[Federal Register Volume 84, Number 37 (Monday, February 25, 2019)]
[Proposed Rules]
[Pages 5972-5977]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-02941]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

42 CFR Part 88

[NIOSH Docket 094]


World Trade Center Health Program; Petition 020--Stroke; Finding 
of Insufficient Evidence

AGENCY: Centers for Disease Control and Prevention, HHS.

ACTION: Denial of petition for addition of a health condition.

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SUMMARY: On August 26, 2018, the Administrator of the World Trade 
Center (WTC) Health Program received a petition (Petition 020) to add 
``two forms of stroke, both ischemic and non-aneurysmal hemorrhagic,'' 
to the List of WTC-Related Health Conditions (List). Upon reviewing the 
scientific and medical literature, including information provided by 
the petitioner, the Administrator has determined that the available 
evidence does not have the potential to provide a basis for a decision 
on whether to add stroke to the List. The Administrator also finds that 
insufficient evidence exists to request a recommendation of the WTC 
Health Program Scientific/Technical Advisory Committee (STAC), to 
publish a proposed rule, or to publish a determination not to publish a 
proposed rule.

DATES: The Administrator of the WTC Health Program is denying this 
petition for the addition of a health condition as of February 25, 
2019.

ADDRESSES: Visit the WTC Health Program website at https://www.cdc.gov/wtc/received.html to review Petition 020.

FOR FURTHER INFORMATION CONTACT: Rachel Weiss, Program Analyst, 1090 
Tusculum Avenue, MS: C-48, Cincinnati, OH 45226; telephone (855) 818-
1629 (this is a toll-free number); email [email protected].

SUPPLEMENTARY INFORMATION: 

Table of Contents

A. WTC Health Program Statutory Authority
B. Procedures for Evaluating a Petition
C. Petition 020
D. Review of Scientific and Medical Information and Administrator 
Determination
E. Administrator's Final Decision on Whether To Propose the Addition 
of Stroke to the List
F. Approval To Submit Document to the Office of the Federal Register

A. WTC Health Program Statutory Authority

    Title I of the James Zadroga 9/11 Health and Compensation Act of 
2010 (Pub. L. 111-347, as amended by Pub. L. 114-113), added Title 
XXXIII to the Public Health Service (PHS) Act,\1\ establishing the WTC 
Health Program within the Department of Health and

[[Page 5973]]

Human Services (HHS). The WTC Health Program provides medical 
monitoring and treatment benefits to eligible firefighters and related 
personnel, law enforcement officers, and rescue, recovery, and cleanup 
workers who responded to the September 11, 2001, terrorist attacks in 
New York City, at the Pentagon, and in Shanksville, Pennsylvania 
(responders), and to eligible persons who were present in the dust or 
dust cloud on September 11, 2001, or who worked, resided, or attended 
school, childcare, or adult daycare in the New York City disaster area 
(survivors).
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    \1\ Title XXXIII of the PHS Act is codified at 42 U.S.C. 300mm 
to 300mm-61. Those portions of the James Zadroga 9/11 Health and 
Compensation Act of 2010 found in Titles II and III of Public Law 
111-347 do not pertain to the WTC Health Program and are codified 
elsewhere.
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    All references to the Administrator of the WTC Health Program 
(Administrator) in this document mean the Director of the National 
Institute for Occupational Safety and Health (NIOSH) or his designee.
    Pursuant to section 3312(a)(6)(B) of the PHS Act, interested 
parties may petition the Administrator to add a health condition to the 
List in 42 CFR 88.15. Within 90 days after receipt of a valid petition 
to add a condition to the List, the Administrator must take one of the 
following four actions described in section 3312(a)(6)(B) of the PHS 
Act and Sec.  88.16(a)(2) of the Program regulations: (1) Request a 
recommendation of the STAC; (2) publish a proposed rule in the Federal 
Register to add such health condition; (3) publish in the Federal 
Register the Administrator's determination not to publish such a 
proposed rule and the basis for such determination; or (4) publish in 
the Federal Register a determination that insufficient evidence exists 
to take action under (1) through (3) above.

