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)

Funding Opportunity Title
Cancer Target Discovery and Development (CTD2) (U01 Clinical Trial Not Allowed)
Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type
New
Related Notices

None

Funding Opportunity Announcement (FOA) Number
PAR-21-274
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.395, 93.396
Funding Opportunity Purpose

Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) will support the program "Cancer Target Discovery and Development” (CTD2, pronounced cee-tee-dee-squared). CTD2 is focused on efforts that advance cancer research by bridging the knowledge gap between the large volumes of comprehensive molecular characterizations of many cancer types and studies of the underlying etiology of cancer development, progression, and/or metastasis.

The primary purpose of CTD2 is to advance the following areas:

  • Improving the understanding of how mutations in cancer-associated genes affect the protein activity (e.g., gain-of-function, loss-of-function, or neomorphic function) within the cellular pathway(s) they are part of and the cellular changes that result within the context of various tumors and the microenvironment;
  • Identifying new molecular targets with the goal to understand their wiring mechanisms and how to overcome innate and/or acquired resistance to therapies, particularly clinical resistance related to inter- and intra- tumor heterogeneity; and
  • Developing efficient strategies to identify appropriate multiple targets and optimal combination of perturbagens (chemical or biological; immunotherapeutics being a prime example of the latter) with the potential to eliminate all cancer cells, despite their clonal heterogeneity and their surrounding microenvironment.

This FOA solicits applications for U01 cooperative agreement research projects addressing the areas outlined above. The proposed projects should use a combination of state-of-the-art high throughput informatic and experimental approaches to: characterize and validate novel cancer targets; develop precise perturbagens that can affect the proposed targets of cancer treatments and define the mechanism(s) of action; identify molecular markers that can meaningfully predict responses or resistance to anticancer therapies and develop algorithms that can be applied to predict responses to treatments and/or define more precise treatment modalities.

Key Dates

Posted Date
July 12, 2021
Open Date (Earliest Submission Date)
September 06, 2021
Letter of Intent Due Date(s)

30 days prior to the application due date.

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
October 06, 2021 Not Applicable Not Applicable March 2022 May 2022 July 2022
February 08, 2022 Not Applicable Not Applicable July 2022 August 2022 December 2022
October 06, 2022 Not Applicable Not Applicable March 2023 May 2023 July 2023

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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.

Expiration Date
October 07, 2022
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) will support the program "Cancer Target Discovery and Development” (CTD2, pronounced cee-tee-dee-squared). CTD2 will promote efforts to radically improve our understanding of the underlying etiology of cancer initiation, progression, and metastasis and to exploit this knowledge in clinically relevant context which includes intra-tumor heterogeneity, tumor microenvironment and other factors that result in "innate" or acquired treatment resistance.

While there are improvements in our understanding of cancer drivers and their pathways, mechanisms of resistance, and other factors of cancer cell wiring, it is still challenging to enable rapid conversion of molecular data to precision oncology especially in the arena of innate and acquired resistance even as new data sets are becoming available (e.g., cancers from underrepresented minorities, children, data from clinical trials, etc.). This is a strong scientific rationale for an initiative with a strong history of precompetitive collaborations, such as the CTD2 Network, whose goals are to accelerate all knowledge available (be it generated by them only or integrated with other information) to the clinic.

Specifically, the CTD2 FOA solicits applications for research projects focused on identifying and understanding: pathways that influence cancer phenotypes (including understanding the function of the genes/targets which are essential in cancer transformation, maintenance and metastasis); perturbagens that can modulate such pathways; biomarkers predicting responses to treatments, prognosis, and other aspects of cancer etiology that need to be understood in order to develop effective treatments in the future and how to predict them.

The research projects proposed in response to this FOA must combine informatics and complementary experimental approaches. Where appropriate, informatics should be combined with high throughput assays in experiments designed to demonstrate that affecting identified targets can lead to the desirable outcomes such as the abrogation of the cancerous phenotype, the reduction of metastatic potential, and/or selective eradication of cancer cells even for heterogeneous tumors. Informatics may also facilitate the development of probes that specifically affect the function of the prospective targets and other experimental approaches relevant to their characterization. Functional agents (such as small molecules, molecular glues or binders proteolysis targeting chimeras) may be developed and investigated either as phenotype perturbagens in combination with other and novel perturbagens with minimal side-effects for target characterization, validation and/or as prototypes for therapeutics in cell heterogeneous tumors. These combined endeavors should aim to identify a) potential therapeutic targets and validate their relevance; b) understand the wiring of these proteins within specific cancer(s) context, and/or c) to develop probes or perturbagens for pathways that are important in the etiology of cancers; and d) explore if the results are dependent on the defined genetic background (either germline or somatic) of the patient.

