rfa-ts-26-165_rev10.pdf

Office of Innovation and Analytics

Notice of Funding Opportunity

Application due Wednesday, June 10, 2026

Identify and Evaluate Potential Risk Factors for Amyotrophic Lateral Sclerosis Opportunity number: RFA-TS-26-165

Contents

Step 1: Review the Opportunity 4

Basic information 5

Eligibility 7

Agency priorities 11

Program description 14

Step 2: Get Ready to Apply 27

Find the application package 28

Get registered 28

Help applying 29

Step 3: Build Your Application 31

Application checklist 32

Application contents and format 34

Step 4: Understand Review, Selection, and Award 39

Application review 40

Award notices 48

Step 5: Submit Your Application 49

Submission requirements and deadlines 50

Step 6: Learn What Happens After Award 52

Post-award requirements and administration 53

Contacts and Support 57

Before you begin 3

Endnotes 60

Contents 2

Before you begin If you believe you are a good candidate for this funding opportunity, secure your SAM.gov and Grants.gov registrations now. If you are already registered, make sure your registrations are active and up-to-date.

SAM.gov registration (this can take several weeks) You must have an active account with SAM.gov. This includes having a Unique Entity Identifier (UEI).

See Step 2: Get Ready to Apply

Grants.gov registration (this can take several days) You must have an active Grants.gov registration. Doing so requires a Login.gov registration as well.

See Step 2: Get Ready to Apply

Apply by the application due date Applications are due by 5:00 p.m. local time on Wednesday, June 10, 2026.

To help you find what you need, this NOFO uses internal links. In Adobe Reader, you can go back to where you were by pressing Alt + Left Arrow (Windows) or Command + Left Arrow (Mac) on your keyboard.

Before you begin 3 https://sam.gov/ https://grants.gov/

1. Review 2. Get Ready 3. Build 4. Understand 5. Submit 6. Award Contacts

Step 1:

Review the Opportunity

In this step

Basic information 5

Eligibility 7

Agency priorities 11

Program description 14

Basic information Centers for Disease Control and Prevention

Agency for Toxic Substances and Disease Registry

Office of Innovation and Analytics

Seeking innovative research proposals to identify environmental and other associated risk factors that may increase the likelihood of developing amyotrophic lateral sclerosis (ALS).

Have questions?

See Contacts and Support.

Key facts

Opportunity name: Identify and Evaluate Potential Risk Factors for Amyotrophic Lateral Sclerosis (ALS)

Opportunity number:

RFA-TS-26-165

Assistance listing: 93.061

NOFO version: Original

Key dates

Application submission deadline:

Wednesday, June 10, 2026

Informational call:

June 2, 2026

Optional letter of intent deadline:

May 27, 2026

Expected scientific review date: July 6, 2026

Expected secondary review date: July 20, 2026

Expected award date:

August 27, 2026

Expected start date:

September 30, 2026

Expiration date:

December 13, 2026

See Submit your Application for other submission requirements and deadlines that may apply to this NOFO.

Summary CDC/ATSDR invites innovative research proposals to study environmental and other associated risk factors for amyotrophic lateral sclerosis (ALS).

We prioritize studies focused on:

• Military service.

• Contact sports.

• Traumatic brain injury.

• Neuroinflammation.

• Infectious agents.

Proposals funded under this NOFO must address two objectives:

• Identify potential environmental and other associated risk factors for ALS in humans.

• Characterize how or why the risk factors could be associated with or contribute to the etiology, progression, and pathophysiology of ALS in humans.

The proposed research should produce outcomes that will help CDC:

• Better understand the etiology and epidemiology of ALS.

• Prioritize topics for future research initiatives.

• Develop new CDC/ATSDR National ALS Registry risk factor surveys for persons with ALS.

CDC/ATSDR National ALS Registry data are available for researchers to identify potential risk factors for ALS. You’re encouraged to submit proposals

Step 1: Review the Opportunity 5 on research topic areas that are not currently funded by the National ALS Registry.

There are four funding options included in this NOFO:

• Option A - Support research with strong existing evidence such as studies on known environmental or genetic risk factors, research that improves past studies with better data, or investigations linking risk factors to ALS diagnosis and treatment.

• Option B - Support new and exploratory research on ALS risk factors such as studies on risk factors with little existing evidence or research using innovative methods.

• Option C - Understand ALS risk in affected populations, such as studies involving military veterans or investigations of ALS risk factors among military veterans.

• Option D - Analyze biological samples from the Guamanian ALS cluster such as investigation of disease mechanisms and environmental factors, exposure routes, genetic studies and biomarkers and how this could lead to mitigation therapeutics, diagnostics or prevention.

An application may include only one funding option.

Funding details Funding type: Cooperative agreement

Expected awards: 3 The number of awards is subject to available funds and program priorities.

Period of performance: 3 years in 12-month budget periods.

Application type: Renewal

Expected total program funding over the performance period: $4,500,000

Expected total program funding per budget period: $1,500,000

Expected funding per applicant per budget period: $500,000

Maximum award amount per budget period: $500,000 (Funding Option A or D) or $300,000 (Funding Option B or C). An application may include only one funding option.

Minimum award amount per budget period: $0

Step 1: Review the Opportunity 6

Eligibility Eligible applicants Only these types of organizations may apply.

• State governments.

• County governments.

• City or township governments.