B. Procedures for Evaluating a Petition

    In addition to the regulatory provisions, the WTC Health Program 
has developed policies to guide the review of submissions and 
petitions,\2\ as well as the analysis of evidence supporting the 
potential addition of a non-cancer health condition to the List.\3\
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    \2\ See WTC Health Program [2014], Policy and Procedures for 
Handling Submissions and Petitions to Add a Health Condition to the 
List of WTC-Related Health Conditions, May 14, 2014, http://www.cdc.gov/wtc/pdfs/WTCHPPPPetitionHandlingProcedures14May2014.pdf.
    \3\ See WTC Health Program [2017], Policy and Procedures for 
Adding Non-Cancer Conditions to the List of WTC-Related Health 
Conditions, February 14, 2017, https://www.cdc.gov/wtc/pdfs/policies/WTCHP_PP_Adding_NonCancers_14_February_2017-508.pdf.
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    A valid petition must include sufficient medical basis for the 
association between the September 11, 2001, terrorist attacks and the 
health condition to be added; in accordance with WTC Health Program 
policy, reference to a peer-reviewed, published, epidemiologic study 
about the health condition among 9/11-exposed populations or to 
clinical case reports of health conditions in WTC responders or 
survivors may demonstrate the required medical basis.\4\ Studies 
linking 9/11 agents \5\ to the petitioned health condition may also 
provide sufficient medical basis for a valid petition.
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    \4\ See supra note 2.
    \5\ 9/11 agents are chemical, physical, biological, or other 
hazards reported in a published, peer-reviewed exposure assessment 
study of responders, recovery workers, or survivors who were present 
in the New York City disaster area, or at the Pentagon site, or the 
Shanksville, Pennsylvania site, as those locations are defined in 42 
CFR 88.1, as well as those hazards not identified in a published, 
peer-reviewed exposure assessment study, but which are reasonably 
assumed to have been present at any of the three sites. See WTC 
Health Program [2018], Development of the Inventory of 9/11 Agents, 
July 17, 2018, https://wwwn.cdc.gov/ResearchGateway/Content/pdfs/Development_of_the_Inventory_of_9-11_Agents_20180717.pdf.
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    After the Program has determined that a petition is valid, the 
Administrator must direct the Program to conduct a review of the 
scientific literature to determine if the available scientific 
information has the potential to provide a basis for a decision on 
whether to add the health condition to the List.\6\ The literature 
review is a keyword search of relevant scientific databases; peer-
reviewed, published, epidemiologic studies (including direct 
observational studies in the case of health conditions such as 
injuries) about the health condition among 9/11-exposed populations are 
then identified from the initial search results. The Program evaluates 
the scientific quality of each peer-reviewed, published, epidemiologic 
study of the health condition identified in the literature search; the 
Program then compiles the scientific results of each study to assess 
whether a causal relationship between 9/11 exposures and the health 
condition is supported, and evaluates whether the results of the 
studies are representative of the 9/11-exposed population of responders 
and survivors. A health condition may be added to the List if peer-
reviewed, published, epidemiologic studies provide support that the 
health condition is substantially likely \7\ to be causally associated 
with 9/11 exposures. If the evaluation of evidence provided in peer-
reviewed, published, epidemiologic studies of the health condition in 
9/11 populations demonstrates a high, but not substantial, likelihood 
of a causal association between the 9/11 exposures and the health 
condition, then the Administrator may consider additional highly 
relevant scientific evidence regarding exposures to 9/11 agents from 
sources using non-9/11-exposed populations. If that additional 
assessment establishes that the health condition is substantially 
likely to be causally associated with 9/11 exposures among 9/11-exposed 
populations, the health condition may be added to the List.
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    \6\ See supra note 3.
    \7\ The ``substantially likely'' standard is met when the 
scientific evidence, taken as a whole, demonstrates a strong 
relationship between the 9/11 exposures and the health condition.
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C. Petition 020