All investigators with appropriate expertise and capabilities are encouraged to consider the opportunity regardless of whether or not they participated in the previous issuance of the program (RFA-CA-16-014).

Key Definitions for the purpose of this FOA:

  • Target is defined as a specific, defined molecular alteration(s) within cancer cells that is/are necessary for cellular transformation, proliferation, and/or metastasis. It can be due to either a gene mutation(s) (gain or loss of function, or loss of product) or amplification of a gene (increasing the concentration of the product within the cells) or an interaction between two or more proteins.
  • Perturbagen is defined as a modality designed to disrupt specific intracellular https://en.wiktionary.org/wiki/intracellular process (or processes), thereby providing information about the operation of pathways/networks within a cancer cell. Perturbagens may be chemical compounds (small molecules, including molecular glues and/or binders, or proteolysis targeting chimeras), or biologicals (antibodies, proteins), or multi-component tools (e.g., novel CRISPR gene [or genome] modulators). Perturbagens may also serve as prototypes for therapeutic modalities.
  • Informatic(s) is defined as trail-blazing computation method(s) to analyze a) molecular characterization data of cancer(s) to predict targets or functions (e.g., bioinformatics), b) results of small molecule screens in the context of molecular phenotype of the cancer models used (e.g., cheminformatics) to identify perturbagen(s), c) structure-activity predictions of small molecules of any type and/or d) any other computationally intense approach(es), such as artificial intelligence applied to better predict patient response to treatments, etc.

Background

Cancer may be viewed as a disease of the genome. Accordingly, various comprehensive molecular characterization programs (e.g., TCGA (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga), and TARGET (https://ocg.cancer.gov/programs/target) have resulted in large data sets of alterations present in adult and pediatric cancers. Ongoing programs (e.g., Cancer Genome Characterization Initiative (https://ocg.cancer.gov/programs/cgci) etc. continue to provide large data sets detailing cancers’ transcriptome, genome, epigenome, and mutation profiles. Several NCI precision oncology programs are adding to these volumes of data; they use sequencing to characterize tumor RNA and DNA to identify alterations within patients' cancers that may inform treatment decisions in the clinic. Examples are ALCHEMIST (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial, https://www.cancer.gov/types/lung/research/alchemist) the Exceptional Responders Initiative (http://dctd.cancer.gov/MajorInitiatives/NCI-sponsored_trials_in_precision_medicine.htm#h06); the NCI-MATCH enrolling patients 18 years or older, (Molecular Analysis for Therapy Choice, http://www.cancer.gov/about-cancer/treatment/clinical-trials/nci-supported/nci-match and the NCI-COG Pediatric MATCH https://www.cancer.gov/about-cancer/treatment/clinical-trials/nci-supported/pediatric-match. The sequence and other patient data of these programs are accessible through the NCI's Genomic Data Commons (GDC, https://gdc.cancer.gov/) which uses standard set of analytical pipelines and stores the results either under open or controlled access (https://ocg.cancer.gov/resources/open-versus-controlled-access-data) to ensure appropriate patient protection, confidentiality and privacy.

The genomic characterizations of tumor tissues that are annotated with clinical and patient data have provided important information about various molecular changes that are relevant to the etiology of cancer and improved our understanding of cancer drivers and their pathways, mechanisms of resistance, etc. Nonetheless there are still challenges to overcome if we are to enable rapid conversion of molecular data to precision oncology especially in the arena of innate and acquired resistance in all types of cancers in patients of all genetic backgrounds. Inclusion of clinical and patient information improves the correlations but does not confirm mechanisms even when associated with clinical trials. For example, insights are still limited on how cellular alterations affect biochemical and cellular processes. Deeper understanding of these aspects is needed for: a) the development of validated prognostic, diagnostic or response biomarkers; b) identification of the therapeutic targets for the disease in individual patients; and c) predicting and/or explaining small molecule response patterns.

