physiologic (abnormal) stretching which leads 
to lung damage (volutrauma). Trauma caused by the positive pressure 
from the ventilator is called barotrauma. The non-physiologic stress 
and strain produced by barotraumas and volutrauma can promote the 
release of inflammatory chemicals (cytokines) resulting in lung 
inflammation. This biological reaction to mechanical forces is known as 
biotrauma. Serious abnormal conditions included under VILI, that are 
known to be caused by the barotrauma and volutrauma forces generated by 
mechanical ventilators, include pneumothorax (a type of lung collapse), 
pneumomediastinum (abnormal air in the middle portion of the chest), 
lung cysts, systemic air embolism, and acute respiratory distress 
syndrome (ARDS).\77\
---------------------------------------------------------------------------

    \76\ Lee Goldman, MD and J. Claude Bennett, MD, ``Cecil's 
Textbook of Medicine, 21st edition''; (United States of America: 
W.B. Saunders, 2000); 493.
    \77\ Goldman, 493 and Luciano Gattinoni, et al., ``Ventilator-
induced lung injury: The anatomical and physiological framework,'' 
Critical Care Medicine, Oct 2010; S539-S540.
---------------------------------------------------------------------------

    Compelling, reliable, valid, medical and scientific evidence 
indicates that VILI is an injury directly caused by mechanical 
ventilator use. Thus, VILI is proposed to be added to the Table as a 
covered injury for respiratory support devices that are used to 
mechanically ventilate patients who have developed an infection caused 
by a pandemic influenza.
    As mentioned above, diffuse alveolar damage that is identical to 
ARDS may occur as a result of alveolar trauma resulting from mechanical 
ventilation. In addition, ARDS may also be caused by an underlying 
airway disease that leads to the requirement of mechanical ventilation. 
The mechanical ventilation may or may not aggravate a case of ARDS 
caused by something other than a respiratory support device. It may be 
difficult to differentiate the cause for ARDS because it can be caused 
by: (1) An underlying lung disease; (2) a 2009 H1N1 influenza 
pneumonia; or (3) the ventilator treatment needed to support a patient 
with 2009 H1N1 influenza pneumonia. ARDS is a frequent complication of 
severe influenza pneumonia.\78\
---------------------------------------------------------------------------

    \78\ Goldman, 1799.
---------------------------------------------------------------------------

    Because of the difficulties in determining the cause of ARDS, for 
purposes of the Table, ARDS will not be considered part of the VILI 
disease spectrum and will not be added to the Table. However, the 
Program will consider a claim for ARDS leading to serious injury or 
death on a case-by-case basis as a non-Table claim.
    Positive pressure mechanical ventilation may also compromise the 
cardiovascular system because the positive airway pressure during 
inspiration reduces blood return to the heart and may decrease cardiac 
output with decreased profusion.\79\ A decreased cardiac output can 
adversely affect multiple organ systems. Because of the complexity of 
the potential effects of this diminished cardiac output on multiple 
organ systems, these cases will be reviewed on a case-by-case basis.
---------------------------------------------------------------------------

    \79\ Goldman, 493.
---------------------------------------------------------------------------

