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
Integrating Biospecimen Science Approaches into Clinical Assay Development (U01 Clinical Trial Not Allowed)
Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type
Reissue of PAR-18-947
Related Notices
  • October 28, 2021 - Reminder: FORMS-G Grant Application Forms & Instructions Must be Used for Due Dates On or After January 25, 2022 - New Grant Application Instructions Now Available. See Notice NOT-OD-22-018.
  • September 13, 2021 - Updates to the Non-Discrimination Legal Requirements for NIH Recipients. See Notice NOT-OD-21-181.
  • August 5, 2021 - New NIH "FORMS-G" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2022. See Notice NOT-OD-21-169
  • August 5, 2021 - Update: Notification of Upcoming Change in Federal-wide Unique Entity Identifier Requirements. See Notice NOT-OD-21-170
  • April 20, 2021 - Expanding Requirement for eRA Commons IDs to All Senior/Key Personnel. See Notice NOT-OD-21-109
  • November 2, 2021 - Notice of Correction in Expiration Date for PAR-22-049. See Notice NOT-CA-22-008.

Funding Opportunity Announcement (FOA) Number
PAR-22-049
Companion Funding Opportunity
None
Assistance Listing Number(s)
93.393
Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) will support extramural research to investigate and mitigate challenges facing clinical assay development and subsequent analytical validation due to preanalytical variability in tumor tissue biopsies, blood biospecimens utilized as “liquid biopsies", or other biospecimens as described in this FOA. Extramural research funded under this FOA may include investigations of preanalytical variability associated with the procurement and study of small biopsies (core biopsies, small excision samples), blood utilized for "liquid biopsies", tissue swabs, tissue secretions, pleural and esophageal aspirates, feces, or bodily fluids like sweat, urine, CSF, breast milk and saliva. Investigator-designed experiments will explore how different biospecimen preanalytical conditions affect emerging and clinically relevant biomarkers quantified by a variety of testing platforms. The results from this research program will improve the understanding of how analytical quantification of clinically relevant biomarkers is affected by variation in biospecimen collection, processing, and storage procedures. The overall goal is to expedite biomarker clinical assay development through evidence-based standardization of biopsy handling practices.

Key Dates

Posted Date
October 22, 2021
Open Date (Earliest Submission Date)
December 11, 2021
Letter of Intent Due Date(s)

30 days prior to the application due date.

The following table includes NIH standard due dates marked with an asterisk.
Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
January 11, 2022 January 11, 2022 Not Applicable July 2022 October 2022 December 2022
June 07, 2022 June 07, 2022 Not Applicable November 2022 January 2023 April 2023
September 13, 2022 September 13, 2022 Not Applicable March 2023 May 2023 July 2023
January 11, 2023 March 05, 2023 * Not Applicable July 2023 October 2023 December 2023
June 07, 2023 June 07, 2023 Not Applicable November 2023 January 2024 April 2024
September 13, 2023 September 13, 2023 Not Applicable March 2024 May 2024 July 2024
January 11, 2024 March 05, 2024 * Not Applicable July 2024 October 2024 December 2024
June 07, 2024 June 07, 2024 Not Applicable November 2024 January 2025 April 2025
September 13, 2024 September 13, 2024 Not Applicable March 2025 May 2025 July 2025

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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

Expiration Date
New Date September 14, 2024 per issuance of NOT-CA-22-008 . (Original Expiration Date: September 14, 2023)
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

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. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

This Funding Opportunity Announcement (FOA) will support extramural research to investigate and mitigate challenges facing clinical assay development and subsequent analytical validation due to preanalytical variability in biospecimens as described in this FOA. Research funded under this FOA may include investigations of preanalytical variability associated with the procurement and study of small biopsies (core biopsies, small excision samples), blood utilized for "liquid biopsies", tissue swabs, tissue secretions, pleural and esophageal aspirates, feces, or bodily fluids like sweat, urine, CSF, breast milk and saliva. Investigator-designed experiments will explore how different biospecimen preanalytical conditions affect emerging and clinically relevant biomarkers quantified by a variety of testing platforms. The results from this research program will improve the understanding of how analytical quantification of clinically relevant biomarkers is affected by variation in biospecimen collection, processing, and storage procedures. The overall goal is to expedite biomarker clinical assay development through evidence-based standardization of biopsy handling practices.