    On August 26, 2018, the Administrator received a petition (Petition 
020) from a WTC survivor who resided near Ground Zero, requesting the 
addition of ``two forms of stroke, both ischemic and non-aneurysmal 
hemorrhagic,'' to the List.\8\ The petition included eight scientific 
articles, three of which provided sufficient medical basis for the 
petition to be evaluated because they are scientific sources that 
demonstrate a potential link between 9/11 exposure and stroke: \9\ a 
2006 study by Brackbill et al.,\10\ a 2013 study by Jordan et al.,\11\ 
and a 2018 study by Yu et al.\12\
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    \8\ See Petition 020, WTC Health Program: Petitions Received, 
http://www.cdc.gov/wtc/received.html.
    \9\ Five of the studies referenced in Petition 020 were 
insufficient to provide medical basis because they were not 
conducted in 9/11 populations nor did they demonstrate an 
association between any 9/11 agents and stroke; these five studies 
include the following: Truelsen T, Prescott E, Lange P, Schnohr P, 
Boysen G [2001], Lung Function and Risk of Fatal and Non-Fatal 
Stroke, The Copenhagen City Heart Study, Int J Epidemiol 30(1):145-
151; Soderholm M, Zia E, Hedblad B, Engstrom G [2012], Lung Function 
as a Risk Factor for Subarachnoid Hemorrhage, Stroke 43(10):2598-
2603; Chen MH, Pan TL, Li CT, Lin WC, Chen YS, Lee YC, Tsai SJ, Hsu 
JW, Huang KL, Tsai CF, Chang WH, Chen TJ, Su TP, Bai YM [2015], Risk 
of Stroke Among Patients with Post-Traumatic Stress Disorder: 
Nationwide Longitudinal Study, Br J Psychiatry 206(4):302-307; 
Austin V, Crack PJ, Bozinovski S, Miller AA, Vlahos R [2016], COPD 
and Stroke: Are Systemic Inflammation and Oxidative Stress the 
Missing Links? Clin Sci (Lond), 130(13):1039-1050; and Lekoubou A, 
Ovbiagele B [2017], Prevalence and Influence of Chronic Obstructive 
Pulmonary Disease on Stroke Outcomes in Hospitalized Stroke 
Patients, eNeurologicalSci 6:21-24.
    \10\ Brackbill RM, Thorpe LE, DiGrande L, Perrin M, Sapp JH, 
2nd, Wu D, Campolucci S, Walker DJ, Cone J, Pulliam P, Thalji L, 
Farfel MR, Thomas P [2006], Surveillance for World Trade Center 
Disaster Health Effects among Survivors of Collapsed and Damaged 
Buildings, MMWR Surveill Summ 55: 1-18.
    \11\ Jordan HT, Stellman SD, Morabia A, Miller-Archie SA, Alper 
H, Laskaris Z, Brackbill RM, Cone JE [2013], Cardiovascular Disease 
Hospitalizations in Relation to Exposure to the September 11, 2001 
World Trade Center Disaster and Posttraumatic Stress Disorder, J Am 
Heart Assoc 2(5):e000431.
    \12\ Yu S, Alper HE, Nguyen AM, Brackbill RM [2018], Risk of 
Stroke Among Survivors of the September 11, 2001 World Trade Center 
Disaster, J Occup Environ Med 60(8):e371-e376.

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[[Page 5974]]