Extracorporeal Membrane Oxygenation

    As mentioned under the previous section, the 2009 H1N1 influenza 
virus was a worldwide cause of acute respiratory distress syndrome 
(ARDS). Most people with fatal 2009 H1N1 influenza infections died as a 
result of unrelenting hypoxemia (low oxygen levels in the blood) and 
respiratory failure. Conventional treatment of this condition with a 
ventilator can lead to additional lung injury due to factors such as 
barotrauma, volutrauma, and biotrauma. Select patients with severe ARDS 
who do not respond to advanced modes of mechanical ventilation may have 
extracorporeal membrane oxygenation (ECMO) as a treatment option. ECMO 
uses cardiac bypass technology to provide gas exchange (the function of 
the lungs) mechanically outside the body in a bedside machine. This 
temporary takeover of the lung function by ECMO allows ventilator 
settings to be reduced, thereby causing less lung damage and providing 
the opportunity for the lungs to heal and improve.
    With ECMO, catheters are inserted through the skin into large veins 
for drainage and infusion of blood. People on ECMO must have their 
blood thinned (anti-coagulated). ECMO involves the removal of large 
volumes of venous blood from the person receiving treatment, and then 
circulating the blood with a pump outside the body through an 
oxygenator (artificial lung) that inserts oxygen into the blood and a 
carbon dioxide scrubber that removes carbon dioxide. The oxygenated 
blood is then re-infused back into the treated person as arterial 
blood.
    An international registry compiled by the Extracorporeal Life 
Support Organization, referred to as the ``ECMO registry,'' indicates 
that ECMO has been used frequently to treat H1N1 influenza associated 
with respiratory failure. This is likely because critically ill H1N1 
patients are mostly young, otherwise healthy people without other 
significant illnesses who are therefore prime candidates for ECMO. The 
most recent statistics from the H1N1 ECMO registry reflect that as of 
April 13, 2011, there were 323 patients from 76 centers on the 
registry.\80\
---------------------------------------------------------------------------

    \80\ Extracorporeal Life Support Organization, H1N1 ECMO 
Registry, Apr. 13, 2011, http://www.elso.med.umich.edu/h1n1registry.html. At this time Extracorporeal Life Support 
Organization has stopped collecting additional information on H1N1 
cases.
---------------------------------------------------------------------------

    An observational study that examined 68 patients with 2009 H1N1 
influenza-associated ARDS treated with ECMO found that 54 percent of 
patients had bleeding complications (due to the necessary anti-
coagulation), with the most common sources being the catheter insertion 
site (22 percent), the gastrointestinal tract (10 percent), the 
respiratory tract (10 percent), vaginal bleeding (9 percent), and 
intracranial hemorrhage (9 percent).\81\
---------------------------------------------------------------------------

    \81\ Andrew Davies, et al., ``Extracorporeal Membrane 
Oxygenation for 2009 Influenza A (H1N1) Acute Respiratory Distress 
Syndrome,'' Journal of the American Medical Association, Nov. 4, 
2009; 1892.
---------------------------------------------------------------------------

    The above-referenced bleeding complications are related to the use 
of ECMO and may be a consequence of the use of this countermeasure. 
These events constitute serious physical injuries that may be caused by 
the use of ECMO, as supported by compelling, reliable, valid, medical 
and scientific evidence, and therefore are proposed to be added to the 
Table. The time interval for the first manifestation of the covered 
injury is the time period during which the injured person is under the 
effects of the anti-coagulant therapy, including the time needed to 
clear any clinically significant effect after the medication is 
stopped, as measured by relevant coagulation testing.

Pandemic Influenza Diagnostic Testing Devices

    Pandemic influenza diagnostics are tests to identify or otherwise 
aid in the diagnosis of avian or other animal influenza A viruses that 
pose a pandemic threat.\82\ A number of diagnostic tests are available 
to detect the presence of influenza infection in respiratory specimens. 
The tests differ in many ways, including their sensitivity and 
specificity for detecting influenza viruses, their commercial 
availability, processing time, approved clinical setting, and ability 
to distinguish among different influenza virus types and among 
influenza A subtypes (e.g., 2009 H1N1 versus seasonal H1N1 versus 
seasonal H3N2 viruses).
---------------------------------------------------------------------------

    \82\ 73 FR 78362.
---------------------------------------------------------------------------

    The tests most commonly used to diagnose infection with the 2009 
H1N1 virus are the real-time reverse transcriptase polymerase chain 
reaction

[[Page 17989]]

