Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

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.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

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

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

The overall goal of this Notice of Funding Opportunity (NOFO) is to improve the treatment of adult Glioblastoma Multiforme (GBM) by developing novel effective agents that can cross the blood brain barrier (BBB) and testing them in the clinic. To implement this initiative, multi-institutional teams are invited to participate in the Glioblastoma Therapeutics Network (GTN). Each GTN team is expected to drive therapeutic agent(s) from late pre-clinical development, through IND studies, into pilot clinical studies in humans. Successful early-stage trials of these new drugs would transition seamlessly to later stage trials using well-established NCI clinical trial mechanisms.

Definitions and Acronyms for this NOFO

• Adult Glioblastoma (GBM): primary or secondary grade IV glioma in a patient over the age of 18 years.
• BBB: Blood-brain-barrier.
• Development Candidate: a drug-like small molecule or biological therapeutic, the end-product of the lead optimization stage.
• GTN: Glioblastoma Therapeutics Network.
• Internal Advisory Board: panel of experts within the institution(s) of U19, not to include U19 personnel.
• Lead Optimization stage: The Lead Optimization stage begins with one or more lead compounds; the goal of the Lead Optimization stage is to identify a Development Candidate(s) for further development. Activities in the Lead Optimization stage include medicinal chemistry [structure-activity relationships (SAR) for improved potency and selectivity]; in vivo testing in rodents; exploratory pharmacokinetics (PK), metabolism and toxicology; and compound selection based on the outcome of these activities and on the defined compound profile. The Lead Optimization stage is followed by the Preclinical Development stage.
• Preclinical Development stage: The Preclinical Development stage bridges the Lead Optimization stage and pilot or Phase I clinical trials. Activities in Preclinical Development focus on the Development Candidate and include scale-up and formulation; PK, Absorption, Distribution, Metabolism, and Excretion (ADME) and Good Laboratory Practice (GLP) toxicology; efficacy studies using the clinically intended route of delivery; and IND filing. Agents being developed for GBM should demonstrate transit through the BBB as part of the PK studies.
• Pilot clinical study: A pilot clinical study, also termed a Phase 0 study, is a small-scale, exploratory clinical study aimed to test feasibility of methods and procedures, and/or activity of a therapeutic agent. A window-of-opportunity study is one type of pilot clinical study in which the experimental therapy is given after diagnosis and before surgery, allowing for early testing of drug activity in the surgical specimen.

Background

Limited progress has been made in the treatment of adult GBM despite enormous public and private investments in basic, translational, and clinical research. The standard of care (maximal surgical resection followed by adjuvant radiation and temozolomide chemotherapy) has not changed in 15 years and yields a median survival of about 15 months and a 5-year survival of < 5%. Distinct pathophysiologic challenges at least partially explain the lack of progress in GBM therapies. First, GBM is a locally infiltrative brain malignancy without a well-defined border; surgical resection cannot be extended to obtain a tumor free margin. Therefore, adjuvant chemotherapy and radiation therapy (RT) are required after surgery, and the clinical efficacy of these two modalities is critical to treatment success. Second, agents for brain tumors must cross the blood-brain-barrier (BBB) to have a therapeutic effect; poor BBB penetration can lead to limited anticancer activity despite systemic toxicities. Third, in the setting of RT, the dose is limited by RT tolerance of normal brain parenchyma. Finally, the efficacy of other therapies, including targeted agents and immunotherapy, is impeded by GBM's intratumoral genetic heterogeneity and its immunosuppressive tumor microenvironment, which is marked by scant effector T-cell infiltration, preventing the antitumor efficacy of immune checkpoint inhibitors. Clearly, the development and selection of specific agents for GBM need to break new ground if effective treatments are to be found for this disease.

This long-standing unmet need is being addressed by the GTN, which has advanced several agents into early phase clinical trials, with the potential for introduction of additional novel agents in the future. The GTN is a unique framework for team science and improved rigor in preclinical drug development within the GBM community, providing a hub to accelerate movement to the clinic. Key elements of the ongoing GTN, including network coordination, cross-GTN collaborative pilot projects, and administrative oversight by Steering and Executive Committees, will remain in the proposed GTN. The future GTN will incorporate increased emphasis on engaging the external GBM community and timely movement of agent(s) to the clinic. 