Background

Importance of preanalytical factors in biospecimen research

Biospecimen preanalytical variability can affect the reproducibility of clinical research. Biospecimens are the essential starting materials for the biomarker assays that will enable precision medicine. Clinical assays used for diagnosis and therapeutic decision-making are based on assessment of biological molecules (DNA, RNA, and proteins) from a patient’s biospecimen. Such assays are often based on the detection of one or more biomarkers and must be both accurate and reproducible. False positive or negative results from the evaluation of biomarkers in clinical assays can directly affect patient diagnosis, treatment, and outcomes and can lead to over-treatment, under-treatment, or incorrect treatment.

An increasing number of reports demonstrate that preanalytical factors such as the handling of a clinical biospecimen prior to analysis can have a significant impact on assay results, which can in turn affect patient care. Biospecimen preanalytical factors can directly influence molecular results from assays conducted for basic research, biomarker discovery, biomarker validation, and development of validated clinical assays. In fact, preanalytical processing has been highlighted as a significant impediment in the development of predictive biomarkers for oncology. Preanalytical variability has also been identified as a challenge in the implementation of next-generation technologies in the analysis of tissue biopsies. The methods used to collect, process and store small biopsy biospecimens such as core biopsies, fine needle aspirates (FNAs), and lung aspirates, for example, can vary widely within and across medical institutions and laboratories, introducing variability in such preanalytical factors as biopsy method, needle gauge, vacuum-assistance, biospecimen size/volume, duration and temperature of transport, preservation method, temperature and duration of storage, and number of freeze thaw cycles. A wide variety of preanalytical factors alone and in combination, are known to affect the accurate assessment of biomarkers, adding to the complexity of biospecimen challenges for the clinical laboratory.

New knowledge about preanalytical effects can support evidence-based biospecimen procedures for cancer research activities including clinical trials. Smaller biopsies such as FNAs, core biopsies, and lung aspirates present a unique set of preanalytical factors and associated challenges for reliable biomarker assay results. Such biopsies are clinically valuable now and in the future for assessing current and recurrent disease state as well as for assessing the likely efficacy of therapeutic intervention. Research has shown discordant biomarker assay results when comparing such small biopsies with larger tumor resections.

Detection of biomarkers in blood analytes such as cfDNA (cell-free DNA) and CTCs (circulating tumor cells) is a promising approach for non-invasively tracking tumor behavior over time, potentially enhancing cancer management by assessing tumor burden, detecting recurrence, monitoring early response and identifying drug resistance. Preanalytical considerations are also challenging for such “liquid biopsies,” as inconsistency between sample handling protocols and lack of standardization among analytical techniques has created obstacles for translating cfDNA analysis to clinical practice. CTC analysis, including enumeration and characterization, is also affected by preanalytical factors. Challenges introduced by preanalytical variability also affect the isolation and analysis of exosomes and other extracellular vesicles, underscoring the need for rigorous analytical validation.

Bodily fluids such as urine and cerebrospinal fluid (CSF) have also emerged as biospecimens for potential detection of biomarkers in clinical assays that can directly affect patient diagnosis, treatment, and outcomes. Other biospecimen types such as tissue swabs, tissue secretions, pleural and esophageal aspirates, feces, sweat, breast milk and saliva also have potential application in clinical biomarker research and are included in this FOA.

Differences in assay results can be a result of differences in preanalytical factors such as ischemia times, preservation method, and tumor heterogeneity. Such preanalytical factors may alter biomarker measurements and influence the performance of assay technologies. Variability and biases introduced in the early stages of biomarker assay development, if not addressed and understood, can increase the likelihood of irreproducible data and incorrect conclusions. This is of significant concern for NCI clinical research. Basic and applied biospecimen science investigation will provide valuable insights into how to limit variability in clinical assay results from small biopsies.

