Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Funding Opportunity Title

Bridging the Gap Between Cancer Mechanism and Population Science (U01)

Activity Code

U01 Research Project – Cooperative Agreement Program

Announcement Type

New

Related Notices

  • June 3, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same.
  • May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.

Funding Opportunity Announcement (FOA) Number

PAR-13-081

Companion Funding Opportunity

None

Number of Applications

See Section III. 3. Additional Information on Eligibility.

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

93.394; 93.396; 93.393; 93.273

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to encourage applications for projects that bridge biological mechanism to population level scales. By incorporating insights and data from one end of the cancer research spectrum into the framework of the other, projects should be able to cross-validate data gathered at different scales, and explore links between basic biology, population science, and potential health applications in treatment, prevention, diagnosis, and/or screening.  Proposed projects should pose a challenging cancer research question that can be addressed by connecting these two ends of the research spectrum that would be difficult to address or explain through biological or epidemiological investigation alone. Only a single cohesive project integrating aspects from these two areas is allowed in each application.

Key Dates
Posted Date

January 10, 2013

Open Date (Earliest Submission Date)

February 8, 2013

Letter of Intent Due Date(s)

February 8, 2013; October 4, 2013; May 17, 2014; October 4, 2014; May 17, 2015; October 4, 2015

Application Due Date(s)

March 8, 2013; November 4, 2013; June 17, 2014; November 4, 2014; June 17, 2015; November 4, 2015, by 5:00 PM local time of applicant organization.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

May-June, 2013; February-March, 2014; September-October, 2014, February-March, 2015; September-October, 2015; February-March, 2016

Advisory Council Review

August 2013; May 2014; January 2015; May 2015; January 2016; May 2016

Earliest Start Date

September 2013; July 2014; April 2015; July 2015; April 2016; July 2016.

Expiration Date

November 5, 2015

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.


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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) from the National Cancer Institute is to promote projects that bridge biological mechanism to population level scales. By incorporating insights and data from one end of the cancer research spectrum into the framework of the other, the proposed projects should be designed to cross-validate data gathered at different scales, and explore links between basic biology, population science, and potential health applications in treatment, prevention, diagnosis, and/or screening. 

To be responsive to this FOA, each application is expected to pose a challenging cancer research question that can be addressed by connecting these two ends of the research spectrum (but would be difficult to address or explain through biological or epidemiological investigation alone). Projects addressing such questions will require expertise that crosses boundaries of either area. Therefore, it is anticipated that responsive projects will require teams of biologists and epidemiologists along with their computational collaborators and others, as necessary, to address the question posed by the investigators. It is anticipated that some form of model will be included in the project. Thus, projects may connect biological mechanism models and population models, or inform population models with mechanistic insights, or inform mechanistic models with population science insights.

Background

Enormous progress has been made in understanding the genetic, molecular, and cellular components of cancer phenomenon. However, cancer is not just a disease of aberrant molecular interactions or of individual cells. The microenvironment, the immune response, the environmental impact on the individual, and even the host microbiome all play a role. In addition, processes and alterations occurring at these different biological scales interact and affect each other. For example, the interaction between molecular signaling, tumor and stromal pH, and the mechanics of cell adhesion and motility all affect the progression of solid tumors. These interacting systems include relationships between genes in the cancer cells, between signal transduction pathways within a cancer cell, between cells in the tumor, between the tumor and its microenvironment, and between the individual and the macro-environment. In addition, the changing interactions of these various systems in a very dynamic environment underscore the inherent complexity of the disease.

The technological advances of the past decade have resulted in the generation of extensive genomic, proteomic, and other comprehensive "omic" datasets. Other technology advances, such as intravital imaging, isolation of rare cells, and organotypic culturing further contributed to the increasing generation of large -omic data sets. More recently, integrative and systems approaches have emerged that make use of the available large data sets. These approaches utilize bioinformatics and computational methods that can integrate data from disparate data sets, including those collected at different biological scales to compile a more complete understanding of a process.

The field of cancer systems biology builds on the success of these approaches. It is now possible to use different combinations of high-throughput data collection, experimental validation, and computational modeling to address complex questions in cancer biology and to translate that knowledge forward toward clinical application. Computational models of cancer mechanism are used to explore underlying molecular signaling pathways and cell-cell interactions to explain, understand, and predict biological phenotypes and outcomes in individual tumors and patients. In recent years, cancer biologists have begun to advance their network signaling models into the cellular and tissue scales. Examples of NCI-sponsored programs in these directions include the Integrative Cancer Biology (ICBP; http://icbp.nci.nih.gov/) and Physical Sciences and Oncology (PSOC; http://physics.cancer.gov/). The models being developed begin to explain the underlying biological mechanisms behind cancer initiation and progression but generally do not take into account ongoing population dynamics such as changing risk factor profiles of the population, new screening modalities, and treatment regimens. In parallel, epidemiologists and population modelers like those in the Cancer Intervention and Surveillance Network (CISNET; http://cisnet.cancer.gov/) are exploring ways of informing their models and strategies with mechanistic insights.