D. Review of Scientific and Medical Information and Administrator 
Determination

    The Program policy on the addition of non-cancer health conditions 
to the List directs the Program to conduct a literature review on the 
health condition(s) petitioned.\13\ Petition 020 requested the addition 
of ischemic and non-aneurysmal hemorrhagic stroke. Stroke is defined as 
an acute brain injury resulting from either too little blood to supply 
an adequate amount of oxygen to the affected part of the brain or too 
much blood within the cranial cavity.\14\ An ischemic stroke occurs 
when there is an inadequate supply of oxygen-rich blood to the brain, 
such as may occur due to thrombosis, embolism, or systemic 
hypoperfusion. A hemorrhagic stroke occurs when blood builds up and 
leaks in the brain, such as may occur due to an intracerebral or 
subarachnoid hemorrhage, or an aneurysm (a balloon-like bulge in an 
artery that can stretch and burst). A transient ischemic attack, also 
called a TIA or ``mini-stroke,'' is similar to a stroke; it occurs if 
blood flow to a portion of the brain is blocked only for a short time, 
producing a transient episode of neurologic dysfunction without acute 
infarction or death of brain tissue.
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    \13\ Supra note 3.
    \14\ See generally National Heart, Lung, and Blood Institute 
(NHBLI), Health Topics: Stroke, https://www.nhlbi.nih.gov/health-topics/stroke (last accessed on Dec. 12, 2018).
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    In response to Petition 020, the Program conducted a review of the 
scientific literature on stroke, including both ischemic and non-
aneurysmal hemorrhagic, as well as transient ischemic attack.\15\ In 
total, this initial literature review identified 12 studies appearing 
to potentially meet the Program's criteria for further evaluation. 
Three of the studies identified \16\ were peer-reviewed, published, 
epidemiologic studies of stroke in the 9/11-exposed population 
eligible, in accordance with the Program's policy,\17\ for further 
evaluation. The nine remaining studies identified in the literature 
review did not meet the Program's criteria for further evaluation.\18\
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    \15\ Databases searched include: CINAHL, Embase, NIOSHTIC-2, 
ProQuest Health & Safety, PsycINFO, PubMed, Scopus, and Toxicology 
Abstracts/TOXLINE. Studies were also identified using the WTC Health 
Program Research Compendium. Keywords used to conduct the search 
include: Stroke, cerebrovascular accident, transient ischemic 
attack, intracerebral hemorrhage, cerebral hemorrhage, subarachnoid 
hemorrhage, brain ischemia, brain infarction, cerebral infarction. 
The literature search was conducted in English-language journals on 
September 26, 2018.
    \16\ Two of these three studies, Brackbill et al. and Yu et al., 
were also included as medical basis with the petition.
    \17\ See supra note 3.
    \18\ Four of the nine studies, including Jordan et al. which was 
submitted as medical basis for the petition, contained limited 
findings regarding an association between 9/11 exposure and stroke 
that the Program determined warranted additional review. Those four 
studies are summarized in the docket, as ``background information,'' 
to illustrate their inability to provide dispositive information 
about an association between 9/11 exposure and stroke.
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Evaluation of Three Published, Peer-Reviewed Epidemiologic Studies of 
Stroke in the 9/11 Population

    As discussed above, the Program determined that of the 12 studies 
identified in the literature review that appeared to potentially meet 
the criteria for evaluation, only 3 could be fully evaluated because 
they are peer-reviewed, published, epidemiologic studies of stroke in 
the 9/11 population: Brackbill et al. [2006] and Yu et al. [2018], 
which were referenced in Petition 020, and Remch et al. [2018].\19\
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    \19\ Remch M, Laskaris Z, Flory J, Mora-McLaughlin C, Morabia A 
[2018], Post-Traumatic Stress Disorder and Cardiovascular Diseases: 
A Cohort Study of Men and Women Involved in Cleaning the Debris of 