Examples: Effects of preanalytical factors on diagnostic assays

A classic example of how biospecimen preanalytical factors can have a dramatic influence on assay results is companion diagnostic HER2 assays that guide the therapeutic use of trastuzumab, a breast cancer therapeutic. Recommendations for the reliable assessment of HER2 status in patient biospecimens were established 14 years after the initiation of phase 1 clinical trials in 1992. These measures were developed in response to multiple issues with HER2 reproducibility including preanalytical variability. For example, one study showed that the number of patients reported to overexpress HER2 differed by approximately 20% between specimens processed in local pathology departments and those processed in centralized laboratories.

When investigating whether non- standardized approaches between laboratories directly influenced the clinical assay results, the American Society of Clinical Oncologists (ASCO) and the College of American Pathologists (CAP) concluded that several biospecimen preanalytical factors including fixative, delay time to tissue fixation, method of tissue processing, and time in fixative could influence HER2 assay results. A major issue for such guidelines is that there is often a lack of fundamental scientific data on the behavior of clinical biomarker assays in response to biospecimen preanalytical factors. Systematic evaluation and increased understanding of the impact of these factors in the context of particular assay platforms and tissue types, and how to mitigate their impact, are necessary to improve current clinical assays and the development of new biomarker assays.

Preanalytical factors also impact the reproducibility of highly sensitive liquid biopsy assays that require optimized conditions for identification of circulating tumor material. For example, blood collection tube type and a time-to-assay delay affect CTC enumeration and characterization of breast cancer patient samples using the high-definition single-cell analysis assay (HD-SCA). CTC recovery, EpCAM and cytokeratin immunostaining, and nuclear content are also affected by storage time and tube type. Concentration and fragmentation of circulating cell free DNA (cfDNA) are also influenced by differences in sample handling procedures. These examples highlight the crucial importance of biospecimen science in effective development and application of clinical diagnostic assays.

Previous support of Biospecimen Science at the NCI

To begin to address concerns of preanalytical variability, the NCI established the Biospecimen Research Network (BRN) in 2007. Through an extramural funding program, “Biospecimen Research for Molecular Medicine," an online literature database, “The Biospecimen Research Database” (BRD), and an annual conference, “The BRN Symposium,” the BRN program advanced the field of biospecimen science through systematic investigation of the effects of different biospecimen collection, processing, and storage procedures on downstream molecular analyses. Research contracts were competitively awarded to identify and develop novel approaches to identify key preanalytical factors associated with collection, processing, and storing of blood, plasma and tissue. https://biospecimens.cancer.gov/about/researchnetwork/projects/default.asp

Sponsored studies to date include:

  • Studies demonstrating that preservation methods can impact gene expression of a subset of transcripts differentially;
  • Studies on the effects of blood biospecimen collection tubes, processing times, time in freezer, and freeze/thaw cycling on protein integrity;
  • The effects of tube type, time on bench and storage temperature on circulating miRNA detection;
  • An assessment of the effect of cold ischemia on protein detection in breast cancer tissues;
  • The effects of cold and warm ischemia on the detection of gene expression and protein phosphorylation in post resection tissues;
  • Studies to evaluate the effects of cold ischemic time, specimen preservation, and storage methods on RNA yield, RNA Integrity Number (RIN) values, transcript integrity and microarray-based measurements of gene signatures.

Results of these studies have provided valuable data on how biopsies and resections should be handled (e.g., minimize cold ischemia time and utilize core biopsies, when possible, for IHC assays; use RNAlater® for biopsies if possible, when gene expression studies are planned) and have built a solid knowledge base for evidence-based practices for biospecimen collection, processing, and storage when conducting blood-based mass spectrometry investigations. Overall, results from the BRN and work summarized in the BRD suggest that biospecimen preanalytical factors can significantly affect research and clinical assay results. However, preanalytical factors of particular importance for small biopsies relating to procurement and alterations in processing and extraction due to reduced biospecimen size remain largely unexplored. Research also demonstrates that the downstream effects of different preanalytical factors can vary with respect to the specific analyte being evaluated and the analytical platforms and/or assays being used. Thus, new and emerging clinical biomarkers and assays could be affected to unknown extents.