The population science and systems biology communities remain largely isolated from each other and the technical aspects of bridging biological scales in these efforts remain quite difficult. Epidemiologists and population modelers focus on the impact of trends in risk factors, screening behavior, and diffusion of new treatments on trends in human populations in cancer incidence and mortality, as well as how to optimize the implementation of existing and emerging cancer control technologies. For example, computed tomography screening for lung cancer may be optimized in terms of the age to initiate and terminate screens and screening periodicity. These models translate evidence from randomized clinical trials and epidemiologic/observational studies to the population health setting. This translation may involve extrapolating evidence beyond study findings measured in selected populations to the general population. The resulting models may account for the actual or projected trends, such as changes in risk factors or dissemination of the new technologies. Modeling real or hypothetical scenarios allows for the identification of key factors in cancer control strategies influencing cancer mortality. This work informs practice and policy guidelines by synthesizing existing, albeit often incomplete, information to model gaps in available knowledge.

At the center of these efforts are natural history models of cancer. The natural history models usually take the form of a pre-clinical tumor growth model (and polyp growth models for colorectal cancer) linked to a clinical incidence function, and a stage-specific post-diagnosis survival function. While the pre-clinical growth generally cannot be directly observed for humans, these unobservable transitions can be indirectly inferred using various data sources (e.g., exposure data from cohort studies, autopsy data, Surveillance Epidemiology and End Results (SEER) incidence data, U.S. mortality data). Adaptations of this basic formulation include the two-stage clonal expansion models, which statistically models processes responsible for the initiation, promotion, and progression of the tumor, and the cure/no-cure models which explicitly models when the primary tumor sheds its first lethal metastatic cells as a function of its size. While the ultimate output of these models is mortality, the models also estimate intermediate results of public health relevance such as lead time and over-diagnosis rates for a new screening technology. Population models have been used effectively to understand the declines in breast, colorectal, and prostate cancer mortality, to assist the U.S. Preventive Services Task Force to develop recommendations for primary care clinicians and health systems, and to assist the Center for Medicare and Medicaid Services to make reimbursement decisions.

Computational models of cancer biology use experimental data to describe and predict the initiation, development, and progression of cancer, generally modeling cancer processes as a complex system. As with population models, developing and testing these models is a highly iterative process. In contrast to population models, the data used to build and test these models are collected in experiments specifically designed to inform the model. Also in contrast to population models, these models of biological mechanism frequently cover multiple biological scales and utilize diverse data sources with often no gold standard data (e.g., SEER data in population modeling) and few agreed upon standards. Distinctions between models of biological mechanism and population models are not always completely clear, but in general population models include endpoints such as the clinical incidence of cancer, death, and screen detection of cancer, which result from a combination of biological, sociological, and medical care factors. They typically use a relatively simple structure and assumptions which are calibrated and validated to all available epidemiologic and clinical data. Models of biological mechanism typically build a structure that reflects an underlying biology based on experimental data primarily designed to inform the specific mechanisms under study. Many of the predictions made by these models can be directly tested in experimental systems, or validated against clinical specimens. These models begin to explain the underlying biological mechanisms behind cancer initiation and progression but generally do not take into account the sociological and medical care aspects of population level outcomes.

One way to connect these two ends of the cancer research spectrum is through models, conceptual or mathematically formalized, generated at the two scales. Population models are calibrated and validated using a variety of data sources such as autopsy data, SEER incidence data, exposure data from cohort studies, and survival data from randomized clinical trials. Biological mechanism models are calibrated to a completely different set of data sources such as molecular interaction data, gene expression data, cell mechanics data, and small molecule perturbation data. Since these calibration sources are independent and operate at different scales, the interface between the two models represents a unique opportunity to test how well observations at one scale translate to the other. Thus, the interface between the models or conceptual understanding at the two scales represents a portal through which both types of models can gain validity at the other scale. This, in turn, fosters new targeted data collection and acquisition efforts creating more realistic and effective models.

Informing studies of biological mechanism with population scale data or models adds an additional layer of insight which should position them to better inform health applications. Utilizing and integrating data and insights from these multiple non-overlapping sources could assist in trial design issues such as drug selection, scheduling, and dosing, and selection of the patients most likely to benefit. In prevention, modeling may be useful in gaining mechanistic understanding of gene-environment interactions, and developing individualized prevention strategies.

Scope of the FOA and Specific Requirements

The scope of the FOA includes any project that poses and addresses a challenging cancer question that can only be addressed by linking these two ends of the cancer spectrum -- biological mechanism and population.  These attributes are essential for the proposed project to be considered responsive to this FOA.

