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

Consortium on Translational Research in Early Detection of Liver Cancer: Translational Research Centers (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices
Funding Opportunity Announcement (FOA) Number

RFA-CA-17-025

Companion Funding Opportunity
Catalog of Federal Domestic Assistance (CFDA) Number(s)

 93.394  

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) is a part of an initiative designed to establish a Liver Cancer Consortium to advance translational research focused on early detection of liver cancer.  The Consortium will consist of several Translational Research Centers (TRCs, to be supported by this U01 FOA) and a Data Management and Coordinating Center (DMCC, to be supported a companion U24 FOA, RFA-CA-17-028).

The TRCs will conduct studies to improve the surveillance of liver cancer in members of high-risk populations, increase the fraction of liver cancer detected at an early stage, and better stratify patients at risk of developing liver cancer. Research to be conducted by TRCs must be based on appropriate range of biospecimens from cohorts that are focused on cirrhotic patients. A major collaborative effort of the TRCs will be the establishment of a well annotated repository of biospecimens. Biospecimens (blood, other body fluids, and, when feasible, liver tissue) may be already available and/or may be prospectively collected.

To achieve these goals, each proposed TRC should include laboratory and clinical researchers with multi-disciplinary expertise in such areas as early cancer detection, biomarkers, cancer surveillance, imaging, and biospecimen science.

The TRCs will be expected to interact closely with the DMCC and engage in collaborative activities with other members of the Liver Cancer Consortium.

The TRCs individual research projects as well as trans-network collaborative activities of the Consortium will be supported scientifically and coordinated administratively and logistically by the DMCC.

Key Dates
Posted Date

August 21, 2017

Open Date (Earliest Submission Date)

September 24, 2017

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

October 24, 2017, by 5:00 PM local time of applicant organization. All types of applications allowed for this funding opportunity announcement are due on this date.

No late applications will be accepted for this FOA.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

February-March 2018

Advisory Council Review

May 2018

Earliest Start Date

July 2018

Expiration Date

October 25, 2017

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from 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.


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

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

  3. Go to Grants.gov to download an application package to complete the application forms offline or create a Workspace to complete the forms online; submit your application to Grants.gov; and track your application in eRA Commons.
Learn more about the various submission options.

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 establish a Liver Cancer Consortium to advance translational research focused on early detection of liver cancer.  The Consortium will consist of several Translational Research Centers (TRCs, to be supported by this U01 FOA) and a Data Management and Coordinating Center (DMCC, to be supported a companion U24 FOA, RFA-CA-17-028).

The TRCs will conduct studies to improve the surveillance of liver cancer in high-risk populations, increase the fraction of liver cancer detected at an early stage, and better stratify patients at risk of developing liver cancer. Research to be conducted by TRCs must be based on appropriate range of biospecimens from cohorts that are focused on cirrhotic patients. A major collaborative effort of the TRCs will be the establishment of a well annotated repository of biospecimens (blood, other body fluids, and when feasible liver tissue). Biospecimens may be already available and/or may be prospectively collected.

To achieve these goals, each proposed TRC should include laboratory and clinical researchers with multi-disciplinary expertise in such areas as early cancer detection, biomarkers, surveillance, imaging, and biospecimen science.

The TRCs will be expected to interact closely with DMCC and engage into collaborative activities with other members of the Liver Cancer Consortium.

Background

The burden of hepatocellular carcinoma. Worldwide, liver cancer is the second most common cause of cancer-related death, and it is a rising cause of cancer-related deaths in the United States (U.S.) The incidence of hepatocellular carcinoma (HCC) is three times higher in men than women, and there are racial and ethnic differences in liver cancer occurrence. The liver cancer burden is higher in African Americans, Hispanics, and Asians. The etiological/risk factors for liver cancer include viral hepatitis (Hepatitis B virus and Hepatitis C virus), non-alcoholic steatohepatitis (NASH), and alcoholic liver disease (ALD). Approximately 80-90% of HCC occurs in patients with underlying liver cirrhosis. In patients with cirrhosis, the 5-year cumulative risk of liver cancer ranges from 5-30%, depending on the etiology, and patients with advanced cirrhosis represent a high-risk group for liver cancer and are recommended for surveillance.

