Department of Health
and Human Services (HHS)
and Human Services (HHS)
EXPIRED
National Institutes of Health (NIH)
National Cancer Institute (NCI)
U01 Research Project Cooperative Agreements
Reissue of RFA-CA-14-018 - Pediatric Preclinical Testing Consortium: Research Programs (U01)
RFA-CA-20-041 - NCI Pediatric In Vivo Testing Program Coordinating Center (U24 Clinical Trial Not Allowed)
93.395
This Funding Opportunity Announcement (FOA) is for Research Teams to form the NCI Pediatric in Vivo Testing Program (henceforth termed the Ped-In Vivo-TP). The Research Teams of the Ped-In Vivo-TP will determine the activity of pediatric anticancer drug candidates using preclinical models relevant to the cancer(s) on which their team focuses (supported under this FOA) and will work in concert with the Ped-In Vivo-TP Coordinating Center (supported under RFA-CA-20-041). The Research Teams will use genomically characterized pediatric cancer models to develop a rigorous preclinical testing program that will generate reliable data that can be used to inform new agent prioritization decisions for childhood cancer clinical testing.
The Ped-In Vivo-TP is envisioned as a way for NCI to support the Foundation for the National Institutes of Health (FNIH)-organized Public-Private Partnership (PPP) for pediatric preclinical testing. The PPP is being developed to accelerate the pace and to broaden the scope of pediatric preclinical testing of agents being developed for adult cancer indications. Pharmaceutical companies and representatives of regulatory agencies will also participate in the PPP.
This FOA invites applications from Research Teams that have developed panels of genomically characterized pediatric cancer models and that have the capacity for using their panels to test up to 8-10 agents per year. The Ped-In Vivo-TP Awardees will work closely with the Ped-In Vivo-TP Coordinating Center in the testing of agents and in the analysis and reporting of testing results.
30 days prior to the application due date
November 09, 2020
No late applications will be accepted for this Funding Opportunity Announcement.
All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).
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.
Not Applicable
February/March 2021
May 2021
July 2021
Not Applicable
It is critical that applicants follow the instructions in 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 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.
Purpose
The purpose of the NCI Pediatric in Vivo Testing Program (Ped-In Vivo-TP) will be to generate, analyze, and disseminate preclinical data using genomically characterized in vivo models to help inform the development of new and more effective treatments for children with cancer. As such, the proposal is specifically designed to align with objectives of both the FNIH Public-Private Partnership (PPP) for preclinical testing as well as to contribute to the NCI Childhood Cancer Data Initiative (CCDI). As described below, the in vivo testing activities of the Ped-In Vivo-TP will be supported through an anticipated eight awards to Research Teams to plan and conduct in vivo testing (the scope of this FOA) and through a single award to a Coordinating Center for the in vivo testing programs (the topic of FOA RFA-20-041).
The Ped-In Vivo-TP research activities will complement NCI-supported childhood cancer clinical research programs. The systematic preclinical efficacy and pharmacokinetic-pharmacodynamic testing of novel agents by the Ped-In Vivo-TP Research Teams will facilitate the new agent prioritization process of pediatric oncology clinical research programs. The optimized prioritization process should increase the likelihood that agents selected for clinical trials will be efficacious, opening new therapeutic options for more effective treatments for children with cancer.
Background
Introduction. NCI initially supported a pediatric preclinical testing program in 2004 to address challenges associated with developing new therapies for childhood cancers in recognition that these challenges are distinctive from those encountered in developing therapies for the neoplastic diseases of adults. These challenges have been amplified in the intervening years by evolving trends in drug development, particularly the subsetting of patients for clinical evaluation based on the genomic characteristics of their cancers. Pediatric cancer drug development is challenged by the thankfully relatively small number of patients with progressive disease who become eligible for clinical trials of experimental drugs, and this places severe restrictions on the number of novel investigational agents that can be evaluated in children with specific cancers. Furthermore, new anticancer agents are developed primarily for activity against adult neoplastic diseases (e.g. colon, lung, breast, etc.), so that agents with specific activity against childhood malignancies might not be identified. Preclinical testing programs using genomically characterized pediatric cancer models and validated testing methods can contribute by providing reliable testing results to use for agent prioritization decisions so that progress in identifying more effective treatments for children with cancer can be accelerated.
