RFA-JG-25-137 20241230.pdf

Centers for Disease Control and Prevention

Global Health Center

Innovative Approaches for TB Prevention and Case Finding to END TB

RFA-JG-25-137

03/03/2025

Table of Contents Section I. Funding Opportunity Description

Section II. Award Information

Section III. Eligibility Information

Section IV. Application and Submission Information

Section V. Application Review Information

Section VI. Award Administration Information

Section VII. Agency Contacts

Section VIII. Other Information

Overview

Participating Organization(s) Centers for Disease Control and Prevention Components of Participating Organizations Components of Participating Organizations:

Global Health Center Notice of Funding Opportunity (NOFO) Title Innovative Approaches for TB Prevention and Case Finding to END TB Activity Code U01 – Research Project - Cooperative Agreements

Notice of Funding Opportunity Type New Agency Notice of Funding Opportunity Number

RFA-JG-25-137

Assistance Listings Number(s) 93.494 Category of Funding Activity HL - Health NOFO Purpose The World Health Organization’s (WHO) End TB Strategy envisions a world free of tuberculosis (TB)—zero deaths, disease, and suffering due to TB by 2035. This requires reducing the global TB incidence to <100 cases per million people within the next decade.

In 2022, an estimated 10.6 million people developed TB disease, and an estimated 1.3 million people died from TB. In 2022, 88% of all new TB cases were diagnosed in adults (≥15 years of age), with 46% living in Southeast Asia, and 6.3% diagnosed in people living with HIV (PLHIV). Despite being preventable and treatable, large gaps in the detection and treatment of TB cases remain; about 4.2 million TB cases (40%) were not reported in 2021. These detection gaps are larger in populations at increased/higher risk for TB, including but not limited to children, persons with drug-resistant TB (DR-TB), people living with HIV and mobile and migrant populations.

Globally, it is estimated that 2 billion people (one-fourth of the world’s population) may be infected with TB and contribute to future TB cases. Preventing TB transmission and increasing case finding is critical to achieving TB elimination goals.

The purpose of this Notice of Funding Opportunity (NOFO) is to develop, implement, and evaluate evidence-based and innovative approaches to halt progression of TB disease in high burden settings by improving identification and treatment of TB infection and TB disease, including asymptomatic TB, in all populations.

Key Dates Publication Date:

To receive notification of any changes to RFA-JG-25-137, return to the synopsis page of this announcement at www.grants.gov and click on the "Send Me Change Notification Emails" link.

An email address is needed for this service.

Letter of Intent Due Date:

02/03/2025

Application Due Date:

03/03/2025

On-time submission requires that electronic applications be error-free and made available to CDC for processing from the NIH eRA system on or before the deadline date. Applications must be submitted to and validated successfully by Grants.gov no later than 11:59 pm U.S. Eastern Time.

Applicants will use a system or platform to submit their applications through Grants.gov and eRA Commons to CDC. ASSIST, an institutional system to system (S2S) solution, or Grants.gov Workspace are options. ASSIST is a commonly used platform because it provides a validation of all requirements prior to submission and prevents errors.

For more information on accessing or using ASSIST, you can refer to the ASSIST Online Help Site at: https://era.nih.gov/erahelp/assist. Additional support is available from the NIH eRA Service desk via http://grants.nih.gov/support/index.html.

• E-mail: commons@od.nih.gov

• Phone: 301-402-7469 or (toll-free) 1-866-504-9552

• Hours: Monday - Friday, 7 a.m. to 8 p.m. Eastern Time, excluding Federal holidays

Note: HHS/CDC grant submission procedures do not provide a grace period beyond the application due date time to correct any error or warning notices of noncompliance with https://www.grants.gov/ http://grants.nih.gov/support/index.html mailto:commons@od.nih.gov giq3 Highlight application instructions that are identified by Grants.gov or eRA systems (i.e., error correction window).

Scientific Merit Review:

04/09/2025

Secondary Review:

06/04/2025

Estimated Start Date:

09/30/2025

Expiration Date:

03/14/2025

Required Application Instructions It is critical that applicants follow the instructions in the How to Apply - Application Guide except where instructed to do otherwise in this NOFO. Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Note:The Research Strategy component of the Research Plan is limited to 25 pages.

Page Limitations: Pages that exceed the page limits described in this NOFO will be removed and not forwarded for peer review, potentially affecting an application's score.

Applications that do not comply with these instructions may be delayed or may not be accepted for review.

Telecommunications for the Hearing Impaired: TTY 1-888-232-6348

Executive Summary Purpose: The purpose of this NOFO is to develop, implement, and evaluate evidence-based and innovative approaches under the following two thematic components:

• Component A - Halt Progression of TB Disease: Halt progression of TB disease in high-burden settings – with a focus on TB preventive treatment (TPT) with or without increased nutrition.

