Department of Health and Human Services
Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institute of Dental and Craniofacial Research (NIDCR)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Funding Opportunity Title

Advancing Cancer Immunotherapy by Mitigating Immune-Related Adverse Events (irAE) (U01 Clinical Trial Not Allowed)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-CA-19-044

Companion Funding Opportunity

None

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.121, 93.393, 93.353, 93.846, 93.847, 93.855

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) is associated with the Beau Biden Cancer Moonshot InitiativeSM that is intended to accelerate cancer research. Specifically, this FOA targets the following area designated as scientific priority by the Blue Ribbon Panel (BRP): Recommendation B. Create a translational science network devoted exclusively to immunotherapy approaches to treat and prevent adult cancers.

The purpose of this FOA is to support improved cancer immunotherapy research projects that reduce the incidence and/or severity of immune-related adverse events (irAEs) while retaining anti-tumor efficacy. Single investigators and/or multidisciplinary teams with expertise in mechanisms of cancer immunology, immune tolerance, irAEs, autoimmunity, and/or patient characterization and selection are encouraged to propose projects that utilize appropriate model systems, clinical samples, and expertise of these research communities. The specific objectives are to generate new ideas and approaches to better understand and thereby reduce the incidence and/or severity of irAEs resulting from cancer immunotherapy.

Depending on whether the scope of the irAE research is for adult or pediatric immunotherapy, these research projects will become components of the Immuno-Oncology Translational Network (IOTN) or the Pediatric Immunotherapy Discovery and Development Network (PI-DDN).

Key Dates
Posted Date

February 20, 2019

Open Date (Earliest Submission Date)

March 25, 2019

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

April 25, 2019, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.

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.

AIDS Application Due Date(s)

Not applicable

Scientific Merit Review

July/August 2019

Advisory Council Review

October 2019

Earliest Start Date

December 2019

Expiration Date

April 26, 2019

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow 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 the 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.


Table of Contents

Part 1. Overview Information
Part 2. Full Text of the Announcement

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

Part 2. Full Text of Announcement
Section I. Funding Opportunity Description

This funding opportunity announcement (FOA) has the overall goal of accelerating research advances to improve immunotherapy outcomes for diverse adult and pediatric cancers.  Specifically, this FOA is aimed at promoting strategies that will predict, prevent or ameliorate immune-related adverse events (irAEs). The overarching goal is to support studies aimed at generating improved cancer immunotherapies that reduce the incidence and/or severity of irAEs while retaining anti-tumor efficacy. Single investigators and/or multidisciplinary teams with expertise in mechanisms of cancer immunology, immune tolerance, irAEs, autoimmunity, and/or patient characterization and selection are encouraged to propose projects that utilize appropriate model systems, clinical samples, and expertise of these research communities.

Background

NCI convened the Blue Ribbon Panel (BRP) in 2016 to provide recommendations for achieving the Cancer Moonshot's goal of accelerating progress in cancer research, now called the Beau Biden Cancer Moonshot Initiative. The BRP was charged with assessing the state of the science in specific areas and identifying major research opportunities that could uniquely benefit from the support of the Cancer Moonshot and could lead to significant advances in our understanding of cancer and in how to intervene in its initiation and progression. The recommendations focused on areas in which a coordinated effort could profoundly accelerate the pace of progress in the fight against cancer and were not intended to replace existing cancer programs, initiatives, and policies already underway. The BRP final report was approved by the National Cancer Advisory Board and included a recommendation for establishing a translation science network devoted exclusively to discovering and evaluating novel immune-based approaches to treat and prevent adult cancers. The 21st Century Cures Act was signed into law in December 2016 dedicating new funds to support efforts associated with the Beau Biden Cancer Moonshot Initiative, including support for this FOA.

It is expected that research proposed in response to this FOA will engage a pool of scientists from diverse backgrounds, including those from underrepresented groups. In line with NIH-wide policies (NOT-OD-18-210), fostering diversity and addressing underrepresentation in the scientific research workforce is one of the key components of the NCI strategy to facilitate scientific discovery and enhance innovation.

