NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

Required Application Instructions

It is critical that applicants follow the 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) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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) seeks to improve the development of molecular diagnostics for use in NCI-supported clinical trials in cancer. This FOA includes, but is not limited to, the validation of prognostic, predictive or response markers for treatment and markers for cancer control or prevention trials. Applicants should have an assay that has essentially completed analytical validation in human samples and whose importance is well justified for development into a clinical assay. Support through this Revision is to enhance the clinical validation of established assays with little further analytical validation required. Support may be sought to obtain retrospective or prospective specimens from NCI-supported or other clinical trials.

Assays proposed for this FOA may be used to validate existing assays for use in other trials, observational studies or populations involving cancer. Projects that improve standardization of assay performance among laboratories are also encouraged. Projects proposed for this FOA will necessitate multi-disciplinary interaction and collaboration among scientific investigators, clinicians, statisticians and clinical laboratory scientists and staff.

NCI-supported clinical trials increasingly depend upon molecular diagnostics to be measured as targets for therapy (companion diagnostics) or other essential or integral markers for treatment, prevention or cancer control trials. Many of these diagnostics are proposed from investigators in academic or small biotechnical companies that have developed interesting markers based on discovery research. These markers may be pharmacodynamic, mechanism of action as well as predictive or response markers. They may also be related to risk of cancer in prevention or cancer control trials. NCI’s experience is that these investigators generally do not understand the rigor and regulations that clinical laboratory assays must meet. This causes considerable delay and added expense to the performance of clinical trials. This FOA uses a cooperative agreement that enables NCI staff to proactively assist investigators to meet the requirements for analytical and clinical validation of assays and prepare for their use in clinical trials.

Applications to this FOA must propose to analytically and/or clinically validate an existing assay using human specimens in a clinical laboratory into a molecular diagnostic assay that can be used in a clinical trial for the treatment, prevention or control of cancer. The primary elements for achieving the research objectives are:

• Existing assay: an assay that has been reduced to practice in human tissues. An assay may be from discovery research or based on the scientific investigator’s interests but should have essentially completed analytical validation (see below). The clinical use of the assay within a specific disease must be clearly stated and defined.
• Clinical laboratory: a laboratory that provides assay results that either assist in medical decision-making or test postulates or mechanisms of action of clinical, prevention or cancer control treatments or interventions. Assays that support medical-decision-making need to be performed in Clinical Laboratory Improvement Act of 1988 (CLIA)-certified laboratories. Assays to test postulates or mechanisms should conform to Good Laboratory Practice (GLP) or ISO 17025 standards in order to assure that the data generated by the assay are of sufficient quality as to be useful in clinical trials and justify sample collection.
• Molecular diagnostic: a marker measured in a validated assay that is associated with a clinical endpoint in a pre-defined clinical context or situation that yields usable information about prognosis or response to a clinical intervention for treatment, prevention or control of cancer.

• The project must focus on assays whose marker or classifier is likely to be used in treatment, prevention, or cancer control trials. There does not need to be a commitment to a particular trial.
• The project should use technologies already in use or soon to be approved for use in clinical laboratories since this is not a technology development FOA.
• Applications to improve standardization or harmonization of assays among laboratories for use in clinical trials are appropriate for this FOA.

Assay Pre-requisites and Preliminary Data: The applicant must have an assay using human specimens that may be derived from discovery research or the result of previous hypotheses or biological or clinical rationale. The assay may be a multiplex assay or a classifier but must be able after conversion to a clinical assay to be performed in a clinical trial. The assay must be near the end of analytical validation with fine-tuning of cut-offs or thresholds for a positive assay result left for clinical validation. It is expected that the following metrics will have been achieved during analytical validation of the assay:

• Accuracy
• Precision
• Analytical sensitivity
• Analytical specificity including interfering substances
• Reportable range of test results for the test system
• Reference intervals (normal values) with controls and calibrators
• Harmonization of analytical performance if the assay is to be performed in multiple laboratories
• Establishment of appropriate quality control and improvement procedures
• Any other performance characteristic required for test performance with determination of calibration and control procedures.