• Component B - Case Finding and Course of TB Disease: Detect TB infection and TB disease, including asymptomatic TB, using newer tools and products - in all populations including those at increased/higher risk for TB (i.e., PLHIV, children, displaced persons, healthcare workers, economically disadvantaged persons with other co-morbid conditions [alcohol use disorders, diabetes mellitus, persons who use illicit substances, undernourished], and older adults).

https://grants.nih.gov/grants/how-to-apply-application-guide.html

The anticipated total number of awards is up to 2, but only 1 award for each thematic component. Applicants may apply to one or both thematic components by submitting scientifically distinct and separate applications.

• *Mechanism of Support: Cooperative Agreement

• *Funds Available and Anticipated Number of Awards: The estimated total funding available, including direct and indirect costs, for the entire 5-year period of performance is $10,000,000 for both thematic components combined. The number of awards will be up to 2, one per thematic component. Awards issued under this NOFO are contingent upon availability of funds and a sufficient number of meritorious applications. Because the nature and scope of the proposed research will vary from application to application, it is also anticipated that the size and duration of each award may also vary. The total amount awarded and the number of awards will depend upon the number, quality, duration and cost of the applications received.

• *Budget and Period of Performance: The estimated total funding (direct and indirect) for the first year (12-month budget period) will be $2,000,000 with individual awards ranging from $0 to $1,000,000 per thematic component for the first year. The estimated total funding (direct and indirect) for the entire period of performance will be $10,000,000 for both thematic components combined. The project period is anticipated to run from 09/30/2025 to 09/29/2030.

• Average One Year Award Amount:

$2,000,000 The Approximate Total Fiscal Year Funding amount for Year 1 is $2,000,000. The expected number of awards is up to two.

For this NOFO, applicants should apply to the Average One-Year Award Amount/Approximate Average Award amount of $1,000,000 instead of applying to the full $2,000,000 Approximate Total Fiscal Year Funding amount for Year 1. Applicants should develop a proposal to spend up to $1,000,000 for one thematic component.

Applications proposing funding in excess of $1,000,000 for Year 1 per thematic component will be deemed “nonresponsive” and will not move forward to scientific peer review.

• Application Research Strategy Length: Page limits for the Research Strategy are clearly specified in Section IV. “Application and Submission Information” of this announcement.

• Eligible Institutions/Organizations. Institutions/organizations listed in Section III of this announcement are eligible to apply.

• Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization to develop an application for support. CDC does not make awards to individuals directly. Individuals from organizations that are uniquely prepared to examine research relevant to undeserved groups, including sexual orientation and gender identity minorities as well as individuals with disabilities are always encouraged to apply.

• Number of PDs/PIs. There will only be one PD/PI for each application.

• Number of Applications. Applicant organizations may submit more than one application, provided that each application is scientifically distinct meaning that Component A and Component B are submitted as two different applications.

• Application Type. New

• Special Date(s). Letter of intent (LOI) date: February 3, 2025; Application receipt date:

March 3, 2025. Applicants may submit their questions by e-mail to cgherpo@cdc.gov by 11:59 pm ET on December 12, 2024.

Questions received after this time will not be considered for response. All changes, updates including the Q/A will be added as an amendment to the NOFO and will be posted on grants.gov within two weeks after December 12, 2024.

• Application Materials. See Section IV.1 for application materials

Section I. Funding Opportunity Description Statutory Authority This program is authorized under Section 307 of the Public Health Service Act [42 USC 242l], as amended and Section 301(a) of the Public Health Service Act [42 USC 241(a)], as amended.

1. Background and Purpose The End TB Strategy envisions a world free of TB, zero deaths, disease, and suffering due to TB by 2035. This requires reducing the global TB incidence to <100 cases per million people within the next decade [global TB incidence was 133 cases per 100,000 in 2022]. The End TB Strategy serves as a blueprint for countries to end the TB epidemic by driving down TB deaths, and incidence, and eliminating catastrophic costs (>20% of annual household income spent on TB costs). It outlines global impact targets to reduce TB deaths by 95% and cut new cases by 90% by 2035 (compared to 2015), as well as ensure that no family is burdened with catastrophic costs due to TB.

In 2022, an estimated 10.6 million people developed TB disease, and an estimated 1.3 million people died from TB. In 2022, 88% of all new TB cases were diagnosed in adults (≥15 years of age), with 46% living in Southeast Asia, and 6.3% diagnosed in PLHIV. Despite being preventable and treatable, large gaps in the detection and treatment of TB cases remain; only 6.4 million TB cases (60%) were officially reported in 2021. These detection gaps are larger in populations at increased/higher risks for TB, including but not limited to PLHIV, children, persons with DR-TB, and mobile and migrant populations.

Globally, it is estimated that 2 billion people (one-fourth of the world’s population) may be infected with TB and contribute to future TB cases. Preventing TB transmission and infection and increasing case finding is critical to achieving TB elimination goals.

Although the number of people who developed DR-TB (multidrug-resistant TB [MDR-TB] and rifampicin-resistant TB [RR-TB]) was relatively stable between 2020 and 2022, there are substantial gaps in MDR/RR-TB detection and treatment. There were about 410,000 incident cases of MDR/RR-TB in 2022 with an estimated 3.3% as MDR/RR-TB.