Specific Research Objectives of this NOFO

The purpose of this NOFO is to build upon momentum established in the GTN's initial phase by establishing a network (GTN) of highly collaborative U19 teams, each team capable of driving therapeutic agent(s) from pre-clinical development, through IND studies, into pilot clinical studies in humans. Agents proposed for development in the GTN should not have been tested previously in GBM patients. Appropriate development candidates include: (1) novel agents or (2) agents or combinations approved for other indications and repurposed for treatment of GBM following relevant preclinical studies. As developing drugs from the discovery phase is a long, expensive process that often encounters obstacles and failures, this NOFO focuses on agents in the Preclinical Development stage. A unique aspect of the GTN will be the ability of members to leverage models and methodologies for cross-validation of promising agents across the network.

NCI's current research infrastructure (notwithstanding its extensive clinical trials capabilities) needs to expand critical drug development capabilities that are required for a comprehensive, full-scale effort to develop and test effective GBM therapeutic strategies. This would include the qualification of new BBB-penetrating drugs and combinations of therapeutic modalities (including other small molecule and biological agents, and radiation therapy), and the development of functional biomarkers to demonstrate that drugs and/or combinations reach their tumor or microenvironment targets. Successful evaluation of these novel agents and combinations in clinically relevant preclinical models and early-phase proof-of-mechanism clinical trials (that include pharmacokinetics [PK], molecular pharmacodynamic [PD] assays, and imaging) could lead to the translation of new agents into later-stage GBM clinical trials.

Research Scope and Structure of this NOFO

Overall:

• Applicants to this NOFO should propose a multi-institutional team composed of investigators from two or more institutions, two of which can accrue patients to GTN clinical trials from non-overlapping catchment areas, and may be led by multiple PD/PIs, to accelerate the development of the candidate agent(s) proposed.
• Each multi-institutional team in the GTN should propose two scientific projects focused on agent(s) that have completed or are solidly in lead optimization status and are new to the treatment of GBM. Required components of each U19 are an Administrative Core with a network coordinating subgroup; two Research Projects; and one or more Shared Resources Core(s) that serve the Research Projects. Projects and Cores within each team should demonstrate synergy. Each U19 should propose integrated clinical activities to move agents from pre-clinical to clinical stages including the preparation of an IND.
• Each multi-institutional U19 team with the components mentioned above is termed a "U19 Center."
• Although Projects and Cores of each U19 Center will vary with the development stage and type of the proposed agent(s), it is anticipated that successful U19 teams will include outstanding expertise and experience in small molecule or biologics development, such as medicinal chemistry, pre-IND in vivo modeling, drug development (drug formulation, scale-up, ADMET, PK/PD assays and imaging), and clinical trial development and execution. It is imperative that each team include all the necessary expertise to advance the agent(s) to the clinic.
• With the formation of the Network, there is expected cooperation between U19 Centers so that reagents, assay protocols, animal models, patient samples, technologies, and development of clinical protocols are shared. As some teams will be further along in the process than others, when any one of the teams is ready to test their agent(s) in a pilot clinical trial, all other U19 sites are highly encouraged to participate as secondary sites as guided by the GTN Steering Committee and the NCI.

Refer to the NCI NCAB videocast (September 4, 2025) for further details on the GTN. Information specific to biopharmaceutical development may be found here.

Network Coordinating functions in Administrative Cores:

• The GTN requires coordination between U19 Centers and NCI staff for successful harmonization of administrative, scientific and clinical activities.
• The Administrative Core of each U19 Center must include a Network Coordinating Subgroup with responsibilities distinct from those of the U19 Center's Administrative Core. The Network Coordinating Subgroup (NCS) from each U19 Center will join with those from other U19 Centers and together they will form a GTN Coordinating Working Group (GTN CWG). Leadership of the GTN CWG will rotate (e.g., annually) during the project period.  Functions of the GTN CWG include:
  • Administrative coordination of GTN meetings including Steering Committee, Executive Committee, an annual face-to-face meeting, and others as defined by the newly formed GTN.
  • Leadership in development of standard operating procedures to facilitate GTN communication, GTN-wide logistical processes, and GTN data management.
  • Coordination of collaborations between U19 Centers, and leadership in identifying and executing collaborations with scientists outside the GTN using restricted funds.
  • Formation and maintenance of a GTN website
• Upon funding, the GTN Coordinating Working Group will meet to determine necessary functions and how they will jointly perform them.