the World Trade Center Complex, Circ Cardiovasc Qual Outcomes 
11(7):e004572.
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Study Summaries
    1. Brackbill et al. conducted a cross-sectional study \20\ designed 
to assess the physical and mental health conditions and symptoms 
reported by survivors of the WTC towers and nearby buildings between 
September 5, 2003 and November 20, 2004, and to examine the 
relationship between their reported 9/11 exposures and health and 
mental health outcomes. The study used WTC Health Registry data from 
baseline interviews conducted with 8,418 adult survivors who had been 
occupants of collapsed or damaged buildings. Exposure data were 
evaluated and exposures were sorted by location and time proximity to 
exposure events according to whether the participant was present in the 
WTC dust cloud; occupied a collapsed versus damaged building; or 
evacuated before or after the collapse of the first tower. Health 
histories were also collected from Registry interview data, including 
self-reports of physician-diagnosed stroke subsequent to September 11, 
2001. The rate of stroke among adult survivors of collapsed and damaged 
buildings was adjusted for sex and mode of recruitment (physical and 
mental health symptoms tended to be higher among Registry members who 
self-identified than among those identified from a list of building 
survivors with security badges). Brackbill et al. found a statistically 
significant association for stroke among survivors exposed to the WTC 
dust cloud compared to those not exposed to the WTC dust cloud 
[adjusted odds ratio (aOR) = 5.6, 95% CI 1.3-24.4]; however, the 
prevalence of stroke among survivors who evacuated before versus after 
the collapse of the first WTC tower and among those who evacuated from 
collapsed buildings versus damaged buildings was not significantly 
different [aOR = 0.6, 95% CI 0.1-4.5, and aOR = 1.5, 95% CI 0.6-4.0, 
respectively]. According to the authors, this indicated a ``potential 
relation'' between WTC dust exposure and stroke; this finding was 
considered preliminary, however, meriting continued monitoring, because 
the small sample size and cross-sectional design limits the 
interpretation and generalizability of findings. The cross-sectional 
design of this study is a major limitation because it fails to 
establish a temporal relationship between 9/11 exposure and reported 
stroke. Finally, the study did not differentiate between hemorrhagic 
and ischemic stroke, which have different risk factors.
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    \20\ A cross-sectional study is a type of observational study 
that evaluates a sample of persons from a specific population and 
measures the sample's exposures and health outcomes simultaneously. 
Because the presence of disease and the determination of exposure 
are conducted at the same specific point in time, the temporal 
sequence of cause and effect (i.e. did the disease appear before or 
after exposure) generally cannot be determined.
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    2. Yu et al. conducted a cohort study to investigate the risk of 
stroke among 42,527 WTC responders and survivors who experienced PTSD 
and who had intense exposure to WTC dust. Self-reports of WTC dust 
exposure and stroke diagnosis subsequent to September 11, 2001 were 
obtained from WTC Health Registry surveys collected from 2003 to 2016. 
Intense exposure was defined as having been in the WTC dust cloud and 
reporting at least one of the following: Inability to see more than a 
few feet; difficulty walking; difficulty finding shelter; being covered 
with dust; or loss of hearing. Minimal or no-exposure was defined as 
being in the WTC dust but without experiencing intense exposure, or no 
WTC dust exposure at all. After adjusting for sociodemographic 
characteristics, risk factors for stroke (smoking and history of 
hypertension and/or diabetes), and PTSD, the study found that WTC dust 
cloud exposure was independently associated with an increased risk for 
stroke among WTC responders and survivors [aHR = 1.2, 95% CI 1.0-1.4]. 
The study has numerous strengths, including the longitudinal design,