tests (rRT-PCR tests). The rRT-PCR tests identify the 2009 H1N1 virus 
by amplifying the viral genetic material from a sample. A positive 
result indicates that the patient is presumptively infected with the 
2009 H1N1 virus, but it does not identify the stage of infection. A 
negative result does not, by itself, exclude the possibility of the 
2009 H1N1 virus infection.
    Tests, such as a CT scan or magnetic resonance imaging (MRI), 
performed to determine the extent or seriousness or sequelae of 
influenza infection in a patient are not considered diagnostic tests 
for the purpose of diagnosing the presence of pandemic infection in the 
individual or for the purposes of this Program. Only influenza 
diagnostic tests performed for the purpose of identifying the presence 
in the body of the pandemic influenza virus are covered.
    The Secretary considered potential serious injuries due to the use 
or administration of pandemic influenza diagnostics testing devices. 
Adverse events associated with the use or administration of these 
testing devices include potential consequences of an inaccurate result 
and potential discomfort during sample collection. However, these 
diagnostic testing devices are generally not known to cause serious 
physical injury. Therefore, the proposed Table does not list any 
injuries related to pandemic influenza diagnostic testing devices and 
indicates that there presently is ``[N]o condition covered'' for this 
countermeasure. However, injuries may be added to the Table if 
compelling, reliable, valid, medical and scientific evidence develops 
showing causation between a serious physical injury and a diagnostic 
test. The Program will consider a claim from the administration or use 
of diagnostic testing devices leading to serious injury or death on a 
case-by-case basis as a non-Table claim.
    Compensation will not be available merely because a diagnostic test 
provides inaccurate results, such as failure to diagnose a pandemic 
influenza infection that is present or yielding a positive result for a 
pandemic influenza infection that is not present. The Program cannot 
compensate for injuries that are the direct result of the covered 
condition or disease for which the countermeasure was administered or 
used, and that are not the direct result of the administration or use 
of the covered countermeasure (for example, if the covered 
countermeasure is ineffective). See 42 CFR 110.20(d).

 Regulatory Impact Analysis

    HRSA has examined the impact of this rulemaking as required by 
Executive Order 12866 on Regulatory Planning and Review (September 30, 
1993), Executive Order 13563 on Improving Regulation and Regulatory 
Review (January 18, 2011), the Congressional Review Act (5 U.S.C. 
804(2)), the Regulatory Flexibility Act (RFA) (September 19, 1980, Pub. 
L. 96-354), section 202 of the Unfunded Mandates Reform Act of 1995 
(March 2, 1995; Pub. L. 104-4), section 654(c) of the Treasury and 
General Government Appropriations Act of 1999, and Executive Order 
13132 on Federalism (August 4, 1999).
    Executive Order 12866 requires that all regulations reflect 
consideration of alternatives, costs, benefits, incentives, equity, and 
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. In 2011, President Obama supplemented 
and reaffirmed Executive Order 12866. This rulemaking is not being 
treated as a significant regulatory action under section 3(f) of 
Executive Order 12866. Accordingly, the proposed rule has not been 
reviewed by the Office of Management and Budget.
    Executive Order 13563 provides that, to the extent feasible and 
permitted by law, the public must be given a meaningful opportunity to 
comment through the Internet on any proposed regulations, with at least 
a 60-day comment period. In addition, to the extent feasible and 
permitted by law, agencies must provide timely on-line access to both 
proposed and final rules of the rulemaking docket on Regulations.gov, 
including relevant scientific and technical findings, in an open format 
that can be searched and downloaded. Federal agencies must consider 
approaches to maintain the freedom of choice and flexibility, including 
disclosure of relevant information to the public. Regulations must be 
guided by objective scientific evidence, easy to understand, 
consistent, and written in plain language. Furthermore, Federal 
agencies must attempt to coordinate, simplify, and harmonize 
regulations to reduce costs and promote certainty for the public.
    In this NPRM, the Secretary proposes a Table identifying serious 
physical injuries that shall be presumed to result from the 
administration or use of the covered countermeasures, and the time 
interval in which the onset of the first symptom or manifestation of 
each such serious physical injury must manifest in order for such 
presumption to apply. The Secretary is also proposing Table definitions 
and requirements. This proposed rule would have the effect of affording 
certain persons a presumption that particular serious physical injuries 
were sustained as the result of the administration or use of covered 
countermeasures. The Table, if implemented, will establish a 
presumption of causation and relieve requesters of the burden of 
demonstrating causation for covered injuries listed on the Table. 
However, this presumption is rebuttable based on the Secretary's review 
of the evidence. This Table may afford some requesters a new filing 
deadline.
    Other than showing that a serious physical injury or death directly 
resulted from an injury included on the Table for compensation 
purposes, individuals may, in the alternative, receive compensation if 
they are eligible and can show a causation-in-fact relationship between 
an injury or death and a covered countermeasure. This NPRM is based 
upon legal authority.
    Because any resources required to implement the regulatory 
requirements imposed by the Program are not required by virtue of the 
establishment of a Table, and because the Secretary conducted an 
independent analysis concerning any burdens associated with the 
implementation of the Program when the Secretary published the 
companion regulation \83\ setting forth the Program's administrative 
implementation, the Secretary has determined that no resources are 
required to implement the provisions included in this NPRM. Therefore, 
in accordance with the Regulatory Flexibility Act of 1980 (RFA) and the 
Small Business Regulatory Enforcement Fairness Act of 1996, which 
amended the RFA, the Secretary certifies that this NPRM will not have a 
significant impact on a substantial number of small entities.
---------------------------------------------------------------------------

