Department of Health
and Human Services (HHS)
and Human Services (HHS)
National Institutes of Health (NIH)
National Cancer Institute (NCI)
U24 Resource-Related Research Projects Cooperative Agreements
The National Cancer Institute (NCI) is publishing this Funding Opportunity Announcement (FOA) to request applications for the Coordinating Center, Program on the Origins of Gastroesophageal Cancers (U24). This new program will build on recent molecular classifications of gastroesophageal cancers, significant understanding of their cancer genomics, and advances in stem cell research to examine and define how these related cancers initially evolve at the cellular level. The program will address the complex mechanisms and effectors that direct the proliferation and expansion of tumor-initiating cells and their progeny to initiate these cancers. The focus of the FOA is on gastric and gastroesophageal junction adenocarcinomas. The program is envisioned to provide unprecedented opportunities to outline the earliest cellular changes in transformation that precede any histological manifestations or neoplasia. This new program will be composed of up to six large R01 research grants (to be supported by RFA-CA-21-026) and one Coordinating Center grant (to be supported by this FOA).
September 8, 2021
| Application Due Dates | Review and Award Cycles | ||||
|---|---|---|---|---|---|
| New | Renewal / Resubmission / Revision (as allowed) | AIDS | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
| October 08, 2021 | Not Applicable | Not Applicable | March 2022 | May 2022 | July 2022 |
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.
No late applications will be accepted for this FOA.
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts).
Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.
Applications that do not comply with these instructions may be delayed or not accepted for review.
Purpose
The National Cancer Institute (NCI) is publishing this Funding Opportunity Announcement (FOA) to request applications for the Coordinating Center, Program on the Origins of Gastroesophageal Cancers (U24). This new program will build on recent molecular classifications of gastroesophageal cancers, significant understanding of their cancer genomics, and advances in stem cell research to examine and define how these related cancers initially evolve at the cellular level. The program will address the complex mechanisms and effectors that direct the proliferation and expansion of tumor-initiating cells and their progeny to initiate gastroesophageal cancers. The focus of the FOA is on gastric and gastroesophageal junction (GEJ) adenocarcinomas. The program is envisioned to provide unprecedented opportunities to outline the earliest cellular changes in transformation that precede any histological manifestations or neoplasia.
The program will consist of the following components:
The program will thoroughly and comprehensively tackle cancers of the stomach and GEJ regions to compare and contrast the contributions of tumor-initiating cells and their fundamental mechanisms and adopt a community approach to experimental challenges and methodological hurdles.
The Coordinating Center supported by this FOA will be the key entity responsible for facilitating and coordinating this new program and its collaborations, and enabling the resolution of technical challenges, sharing of models and resources, and advancement of technologies.
Background
Gastroesophageal Cancers
Gastroesophageal cancers are aggressive and lethal cancers with poor survival in the United States and worldwide, averaging more than 1.6 million new cases and over 1 million deaths. While the incidence of distal stomach cancer has significantly decreased in the United States and the western European regions, the incidence of cancers of the proximal stomach as well as the lower esophagus and gastroesophageal junction has increased. Etiological factors such as diet, obesity, gastroesophageal reflux disease (GERD), and others may underlie this increase.
Gastroesophageal cancers mainly encompass esophageal squamous cell carcinoma (ESCC), esophageal and gastric cardia adenocarcinomas (including gastroesophageal junction (GEJ) tumors), and distal gastric adenocarcinoma. GEJ tumors are particularly challenging and have inconsistently been considered as either gastric or esophageal, but the Siewert system was developed to address this challenge and to facilitate uniform reporting of their clinical managements and interventions. The majority of the above tumors are adenocarcinomas with shared pathology, genomics, and molecular features.
Gastroesophageal adenocarcinomas generally evolve through augmentation of mucosal injury and repair processes enacted by chronic inflammation that would lead to cancer formation. Risk factors underlying such inflammation include infections (Helicobacter pylori for distal stomach and Epstein Barr for cancer with lymphoid stroma) for sporadic gastric cancers, genetic susceptibility factors for inherited gastric caners, or GERD for esophageal adenocarcinoma. Diet that is poor in fruits and vegetables and rich in salt and nitrates has also been thought to underlie gastric cancer risk mainly in certain ethnic groups. Obesity is cited as an important risk factor particularly for esophageal adenocarcinoma, but the fundamental molecular details are unclear.