• Special district governments.

• Independent school districts.

• Public and state-controlled institutions of higher education.

• Native American tribal governments (federally recognized).

• Public housing authorities and Indian housing authorities.

• Native American tribal organizations, other than federally recognized tribal governments.

• Nonprofits having a 501(c)(3) status, other than institutions of higher education.

• Nonprofits without 501(c)(3) status, other than institutions of higher education.

• Private institutions of higher education.

• Foreign organizations.

• Bona fide agents applying on behalf of state, territorial, local, and tribal government organizations.

Bona fide agents must submit documentation that demonstrates their arrangement with the eligible applicant. See Other Attachments form.

Responsiveness criteria We will review your application to make sure it meets these requirements.

These are the basic requirements you must meet to move forward in the competition. We won’t consider an application that:

• Is from an organization that doesn’t meet all eligibility criteria. See requirements in eligibility.

• Is submitted after the application deadline of Wednesday, June 10, 2026.

• Does not include specific aims in the Research Strategy focused primarily on environmental toxicant-mediated etiology of ALS.

Step 1: Review the Opportunity 7

• Does not include an epidemiology-focused specific aim in the Research Strategy to investigate ALS risk factors using human epidemiological data.

• Does not meet the Qualifications for principal investigator or project director.

• Exceeds the maximum funding amount for any budget period. The proposed budget for each fiscal year must be less than or equal to the maximum funding amount for each budget period of $500,000 (Funding Option A or D) or $300,000 (Funding Option B or C) as outlined in the Funding Details section.

See the application checklist to understand which elements of your application are part of the responsiveness criteria.

Application limits You must follow these limits on the number of applications your organization can submit.

You may submit more than one application per institution if each application is scientifically distinct. The principal investigator (PI) must be different for each application.

Qualifications for principal investigator or project director We invite anyone who has the skills, knowledge, and resources needed to carry out the proposed research as a project director or principal investigator (PD/PI) to work with their organization or institution to apply.

CDC encourages people from all groups to apply.

SF-424 Biographical Sketch requirements The SF-424 Biographical Sketch for the PD/PI or Co-Investigator(s) must include documentation of their:

• Experience in their area of expertise.

• Knowledge directing human epidemiological, environmental health, and ecological empirical research on ALS risk factors, including the use of:

◦ Prospective and retrospective case-controls.

◦ Large epidemiological datasets.

◦ And the toxicological/molecular laboratory approaches that are reflected in the research strategy section of your Research plan.

Step 1: Review the Opportunity 8

You must also document that the PD/PI or Co-Investigator(s) has the knowledge, experience, and expertise necessary to conduct this research and achieve the proposed objectives with at least one of the following:

• A first-authored, peer-reviewed publication, as defined by the NIH National Library of Medicine, directly relevant to the research plan proposed.

• Serve as a principal investigator on a grant, cooperative agreement, or contract in these subject matter areas (include description and references in the biographical sketch).

These experience requirements may be met by the combined experiences of a Principal and Co-Investigator(s) (if applicable). When you cite the relevant publication(s) or research experience, use bold or highlighted text in the SF-424 Biographical Sketch.

Cost sharing and matching funds This program has no cost-sharing requirement, meaning you do not need to contribute to the costs of this project.

If you choose to include cost-sharing funds, we won’t consider it during review. If you receive an award, we will include your voluntary commitment in the award, and you must report on the funds.

Types of cost sharing You can meet your match requirement through any combination of:

• Cash contributed by your organization, partners, or other third parties.

• In-kind (non-cash) contributions from your organization, partners, or other third parties.

Cost-sharing commitments If awarded, you must provide the amount of cost-sharing funds you promised, even if you promised more than the required minimum. We put these commitments in the Notice of Award.

If you don’t provide your promised amount, we may decrease the amount of funding we give you.

You’ll have to include your cost-sharing funds when you fill out your federal financial reports.

Step 1: Review the Opportunity 9

Post-award requirements

Before you apply, make sure you understand the requirements that come with an award.

See Step 6: Learn What Happens After Award for information on regulations that apply, reporting, and more.

Step 1: Review the Opportunity 10

Agency priorities Required alignment with CDC priorities The recipient of this award must implement any funds awarded under this NOFO to effectuate program goals or agency priorities in accordance with the Centers for Disease Control and Prevention (CDC) Priorities when authorized (for a full description of the CDC Priorities, please follow the provided hyperlink).

Funded activities must:

• Align with CDC’s core priorities by demonstrating a commitment to gold-standard science, transparency, and evidence-based practices.

• Support CDC’s mission to protect Americans from infectious and chronic diseases, strengthen public health systems, and advance innovation in health data and infrastructure.

• Contribute to rapid, science-driven responses to health threats, promote global health leadership, and adhere to principles of integrity, accountability, and compliance with applicable laws and federal priorities.

Consistent with CDC’s values, in carrying out any project funded under this NOFO, the recipient must adhere to the following principles where consistent with the authority and scope of the award and its activities:

• A commitment to gold-standard science and ensuring trust, transparency, and credibility: To build trust and improve CDC’s ability to lead during health crises, CDC will increase transparency, be more accountable, and follow strict, gold-standard scientific practices that are open, unbiased, and based on clear evidence.

• A commitment to global leadership: With staff in 63 countries and supporting 20 more, CDC’s Global Health Center:

◦ Works to prevent disease and advance emergency response.

