Notice2025-00692
World Trade Center Health Program; Petitions 031, 036, 039, and 053-Amyotrophic Lateral Sclerosis; Finding of Insufficient Evidence
Primary source
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Published
January 22, 2025
Issuing agencies
Health and Human Services DepartmentCenters for Disease Control and Prevention
Abstract
The Administrator of the World Trade Center (WTC) Health Program received four petitions (Petitions 031, 036, 039, and 053) to add amyotrophic lateral sclerosis (ALS) to the List of WTC-Related Health Conditions (List). Upon reviewing the scientific and medical literature, including information provided by petitioners, the Administrator determined that there is insufficient evidence to support taking further action at this time regarding ALS. 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.
Full Text
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<title>Federal Register, Volume 90 Issue 13 (Wednesday, January 22, 2025)</title>
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[Federal Register Volume 90, Number 13 (Wednesday, January 22, 2025)]
[Notices]
[Pages 7698-7702]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2025-00692]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Centers for Disease Control and Prevention
[NIOSH Docket 094]
World Trade Center Health Program; Petitions 031, 036, 039, and
053--Amyotrophic Lateral Sclerosis; Finding of Insufficient Evidence
AGENCY: Centers for Disease Control and Prevention, Health and Human
Services (HHS).
ACTION: Denial of petitions for addition of a health condition.
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SUMMARY: The Administrator of the World Trade Center (WTC) Health
Program received four petitions (Petitions 031, 036, 039, and 053) to
add amyotrophic lateral sclerosis (ALS) to the List of WTC-Related
Health Conditions (List). Upon reviewing the scientific and medical
literature, including information provided by petitioners, the
Administrator determined that there is insufficient evidence to support
taking further action at this time regarding ALS. 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 these
petitions for the addition of a health condition as of January 22,
2025.
ADDRESSES: Visit the WTC Health Program website at <a href="https://www.cdc.gov/wtc/received.html">https://www.cdc.gov/wtc/received.html</a> to review Petitions 031, 036, 039, and 053.
FOR FURTHER INFORMATION CONTACT: Rachel Weiss, Program Analyst, 1090
Tusculum Avenue, MS: C-48, Cincinnati, OH 45226; telephone (404) 498-
2500 (this is not a toll-free number); email <a href="/cdn-cgi/l/email-protection#a0eee9eff3e8d2c5c7d3e0c3c4c38ec7cfd6"><span class="__cf_email__" data-cfemail="b8f6f1f7ebf0cadddfcbf8dbdcdb96dfd7ce">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
Table of Contents
A. WTC Health Program Statutory Authority
B. Procedures for Evaluating a Petition
C. Petitions 031, 036, 039, and 053
D. Review of Scientific Evaluation
E. Administrator's Final Decision on Whether To Propose the Addition
of Amyotrophic Lateral Sclerosis 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, Pub. L. 116-59,
Pub. L. 117-328, and Pub. L. 118-31), added Title XXXIII to the Public
Health Service (PHS) Act,\1\ thereby establishing the WTC Health
Program within HHS. The WTC Health Program provides medical monitoring
and treatment benefits for health conditions on the List \2\ 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
[[Page 7699]]
New York City, at the Pentagon, and in Shanksville, Pennsylvania
(responders). The Program also provides benefits 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 \3\ (survivors).
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\1\ Title XXXIII of the PHS Act is codified at 42 U.S.C. 300mm
to 300mm-64. 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.
\2\ The List of WTC-Related Health Conditions is established in
42 U.S.C. 300mm-22(a)(3)-(4) and 300mm-32(b); additional conditions
may be added through rulemaking and the complete list is provided in
WTC Health Program regulations at 42 CFR 88.15.
\3\ See 42 U.S.C. 300mm-5(7); 42 CFR 88.1.
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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 WTC Health 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.
More information about the WTC Health Program, including the List
and the petition process, is available at <a href="http://www.cdc.gov/wtc/">www.cdc.gov/wtc/</a>.
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,\4\ as well as the evaluation of evidence supporting the
potential addition of a non-cancer health condition to the List.\5\
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\4\ 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, <a href="http://www.cdc.gov/wtc/pdfs/WTCHPPPPetitionHandlingProcedures14May2014.pdf">http://www.cdc.gov/wtc/pdfs/WTCHPPPPetitionHandlingProcedures14May2014.pdf</a>.
