National Institutes of Health (NIH)
R01 Research Project Grant
November 08, 2024 - This PAR has been reissued as PAR-25-107.
NOT-OD-23-012 Reminder: FORMS-H Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available
NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022
This Funding Opportunity Announcement (FOA) solicits grant applications proposing to utilize bacteria, archaebacteria, bacteriophages, or other non-oncolytic viruses and their natural products to study the underlying mechanisms of the complex interactions between microorganisms, tumors, and the immune system, and to explore their clinical potential for cancer imaging, therapeutics or diagnostics. Projects can focus on using microorganisms as anti-tumor agents, as activators of anti-tumor immunity, or as delivery vehicles for treatment, diagnosis, or imaging, complementing or synergizing with existing tools and approaches. This FOA will support basic mechanistic and preclinical studies in cell culture and animal models. Applicants are encouraged to address both the microbial and tumor aspects of microbial tumor interactions relevant to microbial-based cancer therapy (including therapies for oral cancer), tumor imaging, tumor detection, or diagnosis.
This funding opportunity is part of a broader NCI-sponsored research on microbial based cancer therapy.
Not Applicable
| Application Due Dates | Review and Award Cycles | ||||
|---|---|---|---|---|---|
| New | Renewal / Resubmission / Revision (as allowed) | AIDS | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
| June 05, 2022 * | July 05, 2022 * | Not Applicable | November 2022 | January 2023 | April 2023 |
| October 05, 2022 * | November 05, 2022 * | Not Applicable | March 2023 | May 2023 | July 2023 |
| February 05, 2023 * | March 05, 2023 * | Not Applicable | July 2023 | October 2023 | December 2023 |
| June 05, 2023 * | July 05, 2023 * | Not Applicable | November 2023 | January 2024 | April 2024 |
| October 05, 2023 * | November 05, 2023 * | Not Applicable | March 2024 | May 2024 | July 2024 |
| February 05, 2024 * | March 05, 2024 * | Not Applicable | July 2024 | October 2024 | December 2024 |
| June 05, 2024 * | July 05, 2024 * | Not Applicable | November 2024 | January 2025 | April 2025 |
| October 05, 2024 * | November 05, 2024 * | Not Applicable | March 2025 | May 2025 | July 2025 |
| February 05, 2025 * | March 05, 2025 * | Not Applicable | July 2025 | October 2025 | December 2025 |
All applications are due by 5:00 PM local time of applicant organization.
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).
Conformance to all requirements (both in the Application Guide and the FOA) 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.
Applications that do not comply with these instructions may be delayed or not accepted for review.
Purpose
The purpose of this FOA is to encourage grant applications to study novel microbial-based cancer therapy (including therapies for oral cancer), imaging detection, and diagnosis strategies to overcome the limitations of inadequate conventional cancer imaging and therapies. Solutions may utilize bacteria, archaebacteria, bacteriophages, and other microorganisms and their products (but not oncolytic viruses).
This FOA utilizes the R01 mechanism and is suitable for projects studying the underlying mechanisms of the complex interactions between microorganisms and tumors and the immune system, their therapeutic use, their utilization as delivery vehicles for cancer treatment, and imaging to complement or synergize with current cancer therapy and imaging. This FOA will accept basic, mechanistic, and/or more applied preclinical studies in cell culture, animal models, or in vivo tumors including oral cancer. The R01 mechanism is suitable for projects where supportive preliminary data are available.
This FOA runs in parallel with an FOA of identical scientific scope, PAR-22-086, which uses the Exploratory/Developmental Grant (R21) mechanism.
Background and Rationale
Background and rationale Early clinical observations in the 1880s by Coley pioneered the concept of using bacteria (or their products) as microbial-based cancer therapy and demonstrated that tumor regression coincided with natural bacterial infections, leading to the first use of microbes as antitumor agents. With the development of the more effective and better-understood radiation therapy, and later, chemotherapy-based cancer therapies, this approach was largely abandoned in the 1930s and microbial-based therapy has remained an elusive goal. However, standard cancer therapies have several major disadvantages, including the rarity of complete and sustained remissions of most solid tumors, the development of resistance, frequent failure to clear micrometastases, and relapse. To overcome the limitations of current cancer imaging and therapies, microbial tumor homing and colonization, oncolysis, and activation of anti-tumor immunity are being explored as alternative strategies. Because Bugs as Drugs are potentially self-regenerated cancer therapeutics, the approach may address cancer therapy needs for global health and low resource settings
Mechanisms of Microbial-based Cancer Therapy
Several facultative or obligate anaerobic bacteria possess unique natural or genetically engineered potential to overcome traditional therapeutic limitations by selectively targeting tumors and/or anti-tumor immunity. For example, Salmonella, Escherichia coli, Clostridium, Bifidobacterium, or Listeria are naturally capable of selective homing to tumors when systemically administered, resulting in high levels of colonization and replication in locally hypoxic tumor microenvironments or within tumor tissues leading to killing tumor cells, reprograming the immune system to target cancer cells. Therapeutic bacteria can stimulate the production or localized in the tumor of CD8+T lymphocytes or block immune checkpoint pathways.
