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

Precompetitive Collaboration on Liquid Biopsy for Early Cancer Assessment (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices
Funding Opportunity Announcement (FOA) Number

RFA-CA-17-029

Companion Funding Opportunity

None

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

 93.394  

Funding Opportunity Purpose

 The purpose of this initiative is to establish an Academic-Industrial Partnership Program to develop new and/or validate existing technologies, methods, and assays for the capture and quantification of tumor associated cells, DNA, RNA, or exosomes in body fluids of patients with early stage disease or those at high risk; as well as distinguishing cancer from benign disease; or aggressive from indolent cancers. The precompetitive alliances with industry will harmonize and validate technologies, methods and assays associated with liquid biopsies.

Key Dates

 

Posted Date

August 2, 2017

Open Date (Earliest Submission Date)

September 24, 2017

Letter of Intent Due Date(s)

30 days before application due date

Application Due Date(s)

October 24, 2017 and January 23, 2018, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.

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

March-April and May-June 2018

Advisory Council Review

May 2018 and August 2018

Earliest Start Date

July 2018 and September 2018

Expiration Date

January 24, 2018

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 and support a program of academic-industrial partnerships to advance liquid biopsy technologies suitable for analysis of body fluids from cancer patients with early stage disease and/or individuals at high risk of cancer, as well as distinguishing cancer from benign disease; or aggressive from indolent cancers. Projects proposed should focus on the development of new tools/methods/assays and/or validations of existing technologies/methods/assays (collectively referred to as "technologies"). Relevant technologies may involve, for example, the capture in body fluids and quantification of tumor associated cells, circulating tumor DNA, RNA, or exosomes. 

Applications must be based on partnerships between an academic (non-commercial) entity and a biomedical industry (commercial) entity. All such partnerships supported by this FOA will be expected (and must agree) to interact and work together in precompetitive alliances involving a range of commercial entities participating in the partnerships. These precompetitive alliances should focus on such aspects of data sharing, data integration, standardizing protocols, procedures, and common data elements (CDE).

Key Definitions for the context of this FOA:

  • Liquid Biopsies: denotes clinical tests performed on samples of blood or other body fluids aimed at the detection of characteristics that may reveal patients' cancers. For the purposes of this FOA, the definition encompasses detection/monitoring of all tumor-associated circulating cells, nucleic acids, and extracellular vesicles in blood and/or other biofluids.  
  • Technologies for early cancer assessment: refers collectively to tools, methods, assays, and other technical aspects relevant to the early detection and characterization of human pre-cancers and early stage cancers.
  • Pre-competitive collaboration: refers to the situation when entities (that might ultimately become commercial competitors) share information and collaborate on early stages of research and development and/or specific, defined aspects/domains (e.g., establishing standards, best practices), where joint efforts may be beneficial to all stakeholders. It is a means of efficient utilization and sharing of resources that allows effective movement to market competition.
  • Partnership team - each application must involve a team with complementary expertise representing investigators from academia and biomedical industry; thus, for the purposes of this FOA, such teams are referred to as a "Partnership Teams" and the entire endeavors proposed for U01 awards as "Partnerships".
 
Background

In the era of personalized medicine, it is desirable to have noninvasive or minimally invasive methods to determine and follow longitudinally the molecular composition and characterization of a patient’s tumor, which will help gain a broader understanding of the disease. One such approach is through liquid biopsy that can be used to molecularly characterize the tumor and monitor genetic changes over time using repeat sampling of biofluids. Liquid biopsy generally refers to detecting circulating tumor cells (CTC), circulating tumor DNA (ctDNA), circulating exosomes and other analytes in body fluids, such as serum, plasma, urine, etc. Liquid biopsies have the potential to help clinicians screen for disease, stratify patients, and follow patients undergoing surveillance. It can also offer an opportunity to detect early lesions in cases where biopsy is difficult, such as brain cancer as it has been shown that tumor DNA can be found in the cerebrospinal fluid.

