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). 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

The purpose of this Funding Opportunity Announcement (FOA) is to support research projects that delineate and compare the underlying biological mechanisms that drive cancer phenotype and response to perturbations between two or more patient-derived models of cancer originating from a common patient sample.

Awardees are expected to form a patient-derived models of cancer (PDMC) consortium and participate in activities as appropriate to their projects that will provide a framework to accelerate multidisciplinary efforts to address compelling fundamental cancer biology questions through PDMC comparisons.

The oncology community has recently focused on the development of patient-derived models of cancer (PDMC) platforms including, but not limited to, patient-derived xenografts (PDXs), organoids, spheroids, induced pluripotent stem cells (iPSC), conditionally-reprogrammed cells (CRCs). Each of these platforms has both merits and drawbacks with regard to their utility and in faithful representation of tumor architecture, microenvironment, cellular composition and heterogeneity, stem-differentiation states, growth patterns and responses to perturbagens, with respect to the patient specimen from which the model was initially derived. Researchers often optimize methodologies or interpret data for a single PDMC platform in isolation of other PDMC approaches. This barrier has hampered investigation of fundamental cancer biology questions that address how basic phenotypic features and processes present in the original patient specimen are either preserved or become altered by the environment and growth conditions that are unique to each specific PDMC platform. These distinctions are critical in deciphering applicability of PDMC as a representation of the intrinsic cancer biology in the original tumor. Systematic comparisons of PDMC parameters related to biological and physical microenvironment that impact cancer phenotype(s) and responsiveness to therapeutics or stressors are needed. This FOA encourages researchers to combine expertise in specific PDMC platforms and collaboratively study cancer biology across these PDMC approaches. It is anticipated that this "PDMC comparison approach" can reveal new mechanistic understanding of basic cancer biology and be complementary to translational application of PDMC aimed at drug screening, target identification, and biomarker discovery.

A major goal of this FOA is to stimulate research that will broaden our understanding of how key cancer biology features, processes, and/or responses to perturbagens are influenced by the respective environments and growth conditions of specific PDMC platforms. This FOA seeks applications describing research that systematically examines cancer cell biology and phenotypes using investigator-identified approaches and techniques, wherein individual tumor specimens are respectively studied in the context of two or more types of PDMC platforms.

Tumor specimens proposed for examination may represent any type and stage of cancer. It is anticipated that investigators will systematically examine a number of different tumor specimens that are collectively representative of tumors in a particular cancer cohort. The objective of the FOA is to stimulate research where cancer biology is compared between pairings of PDMC platforms, wherein each PDMC comparison set is derived from a single tumor specimen from the same patient. The scope of proposed studies should balance a sufficient number of PDMC comparison sets to achieve a meaningful interpretation of cancer biology similarities and differences across the PDMC platform types under study, as guided by biostatical methodology.

Ideally, one tumor specimen would be split to concurrently generate PDMC of two (or more) PDMC platform types, which would constitute a single PDMC comparison set. Alternatively, a PDMC comparison set could be the result of inter-conversion of a single existing PDMC specimen of one type to another type of PDMC. In either case, the number of PDMC comparison sets would be proportionate to the number of original tumor specimens that represent the cancer cohort. A series of PDMC comparison sets may be generated in the project period or derived from existing specimen stocks.

Examples of a respective PDMC comparison set that would be considered appropriate for this FOA include, but are not limited to the following:

• Concurrent allocation of a single tumor specimen into two or more discrete PDMC platform types (e.g., organoid and PDX; CRC and PDX; organoid and CRC; PDX, organoid, and CRC).
• Orthotropic engraftment and expansion in mice (PDX) of a previously established and characterized organoid or CRC line originally derived from a single tumor specimen.
• Expansion of an organoid or CRC line from a previously established and characterized PDX model originally derived from a single tumor specimen.
• Generation of an organoid from cancer stem cells derived from a human tumor specimen and the relevant cell-type specific iPSCs derived from the same patient.
• Expansion of previously established and characterized cancer stem cell spheroids originally derived from a single tumor specimen as PDX in mice.
• Generation of two or more discrete PDMC types (e.g., PDX, organoid, and CRC) derived from the same circulating tumor cell clone.

Examples of research approaches that would NOT be appropriate or within the scope of this FOA:

• Research applications that propose to use a PDMC platform of only one type (e.g., PDX only).
• Research applications that seek to compare different types of PDMC platforms, but each individual PDMC is derived from a different patient and/or tumor.
• Research applications that propose to screen drug responses without a research strategy that examines the underlying intrinsic cancer cell biology related to these responses.