Research Projects and Shared Resources Cores:

• Projects focusing on small molecules are preferred; biologic agents that target either the tumor or the immunosuppressive microenvironment and that meet the criteria for this NOFO are also encouraged.
• Research projects may be hypothesis-driven or hypothesis-generating. Specific Aims of a Research project may encompass the Preclinical Development Stage with emphasis on IND-enabling studies and/or pilot clinical studies.
• Each Research project must be led by a minimum of two co-leaders: one laboratory scientist and one clinical researcher.
• Agent(s) should have completed, or be solidly in, the lead optimization stage of drug discovery and must be new to the treatment of GBM. If an agent has shown promise in preclinical studies but is still at the lead optimization stage of drug discovery, the investigators should state how lead optimization will be accomplished within the first grant period.
• Published or preliminary data demonstrating success in discovery of one or more Development Candidates is necessary for NOFO responsiveness. Specifically, data demonstrating the following for new or repurposed agents are required: validation of the proposed target(s) for GBM; process of lead selection, including structure-activity relationship data if the agent is a small molecule; potent target activity (IC50 in primary assay); selectivity for tumor versus normal cells, and selectivity for the proposed target versus analogous targets; chemical solubility; exploratory PK, metabolism and toxicology; and in vivo testing in at least one model of GBM.
• Successful development of agents for GBM depends on the use of preclinical models that closely mimic human adult GBM including assessment of passage through the BBB and ideally allow for repeated assessment of tumors over the course of disease treatment.
• Availability of primary human GBM samples and PDX models is also important for efficacy testing in vitro and in vivo and, possibly, development of predictive biomarkers to guide pilot clinical studies. Applicants shall consider the NIH initiative to prioritize human-based research when proposing model systems.
• In the preclinical phases of the studies, inclusion of existing NCI resources is encouraged, when available and appropriate for the proposed study. These resources may include but are not limited to those in the NCI Developmental Therapeutics Program, the PDX Models Repository, the NCI Formulary, the DCTD Clinical Pharmacodynamic Biomarkers Program, and the Cancer Immune Monitoring and Analysis Centers (CIMACs). Applicants to this NOFO may include expertise from contract research laboratories or through public-private partnerships.

Steering Committee (SC): A Steering Committee (SC) will be formed during the first year of the GTN. Refer to Section VI.2 Cooperative Agreement Terms and Conditions for details.

Executive Committee (EC): An Executive Committee will be formed during the first year of the GTN. Refer to Section VI.2 Cooperative Agreement Terms and Conditions for details.

Responsiveness to this RFA

The following non-exhaustive list of examples, in support of a focused drug development effort with a near term trajectory to pilot clinical testing would be responsive to this RFA. Studies that:

• Investigate small molecules or biological agents that have not been tested in GBM clinical trials. Included are studies of agents at or beyond the lead optimization stage of drug development that:
• Address a target or process that is new to GBM.
• Target a challenging aspect of GBM biology such as infiltration into brain parenchyma or passage through the BBB.
• Address a known GBM target in a novel way (for example an allosteric inhibitor rather than one that inhibits an enzyme's active site or an alternate up- or downstream protein in a molecular pathway), are repurposed and approved for other indications and have shown strong preclinical data in GBM.
• Assess combination(s) of new agents with standard-of-care chemotherapy and/or radiation therapy.
• Assess combination(s) of new agents with non-standard-of-care treatments.
• Assess whether a single agent(s) and combinations reach their molecular target(s) at the concentration(s) required for adequate drug effect, in preclinical model(s) and/or proof-of-mechanism clinical studies.
• Investigate novel immunotherapies for GBM that are at advanced stages of pre-clinical development. Studies of immunosuppression, use of syngeneic or humanized animal models, and development of predictive and prognostic biomarkers of response and resistance are responsive.
• Investigate novel radiation therapy (RT) approaches and GBM radio-sensitizing agents that are at advanced stages of pre-clinical drug development.
• Investigate RT effects on BBB and the impact of barrier disruption on entry of the proposed novel agent across BBB.
• Employ existing GBM preclinical animal models with demonstrated relevance to human GBM. It is likely that projects will require a panel of in vivo models to reflect heterogeneity of tumor cells and the complex microenvironment of GBM.
• Use human pre- and post-surgical specimens for preclinical studies to assess proof-of-mechanism or resistance mechanisms.
• Further develop and test molecular and functional imaging capabilities in preclinical and clinical settings. As only a subset of GBM patients qualify for surgical resection, developing advanced functional imaging capabilities that could study drug effects non-invasively is a critical necessity.
• Leverage industry support, when possible, to expand the portfolio of drugs available for preclinical testing.