One key to the development of successful therapy is the identification of the dysregulated critical-function cellular pathway nodes and networks whose inhibition results, within specific cellular context, in cancer cells’ system failure and therefore elimination. Biochemical approaches to identify dysregulated pathways are important but many can be specific for only the given alteration(s) or cellular context, making use of these approaches laborious, time consuming and costly. Moreover, plentitude of evidence points to the importance of yet another confounding component of the cancer phenotype: the heterogeneous, polyclonal nature of tumors, their infiltration by arteries and other cells and the surrounding microenvironment. It is not clear how differences in cellular composition (stroma, tumor-associated fibroblasts, adjacent tissue, endothelium, various clones of transformed cells, etc.) affect each patient’s response to standard care or incipient precision oncology treatments. In addition, the alterations underlying specific cancer types need to be interpreted within the complex networks of interactions that occur in various differentiation states of the cell type of origin and the genetic background of the individual which may have diverse consequences. Therefore, to translate the compendia of molecular data into insights about cancers that will be applicable in the clinic, new approaches are needed that combine broad bioinformatic analyses, comprehensive experimental characterizations, probing of cancer-defining molecular interdependencies using high throughput methodologies and systems biology tools.

Among the collaborative activities of the current CTD2 Network are a Cell Review “An expanded universe of cancer targets” as emerging research indicates that the diversity of therapeutic targets engendered by non-oncogene dependencies is much larger than the list of recurrently mutated genes thereby providing novel opportunities for clinical translation (https://pubmed.ncbi.nlm.nih.gov/33667368/), development of new informatic tools (https://ocg.cancer.gov/programs/ctd2/analytical-tools) and generated data which was used to support the establishment of a number of phase I clinical trial protocols. All data generated by the CTD2 initiative is deposited in standard formats in the NCI-hosted Data Portal (https://ctd2.nci.nih.gov/dataPortal/).

The Network created a web interface, the CTD2 Dashboard (http://ctd2-dashboard.nci.nih.gov/), which allows any interested user to mine data-driven observations and conclusions to generate new hypotheses or better understand the results in relation to the context of the tissue type that they are interested in. The Network Centers also developed and published a process of validation and maturation of targets, biomarkers, and perturbagens (https://pubmed.ncbi.nlm.nih.gov/27401613/) and it is expected that the Centers that will be funded will utilize the process and improve on it.

Specific Research Objectives

Main Goals. All projects proposed in response to this FOA must be relevant to the overarching goals of understanding the wiring of cancer cells in vivo (i.e. within the patient),  identifying novel candidate therapeutic targets and/or small molecular modulators of cancer phenotypes, developing bioinformatic approaches to allow translation of molecular characterization data to precision oncology, and/or identifying biological or predictive markers within patient tumors that are known to be heterogeneous, i.e., composed of cancer subclones and infiltrated by stroma, vasculature, etc. In addition, another goal is to improve and apply experimental approaches that allow rapid identification of potential candidate drug targets, diagnostic or prognostic markers, and novel small molecule perturbagens across the many cancer subtypes for which adequate characterization datasets are available now and those that will be available within the next couple of years.

The proposed projects should address at a minimum two of the three research areas defined below:

Area 1. Improving understanding of gene functions in pathways and cellular wiring important in cancer initiation, progression, and metastasis within context of a few human tumors;

Area 2. Identifying and confirming biological candidate targets, and possibly associated predictive markers, involved in cancer etiology which are amenable to modulation; use the data to predict outcome of combination treatment through use of decision trees and/or artificial intelligence; and

Area 3. Identifying perturbagens (chemical or biological; immunotherapeutics being a prime example of the latter) that modulate a target's function within the context of the specific cancer cell type(s). Particularly desirable will be search for perturbagen combination capable of minimizing or eliminating resistance to therapies.

Note: Studies in all three areas must explore cancer complexity in terms of inter-patient and intra-tumor heterogeneities and their impact, e.g., on innate or acquired resistance to therapy and in more than one cancer type. It is expected that high-throughput approaches will be part of the experimental strategies. Each application should include studies of multiple cancer sub/types and continue the ethos of broadly sharing knowledge, resources and algorithms through the CTD2 web site, Dashboard and Data Portal.