    \83\ 75 FR 64955.
---------------------------------------------------------------------------

    The Secretary has also determined that this NPRM 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. The 
Secretary has determined that this NPRM 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

[[Page 17990]]

1995. This NPRM comports with the 2011 supplemental requirements.

Unfunded Mandates Reform Act of 1995

    The Secretary has determined that this NPRM 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.

Federalism Impact Statement

    The Secretary has also reviewed this NPRM in accordance with 
Executive Order 13132 regarding federalism, and has determined that it 
does not have ``federalism implications.'' This NPRM, if implemented, 
would not ``have substantial direct effects on the States, or on the 
relationship between the national government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government.''

Impact on Family Well-Being

    This NPRM will not adversely affect the following elements of 
family well-being: 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. In fact, this NPRM may have a positive impact on the 
disposable income and poverty elements of family well-being to the 
extent that injured persons or their families may receive medical, lost 
employment income, and/or death benefits paid under this part without 
imposing a corresponding burden on them.

Paperwork Reduction Act of 1995, as Amended

    This NPRM has no information collection requirements.

List of Subjects in 42 CFR Part 110

    Anaphylaxis, Anticoagulation, Antiviral, Avian, Benefits, 
Biologics, Bleeding, Bursitis, Compensation, Countermeasure, 
Declaration, Deltoid, Diagnostics, Device, Eligibility, Extra-Corporeal 
Membrane Oxygenation (ECMO), Fisher Syndrome, Guillain-Barre Syndrome, 
2009 H1N1, Influenza, Injury Table, Immunization, Oseltamivir, 
Pandemic, Peramivir, Public Readiness and Emergency Preparedness Act 
(PREP Act), Radiation Syndrome, Respiratory Protection, Relenza, 
Respirator, Respirator Support, Tamiflu, Tracheal Stenosis, Vaccine, 
Vasovagal Syncope, Ventilator, Ventilator-Associated Pneumonia and 
Tracheobronchitis, Ventilator-Induced Lung Injury, Zanamivir.

    Dated: February 28, 2014.
Mary Wakefield,
Administrator, Health Resources and Services Administration.
    Approved: March 13, 2014.
Kathleen Sebelius,
Secretary.
    Therefore, for the reasons stated in the preamble, the Department 
of Health and Human Services proposes to amend 42 CFR part 110 as 
follows:

PART 110--COUNTERMEASURES INJURY COMPENSATION PROGRAM

0
1. The authority citation for part 110 continues to read as follows:

    Authority: 42 U.S.C. 247d-6e.

0
2. Add Sec.  110.100 to subpart K to read as follows:


Sec.  110.100  Injury tables.

    (a) Pandemic Influenza Countermeasures Injury Table.

