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Department of Health and Human Services
Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)

Funding Opportunity Title

Coordinating Center for Canine Immunotherapy Trials and Correlative Studies (U24)

Activity Code

U24 Resource-Related Research Projects Cooperative Agreements

Announcement Type

New

Related Notices
Funding Opportunity Announcement (FOA) Number

RFA-CA-17-002

Companion Funding Opportunity

RFA-CA-17-001, U01 Research Project--Cooperative Agreements

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.393, 93.394, 93.395, 93.396, 93.399

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) will support a coordinating center for a network of cooperative agreements (see U01 FOA RFA-CA-17-001) that will conduct clinical trials in pet dogs with spontaneous tumors and perform laboratory correlative studies associated with the clinical trials. This FOA will work with the NCI Comparative Oncology Program (COP) of the NCI's Center for Cancer Research as an integral component and will provide statistical support; assist with the development and standardization of clinical protocols and laboratory immune monitoring assays; assist with the implementation of clinical studies in immunotherapy and combination agents including accrual to the trials; manage clinical and correlative data from all U01 sites and their collaborators including immune-related adverse events; facilitate the sharing of agents, specimens, and data; and create an ad hoc steering committee of required expertise--both inside and outside the U01 network, including the PD/PIs of the U01s, representatives of the COP and the NCI Program Official--to ensure that the goals of the network are accomplished.

Key Dates

Posted Date

December 16, 2016

Open Date (Earliest Submission Date)

February 7, 2017

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

March 7, 2017, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

Not applicable

Scientific Merit Review

New Dates: May-June 2017

Advisory Council Review

New Date: August 2017

Earliest Start Date

New Date: September 2017 as per issuance of NOT-CA-17-016

Expiration Date

March 8, 2017

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.


Table of Contents

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


Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Purpose

This Funding Opportunity Announcement (FOA) will support a coordinating center for a network of cooperative agreements (see U01 FOA RFA-CA-17-001) that will conduct immunotherapy clinical trials in pet dogs with spontaneous tumors and perform laboratory correlative studies associated with the clinical trials. This FOA will work with the NCI Comparative Oncology Program (COP) of the NCI's Center for Cancer Research as an integral component and will provide statistical support; assist with the development and standardization of clinical protocols and laboratory immune monitoring assays; assist with the implementation of clinical studies in immunotherapy and combination agents including accrual to the trials; manage clinical and correlative data from all U01 sites and their collaborators including immune-related adverse events; facilitate the sharing of agents, specimens, and data; and create an ad hoc steering committee of required expertise--both inside and outside the U01 network, including the PD/PIs of the U01s, representatives of the COP and the NCI Project Collaborators --to ensure that the goals of the network are accomplished. The COP oversees the Comparative Oncology Trials Consortium--a network of 22 veterinary medical colleges that perform canine clinical trials.

Background

Advances in Immunotherapy for Cancer Treatment: The past several years have seen an enormous advance in the use of immunotherapy approaches for cancer treatment in humans. In particular, the use of checkpoint inhibitor antibodies, such as anti-CTLA4 and anti-PD1, which bind to suppressor elements on immune cells and increase the magnitude and extent of effector cell immune responses, has achieved significant responses in patients with certain organ-site malignancies, such as melanoma, renal cell carcinoma, bladder cancer, and non-small cell lung cancer (NSCLC), with durable responses in a significant number of these patients. Initially, it was thought that the expression of PD-L1 on the surface of tumor cells could serve as a biomarker for responsiveness to anti-PD1 therapy, but several studies have shown that the correlations between expression and response are complex; the majority of patients with PD-L1-expressing tumors do not respond to PD-1/PD-L1 pathway blockade, while responses are occasionally seen in PD-L1 non-expressers. It is thought that sensitivity to PD-1 blockade in NSCLC depends primarily on a high non-synonymous mutation load in the tumor (generating neoantigens) and less on the expression of PD-L1 on the tumor surface although that does play some role.

Mutations and Susceptibility to Checkpoint Inhibitors: Certain mutations, such as mismatch repair defects in a subset of colon and other cancers, appear to predict susceptibility to the effects of checkpoint inhibitors, as shown by longer progression-free survival in patients with these mutations. The magnitude of T cell infiltration of tumor is also a factor, but not an independent biomarker. The specificity and affinity of the engagement of T cells with tumor cell neoantigens in the context of the patient’s HLA haplotype are probably important as well. However, the success of immunotherapy approaches has been difficult to predict.