Recent research efforts on liquid biopsies have focused on detection of CTCs, ctDNA, epigenetic changes, and alterations in miRNA expression in extracellular vesicles. Both CTCs and ctDNA have shown great potential for use in diagnosis, predicting response to therapy and monitoring relapse; their usefulness for early detection/screening has been more difficult to establish. This difficulty reflects both analytical and biological challenges. The biological difficultly is that early stage cancers release very few copies of mutant DNA and very few tumor cells into the blood.  Detecting these low levels of CTCs and ctDNAs in the presence of very high levels of other types of cells or normal DNA is technologically challenging. However, recent advances in the development of ultrasensitive methods for capturing and quantifying tumor cells and DNA from biofluids indicate that liquid biopsies have great potential for early detection or screening. An advantage of CTCs and ctDNA over other types of cancer biomarkers is that they are more direct indicators of the disease and more closely mirror the alterations of the cancer cells. They are also less likely to be affected by the method of isolation. Combining data from several different types of liquid biopsies (CTCs, other types of circulating cells, ctDNA or tumor-derived extracellular vesicles) or with other forms of biomarkers (proteins, miRNAs, metabolites, etc.) may provide complementary information resulting in more accurate and sensitive early detection methods. This will require the development of computational tools or new algorithms to integrate data and to identify novel biomarker signatures.

For CTCs to be useful for early detection, improved methods that can isolate and characterize CTC heterogeneity are needed.  Similarly, progress on the use of ctDNA for diagnosis, prediction of response to therapy and monitoring for relapse has been greater than the use of ctDNA for early detection. Studies have shown that the concentration of ctDNA in early stage disease is lower than that in patients with late stage disease. Capturing and accurately sequencing ctDNA in the presence of a vast excess of normal DNA poses a substantial technological challenge; the mutation prevalence can be less than 0.01% (one mutated copy in a background of 10,000 wild-type alleles). Another challenge for using ctDNA for early detection is that one does not know which mutations will be present in the patient’s blood, thereby necessitating the use of a panel of markers that will detect a cancer. Considering these challenges, there is a need for better technology for detection of ctDNA and preferably in smaller volumes of blood.

Tumor cell DNA isolated from other biofluids, such as cervico-vaginal fluids for ovarian and endometrial cancer cells from which DNA can be purified and sequenced. Similarly, non-small cell lung cancer DNA can be isolated from saliva. The advantage of ctDNA in other biofluids over CTCs is the direct proximity to the potential tumor site and maybe more useful in early detection. However, the generalizability of this approach and its potential usefulness for early detection are unknown and yet to be determined. Similarly, exosomes and other extracellular vesicles, including exosomes can be utilized for detection of gene amplifications as well as mutations. As with CTCs and ctDNA, the challenge for using EVs in a liquid biopsy is isolating and characterizing them in a large background of EVs from normal cells.

Precompetitive collaboration is a term used when competitors share early stages of research and development that are beneficial to all stakeholders. This initiative proposes to support research to advance technologies and use these technologies to develop assays for early cancer detection, to distinguish benign disease from cancer, to distinguish aggressive from nonaggressive cancer, and for use with other classes of biomarkers. Combining the complementary expertise of both academics and industry may increase the likelihood of developing a viable diagnostic assay. 

Academic-Industrial partnerships will strengthen collaborations by creating a vehicle for industry to interact with and, where appropriate, co-fund the development of the required technologies with the NCI-funded applicants. Industry will benefit by having the opportunity to assist in the development and verification of liquid biopsy platforms and to leverage their investments in an already developed resource base and improved access to new resources, expertise, databases and reagents that result from NCI-coordinated efforts.

Main Research Objectives and Requirements

Overall Research Focus and Partnership Teams. Research activities proposed under this FOA must be focused on developing and validating technologies, methods, and assays for liquid biopsy for early detection of cancers.

Academic-Industrial Partnerships. To realize these goals, applicants from academic institutions are expected to develop partnership teams which include industrial scientists. The members of the team representing the industrial partner should already be engaged in the development of liquid biopsy-oriented technologies and/or technologies that are applicable to or can be adapted to liquid biopsies.

The teams should be capable of appropriate verification of technology platforms, assays, devices, etc. as needed to facilitate their adaptation to clinical settings, with academic investigators or clinical experts. The teams are expected to have a range of expertise in such areas as: cancer biology with emphasis on targeted cancer types, biospecimen science, bioinformatics, clinical assay development, technology engineering, and/or other areas as needed for the research proposed.

