Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)

Funding Opportunity Title

Alliance of Glycobiologists for Detection of Cancer (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

Reissue of RFA CA-07-020

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-CA-11-009

Companion FOA

None

Number of Applications

See Section III. 3. Additional Information on Eligibility.

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

93.393, 93.394, 93.395, 93.396

FOA Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to continue support for the program referred to as the “Alliance of Glycobiologists for Detection of Cancer” (http://glycomics.cancer.gov). Through this FOA, the NCI solicits new and competing renewal applications for research projects to elucidate how changes in cellular carbohydrates may promote cancer initiation and progression and use this information to identify glycan-based abnormalities that have the potential to serve as biomarkers for early cancer detection or risk assessment. These changes may be studied at the level of glycoproteins, glycolipids, glycosaminoglycans, and/or their binding proteins. The proposed projects must also address the ability of these biomarker candidates to accurately distinguish individuals with cancer from those without. It is expected that the most promising biomarker candidates will ultimately be tested in clinical validation studies, although such validation studies are not required for the proposed projects.  In addition to planning for the individual research projects, the applicants responding to this FOA must plan for the participation in trans-Alliance activities, including collaborative projects with other awardees.

All investigators with appropriate expertise and capabilities, irrespective of any prior association with the Alliance, are encouraged to consider applying to this FOA.

NOTE on Pre-Application Meeting: The NCI will hold a public pre-application meeting for investigators planning to submit applications in response to this FOA. This meeting will be open to the public and will be also available via NIH teleconferencing technologies. For updates and additional details on the pre-application meeting, please go to the Alliance web site at http://glycomics.cancer.gov. Participation in the meeting, although encouraged, is optional and not required for application submission.

Key Dates
Posted Date

July 28, 2011

Open Date (Earliest Submission Date)

September 7, 2011

Letter of Intent Due Date

September 7, 2011

Application Due Date(s)

October 7, 2011 by 5:00 PM local time of applicant organization.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

March-April, 2012

Advisory Council Review

May 2012

Earliest Start Date(s)

July 1, 2012

Expiration Date

October 8, 2011

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to continue support for the program referred to as the “Alliance of Glycobiologists for Detection of Cancer” (http://glycomics.cancer.gov). Through this FOA, the NCI solicits new and competing renewal applications for research projects to elucidate how changes in cellular carbohydrates may promote cancer initiation and progression and use this information to identify glycan-based abnormalities that have the potential to serve as biomarkers for early cancer detection or risk assessment. These changes may be studied at the level of glycoproteins, glycolipids, glycosaminoglycans, and/or their binding proteins. The proposed projects must also address the ability of these biomarker candidates to accurately distinguish individuals with cancer from those without. It is expected that the most promising biomarker candidates will ultimately be tested in clinical validation studies, although such validation studies are not required for the proposed projects.  In addition to planning for the individual research projects, the applicants responding to this FOA must plan for the participation in trans-Alliance activities, including collaborative projects with other awardees.

All investigators with appropriate expertise and capabilities, irrespective of any prior association with the Alliance, are encouraged to consider applying to this FOA.

Scientific Background

The majority of research on cancer biomarkers has focused on cancer-specific changes at the genomic, epigenetic, transcriptomic, and proteomic levels. However, there are other aspects of cellular biochemistry in which cancer cells differ from their normal counterparts. Complex carbohydrates represent one such set of molecules that play major roles in oncogenesis, but their potential to serve as cancer biomarkers remains under-explored. Among the multitude of possible glycan changes, only a limited number are detected in cancers. Studies suggest that various cancer-specific alterations in carbohydrate structures may confer survival advantage on cells harboring these alterations and, thereby, contribute to cancer progression. These findings indicate also the potential of glycomic aberrations as targets for cancer prevention and/or as cancer biomarkers. Despite their importance, the potential of abnormally glycosylated molecules to serve as cancer biomarkers remains unrealized. This situation stems in part from the technical challenges encountered in analyzing complex carbohydrate structures. Cellular biosynthesis of glycans is a non-template process that is capable of generating a large variety of branched structures. In addition, the complexity of carbohydrate structural chemistry, makes it difficult to distinguish glycan isomers. Despite these difficulties, recent advances in glycomic technologies make systematic studies of glycan-based biomarkers feasible.

