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.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This Funding Opportunity Announcement (FOA) solicits grant applications proposing exploratory research projects focused on further development and validation of emerging technologies that improve the quality of the samples used for cancer research or clinical care. This includes the ability to address issues related to pre-analytical degradation of targeted analytes during the collection, processing, handling, and/or storage of cancer-relevant biospecimens. The overall goal is to support the development of highly innovative technologies capable of maximizing or otherwise interrogating the quality and utility of biological samples used for downstream analyses.

FOA Emphasis. The FOA utilizes the R33 mechanism which is suitable for projects where proof-of-principle of the proposed technology or methodology has been demonstrated and supportive preliminary data are available. Proposed projects should offer new tools, devices, instrumentation, and associated methods to preserve or protect sample integrity, or establish verification criteria for quality assessment/quality control and handling under diverse conditions. These technologies are expected to accelerate and/or enhance research in cancer biology, early detection and screening, clinical diagnosis, treatment, epidemiology, or address issues associated with cancer health disparities, by reducing pre-analytical variations that affect biospecimen sample quality. Projects proposed to this FOA may involve further development of a novel technology to address an unmet technical measurement or targeting need in cancer research or clinical care, but must include a rigorous validation strategy to establish repeatable, reliable performance of the technology in a cancer-relevant biological context of use. Projects proposing to use existing technologies where the novelty resides in the application of the technology or the biological or clinical question being pursued, and not the technical capabilities being developed, are not appropriate for this FOA and will not be reviewed.

This funding opportunity is part of a broader NCI-sponsored Innovative Molecular Analysis Technologies (IMAT) Program (https://innovation.cancer.gov/).

Since its inception in 1998, the IMAT Program has focused on stimulating and accelerating the development, integration, maturation, and dissemination of the most novel and highly innovative technologies in support of cancer research and medicine. Together with the NCI's other technology-focused programs, the IMAT program continues to support the development of tools and methods that enable cancer researchers to make new discoveries, enhance our understanding of cancer etiology and proliferation, improve detection capabilities, develop diagnostic methods and treatment strategies, conduct population-scale studies, address and reduce disparities in clinical care, and assist in clinical decision-making.

The current issuance of the IMAT Program consists of four separate FOAs that cover the following two areas:

• Molecular and Cellular Analysis Technology Development for Cancer Research is intended to support the development of technologies that are novel and potentially transformative to the molecular and cellular analysis of cancer, which may in turn accelerate basic or clinical cancer research. Applications must offer novel measurement, probing, or targeting of cancer relevant targets at the molecular or cellular level.
• RFA-CA-18-002 (R21): Supports an early-stage feasibility study (inception through preliminary development) to demonstrate core functional capabilities of the proposed technology.
• RFA-CA-18-003 (R33): Assumes completion of the initial phase of development and supports the advanced development and robust validation of the technology.
• Cancer-relevant Biospecimen Science Technologies is centered on the development and validation of novel technologies to improve or assess the quality of cancer-relevant biospecimens for research or clinical care. Applications must offer novel approaches for procurement, preservation, and/or isolation of proteins, DNA, RNA and other small molecules from biospecimens or otherwise assess their biological integrity. The emphasis is on reducing the impact of pre-analytical variations in the collection, processing, handling, and preservation of cancer-relevant biospecimens or their derivatives to improve their quality and utility for cancer research or clinical care.
• RFA-CA-18-004 (R21): Supports an early-stage feasibility study (inception through preliminary development) to demonstrate core functional capabilities of the proposed technology.
• RFA-CA-18-005 (this FOA, R33): Assumes completion of the initial phase of development and supports the advanced development and robust validation of the technology.

Additional information about the IMAT Program and its individual FOAs can be found at http://innovation.cancer.gov.

The proposed projects must be focused on innovative, biospecimen science-relevant technologies and methodologies that either improve the quality and utility of biospecimens and/or samples derived from biospecimens for cancer research and/or clinical care or otherwise seek to measure the quality of those samples and determine their fitness for downstream analyses. The proposed technology may be targeted for the needs of basic, preventative, diagnostic, translational, epidemiological, health disparities, and/or clinical cancer research or for broad potential use in cancer research.

In addition, all projects proposed in response to this FOA must involve all of the following general attributes:

• Potential for substantial improvements over current approaches and/or adding qualitatively new research capabilities.
• Offers novel capabilities that may be judged by appropriate experts as potentially transformative to research in laboratory and/or clinical settings, and beyond providing incremental improvements to existing capabilities.
• Rigorous study design with a verifiable approach, based on well-defined, quantitative milestones (see below for description of quantitative milestones).

For details on addressing these requirements, see Section IV. Application and Submission Information.

Responsive technologies include relevant techniques, tools, instrumentation, devices, and associated methods. These technologies must focus on offering improved capabilities for procuring, preserving and/or preparing cancer biospecimens for basic or clinical research purposes with a focus on improving the integrity of targeted molecular and/or cellular features or otherwise allow for assessment of analytical integrity in specimens of unknown quality.