[[Page 5975]]

adequate control of confounding and a large number of participants with 
small loss to follow up. Limitations included that stroke was self-
reported and the authors did not distinguish between hemorrhagic and 
ischemic stroke.
    3. Remch et al. conducted a cohort study to determine whether PTSD 
is a risk factor for myocardial infarction and stroke. The study used 
data collected between January 2012 and June 2013 from World Trade 
Center (WTC)-Heart, a WTC Health Program Research Program-funded cohort 
study of 6,481 Program members who were non-firefighter workers and 
volunteers engaged in rescue, recovery, restoration of services, 
cleanup, or other support work on or after September 11, 2001. Exposure 
was reported in a self-administered questionnaire, which asked 
participants about when they started to work at Ground Zero, whether 
they were in the dust cloud, whether they worked on or near the pile or 
the pit (the remains of the WTC towers), and whether a respiratory 
protective device was worn. Stroke was self-reported and tentatively 
confirmed by additional personal interviews conducted by phone. 
Approximately 60 percent of self-reported stroke cases were confirmed 
by medical records documenting typical stroke symptoms and either 
supportive medical imaging or sonographic signs. Cases of stroke were 
also identified in the New York State Department of Health's, Statewide 
Planning and Research Cooperative System (SPARCS) database by searching 
for hospitalized cohort members with a discharge diagnosis of stroke. 
However, the study did not report whether the participants who 
experienced recurrent strokes (of the 53 reported strokes, 15 were 
recurrent) had their first stroke before September 11, 2001, and 
whether the first stroke may have been the cause of subsequent 
recurrent strokes. Based on their analysis, Remch et al. concluded that 
none of the 9/11 exposure variables (i.e., timing and intensity of WTC 
dust and dust cloud exposure, use of respiratory protection) were 
independently associated with subsequent stroke. It should be noted, 
however, that detailed data to support these findings were not 
presented in the article apart from the finding that the risk of stroke 
was not significantly reduced by the use of a respirator [aHR = 0.8, 
95% CI 0.4-1.8]. The study also concluded that PTSD was an independent 
determinant of stroke in both men and women, before and after 
controlling for use of a respirator during debris cleanup, 
cardiovascular risk factors, and depression. Remch et al. has multiple 
strengths, including the cohort-study design, active follow-up, 
validation of stroke using SPARCS, and adjustment for cardiovascular 
risk factors, including smoking and depression. Limitations include 
PTSD being self-reported, as well as the lack of distinction between 
hemorrhagic and ischemic stroke and the failure to clarify whether pre-
September 11, 2001 and recurrent strokes were appropriately analyzed. 
Moreover, the study focused on assessing whether those with PTSD are at 
increased risk of myocardial infarction or stroke; determining the 
effect of WTC dust exposure on those outcomes was of secondary 
importance. Finally, the authors did not provide detailed findings 
using exposure data, apart from reporting on respirator use and non-
use; even where respirator use was reported, however, information on 
frequency and time of use was not provided.
Evaluation of Studies Using Select Bradford Hill Criteria
    Together, the three studies by Brackbill et al., Yu et al., and 
Remch et al. were assessed to determine whether a causal relationship 
between 9/11 exposures and stroke is supported.\21\ As described in the 
policy on the addition of non-cancer health conditions to the List,\22\ 
the WTC Health Program uses the following Bradford Hill criteria to 
evaluate studies of 9/11-exposed populations: strength of association, 
precision of the risk estimate, consistency of association, biological 
gradient, and plausibility and coherence.
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    \21\ Although the Brackbill et al. and Yu et al. studies were 
both conducted in the WTC Health Registry population, the Yu et al. 
study is not a follow-up to the Brackbill et al. study and each was 
evaluated independently in this action.
    \22\ WTC Health Program [2017], Policy and Procedures for Adding 
Non-Cancer Conditions to the List of WTC-Related Health Conditions, 
February 14, 2017 at 3-4, https://www.cdc.gov/wtc/pdfs/policies/WTCHP_PP_Adding_NonCancers_14_February_2017-508.pdf.
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    Strength of association: \23\ Of the three studies, Brackbill et 
al. reported a strong association between exposure to WTC dust and the 
risk of stroke in WTC survivors; Yu et al. reported a moderate 
association between WTC dust exposure and stroke in WTC responders and 
survivors; and Remch et al. reported no association between WTC dust 
exposure and risk of stroke in WTC responders.
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    \23\ It is generally thought that strong associations are more 
likely to be causal than weak associations; however, a weak 
association does not rule out a causal relationship.
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    Precision of risk estimate: \24\ Although both Brackbill et al. and 
Yu et al. were conducted using WTC Health Registry data, the more 
recent study by Yu is more precise because the sample size is larger; 
in contrast, Brackbill reported very wide confidence intervals. Remch 
et al. studied a cohort of responders in the WTC Health Program; 
despite reporting a relatively large number of stroke cases, the 
precision of the study findings could not be evaluated because detailed 
findings (i.e., number of stroke cases associated with different levels 
of 9/11 exposure, risk estimates, and confidence intervals) regarding 
possible association between 9/11 exposure and stroke were not 
reported.
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    \24\ The uncertainty inherent in estimating the strength of 
association between exposure and health effect (effect size) from 
observational data is expressed as a confidence interval, 
illustrating a range of values that contains the true effect size. A 
narrow confidence interval indicates a more precise measure of the 
effect size and a wider interval indicates greater uncertainty. See 
supra note 22.
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    Consistency of association: \25\ The findings were not consistent 
across the three studies: The WTC Health Registry studies showed 
increased risk of stroke with exposure to the WTC dust cloud; Remch et 
al. did not find an association between intermediate or high exposure 
and the risk of stroke.
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    \25\ Consistent findings are demonstrated when they have been 
repeatedly reported by multiple studies.
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    Biological gradient: \26\ None of the three studies reported 
exposure-response. Although Brackbill et al. and Yu et al. each found a 
positive association between 9/11 exposure and stroke, they both 
conducted limited, binary evaluations of exposure variables: Brackbill 
et al. sorted exposures according to location and temporal proximity to 
the WTC dust and dust cloud, and Yu et al. sorted exposures by 
determining if study subjects were intensely exposed to the dust and 
dust cloud. Neither study fully analyzed stroke in the context of a 
full exposure-response assessment. Remch et al., which did not find a 
positive association between 9/11 exposure and stroke, also did not 
report exposure-response.
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    \26\ Studies establish an exposure-response relationship by 
demonstrating that increases in exposure (i.e., exposures of greater 
intensity and/or longer duration) are associated with a greater 
incidence of disease. A thorough evaluation of exposure-response 
requires analysis of multiple levels of exposure such that the 
investigator can demonstrate that the risk increases with increasing 
levels of exposure.
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    Plausibility and coherence: \27\ Brackbill et al. and Yu et al. 
each mentioned that other studies have found an association between 
stroke and air pollution, which primarily comprises