Genetically-engineered/Humanized Animal Models: Animal models have been tremendously important tools in human cancer research. Immunocompetent mouse models, including syngeneic, transgenic, and genetically engineered mouse models (GEMMs), as well as a number of immunodeficient xenograft models, have been employed for decades. GEMMs carry many of the same mutations as do the corresponding human tumors and often develop tumors on a compressed timeline compared with the natural history of the human tumor; but these tumors do not in general replicate the genetic complexity of the human tumor, including its heterogeneity. GEMMs therefore are not optimal for testing the response of drugs and immunotherapeutic agents to be used in humans. Immune deficient models, including patient-derived xenografts (PDXs) carrying human primary tumors, have been used to predict patient response to drugs, but they lack an intact immune system and are therefore inadequate for testing the effect of immunotherapies.

More recently, humanized mouse models have been developed that accept and engraft human tissue, specifically human hematopoietic stem cells, and express human cytokine genes. However, a perfect humanized mouse model appropriate for immunotherapy studies would require specific human MHC class I and II elements to match those of the patients tumors; no such models are currently available.

Use and Advantages of Companion Animals (Pet Dogs) for Immunotherapy: Another approach to both targeted therapy and immunotherapy research is the use of companion animals, such as pet dogs. Canine patients with spontaneous tumors have a number of advantages over mice as therapeutic models. Briefly, the canine genome is similar to that of human; the complexity of canine tumors in terms of heterogeneity, their relationship to the tumor microenvironment, and the development of resistance to treatment are closely related to cancer in human patients; dogs are immunocompetent; dogs are relatively outbred compared with laboratory animals (although some breeds have greater susceptibility to certain forms of cancer); few standards of care and few agents are approved for the treatment of cancer in dogs, and therefore investigational agents can be considered even in early or minimal residual disease states; there is an established track record of responsiveness to known chemotherapeutic agents; for many cancers, dogs and humans share major cytogenomic aberrations in signaling pathways; and spontaneously-occurring cancers in pet dogs have been increasing as a result of increased life expectancy because of a higher standard and wider availability of quality veterinary medical care. It has been shown that canine PD-1 and PD-L1 genes are conserved among dog breeds and that the pathway is associated, as in humans, with T cell exhaustion that can be overcome with PD-1 or PD-L1 blockade.

Although it has not been demonstrated in dogs, it is probable that blockade of the PD-1/PD-L1 pathway will not result in a strong anti-tumor effect unless there is a high tumor mutational load or, in some cases, a few strong mutations that translate into the expression of neoantigens recognizable by the canine immune system. Mutations in human tumors do not necessarily parallel the equivalent mutations in canine tumors. For example, although both human and canine melanomas are similar in their activation of the AKT/mTOR pathway and other pathway dysregulation, B-raf mutations are rare in canine melanoma. Conversely, the frequency of BRAF mutations is higher in canine urothelial carcinoma and prostate cancer compared with human tumors. Identification of the specific somatic mutations in canine cancers and understanding why some mutations become tumor neoantigens important for effective immunotherapy will shed light on parallel mechanisms in human cancer.

Specific Research Objectives

The long-term objective of the NCI is to establish the suitability of canine models to study single and combination immunomodulating agents, ideally with molecularly targeted drugs, chemotherapy, or radiation, for the purpose of translating the canine findings to human studies.

For this FOA, the objective is to establish a Coordinating Center for the network of laboratory scientists and canine clinical trialists to study the anti-tumor effects, including mechanisms of action and immune-related adverse events, of immunotherapy agents and novel combinations of immunotherapy and other modalities in canine patients with spontaneous tumors. An essential goal of the network will be to determine whether or not canine cancer is a close model of human malignant disease, and if so, whether immunotherapy alone or in combination with other modalities in canine models will inform the design of therapies in humans.

Scope of this FOA

This FOA is intended to solicit applications that propose to coordinate and govern the network of U01 awardees that will conduct:

(a) one or more clinical trials in canine patients with spontaneous tumors that will be treated with a single agent immune modifier or a combination of immunotherapy and one or more other agents (a second immune modifier, a molecularly targeted agent, chemotherapy, and/or radiation); and,

(b) one or more clinical correlative studies (using biopsy or surgical specimens and controls from the clinical trial) in the laboratory that seek to describe, characterize, and understand the cellular and molecular mechanisms that determine the anti-tumor response (or non-response) in dogs with spontaneous tumors that participate in the clinical trials.