General areas of interest include, but are not limited to, the following:

• Novel technologies to benchmark or otherwise assess the biological integrity of classes of molecular analytes (e.g., determine fitness-for-purpose for targeted analysis of protein complexes, non-coding RNA, classes of epigenetic lesions, etc);
• Novel technologies and techniques to provide high-quality preservation of specific classes of molecules, sub-cellular components, whole cells or bulk tissue;
• New methods, tools, and procedures that may generally facilitate the preparation of biospecimens for classes of molecular analysis (e.g., genomic or RNA sequencing, mass spectrometry-based protein profiling or metabolite analysis, etc);
• Technologies that can allow for rigorous and/or expeditious collection of various relevant types of biospecimens while ensuring sufficiently high quality for epidemiological cancer research;
• Technologies or tools that may help overcome various barriers in research on the incidence, prevalence, mortality, and burden of cancer among members of underserved populations; and
• Technologies to facilitate the collection of relevant biological data for examining the factors contributing to cancer health disparities (e.g., for cancer sub-types and differences across individuals with diverse racial/ethnic backgrounds).

IMPORTANT NOTE: Researchers uncertain as to whether their intended technology development project meets the requirements of this FOA are encouraged to contact the Scientific/Research Contact listed below.

The following aspects/characteristics remain outside the scope of the IMAT Program and this FOA. Applications proposing projects with any of the following characteristics will not be reviewed:

• Pursuit of a biological or clinical hypothesis for which the novelty of the project resides in the biological or clinical question (i.e., traditional biological-hypothesis driven research) and NOT in the novel technical capability being developed;
• Use of existing technologies (for which a proof-of-concept has already been demonstrated in a cancer relevant biological system) that may be ready for advanced development and validation without substantial further developmental efforts;
• Technologies for whole-body or in vivo imaging;
• Inclusion of clinical trials or toxicology studies beyond those required to demonstrate the capabilities of the technology;
• Biomarker discovery or biomarker validation;
• Development of specific contrast agents (though generalizable contrast agents are allowed);
• Development of drugs or therapies; and/or
• Projects focused primarily on software/informatics solutions, database development, data mining, statistical tools, and computational/mathematical modeling (including those applicable to drug and/or patient responses) with the exception of projects which include software development for embedding in new devices or limited amounts of computational efforts as might be needed to develop new devices or methods.

As there are several unique review considerations for this FOA, applicants must address the requested items outlined for the Research Plan in Section IV.2. Application and Submission Information.

Related IMAT FOA: Applicants proposing projects that still involve a critical question as to overall feasibility of the approach should consider applying to the companion FOA (RFA-CA-18-004) which uses the R21 mechanism. NOTE: Applications proposing to merge complimentary technologies without a substantial requirement for further development or clear need for analytical validation are beyond the scope of the IMAT program solicitations altogether.

Other technology-related funding opportunities. Researchers focusing on new bioinformatics or statistical techniques, tools, and/or software development solutions should consider one of the Informatics Technologies for Cancer Research (ITCR; http://itcr.nci.nih.gov) opportunities or one of the Biomedical Information Science and Technology Initiative (BISTI; http://bisti.nih.gov) opportunities. Researchers who emphasize the assessment of whole body or in vivo imaging technologies as the primary focus of their projects should contact the Cancer Imaging Program (CIP; http://imaging.cancer.gov/) for information on appropriate funding opportunities.

An annual meeting of all investigators funded through this program will be held to share progress and research insights that may lead to further progress in the development of technologies for cancer research and clinical care for cancer patients. All investigators supported through this FOA are required to attend this meeting each year, lasting 2-3 days, unless otherwise notified by NCI program officials.

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

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

Higher Education Institutions

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

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

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

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.

Applicant Organizations

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

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

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

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

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.

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

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

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:

• 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:

Tony Dickherber, Ph.D.
Center for Strategic Scientific InitiativesNational Cancer Institute (NCI)
31 Center Drive, Room 10A33
Bethesda, MD 20892
Telephone: 301-547-9980
Email: [email protected]

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

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.

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.

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: Include a brief sub-section "Statement of Potential Impact" on the expected potential of the proposed technology to transform cancer research and clinical practice. The following questions should be addressed with this statement.