In addition, all proposed projects should incorporate the following aspects:

An appropriate combination of computational analyses of the available cancer characterization data with systematic (and preferably high-throughput) experimental approaches that should involve:

  • Various types of available genomic data (examples are listed in the Background section; all data to be used should be accessible through the NCI GDC or other public repositories);
  • Experimental cancer models that must be properly molecularly characterized to ensure that they recapitulate as much as possible the characteristics of tumors in patients;
  • Investigation of pathway(s) within the context of multiple cancer types, or if appropriate, understanding the role it/they play(s) in a single cancer type.

Examples of topics to be addressed include, but are not limited to, the following:

  • Study in vivo oncogenic mechanisms (e.g. metastasis, stromal interactions and immune/inflammatory response) using novel in vivo technologies to screen epi/genome of cancer cells, monitor cellular interactions, and track malignant cell movement.
  • Use of novel genetic and chemical tools (e.g. perturbagens) to study the modification or disruption of protein rewiring of cancer cell circuitry.
  • Identify novel protein-protein interactions essential in cancer initiation, maintenance and metastasis.
  • Develop and apply novel CRISPR methodologies with or without small molecule perturbagens to dissect cancer transformed phenotypes.
  • Develop small molecules with minimal off-target effects which can be used in structure action studies, as precursor for improving interactions with cancer targets, etc.
  • Use molecular glues to discover or modify protein-protein interactions or alter the proteome of cancer cells. The cellular context is an important consideration.
  • Generate high throughput screening data sets with small molecules, CRISPRs, and other approaches in well characterized cancer models, such as organoids, conditionally reprogrammed cells, etc.
  • Identify and confirm candidate targets and, if possible, associated predictive markers, involved in cancer etiology, which are amenable to modulation.
  • Incorporate information of the patients' genetic background in addressing the intra-tumor heterogeneity and modulation of target functions or response to perturbagens. Studying tumor mechanisms in various ethnic backgrounds is an advantage.

Examples of concepts that could serve as building blocks for projects to be proposed are listed below. Note that these examples are non-exclusive. Projects are expected to combine, as appropriate, various relevant novel concepts and approaches.

    •  
  • Functional probes (e.g., small molecules, genome/transcriptome modulators such as those based on CRISPRs, etc.) can be investigated either as phenotype perturbagens for target characterization, validation, and/or as prototypes for therapeutic agents;
  • Combinatorial approaches aimed to overcome treatment resistance usually seen with monotherapy so as to successfully eliminate all transformed cancer cells within a tumor, and if possible other transformed cell like tumor-associated fibroblasts, e.g. using synthetic lethal screens, immunotherapy together with small molecules, etc.;
  • In each cancer type selected for study, identification of candidate targets by use of novel or improved integrated genomic systems biology methods that will lead to enhanced understanding of multiple signaling and other key cancer processes and determination which are amenable to modulation;
  • Prediction of primary or acquired mechanism(s) of resistance to therapy based on patients' genetic background and cancer-specific alterations;
  • Definition of cancer-relevant pathways, wiring diagrams and gene redundancies as well as the approaches to overcome them;
  • Identification of challenging, unconventional, or rarely addressed targets such as those involved in specific protein-protein interactions, specific protein-DNA interactions, specific protein-RNA interactions, metabolism, regulatory RNA functions, and others;
  • Determination of the complex dependencies within each cancer type and the identification of combination of targets which could be exploited for therapeutic interventions;
  • Confirmation that identified targets are involved in cancer's initiation, maintenance, progression, and/or metastasis (either across many cancer types or within a cancer type); and
  • Exploration of targets or combinations of screening approaches to determine the underlying mechanisms of treatment resistance, including impact of intra-tumor heterogeneity or evaluation of resistance, and/or identification of biological modulators.

CTD2 as a Network

The CTD2 awardees will be expected to form an interactive Network, with a Steering Committee as the governing body (for details see Section VI.2. Terms and Conditions of Cooperative Agreements). The programmatic goals and funding priority of the CTD2 initiative are to ensure research of as many cancer types as possible. Still, it is possible that multiple awardees may investigate the same specific cancer type provided that their approaches and research emphasis are complementary.