Types of Studies: Hypothesis-driven, Descriptive, and Clinically Translational

Studies designed to measure and compare cancer cell intrinsic processes, mechanisms, and/or features may not necessarily be hypothesis-driven; however, cohesive research projects that inform the utility of respective PDMC to advance mechanistic understanding of environment and growth conditions that drive cancer phenotype and response to perturbations are considered to be of high programmatic priority. Immediate clinically translational potential of the proposed research project is NOT a requirement for this FOA.

Research Projects related to Cancer Health Disparities

Investigators conducting basic research on PDMC that originate from cancers that are more serious or members of racially and ethnically diverse and underserved populations are encouraged to apply.

Transdisciplinary Applicant Teams

Applicant teams are expected to have key personnel with demonstrated expertise in the types of PDMC to be investigated and compared at the time of application. Due to the nature of PDMC comparison projects and the U01 focus on collaboration and expertise sharing, this FOA strongly encourages the use of the multi-PD/PI mechanism. Projects proposed for this FOA require multi-disciplinary interactions that include teams that conduct, coordinate, and/or implement tumor specimen procurement and biospecimen pathology, two or more PDMC platforms, cancer biology experiments and computational-data sciences. Investigators may come from the same or different departments within an institution, or from different institutions.

Data Harmonization and Sharing

Because of the likelihood that some funded applications will examine similar types of PDMC and address interconnected cancer biology questions, awardees of this FOA will be encouraged to participate in post-award standardization and harmonization efforts, as scientifically appropriate.

Alternative Funding Opportunities

The NCI has opportunities for PDMC-related research that complement this FOA. Applicants interested in high throughput screening of perturbagens, target validation, and genomics approaches may refer to the Cancer Target Discovery and Development (CTD2) program (https://ocg.cancer.gov/programs/ctd2).

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:

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
• 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.

Multi-PD/PI U01 applications that collaboratively use a common set of cancer biology methods to examine the respective PDMC comparison sets 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 must obtain 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.

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. 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:

Michael Graham Espey, Ph.D.
Division of Cancer Biology (DCB)
National Cancer Institute (NCI)
Telephone: 240-276-7619
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

• For this specific FOA, the Research Strategy section is limited to 30 pages.

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: State the specific aims of the research project and provide the rationale for the basic cancer biology questions that will be addressed through the proposed PDMC comparison approaches. In the context of the cancer biology question, theme or focus, provide the rationale for the proposed types of PDMC platforms that are to be compared.

Research Strategy: Applicants should structure the Research Strategy using the standard sub-sections Significance, Innovation, and Approach as defined in the standard SF424 instructions. Under these sub-sections, address the following specific aspects:

• Highlight the collective team expertise and level of competency in the types of PDMC platforms to be investigated and compared.
• Describe in detail the pipeline for human tumor specimen procurement, patient consent, clinical information to be collected, pathology characterization and the process to track and store specimens.
• Highlight any innovative cancer biology and PDMC techniques or methodologies utilized or developed within the context of the proposed research.
• For research projects that propose to expose the different PDMC types to a set of common perturbagen(s), describe the approach to interpret these data in the context of potential differences in exposure (route, dose, timing) between the types of PDMC platforms being compared.
• Explain how the research project will contribute to the goals of the PDMC Consortium. Describe the structure for harmonization of data outputs that will be used for Consortium activities.

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 and Model Organism Sharing Plan where appropriate.
• Sharing plans are expected to address the NIH Genomic Data Sharing Policy if applicable, i.e., if the proposed studies will generate large-scale human or non-human genomic data (see NOT-OD-15-027 for additional guidance).
• Data, software, and computational models from this FOA are expected to be shared in accordance with the policies determined by PDMC Steering Committee. For more information, see the Cooperative Agreement Terms and Conditions of Award in Section VI of this FOA.

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 PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Form only available in FORMS-E application packages for use with due dates on or after January 25, 2018.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials 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 a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study: 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 described throughout 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). 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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Applicants are required to follow our Post Submission Application Materials policy.

Important Update: See NOT-OD-18-228 for updated review language for due dates on or after January 25, 2019.

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.

For this particular announcement, note the following:

Studies designed to measure and compare cancer cell intrinsic processes and/or features may not necessarily be hypothesis driven; however, cohesive research projects that inform the utility of respective PDMC to advance mechanistic understanding of environment and growth conditions that drive cancer phenotype and/or response to perturbations or stresses are also acceptable.

Immediate clinically translational potential of the proposed project is NOT a requirement for this FOA.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

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

Specific for this FOA: Does the proposed research project have the potential to inform or substantially improve the choice of specific type(s) of PDMC to address compelling and/or fundamental questions in cancer biology?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific for this FOA: What is the team's level of competency in each of the PDMC platform types to be investigated and compared? How strong is the plan to coordinate the multidisciplinary elements within a team (e.g., tumor procurement, pathology, two or more PDMC models, cancer biology, data harmonization)?