◦ Detect health threats early, sends response teams, trains health workers, and provides personal protective equipment, vaccines, and medicines.

◦ Test disease samples from around the world to prepare for flu and other serious outbreaks.

◦ Has strengthened systems to better protect people at home and abroad after the COVID-19 outbreak.

1. Review 2. Get Ready 3. Build 4. Understand 5. Submit 6. Award Contacts

Step 1: Review the Opportunity 11 https://www.cdc.gov/about/cdc/index.html

• A commitment to ensuring rapid, evidence-based responses to crises:

During public health emergencies, ensuring rapid, science-driven responses is critical to minimizing harm, maintaining public trust, and restoring stability. To meet this goal, CDC must continue to strengthen its emergency response systems by:

◦ Streamlining internal processes.

◦ Improving risk communication strategies.

◦ Ensuring that laboratory capacity is fully equipped and tested—capable of rapidly developing and deploying scalable diagnostics during crises.

◦ Embedding structures for real-time learning, independent after-action reviews, and the application of lessons learned will ensure that each crisis response is smarter, faster, and more effective than the last.

• A commitment to vaccine safety and efficacy research: CDC will apply “gold-standard” science to all of its vaccine safety and effectiveness research. It will make vaccine data, research methods, and related datasets publicly available through simple data use agreements to improve transparency, accountability, and trust.

• A commitment to advancing our understanding of the causes of autism spectrum disorder (ASD), neurodevelopmental disorders (NDDs), and chronic disease: CDC conducts research and works with partners to better understand the causes of autism spectrum disorder, neurodevelopmental disorders, and chronic diseases. It will use new and existing data to study the rise in these conditions, including the increase in autism diagnoses from 1 in 150 to nearly 1 in 31 over the past 25 years.

• A commitment to modernizing public health infrastructure and enhancing our approach to health data: CDC will modernize public health infrastructure to create a faster, more efficient health system that can detect and respond to outbreaks in real time. This effort includes:

◦ Replacing data silos with integrated systems.

◦ Using advanced technology.

◦ Strengthening partnerships with states to ensure shared responsibility and strong local health data systems.

◦ Emphasizing collaboration across federal and state partners, resilient and adaptable systems, and accountability for funded programs to ensure they align with these priorities and federal requirements.

Step 1: Review the Opportunity 12

• Conflicts of interest: CDC will not support funding programs with conflicts of interest and ensure its work is based on transparent, unbiased science.

• Immigration: CDC funds will not be used to support or encourage illegal immigration, consistent with federal law.

• Protecting life and the family: CDC funds will not be used to support elective abortions, consistent with the Hyde Amendment, and will promote maternal health, the dignity of life, and strong families.

• Ending disorder on America’s streets: CDC will prioritize evidence-based programs that reduce homelessness, drug use, and public disorder. It will support comprehensive services for people with serious mental illness and substance use disorder. CDC will not support housing first strategies, harm-reduction or safe consumption sites, or related activities. To the extent allowable by federal law, CDC intends to give priority to grantees in States and municipalities that have laws and policies that support and enforce CDC’s priorities.

• Gender ideology and protecting children: CDC will not fund medical interventions for minors seeking gender transition and will define sex based on biological criteria.

• DEI: CDC will not support DEI initiatives based on group identity and focus on merit-based, evidence-driven approaches to improve health outcomes.

• Parental rights: CDC will support policies that protect parental authority, promote transparency, and give parents greater control over their children’s education.

The recipient must demonstrate ongoing compliance with the full description and listing of CDC values and priorities, in all programs that are authorized to advance them, through program design, implementation, reporting, and evaluation.

Failure to meaningfully align funded activities with the applicable requirements may result in corrective action, additional reporting requirements, or other enforcement actions consistent with federal grant regulations found at 2 CFR Part 200 and the terms and conditions of this award. The full CDC Priorities Statement can be found here: Centers for Disease Control and Prevention (CDC) Priorities.

1. Review 2. Get Ready 3. Build 4. Understand 5. Submit 6. Award Contacts

Step 1: Review the Opportunity 13 https://opa.hhs.gov/sites/default/files/2025-11/gender-dysphoria-report.pdf

Program description Background The Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry (CDC/ATSDR) are committed to protecting people’s health from environmental hazards by:

• Investigating the relationship between environmental factors and health.

• Developing guidance.

• Building partnerships to support healthy decision making.

The intent of the CDC/ATSDR extramural research program is to fund research that promotes healthy community environments by assessing the available scientific data to determine whether people are at risk because of their exposures to harmful chemicals in the environment.

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive and often fatal neuromuscular disease that presents in familial (fALS) and sporadic (sALS) forms. As of 2017, over 30,000 people in the U.S.

lived with ALS. Most people die within two to five years of being diagnosed with the disease.[1] Approximately 5 to 10% of all ALS cases can be attributed to familial, or heritable, genetic mutations.

Most ALS cases are sporadic. And while the underlying cause(s) are largely unknown, a complex set of risk factors may interact to produce the disease.[2],[3],[4],[5],[6] These include:

• Genetic susceptibility.

• Environment.

• Time.

• Occupation.

Studies have evaluated possible ALS risk factors.[7],[8],[9],[10],[11],[12],[13],[14]

Examined risk factors include:

• Familial and sporadic genetic susceptibility.