Applicants may propose projects to address any of the numerous technical challenges involved in linking models and data across these scales. Possible technical challenges include but are not limited to developing methods that accommodate the different mathematical methods to explain data at the different scales, lack of quantitative data at intermediate scales (cell, tissue, etc.), difficulty in finding effective interface parameters or bridges (both conceptual and technical), and solving computational demands when transitioning from single tumor to a population of individuals. Technical challenges inherent in crossing scales or informing one scale with data, models, and/or insights from the other scale should be effectively formulated, and strategies for solution of these technical challenges should be conceptualized in an innovative and practical manner. 

This FOA encourages collaborations between epidemiologists and biologists along with their computational and technical collaborators who would together identify and pose new methods to address an important problem spanning these two ends of the research spectrum. The projects should develop and apply new methods to bridge the scales and inform the chosen question. It is anticipated that projects will add new expertise, data, insights, and/or models to current successful projects. For example, investigators may propose to validate or recalibrate their biological mechanism model using orthogonal population level data, to validate their population data using orthogonal biological data, or to find a method of bridging a model of biological mechanism and a population model to explain or explore a cancer question that spans these models. Investigators may also propose to explore provocative observations at the population scale to inform further biological experimentation and mechanistic understanding of the population level phenomenon or to reconcile mechanistic observations or models that are inconsistent with population level data.

Note: Only a single, cohesive project per application is allowed in response to this FOA. Applications proposing multiple projects will be considered non-responsive (non-responsive applications will not be reviewed)

Applicants interested in proposing more than one project may do so by submitting multiple applications.

Examples of projects that would be considered responsive to this FOA include but are not limited to the following:

NIAAA Areas of Interest. The NIAAA is interested in applications that will meet all the requirements specified in the FOA but with the topic of the project relevant to the intersection of alcohol and cancer.  Examples of topics of interest include but are not limited to the relationship between alcohol consumption and cancers of the upper aerodigestive tract, breast, colon/rectum, and pancreas.  Applicants are strongly encouraged to contact the NIAAA program officer prior to preparing an application to discuss topicality and responsiveness.

The following will be considered non-responsive for this FOA:

Section II. Award Information
Funding Instrument

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

Application Types Allowed

New
Resubmission (but only of applications submitted previously to this FOA)

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

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

Application budgets are expected to differ, reflecting the actual needs of the proposed projects. It is anticipated and encouraged, however, that most requests remain between $250,000 and $450,000 per year direct costs commensurate with the scope and complexity of the proposed projects. In exceptional and well-justified circumstances larger budgets may be requested but all requests must not exceed $700,000 direct costs per year.

Award Project Period

Applicants may request project periods of up to 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 Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

Applicant organizations must complete the following registrations as described in the SF424 (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(s)/PI(s)) 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 6 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(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.

Because it is anticipated that these research projects will involve senior investigators from multiple disciplines, applicants are encouraged to take advantage of the multi-PD/PI option.

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 that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

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.

For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

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:

Jennifer Couch, Ph.D.
Division of Cancer Biology
National Cancer Institute
9609 Medical Center Drive, Room 6W332
Bethesda, MD 20892-9747 (for regular mail)
Rockville, MD 20850 (for express delivery)
Telephone: 240-276-6210
E-mail: couchj@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 submission of applications for this FOA. 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.

Budget Component

Applicants must complete detailed budget using the R&R Budget Component, as well as subaward/consortium budget component(s) as appropriate.

PHS 398 Research Plan Component

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

Research Strategy

As a part of Research Strategy section, applicants are requested to clearly address (under separate subheadings) the following aspects:

1) Overall Objectives and Significance define the challenging cancer question that could only be addressed by bridging from the biological to the population scales. Identify the gaps that the project is intended to fill. Outline the projected impact of the proposed work.

2) Background Information on Proposed Models and Approaches (use separate blocks for biological models and population scale models): This section should describe the current understanding of the specific biological mechanisms to be explored, the relevant data sources, and the conceptual and/or computational model to be employed. In addition, this section should also describe the existing population level or epidemiologic scientific knowledge to be tapped, including relevant data sources, results of studies, and/or computational models to be employed.

3) Integration of the Mechanistic and Population Level Scales: In this main part of Research Strategy applicants should: describe the research strategy for each of the specific aims and technical approaches; address challenges of linking the two scales (the necessary choices of interface functions between the scales, computational challenges, etc.); identify potential pitfalls/alternative approaches; and define specific, verifiable metrics of success.

Applications that fail to address these elements will be considered non-responsive and will not be reviewed.

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 modification:

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 Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions 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 applications before 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 before the deadline 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 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 Applying Electronically.

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.