Preliminary data should define the current status of the assay as well as justify support for optimization and usability in a clinical trial.

Objectives for the Clinical Validation Supplement: The objectives for completion of the clinical validation of assays are:

• Definition of the sensitivity and specificity of the assay result with the defined clinical endpoint within the described clinical context of use
• Estimation of the prevalence of the marker within subjects or patients for the intended clinical context
• Establishment of an appropriate cut-off or threshold for the assay using appropriate statistical analysis
• Demonstration of the association of the result of the assay with a clinical endpoint (e.g., survival, response, disease presence or absence) in samples from patients that have been treated or exposed to a uniform intervention or observation for treatment, prevention or cancer control trials

The projects proposed for this FOA will necessitate multi-disciplinary interaction and collaboration among scientific investigators, clinicians, statisticians and clinical laboratory scientists and staff. Therefore, in addition to the PD/PI, the Investigators' Team should include the following participants:

• Clinical Investigator: Investigator(s) who define the intended clinical context of use for the marker and its assay and will oversee their incorporation into a potential trial likely to be oncologist(s) who treat patients but may be a translational scientist.
• Clinical Laboratory Staff: Staff who will perform the translation of the assay into a clinical assay. The staff may work in a CLIA-certified clinical laboratory but do not need to do so if the assay is not intended to be used for medical decision-making. In that case the assay is likely to be for hypothesis or mechanism of action testing and the clinical laboratory staff and their laboratory need to be aware of Good Laboratory Practices and/or ISO 17025 standards and perform to that level of quality but not necessarily be certified. In any case, the clinical laboratory staff need to be aware of the Westgard rules.
• Statistician: A statistician familiar with the needs of marker studies should be part of the team, when power calculations need to be provided for assessing the use of the assay and its marker within the intended clinical context.
• Commercial Developer (optional): While not necessary for all projects, successful assays will need to be distributed and supported. Therefore, collaboration with a commercial partner who will support the distribution and commercialization of the assay is encouraged, but not required.

Research projects that are not appropriate for this FOA

Because this FOA is not meant to support trials that assess the clinical utility of a marker/assay but is intended to get assays to the point where their clinical utility could be assessed in other trials, projects that are not appropriate for this FOA include technology development such as those covered by the Innovative Molecular Analysis Technologies Program (IMAT) or the Early Detection Research Network (EDRN) at the NCI.

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 in response to 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:

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• County Governments
• 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) 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

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.

The parent project must be an active NIH U10 project. There must be at least two years (24 months) remaining on the project at the estimated time of award. One of the PD(s)/PI(s) on the revision must be the same as the PD(s)/PI(s) on the parent grant but other PD(s)/PI(s) may be the leaders of the assay validation team. Multi-PD/PI applications are encouraged.

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).

Applicants can access the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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:

Tracy Lively, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5944
Email: livelyt@mail.nih.gov

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12
Project (use for Research Project)	12

Additional page limits 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 a multi-component application.

Revision applications must include an Overall component and the components that are affected by the revision.

The application should consist of the following components:

• Overall: required
• Project: required; maximum of one

When preparing your application in ASSIST, use Component Type Overall .

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

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is required in the Overall component.

Specific Aims: Describe the theme and goals of the collaborative randomized controlled trial research center of the parent award and how the proposed project supports the research center's goals.

Research Strategy: The Overall section must contain justification for the use of the multi-site randomized controlled trial research center's infrastructure and studies and describe those goals that are not readily attainable through individual research grants. This section should include a description of the objectives of the trial research center as a whole and how the proposed assay validation project may support and enhance the goals of the trial research center. Included in this section should be evidence of scientific and administrative integration of the proposed assay validation project with the trial research center, for example describe how to achieve coordination, interrelationships, and synergy between the project and the trial research center, its trials and resource cores. The special benefits associated with being part of the collaborative trial research center study must be addressed. Describe the administrative structure of the overall project or center and the interrelationships among the center components that will contribute to the probability of success of the center as a whole. Support for the proposed assay validation project should be justified in terms of its essential function and service to the overall goals of the multi-site trial research center.