Scientific Scope of this FOA

Advancing Cancer Immunotherapy by Mitigating Immune-Related Adverse Events (irAEs) Research Projects

Cancer immunotherapies including checkpoint inhibitors, adoptive cell transfer using ex vivo-stimulated tumor-infiltrating lymphocytes or genetically-engineered T cells, and immune modulators have led to durable long-term survival in subgroups of adult and pediatric cancer patients. However, systemic delivery of these therapies has also led to breaches in self-tolerance resulting in mild to severe inflammatory reactions across a variety of organ systems and in some instances, life-threatening autoimmunity. Instances of irAEs across multiple body sites including gastrointestinal tract, skin, kidney, pancreas, liver, pituitary, and central and peripheral nervous systems have been reported. While colitis, diabetes, hepatitis, pneumonitis, hypophysitis, epidermal necrolysis, and other irAEs are well documented, irAEs with rheumatic and musculoskeletal phenotypes are less well-characterized and are likely under-reported to date, since potentially any tissue can be injured by immunotherapies that may disrupt self-tolerance protection of normal tissues. The incidence and severity of irAEs has been shown in some cases to correlate with overall patient response and survival following checkpoint blockade, suggesting that both anti-tumor and autoimmune responses are sensitive to anti-checkpoint immunotherapy. Although treatment with steroids can sometimes reverse these irAEs, steroid-associated immunosuppression may compromise the anti-tumor activity of the immunotherapy. As checkpoint blockade and other immunotherapy approaches are expanded to more cancer indications and in ever-more-effective combinations, controlling non-specific inflammation and tissue-directed autoimmunity in the setting of immuno-oncology will be a critical goal for these next-generation cancer immunotherapies.

Checkpoint blockade using monoclonal antibodies targeting the CTLA-4 and PD-1/PD-L1 pathways have led to impressive anti-cancer responses and is revolutionizing cancer therapy. Interestingly, the spectrum of irAEs varies somewhat depending on which pathway is blocked.  For example, more gastrointestinal irAEs were associated with blocking CTLA-4 compared to blocking the PD-1/PD-L1. Thus, questions remain regarding how CTLA-4 and PD-1/PD-L1 checkpoint blockade remodels immune responses, such as whether the inflammatory responses represent non-specific immune activation or unmasking of occult autoimmune cells, as well as the role of tumor type and host genetics in determining the severity of response and the tissues/organs affected.  While CTLA-4 and PD-1/PD-L1 are the principal immune checkpoints currently targeted therapeutically, additional immune-suppressive checkpoint molecules such as lymphocyte-activation gene 3 (LAG-3), T cell immunoglobulin mucin 3 (TIM-3), VISTA, and CD47 as well as immune-activating checkpoint molecules such as 4-1BB and glucocorticoid-induced TNFR family related gene (GITR) will add to the immunotherapy armamentarium. As these additional checkpoint molecules are targeted for cancer immunotherapy, novel pathways leading to irAEs may be revealed and will need to be understood.  Answers to these questions may guide clinicians on how to better regulate off-target inflammatory responses without impeding anti-tumor immune responses. 

Another immunotherapy approach, using engineered chimeric antigen receptor (CAR) T cells targeted to specific tumor antigens, such as CD19, has been shown to be very effective in “redirected” killing of tumor cells in vitro and when transferred back into patients, and has been highly successful in treating certain blood cancers. Nonetheless, for most cancers, we know little about what antigens can be safely and effectively targeted to discriminate cancer from normal tissues. Thus, CAR T cell immunotherapy has been associated with “on-target, off-tumor” adverse events such as B cell aplasia when CAR T cells are designed to attack CD19-expressing B cell tumors. Additional toxicities associated with adoptive T-cell therapies include cytokine-release syndrome, neurotoxicity, and macrophage-activation syndrome. While one approach to improve engineered T cell therapies involves identifying antigens or antigen combinations that are unique to cancers and can be targeted by CARs, another approach is to design tolerance circuits that would prevent CAR T cells from attacking healthy normal tissues. 