The structures of all oligosaccharides synthesized by a cell result from the concerted action of a series of highly specific glycosyltransferases, glycosidases, and modification enzymes (sulfotransferases, acetylases, etc.) which are mostly localized in the endoplasmic reticulum and the Golgi apparatus. Glycan synthesis proceeds by the sequential addition/removal of individual saccharide units. Abnormal expression of even a single enzyme participating in this process may alter the subsequent steps and give rise to aberrant oligosaccharide structures. The glycome synthetic machinery is frequently modified during oncogenic transformation leading to the accumulation of aberrant products. For example, abnormal or unusual glycan moieties are often detected on the surface of tumor cells, as well as among secreted glycoproteins. Many well known tumor-associated antigens are glycolipids or glycoproteins that contain aberrant glycan structures.

Glycosylated biomolecules offer several advantages as a potential source of cancer biomarkers. While protein biomarkers frequently occur in low abundance, distinctive cellular glycan structures, including those that are tumor-specific, are typically fairly abundant. Such structures are usually synthesized in multiple copies on a single glycoprotein molecule. In addition, the same tumor-specific glycan structures may be present on several different glycoproteins. Importantly, many currently used biomarker molecules, such as prostate specific antigen, CA125, and carcinoembryonic antigen, are monitored solely based on protein levels, not on their tumor-specific glycan moieties. Several studies have shown that the clinical performance of these biomarkers may be improved by including an analysis of their glycan moieties. Furthermore, tumor-derived glycoproteins found in blood may bear aberrant tumor-derived glycans allowing them to be distinguished from glycoproteins produced by the liver. Glycoproteins secreted from a tumor may also be identifiable in body fluids that are typically amenable for clinical testing. As the cell surface localization of most glycoproteins, proteoglycans, and glycolipids exposes them to the immune system, aberrant glycans on tumor cells can invoke an immune response.

Research Objectives

This Program is designed to take advantage of recent advances in glycobiology with the overarching goal to systematically explore novel glycan-based diagnostic strategies for early cancer detection and/or glycan-based strategies for cancer prevention. This goal is in line with the strategic focus of the NCI on early detection, prevention, and prediction of cancer risk. 

General Requirements and Scope of Applications

To address the goals of this FOA, projects proposed must be focused on an appropriate combination of the following three areas of studies:

1)    Elucidation of the biological basis by which changes in glycan structure contribute to cancer initiation and progression;

2)    Exploration of aberrant glycan structures to serve as biomarkers for the detection of early stage cancers; and

3)    Discovery of new glycan-based targets suitable for cancer prevention.

Moreover, the proposed projects should be designed so as their outcomes can serve as the basis for further clinically-oriented efforts, such as development of diagnostic tests for early stage cancers or interventions to aid in cancer prevention. 

For biomarker discovery and/or development, applicants may propose either an unbiased approach or a hypothesis-driven approach derived from the exploration of cancer-specific glycan biology.  Such efforts should include testing of biomarker candidates to determine their sensitivity and specificity. Such studies are expected to use well-annotated specimens from cancer patients and appropriate controls (specimens from cancer-free subjects).

Some investigated biomarker candidates might be applicable to purposes other than stated above, e.g., as markers for cancer risk, prognosis, monitoring of cancer recurrence, or prediction of therapeutic responses. Moreover, the proposed studies may be relevant to and eventually inspire studies on new therapeutic strategies. However, the proposed applications must be focused specifically on early cancer detection, diagnosis, and cancer prevention. Applications focused predominantly on therapeutic aspects will not be considered responsive to this FOA.

Examples of topics or strategies that can be proposed are listed below, but note that these lists are by no means inclusive. The term “glycomics-relevant genes” is used to refer to genes encoding proteins participating in the synthesis of monosaccharides or complex carbohydrates, posttranslational aspects of glycoprotein maturation, and/or glycan binding/recognition.

Examples of Investigations Relevant to Tumor Glycobiology

Expression Profiling of Tumors  - identify changes in the expression of glycomics-relevant genes. These changes may be studied to explain specific alterations in glycosylation observed with cancers and/or to predict changes in glycan structures that become evident during oncogenesis.

Identification and Characterization of Genomic Aberrations - mutations, changes in DNA segment copy number, loss of heterozygosity, and/or epigenetic changes in glycomics-relevant genes.  Functional effects of these aberrations on the expression of specific glycomics-relevant genes may also be studied to gain in-depth insights into how the glycobiology of tumor cells is altered.