The U24 Coordinating Center should provide research support by:

  • Providing logistic infrastructure to support the activities of the Consortium awardees and the Steering Committee;
  • Helping coordinate collaborative research efforts that involve multiple Centers;
  • Helping to develop/implement the clinical studies in immunotherapy and therapeutic combinations;
  • Assisting in the standardization of clinical and laboratory immune monitoring protocols;
  • Managing clinical and correlative data from all sites--including immune-related adverse events;
  • Working with the NCI to contribute data to a public access database;
  • Providing statistical support;
  • Facilitating sharing of agents, specimens, and data;
  • Reporting progress in an annual report as required by the NCI.
Network Structure

The U24 Coordinating Center will act as the hub for the clinical and laboratory activities of the U01 network. Each U01 will involve both academic scientists who have had experience working with canine models, and veterinary oncologists who are associated with one of the veterinary medical institutions that may be part of the Comparative Oncology Trials Consortium (COTC) which is overseen by the NCI Center for Cancer Research's Comparative Oncology Program (COP). Industry partners may also participate in the U01 award.

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

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed

New
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

NCI intends to fund 1 award, corresponding to a direct cost of $350,000, for fiscal year 2017. Future year amounts will depend on annual appropriations.

Award Budget

Budgets for direct costs may not exceed $350,000 per year.

Award Project Period

The maximum project period is 5 years.

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

Section III. Eligibility Information
1. Eligible Applicants
Eligible Organizations

Higher Education Institutions

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

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

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)
  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession

Other

  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
Foreign Institutions

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.

Required Registrations

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.

Eligible Individuals (Program Director/Principal Investigator)

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.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility
Number of Applications

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).
Section IV. Application and Submission Information
1. Requesting an Application Package

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Letter of Intent

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:

Toby T. Hecht, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5683
Email: hechtt@mail.nih.gov

Page Limitations

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

Instructions for Application Submission

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.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims: Outline the Specific Aims of the proposed Coordinating Center. A timeline of the initiation and completion of the aims may also be included.

Research Strategy: The applicants should provide a detailed description of how they will address:

  • Development and implementation of canine immunotherapy and combination clinical trials which involve one or more components of the U01 network;
  • Management of clinical and correlative data from all sites;
  • Statistical support needed for both clinical and laboratory protocols;
  • Facilitation of sharing agents, specimens, and data;
  • Creation of an appropriate infrastructure to support the activities of the Consortium Steering Committee;
  • Standardization of clinical and laboratory immune monitoring protocols.

Letters of Support: In some applications, applicants will include collaborations with industry partners or other laboratories that will provide assays or canine-specific or other agents for the canine clinical trial or correlative study. Letters of support from these entities will be required.

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 both a Data Sharing Plan and a 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.

PHS Inclusion Enrollment Report

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

PHS Assignment Request Form

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

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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.

7. Other Submission Requirements and Information

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NCI, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy.

Section V. Application Review Information
1. Criteria

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.

A primary objective of this FOA is to establish a Coordinating Center for the network of laboratory scientists and canine clinical trialists to study the anti-tumor effects of immunotherapy agents and novel combinations of immunotherapy and other modalities in canine patients with spontaneous tumors. While the CC will not directly produce scientific data, it is expected that it will facilitate information, data, model, and specimen sharing, administrative management, and additional research services as appropriate.

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Center 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).

Scored Review Criteria

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.

Significance

Does the proposed Center address the needs of the U01 research network that it will coordinate? Is the scope of activities proposed for the Center appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research network?

Specific to this FOA: Does the U24 application sufficiently address the tasks described in the scope of the FOA section under Network Structure?

Investigator(s)

Are the PD(s)/PI(s) and other personnel well suited to their roles in the Center? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing canine clinical and correlative study research across institutions? Do the investigators demonstrate significant experience with coordinating collaborative clinical research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills, including statistical expertise; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the Center? Does the applicant have experience overseeing selection and management of subawards, if needed?

Specific to this FOA: If the applicant is an academic institution, is there a proven track record of working with veterinary medical colleges and industrial partners? If the applicant is a veterinary medical college, is there a proven track record of working with academic centers and industrial partners?

