```

[Federal Register Volume 90, Number 13 (Wednesday, January 22, 2025)]
[Notices]
[Pages 7698-7702]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2025-00692]

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

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.

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

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 https://www.cdc.gov/wtc/received.html 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 [email protected].

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).
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    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 www.cdc.gov/wtc/.

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\
---------------------------------------------------------------------------

    \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, http://www.cdc.gov/wtc/pdfs/WTCHPPPPetitionHandlingProcedures14May2014.pdf.
    \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, https://www.cdc.gov/wtc/pdfs/policies/WTCHP_PP_Adding_NonCancer_Health_Conditions_20241018.pdf.
---------------------------------------------------------------------------

    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.
---------------------------------------------------------------------------

    \6\ Id. at 6.
---------------------------------------------------------------------------

    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:
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    (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.
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    More information about the WTC Health Program, including the List 
and the petition process, is available at www.cdc.gov/wtc/.

[[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:
---------------------------------------------------------------------------

    \10\ See Petition 031, WTC Health Program: Petitions Received, 
http://www.cdc.gov/wtc/received.html.
---------------------------------------------------------------------------

     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.
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

     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.
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

     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.
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    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:
---------------------------------------------------------------------------

    \14\ See Petition 039, WTC Health Program: Petitions Received, 
http://www.cdc.gov/wtc/received.html.
    \15\ NB: The petition numbers are out of order because the WTC 
Health Program processed the second submission first.
---------------------------------------------------------------------------

     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.
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    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:
---------------------------------------------------------------------------

    \17\ See Petition 053, WTC Health Program: Petitions Received, 
http://www.cdc.gov/wtc/received.html.
---------------------------------------------------------------------------

     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.
     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\
---------------------------------------------------------------------------

    \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).
---------------------------------------------------------------------------

    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:
---------------------------------------------------------------------------

    \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 https://www.cdc.gov/niosh/ltas/pdf/Rate-Info-Table-1.pdf. 
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.
---------------------------------------------------------------------------

     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).
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

     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\
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

     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).
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

     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).
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

     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).
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

     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).
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

    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\
---------------------------------------------------------------------------

    \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, https://wwwn.cdc.gov/ResearchGateway/Content/pdfs/Development_of_the_Inventory_of_9-11_Agents_20180717.pdf.
    \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.
---------------------------------------------------------------------------

    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.
---------------------------------------------------------------------------

    \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
```