National Institutes of Health (NIH)
National Cancer Institute (NCI)
Precompetitive Collaboration on Liquid Biopsy for Early Cancer Assessment (U01)
U01 Research Project – Cooperative Agreements
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.
August 2, 2017
September 24, 2017
30 days before application due date
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.
March-April and May-June 2018
May 2018 and August 2018
July 2018 and September 2018
January 24, 2018
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.
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
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:
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.
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:
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:
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:
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:
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.
See Section VIII. Other Information for award authorities and regulations.
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.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
NCI intends to commit $5million in FY 2018 to fund 6-8 awards.
The requested budget must not exceed $600,000 per year (in direct costs).
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.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
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
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.
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.
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.
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.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
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:
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.
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.
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
Lynn Sorbara, Ph.D.
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.
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.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
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:
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.
All instructions in the SF424 (R&R) Application Guide must be followed.
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.”
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
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:
Project Management Plan. The Project Management Plan should cover the following requirements:
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:
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:
Applicants should list and summarize the materials, technologies and/or expertise that they can provide within the precompetitive collaborative environment.
Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.
All instructions in the SF424 (R&R) Application Guide must be followed.
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
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.
This initiative is not subject to intergovernmental review.
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.
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.
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.
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.
Applicants are required to follow the instructions for post-submission materials, as described in the policy.
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.
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).
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 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?
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?
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?
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?
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?
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 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.
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.
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.
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 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.
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:
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:
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.
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.
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
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:
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:
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:
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:
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.
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.
We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.
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)
(Questions regarding application instructions and process, finding NIH grant
Email: GrantsInfo@nih.gov (preferred method of contact)
For general inquiries regarding early cancer detection and liquid biopsy, contact:
Sudhir Srivastava, MPH, PHD
National Cancer Institute
For inquiries specifically related to this FOA, contact:
Lynn Sorbara, PhD
National Cancer Institute
National Cancer Institute (NCI)
National Cancer Institute
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.
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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