History. The Pediatric Preclinical Testing Consortium (PPTC) has been supported through an NCI cooperative agreement mechanism since 2015. Five Research Programs have performed in vivo testing for the following tumor types:
The PPTC Coordinating Center has provided administrative, logistical, and statistical support. Information about the PPTC is available at the PPTC website. The PPTC statistical analysis procedures for analyzing in vivo testing results are also available at the PPTC website.
Impact of Recent Legislation. The importance of a robust pediatric preclinical testing program is heightened in the current environment by provisions of the FDA Reauthorization Act of 2017 (FDARA) that amended the Pediatric Research Equity Act (PREA) in section 505B of the Federal Food, Drug, and Cosmetic Act (FDCA) to add a new molecularly targeted pediatric investigation requirement for certain oncology medicine applications. Specifically, this requirement applies to the sponsor of an original new drug application (NDA) or biologics license application (BLA) for a new active ingredient submitted on or after August 18, 2020, if the drug is intended for the treatment of an adult cancer and directed at a molecular target that [FDA] determines to be substantially relevant to the growth or progression of a pediatric cancer. If these criteria are met, the sponsor must conduct a molecularly targeted pediatric cancer investigation designed to yield clinically meaningful pediatric study data regarding dosing, safety, and preliminary efficacy to inform potential pediatric labeling beginning in August 2020. The FDA’s initial list of potentially relevant molecular potential pediatric targets included over 200 distinct molecular entities. Pharmaceutical company representatives estimate that as many as 200 agents per year will require some type of evaluation for their relevance to childhood cancers.
Relationship to FNIH Public-Private Partnership for Pediatric Preclinical Testing. Catalyzed by both the legislation described above and by the need to address the challenges created by the need for evaluations of large numbers of investigational agents for their relevance to childhood cancers, NCI, FDA, and the Pharmaceutical Research and Manufacturers of America (PhRMA) approached the Foundation for the National Institutes of Health (FNIH) to convene stakeholders to develop a public-private partnership (PPP) to create centralized resources for a more systematic, global, and robust approach to pediatric preclinical testing of cancer therapies. In September 2019, FNIH sponsored a meeting to discuss Potential Preclinical Pediatric Oncology Public-Private Partnership (PPP) that brought together representatives from pharmaceutical companies, NCI, FDA, and academia to develop a research agenda for a pediatric preclinical testing PPP. The FNIH PPP white paper (available upon request from the Scientific/Research Contact, which was based on the meeting discussions and follow-up discussions, described the following specific tasks for the PPP:
This FOA and the accompanying FOA for the Ped-In Vivo-TP Research Teams can be viewed as research programs through which NCI will be supporting the establishment of the pediatric preclinical testing PPP being developed by FNIH.
Research Objectives and Requirements
The Ped-In Vivo-TP will consist of academic Research Teams with expertise in the cancer types for which they are responsible for testing. A goal in establishing the Ped-In Vivo-TP will be for the program to broadly represent the range of cancers that occur in children. As such, for the eight awards that are anticipated, 6-7 are anticipated to have a focus on pediatric solid tumors as well as CNS tumors and 1-2 are anticipated to have a focus on pediatric leukemias (ALL and AML). An open competition will be utilized for selection of the in vivo Research Teams of the Ped-In Vivo-TP, with Research Teams that are not currently participating in the PPTC encouraged to apply along with current members.
Each team is expected to propose models that have been genomically characterized (whole exome sequencing and RNA-seq at a minimum) so that models can be selected for testing based on their biological characteristics. Research teams will be expected to document the extent to which the models that they propose to utilize in the Ped-In Vivo-TP faithfully recapitulate key biological and molecular characteristics of the childhood cancers that they are intended to represent.
The preclinical models utilized may include those derived from patient specimens by xenografting in immunodeficient mice, murine genetic models engineered to reflect the characteristics of specific pediatric cancers, and/or murine syngeneic models of childhood cancers. Leukemia models are expected to represent systemic disease, while for solid tumors and CNS tumors, either subcutaneous or orthotopic models or metastatic models may be suitable. Applicants will be expected to justify why the models that they have proposed are suitable for testing selected anticancer agents and for providing insight into the potential relevance of these agents for selected childhood cancers. Priority will be given to models that reflect cancers with poor outcome, either because of the intrinsic treatment resistance of the disease or because of the models being established from patients with relapsed/recurrent disease.