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?

Is 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.

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 peer review 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.

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

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

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

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

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NCI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• 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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.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 https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/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 https://www.hhs.gov/ocr/about-us/contact-us/index.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 (DHHS) grant administration regulations at 45 CFR Part 75, 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.

Primary Responsibilities of the PD(s)/PI(s)

Each of the PD(s)/PI(s) retains the primary responsibility, authority, and dominant role for planning, directing, and executing the activities of the award under this FOA. The PD(s)/PI(s) assume responsibility and accountability to the applicant organization officials and to the NCI for the performance and proper conduct of the research supported by the PDMC U01 award in accordance with these terms and conditions of the award.

Specific PD(s)/PI(s) responsibilities and rights will be to:

• Oversee and direct the project as a whole, including the dissemination of approaches, methods, models, software, and tools broadly to the cancer research community. Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
• Acknowledge the PDMC Consortium and indicate the appropriate U01 grant number on all scientific research publications related to the PDMC U01 award.
• Work closely with the NCI Program Director or Project Scientist (see below) on the coordination and management of PDMC research program activities. These actions involve (but will not be limited to) participation in annual PDMC Consortium meetings, working groups, and teleconferences with NCI scientific and program staff and other awarded investigators, as needed.
• Serve on the PDMC Steering Committee. The PDMC U01 PD/PI (contact PD/PI for applications with multiple PDs/PIs) is required to serve as a member of the Steering Committee and will collectively have one vote. PD/PI will serve as chairperson of PDMC Steering Committee that will rotate on a timely basis among all PD/PI members.
• Ensure that data are shared as appropriate and in accordance with the data sharing plan and NCI policies.

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

Primary Responsibilities of the NCI Staff:

NCI staff, acting as Project Scientist will have scientific and programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

Specifically, the NCI Project Scientist will:

• Be a staff member is a scientist who is selected because of relevant scientific content-area expertise and experience with regard to the scientific goals and objectives of a given U01 award. These staff members will have substantial scientific and programmatic involvement as facilitators through technical assistance, advice, coordination, and collaboration above and beyond the levels required normally for program stewardship of grants.
• Monitor the scientific progress of the entire Consortium and serve as a liaison between the PDMC Steering Committee, the PDMC Consortium investigators, and the NCI.
• Serve as a voting member of the PDMC Steering Committee.
• Organize and conduct regular meetings to share PDMC Consortium progress either by teleconference, videoconference, or face-to-face, as needed.
• Assist the Steering Committee to coordinate and co-organize PDMC annual meetings, working groups and teleconferences as needed.
• Coordinate and facilitate interactions and scientific integration, and collaboration among the PDMC U01 awardees and across complementary NCI programs, projects, and centers that use PDMC models.
• Assist the Steering Committee in developing and drafting operating policies and policies for dealing with recurring situations that require coordinated action.
• Assist in avoiding unwarranted duplication efforts with other projects funded within the PDMC Consortium.
• Suggest post-award modifications to projects when certain objectives of the FOA are not met. Specifically, the NCI Project Scientist may recommend a significant change in the level of support, withholding of support, suspension, or termination of a U01 award for lack of adherence to required policies and/or procedures, or failure to comply with the Terms and Conditions of award.

Additionally, an NCI Program Director acting as the NIH Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. A Program Official may also have substantial programmatic involvement (as a Project Scientist) and may be the same person as Project Scientist.

Areas of Joint Responsibility

The NCI Project Scientist and the PDs/PIs of the Cooperative Agreement awards funded under this FOA will be jointly responsible for:

• Formation of the Steering Committee and defining of membership rules.
• Determining areas of shared research interest for the PDMC Consortium, development of research priorities and collaborative opportunities, in order to further the goals of the PDMC Consortium as well as with other complementary NCI programs that use PDMC.
• Developing common scientific and administrative policies, guidelines, and procedures, best practices including optimization of specific PDMC, PDMC best practices, data elements for harmonization, and sharing and dissemination of data and resources as appropriate.

Dispute Resolution

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS 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 CenterTelephone: 800-518-4726

Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

For general FOA questions and specific questions about cancer biology:

Michael Graham Espey, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-7619
Email: [email protected]

For questions on cancer health disparities:

Tiffany Wallace, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5114
Email: [email protected]

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected]

Jennifer Edwards
National Cancer Institute (NCI)
Telephone: 301-631-3005
Email: [email protected]

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.