Immunomodulators such as cytokines (IL-2, -12, -15), growth factors (Flt3L), agonist mAbs (anti-CD40 mAb, anti-OX40 mAb), Toll-Like Receptor (TLR) agonists, oncolytic virus therapies, and cancer vaccines are all parts of the immunotherapy armamentarium that can potentially be used in combination, and/or with checkpoint blockade.  Thus, as immunotherapeutic approaches and combination immunotherapies become more complex, improving their design to avoid or diminish destructive inflammatory or autoimmune toxicities is an emerging critical need.  Furthermore, immunotherapy clinical trial protocols have excluded individuals with known autoimmune disease. Several immune checkpoint inhibitors are now approved and can be used as standard of care therapy; they can therefore potentially be given to cancer patients with pre-existing autoimmune disease although this population is not well-studied in a clinical setting. In one study including patients with known preexisting autoimmune disease treated with ipilimumab, a subset of patients experienced flares of their autoimmune condition and some developed a new irAE, suggesting that the rate of irAEs could increase in this population.  A trans-NIH sponsored Conference on Cancer, Autoimmunity and Immunology, held on March 22-23, 2018, addressed the potential convergence of the fields of cancer immunotherapy irAEs and classic autoimmune diseases.  More interaction among scientists in these fields will help promote the realization of the full potential of immunotherapy, i.e., to destroy cancer cells while avoiding damage to normal, healthy tissues or exacerbating pre-existing autoimmune conditions.

Research Objectives

This FOA will support research projects in the specific area of cancer immunotherapy-related adverse events. Research is encouraged in understanding mechanisms of immune reactivity/tolerance and/or autoimmune pathways that could be applied to improving immunotherapeutic approaches while simultaneously eliminating or reducing the severity of inflammatory or autoimmune responses. A related area of interest is studies designed to enhance the target specificity of immunotherapeutic reagents, to reduce or prevent irAEs. An additional area of interest is the identification of predictive biomarkers of cancer patients at risk for developing irAEs. Understanding risk factors for developing an irAE would better inform patient stratification at the start of therapy and influence clinical monitoring. Achieving the goals of this FOA should establish a deeper understanding of the origins and activation pathways leading to inflammatory or autoimmune adverse events that currently limit the use of various immunotherapy regimens in patients. Studies focused on irAEs associated with immunotherapies for both adult and pediatric cancers are encouraged. Research may include, but is not limited to:

National Cancer Institute (NCI) Statement of Interest:

NCI Division of Cancer Biology (DCB): NCI DCB is interested in supporting studies focused on cellular mechanisms leading to irAEs during/after cancer immunotherapy, including, but not limited to:

  • Developing model systems (in vitro tissue models, animal models, in silico and computational models, synthetic and engineered immune model systems, etc.) to study the regulation of immune responses affected by immunotherapy strategies and leading to irAEs;
  • Identifying tumor antigens and epitopes with minimal or tolerable expression on normal tissues as potential immunotherapeutic targets to minimize irAEs;
  • Achieving a mechanistic understanding of critical cell participants, or new cellular functions of known cell participants, in tumor-directed immunity and its regulation affected by immunotherapy strategies and leading to irAEs;
  • Identifying and generating a mechanistic understanding of critical components of the TME as potential therapeutic targets to mitigate irAEs during cancer immunotherapy;
  • Identifying and generating a mechanistic understanding of key immunotherapy-relevant immune modulators as potential therapeutic targets to overcome irAEs; and
  • Investigating the role of the microbiome in the generation or prevention of irAEs resulting from cancer immunotherapies.

NCI Division of Cancer Treatment and Diagnosis (DCTD): The NCI DCTD is interested in supporting studies focused on, but not limited to:

  • Developing animal or non-animal preclinical models for defined immunotherapy approaches that reproduce irAEs observed in human patients;
  • Developing and evaluating candidate agents for mitigation of irAEs that do not limit the anti-tumor activity of immunotherapy regimens in clinically-relevant preclinical study models;
  • Developing in vivo imaging or analytical tools for quantitative measurement of localized immunological signatures to help define uncontrolled and injurious inflammation during and after cancer immunotherapy;
  • Identifying candidate biomarkers (e.g., genome including genetic polymorphisms, proteome including enzymes, cytokines and cell surface antigens, metabolome, microbiome, T-cell receptor repertoires, autoantibodies against specific tissues affected, imaging, etc.) for predicting, monitoring, or managing on- and/or post-treatment irAEs by analyzing specimens from patients treated with immunotherapies;
  • Validating biomarkers during correlative studies associated with prospective clinical trials of immunotherapies that may be used in predicting, controlling, and managing immunotherapy-associated irAEs in cancer patients; and
  • Establishing clinically-informative biomarker candidates that will ultimately improve clinical trial design and guide physicians as they select and sequence therapies involving immunotherapy interventions to minimize or avoid life-threatening irAEs in individual cancer patients.