Non-responsive Applications

Applications considered to be non-responsive to this NOFO and not eligible for review include applications that:

• focus on cancers other than adult GBM or Astrocytoma IDH mutant grade 4.
• focus on the biology of GBM and its tumor microenvironment and not on the development of novel therapeutics for GBM.
• propose early drug discovery projects at a stage before the lead optimization stage.
• lack GBM-specific preclinical data on the candidate drug(s). 

IMPORTANT NOTE: Applicants uncertain whether their intended project meets the requirements of this NOFO are encouraged to send an email as listed in Section VII.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions - Includes all types

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

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)

Local 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)

Federal Governments

• 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 Organizations/International Collaborations

Non-domestic (non-U.S.) Entities (Foreign Organization) 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 not allowed. 

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply- 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• System for Award Management (SAM) – 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. Foreign organizations must obtain a NATO Commercial and Government Entity (NCAGE) Code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; all registrations must be in place by time of submission. 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 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. Obtaining an eRA Commons account can take up to 2 weeks.

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help. 

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. 

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 How to Apply - Application Guide.

Investigators can serve as a PI/multi-PI on only one GTN U19 application. However, investigators may have other roles (i.e., project leader, Core director) on multiple GTN U19s concurrently, even from more than one institution. Each lead institution is limited to one GTN U19 application.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2- Definitions of Terms.

3. Additional Information on Eligibility

Number of Applications

Only one application per institution (normally identified by having a unique entity identifier (UEI) number or NIH IPF number) is allowed

The NIH will not accept duplicate or highly overlapping applications under review at the same time per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. 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 NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this NOFO. See the administrative office for instructions if planning to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the Multi-Project (M) Instructions in the How to Apply - Application Guide, except where instructed in this notice of funding opportunity to do otherwise (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts) and where instructions in the How to Apply - Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Page Limitations

All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in How to Apply- Application Guide and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required
• Shared Resources Cores: one required
• Research Projects: two required

Overall Component

When preparing the application, use Component Type 'Overall'.

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions, as noted.

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

Follow standard instructions.

Research & Related Other Project Information (Overall)

Follow standard instructions.

In addition to standard items, describe existing facilities and/or other resources (such as existing institutional shared resource cores) available to the proposed U19.

As applicable and pertinent to the proposed research, describe partnerships (e.g., with industrial entities) that will provide relevant capabilities.

Project/Performance Site Locations (Overall)

Enter primary site only.

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

Research and Related Senior/Key Person Profile (Overall)

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

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

Budget (Overall)

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

A minimum total effort for each Overall PD/PI or MPI of the U19 is 2.4 person months (PM) in aggregate for all functions served on the U19; effort cannot be reduced below this level during the entire project period.

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

PHS 398 Research Plan (Overall)

All U19s must have the following structure:

• An Administrative Core with a Network Coordinating Subgroup
• Two Research Projects
• At least one Shared Research Core. A Shared Research Core may serve one or two projects.

Overall Specific Aims: List the aims of the proposed U19. Summarize the expected outcome(s) of the U19 as a whole, including the impact that the results of the proposed translational research will have on GBM treatment. Briefly, describe how the U19 is structured and how the components alone and together fit into the overall goals.

Overall Research Strategy: This section should summarize the structure and the overall research strategy for the multi-component, multi-institutional application. The overall concept of the U19 should be conveyed by describing how the development and testing of novel therapies for GBM will be approached. Summarize the special features in the environment and/or resources that make this U19 strong or unique to the overarching goals of the GTN. The Research Strategy should be organized into sections that address the following: Overall Significance; Overall Innovation; Overall Approach; Overall Investigators; and Overall Environment. Specifics of Research Projects and Cores should be described separately.