Need for continued research in biospecimen science

Measurement and validation of clinically relevant biomarkers using diagnostic assays are increasingly challenging as reliance on smaller biospecimens increases and new biomarkers and analysis platforms emerge. Particularly in NCI-sponsored treatment trials such as the NCI Experimental Therapeutics Clinical Trials Network (ETCTN), there is a need for accurate assays for integral markers used for selection of patients, integrated markers for evaluation of the clinical correlation of biomarkers for new agents, and pharmacodynamic markers that indicate whether the target has been engaged.

To generate the biospecimen science data needed to address today’s clinical biomarker assay challenges, an integrated approach is required that addresses how preanalytical factors introduced during biospecimen handling affect clinical biomarker assay performance. The need is critical given that diminished reliability and effectiveness of clinical biomarker assays could adversely affect patient care and drug development.

Research Objectives and Scope

This Funding Opportunity Announcement (FOA) will support extramural research to investigate and mitigate challenges facing clinical assay development and subsequent analytical validation due to preanalytical variability in tumor biopsies, blood biospecimens utilized as “liquid biopsies", and other biospecimen types as described in this FOA. This FOA will fund research to support clinical assay development and validation through the identification and mitigation of preanalytical factors associated with collection, processing, and storage that negatively influence clinical assay results and reproducibility.

Using a cooperative agreement mechanism, the research will be conducted by a collaborative, interdisciplinary network that integrates clinical researchers with academic and private sector scientists in projects that focus on preanalytical challenges specific to:

  • tumor tissue biopsies such as FNAs, core biopsies, small excisions, or pleural fluid aspirates, and/or
  • blood liquid biopsy assays targeting cfDNA, microRNA, CTC’s, exosomes and metabolites, and/or
  • other biospecimens such as tissue swabs, tissue secretions, esophageal aspirates, feces, sweat, urine, CSF, breast milk, BAL and/or saliva

Potential preanalytical issues to address in solid tumors (FNA, Core biopsies, Excisions) may include but are not limited to biopsy methodology in a medical setting, tumor heterogeneity, preservation method (formalin, RNAlater, frozen, other), tissue processing, timing and temperature considerations, tradeoffs (morphology vs. molecular preservation), shipping and storage considerations. Similarly, potential preanalytical issues to address in liquid biopsies may include but are not limited to collection device in a medical setting, collection methodology in a medical setting, timing and temperature considerations, processing, shipping and storage considerations.

The FOA intends to fund dedicated studies in biospecimen science to increase the success of clinical biomarker assays in cancer research. The research will align with current efforts to optimize clinical biomarker assays utilized in clinical trial networks and will produce the data needed for evidence-based biospecimen practices to support clinical trials. Applications to improve standardization or harmonization of assays targeted for use in clinical trials may be appropriate for this FOA.

The work of the program will be centered on emerging and clinically relevant biomarker assays for a variety of molecular platforms. The FOA intends to fund clinically relevant emerging/established biomarkers (not discovery approaches) and may involve existing and emerging molecular platforms. Investigators will propose and design experiments to test assay performance and limits of detection of biomarkers under different preanalytical conditions. The work will be conducted by multidisciplinary scientific teams that may include pathologists, oncologists, radiologists, molecular biologists, and statisticians, as the work requires expertise and perspectives in clinical medicine, knowledge of the unique issues related to obtaining biopsy biospecimens, biology and technology platforms, and experimental design and analysis. A particular focus of this funding program is to address biomarker assay challenges that arise across early phase treatment trials. To best understand and address these challenges, applicant teams may wish to include investigators currently involved in Phase I and Phase II treatment trials.