National Institute of Allergy and Infectious Diseases (NIAID) Statement of Interest:  NIAID is interested in supporting studies that focus on understanding mechanisms regulating immune tolerance, T cell exhaustion, and host factors associated with irAEs associated with cancer immunotherapies. Examples of NIAID’s interests include the following types of research:

  • Identifying tolerance pathways that could be exploited to prevent “on-target, off-tumor” adverse events resulting from engineered anti-tumor immune cells (T or NK cells) attacking healthy tissues;
  • Deciphering mechanisms of T-cell exhaustion or tolerance to support the identification of new immunotherapeutic targets;
  • Regulating "off-target" non-specific inflammatory and autoimmune responses while using checkpoint blockade without impeding anti-tumor immune responses;
  • Addressing cancer immunotherapy in patients with underlying autoimmune diseases - including those, like lupus, that disproportionately affect racial and ethnic populations; and
  • Identifying predictive biomarkers for the onset of irAEs (e.g., genetics, epigenetics, microbiome, and overall immune status).

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Statement of Interest:  NIAMS is interested in supporting basic, translational, and/or clinical studies focused on:

  • Understanding mechanisms related to irAEs that are covered under NIAMS mission areas (i.e. rheumatological, skin-related, musculoskeletal); and
  • Addressing cancer immunotherapy irAEs in patients with underlying rheumatic and/or autoimmune skin diseases.
  • Please see NIAMS long-range plan: NIAMS: Long Range Plan

National Institute of Dental and Craniofacial Research (NIDCR) Statement of Interest:  NIDCR is interested in supporting basic, translational, and clinical studies of immunotherapy-related adverse events that are relevant to the NIDCR's mission and strategic plan:

  • Investigating adverse effects of immunomodulatory drugs and biologics on dental, oral and craniofacial health and how biological variables (e.g., sex/gender, age) alter the risk for adverse effects; and
  • Supporting basic and preclinical research on elucidating the causes of immunotoxicity associated with immunoregulatory interventions to treat oral diseases or to treat oral mucosal complications in immune-compromised patients.
  • Potential applicants are encouraged to speak with a NIDCR program official to discuss the relevance of proposed research topic(s).

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Statement of Interest:  NIDDK is interested in supporting basic, translational, and clinical studies that focus on:

  • Understanding mechanisms of irAEs, especially projects that explore commonalities with spontaneous autoimmune or inflammatory diseases in our mission such as type 1 diabetes and gastrointestinal disorders;
  • Identifying biomarkers and therapeutic targets for autoimmune endocrine and digestive diseases through the study of irAEs; and
  • Understanding and reducing the risks of cancer immunotherapy for patients with (or at risk for) underlying autoimmune endocrine diseases or gastrointestinal disorders.
Non-responsive Projects

The following projects remain outside the scope of this FOA. Applications proposing any of the following studies will not be reviewed:

  • Studies that seek only to identify new tumor antigens or epitopes.
  • Studies that seek only to design new immunotherapies rather than addressing irAEs resulting from cancer immunotherapy.

Applicants are encouraged to reach out to the Scientific/Research Contact listed in Section VII. Agency Contacts to ensure appropriate alignment of projects with available funding opportunities.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed

New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. NIH intends to commit $5,000,000 in total costs in FY2020 to fund 5-10 awards.

Award Budget

Each application budget is limited to $375,000 in direct costs (exclusive of F&A consortium costs) per year.

Award Project Period

The total project period may not exceed 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.

Section III. Eligibility Information
1. Eligible Applicants
Eligible Organizations

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)

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)
  • 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
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

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.

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. 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.
  • 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. 
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons.  Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but 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 DUNS number and 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.

Eligible Individuals (Program Director/Principal Investigator)

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.

3. Additional Information on Eligibility
Number of Applications

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.  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 NOT-OD-11-101).
Section IV. Application and Submission Information
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 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:

Lillian S. Kuo, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-292-4621
Email: Lillian.Kuo@nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

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.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide must be followed.  

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide must be followed.  

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide must be followed.  