• Employment in certain occupations.

• Exposure to heavy metals, cyanotoxins and infectious agents.

• Physical activity.

• Trauma (e.g., traumatic brain injuries, concussions).

Step 1: Review the Opportunity 14

ATSDR is seeking investigator-initiated research that will identify and evaluate environmental and other associated risk factors that contribute to ALS, with a preferred focus on factors related to:

• Military service.

• Contact sports.

• Traumatic brain injury.

• Neuroinflammation.

• Infectious agents.

Military Service Past population-based cohort studies provide limited and suggestive evidence that associates military service in World War II, the Korean, Vietnam, and Gulf Wars with the development of ALS.[15],[16],[17],[18],[19],[20]

While the reasons for increased ALS risk among military veterans are unknown, selective environmental exposures during military service may play a part in increased risk. Examined examples include exposure to persistent organic pollutants, herbicides (including Agent Orange), ionizing radiation, burn agents, cyanotoxins.[21] [22] [23] [24] In addition, the duration of time served and exposure to repetitive explosion-mediated blast overpressure in combat settings, leading to traumatic brain injury (TBI), may also contribute to susceptibility and severity of ALS. [25],[26]

We seek additional research to determine if and how these or other military service-related factors contribute to an increased risk of ALS. These investigations should include study approaches that are statistically well-powered and that adequately control for potential biases and confounding factors.[27]

Contact sports and traumatic brain injury Participating in some contact sports (e.g., American football and soccer) is associated with an increased risk of developing ALS for athletes. Past studies cite intense physical activity, head and neck musculoskeletal trauma, and repeated concussions leading to mild, moderate, or severe TBI as potential contributing factors.[28], [29], [30],[31],[32] However, it is unclear to what degree contact sports-related TBI, and the severity and repetition of TBI, influence ALS development.

We’re seeking additional research that:

• Examines the role of impact-mediated TBI from participating in contact sports in the development of ALS.

Step 1: Review the Opportunity 15

• Considers differential diagnosis of and co-morbidity with ALS and chronic traumatic encephalopathy post-TBI[33],[34].

• Investigates whether and how additional risk factors can work in concert with TBI to increase ALS risk.[35],[36] Such risk factors may include:

◦ Athlete’s exposure to playing field pesticides or grass or soil-associated infectious agents.

◦ The intensity of physical activity.

◦ Athlete demographics, including pre-existing genetic susceptibility, sex, and age at the time of exposure.

Neuroinflammation and infectious agents Neuroinflammation is a primary cause of secondary brain injury following TBI.

Emerging research suggests that neuroinflammation, including dysregulated innate immune system activation, may contribute to the development of ALS through neuronal toxicity. [37],[38]

We’re seeking research to:

• Understand the role of TBI in neuroinflammatory and innate immune response pathways in the development of ALS.

• Identify relevant inflammatory and immune biomarkers in persons with ALS.

We’re also seeking further research on how infectious agents may contribute to ALS, especially their effects on neuroinflammation and immune response.

Past studies have suggested that exposure to microbial infectious agents, including mycoplasma, cyanobacterial neurotoxins, fungal neurotoxins, and viruses, may be a risk factor for ALS.[39],[40] ,[41],[42],[43]

CDC/ATSDR National ALS Registry Uncertainty about the incidence and prevalence of ALS, the etiology of the disease, and risk factors associated with disease development and progression created a need for structured data collection. The ALS Registry Act (P.L. 110-373 (2008)), passed in October 2008, amends the Public Health Service Act to require the Secretary of DHHS, acting through the Director of CDC, to:

• Develop a system to collect data on ALS.

• Establish a national registry for the collection and storage of ALS data.

In October 2010, the ATSDR, in partnership with CDC, launched the National ALS Registry to collect data to:

Step 1: Review the Opportunity 16

• Describe the incidence and prevalence of ALS in the U.S.

• Examine factors, such as environmental, occupational, and genetics, that might be associated with the disease.

• Better outline key demographic factors (such as age, race or ethnicity, sex, and family history of individuals who are diagnosed with the disease) associated with the disease.

• Facilitate examination of the connection between ALS and other motor neuron disorders that can be confused with ALS, misdiagnosed as ALS, and in some cases progress to ALS.

CDC/ATSDR National ALS Registry data are available for researchers to identify potential risk factors for ALS. Per 42 USC 280g-7(d)(1)(B), access to ALS Registry data must comply with privacy statues and regulations.

National strategic priorities CDC/ATSDR is responsible for developing and maintaining the congressionally-mandated National ALS Registry.

Related work A listing of currently funded and previously funded grants can be found on the CDC website.

Purpose ATSDR seeks to identify and evaluate risk factors that contribute to ALS. We’re focusing on research proposals that will examine factors related to:

• Military service.

• Contact sports.

• Traumatic brain injury.

• Environmental exposures.

• Neuroinflammation.

• Infectious agents.

The proposed research should be innovative and produce outcomes that will help ATSDR:

• Better understand the etiology and epidemiology of ALS.

• Prioritize topics for future research initiatives.

• Inform the development of new ATSDR ALS Registry risk factor surveys for persons with ALS.