To facilitate and enhance interactions across the Network, the CTD2 awardees will be expected to share their data and resources. Moreover, it is also expected that final validated results will be made publicly available (through the CTD2 web site maintained by the NCI, https://ctd2.nci.nih.gov/dataPortal/, and the Dashboard, http://ctd2-dashboard.nci.nih.gov/ (for details see Data Sharing Plan in Section IV). Examples of CTD2 Network activities are above in the background section.

In addition, the CTD2 awardees will participate in collaborative research activities e.g., pilot exploration of emerging/novel opportunities that could enrich the original project by taking advantage of experience and/or research developed by other awardees. The collaborations are presented to the Steering Committee for input and discussion and the written proposal is submitted the NCI program director.

Non-Responsive Applications

The following research directions and types of projects will be considered non-responsive. (Non-responsive applications will not be reviewed.)

    •  
  • Large-scale molecular (genomic) characterization studies of cancers, cancer subtypes, and cancer models;
  • Studies aimed at in-depth elucidation of the role of a specific, individual cancer alteration in the mechanisms of cancer initiation, progression, metastasis and/or therapy;
  • Studies explicitly centered only on the identification of cancer biomarkers (even though some targets to be identified may be of value as potential clinical biomarkers of diagnosis, progression, or metastasis);
  • Studies focused entirely on target types that are already well studied, which includes kinases, phosphatases, and RAS (as RAS is a subject of a separate NCI-funded effort http://www.cancer.gov/research/key-initiatives/ras) just to name a few;
  • Studies utilizing perturbagens with known complicated off-target effects such as RNAi (e.g., shRNAs);
  • Studies of targets for a specific known anticancer agent(s), e.g. BCR-ABL, TP53 and others;
  • Development of anticancer drugs beyond the early, mechanistic proof-of-concept/prototype stages;
  • Initiation of clinical trials, including tasks such as development of study design, identification of collaborators, enrollment sites, etc.;
  • Studies using cancer cell models or xenografts without adequate experimental validation that they include the relevant molecular aberrations found in the tumor from which they were derived as well as clinical and outcome information; and
  • Development of new cancer models.

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
Resubmission

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.

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

NCI intends to commit $12 million in total costs in FY 2017 to fund up to 12 awards.  The number of awards is contingent upon NCI appropriations and the submission of a sufficient number of meritorious applications.  It is expected that funds will be available in subsequent years, but the funding and the amounts will depend on annual appropriations.

Award Budget

Budgets up to $750,000 direct costs per year may be requested.

Award Project Period

A maximum project period of up to 5 years may be requested.

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)

Federal Governments

  • 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.
  • 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 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:

Jean C Zenklusen, Lic.Chem., Ph.D.
National Cancer Institute (NCI)
Telephone: 240-781-3409
Email: jz44m@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.

Facilities and Resources: Include any information about available unique resources and/or special capabilities that may be relevant for future network collaborative research activities.

Other Attachments: If pertinent to the project goals, applicants may upload supplementary information in tabular form. For example:

  • Summary table listing unique perturbagens (small molecules, biologicals, etc.) to be used in the proposed project and their key properties (e.g. any structural characteristics, known or anticipated targets, etc.) and/or
  • Summary table of novel cancer models to be used, including their main molecular characteristics, links to public repositories housing the model-relevant information, etc.
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.

PD/PI Effort Commitment.Any PD/PI (whether designated as contact or not) must commit a minimum of 1.2 person-months effort per year to the award. This commitment cannot be reduced in later years of the award.

Trans-Network Activities.Applicants must budget a set-aside of funds for future joint trans-Network activities (such as collaborative pilot studies). The use of these funds will be restricted to activities reviewed and recommended to the PD/PI by the Steering Committee. The amounts budgeted for this set-aside should amount to 5% of budget direct costs in year 1 of the project period and from 20% to 25% of budget direct costs in subsequent years. These amounts should be presented in the Other Expenses category under the heading “Restricted Network Collaborative Fund.”

Travel Funds.Applicants must budget for travel and per diem expenses to participate in Steering Committee meetings as indicated below.

  • In the first year, applicants should budget travel funds for the PD(s)/PI(s) and other investigators (up to four persons total) to attend a "kick-off" Steering Committee meeting.
  • For the subsequent years, applicants should budget analogous travel funds for up to five persons (including PDs/PIs) to attend yearly Steering Committee meetings.
  • In addition, applicants should budget for one person per year (average) for travel to attend Workshops at the NCI.
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 standard outline of the specific aims of the project, identify the overall research focus by referring to Areas 1-3 defined in Section I.