Hepatitis B/C viruses in liver cancer. Viral hepatitis is a major etiologic factor for liver cancer in the U.S. Hepatitis C virus (HCV) infects approximately 1% of the U.S. population and approximately 50-60% of the patients with HCC are infected with HCV. Direct acting antivirals are successful in the treatment of chronic HCV infections but the risk of developing HCC is not completely eliminated. Globally, Hepatitis B virus (HBV) is the most frequent underlying cause of liver cancer. In the United States, approximately 20% of the HCC cases are attributable to HBV. There is a need for effective surveillance, early detection, and improved screening technologies for HBV-associated liver cancer.

Non-viral liver pathologies reflecting increased risk for liver cancer. It is estimated that currently 25% of the U.S. population has NAFLD (Non-alcoholic fatty liver disease) which can progress to NASH. Cirrhosis can develop in patients with NASH resulting in an increased risk for HCC. Alcoholic liver disease (ALD) is a burden in Western countries and is rising worldwide. Heavy alcohol abuse results in liver cirrhosis which greatly increases the risk for liver cancer. With the increase in obesity and metabolic syndrome, there is greater prevalence of these underlying liver diseases in the U.S. population and in future more HCC may be attributable to NASH.

Need for early detection of liver cancers. The prognosis of patients with HCC largely depends on the tumor stage at the time of diagnosis. If detected early, liver cancer patients can undergo transplantation or resection and achieve 5-year survival of 70%. In contrast, patients with advanced stage HCC are only eligible for palliative treatments and have a median survival of less than one year. Unfortunately, current surveillance protocols do not detect many HCCs until they are late stage. In the U.S. and Europe, surveillance guidelines for patients with cirrhosis is hepatic ultrasound every 6 months. Ultrasound has a sensitivity of approximately 60% for early stage HCC and a specificity of approximately 85-90%. The performance of ultrasound is operator dependent, which reduces its reproducibility, and is less accurate in obese patients. Improved biomarkers and imaging methods are needed that can enhance surveillance, better stratify patients, and increase the fraction of HCC detected at an early stage.

Challenges and opportunities in HCC research. The following aspects reflect major unmet clinical needs related to HCC and should be viewed as high priority areas for translational research.

  • Current biomarkers for HCC surveillance and/or early detection lack adequate sensitivity and specificity. Validation/verification studies that combine biomarkers, utilize clinical parameters, and/or include imaging modalities in cohorts of patients with cirrhosis are needed to improve the surveillance and increase the detectability of early-stage HCC.
  • Access to large cohorts of patients with cirrhosis attributable to viral hepatitis [HBV or HCV], NASH, or ALD is a challenge that needs to be addressed to identify biomarkers and clinical parameters associated with the different etiologies for the early detection of HCC in these patients.
  • Given the high prevalence of cirrhosis, it is important to understand the risk of progression to HCC in cirrhotic patients. The identification and stratification of patients with cirrhosis, who are at a particularly high-risk for progression to HCC, is likely to result in considerable clinical benefits.
  • The liver cancer burden is higher in minority populations, i.e., African Americans, Hispanics, and Asians. The performance of biomarkers in different racial and ethnic populations needs to be better understood.

All these aspects need to be studied to achieve progress in HCC early detection and, ultimately, increase the survival of HCC patients.

Specific Objectives and Requirements

Main Areas of Research Focus. Each Translational Research Center proposed in response to this FOA must focus on research relevant to one or more of the main goals for the liver cancer consortium, which comprise the following areas:

Area 1: Improving the surveillance for liver cancers in patients with cirrhosis;

Area 2: Increasing the detectability of liver cancers at early stages; and/or

Area 3: Approaches to better stratify patients with cirrhosis, who are at risk of developing liver cancer.

Examples of specific directions relevant to these broad areas include, but are not limited to, the following research activities:

  • Establishing cohorts of cirrhotic patients to study risks for liver cancer associated with viral infections (HCV or HBV), NASH, or ALD;
  • Stratifying cirrhotic patients to identify those patients at highest risk for progression to liver cancer;
  • Identifying and/or validating biomarkers for HCC arising from different etiologies (e.g., viral and NASH, or ALD);
  • Identifying and/or validating biomarkers for HCC associated with racial and/or ethnic differences;
  • Longitudinal collection and analysis of samples and/or images from cirrhotic patients to determine the likely progression to liver cancer within a defined period of time (e.g., 1-2 years);
  • Studies on changes in the viral genome and associated risk of HCC;
  • Integration of imaging approaches with biomarkers; and/or
  • Improve imaging modalities for surveillance and early detection of liver cancer.