Undernutrition is a major risk factor for TB with a 19% population attributable fraction – which is higher than HIV and diabetes. Undernutrition also leads to unfavorable TB treatment outcomes and mortality. Additionally, it increases comorbidity with other key TB risk factors including HIV and alcohol use. Undernutrition can be treated safely and inexpensively.

Despite the enormous toll on health and well-being, the response to TB has been slow and underfunded, particularly around research with only half of the annual target reached. The third pillar of the End TB Strategy intensified research and innovation recognizes that achieving substantial reductions in TB incidence and mortality will require:

• Discovery, development, and rapid uptake of new tools, interventions, and strategies, including evaluations of new tests for TB infection and disease; and

• Research to optimize implementation and impact of new interventions including digital technologies.

The BCG vaccine has been around for almost a century. However, it does not provide adequate protection in adolescents and adults. Therefore, a new TB vaccine is a crucial prevention tool needed to End TB. There are several TB vaccine candidates under clinical development and about a dozen are in active trials. These trials cover a diverse candidate population including PLHIV, children, adolescents and adults.

This NOFO is not intended for animal research; basic biomedical research; nor biomarker, drug, device, or vaccine development.

Healthy People 2030 and other National Strategic Priorities This NOFO aligns with CDC’s current Global Health Strategy, including protecting Americans and populations across the globe by strengthening global public health prevention, detection, and response; saving lives, improving health outcomes, and fostering healthy populations globally;

and leading the advancement of global public health science and serving as a leading source of credible scientific information.

This program addresses the “Healthy People 2030” focus area of the Global Health Goal:

Improve health by preventing, detecting, and responding to public health events worldwide.

Other Public Health Priorities and Strategies

This NOFO aligns with the National Action Plan for Combating Antibiotic-Resistant Bacteria, 2020-2025 [carb-national-action-plan-2020-2025.pdf (hhs.gov)].

The U.S. Department of Health and Human Services’ Centers for Disease Control and Prevention (HHS/CDC) works with host countries and other key partners to assess the needs of each country and design a customized program of assistance that fits within the host nation’s strategic plan and partnership framework. In an effort to ensure maximum cost efficiencies and program effectiveness, HHS/CDC also supports coordination with and among partners and integration of activities that promote Global Health Initiative principles. As such, recipients may be requested to participate in programmatic activities that include the following activities:

• Scale up evidence-based programs to identify and close the major TB gaps, among all populations at risk of TB infection and all forms of drug-sensitive and drug-resistant TB disease;

• Increase impact through strategic coordination and integration;

• Strengthen and leverage key multilateral organizations, global health partnerships, and private sector engagement;

https://www.hhs.gov/sites/default/files/carb-national-action-plan-2020-2025.pdf

• Encourage country ownership and invest in country-led plans;

• Build sustainability through investments in health systems;

• Enhance health equity and reduce disparities in access to and uptake of TB services;

• Assess demand, implementation readiness, and deployment strategies for next generation

TB vaccines;

• Strengthen performance metrics, monitoring, and evaluation for program improvement;

and

• Promote research, development, and innovation to develop a body of knowledge, enhance awareness, and increase the skills and abilities of partners.

Geographic prioritization may change over the course of the period of performance based on the burden of disease and evolving program priorities.

Any Personally Identifiable Information (PII) collected as part of the activities of this NOFO should be managed in a manner that protects individual-level data to the extent allowed by applicable law.

Public Health Impact The health targets of the United Nations Sustainable Development Goals (SDGs) build on historic gains made under the United Nations Millennium Development Goals. The SDG target to “end the TB epidemic” by 2030 and more specifically the End TB Strategy include ensuring that no family is burdened with catastrophic expenses due to TB, and achieving a 90% reduction in TB deaths and an 80% reduction in TB incidence compared with levels in 2015, with targets for further reductions (95% and 90%, respectively) by 2035. However, there is still an enormous gap between current progress and the vision of the SDGs.

There is a need for public health research to deliver innovation for new and existing technologies, and to enable integrated people-centered prevention and case finding approaches.

The overall impact aimed through this NOFO is to develop, implement, and evaluate evidence-based and innovative approaches to halt the progression of TB disease. This will be done by identifying tools, strategies, and practices that can be incorporated into routine TB care in the future. Results from these innovative activities will provide local Ministries of Health and other key partners with the evidence base to support future adoption and scale-up of strategies that will maximize population-level impact of TB prevention efforts and TB case finding.

Relevant Work CDC's global TB mission and strategies are aligned with the WHO's End TB Strategy, 2022 update, WHO’s Global Strategy for TB research and innovation (2020–2023), the Stop TB Partnership’s Global Plan to End TB (2023–2030), the United Nations SDGs for TB, and the 2018 and 2023 United Nations Political Declaration on the Fight Against TB. CDC works with technical organizations (Ministries of Health; the Global Fund to Fight AIDS, TB, and Malaria;

and other U.S. agencies) to strengthen TB control programs to prevent, diagnose, and treat all forms of TB, including HIV-associated TB and drug-resistant TB.