[[Page 5976]]

small particulate matter (PM2.5). Both Brackbill et al. and 
Yu et al. also noted that the WTC dust and dust cloud contained a 
unique mixture of construction debris and combustion products,\28\ 
including small particulate matter (PM2.5) as well as large 
particulate matter (>PM10) not typically found in air 
pollution.\29\ Although the comparison of air pollution to WTC dust is 
imperfect because of the high concentration of >PM10 in WTC 
dust and dust cloud samples, it is nevertheless instructive due to the 
documented health effects of PM2.5 exposure, including 
stroke.\30\ While the association between WTC dust and stroke seems 
plausible because of the presence of PM2.5, the underlying 
biological mechanisms through which small particulate matter exerts its 
effect on the vascular system is still an area of study.
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    \27\ Study findings demonstrate a basis in scientific theory 
that supports the relationship between the exposure and the health 
effect, and do not conflict with known facts about the biology of 
the health condition.
    \28\ The WTC Health Program's Inventory of 9/11 Agents 
(available at https://wwwn.cdc.gov/ResearchGateway/Content/pdfs/Development_of_the_Inventory_of_9-11_Agents_20180717.pdf) identifies 
chemical, physical, biologic, and other hazards as having been 
present at any of the three disaster sites. Of the 352 chemical 9/11 
agents identified from air and settled dust sampling studies and 
from biological monitoring studies, five are types of WTC dust, 
including: WTC Dust: Glass shards, WTC Dust: PM10, WTC 
Dust: PM2.5, WTC Dust: Particles >2 [mu]m, and WTC Dust: 
Particles >5 [mu]m. The remaining 347 chemicals are identified by 
name. See supra note 5.
    \29\ Brackbill et al. [2006] supra note 10 at 12; Yu et al. 
[2018] supra note 11 at e375, and Lioy PJ, Weisel CP, Millette JR, 
Eisenreich S, Vallero D, Offenberg J, Buckley B, Turpin B, Zhong M, 
Cohen MD, Prophete C, Yang I, Stiles R, Chee G, Johnson W, Porcja R, 
Alimokhtari S, Hale RC, Weschler C, Chen LC [2002], Characterization 
of the dust/smoke aerosol that settled east of the World Trade 
Center (WTC) in Lower Manhattan after the collapse of the WTC 11 
September 2001, Env Health Perspect 110:703-714.
    \30\ Feigin VL, Roth GA, Naghavi M, Parmar P, Krishnamurthi R, 
Chugh S, Mensah GA, Norrving B, Shiue I, Ng M, Estep K, Cercy K, 
Murray CJL, Forouzanfar MH [2016], Global Burden of Stroke and Risk 
Factors in 188 Countries, During 1990-2013: A Systematic Analysis 
for the Global Burden of Disease Study 2013, Lancet Neurol 
15(9):913-924; B[eacute]jot Y, Reis J, Giroud M, Feigin V [2018], A 
Review of Epidemiological Research on Stroke and Dementia and 
Exposure to Air Pollution, Int J Stroke 13(7):687-695.
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Evaluation of Representativeness of Studies
    Finally, the three studies were reviewed to determine whether both 
the WTC responder and survivor cohorts studied are representative of 
the entire 9/11-exposed population, and whether the results can be 
extrapolated. The cohort studied by Brackbill et al. consisted of 
survivors enrolled in the WTC Health Registry; the population studied 
by Yu et al. included responders and survivors enrolled in the WTC 
Health Registry; the population studied by Remch et al. only included 
non-firefighter responders who were members of the WTC-Heart cohort 
within the WTC Health Program. Although Brackbill et al. and Yu et al. 
consisted of Registry members, the former only included 8,418 adult 
survivors of collapsed buildings and buildings with major or moderate 
damage, while the latter included 42,527 survivors and responders of 
the WTC attack.\31\ According to an assessment of the WTC Health 
Registry by Kim et al. [2018],\32\ although enrollment was voluntary, 
extensive outreach efforts show that selection bias is unlikely for 
this cohort. The cohort studied by Remch et al. is nested within the 
WTC Health Program and appears to be representative of the population 
served by the clinics where recruitment took place. As a result, the 
Program determined that the results of the three evaluated studies can 
be extrapolated to the entire 9/11-exposed population.
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    \31\ For more information on the WTC Health Registry cohort and 
recruitment methods, see: Farfel M, DiGrande L, Brackbill R, Prann 
A, Cone J, Friedman S, Walker DJ, Pezeshki G, Thomas P, Galea S, 
Williamson D, Frieden TR, Thorpe L [2008], An Overview of 9/11 
Experiences and Respiratory and Mental Health Conditions among World 
Trade Center Health Registry Enrollees, J Urban Health 85(6):880-
909.
    \32\ Kim H, Baidwan NK, Kriebel D, Cifuentes M, Baron S [2018], 
Asthma among World Trade Center First Responders: A Qualitative 
Synthesis and Bias Assessment, Int J Environ Res Public Health 
15(6):1053.
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Summary of Evaluation
    Although the studies described and evaluated above provide evidence 
that suggests a possible association between 9/11 exposure and stroke, 
the evidence is insufficient to conclude that stroke is either 
substantially likely \33\ or highly likely \34\ to be causally 
associated with 9/11 exposures among 9/11-exposed populations. The 
evidence provided by the three studies is insufficient to support an 
addition to the List for several reasons. Most importantly, the results 
of the three studies lacked consistency: Two studies found a positive 
association between 9/11 exposure and stroke (Brackbill et al. and Yu 
et al.), and one did not (Remch et al.). The two studies that found a 
positive association between 9/11 exposure and stroke relied on self-
reported stroke, which may be prone to recall bias and the 
imperfections of human memory. In contrast, Remch et al. confirmed the 
presence of stroke using medical records and SPARCS data, but failed to 
find an association between 9/11 exposure and stroke. Another 
limitation common to all three studies was the lack of differentiation 
between hemorrhagic and ischemic stroke; these two variants have 
different pathophysiology and causes, and therefore it is not clear if 
the reported incidence of stroke refers to one or both types of stroke. 
Finally, the absence of an exposure-response analysis in all of the 
studies means that the biological gradient is not adequately assessed. 
In conclusion, when all three studies are considered together, their 
limitations and lack of consistent findings do not provide adequate 
evidence to propose the addition of stroke to the List. Without 
significant positive findings from studies with sufficient sample size, 
objective confirmation of stroke, and an assessment of exposure-
response, the available evidence does not demonstrate that stroke is 
either substantially likely or highly likely to be causally associated 
with 9/11 exposures among 9/11-exposed populations.
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    \33\ See supra note 3 at sec. III.B.1.c.(1).
    \34\ See supra note 3 at sec. III.B.1.c.(2).
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E. Administrator's Final Decision on Whether To Propose the Addition of 
Stroke to the List