Roles of the Translational Research Centers in the Liver Cancer Consortium.

  • Individual Research Projects. Each proposed Translational Research Center for support through this FOA must include a well-developed individual research project. The projects should be based on appropriate available biospecimen resources and capability for the inclusion of patients with different racial or ethnic backgrounds. The proposed project must have a clear translational potential for and relevance to at least one of the main Research Areas defined above. Each project should also be founded on evidence-based rationale and preliminary data.
  • Trans-Network Activities. In addition to conducting an individual research project, the Translational Research Center investigators will be required to engage in various trans-Network activities, which are expected to include:
  • Participating in collaborative Network projects with other Consortium awardees (e.g., biomarker studies with or without imaging);
  • Contributing to the establishment of a Network biospecimen repository and database;
  • Engaging, as appropriate, in other collaborative activities, sharing resources and expertise, etc.; and
  • Submitting data (e.g., biomarker, imaging, Common Data Elements etc.) to the Data Management and Coordinating Center.
  • Interactions with Data Management and Coordinating Center (DMCC). Each U01 awardee will be required to interact closely with DMCC, including working jointly on processing and analyses of various types of TRC-generated data as well as clinical annotations (e.g., biomarker, imaging, Common Data Elements etc.)
  • DMCC which will support and assist the TRCs and trans-Network activities in such aspects as:  
  • Supporting the development of collaborative studies;
  • Coordinating collaborative efforts to establish a Consortium-wide database of biospecimens (including their clinical annotations, usage tracking, etc.);
  • Coordinating biomarker validation studies;
  • Providing statistical and data analyses support;
  • Providing centralized management of data generated by all Consortium awardees; and
  • Providing operational and logistical support of various other Network activities.

Biomarker-based Research Approaches.

Regardless of specific area(s) of research proposed, all research projects should include biomarker-based research approaches. Although the degree of emphasis on that aspect may vary (depending on project objectives), it is a general expectation that biomarker-based approaches will be a prominent element of all studies. 

Accordingly, all the proposed Translational Research Centers must have appropriate capabilities to achieve their research goals through a systematic, evidence-based development and validation of biomarkers. Generally, such activities are expected to be aligned with the five-phase approach outlined below. The full details available using the following link - https://edrn.nci.nih.gov/docs/EDRN5.pdf. (see page 18 for a listing and description of the 5 phases).

Phase 1: The pre-clinical exploratory phase;

Phase 2: The validation phase (case/control);

Phase 3: The retrospective longitudinal phase;

Phase 4: The prospective screening study phase; and

Phase 5: The cancer control phase.

Biomarker research proposed for this FOA should mainly focus on Phases 2 and/or 3, as indicated above. Therefore, for all biomarkers proposed for further exploration, preliminary data covering at least the pre-clinical exploratory phase (Phase 1) are required.

Sources of Biospecimens and Clinical Data. Research activities outlined above require that all applicants have adequate access to samples from existing cohorts of high-risk individuals (e.g., cirrhotic patients), prospective collection of serial biospecimens and clinical imaging data. Imaging data in combination with biospecimens is preferable. Investigators with existing biospecimens are encouraged to share these resources with the consortium, if appropriate and feasible. For specimens collected under the U01 award, the investigators must be willing to aid in the recruitment of sufficient numbers of patients with different etiologies (i.e., viral and non-viral) and different ethnic and racial backgrounds and share these biospecimens with the consortium. This will help ensure consortium access to these resources.

Note on Biospecimen Sources: To the extent possible, investigators will be expected to leverage resources, such as established relevant cohorts from domestic and/or foreign collaborators, if relevant. There will be limited resources for the establishment of new patient cohorts, so the leveraging of supplementing of existing cohorts is encouraged. For example, PAR-14-301, NIDDK Central Repositories Non-renewable Sample Access (X01), allows investigators to apply for samples and data from numerous clinical studies.