Additionally, along with global partners, CDC TB experts are focusing on a distinct set of strategies as part of CDC's effort to decrease the incidence and mortality that TB causes globally:

• CDC protects Americans both domestically and abroad by working on the frontlines and providing expert technical advice, guidance, and training in high-burden TB and TB/HIV countries.

• CDC and partners are preventing TB transmission, by identifying TB hotspots for targeted screening, strengthening infection control practices in health facilities and communities, using early diagnosis and treatment as prevention, and scaling treatment to prevent TB among people who are at increased/higher risk for TB.

• CDC and partners are expanding access to better screening, improving case-finding approaches to identify new patients, enhancing testing strategies to optimize diagnostics, and providing training and technical support to scale accurate and reliable diagnostic tools.

In 2020, under the NOFO GH-20-001 titled, “Develop, Implement, and Evaluate Evidence-based, Innovative Approaches to Prevent, Find, and Cure Tuberculosis in High-Burden Settings”, CDC funded a five-year project titled, “Closing – TB GAPs – for people living with HIV: TB Guidance for Adaptable Patient-Centered Service.” TB GAPS aims to find and prevent TB in children and adolescents, while simultaneously determining the most cost-effective prevention strategy and promoting best practices to sustain impact, in five sub-Saharan African countries, including Eswatini, Lesotho, Malawi, Tanzania, and Uganda.

Selected publications related to the two research thematic components of the above referenced NOFO include:

• Bhargava, Anurag, et al. "Nutritional supplementation to prevent tuberculosis incidence in household contacts of patients with pulmonary tuberculosis in India (RATIONS): a field-based, open-label, cluster-randomised, controlled trial." The Lancet 402.10402 (2023): 627-640.

• Coussens, Anna K., et al. "Classification of early tuberculosis states to guide research for improved care and prevention: an international Delphi consensus exercise." The Lancet Respiratory Medicine (2024).

• Pai, Madhukar, Puneet K. Dewan, and Soumya Swaminathan. "Transforming tuberculosis diagnosis." Nature Microbiology 8.5 (2023): 756-759.

• Yanes-Lane, Mercedes, et al. "Tuberculosis preventive therapy for people living with HIV: A systematic review and network meta-analysis." PLoS Medicine 18.9 (2021):

e1003738.

• Branigan, David. “2023 Pipeline Report: Tuberculosis Diagnostics.” Treatment Action Group (2023).

2. Approach Research projects applied under this NOFO should reflect the applicant’s current and projected capacities and capabilities in implementing research to prevent TB transmission, find cases, and understand the spectrum of TB disease in high-burden TB settings and in all populations, including those who are at increased/higher risk for TB. Essential for the conduct of these activities is the institutional and investigator capacity necessary to perform this work. Applicants are encouraged to request support for the development of local research capacity necessary for the conduct of the proposed study/studies, and to propose studies that are feasible with maximum impact within the local capacity and context.

It is expected the research findings will be broadly disseminated and translated into public health practice to facilitate the development and implementation of new and better program models, or program improvement strategies, with immediate implementation within local communities of practice. There should be an opportunity to look at real-time data and the possibility of sharing early findings with programs to make real-time impact.

Recipient(s) will be expected to have the capacity to be able to conduct evaluation and research that assesses patient or population-level outcomes and the determinants and/or risk factors of those outcomes within clinical and community TB programs. Capacity in this context includes any necessary technical knowledge and skills required to support research activities (i.e., clinical, decentralized, and/or laboratory-based diagnostic expertise).

This NOFO includes two thematic components: Component A “Halt Progression of TB Disease” and Component B “Case Finding and Course of TB Disease.” Objectives specific to each thematic component are stated below. Applicants may apply to one or both thematic components. If applying for both thematic components A and B, applicant must submit a scientifically distinct and separate application for each thematic component.

Application for each thematic component should be completed based on the application instructions in Section IV.

Objectives/Outcomes The expected objectives for each thematic component are:

COMPONENT A

• Halt Progression of TB Disease – Break the cycle of TB transmission through prevention strategies focusing on TPT with or without nutritional support:

o Develop and test innovative strategies to improve/optimize TPT regimens beyond PLHIV, including among TB contacts, healthcare workers, pregnant and breastfeeding women, and those with a risk of TB acquisition related to contact with TB patients.

o Define the duration of TPT efficacy for different TB disease burden settings.

o Assess the utility of repeat TPT, including after subsequent exposure.

o Assess the impact of the combination of TPT and nutrition to prevent TB disease.

o Explore and optimize innovative nutrition support strategies for TB disease prevention among those on TPT.

o Assess financial and disease implications of nutrition support as TB disease prevention for those on TPT.

COMPONENT B

• Case Finding and Course of TB Disease – Improve/optimize case finding and understand the spectrum of TB disease:

o Improve the quality and feasibility of contact tracing.

o Use of innovative approaches like social networks for TB contact tracing and case finding.

o Evaluate the effectiveness of new tools (e.g., artificial intelligence (AI), diagnostic tools and tests, etc.), algorithms, and strategies for screening and diagnosis of TB in different settings (e.g., at different health entry points, communities, hotspots or high transmission areas, congregate settings, self-screening/testing, etc.).

o Improve detection of the spectrum of TB disease and the impact of asymptomatic TB in disease transmission.

o Understand the burden of post-TB lung disease and the extent to which TB is a contributing factor.