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 (SAM). 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, NIH and for responsiveness by the NCI. Applications that are incomplete or non-responsive 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.

For this particular announcement, note the following:

The focus of this FOA is on bridging biological mechanisms and population level scales in a cohesive attempt to address a challenging cancer research question. It is expected that such a central question would be difficult to explore or explain through biological or epidemiological investigation alone.  Thus, the emphasis is on creative connections between these two ends of the research spectrum. It is anticipated that the outcomes of the proposed projects will either inform population models with mechanistic insights or inform mechanistic models with population science insights.

Overall Impact

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

Scored Review Criteria

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

Significance

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

To what extent does the project pose a challenging cancer question that can only be addressed by linking these two ends of the cancer spectrum, i.e., biological mechanism and population?

Investigator(s)    

Are the PD(s)/PI(s), 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?

Specific for this FOA: Does the team include appropriate expertise from the population and biology scales as well as appropriate computational collaborators?

Innovation

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

Specific for this FOA: Are salient technical challenges inherent in crossing scales or informing one scale with data, models, and/or insights from the other scale been effectively formulated?  Have strategies for solution of these technical challenges been conceptualized in an innovative and practical manner?

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?

Specific for this FOA: Does the approach properly balance the competing goals of innovation with technical and computationally feasibility?   

Environment

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

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the 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

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

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

Applications from Foreign Organizations

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 convened by the 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:

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’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 the DUNS, SAM 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 (HHS) 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) Authorities and Responsibilities

The PD(s)/PI(s) will have primary authority and responsibility to define objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of studies conducted under this program. The PD(s)/PI(s) assume responsibility and accountability to the applicant organization officials and to the NCI for the performance and proper conduct of the research supported by the U01 award. Specific responsibilities and rights include:

Each U01 awardee 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 HHS, PHS, and NIH policies.

NCI Staff Responsibilities

A designated NCI Program Staff member, acting as Project Scientists, will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. Specifically, the NCI Project Scientists will:          

Additionally, an NCI Program Director acting as the Program Official will be responsible for the normal scientific and programmatic stewardship of the awards and will be named in the award notice. The Program Official may also have substantial programmatic involvement (as a Project Scientist) and may be the same person as Project Scientist. In that case, the individual involved will not attend peer review meetings, or will seek NCI waiver according to the NCI procedures for management of conflict of interest.

Areas of Joint Responsibility

The NCI Project Scientist and the PD/PIs of the U01 awards funded under the Bridging the Gap between Cancer Mechanism and Population program will be jointly responsible for the coordination of intra-program activities and the scientific integration of individual projects with other appropriate NCI consortia such as CISNET and ICBP.

Although the Bridging the Gap between Cancer Mechanism and Population program will not have any separate formal governing body, these activities may involve the formation of a Coordinating Group. The primary role of Coordinating Group will be to serve as interface between the individual Bridging the Gap between Cancer Mechanism and Population projects and appropriate NCI programs and to facilitate reaching consensus with regard to the integration of research efforts.

Coordinating Group will include senior representatives of each U01 project, the NCI Project Scientist, and, if desirable, other NCI staff members involved in the ICBP or CISNET programs. Meetings of the Coordinating Group may be virtual or by teleconference.

The NCI Project Scientist will initiate the formation of the Coordinating Group and will facilitate its activities.

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 academic members who are not involved in the study will be convened. 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 HHS regulation 45 CFR Part 16.

3. Reporting

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) 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)

For issues related primarily to biological mechanisms, please direct inquiries to:

Jennifer Couch, Ph.D.
Division of Cancer Biology (DCB)
National Cancer Institute (NCI)
Telephone: 240-276-6210
E-mail: couchj@mail.nih.gov

For issues related primarily to population science, please direct inquiries to:

Eric J. (Rocky) Feuer, Ph.D.
Division of Cancer Control and Population Sciences (DCCPS)
National Cancer Institute (NCI)
Telephone: 240-276-6772
E-mail: rf41u@nih.gov

For issues related to alcohol and cancer, please direct inquiries to:

Philip J. Brooks, Ph.D.
Division of Metabolism and Health Effects
National Institute on Alcohol Abuse and Alcoholism
Telephone: 301-402-0883
Fax: 301-594-0673
Email: pjbrooks@mail.nih.gov

Peer Review Contact(s)

Referral Officer
Division of Extramural Activities
National Cancer Institute
Telephone: 240-276-6390
E-mail: ncirefof@dea.nci.nih.gov

Financial/Grants Management Contact(s)

Rebecca Brightful
Office of Grants Administration (OGA)
National Cancer Institute (NCI)
Telephone: 301-631-3011
Email: brightfr@mail.nih.gov

Judy Fox
Grants Management Branch
National Institute on Alcohol Abuse and Alcoholism
Telephone: 301-443-4704
Email: jfox@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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