Two types of research activities are required for each Partnership proposed:

I. An individual research project addressing the development and/or validation of liquid biopsy-oriented technology that could offer substantial clinical benefits. Such projects could be of the following types, depending on the stage of development and characteristics of a given technology:

  • Technology Development/Refinement - with emphasis on development and/or modification of existing technologies, methods, assays and tests for analytic verification and validation using relevant liquid biopsy human biospecimens. The feasibility of the proposed goals must be supported by strong preliminary data and/or other scientific justification. The proposed platform/method/assay should have the potential to reach clinical testing within the timeframe of this initiative.
  • Technology Harmonization/Verification - with emphasis on comparisons of such aspects as sensitivity, accuracy, and/or reproducibility in detecting targets by different approaches using the same set of human clinical biospecimens; such comparative studies between the various technologies of liquid biopsy must be conducted in well-annotated samples and, when necessary, data should be compared to tissue biopsy in establishing that the clinical tests can detect the established disease.

II. Collaborative efforts with other partnerships within the Liquid Biopsy Consortium. Each awardee will be required to engage in collaborations with other Partnerships in the Network. These collaborative efforts are expected to be pre-competitive in nature and benefit all stakeholders.

Specific activities to be carried out will be determined post-award by the Liquid Biopsy Consortium Steering Committee. Nonetheless, all applicants should anticipate (and be prepared for) the following types of precompetitive activities:

  • Collaborative research on aspects generally relevant across various liquid biopsy-oriented technologies--establishing standards, best practices, planning and development of resources and reagents, including the collection of biospecimens, necessary to move a technology toward clinical utility etc.;
  • Sharing biospecimens with other Partnerships (required for biospecimens to be collected under the Partnership award); and
  • Validation and clinical application of sufficiently advanced technologies - technologies that have successfully completed the "Harmonization/Verification" phase may be selected for trans-Consortium studies using appropriate cohorts of longitudinally collected samples (that would include pre-clinical samples) as well as samples representing diverse/minority populations. In the context of this FOA, pre-clinical samples are those that are obtained from subjects prior to the onset of clinical symptoms.

Neoplasms/Organ Types. Research proposed should be focused on those neoplasms/organ types for which liquid biopsy is likely to offer substantial clinical benefits. For example, an organ type(s) may be selected for which:

  • There is a high prevalence of detection of non-lethal cancers associated with current screening methodologies;
  • No tools exist for noninvasive monitoring of disease progression from indolent to malignant cancer;
  • No noninvasive tools exist for early cancer detection in high-risk populations (genetic and/or familial predispositions); and/or
  • Tumors that are inaccessible to tissue biopsy.

Specific Directions of Interest. Research proposed is expected to be relevant to the challenges identified in the Background described above, that is, to improve the level of detection, sensitivity and specificity for a proposed clinical application and/or technology for capturing, isolating, purifying and characterizing circulating analytes, CTCs, ctDNA, EVs, etc. for early stage disease.

Possible focus areas include (but are not limited to) the following examples:

  • Development of new and/or validation of existing technologies, methods, assays for the detection and quantification of tumor-associated circulating cells including tumor associated macrophages, platelets and tumor regulating stroma cells from blood and/or other body fluids.
  • Development of assays that can detect/screen for multiple types of cancer from a single plasma sample (e.g. colon, lung, pancreas, breast, prostate).  The assays would need to distinguish the cancer type and be compared to imaging or tissue biopsies for a definitive diagnosis.
  • Development of biosensors for real time monitoring of circulating tumor DNA, cells, exosomes and other analytes.
Non-Responsive Projects

The following types of activities remain outside of the scope of this FOA and non-responsive to this FOA.  Applications proposing such activities will not be reviewed.

  • Approaches that are not focused primarily on human liquid biopsies;
  • Development of new technologies for which there is lack of evidence (preliminary results and/or cancer biology literature data) that the targeted analyte(s) is(are) present in liquid biopsies;
  • Commercialization of assays or technologies;
  • Primary focus on software/informatics solutions, database development, data mining, statistical tools, and computational/mathematical modeling.

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

NCI intends to commit $5million in FY 2018 to fund 6-8 awards.

Award Budget

 The requested budget must not exceed $600,000 per year (in direct costs).

Award Project Period

 The total project period requested may not exceed 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

  • 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:

o   Hispanic-serving Institutions

o   Historically Black Colleges and Universities (HBCUs)

o   Tribally Controlled Colleges and Universities (TCCUs)

o   Alaska Native and Native Hawaiian Serving Institutions

o   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
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 and each reflects a different partnership team.