The expected short-term outcomes for each thematic component are:

COMPONENT A

• Halt Progression of TB Disease o Improved prioritization of patients for TPT based on the best combination of evidence-based risk factors.

o Improved understanding of TPT effectiveness over time and across various populations.

o Identification of feasibility and effectiveness of adding nutrition to TPT as an additional TB prevention strategy.

o Measurement of cost-effectiveness and health outcomes of nutrition support programs for TB prevention.

COMPONENT B

• Case Finding and Course of TB Disease o Increased yield of screening o Increased yield of laboratory-confirmed and diagnosed cases o Increased and/or earlier TB treatment initiation among those diagnosed o Increased knowledge about the course of TB disease, the contribution of asymptomatic TB in disease transmission, the burden of post-TB lung disease, and the contribution of TB on post-TB lung disease

The expected intermediate outcomes for each thematic component are:

COMPONENT A

• Halt Progression of TB Disease o Reduced TB infection o Reduced incidence of TB disease

COMPONENT B

• Case Finding and Course of TB Disease o Improved bacteriological confirmation and case detection for all forms of TB o Increased TPT initiation among contacts o Increased and/or earlier TB treatment initiation among those diagnosed o Scale-up of strategies for contact tracing o Improved use of molecular WHO-recommended rapid diagnostics (mWRDs) through routine or novel practices o Scale-up of interventions to diagnose asymptomatic TB giq3 Highlight giq3 Highlight o Identification and prediction of the progression of the disease o Improved integration of new tools and tests into routine practice o Adoption of successful approaches into national guidelines

The expected long-term outcomes for each thematic area are:

COMPONENT A

• Halt Progression of TB Disease o Reduced TB morbidity and mortality in high-burden settings and populations

COMPONENT B

• Case Finding and Course of TB Disease o Reduced TB morbidity and mortality in high-burden settings and populations

Applicants may propose other objectives with research activities, or outcomes from those listed above for each thematic component.

In furtherance of the underlying purposes of this NOFO, Recipient is expected to provide copies of and/or access to all data, software, tools, training materials, guidelines, and systems developed under this NOFO to Ministry of Health and other relevant stakeholders, including HHS/CDC, for appropriate use consistent with underlying authorities.

The project(s) should be registered at Home | ClinicalTrials.gov, as applicable.

Population of Focus The CDC Division of Global HIV and Tuberculosis (DGHT), Global Tuberculosis Branch (GTB) focuses on specific countries where GTB can apply core strengths to maximize impact.

For the purposes of this NOFO, applicants with experience, working relationships, and collaborative partners in one or more of the following countries (*bold signifies a GTB priority country) are strongly encouraged to apply:

*Botswana, Cambodia, Cameroon, Côte d’Ivoire, Democratic Republic of the Congo, *Eswatini, *Ethiopia, Ghana, *Haiti, *India, *Kenya, *Lesotho, *Malawi, *Mozambique, *Namibia, *Nigeria, Philippines, *Rwanda, *South Africa, South Sudan, *Tanzania, *Uganda, *Vietnam, *Zambia, and *Zimbabwe

CDC will only consider proposals including work in the countries listed above; if proposals include work in countries not listed above, they will not be considered for funding. Priority countries are high TB, drug-resistant TB (DR TB), and TB/HIV burden countries with a strong on the ground DGHT program presence. Proposals including work in countries signified as a GTB priority above (bolded with asterisk) will be preferred.

CDC encourages research proposals that are inclusive of all populations affected by TB without regard to race, ethnicity, gender identity, sexual orientation, and socioeconomic status. However, given that TB disproportionally affects some populations at increased/higher risk, proposals that include (but are not limited to) the following populations at increased/higher risk for TB will be prioritized: persons exposed to active TB disease (household contacts and social contacts), children, pregnant and breastfeeding women, PLHIV, racial and ethnic minorities, healthcare workers, older adults, migrants or mobile populations, and those with co-morbid health conditions that increase the risk for TB or complicate TB treatment and care (e.g., diabetes https://clinicaltrials.gov/ https://www.cdc.gov/global-hiv-tb/php/where-we-work/index.html mellitus, undernutrition, alcohol use disorders, substance use disorders, other respiratory diseases). Populations at increased/higher risk for TB may also include persons living in rural areas or underserved neighborhood, who often encounter barriers to accessing healthcare services. TB also intersects with a variety of social factors: including unstable housing, food security, poverty, incarceration, and inadequate education; proposals that account for these factors will also be prioritized.

Collaboration/Partnerships The specific activities submitted as part of this NOFO should take place in high-burden TB settings. The recipient(s) will be expected to collaborate not only with CDC, but also with other partners, including (but not limited) to local Ministries of Health and WHO, to avoid duplication and promote synergies across proposed or planned activities. The recipient(s) will be expected to work closely with local and international agencies or organizations and other government entities responsible for engaging in the global elimination of TB.