SF424(R&R) Senior/Key Person Profile

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. Applicants must budget for travel and per diem expenses for Steering Committee meetings. Applicants should plan for at least two senior investigators (all PDs/PIs, if desirable, or the PD/PI and a senior investigator if multi-PD(s)/PI(s) option is not used) to attend at least one in-person Steering Committee meeting per year.

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide must be followed.  

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aims: In addition to the specific aims and approach (es), applicants should include the relevance of the research to the objectives of this FOA.

Research Strategy: The Research Strategy section should describe the following:

  • Expected impact on mitigating immune related adverse events;
  • Significance of the proposed project for minimizing immune related adverse events for future clinical treatment of the cancer;
  • Pre-clinical research approaches (along with potential pitfalls and alternative strategies) that address the overall goals of the FOA;
  • Clinical relevance of the pre-clinical study models and the proposed strategies; and
  • Timeline for achieving the project goals.

Health Disparities: If applicable to the type of research being proposed, address how minority health, health disparity populations or data will be integrated into the proposed studies. Highlight, as relevant, any opportunities that, if implemented, can reduce the burden of cancer in the health disparities that currently exist.  In this context, efforts are encouraged to address the needs of minority health populations and those from urban and rural areas who are poor and medically underserved, who continue to suffer disproportionately from certain cancers and have higher morbidity and mortality rates.

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, with the following modification:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
  • Addressing the Cancer Moonshot Public Access Pilot Program: Utilizing the provision outlined in the 21st Century Cures Act, NCI has established a data sharing policy for projects that are funded as part of the Beau Biden Cancer Moonshot Initiative SM that requires applicants to submit a Public Access and Data Sharing Plan that (1) describes their proposed process for making resulting Publications and to the extent possible, the Underlying Primary Data immediately and broadly available to the public; (2) if applicable, provides a justification to NCI if such sharing is not possible.  NCI will give competitive preference and funding priority to applications with a data sharing plan that complies with the strategy described here: https://www.cancer.gov/research/key-initiatives/moonshot-cancer-initiative/funding/public-access-policy. The data sharing plan will become a term and condition of award.
  • Guiding Principles for Cancer Moonshot Biobanking Activities: The goal in developing these guiding principles is to accelerate research by a) increasing the availability of biospecimens for Cancer Moonshot-related and other biomedical research through facilitation of investigator to investigator sharing of biospecimens, and b) increasing the reproducibility of Cancer Moonshot research through improved biospecimen practices and corresponding annotation. These guiding principles also seek to facilitate, where possible, increased engagement of research participants through researchers’ communication of aggregate research results and, in some cases, individual genomic findings that may be medically actionable for research participants.  NCI will give competitive preference and funding priority to applications that conform to the "Guiding Principles for Cancer Moonshot Biobanking Activities" (http://biospecimens.cancer.gov/programs/cancermoonshot/principles) and are consistent with the "2016 NCI Best Practices for Biospecimen Resources" (https://biospecimens.cancer.gov/bestpractices/).

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information

When involving NIH-defined human subjects research, clinical research, and/or 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.

PHS Assignment Request Form

All instructions in the SF424 (R&R) Application Guide must be followed. 

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

4. Submission Dates and Times

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.

6. Funding Restrictions

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.

7. Other Submission Requirements and Information

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 field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. 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 DUNS number it provides 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.

Post Submission Materials

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.

Section V. Application Review Information
1. Criteria

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.

Overall Impact

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 to this FOA: How well does the project proposed advance cancer immunotherapy research by mitigating immune-related adverse events?    

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 to this FOA: How well do Program Director (PD)/PI, multiple PD(s)/PI(s) and key personnel/consultants demonstrate strong scientific expertise in immuno-oncology and other scientific specialties required in the team to achieve the proposed goals? Are the investigators willing to collaborate with members of the IOTN or PI-DDN Steering Committee?       

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?

Specific to this FOA: Does the applicant propose innovative plans for leveraging expertise and resources, integrating clinically-relevant information, and advancing research to develop strategies that will predict, prevent or ameliorate immune-related adverse events?       

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? 