Research Strategy: In addition to standard items, address all of the aspects listed below in the sub-sections as indicated.

Under "Significance", address the following:

  • Introduce the research problem to be explored, explaining the distribution of emphasis across Research Areas 1-3, as applicable (noting that at least two of these three areas must be comprehensively covered);
  • Based on your preliminary data mining and other rationale, present your hypothesis about the putative new targets, target combinations, development of resistance etc. to be explored and the context(s) in which these targets may be relevant (e.g., specific cancer types, multiple cancer types, gender, ethnicity-dependent factors, drug resistance, etc.); and
  • Using a separate sub-heading "Statement of Translational Relevance", explain how the expected findings may advance the understanding of cancer mechanisms with specific, defined molecular characteristics and inform improvements in clinically relevant areas, e.g. patient outcomes.

Under "Innovation", address the following:

  • Highlight any innovative and/or unique informatics tools, experimental approaches, novel cancer models, etc., that you have available and plan to use; and
  • Discuss any expected improvements in informatics and/or experimental approaches, which would allow rapid and complete identification of potential candidate drug targets, diagnostic or prognostic markers, and/or perturbagens across multiple cancer types and subtypes.

Under "Approach", address the following:

  • Provide Preliminary Data in support of both informatic and experimental approaches;
  • Describe the strategy for both informatic and experimental studies, including (in addition to typical content) specific elements such as:
    • Identify (and justify) types and sources of publicly available molecular cancer characterization data to be used for bioinformatics analyses;
    • Include a brief outline of the available and planned computational setup and general workflow, indicating how the project will take advantage of the CDT2 Data Portal;
    • Explain how the proposed efforts will accommodate the continued generation and availability of new (and/or expanded) data sets over the project period (e.g., possible study expansion to cover additional cancer types);
  • Identify clearly which cancer types will be investigated (note that a project focused on a single cancer type is unlikely to be selected for funding);
  • Provide rationale for the selection of cancer models for such studies, including the required background information on the availability of molecular profiles and documentation that such models recapitulate the characteristics of clinical tumors;
  • If you propose that a pathway may be essential for the etiology of multiple cancer types, explain how the function of that pathway and its perturbation will be experimentally explored (in all applicable cancer types or in a subset; the latter should be justified);
  • If only a subset of cancer types affected by a pathway are studied, include as part of the justification how you plan to address intrinsic or acquired drug resistance and if the results can be extended to the other cancer types;
  • Describe and justify the high-throughput screening approaches you will use to address your specific aims;
  • Explain how the outcomes of the proposed project can be adapted by the research community at-large to accelerate progress in studies of cancer biology, including the understanding of the cellular wiring of the components and the impact on therapeutic development;
  • Projects that include the study of synthetic lethality, such as protein-protein interactions, small molecule and immunotherapy combinations, or regulatory RNA functions, describe how they are identified, and addressed. Also explain how they improve the precision of interactions with specific targets;
  • For projects that include the development of probes (e.g., small molecules which function as molecular glues, PROTACs or "CRISPRs"), that modulate the targets (and their function) address how they improve the interpretation of the experiments and the understanding of cancer mechanisms within different cellular context;
  • Explain how the functional aspects of the putative target candidates will be probed, describing, e.g., strategies to interfere with the functions of the identified potential targets, development of perturbagens, if applicable, and other aspects to ensure a robust path for validation of targets, biomarkers, etc.;
  • For methodological improvements proposed, include specific, preferably quantitative benchmarks.; and
  • For novel technical approaches, i.e. that have not been utilized in the CTD2 Network to date, outline relevant aspects/parameters that will have to be considered to ensure integration with other types of data and outlets for CTD2 results (e.g., data format file structure that you plan to utilize for submitting such data to the CTD2 Data Portal).
  • Using a separate subheading “Trans-Network Collaborative Research Activities”, describe briefly the following items:
    • What the Network can do to enhance your project: Outline the possible directions for trans-Network collaborative efforts that can benefit your proposed project, e.g., by exploring new/additional datasets. Depending on the specific needs and experimental approaches of your project, you may consider such aspects as:
      • Using multiple "read-outs" in high-throughput screens by the Centers in the Network to enhance the interpretation of the results and/or;
      • For projects using the CRISPR technology, benefits to be gained by access to the various specific constructs and guide RNAs, “control” screening models/cell lines etc.
  • What you may offer for other Network projects: List unique strengths of your team that may be useful for other CTD2 awardees.