Roles of Glycans in Inflammation - research on the roles of glycans and their complementary glycan binding proteins in chronic inflammation or interactions of immune cells with affected tissues that contribute to cancer initiation or progression.

Cancer Precursor or Stem Cells – research on changes in glycomic structures affecting properties in these cells and surrounding stroma and how these changes may contribute to oncogenesis.

Examples of Research Strategies for Glycan-Based Biomarkers

Glycan Structural Analysis - Identification of glycan structures that are unique to certain cancers. Due to the complexity of chemical linkages in oligosaccharides, structural analysis of all biomarker candidates should include, where possible, detailed elucidation of all glycosidic bonds including sites of attachment to defined saccharides and anomeric configurations. If glycan modifications are discovered, their chemical characteristics must be determined. The ability to localize these glycan biomarker candidates to specific glycoproteins (or proteoglycans), and possibly even sites of attachment to defined residues on the polypeptide core, may significantly improve specificities of the biomarkers.

Glycan Profile Comparisons - Glycan profiles of tissue specimens may be useful for cancer diagnostics. It may be feasible to expand the glycan biomarker analysis beyond tissue samples. For example, informative glycan profiles may be obtained by using body fluids such as serum, urine, stool, lavages, etc.

Glycan Array Technologies - Glycan arrays could be used to analyze the specificity of tumor-derived carbohydrate-binding proteins, discover cancer specific autoantibodies, or determine the binding of tumor cells to defined oligosaccharide structures. Other innovative uses of glycan arrays for biomarker discovery or testing will also be considered.

Lectins – Lectins could be used as a glycan biomarker discovery tool and could be employed in tests to detect or measure such biomarkers. Differential lectin binding to glycans of cancer specimens may be useful for screening for potential biomarkers. In such a case, the experimental design must also involve complete structural determinations of relevant oligosaccharides by other methods.

Carbohydrate-Specific Monoclonal Antibodies – Epitopes recognized by carbohydrate-specific monoclonal antibodies often show greater specificity than that of lectins. Applicants proposing to use monoclonal antibodies for detection of specific glycan structures must consider the possibility that the antibody may cross-react with a series of related structures and, consequently, it may be essential to corroborate the structures of any purported biomarkers by other methods.

Glycan Biomarkers Derived from Body Fluids - Applicants are encouraged to include the use of body fluids or other specimens obtained from human subjects by minimally invasive procedures. Clinical test development will be easier if biomarkers are identifiable in serum or plasma, urine, stool, and saliva. Still, other types of specimens requiring somewhat more invasive procedures (lavages, fine needle aspirates, samples obtained endoscopically, etc.) may be appropriate for certain cancers.

Biological Models. Despite certain drawbacks, cell lines derived from human tumors may prove beneficial in the search for effective diagnostic biomarkers provided that the identified glycan structures are also present in patients with cancer.

The use of animal models will not be considered responsive to this FOA unless compelling evidence is provided that the proposed animal model displays equivalent biomarkers to those found in the corresponding human tumors. Studies using human tumor xenografts in animals, however, may be appropriate for the goals of this FOA.

Investigator Teams. Groups responding to this FOA will need diverse expertise and capabilities to effectively carry out the proposed research projects and productively contribute to trans-Alliance activities. It is expected that these capabilities will include at least the following areas:

A. Glycobiology and Glycomic Biomarker Discovery. It is anticipated that the PD(s)/PI(s) will have expertise in tumor glycobiology and glycomic biomarker discovery and development.  In addition to glycobiologists, investigators with expertise in related disciplines, such as proteomics, immunology, and cell biology may also strengthen the proposed projects.

B. Carbohydrate Analytical Expertise. Thorough characterization of the complex carbohydrates to be investigated requires expertise in glycomic technologies and strong analytical skills relevant to structural or synthetic carbohydrate methodologies. Groups that may not have these capabilities “in house” are strongly encouraged to establish collaborations with outside investigators having relevant expertise in complex carbohydrate chemistry.

C. Statistical Support. Analysis of multidimensional data from a multitude of samples requires biostatistical expertise. Every team should have access to the expertise to analyze diagnostic parameters of cancer biomarkers, to design case/control studies to determine biomarker performance using patient samples, and to analyze the statistical significance of the results from these studies.