Applicants should clearly specify how local partners will lead or assist these projects, how research capacity will be strengthened at local institutions, and how research findings will be disseminated to have maximum impact on public health.

Evaluation/Performance Measurement The application should include measurable goals and aims based on a 5-year research project period. The recipient will establish specific, measurable, achievable, realistic, time-phased, inclusion, and equitable (SMARTIE) project objectives for each activity described in the application’s project plan, and describe the development and implementation of project performance measures based on specific programmatic objectives.

The overall CDC Evaluation and Performance Measurement Strategy will focus on both process and outcome evaluation. Process evaluation is conducted to monitor activities during the implementation and operation of a program while an outcome evaluation examines the long-term successes and accomplishments of a program.

A plan for study activation visits (SAV) for each project to be conducted by the study team should be included with the application. The SAV is required to ensure that the proposed activities have met all regulatory requirements to begin the data collection phase of the research.

The overall objective of the SAV is to assess the readiness level of the staff and research sites from the perspective of protection of human subjects and adherence to the research protocol.

CDC staff will join the SAV.

A plan for ongoing monitoring of study activities should also be included in the application, including investigator monitoring of regulatory compliance, data quality, and laboratory quality, as applicable to the proposed research.

A timeline with measures of study progress should be described in the application. Progress towards those measures will be reported monthly, annually, and at project closeout.

Data use and data sharing agreements should be developed at the time of individual protocol development. It is expected all data should be de-identified and retained at CDC until all analyses are completed, and planned manuscripts are published. All data should be archived under the CDC retention policy guidelines.

Translation Plan

The application should include a timeline for completing the report of the main research findings and for developing and implementing a plan in collaboration with all relevant partners to disseminate the results/findings. This plan should include a process for sharing data, adapting project instruments and training materials that are relevant for programmatic use, and making these widely available to the Ministries of Health and other local partners, and to the global public health community. The plan should be specific to the project’s objectives and be designed to ensure that the research findings can be utilized rapidly and broadly for maximum public health impact.

In addition, the recipient(s) will be expected to pursue dissemination avenues in public domains, such as workshops, regional meetings, and through informal channels (e.g., website, newsletters). Use of public health journals, as well as national and international conferences should be pursued to share with global TB partners to the greatest extent possible the best practices. Identified best practices could be used by other countries to improve their national TB programs for the total treatment cascade.

3. Funding Strategy N/A

Section II. Award Information Funding Instrument Type:

CA (Cooperative Agreement) A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed:

New - An application that is submitted for funding for the first time. Includes multiple submission attempts within the same round.

Estimated Total Funding:

$10,000,000 Year 1: $2,000,000 Year 2: $2,000,000 Year 3: $2,000,000 Year 4: $2,000,000 Year 5: $2,000,000

Anticipated Number of Awards:

The Approximate Total Fiscal Year Funding amount for Year 1 is $2,000,000. The expected number of awards is up to two.

For this NOFO, applicants should develop a proposal to spend up to $1,000,000 for one thematic component per budget year. Applications proposing funding in excess of $1,000,000 for Year 1 per thematic component will be deemed “nonresponsive” and will not move forward to scientific peer review.

Awards issued under this NOFO are contingent on the availability of funds and submission of a sufficient number of meritorious applications.

Award Ceiling:

$2,000,000 Per Budget Period

Award Floor:

$0 Per Budget Period

Total Period of Performance Length:

5 year(s)

Throughout the Period of Performance, CDC's commitment to continuation of awards will depend on the availability of funds, evidence of satisfactory progress by the recipient (as documented in required reports), and CDC’s determination that continued funding is in the best interest of the Federal government.

HHS/CDC grants policies as described in the HHS Grants Policy Statement (https://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf) will apply to the applications submitted and awards made in response to this NOFO.

If you are successful and receive a Notice of Award, in accepting the award, you agree that the award and any activities thereunder are subject to all provisions of 45 CFR Part 75, currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Section III. Eligibility Information

1. Eligible Applicants Eligibility Category:

00 (State governments)

01 (County governments)

02 (City or township governments)

04 (Special district governments)

05 (Independent school districts)

06 (Public and State controlled institutions of higher education)

07 (Native American tribal governments (Federally recognized))

08 (Public housing authorities/Indian housing authorities) https://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf

11 (Native American tribal organizations (other than Federally recognized tribal governments))

12 (Nonprofits having a 501(c)(3) status with the IRS, other than institutions of higher education)

13 (Nonprofits without 501(c)(3) status with the IRS, other than institutions of higher education)

20 (Private institutions of higher education)

22 (For profit organizations other than small businesses)

23 (Small businesses)

25 (Others (see text field entitled "Additional Information on Eligibility" for clarification))

99 (Unrestricted (i.e., open to any type of entity above), subject to any clarification in text field entitled "Additional Information on Eligibility")

Additional Eligibility Category:

The following types of Higher Education Institutions are always encouraged to apply for CDC support as Public or Private Institutions of Higher Education:

Hispanic-serving Institutions

Historically Black Colleges and Universities (HBCUs)

Tribally Controlled Colleges and Universities (TCCUs)

Alaska Native and Native Hawaiian Serving Institutions

Nonprofits (Other than Institutions of Higher Education):

Nonprofits (Other than Institutions of Higher Education)

Governments:

Eligible Agencies of the Federal Government

U.S. Territory or Possession

Other:

Faith-based or Community-based Organizations

Regional Organizations

Foreign Organizations: a Foreign Organization is a public or private organization, whether non-profit or for-profit, located in a country other than the United States (U.S.) and its territories that is subject to the laws of the country in which it is located, irrespective of the citizenship of project staff or place of performance.

Bona Fide Agents: A Bona Fide Agent is an agency/organization identified by the state as eligible to submit an application under the state eligibility in lieu of a state application. If applying as a bona fide agent of a state or local government, a legal, binding agreement from the state or local government as documentation of the status is required. Attach with "Other Attachment Forms."

Federally Funded Research and Development Centers (FFRDCs): FFRDCs are operated, managed, and/or administered by a university or consortium of universities, other not-for-profit or nonprofit organization, or an industrial firm, as an autonomous organization or as an identifiable separate operating unit of a parent organization. A FFRDC meets some special long-term research or development need which cannot be met as effectively by an agency's existing in-house or contractor resources. FFRDC's enable agencies to use private sector resources to accomplish tasks that are integral to the mission and operation of the sponsoring agency. For more information on FFRDCs, go to https://gov.ecfr.io/cgi-bin/searchECFR.

2. Foreign Organizations Foreign Organizations are eligible to apply.

Foreign (non-US) organizations must follow policies described in the HHS Grants Policy Statement (http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf), and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide. International registrants can confirm UEI by viewing the organizational registration on SAM.gov. Special Instructions for acquiring a Commercial and Governmental Entity (NCAGE) Code: NCAGE Tool / Products / NCS Help Center (nato.int).

Foreign components of U.S. Organizations are eligible to apply.

For this announcement, applicants may include collaborators or consultants from foreign institutions. All applicable federal laws and policies apply.

3. Additional Information on Eligibility N/A

4. Justification for Less than Maximum Competition N/A

5. Responsiveness Any application that does not fully respond to the items in this section will be deemed "nonresponsive" and will not be moved forward for scientific peer review:

• If the application proposes funding in excess of $1,000,000 for the first year (12-month budget period) per thematic component and each subsequent 12-month budget period (direct and indirect).

• If the application is incomplete, meaning required elements of the application package are missing. The applicant will be notified that the application did not meet submission requirements.

• Late submissions will be considered non-responsive. See Part 1. Overview Information - Key Dates, for more information on Submission Dates and Time.

• Total amount of appendices should not include more than 50 pages. For this purpose, all appendices must have page numbers and must be clearly identified in the Table of Contents.

https://gov.ecfr.io/cgi-bin/searchECFR?ob=r&idno=&q1=FFRDC&r=&SID=1510a9feb7999d185d40b026ad998cc0&mc=true http://www.hhs.gov/asfr/ogapa/aboutog/hhsgps107.pdf https://eportal.nspa.nato.int/Codification/Support/en/Products/NCAGE/ https://eportal.nspa.nato.int/Codification/Support/en/Products/NCAGE/ https://am.grantsolutions.gov/foa/#/announcements/foa-content?foaId=28273:~:text=Key%20Date-,Key%20Dates,-Publication%20Date%3A https://am.grantsolutions.gov/foa/#/announcements/foa-content?foaId=28273:~:text=Key%20Date-,Key%20Dates,-Publication%20Date%3A

6. Required Registrations Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Unique Entity Identifier (UEI) number in order to begin each of the following registrations.

PLEASE NOTE: Effective April 4, 2022, applicants must have a Unique Entity Identifier (UEI) at the time of application submission. The UEI replaced the Data Universal Numbering System (DUNS) and is generated as part of SAM.gov registration. Current SAM.gov registrants have already been assigned their UEI and can view it in SAM.gov and Grants.gov. Additional information is available on the GSA website, SAM.gov, and Grants.gov-Finding the UEI.

(Foreign entities only): Special Instructions for acquiring a Commercial and Governmental Entity (NCAGE) Code: NCAGE Tool / Products / NCS Help Center (nato.int).

System for Award Management (SAM) – must maintain current registration in SAM (the replacement system for the Central Contractor Registration) to be renewed annually, SAM.gov.

Grants.gov eRA Commons

All applicant organizations must register with Grants.gov. Please visit www.Grants.gov at least 30 days prior to submitting your application to familiarize yourself with the registration and submission processes. The one-time registration process will take three to five days to complete.

However, it is best to start the registration process at least two weeks prior to application submission.