Landmark genomics studies led by the NIH Cancer Genome Atlas Program distinguished gastroesophageal adenocarcinomas from ESCC, which resembled squamous lesions from other organs. On the other hand, esophageal adenocarcinoma tumors, the chromosomal unstable subtype of most type II/III tumors (GEJ, cardia), and approximately 50% of distal gastric adenocarcinoma showed significant genomics similarity. This finding has critically underlined the molecular connections between these tumors irrespective of their anatomical locations and reflected, together with other studies, that gastroesophageal adenocarcinomas may represent a distinct disease entity.
Cell(s) of Origin
While research on the biology of gastroesophageal cancers and their precursors has revealed various molecular and cellular mechanisms associated with malignant conversion, limited information is available on the true identity of the cell(s) of origin for these cancers and where in the gastroesophageal field it all starts. Investigations in this important yet complicated research area require coordination, collaboration, and access to in vivo and in vitro models that can track the cell of origin correctly and reproducibly. Inadequate coordination and access to resources compounded by methodological limitations is impeding this research area.
Various theories are proposed concerning the cell of origin underlying gastroesophageal cancers that highlight the controversies and sometimes disagreements existing in this field of research. For the esophagus, they include: a) esophageal squamous epithelial trans-differentiation or trans-commitment to columnar cells of the precursor lesion Barrett’s metaplasia; b) progenitor cells in esophageal submucosal glands or their ducts; c) stem/progenitor cells in gastric cardia; d) cells at the gastroesophageal junction including residual embryonic cells or transitional basal cells; and e) circulating bone marrow cells. For all these proposed cells of origin, the mechanisms underlying their recruitment and participation are rather similar and initiated by mucosal injury and inflammation from reflux leading to esophageal ulceration. This may promote the involvement/migration of these highly dynamic cells from certain area(s) of the gastrointestinal continuum perhaps as an initial wound-healing response. The migration will be followed by trans-commitment of these cells to re-epithelize the damaged mucosa, thus producing a new but abnormal epithelium and eventually transformation. The placement of these cells at the peak of the cell hierarchy and their interactions with various extrinsic and local effectors can lead to both self-renewing tumorigenic cells and differentiated non-tumorigenic cells that may explain the genetic and phenotypic heterogeneity of these cancers.
For gastric cancer, studies have pointed to gastric stem cells as the probable cell of origin for this cancer. Gastric epithelial cell homeostasis is upheld by long lived stem cells and their niche, a complex environment composed of a subgroup of epithelial cells, supporting factors/signaling elements, and stroma. Genetic and epigenetic changes in these cells lead to their conversion to oncogenic cells and abnormal expansion culminating in transformation and gastric cancer. The Lgr5+ stem cells (leucine-rich repeat-containing G-protein coupled receptor 5) is viewed to underlie the origin of gastrointestinal cancers in general; however, gastric Lgr5+ cells may not be active stem cells and function as a reserve cell population in the corpus and the antral regions. Gastric chief cells that are present at the corpus gland base and express Lgr5 are thought to function as the reserve stem cells during gastric injury. There are also other reserve stem/progenitor cells that have the capacity to convert to Lgr5+ cells in response to injury. For example, the Villin -gal/(+) and Mist1(+) cells residing at the isthmus have specific physiologic functions in gastric mucosal development but chronic inflammation combined with specific mutation can lead to intestinal and diffuse gastric cancer. In the cardia region that is close to the esophagus, cardia glands also home Lgr5+ stem cells at their base and these cells have been implicated in the initiation of esophageal cancer.
Gastric cancer is also thought to originate from bone marrow-derived cells that are recruited to the stomach by inflammatory chemokines and other effectors. The Helicobacter pylori-induced multi-step transformation of gastric epithelium is shown to be associated with significant accumulation of bone marrow derived cells. This and other findings reflect that such cells could be the potential source of gastric cancer tumor-initiating cells and would migrate to the inflamed tissue environment, undergo abnormal transformation, and promote tumor initiation. Other research, however, could not detect these cells in the epithelium or glands of gastric cancer induced by carcinogen or infection with H. Felis.