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:

Lynn Sorbara, Ph.D.
Telephone: 240-276-7135
Fax: 240-276-7845
Email: lynns@mail.nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed with the specific term of this FOA.

  • Research Strategy Section 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.

Other Attachments: Applicants must provide the following additional materials specified below in support of their application. Each attachment should be uploaded as a separate PDF using the indicated filenames (which will serve as application bookmarks).

Attachment 1: Biospecimen Procurement (use filename Biospecimens).

In this attachment, a detailed description of the proposed prospective and/or retrospective collection of human biospecimens should be discussed and the following documentation included: 

  • Information on the types of patients and control subjects, clinical information the applicants plan to obtain, and types of specimens by organ site to be collected. 
  • If the applicants have existing repositories, then a list of types and number of available specimens by organ site should be described.

Attachment 2. Quality Control and Quality Assurance (use filename QC-QA).

Provide documentation reflecting your previous efforts relevant to quality control and quality assurance issues and related considerations that may arise in multi-institutional studies. For example, include documentation of confirmation of pathology and radiology reports and inter-laboratory comparisons of test results and procedures.

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. The following additional instructions apply for this FOA.

a) PD/PI Effort Commitment. The minimal effort commitment for the contact PD/PI must be 1.8 person-months per year. The effort commitment for other PDs/PIs (if multiple) must be a minimum of 1.2 person-months. These effort commitments cannot be reduced in later years of the award.

b) Travel Expenses. Applicants must budget travel funds for two persons (two PDs/PIs or the PD/PI and an additional senior investigator) to attend one Steering Committee meeting per year.

c) Consortium Collaborative Fund. Applicants must set aside $100,000 of their annual direct budgets for a Consortium Collaborative Fund. This fund will support acquiring preclinical /prediagnostic samples for validation; testing and incorporation of technology/markers developed by the Liquid Biopsy Consortium members; establishing a collaboration to evaluate technology/markers discovered in more than one laboratory for independent cross-laboratory validation. The use of these set-aside funds will be restricted to the collaborative activities reviewed and approved by the Liquid Biopsy Consortium Steering Committee.  This set-aside amount should be listed in the Other Expenses category under the heading “Consortium Collaborative Funds.”

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 scope of the proposed research and its relevance to specific unmet clinical needs in the early detection of cancer by use of liquid biopsy.  The specific aims to be pursued must be also described.

Research Strategy: Research Strategy must consist of the Sub-sections A-E outlined below:

Sub-section A. Overview

Outline the overall research theme of the proposed work. Identify the gap(s) or challenge(s) for clinical utility/testing of liquid biopsy for early detection of cancer that your partnership team intends to overcome. Address the overall translational potential and relevance of the studies to clinical management of early cancer detection. Summarize the main collective strengths of the partnership/team members in the context of these goals.

Sub-section B. Significance and Background

Applicants must provide a description of the proposed project, its Significance, Background, and Innovation in the context of a specific unmet clinical need in early detection of cancer by use of liquid biopsy. Applicants must address the current state-of-the-science of the fields of use of liquid biopsy in early cancer detection, diagnosis, and prognosis and include preliminary findings as they relate to their proposed projects. 

Sub-section C. Partnership Teams

Outline the complementary multidisciplinary scientific expertise required for the integration and comprehensive approaches to the key research problems proposed and how the partnership team provides that expertise. Explain how the diverse expertise of the team members increases the capability for innovation, the ability to anticipate new directions, and the flexibility to redirect research when needed. The specific roles and responsibilities of each of the members of the partnership teams should be delineated. Whereas prior collaborations between the academic and industrial partners are not required, sufficient information about partnership organization and functioning must be provided so the reviewers can assess whether the proposed partnership is likely to interact efficiently

Sub-section D. Approach.