All Senior/Key Personnel (including Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing Principal Investigator (PD/PI) eRA Commons account is affiliated with the eRA commons account of the applicant organization. All registrations must be successfully completed and active before the application due date. Applicant organizations are strongly encouraged to start the eRA Commons registration process at least four (4) weeks prior to the application due date. ASSIST requires that applicant users have an active eRA Commons account in order to prepare an application. It also requires that the applicant organization's Signing Official have an active eRA Commons Signing Official account in order to initiate the submission process.

During the submission process, ASSIST will prompt the Signing Official to enter their Grants.gov Authorized Organizational Representative (AOR) credentials in order to complete the submission, therefore the applicant organization must ensure that their Grants.gov AOR credentials are active.

7. Universal Identifier Requirements and System for Award Management

(SAM)

All applicant organizations must obtain a Unique Entity Identifier (UEI) number as the Universal Identifier when applying for Federal grants or cooperative agreements. The UEI number is a twelve-digit number assigned by SAM.gov. An AOR should be consulted to determine the appropriate number. If the organization does not have a UEI number, an AOR should register through SAM.gov. Note this is an organizational number. Individual Program https://www.gsa.gov/about-us/organization/federal-acquisition-service/technology-transformation-services/integrated-award-environment-iae/iae-systems-information-kit/unique-entity-id-is-here https://sam.gov/content/home https://grantsgovprod.wordpress.com/2021/09/14/how-to-find-an-applicants-uei-within-grants-gov/ https://grantsgovprod.wordpress.com/2021/09/14/how-to-find-an-applicants-uei-within-grants-gov/ https://eportal.nspa.nato.int/Codification/Support/en/Products/NCAGE/ https://sam.gov/content.gov https://grants.gov https://public.era.nih.gov/commons https://www.Grants.gov

Directors/Principal Investigators do not need to register for a UEI number.

Additionally, organizations must maintain the registration with current information at all times during which it has an application under consideration for funding by CDC and, if an award is made, until a final financial report is submitted or the final payment is received, whichever is later.

SAM.gov is the primary registrant database for the Federal government and is the repository into which an entity must provide information required for the conduct of business as a recipient.

Additional information about registration procedures may be found at SAM.gov and the SAM.gov Knowledge Base.

If an award is granted, the recipient organization must notify potential sub-recipients that no organization may receive a subaward under the grant unless the organization has provided its UEI number to the recipient organization.

8. Eligible Individuals (Project Director/Principal Investigator) in Organizations/Institutions Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization to develop an application for support. CDC does not make awards to individuals directly. Individuals from organizations that are uniquely prepared to examine research relevant to undeserved groups, including sexual orientation and gender identity minorities as well as individuals with disabilities are always encouraged to apply.

9. Cost Sharing This NOFO does not require cost sharing as defined in the HHS Grants Policy Statement (http://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf).

10. Number of Applications As defined in the HHS Grants Policy Statement, (https://www.hhs.gov/sites/default/files/grants/grants/policies-regulations/hhsgps107.pdf), applications received in response to the same Notice of Funding Opportunity generally are scored individually and then ranked with other applications under peer review in their order of relative programmatic, technical, or scientific merit. HHS/CDC will not accept any application in response to this NOFO that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application.

Applicants may apply to one or both thematic components (A/B) by submitting scientifically distinct and separate applications.

The applicant should make sure to title each of the applications to be distinctly different for the system to accept both the applications.

If more than one applicant from the same institute applies, there will only be one award made per institution to ensure diversity across recipients.

https://sam.gov/content/home https://nam12.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.fsd.gov%2Fgsafsd_sp%3Fid%3Dgsa_kb_view2%26kb_id%3Df66d8e6cdb76d4100d73f81d0f9619c6&data=04%7C01%7Ccshifflett%40dminc.com%7C8eee7a2adab549a3b3c008d925e9a364%7Cdb7ac9ef779d46e59bca00509580ad6b%7C0%7C0%7C637582507851821018%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C1000&sdata=UrR%2B%2FM2wWF2fZG05Z8O6JS2C3FXXSl%2F7B3%2FB45XHRrg%3D&reserved=0

Section IV. Application and Submission Information

1. Address to Request Application Package Applicants will use a system or platform to submit their applications through Grants.gov and eRA Commons to CDC. ASSIST, an institutional system to system (S2S) solution, or Grants.gov Workspace are options. ASSIST is a commonly used platform because, unlike other platforms, it provides a validation of all requirements prior to submission and prevents errors.

To use ASSIST, applicants must visit https://public.era.nih.gov where you can login using your eRA Commons credentials, and enter the Notice of Funding Opportunity Number to initiate the application, and begin the application preparation process.

If you experience problems accessing or using ASSIST, you can refer to the ASSIST Online Help Site at: https://era.nih.gov/erahelp/assist. Additional support is available from the NIH eRA Service desk via: http://grants.nih.gov/support/index.html

• Email: commons@od.nih.gov

• Phone: 301-402-7469 or (toll-free) 1-866-504-9552.

Hours: Monday - Friday, 7 a.m. to 8 p.m. Eastern Time, excluding Federal holidays.

2. Content and Form of Application Submission Application guides for FORMS-H application packages are posted to the How to…