\5\ See WTC Health Program [2024], Policy and Procedures for
Adding Non-Cancer Conditions to the List of WTC-Related Health
Conditions, October 18, 2024, <a href="https://www.cdc.gov/wtc/pdfs/policies/WTCHP_PP_Adding_NonCancer_Health_Conditions_20241018.pdf">https://www.cdc.gov/wtc/pdfs/policies/WTCHP_PP_Adding_NonCancer_Health_Conditions_20241018.pdf</a>.
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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 and Procedures for Handling Submissions and Petitions to Add a
Health Condition to the List of WTC-Related Health Conditions,
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. In accordance with 42 CFR
88.16(a)(5), the Administrator is required to consider a new petition
for a previously-evaluated health condition determined not to qualify
for addition to the List only if the new petition presents a new
medical basis for the association between 9/11 exposures and the
condition to be added. A new medical basis is evidence not previously
reviewed by the Administrator.
After the Program has determined that a petition is valid, and in
accordance with the Policy and Procedures for Adding Non-Cancer
Conditions to the List of WTC-Related Health Conditions (Policy and
Procedures), the Administrator directs the WTC Health Program Science
Team (Science Team) 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 intended to identify peer-reviewed, published,
epidemiologic studies about the health condition among 9/11-exposed
populations.
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\6\ Id. at 6.
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Using validity indicators detailed in the Policy and Procedures,
the Science Team evaluates the scientific quality of each peer-
reviewed, published, epidemiologic study of the health condition that
exhibits the potential to provide a basis for deciding whether to
propose adding the health condition to the List identified in the
literature search. The Science Team then evaluates the studies,
individually and together, to characterize the evidence of a causal
association between 9/11 exposures and the health condition. The
Science Team's evaluation includes consideration of the Bradford Hill
weight of evidence criteria,\7\ study limitations, and whether the
studies are representative of the 9/11-exposed population of responders
and survivors. After assessing the degree to which the evidence
supports a causal association between 9/11 exposures and the health
condition, the Science Team will assign the evidence to one of the
following five categories:
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\7\ Hill AB [1965], The Environment and Disease: Association or
Causation? Proc R Soc Med 58(5):295-300. According to the Policy and
Procedures for Adding Non-Cancer Conditions to the List of WTC-
Related Health Conditions, the ``Bradford Hill criteria are a
leading weight of evidence framework which comprises nine aspects of
association. These aspects comprise strength of association,
consistency, specificity, temporality, biological gradient,
plausibility, coherence, experiment, and analogy.'' See supra note 5
at 9, footnote 21.
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(1) substantial likelihood of causal association,
(2) high likelihood of causal association,
(3) limited likelihood of causal association,
(4) no likelihood of causal association, or
(5) inadequate evidence to determine the likelihood of causal
association.
The Science Team provides the outcome of its evaluation to the
Administrator. A health condition may be added to the List if peer-
reviewed, published, epidemiologic studies provide support that there
is a substantial likelihood of a causal association between the health
condition and 9/11 exposures (Category 1).\8\ 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 (Category 2),\9\ then the
Administrator may consider additional highly relevant scientific
evidence regarding exposures to 9/11 agents in non-9/11 exposure
scenarios. If that additional assessment establishes that there is now
sufficient evidence to support the conclusion that a causal association
between the 9/11 exposures and the health condition is substantially
likely among 9/11-exposed populations (Category 1), the health
condition may be proposed for addition to the List.
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\8\ Substantial likelihood of causal association means that the
association is strongly supported by evidence from high-quality,
peer-reviewed, published epidemiologic studies of the health
condition in 9/11-exposed populations and there is high confidence
that the association cannot be explained by chance, bias,
confounding, or any other alternative explanation. See supra note 5
at 12.
\9\ High likelihood of causal association means that the
scientific evidence, taken as a whole, demonstrates that the
likelihood of a causal association is less than substantial, but
definitively more than limited. Therefore, there is some meaningful
likelihood that the association can be explained by chance, bias,
confounding, or another alternative explanation. See supra note 5 at
12.
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More information about the WTC Health Program, including the List
and the petition process, is available at <a href="http://www.cdc.gov/wtc/">www.cdc.gov/wtc/</a>.