Microbial products (including microbial toxins) and microbial metabolites are also associated with anti-tumor activities. Microbial metabolites can inhibit tumor cells growth in vitro, modulate T-cell response to checkpoint inhibitors, reduce carcinogenic inflammation, inhibit tumor cell invasion and migration, suppress histone deacetylase activity, and induce apoptosis
Cancer Clinical Needs and Challenges
There is a need for improved cancer therapies (including therapies for oral cancer), especially for solid tumors where conventional therapies often fail under conditions such as poorly vascularized tumors with inadequate blood perfusion, hypoxia, nutritional deprivation, tumor interstitial pressure, immature lymphatic system, immunosuppressive microenvironment, tumor dormancy, distant tumor metastasis, slowly dividing cells resistant to treatment, or islands of microinvasive tumor cells buried within normal tissues and drug resistance. In addition, it is important to develop new cancer immunotherapy modalities. Among the most attractive characteristics of microbial agents for anticancer therapies is their capacity for tumor-specific targeting and activation of the immune system. Thus, for example, it may be possible to develop a bacteria-based cancer treatment platform for in situ release of immune checkpoint inhibitors.
Recent research advancements in bacterial anti-cancer activities
Multiple studies have demonstrated that anaerobic microorganisms have the unique ability to grow selectively in hypoxic immunosuppressed areas of solid tumors that often are not accessible to drugs. More recently, an integrated bacterial cancer treatment approach utilizing a single multi-function, bacterial payloads for cancer imaging, activation of the immune system, and tumor cell killing were demonstrated. A white paper on the Challenges and Opportunities of Microbial Anti-Cancer Therapy and Prevention summarizes the potential of microbial therapy and recent research advances. Promising results from these studies and the availability of sophisticated gene-editing technology, offer the prospect of developing new concepts and strategies for the use of microbial therapies to mitigate or solve unmet clinical needs. Other studies have shown that gut microbial metabolites can modify the transcription, epigenetics, and metabolism of host immune cells, which can be utilized to activate the immune system. While recent research demonstrates the potential of microbial-based cancer therapy, more research is needed to realize this potential and to bring novel microbial-based therapies to the clinic especially for conditions where conventional cancer therapies are inadequate
Scope and Research Objectives of this FOA
The complex nature of the interactions between the microbe, tumor, and immune system requires multidisciplinary collaboration between microbiologists, cancer researchers, and immunologists with the goal of developing innovative approaches to improve our understanding of this system and utilize it for cancer therapy. This initiative seeks to support studies of tumor-microbe interactions needed to develop new cancer imaging and therapy strategies that address unmet clinical needs. The multi-disciplinary research teams are expected to conduct cutting-edge research aimed at advancing pre-clinical development of novel bacteria-based anticancer therapeutic or diagnostic agents. The goal is to conduct research that could have a major impact on cancer therapy and related research
Multi-disciplinary research teams are expected to conduct cutting-edge research within the scope of the FOA (see above) aimed at advancing pre-clinical development of novel microbial-based anticancer therapeutic agents, cancer imaging, and diagnostics technologies, or to study the complex biology involved in the interplay of microbe-tumor-immune system interactions. Applicants applying to this FOA are expected to address both the microbial and the tumor aspects of microbial cancer therapy, the goal is to conduct research that could have a major impact on cancer therapy and related research.
Potential areas of research may include, but are not limited to:
- The basic biology of the underlying microbe-tumor interactions such as invasion, lysis, antigen presentation, and other microbe-initiated tumor cell death.
- Microbial (or microbial products) interactions with the immune system, including microbial induction of specific antitumor immunity for primary and metastatic tumors, including immune engagement, more robust tumor antigen presentation, immunostimulatory constructs such as “trojan horse” delivery of novel antigen expressions to overcome immune suppression.
- Tumor cell inactivation (including colonization, disrupting cell function, activation of cell death programs, etc.)