Note: Do not describe any specific lines of experiments for the collaborative activities in the application, as they will be defined based on the collective input from CTD2 investigators and following review and recommendations by the Steering Committee.

Note:Supplementary documentation for such aspects as the characteristics of cancer models or perturbagens available may be uploaded under "Other Attachments."

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.

The following modifications also apply:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan which is aligned with the FAIR (Findability, Accesibility, Interoperability and Reuse) requirements for data management and stewardship.
  • This plan should also address sharing of resources such as, cancer models, protocols, reagents and other tools that a Center develops;
  • The plans should address standardized data sharing formats that are compatible with  Cancer Data Standards Registry and Repository (caDSR);
  • The plan should also include a practical process for submitting data to the CTD2 Data Portal (defining timelines, frequency of updates, data quality control, etc.) and no later than when a manuscript is accepted for publication;
  • Awardees are expected to work together to develop and implement common, uniform standard operating procedures (SOP) and technical formats for depositing data into public databases. Examples of what has already been achieved can be found on the CTD2 Data Portal (https://ctd2.nci.nih.gov/dataPortal/). It is expected that these data reporting solutions will be compliant with generally accepted publicly available standards. Human subject characterization data (i.e., “clinical data”) is expected to conform to cancer Common Data Elements registered in the cancer Data Standards Repository; for examples see (https://wiki.nci.nih.gov/display/caDSR/caDSR+Database+and+Tools). Data generating methods and analysis algorithms are expected to be defined in sufficient detail to enable duplication by other investigators (GitHub is an example of a code repository); and
  • For the preparation of Data Sharing Plans, applicants are strongly encouraged to consult the approved data release policy developed by the current CTD2 Network. The data sharing policies used for CTD2 projects are fully consistent with all the expectations for awards to be made under this FOA as well.
  • Submission of validated data in the CTD2 Dashboard is strongly encouraged.
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 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.

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, NIH. Applications that are incomplete or non-compliant 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 for this FOA:What is the potential of the proposed project in terms of contributing significantly and meaningfully to the overarching goals of the entire CTD2 Initiative, i.e., to improve understanding of cancer gene function in pathways and cellular wiring; identify novel candidate therapeutic targets, molecular modulators of cancer phenotypes, and/or biological markers using new and/or improved approaches; and improve prediction of outcomes of combination treatments? How significant is the proposed research in terms of improving understanding of cancers' etiology and identifying targets, markers and/or precise modulators (with minimal off-target action) within the context of each tumor's heterogeneity? What is the likelihood that the proposed study will inspire and/or facilitate future development of novel therapeutic modalities and/or provide rationale for other types of clinically relevant studies?

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: How appropriate are the depth and balance of needed expertise (informatics vs. experimental, including disease experts) across the members of the team?

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?

Specific for this FOA: How compelling are the proposed approaches in terms of breadth of coverage, throughput, efficiency, etc.? How adequate are the applicants' plans and capacity to study proposed ideas across multiple cancer types? Given the scientific goals of the proposed project, is there sufficient attention to technology/methodology improvements? How strong are the plans for the necessary informatics infrastructure, including data/information transfers and exchanges, to be developed? Are they sufficient for both the anticipated needs of the proposed project and sharing across the entire CTD2 program?

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

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 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.

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 recipient'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.

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 awardee 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. 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 laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. 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 http://www.hhs.gov/ocr/civilrights/understanding/section1557/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.

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 “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 OMB administrative guidelines, HHS 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.