Composition of Translational Research Teams. For the outlined goals and activities, it is anticipated that each Translational Research Center proposed will need to include translational and clinical researchers with multi-disciplinary expertise in the areas of early detection, biomarkers, cancer surveillance, imaging, and biorepositories.

Note: Given the prevalence of different HCC etiologies in different countries and regions, applicants are encouraged to consider including an international partner, if directly relevant for the proposed research. Applicants can engage in collaborations with international partners, but the research must have direct application to the liver cancer etiologies found in the U.S. populations (i.e., HCV, HBV, NASH, and ALD).

Non-responsive Research Projects

This FOA will not support the types of studies listed below. Applications proposing such studies will be viewed as non-responsive. Non-responsive applications will not be reviewed.

  • Studies not directly relevant to at least one of the three Main Areas of Research Focus defined above;
  • Projects focused on the discovery of new biomarkers without any translational component;
  • Studies on biomarkers that are not directly relevant to early HCC detection (such as biomarkers of treatment outcomes); and
  • Studies aimed at understanding of fundamental biological mechanisms, such as growth regulation, cell cycle control, or other basic studies.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information
Funding Instrument

 Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed

New

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

Funds Available and Anticipated Number of Awards

 NIH intends commit $4.4 million in Fiscal Year 2018 to fund up to five awards.

Award Budget

An Applicant may request a budget of up to $550,000 per year (direct costs).

Award Project Period

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

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

Section III. Eligibility Information
1. Eligible Applicants
Eligible Organizations

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)

Governments

  • State Governments
  • County Governments
  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession

Other

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. 
  • eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
  • Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.   

2. Cost Sharing

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

3. Additional Information on Eligibility
Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).
Section IV. Application and Submission Information
1. Requesting an Application Package

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions 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:

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

The letter of intent should be sent to:

Jo Ann Rinaudo, Ph.D.
Telephone: 240-276-7133
Fax: 240-276-7845
Email: rinaudoj@mail.nih.gov

Page Limitations

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

For this specific FOA, the Research Strategy is limited to 30 pages.

Instructions for Application Submission

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide must be followed.  

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide must be followed.  

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide must be followed. 

R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

a) The contact PD/PI must commit a minimum of 1.8 person-months effort per year to the U01 award. The commitment cannot be reduced in later years of the award. The other PD(s)/PI(s) (if designated) must devote a minimum of 1.2 person-months effort per year to their respective projects.

b) Applicants must budget for travel and per diem expenses for Steering Committee meetings. In the first year, applicants should plan for at least two senior investigators (all PDs/PIs, if desirable, or the PD/PI and a senior investigator if multi-PD(s)/PI(s) option is not used), to attend a Planning Meeting and one Steering Committee Meeting. In the second and subsequent years, applicants should plan for at least two senior investigators (all PDs/PIs, if desirable, or the PD/PI and a senior investigator if multi-PD(s)/PI(s) option is not used) to attend one Steering Committee meeting per year.

c) Restricted Network Collaborative Fund. Starting in Year 2, Applicants must set-aside $100,000 of their annual direct budget for future joint trans-Network activities (such as collaborative studies).  The use of these funds will be restricted to activities reviewed and recommended by the Steering Committee.  The set-aside amount should be listed in the Other Expenses category under the heading “Restricted Network Collaborative Fund.” 

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide must be followed.  

PHS 398 Research Plan

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

Specific Aims: Outline the overall goals for the proposed Translational Center and define the goals and specific aims of the individual research project.

Research Strategy: Research Strategy must consist of the Sub-sections, A-D, as defined below. Applicants must address all aspects indicated but additional aspects may also be included.

Sub-section A. Translational Center Overview

  • Outline how the proposed Translational Center will advance at least one of the three Priority Areas identified in Section I;
  • If more than one of these Priority Areas is to be addressed, provide rationale and explain succinctly how the efforts will be balanced/integrated and how the broader scope is expected to help advance the overall goals; and
  • Summarize the main collective strengths of the team (without repeating information in individual biosketches) and, as applicable, explain the roles of vital collaborations (e.g., with foreign investigators) and other key aspects pertinent to Center goals. The planned interactions among the members of the collaborative should be outlined. The ability of the investigators to work as a team and to contribute to the goals of the consortium should be stated.