Letters of Support: Letters of support for Projects must be included in the appropriate components.

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: 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 preparing your application in ASSIST, use Component Type Project.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component.

Specific Aims: Describe the specific aims of the research project.

Research Strategy: Organize the Research Strategy in the sections identified below:

1) Background and Significance

• Define the cancer problem to be addressed, including the marker and its assay and how they fit the intended clinical context in which they will be used.
• Provide the biologic or discovery research rationale for the marker and its importance.
• Outline the proposed assay and its marker and its potential for affecting the intended clinical context in treatment, prevention or cancer control trials.

2) Preliminary Data

• Describe the current state of analytical validation of the assay in human specimens within the intended clinical context, including the current reagents and technologies and types of specimens that the assay will use (e.g., fresh frozen or formalin-fixed tissue, serum or plasma)
• Describe the status of analytical validation for each of the pre-requisites described in Section I above.

3) Approach

• Plans for additional optimization of analytical validation primarily limited to establishing thresholds or cut-offs for assay
• Plans to accrue specimens to perform clinical validation of assay including identification of the clinical resource or trial that will provide specimens, documentation of appropriate availability and pre-approvals to get specimens (i.e. indication that the repository holder identifies availability of specimens and that there is an appropriate process to get the specimens with reasonable certainty)
• Provision of a statistical power analysis that defines the number of specimens needed
• Plan for clinical validation of the assay within the intended clinical context of use
• Plans to address regulatory requirements needed to get assay into clinical trial
• Identification of Potential Pitfalls and Alternative Approaches to overcome obstacles to clinical validation of the assay
• Plans to address the regulatory issues regarding use of the marker in clinical trials and its assay within its intended clinical context. This includes the possibility of controlling intellectual property, evaluation of the significant risk of the assay and marker within the clinical context of a clinical trial and plans for collaboration with commercial entities to support the assay if it is successful.

Milestones and Timeline

The applicant and the clinical laboratory staff must propose milestones for clinical validation.

A timeline (Gantt chart) including milestones is required.

Letters of Support: Letters of support for the Projects must be included in the appropriate components.

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: 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 Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

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

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) using ASSIST or other electronic submission systems. 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.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: https://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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) and component Project Leads 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.

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 (SAM). 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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Applicants are required to follow our Post Submission Application Materials 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?

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?

In addition, are clinical laboratory staff integrated into 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?

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.

Integration

How will the administrative structure of the overall project contribute to its probability of success? Does the application clearly describe and justify the proposed administrative and organizational structure? Is the proposed structure adequate to support and encourage optimal interactions among participants of the overall project? Does the administrative plan provide for internal quality control of ongoing research, management of day-to-day program activities and for fair and effective communication and cooperation among members of this proposed collaborative study, including resolution of disputes?

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

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

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.

Not Applicable

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 .

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:

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

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

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

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.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 45 CFR Part 75 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

Defining the overall research objectives and approaches of the consortium;

• Determining experimental approaches, designing protocols, setting project milestones, and overseeing the conduct of experiments;
• Overseeing and coordinating the effort of the multi-disciplinary team and participating institutions and ensuring their optimal integration;
• Overseeing the conduct of research projects and ensuring their scientific rigor;
• Ensuring compliance with the applicable mandatory regulations (including protection of human subjects);
• Adhering to the NIH policies regarding intellectual property, data release, and other policies that might be established during the course of this activity;
• Submitting twice a year during the revision supplement updates on progress and problems in a brief format as agreed upon with the NCI;
• Submitting monthly updates on human subject and accrual reports upon initiation of validation studies;
• Participating as Members of the Steering Committee;
• Implementing guidelines and procedures developed by the Steering Committee;
• Participating in monthly teleconferences with NCI program staff;
• Attending annual Steering Committee meetings organized by the NCI
• Awardees will retain custody of and have primary rights to the data, technologies, and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies

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

An NCI Program staff member(s) acting as a Project Scientist(s) will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. Additional NCI staff members may be designated also to have substantial involvement. The NCI Project Scientist(s) and any other substantially involved staff members will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications. If such participation is deemed essential, these individuals will seek NCI waiver according to the NCI procedures for management of conflict of interest.