    Pursuant to PHS Act, Sec.  3312(a)(6)(B)(iv) and 42 CFR 
88.16(a)(2)(iv), the Administrator has determined that insufficient 
evidence is available to take further action at this time, including 
proposing the addition of stroke to the List (pursuant to PHS Act, 
Sec.  3312(a)(6)(B)(ii) and 42 CFR 88.16(a)(2)(ii)) or publishing a 
determination not to publish a proposed rule in the Federal Register 
(pursuant to PHS Act, Sec.  3312(a)(6)(B)(iii) and 42 CFR 
88.16(a)(2)(iii)). The Administrator has also determined that 
requesting a recommendation from the STAC (pursuant to PHS Act, Sec.  
3312(a)(6)(B)(i) and 42 CFR 88.16(a)(2)(i)) is unwarranted.
    For the reasons discussed above, the Petition 020 request to add 
stroke to the List of WTC-Related Health Conditions is denied.

F. Approval To Submit Document to the Office of the Federal Register

    The Secretary, HHS, or his designee, the Director, Centers for 
Disease Control and Prevention (CDC) and Administrator, Agency for 
Toxic Substances and Disease Registry (ATSDR), authorized the 
undersigned, the Administrator of the WTC Health Program, to sign and 
submit the document to the Office of the Federal Register for 
publication as an official document of the WTC Health Program. Robert 
Redfield M.D., Director, CDC, and Administrator, ATSDR, approved

[[Page 5977]]

this document for publication on February 14, 2019.

John J. Howard,
Administrator, World Trade Center Health Program and Director, National 
Institute for Occupational Safety and Health, Centers for Disease 
Control and Prevention, Department of Health and Human Services.
[FR Doc. 2019-02941 Filed 2-22-19; 8:45 am]
 BILLING CODE 4163-18-P