Despite the above advances, major questions remain concerning: a) the exact identity of the cells underlying gastroesophageal cancer initiation; b) how the cells are being recruited or influenced by the inflamed mucosa; c) what are the intrinsic and extrinsic effectors regulating these cells; d) is one or more cell-whether regional or from neighboring areas-involved in the wound-healing response that could potentially lead to transformation; and e) are the initial events defined in animal models reflect the actual events in the human disease.
Ethnic, Racial, and Gender Disparities
Ethnic and racial disparities are reported in the incidence of gastric cancer in the USA. The disease is infrequent in whites with some exceptions (please see below) but people from Hispanic, African American, or Asian communities have a high disease burden with an incidence that is double the rate reported in whites. There is also a high incidence in immigrants from specific countries including non-Asian countries. The Asian population has a larger and disproportionate tumor burden compared to their representation in the overall population. In general, diet such as pickled and salted food has been considered as a risk factor for gastric cancer in these communities, but biological and genetic variables have been defined that contribute to the cancer risk and would be important to consider and integrate in research about the cellular origins of gastric cancer.
In addition to the ethnic and racial disparities, recent epidemiological studies have highlighted an increase in cancers of the gastric corpus, body, and to a lesser extent, fundus regions in non-Hispanic white women who are younger than 50 years of age. The gastric cancer male/female incidence rate ratio for these younger patients (aged 25-29 years) is 1.0 (compared to 2.5 for patients aged > 60 years). The histologic and molecular subtypes of this young onset cancer is not clear nor are the risk factors causing it. The decline in Helicobacter pylori infection and other factors including reproductive have been theorized as potential reasons for this increase.
For esophageal cancer, the trend is rather different and despite their similar risks theoretically, Caucasians and African Americans have a significant difference in esophageal adenocarcinoma incidence rate. The rate of esophageal adenocarcinoma is 4.5-fold higher in whites (incidence rate, 2.4/100,000 person-years) relative to African Americans (incidence rate, 0.5/100,000 person-years). This disparity is poorly understood but thought to point to differences in protective or susceptibility mechanisms for cancer. The expression of the glutathione’s transferase theta 2 (GSTT2) gene in African American esophageal normal mucosa is higher compared to mucosa from Caucasians. As this enzyme has a protective role against oxidative damage, lower levels of GSTT2 may leave the esophageal mucosa in Caucasians more susceptible to damage from GERD.
The above findings show that multiple effectors, some known and some postulated to have a role, exert complex effects on the transformation of gastroesophageal mucosa in various ethnic/racial/gender groups. Mechanistically, it is unclear how genetic/epigenetic/biological susceptibility factors work with chronic inflammation, wounding and eventual involvement of tumor-initiating cells to initiate the transformation. It is critical that ethnic, racial, and gender considerations be clearly integrated in the planning of this research program.
Functions of the Coordinating Center
The Coordinating Center will be responsible for implementing the plans for coordinating and facilitating the research activities conducted by the Program on the Origins of Gastroesophageal Cancers, and interactions across the research projects (to be funded under the companion FOA, RFA-CA-21-026). Therefore, the Coordinating Center must meet the following key attributes:
(A) Leadership and Management Vision. The Coordinating Center must be able to assume the coordination of the research activities performed by the program research grants. Accordingly, the Coordinating Center must demonstrate a clear leadership, innovative thinking, and capacity to provide scientific oversight and management of a transdisciplinary research team.
(B) Administrative and Logistical Support: The Coordinating Center is expected to provide the infrastructure required for promoting scientific collaborations across the grant projects, connect available resources, integrate research activities, and facilitate resources and technologies utilization across the program. The Coordinating Center is expected to organize the annual investigators meeting, recurring conference calls, and scientific webinars, and facilitate program discussions of challenges and formulation of solutions and new ideas. The Coordinating Center is also expected to provide statistical and computational support to program investigators.