------------------------------------------------------------------------
                                                     Time interval (for
                                                      first symptom or
                                                      manifestation of
   Covered countermeasures      Serious physical       onset of injury
      under secretarial         injury (illness,    after administration
        declarations           disability, injury,    or use of covered
                                or condition) \1\      countermeasure,
                                                      unless otherwise
                                                         specified)
------------------------------------------------------------------------
I. Pandemic influenza         A. Anaphylaxis......  A. 0-4 hours.
 vaccines administered by     B. Deltoid Bursitis.  B. 0-48 hours.
 needle into or through the   C. Vasovagal Syncope  C. 0-1 hour.
 skin.
II. Pandemic influenza        A. Anaphylaxis......  A. 0-4 hours.
 intranasal vaccines.
III. Pandemic influenza 2009  A. Guillain-          A. 3-42 days (not
 H1N1 vaccine.                 Barr[egrave]          less than 72 hours
                               Syndrome.             and not more than
                                                     42 days).
IV. Oseltamivir Phosphate     A. Anaphylaxis......  A. 0-4 hours.
 (Tamiflu) when administered
 or used for pandemic
 influenza.
V. Zanamivir (Relenza) when   A. Anaphylaxis......  A. 0-4 hours.
 administered or used for
 pandemic influenza.
VI. Peramivir when            A. Anaphylaxis......  A. 0-4 hours.
 administered or used for
 2009 H1N1 influenza.
VII. Pandemic influenza       A. No condition       A. Not applicable.
 personal respiratory          covered \2\.
 protection devices.
VIII. Pandemic influenza      A. Postintubation     A. 2-42 days (not
 respiratory support devices.  Tracheal Stenosis.    less than 48 hours
                                                     and not more than
                                                     42 days) after
                                                     extubation (removal
                                                     of a tracheostomy
                                                     or endotracheal
                                                     tube).
                              B. Ventilator-        B. More than 48
                               Associated            hours after
                               Pneumonia and         intubation
                               Ventilator-           (placement of an
                               Associated            endotracheal or
                               Tracheobronchitis.    tracheostomy tube)
                                                     and up to 48 hours
                                                     after extubation
                                                     (removal of the
                                                     tube).
                              C. Ventilator-        C. Throughout the
                               Induced Lung Injury.  time of intubation
                                                     (breathing through
                                                     an endotracheal or
                                                     tracheostomy tube)
                                                     and up to 48 hours
                                                     after extubation
                                                     (removal of the
                                                     tube).
IX. Pandemic influenza        A. Bleeding Events..  A. Throughout the
 respiratory support device:                         time of
 extra-corporeal membrane                            anticoagulation
 oxygenation (ECMO).                                 treatment for ECMO
                                                     therapy, including
                                                     the time needed to
                                                     clear the effect of
                                                     the anti-coagulant
                                                     treatment from the
                                                     body.

[[Page 17991]]

 
X. Pandemic influenza         A. No condition       A. Not applicable.
 diagnostic testing devices.   covered.
------------------------------------------------------------------------
\1\ Serious physical injury as defined in 42 CFR 110.3(z). Only injuries
  that warranted hospitalization (whether or not the person was actually
  hospitalized) or injuries that led to a significant loss of function
  or disability will be considered serious physical injuries.
\2\ The use of ``No condition covered'' in the Table reflects that the
  Secretary at this time does not find compelling, reliable, valid,
  medical and scientific evidence to support that any serious injury is
  presumed to be caused by the associated covered countermeasure. For
  injuries alleged to be due to covered countermeasures for which there
  is no associated Table injury, requesters must demonstrate that the
  injury occurred as the direct result of the administration or use of
  the covered countermeasure. See 42 CFR 110.20(b), (c).