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

  • Defining the research plan and goals;
  • Overseeing the execution of the projects and coordinating/overseeing research design;
  • Ensuring compliance with the mandatory regulations (including protection of human subjects);
  • Overseeing establishment and maintenance of appropriate quality control procedures;
  • Overseeing final data analysis and interpretation and preparation of publications;
  • Serving as a voting member of the CTD2 Steering Committee and participating (along with other collaborating investigators as appropriate) in the annual Steering Committee meetings;
  • Implementing the recommendations of the CTD2 Steering Committee to the extent consistent with the applicable grant regulations;
  • Ensuring and overseeing sharing results, resources, methods, etc. within the CTD2 Network and with the scientific community upon validation;
  • Attend, if invited, a biannual meeting at which members from this and other NCI-funded initiatives will share their results and learn from each other.
  • Participating in trans-Network collaborative activities (to be supported by the restricted set-aside funds) prioritized and recommended by the Steering Committee; and
  • Any PD/PI on a CTD2 award must maintain effort commitment of at least 1.2 person-month in each year of the award.

Awardees will be expected to work together and develop and implement common, uniform standard operating procedures (SOP) and technical formats for depositing data into public databases. It is expected that these data reporting solutions will be compliant with generally accepted publicly available standards. Human subject characterization data (i.e., “clinical data”) shall be described using Common Data Elements registered in the caDSR (Cancer Data Standards Registry and Repository). Data-generating methods and analysis algorithms shall be described in sufficient detail to enable duplication by other investigators.

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.

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

A designated NCI Program Director(s) acting as a Project Scientist(s) will have the following responsibilities:

  • Participating in the activities of CTD2 Steering Committee;
  • Providing technical assistance and advice to the awardees as appropriate;
  • Stimulating interactions among awardees;
  • Monitoring progress of the program as a whole and the specific studies conducted;
  • Conducting periodic site visits for discussions with awardee research teams;
  • Facilitating interactions/collaborations between the CTD2 awardees and other NCI-sponsored programs, investigators, or organizations that may contribute to the CTD2 goals;
  • Serving as a liaison between the CTD2 awardees and NCI staff members and investigators that may provide additional expertise and/or resources to the program;
  • Approving the release of funds from the restricted set-aside portions of the budget for collaborative trans-Network activities recommended by the Steering Committee;
  • Monitoring the adherence of the awardees to the approved data sharing plans; and
  • Coordinating the additional resources that NCI will establish for the CTD2 program, including electronic communication support (see details below).

The NCI will also assist the awardees by establishing and maintaining communication resources (such as a NCI-Hub site) for intra-Network document sharing, hosting CTD2 Data Portal,https://ctd2.nci.nih.gov/dataPortal/, and Dashboardhttp://ctd2-dashboard.nci.nih.gov/; and Network webpages for data, information and resource sharing with the scientific community at large.

The NCI reserves the right to adjust funding, withhold, suspend, or phase out the support to the awardee if the team is unable to meet the performance requirements set forth in these Terms and Conditions of Award, or significantly lower the level of performance.

A NCI Program Director acting as the Program Official 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 Steering Committee will serve as the main governing board for CTD2. The CTD2 Steering Committee will consist of the following voting members:

  • One representative of each awardee (a PD/PI); and
  • One NCI representative.

Each voting member will have one vote. The Steering Committee will be chaired by one of the CTD2 PDs/PIs on rotating basis to be determined upon start of the Program. In the absence of PD/PI, a designated senior investigator will chair Steering Committee meeting.

Additional NIH/NCI representatives may participate in the Steering Committee meetings as non-voting members as needed.

The Steering Committee may form subcommittees as needed. NCI Project Scientist may participate in such sub-committees as he/she deems relevant. Other NIH/NCI staff members or non-NIH scientists may be invited as members of such sub-committees.

The main functions of the Steering Committee will include the following:

  • Coordination of the development and implementation of common, uniform standard operating procedures (SOP) and technical formats for depositing data into public databases by all CTD2 awardees;
  • Establishing procedures guiding how collaborative activities/pilot studies (to be supported by the restricted set-aside funds on each CTD2 award) will be initiated, formulated, and presented to the Steering Committee for recommendation regarding collaborative execution;
  • Reviewing (with the help of external reviewers if needed), prioritizing, and recommending for activation trans-Network collaborative activities to be supported by these restricted set-aside funds; and
  • Reviewing on a regular basis the overall performance of the CTD2 as a Network.

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)

Jean C Zenklusen, Lic.Chem., Ph.D. 
National Cancer Institute (NCI)
Telephone: 240-781-3409
Email: jz44m@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)

Sean Hine
National Cancer Institute (NCI)
Telephone: 301-276-6291
Email: hines@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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