1. Review 2. Get Ready 3. Build 4. Understand 5. Submit 6. Award Contacts

Step 1: Review the Opportunity 17 https://www.cdc.gov/als/abouttheregistrymain/als-registry-public-law.html https://www.cdc.gov/als/abouttheregistrymain/index.html https://www.cdc.gov/als/hcp/aboutalsregistryresearchapplicationinfo/external-research.html

You’re encouraged to submit proposals on research topic areas not currently funded by the National ALS Registry. We’re especially interested in innovative research applications that propose to conduct an epidemiological investigation using the National ALS Registry and/or using a third-party ALS registry. Examples of ALS registry research that CDC/ATSDR has previously funded can be found on the CDC website.

Objectives and outcomes This section includes the outcomes we expect you to report progress on and achieve within the period of performance if you receive funding.

Applications funded under this NOFO must address two objectives to achieve the following outcomes:

• Better understand ALS risk factors.

• Identify possible etiologies to reduce patient morbidity and mortality.

Objective One Identify potential risk factors for ALS in humans, including at least one of the risk factors listed below:

• Environmental and other associated risks, including from past military service.

• Traumatic brain injuries, including blast or impact TBI associated with military service or contact sports such as American football or soccer.

• Injury or microbial infection (e.g., bacterial, fungal, viral) resulting in neuroinflammation or innate immune system activation.

• Nutritional intake, or lack thereof.

• Pharmaceutical use (e.g., statins).

Objective Two Characterize how or why the risk factors could be associated with or contribute to the etiology, progression, and pathophysiology of ALS in humans.

This NOFO offers four funding options to address the two research objectives.

You may submit a research proposal under Funding Option A, B, C, or D.

Funding Option A

Funding Option A supports ALS risk factor research investigations that have an existing, well-substantiated evidence base and would benefit from strengthened rigorous evaluation.

1. Review 2. Get Ready 3. Build 4. Understand 5. Submit 6. Award Contacts

Step 1: Review the Opportunity 18 https://www.cdc.gov/als/hcp/aboutalsregistryresearchapplicationinfo/external-research.html https://www.cdc.gov/als/hcp/aboutalsregistryresearchapplicationinfo/external-research.html?CDC_AAref_Val=https://www.cdc.gov/als/ALSExternalResearchfundedbyRegistry.html

Examples of proposals appropriate for Funding Option A include:

• Investigations on well-substantiated environmental, genetic, and other ALS risk factors that can be strengthened by prospective and retrospective longitudinal studies with appropriately addressed confounders.

• Studies that improve upon past investigations with increased statistical power and expanded ALS and/or control population cohorts.

• Studies that seek to link risk factors to clinical diagnosis, treatment, and outcomes.

Awards made under Funding Option A will be funded for up to $500,000 per year (including direct and indirect costs), for a period of performance of up to 3 years, if funds are available.

Funding Option B

Funding Option B supports novel ALS risk factor research investigations that:

• May or may not have an existing evidence base.

• May be supported by limited and insufficient preliminary research.

• Are exploratory and developmental in nature.

Examples of proposals appropriate for Funding Option B include:

• Investigations on risk factors without an existing evidence base. For example:

◦ Gut microbiome and other genomic, dietary, or metabolic risk factors.

◦ Aviation and other radiation-related risk factors.

◦ Sports-related risk factors other than TBI (e.g., strenuous physical activity).

• Investigations on risk factors that use novel approaches.

Awards made under Funding Option B will be funded for up to $300,000 per year (including direct and indirect costs), for a period of performance of up to 3 years, if funds are available.

Funding Option C

Funding Option C supports research and better understanding of ALS risk factors, including prevalence and incidence in disproportionally impacted communities, such as military veterans.

Examples of proposals appropriate for Funding Option C include research related to:

Step 1: Review the Opportunity 19

• Populations disproportionately impacted, such as military veterans or those with increased susceptibility to ALS.

Awards made under Funding Option C will be funded for up to $300,000 per year (including direct and indirect costs), for a period of performance of up to 3 years, if funds are available.

Funding Option D

Funding Option D supports the analyses of biological fluids and tissues for the Guamanian ALS cluster.[44] This collection presents a unique opportunity to study the role of potential hereditary characteristics of pathogenic gene(s) and the contribution of environmental factors in disease development because:

• They’re one of the largest retrospective ALS clusters.

• They were collected by investigators as part of a clinical and epidemiological study in Guam due to a sudden peak and decline of ALS incidence in the region during the 1950s.

• The biospecimen are unique to the local population of Guam and nearby islands, affected descendants of those diagnosed with ALS, and its geography.

Examples of proposals appropriate for Funding Option D include:

• Investigations on the potential disease mechanism underlying clinical phenotype, environmental risk factors, biomarkers, genetic markers or mutations and/or modifications that may be unique to the Guamanian ALS biospecimen, and gene-environment interaction.

• Studies where the successful outcome may add significant scientific knowledge and better understanding of the disease mechanism contributing to both familial (hereditary) and sporadic (no evident hereditary cause) ALS cases.

Awards made under Funding Option D will be funded for up to $500,000 per year (including direct and indirect costs) for a period of performance of up to 3 years, if funds are available.

You must clearly indicate in the abstract whether the research proposal will fall under either Funding Option A, B, C, or D. An application may include only one funding option.

For Options A, B, or C, you may use data from the National ALS Registry if you follow all applicable privacy laws and regulations. However, using National ALS Registry data is not required for any of the funding options.