[[Page 7700]]
C. Petitions 031, 036, 039, and 053
The Administrator of the WTC Health Program received four petitions
requesting the addition of amyotrophic lateral sclerosis to the List of
WTC-Related Health Conditions between 2021 and 2024. Of the scientific
references provided in each petition, six were found to meet the
validity requirement of being peer-reviewed, published, epidemiologic
studies about the health condition among 9/11-exposed populations or to
clinical case reports of health conditions in WTC responders or
survivors. Each petition and its medical basis is described below.
On July 12, 2021, the Administrator received a petition (Petition
031) from a WTC responder requesting the addition of ``Amyotrophic
Lateral Sclerosis (ALS)'' to the List.\10\ The petition's validity was
established by references to three peer-reviewed, published,
epidemiologic studies that demonstrate a medical basis for the
association between 9/11 exposures and ALS. The referenced studies and
literature reviews each individually establishing a medical basis are
as follows:
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\10\ See Petition 031, WTC Health Program: Petitions Received,
<a href="http://www.cdc.gov/wtc/received.html">http://www.cdc.gov/wtc/received.html</a>.
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<bullet> Neurodegenerative Diseases: Occupational Occurrence and
Potential Risk Factors, 1982 through 1991, by Schulte et al.
[1996],\11\ is a peer-reviewed, published case-control study of
occupational exposures and neurodegenerative diseases, including ALS,
using death certificate data in a national mortality surveillance
database.
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\11\ Schulte PA, Burnett CA, Boeniger MF, Johnson J [1996],
Neurodegenerative Diseases: Occupational Occurrence and Potential
Risk Factors, 1982 through 1991, Am J Public Health 86(9):1281-8.
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<bullet> Toxicant Exposure and Bioaccumulation: A Common and
Potentially Reversible Cause of Cognitive Dysfunction and Dementia, by
Genuis and Kelln [2015],\12\ is a peer-reviewed, published review
article of the literature on bioaccumulation following exposure to
toxicants, some of which are 9/11 agents, and increased risk of
cognitive dysfunction and dementia resulting from neurodegenerative
diseases including ALS.
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\12\ Genuis SJ and Kelln KL [2015], Toxicant Exposure and
Bioaccumulation: A Common and Potentially Reversible Cause of
Cognitive Dysfunction and Dementia, Behav Neurol 2015:620143.
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<bullet> Military Service, Deployments, and Exposures in Relation
to Amyotrophic Lateral Sclerosis Etiology and Survival, by Beard and
Kamel [2015],\13\ is a peer-reviewed, published review of the evidence
associating ALS and motor neuron diseases (MNDs) with military service,
deployments, and exposures, from peer-reviewed epidemiologic studies
published through 2013. These three studies suggest a potential
association between exposure to 9/11 agents (specifically experiences
that might cause psychological harm, physical hazards, and chemical
hazards, including heavy metals) and ALS, and thus provided a
sufficient medical basis to consider the submission a valid petition.
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\13\ Beard JD and Kamel F [2015], Military Service, Deployments,
and Exposures in Relation to Amyotrophic Lateral Sclerosis Etiology
and Survival, Epidemiol Rev 37(1):55-70.
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On April 7, 2022, the Administrator received a petition (Petition
039), requesting the addition of ``Amyotrophic Lateral Sclerosis (ALS),
Lou Gehrig's disease,'' to the List.\14\ A second petition (Petition
036), submitted by the same petitioner, was received by the
Administrator on April 14, 2022.\15\ The petitions' validity was
established by references to one peer-reviewed, published,
epidemiologic study that demonstrates a positive association between 9/
11 exposures and ALS:
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\14\ See Petition 039, WTC Health Program: Petitions Received,
<a href="http://www.cdc.gov/wtc/received.html">http://www.cdc.gov/wtc/received.html</a>.
\15\ NB: The petition numbers are out of order because the WTC
Health Program processed the second submission first.
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<bullet> Prospective study of chemical exposures and amyotrophic
lateral sclerosis, by Weisskopf et al. [2009],\16\ is a peer-reviewed,
published prospective cohort study of the relationship between exposure
to chemicals, including formaldehyde (a 9/11 agent), and ALS in over 1
million cancer prevention study participants.