Clinical Specimens.  Access to quality clinical specimens is essential for the discovery of effective biomarkers and for testing their diagnostic performance. Projects proposed in response to this FOA must be based on biospecimens collected using standard operating procedures and with good clinical annotations.  Therefore, each team must demonstrate access to sufficient clinical specimens either by identifying an appropriate clinical partner who can provide specimens or by obtaining access to suitable tissue banks (see links below). Note that this FOA will not support prospective patient accrual to support the discovery or development of biomarkers. Clinical partners should have the specimens already collected and available, or demonstrate the ability to provide prospectively collected specimens through their existing, separately funded resources. Details concerning extent and nature of archived specimens available should be specified. The NCI Specimen Resource Locator (http://pluto3.nci.nih.gov/tissue/default.htm) is a resource that investigators can use to locate appropriate human tissue collections for their research projects. See details below on other biospecimen-relevant resources available to the Alliance.

Note: Even though technology development as such remains beyond the scope of this FOA, in planning their research projects, applicants are encouraged and expected to devote some efforts to the adaptation of important technical developments that may occur during the duration of the project.

Interactive Structure of the Alliance

The awardees funded under this FOA will form an interactive network termed the Alliance of Glycobiologists for Detection of Cancer with a Steering Committee as the governing body (for details see Section VI.2. Terms and Conditions of Cooperative Agreements). In addition to the support of individual research projects, the goal of this FOA is to facilitate complementary interactions across the Alliance. The planned interactions will include participation of the awardees in collaborative research projects that will be supported by dedicated set-aside funds to be included in all budget requests (see Section IV. 2. Content and Form of Application Submission of this FOA). Collaborative research projects and other joint trans-Alliance activities will be reviewed by the Steering Committee and recommended for approval by the NCI. The Steering Committee will establish specific procedures guiding how these collaborative projects will be formulated and proposed for approval and collaborative execution. Thus, no description or plans for these projects are to be included in the application. Nonetheless, applicants are encouraged to indicate their unique expertise and capabilities that may be useful for such joint endeavors as well as outline general directions that, in their opinion, will particularly warrant joint exploration.

Partnering with other Glycomics and Biomarkers-oriented Programs and Resources

The Alliance is expected to interact in partnership with several other major programs funded by the National Institutes of Health that focus on glycomics and/or cancer biomarkers.

Individual projects and the entire Alliance may benefit from access to resources available from the following glycomics-oriented programs supported by NIH:

1) The Consortium for Functional Glycomics (CFG) (http://www.functionalglycomics.org) supported by the National Institute of General Medical Sciences (NIGMS) as well as other NIGMS-supported initiatives can provide chemical reagents, glycol-enzymes, research protocols, and database resources to interested qualifying investigators. NIGMS will continue to support the following CFG resources: CFG databases, production of glycan arrays, the glycan array screening facilities, the glyco-enzyme initiative, the CFG transgenic mouse models, glycan library, and screening on the CFG glycomics-related gene array (on a fee for service basis).

2) The three Glycomics and Glycotechnology Resource Centers (http://www.ncrr.nih.gov/Glycomics) presently supported by the National Center for Research Resources (NCRR) are focused on the unique analytical challenges of carbohydrates and glycoconjugates. These centers include The Integrated Technology Resource for Biomedical Glycomics (http://glycomics.ccrc.uga.edu/), The Research Resource for Integrated Glycotechnology (http://glycotech.ccrc.uga.edu/), and The Resource for Mass Spectrometry in Biology and Medicine (http://www.bumc.bu.edu/msr/). Their shared goal is to create novel, highly effective technologies and methods, with a strong focus on support for the research community and sharing a range of expertise, technology, and resources. For more information, see the web sites of individual centers. In the context of the NIH reorganization plans, these centers will continue to be supported within the NIH.

3) The Programs of Excellence in Glycosciences (http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-10-026.html ) supported by the National Heart, Lung, and Blood Institute (NHLBI) have common interests with the Alliance in how carbohydrates and their binding proteins function in disease. Applicants may consider these programs for sharing resources and expertise.

All applicants are encouraged to consider the resource capabilities of these programs in planning their research projects. These programs may also serve as a valuable source of potential collaborators in glycomics-related areas.