    (b) Qualifications and aids to interpretation (table definitions 
and requirements). The following definitions and requirements shall 
apply to the Table set forth in this subpart and only apply for 
purposes of this subpart.
    (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 sequelae. Signs and symptoms begin minutes to a few 
hours after exposure. Death, if it occurs, usually results from airway 
obstruction caused by laryngeal edema or bronchospasm and may be 
associated with cardiovascular collapse. Other significant clinical 
signs and symptoms may include the following: Cyanosis, hypotension, 
bradycardia, tachycardia, arrhythmia, edema of the pharynx and/or 
trachea and/or larynx with stridor and dyspnea. There are no specific 
pathological findings to confirm a diagnosis of anaphylaxis.
    (2) Deltoid Bursitis. Deltoid bursitis is an inflammation of the 
bursa that lies beneath the deltoid muscle and between the acromion 
process and the rotator cuff. Subdeltoid bursitis manifests with pain 
in the lateral aspect of the shoulder similar to rotator cuff 
tendonitis. The presence of tenderness on direct palpation beneath the 
acromion process distinguishes this bursitis from rotator cuff 
tendonitis. Similar to tendonitis, isolated bursitis will have full 
passive range of motion. Other causes of bursitis such as trauma (other 
than from vaccination), metabolic disorders, and systemic diseases such 
as rheumatoid arthritis, dialysis, and infection will not be considered 
Table injuries. This list is not exhaustive. The deltoid bursitis must 
occur in the same shoulder that received the pandemic influenza 
vaccine.
    (3) Vasovagal Syncope. Vasovagal syncope (also sometimes called 
neurocardiogenic syncope) means loss of consciousness (fainting) and 
loss of postural tone caused by a transient decrease in blood flow to 
the brain occurring after the administration of an injected 
countermeasure. Vasovagal syncope is usually a benign condition but may 
result in falling and injury with significant sequelae. 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. 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; psychiatric conditions; seizures; trauma; and 
situational as can occur with urination, defecation, or cough. This 
list is not complete. Episodes of recurrent syncope occurring after the 
applicable time period are not considered to be sequelae of an episode 
of syncope meeting the Table requirements.
    (4) Guillain-Barre 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 bilateral flaccid limb weakness and decreased or absent 
deep tendon reflexes in weak limbs; 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); and, the absence of an identified more 
likely alternative diagnosis. Death may occur without a clinical 
plateau.
    (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 bilateral ophthalmoparesis; 
bilateral reduced or absent tendon reflexes; ataxia; the absence of 
limb weakness (the presence of limb weakness suggests a diagnosis of 
AIDP); 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.
    (iv) Evidence that is supportive, but not required, of a diagnosis 
of all subtypes of GBS includes

[[Page 17992]]