- Novel microbial species that might have therapeutic/imaging potential e.g., soil, aquatic and plant, bacteria, archaebacteria, bacteriophages, and other non-oncolytic viruses as potential therapeutics to overcome the issues of microbial pathogenicity and clearance by the immune system
- The dynamics of microbe-tumor interactions and biological factors limiting the effectiveness of microbial-based cancer therapy
- The molecular mechanisms by which microbes and microbial products modulate cancer treatment responsiveness
- Interaction between microbes or microbial products with the immune system to develop novel cancer immunotherapies
- Novel microbial cancer-targeting approaches
- Novel microbial anti-cancer products (including microbial toxins) and microbial metabolites
- Integrated multi-function bacterial payload for cancer imaging and therapy
- Microbial bioreactors for self-supplied tumor localized antitumor agents.
- Microbial based imaging for cancer detection and diagnosis
- Approaches for treating poorly vascularized hypoxic solid tumors or islands of microinvasive tumor cells buried within normal tissue.
- Approaches for treating distant tumor metastasis
- Activation of anti-tumor immunity (including expressing foreign proteins on the surface of the tumor cell)
- Microbial based asymptomatic cancer detection
- Activation of dormant tumor cells
- Natural or engineered non-pathogenic microbes with therapeutic potential to selectively infect and treat cancers of various organs, solid tumors, metastasis, microinvasion, hypoxic or poorly vascularized tissues not accessible to chemical or monoclonal antibody drugs;
- Targeting specificity for primary and metastatic tumors, hypoxic tissues, poorly vascularized tissues, neovascularization, or slowly dividing/dormant cancer cells
- Novel microbial drug delivery approaches and microbial payload delivery of anti-cancer drugs, imaging agents, radiotherapy, other tumor-relevant payloads.
- Long-lasting approaches to anti-cancer immunity, such as the surface expression of foreign proteins to induce a strong response or overcome immune suppression.
- Tumor cell inactivation, such as colonization, cell function disruption, programmed cell death activation;
- Approaches to balance among microbe-initiated immune stimulation, cancer neoantigen presentation, therapeutic microbes clearance, and microbial pathogenicity for more nearly optimal safety and efficacy of microbial-based anti-cancer agents;
- Strategies to prevent a recurrence, such as prolonging microbial therapy efficacy with libraries of “foreign” antigens to restimulate the immune system after loss of initial antigen efficacy.
Microbial-based Cancer Detection and Diagnosis
Microbial species with cancer-selective homing to tumors and colonization have the potential to overcome traditional cancer detection and diagnosis limitations, especially for asymptomatic cancers. Microbes are potentially useful for tumor detection and diagnosis and may provide information about the tumor organ site and characteristics, which facilitates cancer staging, management, and treatment
Microbial-based Cancer Detection and Diagnosis Specific Research Areas:
- Enhancing bacterial tumor colonization for cancer detection and diagnosis applications
- Analysis of microbial-cancer specific organ targeting for cancer detection and diagnosis
- Microbial-based cancer diagnosis/detection technologies (including blood microbial “biomarkers”, DNA, metabolite, or other microbial characteristics
- Manipulation of the microbial tumor population to improve cancer therapy
- Microbial labeling for microbial-based cancer imaging detection
- Microbial-based cancer distant tumor metastasis detection
- Microbial-based detection of asymptomatic cancers
Microbial-based Cancer Imaging
Many facultative or obligate anaerobic bacteria and engineered bacteria are capable of selective homing and penetrating tumors when systemically administered which is potentially useful for tumor in vivo imaging. By using tumor-specific colonization properties of labeled bacteria, it may be possible to enhance the resolution and sensitivity of various in vivo tumor imaging modalities including CT, MRI, PET, SPECT, ultrasound, optical imaging, etc. for tumor margin detection/excision.
Cancer Imaging Specific Research Areas:
- Enhancing bacterial tumor colonization and penetration for imaging applications
- Microbial-specific contrast agents and molecular imaging probes for the various in vivo imaging modalities
- Microbial labeling for microbial-based cancer detection
- Developing precise spatiotemporal resolution (including computation and image manipulation) of microbial-based cancer imaging
- Microbial-based image-guided tumor margin detection/accurate excision
- Microbial-based cancer distant tumor metastasis imaging
- Microbial-based image-guided drug, gene, or radiation therapy in vivo
Researchers who emphasize on applying cancer imaging technologies for assessing in vivo changes occurred in the local tumor microenvironment or tumor-induced systemic environment as the result of microbial based intervention should consider applying to PAR-21-294, Molecular Imaging of Inflammation in Cancer (R01 Clinical Trial Not Allowed).
NCI's Center for Global Health
Microbial-based cancer therapy may provide new opportunities, because of the relative simplicity of microbial culturing, microbes may have the potential to be self-regenerating cancer therapeutics, the ultimate sustainable cancer treatment for Low and Low Middle Income Countries (LMIC).