• How is the new capability provided by the proposed technology potentially transformative and why may it be expected to produce an unusually high impact on biomedical research and medicine? (i.e., describe the potentially transformative outcomes that might be realized should this technology be successfully developed)
• If applicable, how will the proposed technology overcome limitations for currently available technologies or alternative approaches? (i.e., provide evidence to substantiate the claim of innovativeness beyond currently available technologies)

Research Strategy: Applicants must address the following required aspects:

• Advanced Development and Validation of Cancer-relevant Technology. Applications must focus on further development of a novel technology beyond the early-stage proof of concept demonstration and engage a rigorous validation of technologies and/or methodologies that improve the quality and utility of biospecimens and/or samples derived from biospecimens for cancer research and/or clinical care. Applications should provide appropriate background/preliminary data to justify that the proposed technology has passed the pilot developmental stage and shows promise. Applications based on work supported by a prior IMAT R21 award must include a listing of the approved quantitative milestones from the R21 Notice of Award and discuss the extent to which these have been achieved. For applications not based on work supported by a prior IMAT R21 award, an equivalent level of evidence should be provided. Describe the strategy and specific research steps to evaluate and rigorously validate the proposed technology within the context of its intended use (see quantitative milestones, below).
• Substantial Improvement and/or New Capabilities. All proposed technologies must offer the potential for substantial improvements over existing approaches or technologies and/or add qualitatively new research capabilities inaccessible to current technologies.
• Transformative Potential. Define clearly the unmet technical need from the research community being targeted by the technology and describe its anticipated use in laboratory research and/or clinical settings. The proposed technology should target unmet needs in basic, preventative, diagnostic, translational, epidemiological, health disparities, and/or clinical cancer research. Claimed potential impact is expected to be in line with the specific quantitative milestones (next bullet).
• Quantitative Milestones. Quantitative Milestones are objectively assessable measures for determining targeted performance capabilities. They should be carefully selected and precisely defined, and should clearly detail the expected advantages of the proposed technology relative to existing technologies/approaches. Appropriately targeted quantitative milestones requires that the underlying experimental results have been subjected to appropriate statistical analysis, yielding a reasonable level of certainty that the targeted level of performance has been achieved.

Additional Information on Quantitative Milestones

Within Research Strategy there must be a dedicated subsection labeled "Quantitative Milestones". Milestones should be well-described, quantifiable, and scientifically justified. Critical components for proposed milestones include the numerically described target of performance as well as the means by which it will be assessed. The milestones will be a means of supporting success for the validation of the technology. Milestones should include the relevant statistical context for the targeted parameter. Whenever appropriate, present the proposed milestones in the context of current technologies to substantiate the anticipated transformative potential. All milestones should be described within the context in which they would be assessed, statistical strength of the resulting measures, and the approach by which they will be determined.

Specific aims may not be regarded as milestones. The specific aims describe the goals and intended path of the research. Quantitative milestones provide the means for objectively assessing progress against those aims and substantiates the potential impact the technology might have on cancer research or clinical care. The project will be evaluated for success based on the completion of the milestones proposed. For some specific aims, it may be sufficient to define a single milestone. For others, multiple milestones may be more appropriate.

An example of a properly described quantitative milestone could be achieving improved recovery of spike-in molecular additives from whole blood with 99.0% efficiency (+/- 0.5%) under conditions a, b and c, over a concentration range from p to q. Other types of quantitative milestones might include:

• Improved preservation of phosphorylated proteins in tissue blocks by "n" % over snap freezing methods;
• Ability to process "x" mL of whole blood in "y" minutes, with "z"% efficiency for capture of targeted circulating cell free DNA;
• Demonstration that technology can identify "x" % degradation of mRNA due to nuclease activity from 1 to 72 hours after tissue resection, and correlate with % error upon RNA-Seq analysis; or
• Demonstration of multiplexed mRNA isolation/cDNA generation with at least an order of magnitude higher throughput than the current "best" technology while maintaining quality sufficient for qRT-PCR.

Please note these additional milestone types should still be properly described in an experimental context as demonstrated in the example above. An application lacking quantitative milestones as determined by the NCI program staff will not be reviewed.

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

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:

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

Use only for applications with due dates on or after January 25, 2018. When involving NIH-defined human subjects research, clinical research, and/or 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 with the following additional instructions:

Delayed Onset Study

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

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

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

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.

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 NCI, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. For submission of short (up to 2 min) video clips (e.g., for depicting functional elements of the technology), applicants are required to follow instructions defined in NOT-OD-12-141. Any instructions provided here are in addition to the instructions 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?

In addition, specific for this FOA: What is the potential of the proposed technology to transform cancer research or clinical practice if the project is successfully completed? Are the expectations in that area realistic and in line with the planned developmental efforts? Do the proposed milestones support a transformative capacity for a cancer-relevant field of research or clinical care? Does the proposed technology have the potential to be widely adopted by the relevant research community?

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?

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?

In addition, specific for this FOA: Does the proposed technology offer clear and significant improvement over currently available methods and platforms? Will the proposed technology offer new possibilities for cancer research or oncological practice relative to the current methods?

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?

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.

Milestones

Are the milestones and their associated criteria sufficient, appropriate, quantitative, and rigorous to serve as strategic and objective benchmarks of project progress? Are they sufficiently realistic? Will the proposed milestones allow sufficiently for technical and analytical validation of the novel technology for adoption by intended end users?

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.

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.

Not Applicable

Not Applicable

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

Applications from Foreign Organizations

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

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support