Sub-section B. Significance and Background

  • Relevance to Liver Cancer.
  • Outline the significance of the proposed research project in the context of the overall translational potential and the anticipated outcomes; and
  • Describe clearly the relevance to cancer surveillance, early detection and/or risk stratification for liver cancer, identifying a specific unmet clinical need(s) that will be addressed.
  • Background and Preliminary Data.
  • Summarize the current state-of-the-science in the specific research direction pursued;
  • Describe preliminary findings on which the proposed project is based; and
  • For biomarkers proposed to be studied, provide preliminary data on their performance characteristics (including sensitivity and specificity) and other relevant information, if available (e.g., on differences in their performance associated with different HCC etiology and/or patient race/ethnicity).

Sub-section C. Approach

In addition to standard aspects for Approach, applicants must specifically address all the items listed below using the headings identified.

Patient Cohorts and Biospecimens. The applicants should identify the specific cohort(s) of cirrhotic patients to be included in the proposed project (i.e., HCV, HBV, NASH or ALD) and their relevance to the proposed research. Provide a detailed description of the biospecimen resources available. Include both prospective and/or retrospective collections of biospecimens, as well as secured access to existing biospecimen repositories. Include the following information:

  • Summary tables with information on the available, existing repositories. Include the types of patients (e.g., cirrhotic patients with viral or non-viral etiologies), clinical information and types of specimens collected (serum, plasma, DNA, other) and the number of available specimens. 
  • Ability to recruit a set number of patients with specific clinical parameters (e.g., cirrhotic patients with viral or non-viral etiologies).
  • Access to existing available biorepositories with the appropriate clinical parameters (e.g., cirrhotic patients with viral or non-viral etiologies).

If foreign collaborations are proposed to increase the scope and range of biospecimens, indicate how such collaborations will be applicable to the liver cancer etiologies predominant in the U.S. populations (i.e., HCV, HBV, NASH, and ALD).

Biomarkers. Describe the proposed biomarker research activities in terms of Phases 2 and 3 of the five-phase approach (as defined in Section I). The description should include, at a minimum, the following elements.

  • With the focus on Phases 2 and/or 3, identify the biomarkers for which preliminary data document their appropriate performance characteristics:
  • Describe analytical studies needed to establish and compare the sensitivity and specificity as well as the predictive accuracy of biomarkers in a clinical context, including inter- and intra-laboratory comparison studies.
  • When describing study design for individual proposed research, indicate how statistical power is defined in multiple tests (biomarker) and what sample size is required to achieve this power.  Examples of power definition include: (a) the probability to detect at least one of possible true nonzero effect; (b) the probability to detect all nonzero effects; and (c) true discovery rate, etc.  For case-control study designs, define clearly whether matching is involved, what cofounders are adjusted for (and why), and specify other relevant factors. Biomarkers and/or imaging modalities should be verified in prospectively-collected samples and/or images from cirrhotic patients to determine the likely progression to liver cancer within a defined period of time (e.g., 1-3 years). 

Sub-section D. Anticipated/Potential Contributions to Collaborative Trans-Network Activities

Outline how the proposed TRC can participate in collaborative efforts with other TRCs. Consider addressing, as appropriate, such aspects as:

  • List areas in which your TRC team may be able to collaborate, share resources (biospecimens, procedures, bioinformatic tools, etc.) with other TRCs.
  • Indicate areas in which your TRC and its individual project may be facilitated by external expertise, tools and/or other resources that may become available through other TRCs.

Letters of Support

In addition to letters from collaborators and consultants, applicants must include letters provided by biospecimen repositories or cohorts on specimens and associated information available for the purposes of the proposed studies. Letters of collaboration from investigators directly involved in relevant cohort studies should clearly indicate their planned commitment level to the consortium.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
  • Specimen/Data Sharing: The plan should explain how the proposed TRC will share biospecimens and associated clinical and research information with other liver cancer consortium investigators, pursuant to the terms of an informed consent. The plan should address how the TRC would structure an informed consent document with considerations for the wider sharing of data and specimens.  It is expected that at least specimens, whose collection will be supported by this FOA, will be shared, if available. Therefore, applicants should describe how the TRC would provide information about the availability of biospecimens at their institutions as well as associated clinical/demographic information to the biospecimen database and tracking system, to be created and maintained by the Data Management and Coordinating Center, consistent with achieving goals of the consortium.
  • Applicants are also expected that any biospecimens that are prospectively collected under the U01 award that remain upon completion of the award (and are no longer needed for the U01 awardee) are deposited to the NCI at Frederick Central Repository (https://frederick.cancer.gov/science/clinical#repo).