Describe the overall strategy, methodology, and statistical methods and analysis of the specific aims of the project. Potential problems, alternate strategies, and benchmarks for success should be detailed. In addition, the following specific items need to be included (applications lacking these items will be deemed incomplete and will not be reviewed):

Technology Development Plan. The Plan should detail the following:

  • A clear description of the goal(s) of the project, including one or more intermediate or final products, or stage(s) of product development to be completed during the award period. The scientific rationale must be established by prior discovery, translational and/or clinical research that provides the scientific basis for the proposed strategy. A specific final product profile that is intended for licensing indication is not requested;
  • A statement of the intended use/indication of the proposed product and the public health gap the product is intended to fill;
  • Descriptions of preclinical product development activities pertaining to the product proposed. 
  • The performance specifications of the product (diagnostic assay, method, technology, etc.), should have to demonstrate that it is equivalent or superior to the current gold standard for identifying the proposed agent(s), including analytical sensitivity (limit of detection), specificity, and analytical reproducibility (test replicates at different agent concentrations, at different sites, etc.), as well as clinical sensitivity and specificity in appropriate human samples. If no FDA-cleared test is available for the agent(s), the specifications should be equivalent to or exceed performance specifications of FDA-cleared tests for similar types of agent(s);
  • Data that support the selection of the candidate technology for further development, including an assessment of the present capacity of the diagnostic method, technology or assay to meet the performance specifications;
  • Discussions with FDA, if any, that are relevant to development activities for the candidate product.

Project Management Plan. The Project Management Plan should cover the following requirements:

  • A tentative timeline for conducting the proposed studies (with brief descriptions of how the goals of each of the proposed specific aims will be achieved on a year-by-year basis by providing tentative, interim milestones).
  • Overall Project Milestones must be well described, quantitative, and scientifically justified. Discuss the milestones as a means of judging the success of the proposed studies during the initial 3 years of support by the award. Specific aims may not be regarded as milestones (unless they include quantitative end points). The specific aims describe the goals and intended path of the proposed research. Quantitative milestones are a way of determining whether an applicant has successfully reached the specified goals. In most cases, applicants should provide a milestone for each specific aim. Milestones should be clearly stated and presented in a quantitative manner, such as numerical specifications of sensitivity and specificity or a count of some newly discovered molecules or molecular pattern(s) that can be used as biomarkers for early cancer detection, risk assessment, diagnosis or prognosis of cancer.
  • Applicants should elaborate on a decision-tree scheme to be used during technology development to determine the stages at which a specific technology should be pursued for the harmonization and application stages of the Liquid Biopsy Consortium's effort. The criteria that will be used to make these decisions should be specified, as appropriate, as well as the alternative steps that will be taken should certain biomarkers be dropped at any stage (i.e., will only the best performing biomarkers from a large set be retained [‘go’ or ‘no go’ decision] or will a new approach to technology development for liquid biopsy be taken to identify new analytes/biomarkers?).

Sub-section E. Anticipated/Potential Contributions to Precompetitive Collaborations.

Outline how the proposed partnership team can participate in collaborative efforts with other partnership teams in the planning and development of resources and reagents, including biospecimens, necessary to move a technology toward clinical testing. Consider addressing, as appropriate, such aspects as:

  • Identify the domain(s) suitable for precompetitive research in liquid biopsy technology(-ies) to leverage the capabilities of many organizations, including government and academia.
  • List areas your partnership team may be able to collaborate with other partnership teams, e.g., sharing the details of internal quality systems for liquid biopsy, enhancing standards, discussing experience on corrective actions and best and less-than-best practices in developing liquid biopsy technologies. Identify technology(-ies) that may be ready for cross-comparison, harmonization, and application.
  • Describe plans for sharing standard operating procedures, the formatting and standards for comparing various liquid biopsy technologies and developing internal standards.
  • Outline collaborative strategies that allow individual scientific collaborations to advance more rapidly by identifying potential collaborators throughout the Liquid Biopsy Consortium. In doing so, this would support breakthrough technologies by understanding the capabilities of the technologies in cancer and beyond and identifying appropriate patient cohorts as a source biological specimens.

Sub-section F. Human Biospecimen Procurement.

Applicants should describe their ability to procure specimens prospectively, collect epidemiological and clinical data using the NIH “Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/); and to process, track, and store specimens.  Details for any proposed retrospective and/or prospective specimen collections, either new or ongoing, that will be used for liquid biopsy consortium activities should be delineated.  The description should include information on the types of patients and control subjects to be accrued, clinical information to be collected, and types of specimens to be collected.  Active prospective collections can be proposed only for studies proposed in this application and in collaboration with NCTN Clinical Trials Groups or any ongoing trials that provide a unique opportunity for prospective longitudinal collection for major epithelial cancers to ensure the success of the collaborative Consortium research projects. 