Step 1: Review the Opportunity 20

Collaborations As a recipient, you’re required to carry out the majority (60% or more) of the proposed research work plan. Document how you’ll do so in SF-424 Research and Related Budget. You cannot serve as a “pass through” to fund another entity to conduct the majority of the research.

Partnerships between your institution and outside entities may be necessary or advantageous to complete the proposed work. Your application must clearly describe each partners’ roles and responsibilities. This includes demonstrating your access to planned data sources and study populations, and all partnerships necessary to complete the proposed project.

You should clearly describe the nature and extent of the proposed partnership for the proposed research in the Research Strategy section of your application, including:

• Roles and responsibilities of the Principal Investigator(s).

• Roles and responsibilities of the outside entities or partner agencies.

• Existing working relationship between Principal Investigator(s) and outside entities or partner agencies.

• Plans for the proposed research.

• Nature and extent of the involvement to be provided by the applicant institution and outside entity.

• How the partnership will ensure implementation and sustainability of the proposed evaluation.

Evidence of access to the data from outside entities may be demonstrated by data sharing agreements, memoranda of understanding, or Letters of Support detailing the data availability. Refer to the Scored Criteria section to review how collaborations and partnerships will be considered.

Evaluation and performance measurement You’re expected to provide an evaluation and performance measurement plan with measures of effectiveness in your application. The plan must demonstrate that you’ll be able to accomplish the objectives of your proposal.

The measures of effectiveness must relate to the goals stated in the Purpose section. They should measure the intended outputs and outcomes as described in the Objectives and outcomes section. The outcomes you’ll evaluate should be clearly specified.

Performance measures should include:

• Number of study participants recruited.

Step 1: Review the Opportunity 21

• Participation rate.

• Types of samples collected.

Paperwork Reduction Act Any activities involving information collection from 10 or more individuals or organizations may require the Paperwork Reduction Act (PRA) approval. The PRA requires review and approval of the information collection by the White House Office of Management and Budget.

To determine if a proposed activity requires PRA approval, contact your project officer. Collections include items like surveys and questionnaires. If you have collections requiring PRA approval, CDC is responsible for working with OMB to gain the approval.

For more information about CDC’s requirements under PRA see CDC Paperwork Reduction Act Compliance.

Funding policies and limitations Changes in HHS regulations As of October 1, 2025, HHS adopted 2 CFR 200, with some exceptions included in 2 CFR 300. These regulations replace those in 45 CFR 75. You can find details in HHS Summary of Regulatory Changes, which is posted in the Grants.gov Related Documents tab for this opportunity.

General guidance All activities proposed in your application and budget narrative must align with applicable law, including but not limited to statutes, executive orders, federal regulations and applicable judicial holdings. Accordingly, discretionary awards shall not be used to fund, promote, encourage, subsidize, or facilitate;

racial preferences or other forms of racial discrimination by the recipient, including activities where race or intentional proxies for race will be used as a selection criterion for employment or program participation; denial by the recipient of the sex binary in humans, or the belief that sex is a chosen or mutable characteristic; illegal immigration; or any other initiatives that compromise public safety. If an application does not align, the application will not receive funding to the extent permitted by law and applicable court orders.

• You may use funds only for reasonable program purposes consistent with the award, its terms and conditions, and federal laws and

1. Review 2. Get Ready 3. Build 4. Understand 5. Submit 6. Award Contacts

Step 1: Review the Opportunity 22 https://www.cdc.gov/scientific-integrity/php/public-information-collection/?CDC_AAref_Val=https://www.cdc.gov/os/integrity/reducepublicburden/index.htm https://www.cdc.gov/scientific-integrity/php/public-information-collection/?CDC_AAref_Val=https://www.cdc.gov/os/integrity/reducepublicburden/index.htm https://www.ecfr.gov/current/title-2/part-200 https://www.ecfr.gov/current/title-2/subtitle-B/chapter-III/part-300 regulations that apply to the award. If you have questions about these purposes, ask the grants management specialist.

• Your budget is arranged in eight categories: salaries and wages, fringe benefits, travel, equipment, supplies, contractual, other (includes consultant costs), and indirect costs.

• Support beyond the first budget year will depend on:

◦ Appropriation of funds.

◦ Satisfactory progress in meeting your project’s objectives.

◦ A decision that continued funding is in the government’s best interest.

• Generally, you may not use funds to purchase furniture or equipment.

Clearly identify and justify any such proposed spending in the budget.

• If we receive more funding for this program, we will consider:

◦ Funding more applicants.

◦ Extending the period of performance.

◦ Awarding supplemental funding.

Unallowable costs You may not use funds for:

• Clinical care, except as allowed by law.

• Pre-award costs, unless we give you prior written approval.

• Other than for normal and recognized executive-legislative relationships:

◦ Publicity or propaganda purposes, including preparing, distributing, or using any material designed to support or defeat the enactment of legislation before any legislative body.

◦ The salary or expenses of any grant or contract recipient, or agent acting for such recipient, related to any activity designed to influence the enactment of legislation, appropriations, regulation, administrative action, or executive order proposed or pending before any legislative body.

See Anti-Lobbying Restrictions for CDC Recipients.

For guidance on some types of costs that we restrict or do not allow, see 2 CFR 200.420, Considerations for Selected Items of Cost.