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) For all types of GBS, the onset of symptoms less than three 
days (72 hours) after exposure to the influenza vaccine excludes 
vaccine exposure as a cause.
    (vi) To qualify as GBS, there must not be a more likely alternative 
diagnosis for the weakness. 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.
    (5) Tracheal Stenosis. (i) Postintubation tracheal stenosis means 
an iatrogenic (caused by medical treatment) and symptomatic stricture 
of the airway (narrowing of the windpipe) resulting from:
    (A) Trauma or necrosis from an endotracheal tube;
    (B) Stomal injury from a tracheostomy; or
    (C) A combination of the two.
    (ii) Tracheal stenosis or narrowing due to tumors (malignant or 
benign), infections of the trachea (such as tuberculosis, fungal 
diseases), radiotherapy, tracheal surgery, trauma, congenital, and 
inflammatory or autoimmune diseases will not be considered 
postintubation tracheal stenosis. Postintubation tracheal stenosis 
requires either tracheostomy with placement of a tracheostomy tube or 
endotracheal intubation. Diagnosis requires symptoms of upper airway 
obstruction such as stridor (inspiratory wheeze) or exertional dyspnea 
(increased shortness of breath with exertion), and positive radiologic 
studies showing abnormal narrowing of the trachea or bronchoscopic 
evaluation that demonstrates abnormal narrowing.
    (6) Ventilator-Associated Pneumonia (VAP) and Ventilator-Associated 
Tracheobronchitis (VAT). (i) Definition-VAP is defined as an iatrogenic 
pneumonia caused by the medical treatment of mechanical ventilation. 
Similarly, VAT is an iatrogenic infection of the trachea and/or bronchi 
caused by mechanical ventilation. The initial manifestation of VAP and 
VAT must occur more than 48 hours after intubation (placement of the 
breathing tube) and up to 48 hours after extubation (removal of the 
breathing tube). VAP will be considered to be present when the patient 
demonstrates a new or progressive radiographic infiltrate in the lungs 
that is consistent with pneumonia, fever, leukocytosis (increased white 
blood cell count) or leucopenia (decreased white blood cell count), 
purulent (containing pus) tracheal secretions from a tracheal aspirate, 
and a positive lower respiratory tract culture. The positive lower 
respiratory tract culture is a diagnostic requirement only if there has 
not been a change in antibiotics in the 72 hours prior to collection of 
the culture. In addition, a tracheal aspirate that does not demonstrate 
bacteria or inflammatory cells in a patient without a change in 
antibiotics in the previous 72 hours is unlikely to be VAP and shall 
not be considered a condition set forth in the Table.
    (ii) VAT will be considered to be present when the patient 
demonstrates fever, leukocytosis or leukopenia, purulent tracheal 
secretions, and a positive tracheal aspirate culture in the absence of 
a change of antibiotics within the 72 hours prior to culture. Tracheal 
colonization with microorganisms is common in intubated patients, but 
in the absence of clinical findings is not a sign of VAT.
    (7) Ventilator-Induced Lung Injury (VILI). VILI results from 
mechanical trauma such as volutrauma leading to rupture of alveoli (air 
sacs in the lungs where oxygen and carbon dioxide are exchanged with 
the blood) with subsequent abnormal leakage of air. VILI manifests as 
iatrogenic pneumothorax (abnormal air from alveolar rupture in the 
pleural space), pneumomediastinum (abnormal air from alveolar rupture 
in the mediastinum (middle part of the chest between the lungs)), 
pulmonary interstitial emphysema (abnormal air in the lung interstitial 
space between the alveoli), subpleural air cysts (an extreme form of 
pulmonary emphysema where the abnormal air in the interstitial space 
has pooled into larger pockets), subcutaneous emphysema (abnormal air 
from alveolar rupture that has dissected into the skin), 
pneumopericardium (abnormal air from alveolar rupture that has traveled 
to the pericardium (covering of the heart)), pneumoperitoneum (abnormal 
air from alveolar rupture that has moved into the abdominal space), or 
systemic air embolism (abnormal air from alveolar rupture that has 
moved into the blood). These manifestations must occur in patients who 
are being mechanically ventilated at the time of initial manifestation 
of the VILI.
    (8) Bleeding events. Bleeding events are defined as excessive or 
abnormal bleeding in patients under the pharmacologic effects of 
anticoagulant therapy provided for extracorporeal membrane oxygenation 
(ECMO) treatment.
    (c) Covered countermeasures. (1) Pandemic influenza vaccines. See 
the most recent Secretarial declaration at http://www.gpo.gov/fdsys/pkg/FR-2010-03-05/pdf/2010-4644.pdf. Any amendments will be 
automatically incorporated into this declaration and be published in 
the Federal Register.
    (2) Tamiflu. See the most recent Secretarial declaration at http://www.gpo.gov/fdsys/pkg/FR-2009-06-19/pdf/E9-14412.pdf. Any amendments 
will be automatically incorporated into this declaration and be 
published in the Federal Register.
    (3) Relenza. See the most recent Secretarial declaration at http://www.gpo.gov/fdsys/pkg/FR-2009-06-19/pdf/E9-14412.pdf. Any amendments 
will be automatically incorporated into this declaration and be 
published in the Federal Register.
    (4) Peramivir. See the most recent Secretarial declaration at 
http://www.gpo.gov/fdsys/pkg/FR-2009-10-02/pdf/E9-23761.pdf. Any 
amendments will be automatically incorporated into this declaration and 
be published in the Federal Register.
    (5) Personal respiratory protection devices. See the most recent 
Secretarial declaration at http://www.gpo.gov/fdsys/pkg/FR-2008-12-22/pdf/E8-30510.pdf. Any amendments will be automatically incorporated 
into this declaration and published in the Federal Register.
    (6) Respiratory support devices. See the most recent Secretarial 
declaration at http://www.gpo.gov/fdsys/pkg/FR-2008-12-22/pdf/E8-30510.pdf. Any amendments will be automatically

[[Page 17993]]

incorporated into this declaration and published in the Federal 
Register.
    (7) Diagnostic testing devices. See the most recent Secretarial 
declaration at http://www.gpo.gov/fdsys/pkg/FR-2008-12-22/pdf/E8-30510.pdf. Any amendments will be automatically incorporated into this 
declaration and published in the Federal Register.

[FR Doc. 2014-06102 Filed 3-28-14; 8:45 am]
BILLING CODE 4165-15-P