Overall Significance

• Describe why the proposed U19 is important in the context of the known challenges to treatment of GBM.
• Explain how successful development and testing of the novel therapeutic agent(s) proposed could change clinical treatment of GBM.

Overall Innovation

• Describe the therapeutic agent(s) and/or combinations that are new to the treatment of GBM. If similar agents and/or combinations have been tested in preclinical or clinical studies of GBM, explain how those in the U19 are novel, with increased likelihood to succeed.
• Summarize the novel theoretical concepts approaches/methodologies, instrumentation, or intervention(s) to be developed or used in the Research Projects and/or Shared Research Cores.
• Describe innovative approaches in proposed clinical trials that are likely to provide results that will move the study along the translational continuum.

Overall Approach

• Include an overview schematic of the structure of the U19 and the interactions and collaborations among the U19 components. Include outside resources (e.g., contracts, industry) that will provide resources or expertise, even if funding is not requested through the U19.
• Provide a narrative description of the overall structure that clearly outlines all resources and expertise to move the novel therapeutic agent(s) and/or combination(s) from drug development to preclinical testing and into Phase I clinical trials. Provide a rationale for the selection of Research Projects and Shared Resources Core(s).
• Describe plans and timelines for pilot clinical testing of proposed novel agent(s).
• Provide preliminary data that led to proposing the U19 application. Detailed preliminary studies sections should be included in the individual Research Projects and Shared Resources Cores. Cross-reference information when applicable.
• Explain how the proposed Research Projects and Shared Resources Core(s) will, together, address the overall goals of the U19.
• State the overall milestones of the U19 that are anticipated in the funding period. 

 Overall Investigators

• Succinctly describe specific expertise of the Overall PDs/PIs and Project Leaders that make them appropriate for their associated roles on the U19 team. For the Overall PD(s)/PI(s), describe prior experience leading multi-institutional, multi-disciplinary research endeavors.
• Describe the specific capabilities of the Network Coordinating Subgroup.
• Describe how this selected team has collaborated and published together in the past.
• Describe how the scientific, clinical and/or technical expertise of the U19 team is complementary and will strengthen the GTN.

Overall Environment

• Summarize the unique aspects of the participating organizations that are important to the success of the U19.
• Describe the clinical catchment areas that will be included in this U19. Applications must be multi-institutional and have clinical trial catchment areas that do not overlap.
• Describe how the scientific, clinical and/or technical resources of the U19 team will strengthen the GTN.

Renewal applications:

• Include a section that summarizes the Projects and Cores from the previous grant period and explains how progress made in the previous grant period supports proposed Projects and Cores in the renewal application.
• If Project(s) and Core(s) in this renewal application are extensions of or are closely related to those from the previous grant period, then detailed progress sections may be included in Research Project or Shared Resources Cores sections. 
• Summarize the major achievements of the overall U19 Center in the previous funding period including evidence of productive collaborations, and provide justification for adding new projects or cores, or for deleting components previously supported.

Letters of Support: Attach letters of support relevant to the Program as a whole (e.g., letters of institutional support). Letters of support relevant to specific Projects or Cores should be attached in the relevant Project or Core Research Plan forms.

Resource Sharing Plan:
Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Other Plan(s): 

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

• A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format. Where the DMS Plan Format Page requires a "Yes or No" response, no additional narrative is allowed. The Data Management and Sharing (DMS) Plan must be provided in the Overall component.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in How to Apply- Application Guide; any instructions provided here are in addition to the How to Apply - Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply - 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, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply - Application Guide must be followed.

Delayed Onset Study

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 How to Apply- Application Guide must be followed.

PHS Assignment Request Form (Overall)

All instructions in the How to Apply- Application Guide must be followed.

Administrative Core

When preparing your application, use Component Type 'Admin Core.'

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions, as noted. 

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Administrative Core)

Follow standard instructions.

Research & Related Other Project Information (Administrative Core)

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

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

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

Project /Performance Site Location(s) (Administrative Core)

List all performance sites that apply to the specific component.