The Early Detection Research Network (EDRN) (http://edrn.nci.nih.gov/), which is funded by NCI, is a consortium to promote clinical validation of cancer biomarkers for early detection, risk assessment, and diagnosis.  As the development of promising glycan biomarkers by the Alliance progresses, they should be considered for clinical validation studies. The EDRN will collaborate with the Alliance to facilitate validation of glycomic cancer biomarkers in several ways. Assistance with study design and statistical analysis is available from the EDRN Data Management and Coordinating Center. The EDRN Clinical Validation Centers may assist with patient accrual and collection of clinical specimens for validation studies. These centers may also be able to provide access to clinical specimens during the discovery or developmental phases of biomarker investigation. Specimen reference sets are also available from the EDRN for testing biomarkers in blinded studies for verification purposes. EDRN Biomarker Reference Laboratories may be able to participate in the development and standardization of specific tests and offer cross-laboratory confirmation of test results. Applicants should be aware, however, that many of the less common cancer types are not currently covered by EDRN investigators.

The EDRN hosts a biospecimen resource termed ERNE that can be used to search for clinical specimens. The search module for ERNE can be found at the following URL: http://edrn.nci.nih.gov/specimens#

To facilitate interactions of the Alliance and its investigators with other relevant NIH programs, representatives of these programs are expected to participate in the Alliance Steering Committee.

Additional Relevant NCI Programs

In addition to the above mentioned glycomics and biomarker-oriented programs, applicants responding to this FOA may consider taking advantage of other relevant NCI Programs such as  The Cancer Genome Atlas (TCGA) (http://cancergenome.nih.gov), the Clinical Proteomic Technologies for Cancer (CPTC) (http://proteomics.cancer.gov), and the Tumor Microenvironment Network (TMEN) (http://tmen.nci.nih.gov). For example, applicants may consider these programs as a source of potential collaborators.

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.

In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the PD/PI, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".  

Application Types Allowed

New
Renewal

The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

NCI intends to commit $3.5 million in FY 2012 to fund six to seven awards.

Award Budget

Application budgets are limited to $350,000 in direct costs for any single year. 

Award Project Period

The maximum period is 5 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information

1. Eligible Applicants
 
Eligible Organizations

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

Governments

Other

Foreign (non-U.S.) components on applications submitted by U.S. Organizations are allowed.

Required Registrations

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) 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 SF 424 (R&R) Application Guide.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Applicants are permitted to submit more than one application to this FOA, however, no more than one award will be funded to an investigator acting as the Program Director/Principal Investigator (PD/PI). A PD/PI may serve as a co-investigator on another award funded by this initiative.

Section IV. Application and Submission Information

1. Requesting an Application Package

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

Descriptive title of proposed research
Name, address, and telephone number of the PD(s)/PI(s)
Names of other key personnel
Participating institutions
Number and title of this funding opportunity

The letter of intent should be sent to:

Karl Krueger, Ph.D.
Division of Cancer Prevention
National Cancer Institute
6130 Executive Boulevard, Suite 3147, MSC 7362
Bethesda, MD 20892-7362
Telephone: (301) 594-1044
Fax: (301) 402-8990
Email: kruegerk@mail.nih.gov

Required and Optional Components

The forms package associated with this FOA includes all applicable components, mandatory and optional.  Please note that some components marked optional in the application package are required for application submission. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

Page Limitations

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

Additional Budget-Related Information:

PHS 398 Research Plan Component

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

Within the 12 page limit of the Research Strategy address the following aspect (under a separate sub-heading):

Trans-Network Activities. In addition to the standard description of the proposed individual Research Project, applicants are expected to include (within the overall page limit for Research Strategy section) a brief description of their unique expertise, resources, and capabilities that may be useful for joint trans-Alliance activities and outline general directions that, in their opinion, will particularly warrant joint exploration through collaborative projects. Applicants must state their willingness to participate in joint activities of the Alliance, including: (1) interactions with other Alliance awardees; (2) participation in planning Alliance-sponsored workshops and symposia and attending these events; (3) serving on the Steering Committee and adhering to its decisions and recommendations; and (4) sharing research resources with other members of the Alliance consistent with achieving the goals of the program.