1. Review 2. Get Ready 3. Build 4. Understand 5. Submit 6. Award Contacts

Step 1: Review the Opportunity 23 https://www.cdc.gov/grants/documents/Anti-Lobbying-Restrictions.pdf https://www.ecfr.gov/current/title-2/section-200.420

Indirect costs Indirect costs are those shared across multiple projects and not easily separated. Learn more at CDC Budget Preparation Guidelines.

To charge indirect costs you can select one of two methods:

Method 1 — Approved rate. If you currently have an indirect cost rate approved by your cognizant federal agency, you may use that rate.

Enclose a copy of the current approved rate agreement in your attachments.

Method 2 — De minimis rate. If you do not have a current negotiated indirect cost rate, you may elect to charge a de minimis rate (see 2 CFR 200.414(f)). This rate is 15% of modified total direct costs (MTDC). See the definition of MTDC (2 CFR 200.1). You can use this rate indefinitely.

For foreign awards: Recipients may charge indirect costs on awards to foreign organizations and foreign public entities performed fully outside of the U.S.

and its territories to support the costs of complying with federal requirements. This rate is fixed at 8% of MTDC, excluding tuition and related fees, direct expenditures for equipment, and subawards over $25,000.

Negotiated indirect costs may be paid to the American University, Beirut, and the World Health Organization.

Other indirect cost policies As described in 2 CFR 200.403(d), you must consistently charge items as either indirect or direct costs and may not double charge.

Indirect costs may include the cost of collecting, managing, sharing, and preserving data.

Salary rate limitation The salary rate limitation in the current appropriations act applies to this program. As of January 2026, the salary rate limitation is $228,800. We update this limitation when it changes.

Program income If you earn any money from your award-supported project activities (known as program income), you must use it for the purposes and under the conditions of the award. Find more about program income at 2 CFR 200.307.

1. Review 2. Get Ready 3. Build 4. Understand 5. Submit 6. Award Contacts

Step 1: Review the Opportunity 24 https://www.cdc.gov/grants/documents/budget-preparation-guidance.pdf https://www.ecfr.gov/current/title-2/section-200.414 https://www.ecfr.gov/current/title-2/section-200.414 https://www.ecfr.gov/current/title-2/part-200#p-200.1(Modified%20Total%20Direct%20Cost%20(MTDC)) https://www.ecfr.gov/current/title-2/part-200#p-200.403(d) https://www.ecfr.gov/current/title-2/section-200.307

Expanded authority For more information on expanded authority and pre-award costs, see the HHS Grants Policy Statement and speak to the grants management contact.

Pre-award costs may be allowable as an expanded authority, but only if we authorize the costs.

Public health data We require that awards include the needed costs and methods to share public health data. You may include the reasonable cost of sharing or archiving public health data as part of your requested budget for first-time or continuation awards. For more information, see Data Management and Access.

Human subjects We will restrict funds related to conducting research involving human subjects until the appropriate assurances and Institutional Review Board (IRB) approvals are in place. To lift the restrictions, we require copies of all current local IRB approval letters, local IRB-approved protocols, and CDC IRB approval letters, when applicable.

If the proposed research project involves more than one institution and will be conducted in the United States, we expect you to:

• Use a single Institutional Review Board (sIRB) to conduct the required ethical review.

• Include a single IRB plan in your research plan and PHS Human Subjects and Clinical Trials Information form, unless either of the following is true:

◦ Review by an sIRB would be prohibited by federal, tribal, or state law, regulation, or policy.

◦ You provide a compelling justification based on ethical or human subject protection issues or other well-justified reasons.

Do not duplicate information in the research plan form and the PHS Human Subjects and Clinical Trials Information form.

In your research plan, discuss the overall strategy, methodology, and analyses of your proposed research. Use the PHS Human Subjects and Clinical Trials Information form to provide detailed information for human subjects studies and clinical trials.

1. Review 2. Get Ready 3. Build 4. Understand 5. Submit 6. Award Contacts

Step 1: Review the Opportunity 25 https://www.hhs.gov/sites/default/files/hhs-grants-policy-statement-october-2024.pdf https://www.cdc.gov/grants/additional-requirements/ar-25.html

We will review and approve exceptions in accordance with 45 CFR part 46 and, as applicable, 21 CFR part 50 and 21 CFR part 56, or we may place a restriction on the award.

Note: The sIRB requirement applies to participating sites in the United States.

Foreign sites participating in CDC-funded, cooperative research studies do not need to follow the requirement for sIRB.

For more information, please consult the scientific and research contact listed for this NOFO.

Statutory authority This program is authorized under Sections 317(k)(2) and 399S of the Public Health Service Act [42 U.S.C. 247b(k)(2) and 42 U.S.C. 280g-7].

1. Review 2. Get Ready 3. Build 4. Understand 5. Submit 6. Award Contacts

Step 1: Review the Opportunity 26 https://nofos.simpler.grants.gov/nofos/%22https://www.ecfr.gov/current/title-45/part-46 https://www.ecfr.gov/current/title-21/part-50 https://www.ecfr.gov/current/title-21/part-56

Step 2:

Get Ready to Apply

In this step

Find the application package 28

Get registered 28

Help applying 29

Find the application package The application package has all the forms you need to apply. You can find it online. Go to Grants Search at Grants.gov or eRA ASSIST and search for opportunity number RFA-TS-26-165. After opening the opportunity, select the “package” tab to see the forms.