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\16\ Weisskopf MG, Morozova N, O'Reilly EJ, McCullough ML, Calle
EE, Thun MJ, Ascherio A [2009], Prospective Study of Chemical
Exposures and Amyotrophic Lateral Sclerosis, J Neurol Neurosurg
Psychiatry 80(5):558-61.
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This study suggests a potential association between exposure to
formaldehyde, a 9/11 agent, and ALS, and thus provided a sufficient
medical basis to consider the submission a valid petition.
On January 30, 2024, the Administrator received a petition
(Petition 053), requesting the addition of ``Amyotrophic Lateral
Sclerosis (ALS)'' to the List.\17\ The petition's validity was
established by references to two peer-reviewed, published,
epidemiologic studies that demonstrate a medical basis for the
association between 9/11 exposures and ALS. The studies establishing a
medical basis are as follows:
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\17\ See Petition 053, WTC Health Program: Petitions Received,
<a href="http://www.cdc.gov/wtc/received.html">http://www.cdc.gov/wtc/received.html</a>.
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<bullet> Occupational Exposures and Neurodegenerative Diseases--A
Systematic Literature Review and Meta-Analyses, by Gunnarsson and Bodin
[2019], is a peer-reviewed, published review article discussing the
links between occupational exposures and neurodegenerative diseases.
<bullet> Blood Metal Levels and Amyotrophic Lateral Sclerosis Risk:
A Prospective Cohort, by Peters et al. [2021], is a prospective cohort
study comparing metal levels in blood samples for ALS patients and
controls, to investigate whether metals such as arsenic, cadmium,
copper, and lead are associated with ALS mortality.
These studies suggest a potential association between cadmium,
lead, and zinc and ALS, and thus provided a sufficient medical basis to
consider the submission a valid petition.
D. Review of Scientific Evaluation
In response to Petitions 031, 036, 039, and 053, and pursuant to
the Policy and Procedures, the WTC Health Program conducted a
systematic literature search to identify peer-reviewed, published,
epidemiologic studies of ALS or motor neuron disease (MND) in 9/11-
exposed populations.\18\
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\18\ The complete list of search terms is as follows:
amyotrophic lateral sclerosis, motor neuron disease, motor neuron
syndrome, lateral sclerosis, Lou Gehrig's disease, neurodegenerative
disorder, amyotrophy, progressive muscular atrophy, ALS, and motor
neuropathy. The following databases were searched: APA
PsycInfo[supreg], CINAHL (EBSCOhost), Embase Classic+Embase, Health
& Safety Science Abstracts (ProQuest), NIOSHTIC-2, Ovid
MEDLINE[supreg], Scopus, and Toxicology Abstracts (ProQuest).
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The literature search conducted by the WTC Health Program found no
studies that directedly examined ALS or MND risk in the 9/11-exposed
population. However, the search identified six peer-reviewed,
published, epidemiologic studies of mortality from nervous systems
disorders, including ALS \19\ in 9/11-exposed populations:
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\19\ All six of the studies examined mortality patterns in the
9/11-exposed population using composite outcomes that included ALS
along with other disorders of the nervous system and sensory organs.
The six studies all used composite outcomes grouped together in the
``NIOSH-119 Death Categories and Corresponding International
Classification of Disease Codes for 1960 through 2004,'' available
at <a href="https://www.cdc.gov/niosh/ltas/pdf/Rate-Info-Table-1.pdf">https://www.cdc.gov/niosh/ltas/pdf/Rate-Info-Table-1.pdf</a>.
Diseases of the nervous system and sense organs, categorized by
NIOSH as ``Major 15,'' includes such health conditions as ALS,
Parkinson's disease, hereditary and idiopathic neuropathy, and many
other nervous system disorders.
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<bullet> A 15-Year Follow-Up Study of Mortality in a Pooled Cohort
of World Trade Center Rescue and Recovery
[[Page 7701]]
Workers, by Li et al. [2023],\20\ examined mortality among 60,631 Fire
Department of New York (FDNY) responders, including firefighters and
emergency medical service providers (n = 15,887), the WTC Health
Program general responder cohort (GRC) (n = 25,657), and the WTC Health
Registry (WTCHR) (n = 19,087).
