Department of Health
and Human Services (HHS)
and Human Services (HHS)
EXPIRED
National Institutes of Health (NIH)
National Cancer Institute (NCI)
U01 Research Project Cooperative Agreements
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:
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.
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.
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts).
Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.
Applications that do not comply with these instructions may be delayed or not accepted for review.
Purpose
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:
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:
Examples of topics to be addressed include, but are not limited to, the following:
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.
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.)
See Section VIII. Other Information for award authorities and regulations.
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.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Not Allowed: Only accepting applications that do not propose clinical trials.
Need help determining whether you are doing a clinical trial?
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.
Budgets up to $750,000 direct costs per year may be requested.
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.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
Federal Governments
Other
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.
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.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
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:
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.
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:
The letter of intent should be sent to:
Jean C Zenklusen, Lic.Chem., Ph.D.
National Cancer Institute (NCI)
Telephone: 240-781-3409
Email: [email protected]
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
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:
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.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, 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:
Under "Innovation", address the following:
Under "Approach", address the following:
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:
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.
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential 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.
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.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
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.
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?
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?
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?
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?
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?
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
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.
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.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
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.
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.
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:
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:
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:
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:
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.
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.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]
Jean C Zenklusen, Lic.Chem., Ph.D.
National Cancer Institute (NCI)
Telephone: 240-781-3409
Email: [email protected]
Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected]
Sean Hine
National Cancer Institute (NCI)
Telephone: 301-276-6291
Email: [email protected]
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.