This FOA will fund multidisciplinary teams that will constitute a collaborative network. These teams may include but are not limited to oncologists, pathologists, radiologists, statisticians, molecular biologists etc. Each team’s application will focus on specific biomarker assays and associated questions in biospecimen science and present a research plan for acquiring the needed biospecimens. The assay may measure a single biomarker or may be a multiplex assay but must be amenable to conversion to a clinical assay that can be used in a clinical trial setting. Preliminary data should define the current status of the assay as well as justify support for optimization and usability in a clinical trial. Research ideas, experimental design approaches, biospecimens, and molecular analysis platforms will be shared across the network as possible to maximize research productivity.

Projects will involve defining workable biospecimen conditions for trials that utilize a particular type of tissue and/or liquid biopsy (e.g. lung aspirates, liver biopsies) in a biomarker assay system (e.g. Next Generation sequencing for mutation-targeted drug trials; multi-analyte IHC/IFA or targeted mass spec for pharmacodynamic assays/pathway analysis) to detect emerging clinical biomarkers. Projects may address biospecimen challenges that are relevant to multiple trials with assays utilizing similar platforms, and/or challenges relevant to specific assays in specific trials. Applications must propose biospecimen science research for assays that are relevant today and for the five-year funding period, with the understanding that new biomarkers and assay platforms may emerge within this time frame.

The program will address the following research questions in biospecimen science to enable clinical assay development utilizing small tissue biopsies and liquid biopsies:

  • A promising biomarker or set of biomarkers has been identified for validation and assay development, but little is known about the biospecimen requirements for the assay.
  • How can one determine whether there is an effect of preanalytical factors on assay performance?
  • How is assay performance affected when biopsy (both solid and liquid) biospecimens are subjected to different preanalytical conditions?
  • Is it likely that preanalytical factors will affect clinical diagnosis using this biomarker and analytical platform?
  • Are different analytical platforms currently targeted for clinical use, e.g., RNAseq or multi-analyte IHC panels, more or less sensitive to preanalytical factors? Can such effects be mitigated with altered biospecimen practices? What stabilization approaches work better for a specific analysis platform?
  • How can the sensitivity of phosphoproteins to preanalytical conditions be mitigated, so that critical phosphoprotein biomarkers can be reliably measured?
  • Can analysis and mitigation of preanalytical variability contribute to an improved, more streamlined approach to assay standardization that reduces expense and increases assay reproducibility and utility?

Non-responsive Applications

Research Projects that are not responsive to this FOA :

  • Technology development projects that are supported by the NCI Innovative Molecular Analysis Technologies (IMAT) program, such as development of novel biospecimen fixatives/technologies.
  • Biomarker discovery projects, projects related to early detection biomarker assays, or projects related to global cancer genomic/proteomic 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
Renewal
Resubmission
Revision

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

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

Award Budget

Application budgets are limited to $250,000 direct costs per year.

Award Project Period

The maximum period is 5 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from 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)

Local Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

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

Other

  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
  • Non-domestic (non-U.S.) Entities (Foreign Institutions)
Foreign Institutions

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

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

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

Required Registrations

Applicant organizations

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) – 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.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. 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, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

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

Letter of Intent

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

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

  • Descriptive title of proposed 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:

Lokesh Agrawal, PhD
National Cancer Institute (NCI)
Telephone: 240-276-5718;
Email: lokesh.agrawal@nih.gov


 

Page Limitations

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

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.

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: In addition to the specific aims and approach(es), applicants should include the relevance of the research to the objectives of this FOA.

Research Strategy: Describe the following:

Overview

The application should clearly define the context of the proposed study and markers in current clinical trials, as well as the ability of the applicant’s team to perform analytical and clinical validation of assays in their laboratory. Applications should outline the overall theme of the proposed research and the unmet clinical need that the proposed research addresses as well as the significance of the proposed studies.