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\20\ Li J, Hall CB, Yung J, Kehm RD, Zeig-Owens R, Singh A, Cone
JE, Brackbill RM, Farfel MR, Qiao B, Schymura MJ, Shapiro MZ, Dasaro
CR, Todd AC, Prezant DJ, Boffetta P [2023]; A 15-Year Follow-Up
Study of Mortality in a Pooled Cohort of World Trade Center Rescue
and Recovery Workers, Environ Res 219:115116.
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<bullet> All-Cause and Cause-Specific Mortality in a Cohort of WTC-
Exposed and Non-WTC-Exposed Firefighters, by Singh et al. [2023],\21\
examined mortality patterns in male FDNY firefighters (n =10,786)
followed through 2016 (163,583 person-years).\22\
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\21\ Singh A, Zeig-Owens R, Cannon M, Webber MP, Goldfarb DG,
Daniels RD, Prezant DJ, Boffetta P, Hall CB [2023], All-Cause and
Cause-Specific Mortality in a Cohort of WTC-Exposed and Non-WTC-
Exposed Firefighters, Occup Environ Med 80(6):297-303.
\22\ Person-years means the cumulative sum of time that all
study participants are under observation.
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<bullet> Mortality among Fire Department of the City of New York
Rescue and Recovery Workers Exposed to the World Trade Center Disaster,
2001-2017, by Colbeth et al. [2020; 2023],\23\ examined mortality
patterns in 15,431 FDNY responders followed through 2017 (248,665
person-years).
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\23\ Colbeth HL, Zeig-Owens R, Hall CB, Webber MP, Schwartz TM,
Prezant DJ [2020], Mortality among Fire Department of the City of
New York Rescue and Recovery Workers Exposed to the World Trade
Center Disaster, 2001-2017, Int J Environ Res Public Health
17(17):6266. Colbeth HL, Zeig-Owens R, Hall CB, Webber MP, et al.
[2023]. Correction: Colbeth et al. Mortality among Fire Department
of the City of New York rescue and recovery workers exposed to the
World Trade Center disaster, 2001-2017, Int J Environ Res Public
Health 2020, 17, 6266, Int J Environ Res Public Health 20(16):6585.
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<bullet> Mortality among Rescue and Recovery Workers and Community
Members Exposed to the September 11, 2001 World Trade Center Terrorist
Attacks, 2003-2014, by Jordan et al. [2018],\24\ examined WTCHR
enrollees categorized as rescue/recovery workers (n = 29,280; 308,340
person-years) and lower Manhattan area community members (n = 39,643;
416,448 person-years).
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\24\ Jordan HT, Stein CR, Li J, Cone JE, Stayner L, Hadler JL,
Brackbill RM, Farfel MR [2018], Mortality among Rescue and Recovery
Workers and Community Members Exposed to the September 11, 2001
World Trade Center Terrorist Attacks, 2003-2014, Environ Res
163:270-279.
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<bullet> Mortality among World Trade Center Rescue and Recovery
Workers, 2002-2011, by Stein et al. [2016],\25\ examined mortality in
GRC responders (n = 30,947; 164,563 person-years).
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\25\ Stein CR, Wallenstein S, Shapiro M, Hashim D, Moline JM,
Udasin I, Crane MA, Luft BJ, Lucchini RG, Holden WL [2016],
Mortality among World Trade Center Rescue and Recovery Workers,
2002-2011, Am J Ind Med 59(2):87-95.
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<bullet> Mortality among Survivors of the Sept 11, 2001, World
Trade Center Disaster: Results from the World Trade Center Health
Registry Cohort, by Jordan et al. [2011],\26\ conducted the first study
of mortality among members of the WTCHR (2003-2009). Registry
participants comprised responders (n = 13,337; 74,967 person-years),
and community members (n = 28,593; 161,519 person-years); however, the
study sample was restricted to participants residing in New York City
at the time of Registry enrollment (n = 41,930).
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\26\ Jordan HT, Brackbill RM, Cone JE, Debchoudhury I, Farfel
MR, Greene CM, Hadler JL, Kennedy J, Li J, Liff J, Stayner L,
Stellman SD [2011], Mortality among Survivors of the Sept 11, 2001,
World Trade Center Disaster: Results from the World Trade Center
Health Registry Cohort, Lancet 378(9794):879-887.