LMIC. Examples of the Center for Global Health specific topics of interest may include:
- Low-cost microbial-based cancer therapies and diagnosis for low resource settings.
- Novel cancer-targeting approaches suitable for LMICs
- Microbial cancer therapy delivery approaches suitable to LMICs
National Institute of Dental and Craniofacial Research (NIDCR)
NIDCR support for this initiative includes research and development of bacterial anticancer agents for the treatment of cancers of the oral cavity, oropharynx, and salivary glands. Therefore, in addition to the general areas of research listed above, examples of NIDCR-specific topics include:
- Microbial-based treatment of oral, salivary gland, or oropharyngeal cancers
- Microbial delivery of anti-cancer therapeutics to oral, salivary gland, or oropharyngeal tissues
- Microbial manipulation of the oral microbiome to reduce the risk of developing cancers of the oral cavity, oropharynx, and salivary gland
- Microbial or microbial metabolite-based inhibition of HPV acquisition, infection, and persistence in the oral cavity to prevent oral cancers
- Microbial-based cancer imaging and applications solely focused on “microbial community-level analysis” will be considered non-responsive for NIDCR.
Team Structure
This FOA encourages the formation of multidisciplinary teams with expertise in microbiology, immunology, and molecular/cellular cancer biology from diverse academic, clinical, or industrial sources to ensure breadth sufficient to accomplish project goals. Each application should address how all project elements are represented, assignment of project modules, and performance targets for completion of all steps.
Non-responsive Applications
Applications that propose the following will be deemed non-responsive to mission of this FOA and not reviewed:
- Research on oncolytic viruses (for NCI).
- Microbial-based cancer imaging and applications solely focused on “microbial community-level analysis” (for NIDCR).
See Section VIII. Other Information for award authorities and regulations.
Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
Renewal
Resubmission
Revision
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Not Allowed: Only accepting applications that do not propose clinical trials.
Need help determining whether you are doing a clinical trial?
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
The maximum project period is 5 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.
1. Eligible Applicants
Higher Education Institutions
- Public/State Controlled Institutions of Higher Education
- Private Institutions of Higher Education
The following types of Higher Education Institutions are always encouraged to apply for NIH 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
- Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)
Nonprofits Other Than Institutions of Higher Education
- Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
- Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
For-Profit Organizations
- Small Businesses
- For-Profit Organizations (Other than Small Businesses)
Local Governments
- State Governments
- County Governments
- City or Township Governments
- Special District Governments
- Indian/Native American Tribal Governments (Federally Recognized)
- Indian/Native American Tribal Governments (Other than Federally Recognized)
Federal Government
- Eligible Agencies of the Federal Government
- U.S. Territory or Possession
Other
- Independent School Districts
- Public Housing Authorities/Indian Housing Authorities
- Native American Tribal Organizations (other than Federally recognized tribal governments)
- Faith-based or Community-based Organizations
- Regional Organizations
- Non-domestic (non-U.S.) Entities (Foreign Institutions)
Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
- System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
- NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
- Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. SAM registrations prior to fall 2021 were updated to include a UEI. For applications due on or after January 25, 2022, the UEI must be provided on the application forms (e.g., FORMS-G); the same UEI must be used for all registrations, as well as on the grant application.
- Dun and Bradstreet Universal Numbering System (DUNS) – Organization registrations prior to April 2022 require applicants to obtain a DUNS prior to registering in SAM. By April 2022, the federal government will stop using the DUNS number as an entity identifier and will transition to the Unique Entity Identifier (UEI) issued by SAM. Prior to April 2022, after obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
- eRA Commons - Once the unique organization identifier (DUNS prior to April 2022; UEI after April 2022) is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
- Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
2. Cost Sharing
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:
- A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
- A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
- An application that has substantial overlap with another application pending appeal of initial peer review (see 2.3.9.4 Similar, Essentially Identical, or Identical Applications)
1. Requesting an Application Package
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
2. Content and Form of Application Submission
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.Letter of Intent
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
- Descriptive title of proposed activity
- Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
- Names of other key personnel
- Participating institution(s)
- Number and title of this funding opportunity
The letter of intent should be sent to:
Avi Rasooly, PhD
National Cancer Institute (NCI)
Telephone: 240-276-6196
Email: [email protected]
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing (DMS) Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
R&R or Modular Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Other Plan(s):
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims: Include a brief sub-section "Statement of Potential Impact" describing the expected potential of the proposed approach to transform cancer therapy and clinical practice. The following questions should be addressed with this statement.