We recommend that you select the Subscribe button from the View Grant Opportunity page for this NOFO to get updates.

If you can’t use Grants.gov to download application materials or have other technical difficulties, including issues with application submission, contact Grants.gov for help.

Get registered You must be registered in both SAM.gov and Grants.gov to apply. You can review the requirements and get started on developing your application before your registrations are complete.

SAM.gov You must have an active account with SAM.gov. When you register, you will also receive your required Unique Entity Identifier (UEI). SAM.gov registration can take several weeks. Begin that process today.

To register, go to SAM.gov Entity Registration and select Get Started. From the same page, you can also select the Entity Registration Checklist for the information you will need to register.

When you register or update your SAM.gov registration, you must agree to the financial assistance general certifications and representations. You must specifically agree to those for grants, not those for contracts, because the two agreements are different. You will have to maintain your registration throughout the life of any award.

You must have a UEI number associated with your organization’s physical location. If your organization has multiple UEI numbers, use the UEI number associated with the location receiving the federal funds.

1. Review 2. Get Ready 3. Build 4. Understand 5. Submit 6. Award Contacts

Step 2: Get Ready to Apply 28 https://grants.gov/search-grants https://public.era.nih.gov/assist/public/login.era?TARGET=https%3A%2F%2Fpublic.era.nih.gov%3A443%2Fassist%2F https://www.grants.gov/support https://www.grants.gov/support https://sam.gov/content/entity-registration https://www.hhs.gov/sites/default/files/financial-assistance-general-certification-representations.pdf

Grants.gov You must also have an active account with Grants.gov. You can see step-by step instructions at the Grants.gov Quick Start Guide for Applicants.

eRA Commons You must register in eRA Commons. Your senior and key personnel must also register and affiliate their accounts with your organization’s account.

Register at least four weeks before the application deadline.

Need help? See Contacts and Support.

Help applying For help with the application process and tips for preparing your application, see How to Apply on our website and the Research Instructions for NIH and Other PHS Agencies [PDF].

If any instructions differ from those in this NOFO, follow the instructions in this NOFO.

For other questions, see Contacts and Support.

1. Review 2. Get Ready 3. Build 4. Understand 5. Submit 6. Award Contacts

Step 2: Get Ready to Apply 29 https://grants.gov/applicants/applicant-registration http://www.grants.gov/quick-start-guide/applicants https://public.era.nih.gov/commonsplus/public/login.era?TARGET=https%3A%2F%2Fpublic.era.nih.gov%3A443%2Fcommons https://www.cdc.gov/grants/applying/index.html https://grants.nih.gov/grants/how-to-apply-application-guide/forms-i/research-forms-i.pdf

Join the informational call For more information about this opportunity, join our informational call. A pre-application webinar call will be conducted on June 2, 2026, to address questions from prospective applicants regarding NOFO RFA-TS-26-165. The call will begin at 2 p.m. Eastern Time (ET) and end at 2:50 p.m. ET, or sooner if all questions are addressed. Questions and answers from the discussion are anticipated to be included in an amended NOFO approximately 3 weeks after the webinar.

Microsoft Teams meeting

• Join the meeting here.

• Meeting ID: 219 231 458 690 976

• Passcode: 6dd2F97B

If you are not able to join through your computer, you can call in by phone.

• +1 404-498-3000,,335092471# United States, Atlanta

• (888) 994-4478,,335092471# United States (Toll-free)

• Find a local number.

• Phone conference ID: 335 092 471#

Joining and participating is voluntary and does not affect eligibility, application scoring, or award selection. You can attend anonymously.

1. Review 2. Get Ready 3. Build 4. Understand 5. Submit 6. Award Contacts

Step 2: Get Ready to Apply 30 https://teams.microsoft.com/meet/219231458690976?p=iJTECIp7BWxMevhwLq tel:+14044983000,,335092471 tel:8889944478,,335092471 https://dialin.teams.microsoft.com/f157e5c8-9e01-4021-b245-b3aec6e9a1bc?id=335092471

Step 3:

Build Your Application

In this step

Application checklist 32

Application contents and format 34

Application checklist You must follow the research instructions [PDF] to complete your application.

In this section, we also provide NOFO-specific guidance for some forms.

Make sure that you have everything you need to apply:

Form Required for

PHS 398 Research Plan form All applications.

• Include Funding Option A, B, C, or

D in the abstract.

• Clearly include the specific aim focused on a human health epidemiological investigation to identify and evaluate ALS risk factors and specifics to identify potential environmental toxicant mediated etiology.

• List sources using human ALS epidemiological data.

SF-424 (R&R) All applications.

PHS 398 Cover Page Supplement form All applications.

SF-424 (R&R) Other Project Information All applications.

SF-424 (R&R) Project/Performance Site Locations All applications.

SF-424 (R&R) Senior/Key Person Profile All applications.

R&R Budget form or HS 398 Modular Budget form

All applications.

• Include only one of these forms, not both, in your application.

• The modular form is typically used by domestic organizations requesting $250,000 or less per budget period in direct costs.

R&R Subaward Budget Attachments form If your application proposes subawards.

PHS Human Subjects and Clinical Trials Information All applications.

PHS Assignment Request form Optional.

1. Review 2. Get Ready 3. Build 4. Understand 5. Submit 6. Award Contacts

Step 3: Build Your Application 32

Form Required for

Other Attachments form All…