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Pursuant to the WTC Health Program's Policy and Procedures, the
Program conducted an evaluation of the six studies identified in the
literature search to determine the likelihood of a causal association
between 9/11 exposures, including exposures to 9/11 agents,\27\ and the
petitioned health condition.\28\ The systematic literature search, the
WTC Health Program Science Team's evaluation and synthesis of the
available literature, and the Science Team's conclusions regarding the
association between 9/11 exposure and ALS are described in full in the
WTC Health Program Science Team Evaluation of Scientific Evidence
Regarding the Addition of Amyotrophic Lateral Sclerosis to the List of
WTC-Related Health Conditions (Scientific Evaluation) found in the
docket for this notice.\29\
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\27\ 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, <a href="https://wwwn.cdc.gov/ResearchGateway/Content/pdfs/Development_of_the_Inventory_of_9-11_Agents_20180717.pdf">https://wwwn.cdc.gov/ResearchGateway/Content/pdfs/Development_of_the_Inventory_of_9-11_Agents_20180717.pdf</a>.
\28\ None of the studies provided to establish medical basis
were found to meet the criteria for further evaluation, although
they are discussed briefly in the Scientific Evaluation, infra note
28.
\29\ World Trade Center Health Program Science Team [2024], WTC
Health Program Science Team Evaluation of Scientific Evidence
Regarding the Addition of Amyotrophic Lateral Sclerosis to the List
of WTC-Related Health Conditions, November 20, 2024.
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The six studies identified as high-quality and summarized in the
Scientific Evaluation were evaluated individually and together to
determine whether they provide a basis to support the addition of ALS
to the List based on a causal relationship between 9/11 exposures to
WTC dust, injury, or experiences and ALS. As described in the Policy
and Procedures, the WTC Health Program uses the following Bradford Hill
criteria to evaluate studies of 9/11-exposed populations: strength of
association \30\ and precision of the risk estimate,\31\ consistency of
association,\32\ specificity,\33\ temporality,\34\ biological
gradient,\35\ and plausibility,\36\ coherence,\37\ and analogy.\38\ In
addition
[[Page 7702]]
to the Bradford Hill criteria, the Science Team also considered the
limitations of the evaluated evidence and whether the evidence
represents the 9/11-exposed population.
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\30\ 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.
\31\ Precision of the risk estimate describes the random error
(``chance'') inherent in estimating the strength of association (the
effect size) between exposure and the health condition. It is often
expressed as a confidence interval illustrating a range of plausible
values of the effect estimate given sampling error. A narrow
confidence interval indicates a more precise measure of the effect
and a wider interval indicates greater uncertainty. While precision
is not a Bradford Hill criterion, the Science Team takes it into
consideration to evaluate the extent of random error in study
estimates.
\32\ Consistent findings are demonstrated when they have been
repeatedly reported by multiple studies. When assessing consistency,
the Science Team also considers differences in study quality that
could explain inconsistent study findings. If only a single study is
available for evaluation, the Science Team will place more emphasis
on evaluating the strength of the association and precision of the
risk estimate.
\33\ Specificity is the premise that an association is more
likely to be causal if it is observed between one cause and one
effect. In practice, epidemiologic examinations of health conditions
in the 9/11-exposed population involve complex exposures to multiple
9/11 agents suspected of causing multifactorial diseases; therefore,
specificity has a limited role in Science Team evaluations.
Specificity has been given no weight in this evaluation due to the
complexity of the proposed association between multiple 9/11 agents
and ALS, a multifactorial disease.
\34\ Temporality is the condition that the 9/11 exposure must
precede the health condition of interest and is typically assessed
when considering aspects of exposure in the study design.
\35\ 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.
\36\ 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.
\37\ Coherence implies that the interpretation of a causal
association agrees with known disease etiology.
\38\ Analogy is used to inform on biological plausibility and
coherence by contrasting the evidence on the suspected causal
association with that from an established association between
similar (analogous) causes or effects.
---------------------------------------------------------------------------
The Science Team discussed its evaluation in full in the Scientific
Evaluation, and summarized its findings in table 5, which is reproduced
here:
------------------------------------------------------------------------
Aspect of associative causal
inference (``Bradford Hill Evaluation findings
Criteria'') [Hill 1965]
------------------------------------------------------------------------
Strength of association (and Among six high-quality studies
estimate precision). identified for evaluation, none
examined ALS risk separately in 9/
11-exposed populations [Colbeth et
al. 2020, 2023; Jordan et al. 2011;
Jordan et al. 2018; Li et al. 2023;
Singh et al. 2023; Stein et al.