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

Research & Related Senior/Key Person Profile (Administrative Core)

ASSIST will default to "Project Lead". If you would like to use a different category, then replace "Project Lead" below with a different Category (e.g., Core Lead).

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

Budget (Administrative Core)

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

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

At least one of the U19 overall PD/PI(s) is expected to serve as Core Lead of the Administrative Core with a minimum effort of 0.6 person months. If multiple PD/PIs serve as co-leads of the Administrative Core, each is expected to devote at least 0.6 person months. The minimum total effort for each PD/PI or MPI of the U19 is 2.4 person months in aggregate for all functions served on the U19. A Network Coordinating Subgroup (NCS) Administrator with a minimum of 0.6 person month effort must be designated as key personnel.

Restricted Funds for cross-GTN Projects

• Each U19 must have a special restricted Pilot Project Fund of $75,000 direct costs for supporting the U19's cross-GTN pilot projects. For years 1-5 of the U19, these funds must be allocated in the "Other Expenses" category on the Budget form as "Restricted Funds for Pilot Projects."   
• Approval of NCI staff is required for the release of restricted funds for proposed pilot projects.
• The funds to support approved pilot projects will be allocated to the U19 recipient institution.

Travel

Travel funds must be included in the proposed budget to support travel for at least one U19 PD/PI to participate in face-to-face Steering Committee Meetings, if appropriate.

Budgets and activities for the Network Coordinating Subgroup and the U19 Administrative Core should not overlap.

PHS 398 Research Plan (Administrative Core)

Specific Aims: Succinctly describe the specific objectives and goals of the Administrative Core.

Research Strategy: The following aspects should be addressed:

Leadership

• For U19 leadership, describe prior experience leading large research endeavors with complex budgets.
• Describe and/or diagram the chain of responsibility for decision-making and administration.
• Provide a succession plan which describes the process by which new leadership will be selected if the U19 PD(s)/PI(s) is no longer willing or able to lead the U19 Program.

Administrative management

• Describe the plans for the fiscal management, clerical support, manuscript preparation, and compliance to NIH public access policy (PMCID), and meeting organizations.
• Discuss how quality control in U19 Research Projects, Core(s), and associated institutions will be administered.
• Describe the plan for regulatory support, clinical protocol development, and clinical trial management.
• Indicate the relationship of the Administrative Core to the administrative structure of the applicant institution and partnering institutions.

Planning and evaluation

• Describe the function and intended areas of expertise of a required internal advisory board.
• Describe how progress of the U19 will be internally evaluated during the project period, how milestones will be assessed, and how decisions to initiate changes will be made.
• Address how the U19 team will handle potential problems and provide alternative strategies in case of milestone delay or failure.   

Integration of U19 components

• Explain how coordination and communication among the Research Projects, Shared Resources Core(s), and participating institutions will be achieved at the overall program level.

Interactions with other U19s

• Elaborate how yearly set-aside funds for cross-U19 collaborations [termed "Collaborative Pilot Projects (CPPs)] and collaborations with scientists outside the GTN will be administered by each U19's Administrative Core and coordinated by each NCS.
• Address how decisions on scientific scope and costs of collaborations will be made. Examples of pilot projects could include model sharing; high-risk, high-reward projects; assay development; and technology development.

Interaction with the Network Coordinating Subgroup (NCS)

• Explain how leadership of the U19 Administrative Core will support responsibilities of the Network Coordinating Subgroup

Renewal applications:

• Include a Progress Report that discusses the accomplishments of the Administrative Core during the current funding period, and the rationale for significant changes that may have occurred during the current funding period.

Network Coordinating Subgroup (NCS)

The Administrative Core of each U19 Center must include an NCS with responsibilities and leadership distinct from those of the U19 Center's Administrative Core. The overarching function of the Network Coordinating Subgroup (NCS) is to work with NCSs from other U19 Centers for harmonization of administrative, scientific and clinical activities. Although the responsibilities of each NCs will be shared with other NCSs, each NCS must explain their capabilities to perform the functions listed below. How these functions will be accomplished should be delineated in the Administrative Core section of the U19 application under a subheading "Network Coordinating Subgroup."