Innovation

Does the application propose novel organizational concepts, management strategies, or instrumentation in coordinating the research network the Center will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts, management strategies or instrumentation proposed?

Approach

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research network the Center will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the network, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the network is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the network? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects?

Specific to this FOA: Does the application have an approach to sharing specimens, assay protocols, and data? Does the application describe the means of partnering with the Comparative Oncology Program of the NCI to facilitate and augment the tasks of the U01s in both the canine clinical area and in the laboratory correlative study area? Does the application detail how statistical support will be provided to the network? Is there a plan for the creation of a Steering Committee and what is the vision for the operation of that committee for the network?

Environment

Will the institutional environment in which the Center will operate contribute to the probability of success in facilitating the research network it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Center proposed? Will the Center benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

Specific to this FOA: If the U24 applicant is also a U01 applicant, will leading the network enhance the work of the U01 and the U01 network?

Additional Review Criteria

Protections for Human Subjects

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.

Inclusion of Women, Minorities, and Children

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.

Vertebrate Animals

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.

Biohazards

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.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

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

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

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.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the 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.
3. Anticipated Announcement and Award Dates

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.

Section VI. Award Administration Information
1. Award Notices

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.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable 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.

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

  • Providing logistic infrastructure to support the activities of the Consortium awardees and the Steering Committee;
  • Working with the U01 awardees to develop and implement canine clinical studies in immunotherapy and combinations;
  • Managing clinical and correlative data from all Consortium U01 sites;
  • Providing statistical support to all U01 sites for both clinical and laboratory protocols.
  • The U24 awardee will facilitate the sharing of agents, specimens, and data.
  • Serving as a voting member on the Consortium Steering Committee; and
  • Adhering to the Steering Committee recommendations and policies (to the extent consistent with applicable grants regulation) to ensure that the goals of the network are accomplished;

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.

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

  • The designated NCI Program staff members will have substantial involvement as Project Scientists in the awards under this FOA.
  • NCI Project Scientists will participate in the following activities:
  • Assisting in avoiding unwarranted duplications of effort across the Network;
  • Helping coordinate collaborative research efforts that involve multiple Centers;
  • Monitoring the operations of the Centers and making recommendations on overall project directions;
  • Reviewing the progress of individual Centers and specific activities shared among the Centers;
  • Participating in the development and evaluation of trans-Network activities;
  • Assisting the Network awardees as a liaison in stimulating their broader interactions with other NCI and NIH programs to disseminate results and outcomes and effectively leverage existing NIH/NCI resources and infrastructures (e.g., databases)

In addition, the members of the Comparative Oncology Program (COP) of the NCI Center for Cancer Research will have substantial roles as Project Collaborators.

NCI COP Project Collaborators will:

  • Participate in the final design of collaborative canine clinical trials within the network;
  • Assist in establishing Standard Operating Procedure for laboratory protocols and assays;
  • Assist in ensuring sufficient accrual of canine subjects for study; and
  • Assist in the distribution of reagents and specimens.

In addition, the NCI Program Director, acting as Program Official, will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The NCI Program Official and Project Scientist may be the same person.

Areas of Joint Responsibility

A Steering Committee will serve as the main governing board of the program.

The committee will consist of the following voting members:

  • One representative from each U01 project award (a PD/PI or a designated senior investigator) who will have one vote;
  • One representative from the U24 (a PD/PI or a designated senior investigator) who will have one vote; and
  • NCI Project Scientists who will have one total vote.

The NCI Project Collaborator(s) will act in an advisory capacity and participate in Steering Committee meetings as non-voting members.

The Steering Committee will have the following primary responsibilities:

  • Establishing Consortium policies and procedures;
  • Establishing policies and procedures for collaborative projects, and protocols;
  • Developing guidelines for the collection and distribution of specimen reference sets for collaborative research; and
  • Oversight of U01 awardees in multi-institutional trials and correlative studies with other U01 awardees coordinated by a U24 Coordinating Center.
  • Serving as a hub for a broader outreach to the entire extramural research community investigating canine immunotherapy

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.

3. Reporting

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.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)

Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

Email: support@grants.gov

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

Telephone: 301-710-0267

Scientific/Research Contact(s)

Toby T. Hecht, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5683
Email: hechtt@mail.nih.gov

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

Office of Grants Administration
National Cancer Institute (NCI)
Telephone: 240-276-6300
Email: Crystal.wolfrey@nih.gov

Section VIII. Other Information

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.

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.


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