2016]. Among the six studies, only
one reported a statistically
significant positive association of
indicating modest excess of
mortality from nervous system
disorders, including ALS, among WTC
Health Registry community members
[Jordan et al. 2018]. The authors
attributed the observed excess to
Alzheimer's disease, not ALS. The
finding strongly depended on the
choice of control group, indicating
a potential for strong selection
bias. The use of composite
outcomes, external reference
groups, and lack of exposure
information are important study
limitations common to all studies
evaluated.
Consistency....................... All but the study by Jordan et al.
[2018] reported less than expected
deaths from nervous disorders when
using an external reference
population. Results supporting a
causal association between 9/11
exposure and composite outcomes of
neurologic diseases including ALS
were not reproduced in different 9/
11-exposed populations (e.g.,
firefighters, general responders,
and community members). The lack of
reproducible results is a strong
limitation of causal inference.
Temporality....................... 9/11 exposure was presumed to
precede ALS onset because all
studies were longitudinal and began
observation on or after 9/11.
However, no studies specifically
examined temporal variations in
risk.
Biological gradient............... One study examined the exposure-
response between categories of 9/11
exposure and mortality from a
composite of other nervous system
disorders (including ALS) in
community members [Jordan et al.
2018]. That study found no evidence
of increasing risk with 9/11
exposure.
Plausibility, Coherence, and There are no established
Analogy. environmental factors that are
causal for ALS; therefore, no 9/11
agent has been identified as a
contributing cause. However, the
literature supports a general
conclusion that a causal
association between a 9/11 agent
(e.g., metals, silica,
formaldehyde) and ALS is plausible,
although unproven.
The assumption that the risk
observed in a composite outcome is
analogous to ALS risk is
unsubstantiated, which is an
important study limitation.
Representativeness................ There was representation of all
groups of 9/11-exposed populations.
------------------------------------------------------------------------
Upon review of the evidence available in peer-reviewed, published,
epidemiological studies regarding ALS among 9/11-exposed populations,
the Science Team has assessed the degree to which the evidence supports
a causal association between 9/11 exposures and ALS and has determined
that the available evidence is inadequate to determine the likelihood
of a causal association \39\ between 9/11 exposures and ALS (Category
5). The Science Team's evaluation and categorization of the evidence
has been provided to the Administrator.
---------------------------------------------------------------------------
\39\ See Policy and Procedures supra note 5 at Sec. V.E.--
Evidence is Inadequate to Determine a Causal Association.
---------------------------------------------------------------------------
E. Administrator's Final Decision on Whether To Propose the Addition of
Amyotrophic Lateral Sclerosis to the List
Based on the Scientific Evaluation and the Science Team's finding
that there is inadequate evidence to determine whether a causal
association exists between 9/11 exposures and ALS, the Administrator
has determined that there is insufficient evidence of causal
association between 9/11 exposures and ALS to propose adding the
condition to the List.\40\ Pursuant to PHS Act, sec. 3312(a)(6)(B)(iv)
and 42 CFR 88.16(a)(2)(iv), and in accordance with Sec. IX.B. of the
Policy and Procedures, the Administrator is publishing this notice of
his determination of insufficient evidence.
---------------------------------------------------------------------------
\40\ See Policy and Procedures supra note 5 at Sec. VIII.B,
proposed additions to the List are made pursuant to PHS Act, sec.
3312(a)(6)(B)(ii) and 42 CFR 88.16(a)(2)(ii). The Administrator has
also determined that insufficient evidence is available to publish 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)); nor is requesting a recommendation from the STAC
(pursuant to PHS Act, sec. 3312(a)(6)(B)(i) and 42 CFR
88.16(a)(2)(i)) warranted.
---------------------------------------------------------------------------
For the reasons discussed above, the request of Petitions 031, 036,
039, and 053 to add ALS 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. Mandy
Cohen M.D., M.P.H., Director, CDC, and Administrator, ATSDR, approved
this document for publication on January 6, 2025.
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. 2025-00692 Filed 1-17-25; 11:15 am]
BILLING CODE 4163-18-P
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