The main activities of the NCI substantially involved staff members include but are not limited to the following aspects:

• Providing input on experimental and clinical approaches, assisting in designing protocols, and consulting on updates to project milestones;
• Providing advice to the awardees on specific scientific, analytical, and clinical issues;
• Assisting and advising awardees with regard to various regulatory and compliance issues;
• Participating in monthly teleconferences with PDs/PIs to monitor progress and facilitate cooperation;
• Monitoring progress of the projects towards meeting milestones and adherence to the strategic goals of the program;
• Tracking monthly accrual of participants for clinical testing to ensure proper completion of this essential step;
• Participating in the activities of the Steering Committee and the implementation of its guidelines and procedures;
• Stimulating interactions among awardees;
• Attending annual Steering Committee meetings organized by the NCI; and
• Contributing to publications and presentations resulting from the project if appropriate.

Additionally, an NCI Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. Some Program Officials may also have substantial programmatic involvement (as Project Scientists/Coordinators). In that case, the individual involved will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications or will seek NCI waiver as stated above.

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

Areas of Joint Responsibility

Steering Committee: The Steering Committee will consist of the following voting members:

• PDs/PIs from each cooperative agreement award (one vote per award even when multiple PDs/PIs are designated); and
• NCI-assigned Project Scientists, a representative each from the Cancer Diagnosis Program and the Cancer Therapy Evaluation Program of the Division of Cancer Treatment and Diagnosis, The Division of Cancer Prevention and the Division of Cancer Control and Population Sciences, who will collectively have one vote for the NIH.

The Committee will be chaired by one of the UH2/UH3 PDs/PIs.

Other NIH staff members may participate in the activities of the Committee as needed as nonvoting members.

The Steering Committee will be responsible for communication and coordination among funded projects, including sharing ideas, logistics, and solutions to technical issues. When feasible and appropriate, the Steering Committee will seek to establish consensus on platform interoperability in areas such as control software, data analysis, communication protocols, and standard power sources. Other shared advice may include promise of clinical potential, manufacturability, regulatory issues, and deployment into local resource limited settings. The members of the Steering Committee will meet once a year in person and by conference calls as needed.

Panel of External Scientific Consultants

Panel of External Scientific Consultants (ESC) will operate as a subcommittee to the Steering Committee, advising the Steering Committee and providing technical expertise to awardees. The members of the panel will be selected by NCI in consultation with the awardees to provide independent assessments and recommendations to awardees on the progress. The panel will consist of scientists with relevant expertise who are not participants in any of the cooperative agreement awards resulting from this FOA. The ESC will meet once a year. Part of this meeting may be in conjunction with the Steering Committee meeting to allow members of both groups to interact directly with each other.

Dispute Resolution:

Any disagreements that may arise in scientific and/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 regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

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

A final progress report, 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.

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

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

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

Magdalena Thurin, PhD
National Cancer Institute (NCI)
Telephone: 240-276-5973
Email: thurinm@mail.nih.gov
(For assays involving immunological diagnostics and non-companion diagnostics for treatment trials)

Tracy Lively, PhD
National Cancer Institute (NCI)
Telephone: 240-276-5944
Email: livelyt@mail.nih.gov
(For response, safety, resistance and risk stratification markers for treatment markers)

Minkyung (Min) Song, PhD
National Cancer Institute (NCI)
Telephone: 240-276-6139
Email: songm@mail.nih.gov
(For companion diagnostics and pharmacodynamic markers for treatment trials)

Asad Umar, DVM, PhD
National Cancer Institute (NCI)
Telephone: 240-276-7070
Email: umara@mail.nih.gov
(For assays involving assays for cancer prevention)

Mukesh Verma, PhD
National Cancer Institute (NCI)
Telephone: 240-276-6889
Email: vermam@mail.nih.gov
(For assays involving cancer epidemiology and population science)

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

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: Woodwars@mail.nih.gov

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.