Specific to this FOA: Is the clinical relevance of the pre-clinical study models and/or the proposed strategies adequately addressed? How well do the proposed studies have potential to address diverse populations of the United States, including minority and underserved populations? Are proposed studies appropriately powered, controlled, randomized, and blinded? Which project resources could be potentially shared among IOTN or PI-DDN investigators and the broader scientific community? Does the application contain acceptable plans for addressing the NCI Cancer Moonshot Public Access and Data Sharing Policy?

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

Not applicable

Renewals

Not applicable

Revisions

Not applicable.

Additional Review Considerations

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

Not applicable

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 NCI, 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:

  • 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.
  • Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

  • 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.

Section VI. Award Administration Information
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 grantee’s business official.

Awardees 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.

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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency.  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. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html.  Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/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. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

NIH Responsibilities under Terms and Conditions of Cooperative Agreement:

In carrying out its stewardship of Beau Biden Cancer Moonshot initiatives, the National Cancer Institute (NCI) and other NIH Institutes will monitor and evaluate progress to meet the expectations set forth by Congress in the 21st Century Cures Act.  Depending whether the scope of the immune-related adverse events (irAEs) research is for adult or pediatric immunotherapy, PD(s)/PI(s) will either become components of the Immuno-Oncology Translational Network (IOTN, reference cooperative agreement terms for https://grants.nih.gov/grants/guide/rfa-files/RFA-CA-19-015.html) or the Pediatric Immunotherapy Discovery and Development Network (PI-DDN, reference cooperative agreement terms for https://grants.nih.gov/grants/guide/rfa-files/RFA-CA-19-004.html).

The PD(s)/PI(s) will have the primary responsibility for:

  • Defining objectives and approaches, and to ensure scientific rigor in the planning, conducting, analyzing, and publishing of results, interpretations, and conclusions of studies conducted under this program;
  • Setting project milestones in consultation with NIH staff, and reporting progress and objectives to NIH staff;
  • Coordinating efforts and cooperating with the other components of the IOTN (for adult cancers) or the PI-DDN (for pediatric cancers) and with NIH Institute/Center (IC) Project Scientists. These actions may involve (but will not be limited to) participation in appropriate coordinating meetings and/or working groups, and/or teleconferences as needed;
  • Overseeing the implementation of an approved data sharing plan and resource sharing plan. Institutions/organizations participating in the respective IOTN (for adult cancers) or the PI-DDN (for pediatric cancers) Consortium will be expected to share with each other knowledge, data, research materials, and any other resources necessary and relevant to the IOTN (for adult cancers) or the PI-DDN (for pediatric cancers);
  • Leveraging, where feasible, technology from related NCI-sponsored informatics initiatives, for example The NCI Informatics Technology for Cancer Research (ITCR, https://itcr.cancer.gov/ program, which supports the development of informatics algorithms, tools, and resources across the continuum of cancer research);
  • Coordinating with and leveraging, where feasible, the technology of The NCI Cancer Research Data Commons, a program that will provide infrastructure to make diverse cancer research data broadly available and to maximize their reuse and impact (https://cbiit.cancer.gov/ncip/cancer-research-data-commons);
  • Maintaining the confidentiality of the information shared by the IOTN (for adult cancers) or the PI-DDN (for pediatric cancers) Consortium, including, without limitation, unpublished data, protocols, data analysis, confidential exchanges between members of the IOTN (for adult cancers) or the PI-DDN (for pediatric cancers), as well as any confidential information received by third party collaborators;
  • Annotating samples through the use of Consortium-defined Common Data Elements (CDEs).
  • Adhering to the IOTN (for adult cancers) or the PI-DDN (for pediatric cancers) Consortium Communication Plan: A consensus Communication Plan will be drafted by the respective Steering Committees of the IOTN (for adult cancers) or the PI-DDN (for pediatric cancers) Consortium. This plan will clearly spell out interactive requirements that all IOTN (for adult cancers) or the PI-DDN (for pediatric cancers) Consortium PD(s)/PI(s) are expected to follow, including: Participating in regular conference calls and contributing to various sub-committees and working groups; Serving as a voting member on the IOTN (for adult cancers) or the PI-DDN (for pediatric cancers) Steering Committee; Participating and presenting findings at the IOTN (for adult cancers) or the PI-DDN (for pediatric cancers) annual investigator meetings; and Coordinating efforts with other members of the IOTN (for adult cancers) or the PI-DDN (for pediatric cancers) consortium.
  • Meeting yearly milestones as defined by PD(s)/PI(s) and NIH IC Project Scientists at the time of award;
  • Participating in NCI-coordinated evaluation of the IOTN (for adult cancers) or the PI-DDN (for pediatric cancers) program.