Preclinical testing by the Research Teams of the Ped-In Vivo-TP may include conventional testing designs with treated and control groups (5-10 animals in each group) and using time-to-event endpoints and response assessments based on serial tumor volume measurements. The single-mouse trial (SMT) design may also be used as it allows a larger number of models to be studied in a cost-effective way. The SMT design is relevant to agents for which tumor-regressing activity is sought, and its primary readout is the maximum tumor volume reduction. The statistical analysis methods employed by the PPTC are available at the PPTC website. Other study designs may be used when determined to be scientifically appropriate to evaluate the activity of agents. In addition, testing of combinations of agents will be an important aspect of the Ped-In Vivo-TP and is anticipated to involve comparisons of the activity of the combination of agents to the activity of the single agents used alone.
Special considerations apply to in vivo testing for pediatric brain tumors as a result of the impact of the blood-brain barrier on tumor drug levels and as a result of the role of the CNS microenvironment in supporting survival and proliferation for some brain tumors. Orthotopic brain tumor models provide a potential approach to addressing these issues, although as a matter of practicality, in vivo testing using subcutaneous flank models may be informative for some agents and for some brain tumor histologies in determining whether testing in more technically challenging orthotopic brain tumor models should be pursued. An additional issue to address with orthotopic models is the assessment of tumor response which requires serial in vivo imaging (e.g., by MRI, bioluminescence or PET-CT) and creates additional logistical challenges.
Requirement for Model Material Transfer Agreement (MTA). Testing of agents by the Ped-In Vivo-TP Research Teams will be performed under terms of a model Material Transfer Agreement (MTA). The terms of the Ped-In Vivo-TP model MTA will be similar to those of the model MTA of the PPTC. At the beginning of the awards for each Ped-In Vivo-TP research team and for the Coordinating Center, NCI will sign an MTA with each awardee's institution for the provision of agents for testing through the Ped-In Vivo-TP. For each agent identified for testing through the Ped-In Vivo-TP, NCI staff members will negotiate MTAs with the entity supplying the agent for testing such that the terms of the MTA with this entity match the terms of the MTAs that NCI has with each of the testing Ped-In Vivo-TP institutions.
Integration of the Ped-In Vivo-TP Research Teams with the Coordinating Center: The Ped-In Vivo-TP awardees will be required to collaborate closely with the Coordinating Center that will be supported under the companion FOA RFA-CA-20-041. The Coordinating Center will be responsible for integrating the activities of the individual Ped-In Vivo-TP Research Teams to create a functional consortium for pediatric preclinical testing. Specifically, the Coordinating Center will provide administrative and logistical coordination, data management and statistical support, and will facilitate Consortium scientific activity through report preparation and through support for manuscript development.
Ped-In Vivo-TP Governance: The Ped-In Vivo-TP Steering Committee (SC) will serve as the body for prioritizing agents for study by the Ped-In Vivo-TP, for defining the overall scope of research plans for agents selected for testing, and for approving the general SOPs under which the Ped-In Vivo-TP operates. The SC will include the PD(s)/PI(s) of the Ped-In Vivo-TP Coordinating Center and the PD(s)/PI(s) of each of the Ped-In Vivo-TP Research Teams, the NCI Project Scientist, and others as appropriate.
The PD(s)/PI(s) of the Ped-in Vivo-TP Coordinating Center and the PD(s)/PI(s) of each of the Ped-In Vivo-TP Research Teams will also be expected to serve on the Scientific Advisory Committee (SAC) of the FNIH PPP for pediatric preclinical testing. The SAC will include: the PD(s)/PI(s) of the Ped-in Vivo-TP Coordinating Center and the PD(s)/PI(s) of each of the Research Teams, the NCI Program Director, FNIH representatives, and others as appropriate. The Ped-InVivo-TP SC may accept recommendations from the PPP SAC for agents to prioritize for testing within the Ped-In Vivo-TP.
See Section VIII. Other Information for award authorities and regulations.
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.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
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NCI intends to commit approximately $5.1 million to fund up to 8 awards in FY 2021.
The application budget is limited to $450,000 in direct costs per year and should reflect the actual needs of the project.
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 from this FOA.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Other
Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
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:
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace 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.
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: The letter of intent should be sent to: Malcolm A. Smith, MD, PhD National Cancer Institute (NCI)
Telephone: (240) 276-6087
Email: Malcolm.Smith@nih.gov
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.
Other Attachments: Applicants must provide the additional supporting materials indicated below.