If the applicants already have specimen repositories that they are willing to make available to Consortium collaborative studies, they should describe the purpose of the study(s) from which samples are being made available and the extent of the clinical information collected.  Applicants with adequate existing repositories that will be available to Consortium investigators should furnish a list of types and number of specimens by organ site and provide information on histopathological stage and clinical grade, mode of detection, and the availability and length of follow-up data. ( For information on potential sources of biospecimens applicants may also see http://epi.grants.cancer.gov/biospecimens.html.)

Applicants should describe procedures for quality control and quality assurance. The procedures and the documentation should include confirmation of pathology and radiology reports and inter-laboratory comparisons of test results and procedures.  The applicants must discuss their experience with quality control issues and other considerations that may arise in multi-institutional studies.  Human subject biospecimen characterization data (i.e., “clinical data”) are expected to conform to cancer Common Data Elements registered in the cancer Data Standards Repository; for examples see (https://wiki.nci.nih.gov/display/caDSR/caDSR+Database+and+Tools.

Note: While completing this sub-section, applicants should note that appropriate supporting documentation regarding Biospecimen Procurements and Quality Control/Quality Assurance must be provided under Other Attachments.

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 collaborations from investigators directly involved in relevant cohort studies should clearly indicate their commitment to the Liquid Biopsy 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.
  • The plan should expressly address sharing prospectively collected specimens with other members of the Liquid Biopsy Consortium. All the biospecimens from any new prospective collections supported under this FOA should become available to all investigators in the Liquid Biopsy Consortium and should be available for network validation studies.
  • As appropriate, the plan should outline sharing applicable standard operating procedures, the formatting and standards for comparing various liquid biopsy technologies, development of internal standards, etc.
  • Applicants are expected to submit an Intellectual Property Management Plan. Applicants should consider pre-existing intellectual property rights associated with the use of existing models/reagents and address appropriate access and licensing arrangements, consistent with achieving the goals of this program.  Applicants and their technology licensing offices are encouraged to seek assistance as needed from the NCI Technology Transfer Center (https://ttc.nci.nih.gov/) in determining whether such arrangements are appropriate and/or adequate.

Applicants should list and summarize the materials, technologies and/or expertise that they can provide within the precompetitive collaborative environment.

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: What is the likelihood that the proposed translational research project will lead to liquid biopsy tool suitable for early cancer detection? What would be the potential for use of that tool in clinical settings? 

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 proposed partnership team have sufficient complementary expertise to effectively manage the steps necessary for successful development of an early detection liquid biopsy tool? Is the composition of the team appropriate and sufficient to address the required clinically relevant aspects of their project (e.g., expertise in oncology, pathology, and related areas)? Are the commitments of investigators on both sides of the partnership (i.e., academia and industry) adequate and sufficient for the goals of the proposed research? How compelling is the evidence that the partners can work together effectively?

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 experimental plans for translation of emerging or new capabilities of liquid biopsy to solve an important clinical problem well thought out, sufficiently comprehensive, and coherent? Does the proposed study describe capabilities for recruitment of appropriate patients for the prospective procurement of specimens and associated clinical and epidemiological data? Are the proposed procedures for quality control and quality assurance sound and sufficient? Do the applicants define the domain of precompetitive research in liquid biopsy technology targeted and their plans for collaboration and sharing of specimens and standard operating procedures? How realistic is the project timeline? Are the milestones proposed rigorous enough and adequate to serve as "go/no-go" options?

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 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 appropriate national Advisory Council or 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 Part 75 (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 responsibilities for:

  • 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 Liquid Biopsy Consortium Steering Committee (the PD/PI and another senior investigator from each Consortium award (U01) 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 Liquid Biopsy Consortium and with NCI staff members;
  • Overseeing the implementation of the approved data sharing plan;
  • Ensuring that experimental data and their format, analytical algorithms, computational modeling and visualizations, and other bioinformatics tools resulting from this FOA are compatible with the NIH-approved bioinformatics platforms, such as those designed and implemented by the NCI Center for Biomedical Informatics and Information Technology (http://cbiit.nci.nih.gov).
  • The PDs/PIs and their awardee institutions will be accountable for implementing the approved research resource sharing plan.
  • All institutions/organizations participating in the Liquid Biopsy Consortium will be expected to share with each other knowledge, data, research materials, and any other resources necessary and relevant to the Liquid Biopsy Consortium.
  • Each Consortium awardee and the entire Liquid Biopsy Consortium programmatic initiative will be subject to external evaluation (coordinated by the NIH).  Consortium Awardees will be expected to participate in such evaluations.
  • 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.
  • Awardees will be required to collaborate with other Consortium awardees on such aspects as developing and conducting trans-Consortium collaborative projects, sharing resources (as applicable: biospecimens, standards, and/or procedures), and other activities of pre-competitive nature that may benefit all participants, as appropriate and consistent with achieving the goals of this program.

NIH staff 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 and industrial partners and will ensure access to other NIH relevant programs. 

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.  A Program Official may also have substantial programmatic involvement (as a Project Scientist). 

Specific activities of substantially involved NCI staff members will include:

  • Advising the awardees on specific scientific and/or analytic issues as well as programmatic priorities;
  • Facilitating access to NCI resources, biospecimens, epidemiological expertise, etc.;
  • Facilitating various activities of the Liquid Biopsy Consortium programs;
  • Participating in the activities of the Liquid Biopsy Consortium Steering Committee;
  • Serving as a liaison between the Steering Committee, the Liquid Biopsy Consortium awardees, and the NIH;
  • Ensure common access to Consortium-generated resources and reagents for the broader cancer research community and facilitating access to NCI resources, biospecimens, epidemiological expertise, etc.
  • Ensuring, in cooperation with the NCI CBIIT, that there are effective mechanisms to enable electronic communication among the Liquid Biopsy Consortium awardees, and between the Liquid Biopsy Consortium and the NCI;
  • Assisting the Steering Committee in developing and drafting operating policies and policies for dealing with recurring situations that require coordinated action;
  • Assisting the investigators in avoiding unwarranted duplications of effort across the Liquid Biopsy Consortium;
  • Co-organizing and participating in the Liquid Biopsy Consortium Steering Committee meetings;
  • Monitoring the scientific progress of individual Consortium awards and the entire program;
  • Reviewing the compliance of Consortium awardees with the recommendations developed by the Steering Committee; and coordinating external evaluation of the Liquid Biopsy Consortium.  

Areas of Joint Responsibility

Steering Committee. The Steering Committee will be the main governing body for the Liquid Biopsy Consortium, as defined below.

The Liquid Biopsy Consortium Steering Committee will consist of the following voting members:

  • Two representatives from each Consortium award (the PD(s)/PI(s) or a PD/PI and a designated senior investigator) who will have one vote each; and
  • The two NCI Project Scientists/Coordinators (who will have one vote each for the NCI).

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

Additional NIH staff members may participate in Steering Committee meetings as non-voting members as needed (for example to provide additional expertise).  The non-voting members may include representatives from NCI extramural divisions and a representative from the National Cancer Institute Center for Biomedical Informatics and Information Technology (NCI CBIIT).

Additional non-voting members to serve in an advisory capacity may be added to the Steering Committee as needed by a decision of the existing voting committee members.

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

The Steering Committee will meet once every year, at locations selected by the Steering Committee in consultation with the NCI. The first meeting will focus on defining the process and procedures for the coordination of the Liquid Biopsy Consortium activities.

Steering Committee responsibilities will include the following aspects:

  • Recommendation for proceeding through the three stages of progress (development, harmonization, and application);
  • Identifying areas of opportunity that can best be exploited with a group effort via the Liquid Biopsy Consortium; coordinate the acquisition and distribution of biospecimens;
  • Encouraging the development of new methodologies and approaches to be shared among the Liquid Biopsy Consortium members;
  • Optimizing the information flow among the teams and the NCI; and
  • Establishing procedures guiding how collaborative activities (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.

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 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)

For general inquiries regarding early cancer detection and liquid biopsy, contact:

Sudhir Srivastava, MPH, PHD
National Cancer Institute
Telephone: 240-276-7028
Email: srivasts@mail.nih.gov

For inquiries specifically related to this FOA, contact:

Lynn Sorbara, PhD
National Cancer Institute
Telephone: 240-276-7135
Email: lynns@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.

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