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.

PHS Inclusion Enrollment Report

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

PHS Assignment Request Form

All instructions in the SF424 (R&R) Application Guide must be followed. 

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by the NCI, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Use of Common Data Elements in NIH-funded Research

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies.  CDEs are data elements that have been identified and defined for use in multiple data sets across different studies.  Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records.  NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g., genome-wide association studies [GWAS]), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository).  NIH has established a “Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection.  The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research.  Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects. For NCI-relevant CDEs, please visit  CDE (Common Data Element) Browser.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy.

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

Scored Review Criteria

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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: How strong is the translational potential of the proposed research in terms of clinically relevant advances in one (or more) of the three Priority Areas of this FOA (i.e.,

improving surveillance for liver cancer in cirrhotic patients; increasing the detectability of liver cancers at early stages; and/or stratifying patients at risk of developing liver cancer)?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific for this FOA: Does the team demonstrate a record of scientific accomplishments in liver cancer research aligned with the goals of this initiative? How well does the interdisciplinary balance (e.g., between translational and clinical researchers) match the scope and goals of the proposed research and the overall goals for the Liver Cancer Consortium? How strong is the research team in terms of expertise in the areas critical for this FOA (early detection, biomarkers and/or imaging, cancer surveillance, and biospecimen science)?

Innovation

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

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? 

Specific for this FOA: Are the sources of biospecimens adequate for the proposed research? In particular, are they based on an appropriate cohort(s) of cirrhotic patients needed for the goals of the project proposed? Do the investigators have sufficient access to the appropriate cohorts and/or demonstrated ability to collect longitudinal biospecimens? Are the selections of biomarkers and/or imaging modalities for verification/validation studies appropriate and well-supported by the preliminary data?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?  

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 Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children 

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not applicable

Renewals

Not applicable

Revisions

Not applicable

Additional Review Considerations

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

Applications from Foreign Organizations

Not applicable

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by 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:

  • May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
  • Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

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

  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.
3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

Section VI. Award Administration Information
1. Award Notices

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

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the 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 terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency.  HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements.  FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award.  An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS.  The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR 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:

The PD/PI (or multiple PDs/PIs, if applicable) under the Consortium auspices will have primary responsibilities in the following areas:

  • Defining objectives and approaches, overseeing planning and conducting experiments, analyzing and interpreting results, and publishing reports of studies conducted under this award.
  • Assuming responsibility and accountability to the applicant organization and to the NCI for the performance and proper conduct of the research in accordance with the terms and conditions of the award;
  • Serving as voting members of the Consortium Steering Committee. In accordance with this cooperative agreement, the PD/PI and another senior investigator (or two PD(s)/PI(s) for multi-PD/PI awards) from each Consortium award (U01) and U24 Data Management and Coordinating Center will be required to attend Steering Committee meetings once a year;
  • Accepting and implementing the goals, priorities, procedures, and policies agreed upon by the Steering Committee to the extent consistent with applicable grant regulations;
  • Coordinating efforts and cooperating with the other components of the Consortium and with NCI Program staff, including participation in collaborative Consortium research activities; and
  • Implementing the approved research resource sharing plan.

In addition:

  • All institutions/organizations participating in the Consortium will be expected to share with each other knowledge, data, research materials, and any other resources necessary and relevant to the Consortium; and
  • Each Consortium awardee and the entire Consortium programmatic initiative will be subject to external evaluation (coordinated by the NIH). Consortium Awardees will be expected to participate in such evaluations.

Additional Responsibilities of U01 Awardees

  • Participation in collaborative Network projects with other Consortium awardees;
  • Contributions to the establishment of a Network biospecimen repository;
  • Follow biospecimen collection protocol and collect the same common data elements that will be established by the Consortium's Steering Committee; and
  • Submit data (e.g., biomarker, imaging, Common Data Elements etc.), generated by the studies, to the Data Management and Coordinating Center.