(C) Data Coordination: The Coordinating Center is expected to support data management and sharing for the program through the generation and management of a centralized hub for data collection and dissemination across the program. The data hub can particularly enable the sharing of data on important resources, models and technologies available across the grant projects consistent with achieving the goals of the program. The Coordinating Center should perform data annotation and standardization and establish standards for data access particularly for technologies and methodological challenges to enable comparisons of the most appropriate and available platforms and sharing of available resources within the program. The Coordinating Center should plan to work with investigators on depositing digitally identifiable data concerning models, resources, technologies and challenges to this searchable data hub. Is should also establish access protocols for these data to permit efficient sharing of unique resources and technologies between investigators.
Evaluation of the Gastroesophageal Origin Program
The program will be expected to undergo an external evaluation process that will be coordinated by the NCI and the Coordinating Center. The evaluation will be based on the progress made by the research grants and milestones achieved towards meeting the scientific goals of the program. Key elements to be considered in the evaluation include the innovation of program research in facilitating the understanding of the origins of gastric and GEJ cancers; concepts, data, and models developed that facilitate this understanding and may emulate the human disease; strengths of the collaborations between awardees and with the Coordinating Center; and other measures of overall success. Specific measures of progress include peer-reviewed publications, achievements of proposed research goals, development of better technologies for cell tracking, and data, resource, and technology sharing between the awardees. Examples of highly successful outcome of the program will include the development of new theories or paradigms on how gastric and GEJ cancers initially form and what types of cells involved that could lead to future preventive interventions.
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 fund one award, corresponding to $500,000 (direct costs), for fiscal year 2022. Future year amounts will depend on annual appropriations.
The award budget should not exceed $500,000 (direct costs), including subawards.
A project period of 5 years is required.
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
For-Profit Organizations
Local Governments
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.
The RFA will be open to all qualified applicants, including new and early-stage investigators, who can establish and lead a Coordinating Center project. A multi-PI collaboration that can bring a new scientific expertise to program coordination is particularly encouraged.
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:
Rihab Yassin, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6230
Email: ry38k@nih.gov
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
with the following exceptions or additional requirements:
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
R&R Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
For this FOA, the Research Strategy must consist of the following sub-sections A, B, C, and D.
Sub-section A. The Coordinating Center Vision
This section must address the following key attributes:
A) The overall vision of the proposed Coordinating Center, its unique concepts, and innovative thinking approaches for coordinating the Program on the Origins of Gastroesophageal Cancers.
B) The applicant(s) scientific leadership and data management experiences that can enable the achievements of the program goals. This includes any experiences in coordinating of and providing scientific support for multi-institutional projects or trans-disciplinary research program, facilitating program communications, coordinating objectives, and facilitating scientific collaborations.
C) Available institutional infrastructures and resources that can enable management of the program including, but are not limited to, facilitating collaborations and interactions between investigators; facilitating the planning of the annual investigators meeting and addressing logistics; facilitating other program meetings and conferences; and facilitating data management and resource sharing.
Sub-section B. Administration and Leadership Module
This section must address the following key attributes:
A) The organization of the leadership structure of the Coordinating Center.
B) Plans for general oversight of the Program on the Origins of Gastroesophageal Cancers.
C) Plans for facilitating communications between the research projects as well as the projects and NCI scientific staff to sustain continuous interactions, consultations, and efficient resolutions of challenges.
Sub-section C. Meetings and Conferences Coordination Module
This section must address the following key attributes:
A) Plans for organizing the annual investigators meeting in collaboration with program investigators and NCI scientific staff. This includes plans for assembling the meeting program, inviting participants, and addressing logistical challenges.
B) Plans for coordinating periodic conference calls for the investigators and for assembling appropriate work groups as needed by the program.
C) Plans for participation in administrative site visits conducted by NCI staff.
D) Available institutional resources to facilitate the administrative and logistical support of these functions.
Sub-section D. Data Coordination Module
This section must address the following key attributes:
A) Plans for providing computational support and statistical analysis for the program.
This includes plans for the generation and management of a centralized hub for data collection and statistical analysis across the program. The data hub will particularly enable the consolidation of data on important resources, models and technologies available across the grant projects for collaborative research and consistent with achieving the goals of the program. Considerations should be given to data annotation and standardization and establishing standards for data access particularly data relevant to technologies and methodological challenges to enable comparisons of the most appropriate and available platforms. Accordingly, the Coordinating Center should plan to work with investigators on depositing digitally identifiable data concerning models, resources, technologies and challenges to this searchable data hub. It should provide detailed instructions to the program investigators on how to access the program data hub. It should also have an interface that can be accessed by the larger scientific community.