- How the new approach provided by the proposed research is potentially transformative and why may it be expected to have a high impact on cancer therapy (i.e., describe the potentially transformative outcomes that might be realized should this approach succeed).
- If applicable, describe how will the proposed approach overcome limitations for currently available therapies or alternative approaches? (i.e., provide evidence to support the claim of effectiveness beyond currently available therapies).
Research Strategy: The Research Strategy should clearly describe or address the following:
- Rationale for choice of comparison groups to assess differences in cognitive changes as a function of cancer-related treatment, imaging or diagnosis.
- Clear justifications for the inclusion of specific cancer treatment regimens (chemotherapy, hormonal and/or molecular targeted therapies) in the research protocol.
- Clear justifications for the choice of microrganism used, cancer site, cancer stage, cognitive assessment approach and schedule for assessments.
- Sound recruitment strategies to obtain a broad range of cognitive ability via outreach/recruitment to understudied and demographically diverse samples (e.g., low socioeconomic status or educational attainment, rural, and race/ethnicity).
- Potential impact of the approach for conditions where conventional cancer therapies are inadequate, such as metastatic tumors, poorly vascularized, hypoxic, solid tumors, dormant or slowly dividing cells resistant to current interventions, islands of microinvasive tumor cells buried within normal tissues and brain tumors.
- If a preclinical animal model research project is proposed, then include:
- Description of the translational relevance of the model and the cognitive science paradigms being used.
- Justification of the translational relevance of the use of tumor-bearing or tumor naïve animal models.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.
- All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.
Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Foreign Institutions
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
3. Unique Entity Identifier and System for Award Management (SAM)
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
5. Intergovernmental Review (E.O. 12372)
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential fieldof the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the unique entity identifier (DUNS number or UEI as required) provided on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Requests of $500,000 or more for direct costs in any year
Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
1. Criteria
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Scored Review Criteria
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Significance
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Specific for this FOA: Does the application address a problem where conventional cancer therapies are inadequate, such as metastatic tumors, poorly vascularized, hypoxic, solid tumors, dormant or slowly dividing cells resistant to current interventions, islands of microinvasive tumor cells buried within normal tissues and brain tumors?
Investigator(s)
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Specific for this FOA: Does the application describe a multidisciplinary team with expertise in microbiology and cancer research? Does the team include expertise in relevant fields such as immunology, molecular or cellular cancer biology?
Innovation
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Approach
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Environment
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
Additional Review Criteria
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Protections for Human Subjects
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
Inclusion of Women, Minorities, and Individuals Across the Lifespan
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Biohazards
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Resubmissions
For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.
Renewals
For Renewals, the committee will consider the progress made in the last funding period.
Revisions
For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Applications from Foreign Organizations
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
Select Agent Research
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Resource Sharing Plans
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
Authentication of Key Biological and/or Chemical Resources:
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
2. Review and Selection Process
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review (CSR), in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications will receive a written critique.
Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
- Scientific and technical merit of the proposed project as determined by scientific peer review.
- Availability of funds.
- Relevance of the proposed project to program priorities.
3. Anticipated Announcement and Award Dates
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
1. Award Notices
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.
Recipients must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
2. Administrative and National Policy Requirements
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:
- Federalwide Research Terms and Conditions
- Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
- Acknowledgment of Federal Funding
If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions 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.
Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html
HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.
- Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.
- For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
- HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
- For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.
Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.
Not Applicable
Data Management and Sharing
Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.
Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.
3. Reporting
When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]
Avi Rasooly, PhD
National Cancer Institute (NCI)
Telephone: 240-276-6196
Email: [email protected]
(Cancer Therapy Applications)
Phil Daschner
National Cancer Institute (NCI)
Telephone: 240-276-6227
Email: [email protected]
(Cancer biology and basic research)
Luis Alejandro Salicrup, PhD
National Cancer Institute (NCI)
Telephone: 240-276-5799
Email: [email protected]
(Global Health)
Miguel Ossandon, PhD
National Cancer Institute (NCI)
Telephone: 240-276-5714
Email: [email protected]
(Microbial Based Cancer Diagnostics)
Yisong Wang, PhD
National Cancer Institute (NCI)
Telephone: [email protected]
Email:240-620-0690
(Microbial based Cancer Imaging)
Zhong Chen, MD, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-529-7083
Email: [email protected]
Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).
Sean Hine
National Cancer Institute (NCI)
Telephone: 240-276-6291
E-mail: [email protected]
Diana Rutberg, MBA
National Institute Of Dental & Craniofacial Research (NIDCR)
Phone: (301) 594-4798
E-mail: [email protected]
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.
and Human Services (HHS)