In addition to standard annual Research Performance Progress Report (RPPR) submissions, Principal Investigators may be expected to supply additional progress-related information.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.  PD(s)/PI(s) are also encouraged to organize and participate in collaborative activities and scientific or programmatic working groups.

NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

Designated Program Director(s) from NCI and other NIH Institutes supporting this initiative will have substantial involvement as Project Scientists. Additionally, a Program Director from NCI (or another appropriate NIH Institute), acting as Program Official, will be responsible for the normal, scientific and programmatic stewardship of the award and will be named in the award notice.

Activities of substantially involved staff members from NCI and other NIH Institutes involved will include:

  • Serving as a voting member on the IOTN (for adult cancers) or the PI-DDN (for pediatric cancers) Steering Committee;
  • Coordinating and facilitating interactions among investigators across the IOTN (for adult cancers) or the PI-DDN (for pediatric cancers);
  • Working closely with investigators on research projects to coordinate and facilitate interactions/collaborations between awardees across the consortium;
  • Assisting the awardees as a resource in facilitating their broader interactions with other NCI and NIH programs for the purpose of leveraging and coordinating existing NIH/NCI resources and infrastructures, such as those within the NCI ITCR program and the NCI Cancer Research Data Commons;
  • Assisting in avoiding unwarranted duplication of effort with other NIH efforts;
  • Suggesting reprogramming efforts, including options to modify projects/programs when certain objectives of this FOA are not met -- specifically, the NIH IC Project Scientists may recommend withholding of support, suspension, or termination of an award for lack of adherence to required IOTN (for adult cancers) or the PI-DDN (for pediatric cancers) Consortium policies and/or procedures;
  • Developing working groups and trans-project efforts as needed;
  • Monitoring progress and direction of awardees and working groups as needed; and
  • Organizing and conducting regular meetings, as needed, to share progress between the awardees of the IOTN (for adult cancers) or the PI-DDN (for pediatric cancers) Consortium either by teleconference, videoconference, or face-to-face interaction.
  • Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

  • The IOTN (for adult cancers) or the PI-DDN (for pediatric cancers) Steering Committee (SC) will serve as the main governing board for the respective Consortia.
  • Awardees will join the existing IOTN (for adult cancers) or the PI-DDN (for pediatric cancers) Steering Committee (SC) which will continue to serve as the main governing board of the IOTN (for adult cancers, reference IOTN cooperative agreement terms for RFA-CA-19-015.html or the PI-DDN (for pediatric cancers, reference PI-DDN cooperative agreement terms for RFA-CA-19-004.html

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

When multiple years are involved, awardees 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.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees 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.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

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: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

Lillian S. Kuo, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-292-4621
Email: Lillian.Kuo@nih.gov

(for immune-related adverse events in adult cancers)

Susan McCarthy, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6200
Email: mccarths@mail.nih.gov  

(for immune-related adverse events in pediatric cancers)

Connie Sommers, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-7187
Email: sommersc@mail.nih.gov

Minkyung Song, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6139
Email: songm@mail.nih.gov

Katarzyna (Kasia) Bourcier, Ph.D.
National Institute of Allergy and Infectious Disease (NIAID)
Telephone: 240-627-3482
Email: bourcierkd@mail.nih.gov

Marie Mancini, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5032
Email: mancinim2@mail.nih.gov

Chiayeng Wang, Ph.D.
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-827-4647
E-mail: chiayeng.wang@nih.gov

Lisa M. Spain, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-451-9871
Email: spainl@mail.nih.gov

Peer Review Contact(s)

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: ncirefof@dea.nci.nih.gov

Financial/Grants Management Contact(s)

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email: Crystal.wolfrey@nih.gov  

Tina Carlisle
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2947
Email: tc48k@nih.gov  

Erik Edgerton
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-7760
Email: edgertont@mail.nih.gov

Diana Rutberg
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
E-mail: rutbergd@mail.nih.gov

Leslie Whipp
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-443-9360
Email: whipplc2@mail.nih.gov

Section VIII. Other Information

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.

Authority and Regulations

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.

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