• Administrative coordination of GTN meetings including Steering Committee, Executive Committee, annual face-to-face meeting, and others as defined by the newly formed GTN.
• Leadership in developing standard operating procedures for GTN functions and data management.
• Coordination of collaborations between U19 Centers [termed "Collaborative Pilot Projects (CPPs)].
• Leadership in identifying and executing collaborations with scientists outside the GTN using restricted funds.
• Liaison between the GTN Coordinating Working Group and the U19's Administrative Core.
• Formation and maintenance of a GTN website that can be transferred to and administered by NCS Administrators across the GTN. The design of the GTN website should allow for public accessibility for the broadest audience including patients, advocacy groups, and the public. Initially, the website should include basic information about the GTN such as goals, Principal Investigator's contact information, and the scope of the U19s.  In the future, it is expected that the public facing GTN website will include GTN achievements (e.g., publications, clinical trials). The website should also feature a restricted access site for U19 grantees to serve as a location for sharing privileged and sensitive information, preliminary data, and information not ready for public release.

Upon funding, the Network Coordinating Subgroups from each U19 will meet to determine how they will jointly perform the functions listed above as a "GTN Coordinating Working Group (GTN CWG)," for example periodicity of meetings, delineation of certain responsibilities to different NCSs.

Administrative Core Letters of Support: Provide letters of support from the Institution(s) and members of the Internal Advisory Board.

• Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide, with the following modification:

Other Plan(s):

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions: 

• Do not include a Data Management and Sharing (DMS) Plan within this Component. If a DMS Plan is required for this NOFO, it must be included within the Overall Component. 

Sharing of genomic data should be consistent with respective NIH and NCI policies (see https://datascience.cancer.gov/data-sharing/genomic-data-sharing).

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the How to Apply- Application Guide; any instructions provided here are in addition to those in the How to Apply- Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Administrative Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions:

If you answered "Yes" to the question "Are Human Subjects Involved?" on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply- Application Guide must be followed.

Delayed Onset Study

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 How to Apply- Application Guide must be followed.

Shared Resources Core(s)

When preparing your application, use Component Type 'Core.'

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

SF424 (R&R) Cover (Shared Resources Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Shared Resources Core(s))

Follow standard instructions.

Research & Related Other Project Information (Shared Resources Core(s))

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

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

Project Narrative: Complete. 'Project Narrative' should be added to the Shared Resources Core(s). 

Project /Performance Site Location(s) (Shared Resources Core(s))

List all performance sites that apply to the specific component.

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

Research & Related Senior/Key Person Profile (Shared Resources Core(s))

In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Core Lead' and provide a valid eRA Commons ID in the Credential field.

• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Shared Resources Core(s))

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

Budgets are also required for each consortium (subcontract) if they are part of any Core.

Core Lead (s) must commit to a minimum of 0.6 PM of effort.

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

PHS 398 Research Plan (Shared Resources Core(s))

Specific Aims: List in priority order, the broad activities and services of the proposed Core. In addition, state each Core's relationship to the U19's goals and how the Core(s) relates to one or two of the Research Projects in the application.

Research Strategy: Shared Services Cores may be proposed as distinct components that support non-hypothesis-driven research activities for one or two of the Research Projects of the U19. Shared Resources Cores may include but are not limited to Clinical, Biospecimen, Biostatistics/Informatics, Medicinal Chemistry, Preclinical Drug Development, or Animal Studies Cores.

• Describe the facilities and/or services that will be provided, how the facilities and/services will meet the specific needs of each project, a prioritization plan for providing the services, and plans for quality control. State the rationale for centralizing activities in a Core rather than including them in individual projects.
• Indicate why the Shared Resources Core is an essential part of the U19, and how the proposed services will facilitate accomplishment of the proposed goals and milestones of the U19.
• If the Core is at a different geographic location than the Research Projects it serves, describe plans for data/sample transfer and communication.
• Describe the role(s) of the Core Lead and key participants, and do not duplicate information provided in the Biosketches or the Budget Justification.
• Shared Resources Cores should not duplicate resources already available at the institution. If the Core augments an existing shared resource supported by an NCI Cancer Center Support Grant (P30), describe how this Core augments or complements the existing resource. The activities of Shared Services Cores must not overlap with each other or with the activities of a Research Project.

