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

This Funding Opportunity Announcement (FOA) will establish a Preclinical Chemo-Radiotherapy Testing Consortium (PCRTC). The initiative will support several individual research programs for in vivo and in vitro testing of investigational anti-tumor drugs as adjuvants to chemo-radiotherapy. (These agents are included in a list at Cancer Therapy Evaluation Program [CTEP] Agents and Active Agreements ). The PCRTC will develop a rigorous preclinical testing program for existing CTEP portfolio molecularly targeted agents, and newly acquired investigational agents when combined with radiation and systemic chemotherapy. The goal of the individual sub-programs will be to generate reliable data that will be reproduced within the PCRTC and used for new agent prioritization decisions and to better inform clinical trial designs. This will enhance the likelihood of positive clinical trials that lead to more effective treatments for cancers treated with radiation.

Background

Curative treatment of cancer requires effective local tumor control. Radiation combined with systemic therapy, most commonly chemotherapy, is a first-line treatment for local control in many patients with solid cancers. Addition of molecularly targeted agents, including immunological agents, has the potential to enhance tumor responses to standard-of-care chemo-radiotherapy. However, the testing of these combinations has not been conducted optimally. Specifically, the initiation of studies combining radiotherapy with new targeted agents has largely been based upon findings of single-agent activity in advanced / recurrent cancers. In addition, modulation of the tumor response by molecular agents has most often been measured with radiation alone, not the more common combination of chemo-radiotherapy. The lack of robust preclinical studies that define mechanistic interactions, biomarkers of activity, sequencing and combinatorial dosing may have contributed to the lack of therapeutic effects seen in various clinical trials of these agents in combination with radiotherapy. Properly informed, the use of radiation as an integral component of precision medicine has the potential to provide increased clinical utility for drugs tested under this initiative. Preclinical studies should also provide further information on the mechanisms of activity of these combined modality treatments, as the mechanism of action of the molecular-targeted drug as a radiation modifier may be different than for the drug used alone.

The ability to physically target radiation to the tumor enhances its therapeutic ratio, but there are still limits to the selectivity of physical targeting due to the radiation sensitivity of adjacent normal tissues. Tumor radiation responses can be further enhanced through targeting of biological processes unique to tumor cells. However, cell signaling and DNA damage response pathways and other immunologic and molecular targets need to be carefully selected, validated and tested for safety as well as efficacy. Pre-clinical testing must be done in the context of existing standard-of-care therapy in order to facilitate entry of these agents into clinical trials and their potential for success. The studies executed under this cooperative agreement will establish whether there is preferential tumor activity of novel drug-radiation combinations and evaluate these combinations for efficacy as well as monitoring potential normal tissue toxicity.

In radiation studies, as in other preclinical testing, there is a need for standardization of assays, for the development of improved models, as well as a framework for cross-validation of pre-clinical results. In this context, the precise targeting, timing and dosing of radiation are significant advantages of this mode of therapy. However, this advantage is lost in pre-clinical studies unless these parameters are properly and accurately defined, measured, and reported. In addition, the timing of drug administration relative to radiation delivery can significantly impact the effects of treatment and needs to be assessed.

Specific Research Objectives

This FOA will support collaborative research by the PTRTC focused on preclinical testing of radiation therapy with molecularly targeted drugs and systemic chemotherapy.

Consortium Goals and Scientific areas appropriate for Applications under this FOA

The first objective of the PTRTC is to enhance pre-clinical testing of NCI-priority molecularly targeted anti-cancer agents for use with radiation and systemic chemotherapy (disease-relevant combined-modality standard of care). A second objective is to strengthen the extramural research infrastructure for pre-clinical testing of novel agents with radiation in the context of standard-of-care treatments through enhanced experimental modeling, design and reporting.

1. Agent selection

• Applicants submitting research projects in response to this FOA should select and justify the CTEP agent(s) they wish to investigate.
• Applicants should obtain approvals for studies with the selected agent(s) with the assistance of CTEP drug monitors and Investigational Drug Branch program staff.
• Upon Company approval, agents will be provided under an NCI CRADA.

2. Preclinical methodology

Projects submitted to this announcement will be expected to utilize state-of-the-art preclinical methodology in preclinical testing of molecularly targeted agents for use with chemo-radiotherapy in the treatment of difficult-to-treat solid tumors. The factors to be considered for investigation include:

• Defining drug and radiation doses (within clinically relevant ranges), timing relative to irradiation, and toxicity in vitro followed by in vivo animal model studies done in the context of current human patient standard-of-care conditions;
• Ensuring accuracy and consistency of irradiation protocols through NIST-traceable dosimetry testing and on-going validation, and detailed, translatable reporting of irradiation set-up details (standard operating procedures) for both in vitro and in vivo studies;
• Including tissue culture models that measure replicative cell death, preferably under conditions that more closely mimic the tumor micro-environment (e.g., utilizing extracellular matrix substrates or 3D culture, testing under physiologic oxygen concentrations, etc.);
• Utilizing biomarkers for the effect of the radiation-drug interaction during in vitro studies, with validation of the biomarker in vivo using state-of-the-art imaging when appropriate;
• Implementing published NIH recommendations regarding the conduct and reporting of in vitro and in vivo studies including, but not limited to thorough statistical analyses of both experimental design and endpoint measures and blinded outcome assessment;
• Incorporating one or more of the following into the testing protocol: genetically annotated patient derived xenografts (and cell lines derived from these patient samples), genetically engineered rodent tumor models with an intact immune response, autochthonous rodent tumor models, rodent model tumor control (TCD-50) assays, companion animal spontaneous tumors;
• Cross-validating studies and comparing the reproducibility and predictive power of new methods of testing to currently used tests;
• Designing and executing pilot projects that begin to address novel mechanisms of activity of combined modality treatments. It is anticipated that these pilot studies will be developed into further funding proposals;
• Investigating and validating novel high- or medium- throughput technologies to help select compounds for further evaluation.

3. Data Management and Sharing

NCI will provide a site for the confidential sharing of documents between investigators and NCI staff and among different investigators. The site will be based on the NCI-Hub platform and administered under the Oncology Models Forum).

Investigators will be expected to deposit dosimetry measurements, standard operating procedures and experimental data to this site for NCI program review and sharing with other consortium members when appropriate.

Research projects that are not appropriate for this FOA

This FOA will NOT support studies of combined modality therapy that do not include CTEP portfolio molecularly targeted agents or studies that do not include radiation.

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.

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:

Eric Bernhard, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5704
Email: [email protected]

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

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

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

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

Facilities & Other Resources. Indicate Institutional and / or Industry support for the application and how this will be provided.

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

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

Budget related to Cooperative Agreement: A minimum of $50,000 direct costs need to be budgeted to fulfill cooperative agreement requirements for NIST traceable dosimetry of all radiation producing equipment, collaborative/confirmatory studies with other PCRTC investigators and pilot projects exploring mechanisms of action of molecular therapeutics with standard of care therapies. It should be anticipated that the distribution of these expenses will evolve during the term of the projects and the Consortium.

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

Research Strategy:

Overview: Because this FOA seeks both to develop novel CTEP agents for clinical application in the context of radiotherapy and enhance pre-clinical testing methods in this context, the research strategy section should address how the different aspects of the application, including models and endpoints used as well as evaluation of endpoints will fulfill these goals. In particular, applicants should address the relevance of the proposed testing approach(es) to informing the design of future clinical trials.

This section should also include a description of:

• Innovations in the proposed models and treatments approaches;
• Plans for pilot studies to address mechanistic questions, including the mechanistic questions to be explored, and how the results will inform future studies and how these will be developed into full research proposals.

Study Design should address the following issues:

• The justification for testing a given molecularly targeted agent with the standard-of-care treatment proposed, including drug dose and timing of administration considerations;
• Statistical validation of design and interpretation;
• Description of steps taken to avoid investigative biases;
• Development, refinement and/or validation of models as appropriate;
• Development / implementation and transferability of standard operating procedures for experimental protocols;
• Plans or protocols in place for reagent validation and genetic annotation;
• A timeline for achieving stated project goals.

Collaborative Responsibilities should be addressed including:

• Willingness to participate in Consortium governance;
• Approaches to working collaboratively with the other PCRTC Consortium awardees for validation of drug-radiation combination study results using the models they propose for their own studies when these are appropriate.

Letters of Support: In addition to the standard items, please provide:

• letters from collaborators documenting access to appropriate samples, animal models and/or specialized reagents;
• letter(s) of support from the grantee institution(s) and any industry (pharmaceutical) partners involved in this application;
• letter(s) documenting ongoing physics support for all proposed radiation sources;
• letter of agreement with a certified dosimetry lab for provision of NIST-traceable dosimetry for the duration of the project.

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.
• Proposed use of the NCIP-Hub Oncology Models Forum site should be included in the Resource 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 PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

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 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?

Specific for this FOA: Because the scope of this FOA is restricted to the testing of molecularly targeted drugs in the CTEP portfolio, , how clinically relevant and applicable are the treatment strategies that are being tested?

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

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

Specific for this FOA: What are the innovations in the proposed models and treatments approaches? How will the pilot studies assess possible mechanisms of activity of the molecularly targeted therapies when combined with standard-of-care?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

Specific for this FOA: How well justified are the pairing of CTEP molecularly targeted agents, standard-of-care therapy and tumor models? What strategies are in place for obtaining NIST-traceable dosimetry of irradiators and ongoing physics support? What standard operating procedures are in place and are these transferable between laboratories? How are biological reagents being validated and genetically annotated, as appropriate?

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?

Specific for this FOA: How strong is the institutional and / or industry support for this application? What form does it take and is it documented?

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 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 (GDS).

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

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

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

As part of the scientific peer review, all applications:

• 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 (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):

The PD(s)/PI(s) will have primary authority and responsibility to define objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of studies conducted under this program. 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 U01 award.