The following strategies should be used, wherever relevant:

  • Define the nature and scope of the investigative and established research approach(es) proposed
  • Determine the specificity and sensitivity and other assay performance parameters of a biomarker assay in the context of specific preanalytic conditions (if available)

Study Design

  • Objectives of the study should be clearly stated and scientific goals or hypotheses should be described in sufficient detail that they can be unambiguously evaluated. Example goals might include assessment of the analytical performance characteristics (e.g., specificity, sensitivity, precision, as applicable) of a biomarker assay in the context of specific biospecimen preanalytic conditions
  • Applications should provide a clear statement of how the proposed research addresses an unmet clinical need
  • Applications should include a statistical justification for the study design regarding the number of specimens required, the number of biomarker evaluations needed for each specimen and so forth; the justification would typically be based on calculation of statistical power, precision of parameter estimates, probability of detection of an effect, or evaluation of other operating characteristics of the study design, as applicable.

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.

The following modifications also apply:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
  • To ensure the validity of the research, PLCO specimens will be coded when released to the investigators and will remain blinded. Specimens will be unblinded upon return of the laboratory data. One year after the unblinding of the PLCO samples, these data will be made available through the PLCO website to the scientific community.

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

  • No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form

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

Foreign Institutions

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

3. 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 How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

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

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

See more tips for avoiding common errors.

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

 

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.  Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following: This FOA will support extramural research to investigate and mitigate challenges facing clinical assay development due to tumor tissue biopsy, liquid biopsy, and other biospecimen preanalytical variability as defined in this FOA. The program will tie in with current efforts to optimize clinical biomarker assays utilized in NCI-sponsored clinical trials. Therefore, reviewers will emphasize:

  • Potential of the proposed project to substantially improve the reliability of specific, clinically relevant biomarker assays;
  • Potential of the proposed project to improve understanding of how biopsy collection, processing, and storage procedures may affect all aspects of analytical performance for current and emerging clinical biomarkers.

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.

 

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific for this FOA:

  • How well is the project focused on the biospecimen preanalytical variability in small tumor tissue biopsies (such as FNAs, core biopsies, blood and other biospecimen types as defined in this FOA)?
  • How will the project advance, improve and affect the development and validation of a clinical biomarker assay(s) that has a clinical significance and can help patient diagnosis, prognosis or treatment? For blood and other biospecimen types intended to be utilized as “liquid biopsies,” how well is the project focused on preanalytical variability that affects the development and validation of a clinical biomarker assay(s) that will be used in cancer treatment trials to evaluate cfDNA, microRNA, CTC’s, DNA, RNA and proteomic signatures, exosomes or metabolites?
  • Is there evidence to suggest that the proposed preanalytical factors for study are problematic for the proposed clinical biomarker assay(s), and that strategies for improvement can be identified?
  • Does the proposed biomarker assay(s) advance, improve and address a significant cancer clinical problem?
  • Will the results of the project advance and contribute to expediting clinical biomarker assay development through the evidence-based standardization of biospecimen handling practices?

 

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 proposed team include multidisciplinary scientific and medical expertise related to biopsy biospecimens accrual, preservation and annotation?
  • Is there appropriate team expertise on clinical biomarker assays utilized in any treatment trials, biology and technology platforms for existing and emerging clinical assays, and experimental design and analysis?
 

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

Specific for this FOA:

  • Have the investigators proposed biomarker assays of clinical significance?
  • How innovative are the preanalytical variables in the proposed context?
  • How well will the proposed project enhance the biospecimen field?
 

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? 
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA:

  • Have the investigators proposed reasonable plans for acquiring biospecimens for the study and subjecting them to known preanalytical variations?
  • Have the investigators shown that the biospecimens can be collected within the time frame?
  • Have mitigation strategies to ensure successful biospecimen collections been proposed, such as partnering with other medical institutions as needed?
  • Have a sufficient number of biospecimens and biomarker evaluations for each biospecimen been proposed, to ensure that the experimental results will be statistically significant?
  • Are quality management of biospecimens, reagents, and analytical platforms addressed to ensure that preanalytical and analytical variability are known as experiments are conducted?
 