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 HHS, PHS, and NIH policies.

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

Designated NCI Program Directors serving as a Project Scientist(s) and a Project Coordinator(s) will be involved in assisting and coordinating interactions and collaborations among the various investigators.

Additionally, an NCI Program Director acting as Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. Program Officials may also have substantial programmatic involvement (as Project Scientists).

Specific activities of substantially involved NCI staff members will include:

  • Advising the awardees on specific scientific issues as well as programmatic priorities;
  • Facilitating access to NCI resources, expertise, etc.;
  • Serving as liaison between the Consortium investigators and NCI staff members;
  • Monitoring the scientific progress of the entire Consortium and the entire program;
  • Promoting collaborative research efforts that involve interactions with other NCI-sponsored programs, projects, and centers;
  • In cooperation with the NCI Center for Bioinformatics, ensuring that there are effective mechanisms to enable the transfer of network generated data from the Consortium Units to the NCI;
  • Coordinating external evaluation of the Consortium;
  • Assisting the Steering Committee in developing and drafting operating policies and policies for dealing with recurring situations that require coordinated action;
  • To facilitate communications among the participants in the Consortium and between the Consortium and the NCI, the NCI will establish and maintain an internet-based information technology solution for rapid data and document transmission and electronic communications for the Consortium; and
  • Developing working groups and trans-project efforts as needed.

Areas of Joint Responsibility include:

Steering Committee: The Steering Committee will be the main governing body for the Consortium. The Steering Committee will be composed of the following voting members:

  • Two representatives from each Consortium U01 Translational Research Center and U24 Data Management and Coordinating Center award (the PD(s)/PI(s) or a PD/PI and a designated senior investigator) who will have one vote each; and
  • NCI Project Coordinator (who will have one vote).

Assigned Project Scientists will participate in Steering Committee meetings as non-voting members. Additional NIH staff members, serving in an advisory capacity, may participate in these meetings as non-voting members. This decision will be made by the existing voting members of the Steering Committee. These members may include representatives from NCI extramural divisions and a representative from the NCI CBIIT.

The Chair of the Steering Committee will be selected from the representatives of all awardees.

In addition, Chairs of other NIH programs may serve on the Consortium Steering Committee as ex officio members.

The Steering Committee will meet once every year, at locations selected by the Steering Committee in consultation with the NCI.

The Steering Committee may decide to establish sub-committees for specific purposes. The NCI Project Coordinator and the NCI Project Scientists will serve on such sub-committees, as they deem appropriate.

Primary responsibilities of the Steering Committee include, but are not limited to, the following activities:

  • Setting the overall research priorities for the Consortium and identifying emerging research opportunities which can be best explored through a joint collaborative effort via the Consortium;
  • Establishing general Consortium policies and procedures;
  • Establishing policies and procedures for collaborative projects, protocols, and Consortium-defined projects, including defining how such collaborative activities/ studies (to be supported by the restricted set-aside funds on each award) will be initiated, formulated, and presented to the Steering Committee for recommendation regarding collaborative execution;
  • Reviewing (with the help of external reviewers if needed), prioritizing, and recommending for activation trans-Network collaborative activities to be supported by these restricted set aside funds; and
  • Developing guidelines for the collection and distribution of specimen reference sets for collaborative research.

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 regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Scientific/Research Contact(s)

Sudhir Srivastava, M.P.H., Ph.D.
National Cancer Institute
Telephone: 240-276-7028
Email: srivasts@mail.nih.gov

Jo Ann Rinaudo, Ph.D.
National Cancer Institute
Telephone: 240-276-7133
Email: rinaudoj@mail.nih.gov

Peer Review Contact(s)

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: ncirefof@dea.nci.nih.gov.

Financial/Grants Management Contact(s)

Sean Hine
National Cancer Institute
Telephone: 240-276-6291
Email: hines@mail.nih.gov

Section VIII. Other Information

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

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.

NIH Office of Extramural Research Logo
Department of Health and Human Services (HHS) - Home Page
Department of Health
and Human Services (HHS)
USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.