B) Plans for establishing access protocols for these data to permit efficient utilization of unique resources and technologies by investigators in the program as well as the larger scientific community as appropriate with the goals of the program. The protocols should address the process for prioritizing access to these resources and tracking the distribution of the models and resources to investigators in timely manners.
C) Plans for facilitating the discussions of technological hurdles, generating resolutions, and sharing information across the program.
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.
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 and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive 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: Does the proposed Coordinating Center provide important concepts and thinking approaches for managing the Program on the Origins of Gastroesophageal Cancers? Are the proposed vision and activities appropriate and can they meet the program needs? Do the Center’s vision and goals provide unique benefits and capacities to the program? Are the Center’s research infrastructure, resources, and scientific expertise adequate to support the program goals?
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: Are the PD(s)/PI(s) and other key staff well suited to lead the Coordinating Center? Do the PD(s)/PI(s) have appropriate experience and training in project or program management and are their managerial and collaborative capabilities adequately supported? Have the investigators demonstrated significant experience in coordinating collaborative trans-disciplinary research? If multi-PDs/PIs, are the expertise and skills complementary and integrated; are the leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the Center? Does the PDs/PIs have experience overseeing data management for multi-projects? How appropriate is the leadership structure of the Center in terms of achieving the overall goals of the Program?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Specific for this FOA: Does the application propose novel concepts and methods for managing and organizing the program? Are the concepts, strategies, or technologies novel in a limited or broader sense? Are the proposed strategies new, refinement, or improvement on current approaches in project management and coordination?
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: Are the overall research strategy of the Center, its organization, and plans for executing program coordination and data management well-reasoned and appropriate to accomplish the goals of the entire program? Can the Center's concepts and strategies ensure robust and unbiased scientific collaborations across the program? Are potential problems, alternative strategies, and benchmarks for success presented? Does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the program? Are the plan for workflow and proposed timelines appropriate? How adequate are the plans to achieve compatibility with the research projects to facilitate and support data collection and statistical analysis for the program? Are there appropriate infrastructure and scientific capacity for collaboration with the research projects and NCI?
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?
Specific for this FOA: Are the institutional infrastructure, facilities, equipment and other resources appropriate and available to the proposed Center to facilitate its mission and potential success? Will the Center benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Protections for Human Subjects
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
Inclusion of Women, Minorities, and Individuals Across the Lifespan
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Biohazards
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Resubmissions
Not Applicable
Renewals
Not Applicable
Revisions
Not Applicable
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) Sharing Model Organisms; and (2) 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.
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
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 U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipient 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 recipient for the project as a whole, although specific tasks and activities may be shared among the recipient and the NIH as defined below.
The PD(s)/PI(s) will have the following primary responsibilities:
The following additional responsibilities will also apply for the Coordinating Center awardee:
NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The designated NCI Program Staff will have substantial involvement as a Project Scientist in the award under this FOA. The specific functions of the substantially involved NCI staff include the following activities:
The NCI reserves the right to adjust funding, withhold, suspend, or terminate the support to the recipient if the investigators are unable to meet the performance requirements set forth in the required policies and procedures.
The NCI may designate additional NCI extramural staff members to have substantial involvement in coordination activities (as Project Scientists). The substantially involved NCI staff members will not attend peer review meetings. If such participation is deemed essential, these individuals will seek NCI waivers according to the NCI procedures for management of conflict of interest.
Additionally, an NCI Program Staff member acting as a 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 Responsibilities include:
The program will meet formally at least one time per year in a face-to-face meeting. A chair of the group will be selected at the first meeting to help coordinate the program's function. The designated chair will meet by teleconference with the NCI Project Scientist and Coordinating Center PI(s) as needed to address the program needs.
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 awardee, an NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two. 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: 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
Rihab Yassin, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6230
Email: ry38k@nih.gov
Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: ncirefof@dea.nci.nih.gov
Amy Bartosch
National Cancer Institute (NCI)
Telephone: 240-276-6375
Email: amy.bartosch@nih.gov
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.
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