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.

   

For research that involves human subjects but does not involve one of the  categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the  categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

 

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

 

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.

 

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.

 

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

 

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

 

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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.

 

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

 

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).

 

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).

 

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.

 

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 will receive a written critique.

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

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. 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 recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

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, Recipients, and Activities, including of note, but not limited to:

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 “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 U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, 2 CFR Part 200 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 recipients 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 for the project as a whole resides with the recipients, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

The PD(s)/PI(s) will have the following primary responsibilities:

  • Defining the overall research objectives and approaches;
  • Determining experimental approaches, designing protocols, setting project milestones, and overseeing the conduct of experiments, including statistical analysis for assessing the use of the assay within the intended clinical context;
  • Overseeing and coordinating the effort of the multi-disciplinary team and participating institutions and ensuring their optimal integration; sharing of biospecimens, if feasible
  • Ensuring compliance with the applicable mandatory regulations (including protection of human subjects);
  • Adhering to the NIH policies regarding intellectual property, data release, and other policies that might be established during the course of this activity;
  • Submitting quarterly updates on human subject and accrual reports
  • Participating as Members of the Steering Committee;
  • Implementing guidelines and procedures developed by the Steering Committee;
  • Participating in monthly teleconferences with NCI program staff;

Recipientss will retain custody of and have primary rights to the data, technologies, and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies

NCI program staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. The substantially involved NCI program staff member(s), acting as Project Scientist(s), will coordinate the various activities of the recipients. Specific responsibilities of the NCI Project Scientist(s) will include the following aspects:

  • Providing input on experimental and clinical approaches, and consulting on updates for project milestones;
  • Providing advice to the recipients on specific scientific, analytical, and clinical issues;
  • Assisting and advising recipients with regard to various regulatory and compliance issues;
  • NCI’s Biospecimen Research Database (BRD)- http://brd.nci.nih.gov will serve as a resource tool for supported investigators to identify published effects of preanalytical factors on particular analytes.
  • Participating in monthly teleconferences with PDs/PIs to monitor progress and facilitate cooperation;
  • Monitoring progress of the projects towards meeting milestones and adherence to the strategic goals of the program;
  • Participating in the activities of the Steering Committee and the implementation of its guidelines and procedures;
  • Stimulating interactions among recipients;
  • Contributing to publications and presentations resulting from the project if appropriate.

Additionally, an NCI Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

NCI reserves the right to terminate or curtail any individual award, if there is insufficient progress towards meeting milestones.

Areas of Joint Responsibility include:

Steering Committee: The Steering Committee (SC) will consist of PI’s, NCI Project Scientist(s), and other scientific experts, including Food and Drug Administration (FDA) and National Institute of Standards and Technology (NIST) scientists and a patient advocate. NIST would provide input on standardization and FDA would provide perspective on the relevance of experimental design and results to regulatory challenges. When feasible and appropriate, the Steering Committee will seek to establish consensus on platform interoperability in areas such as control software, data analysis, communication protocols, and standard power sources. The members of the Steering Committee will meet at least semi-annually by conference calls.

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

  • Establishing policies and procedures for collaborative projects and protocols
  • Setting the overall research priorities for the collaborative networkt and identifying emerging research opportunities which can be best explored through a joint collaborative effort
  • Participating in efforts to develop biospecimen research evidence-based best practices, serving as a resource for a broader outreach to the entire extramural cancer research community

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 recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16

3. Reporting

When multiple years are involved, recipients 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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients 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 the threshold.  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 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 and 2 CFR Part 200 – Award Term and Condition 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, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

Lokesh Agrawal, PhD
National Cancer Institute (NCI)
Telephone:240-276-5718
Email: lokesh.agrawal@nih.gov

Abhi Rao, PhD
National Cancer Institute (NCI)
Telephone: 240-276-5715
Email: abhi.rao@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)

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: Shane.Woodward@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 and 2 CFR Part 200.

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.