Upload these materials as a single pdf file using file names indicated in the list (these file names will become bookmarks in the application).
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Research Strategy: Specific Sub-Sections A-D that must be included in Research Strategy are described below.
Sub-section A. Investigators Capabilities and Experience
Outline the major strengths and collective capabilities of the leadership and the team that will be responsible for preclinical testing, without duplicating information in the biosketches.
NOTE: Testing is to occur at a single site to facilitate coordination and quality control.
Sub-section B. Preliminary Studies for New Applications / Progress Report for Renewal Applications
Sub-section C. Preclinical Models Proposed
Sub-section D. Approach to Preclinical Testing
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.
The following modifications also apply:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Foreign Institutions
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. 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 components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission 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.
Significance
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? 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 to this FOA: What is the likelihood that the proposed research team will be able to implement an in vivo testing program for its intended disease(s) with appropriately molecularly characterized models that can make substantial contributions to the overall Ped-InVivo-TP research program?
Investigator(s)
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Specific to this FOA: Based on past performance, how strong are the qualities of the PI(s) and the entire team in terms of appropriate expertise, training, demonstrated experience, and an ongoing record of accomplishments in conducting pediatric preclinical testing?
Innovation
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Environment
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 to this FOA: Are the applicant's facilities to house and maintain a rodent colony sufficient for the type and quantity of rodents proposed?
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.
Protections for Human Subjects
For research that involves human subjects but does not involve one of the 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 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 Individuals Across the Lifespan
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 individuals of all ages (including children and older adults) 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
For Renewals, the committee will consider the progress made in the last funding period.
Revisions
Not Applicable
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Applications from Foreign Organizations
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
Select Agent Research
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Resource Sharing Plans
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
Authentication of Key Biological and/or Chemical Resources:
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Budget and Period of Support
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 will receive a written critique.
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.
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:
Information regarding the disposition of applications is available 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.
Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
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 laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.
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.
Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.
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.
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.
Responsibilities for the Ped-In Vivo-TP Research Team PD(s)/PI(s) and the Ped-In Vivo-TP Coordinating Center PD(s)/PI(s) are aligned, as both are required to function together to successfully implement the research objectives of the Ped-In Vivo-TP.
The PD(s)/PI(s) will have the primary responsibility for defining the scientific objectives and approaches and providing oversight of all scientific activities of individual Research Programs. Specific responsibilities are listed below.
Responsibilities of the Ped-In Vivo-TP Research Team awardees will include:
NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
A designated NCI Program staff member serving as Project Scientist/Coordinator will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. Additional NCI staff members may also become substantially involved as needed.
The substantially involved NCI staff members will not attend peer review meetings of renewal or supplemental applications. If such participation is essential, these individuals will seek a waiver according to the NCI procedures for management of conflict of interest
Main responsibilities of substantially involved NCI staff members include the following:
Negotiating Material Transfer Agreements (MTAs) with pharmaceutical companies and with Ped-In Vivo-TP Awardees: The Regulatory Affairs Branch (CTEP, NCI) will negotiate MTAs with pharmaceutical companies that will match the terms of MTAs that NCI implements with Ped-In Vivo-TP awardees and that will allow testing of agents by the Ped-In Vivo-.TP
NCI will have access to all data generated under this cooperative agreement and may review the data as necessary. The awardee will retain custody and primary rights to the data consistent with current HHS, PHS and NIH policies. The awardee will comply with the data access provisions of applicable MTAs, and when these agreements are in place the Industry Sponsor will have complete access to the data for any and all regulatory filings.
Agents tested will be provided by pharmaceutical collaborators and academic investigators under MTAs based on the provisions of a standard Model MTA.
The NCI reserves the right to adjust funding, withhold, suspend, or terminate the support to the Ped-In Vivo-TP awardee institution if it is unable to meet the performance requirements set forth in these Terms and Conditions of Award, or significantly change the level of performance.
An NCI Program staff member, acting as the Program Official, will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.
Areas of Joint Responsibility include:
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 Ped-In Vivo-TP SC 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
A final RPPR, 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.
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, application errors and warnings, documenting system problems that threaten submission by the due date, and 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)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov
Malcolm A. Smith, MD, PhD
National Cancer Institute (NCI)
Telephone: (240) 276-6087
Email: Malcolm.Smith@nih.gov
Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: ncirefof@dea.nci.nih.gov
Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email: wolfreyc@mail.nih.gov
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.