Specific responsibilities and rights include:

• Coordinating efforts and cooperating with the other U01 components of the PCRTC and with NCI Program staff. These actions may involve (but will not be limited to) the participation in the appropriate coordinating meetings and/or working groups, and/or teleconferences as needed;
• Overseeing the implementation of approved data sharing and resource sharing plans; Institutions/organizations participating in the Consortium will be expected to share with each other knowledge, data, research materials, and any other resources necessary and relevant to the Consortium, consistent with achieving the goals of this program.

Awardees will retain custody of and have primary rights to the data developed under these awards, subject to Government rights of access consistent with current DHHS, 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:

Resources to be provided by the NCI: Applicants should assume that the NCI will provide the following resources/functions to the PCRTC consortium awardees:

• Logistical support as needed for successful Consortium operations (e.g., for communications with and between Research Programs, NCI, and pharmaceutical collaborators; for hosting and documenting Steering Committee teleconferences/webinars; for organizing annual face-to-face meetings, etc.).
• NCI program staff will facilitate the submission of requests for agents supplied by pharmaceutical companies or other entities to Research Programs

A designated NCI Program Staff member, acting as a Project Scientist, will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards.

Specifically, the NCI Project Scientists will:

• Coordinate and facilitate the interactions among all the U01 awardees under this initiative;
• Work closely with investigators on Collaborative Research projects to coordinate and facilitate interactions/collaborations among the U01 awardees across the Consortium;
• Serve as liaison between the Collaborative Research awardees and NCI staff members and investigators from other NCI programs, and if appropriate, facilitating interactions and scientific integration among the U01 awardees and these programs;
• Review of all major collaborations that the awardee might propose with research groups outside the PCRTC and advise on their appropriateness before implementation to assure consistency with the goals of this FOA;
• Provide technical assistance and advice to the awardees as appropriate;
• Assist in facilitating validation studies between PCRTC members while avoiding unwarranted duplication of effort;
• Monitor institutional commitments and resources to the awardees;
• Suggest reprogramming efforts, including options to modify projects/programs when certain objectives of this FOA are not met -- specifically, the NCI Project Scientist may recommend withholding of support, suspension, or termination of a U01 award for lack of adherence to required policies and/or procedures;
• Develop working groups and trans-project efforts as needed;
• Monitor progress and direction of awardees and working groups as needed; and
• Organize and conduct regular meetings to share progress either by teleconference, videoconference, or face-to-face, as needed between the U01 awardees of the PCRTC and between awardees and NCI Program staff.

In addition, an NCI Program Director acting as the Program Official will be responsible for the normal scientific and programmatic stewardship of the awards and will be named in the award notice. The Program Official may also have substantial programmatic involvement (as a Project Scientist) and may be the same person as Project Scientist. In that case, the individual involved will not attend peer review meetings, or will seek NCI waiver according to the NCI procedures for management of conflict of interest.

Areas of Joint Responsibility include:

Steering Committee: The Steering Committee will be the main governing body for the Consortium - it will be responsible for setting general directions, including prioritizing new CTEP portfolio agents for evaluation, defining the models, approaches and endpoints for testing agents with combined modality therapies, and approving the general procedures under which the consortium will operate, including the paths toward inter-laboratory validation of study results.

The Steering Committee will be composed of the following voting members:

• Two representatives from each Consortium award (the PD(s)/PI(s) or a PD/PI and a designated senior investigator) who will have one vote each; and
• NCI Project Coordinator (who will have one vote).

All PD(s)/PI(s) will be required to serve on the Steering Committee.

The NCI Program Official and Project Scientist(s) will participate in Steering Committee meetings as non-voting members. Additional NIH staff members, serving in an advisory capacity, may also participate in these meetings as non-voting members. This decision will be made by the existing voting members of the Steering Committee. These members may include representatives from NCI extramural divisions.

The NCI Project Scientist and the PD/PIs of the U01 awards funded under PCRTC Consortium will be jointly responsible for the coordination of intra-program activities and the scientific integration of individual projects with other appropriate NCI consortia, if required.

The Steering Committee will meet once every year, at locations selected by the Steering Committee in consultation with the NCI.

The Steering Committee may decide to establish sub-committees for specific purposes. The NCI Project Coordinator will serve on such sub-committees, as they deem appropriate.

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

• Development and implementation of metrics for evaluating the performance of PCRTC Research Programs. Cooperation of the Consortium awardees will be important and expected during evaluation of the programs' progress towards achieving the Consortium goals.
• Data Management and Sharing: NCI will provide a site for the confidential sharing of documents between investigators and NCI staff and among different investigators. The site will be based on the NCI-Hub platform and administered under the NCI-Hub platform and administered under the Oncology Models Forum. Investigators will be expected to deposit Dosimetry measurements, standard operating procedures and experimental data to this site for NCI program review and sharing with other PCRTC members when 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 Consortium 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

Eric Bernhard, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5704
Email: [email protected]

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

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
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.