Given the collaborative nature of the Alliance and its planned collaborative research projects, applicants should describe their experience in and approach to participating in collaborative research.

Applicants must address any specific plans that might be needed to comply with Cooperative Agreement Terms and Conditions of Award as stated in Section VI.2.A of this FOA. 

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modifications:

Appendix

Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Foreign Organizations

Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via 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.

Applicants are responsible for viewing their application 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.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

6. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF 424 (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 Applying Electronically.

Important reminders:
All PD/PIs must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(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.

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 Central Contractor Registration (CCR). 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 by the Center for Scientific Review and for responsiveness by NCI, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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?

In addition, specific for this FOA:

Investigator(s)    

Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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?

In addition, specific for this FOA:

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?   

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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? 

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

In addition, specific for this FOA:

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority 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 six 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 six 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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children 

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. 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

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not Applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact/priority score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NCI , in accordance with NIH peer review policy and procedures, using the stated review criteria. Review group assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee 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 the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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:

A substantial commitment (of at least 1.2 person-months) is expected for any individual designated as the PD/PI (either as a single PD/PI or as one of multiple PDs/PIs) on the application. PDs/PIs on Alliance awards will be required to maintain commitment at least at this minimal level of 1.2 person-month throughout the entire project period.

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

In addition, an 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. If this individual is substantially involved in the Alliance activities, s/he will not attend peer review meetings of renewal and /or supplemental applications or will seek NCI waiver if such participation is essential.

Areas of Joint Responsibility include:

Steering Committee:

The Steering Committee will serve as the main governing body of the Alliance. The Steering Committee will have major scientific management oversight and responsibility for developing, facilitating the conduct and monitoring progress of collaborative projects and reporting study results. All awardees will be required to accept and implement policies approved by the Steering Committee.

The Steering Committee will be composed of the following voting members:

The Steering Committee will select the Chair and Co-chair from among the voting members who are the Alliance PDs/PIs (the NCI representative cannot serve as a chair or co-chair).

The Steering Committee may invite other individuals to participate as non-voting members as needed. To facilitate and enhance the activities of the Alliance, such individuals are expected to include representatives of related glycomic and biomarker oriented partnering programs and representatives of NIH Institutes/Centers supporting those partnering programs. Thus, non-voting members may include:

The Steering Committee will establish subcommittees or working groups to advise the Steering Committee as needed. The NIH staff members (including voting and non-voting members of the Steering Committee) may serve on subcommittees as appropriate. External experts may be included on the subcommittees or working groups, e.g., to assist in the evaluation of proposals for pilot/joint projects.

The Steering Committee will convene after all the awards under this FOA are made and meet at an annual face-to-face Steering Committee meeting and by monthly conference calls. Attendance at these meetings and conference calls is considered an essential part of the award.

Responsibilities of the Steering Committee include, but are not limited to:

The Steering Committee will track Alliance research progress and facilitate as appropriate the process of preparing the results of laboratory investigations and clinical studies for publication in peer-reviewed journals to ensure its timely manner and adherence to the publication policies of the Alliance.

If there is any Alliance-wide validation study to be conducted, the Steering Committee, in consultation with the NCI, will select an investigator to lead such effort.

Dispute Resolution:

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

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

 A final progress report, 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. 

Section VII. Agency Contacts

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

Application Submission Contacts

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Scientific/Research Contact(s)

Karl E. Krueger, Ph.D.
Division of Cancer Prevention
National Cancer Institute
6130 Executive Boulevard, Room 3147, MSC 7362
Bethesda, MD 20892-7362 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 594-1044
Email: kruegerk@mail.nih.gov

Sudhir Srivastava, Ph.D, M.P.H.
Division of Cancer Prevention
National Cancer Institute
6130 Executive Boulevard, Room 3147, MSC 7362
Bethesda, MD 20892-7362 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 435-1594
Email: srivasts@mail.nih.gov

Peer Review Contact(s)

Referral Officer 
Division of Extramural Activities 
National Cancer Institute 
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-3428
FAX: (301) 402-0275
Email: ncirefof@dea.nci.nih.gov.

Financial/Grants Management Contact(s)

Julie Peoples, MA
Office of Grants Administration
National Cancer Institute
6120 Executive Boulevard, Suite 243
Bethesda, MD 20892-7362 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-7208
Email: peoplesj@mail.nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.


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