Renewal applications:

• If Core(s) in the renewal application are extensions of or are closely related to those from the previous grant period, then a progress section should be included.

Letters of Support: Provide letters of support from collaborators detailing nature and extent of participation.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide, with the following modification:

Other Plan(s):

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions: 

• Do not include a Data Management and Sharing (DMS) Plan within this Component. If a DMS Plan is required for this NOFO, it must be included within the Overall Component. 

Sharing of genomic data should be consistent with respective NIH and NCI policies.

Appendix: Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.   

PHS Human Subjects and Clinical Trials Information (Shared Resources Core(s))

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions:

If you answered "Yes" to the question "Are Human Subjects Involved?" on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply- Application Guide must be followed.

Delayed Onset Study

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 How to Apply- Application Guide must be followed.

Research Projects

When preparing your application, use Component Type 'Project.'

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

SF424 (R&R) Cover (Research Projects)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Research Projects)

Follow standard instructions.

Research & Related Other Project Information (Research Projects)

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

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

Project Narrative: Complete. 'Project Narrative' should be added to Projects. 

Project /Performance Site Location(s) (Research Projects)

List all performance sites that apply to the specific component.

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

Research & Related Senior/Key Person Profile (Research Projects)

ASSIST will default to "Project Lead". In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Project Co-Lead' and provide a valid eRA Commons ID in the Credential field.

• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.   

Budget (Research Projects)

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

Each Research Project must be led by a minimum of two co-leaders: one laboratory scientist and one clinical researcher. Each Project Leader should devote effort of at least 0.9 person months per Research Project. 

If the Research Project involves a clinical trial, the applicant is responsible for including the costs of all support for statistical design, data collection, analysis and management, data deposition into NCI or other portals and ClinicalTrials.gov, as well as costs for clinical site monitoring, project management and quality assurance. If clinical trial costs will be covered by sources other than the U19, applicants should indicate the source of funds and provide letters of support. Alternatively, these costs can be incorporated into the budget of relevant Shared Resource Cores. Specific cross-references should be made to clarify how these necessary functions will be supported.

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

PHS 398 Research Plan (Research Projects)

A U19 Research Project may focus on preclinical research and/or clinical trial(s).  Projects may include hypothesis-driven, hypothesis-generating and/or milestone-driven Aims. Aspects of the research that are covered by Shared Resources Cores should be clearly cross-referenced in the Research Plan.

Specific Aims: List the Aims of the proposed Research Project. Concisely describe the hypothesis or hypotheses to be tested and/or milestones to be achieved. A timeline of specific tasks over the project period is encouraged. In addition, state the individual Research Project's relationship to the U19's overall goals and milestones and how it relates to other Research Projects or Cores.

Research Strategy:   

Significance

• Explain the critical barrier(s) to GBM treatment that the proposed Research Project addresses, and how the GBM research field and clinical care will be changed if the proposed aims are achieved.
• Describe the scientific premise for the proposed Project, including consideration of the strengths and weaknesses of published research or preliminary data crucial to the support of the Project.
• Discuss how the proposed project relates to therapeutic development efforts underway in academia and industry.
• For Projects focused on agent drug development, explain the importance of the target, the novel agent and/or the therapeutic combination for improved treatment of GBM.
• Explain how the proposed Project, if successful, will improve scientific knowledge, technical capability, and/or clinical practice in GBM.

Innovation

• Explain how the Project challenges and seeks to shift current translational research or clinical practice paradigms.
• Describe the novelty of the proposed therapeutic agent(s) and/or combination(s) for treatment of GBM. If similar agent(s) or combinations were previously tested in GBM, provide a rationale for pursuing the agents and/or combinations proposed in the U19.
• Describe any novel theoretical concepts, approaches or methodologies, instrumentation or intervention(s) to be developed or used, and any advantage over existing methodologies, instrumentation or intervention(s).

Approach

• Describe the overall strategy, methodology, and analyses to be used to accomplish the specific aims of the project. Include how the data will be collected, analyzed, and interpreted. Emphasize how the proposed experimental design and methods will achieve robust and unbiased results.
• Describe how each of the institutions in the U19 will contribute to the approaches taken in the research projects.
• Discuss potential problems, alternative strategies, benchmarks, and milestones to achieve the stated specific aims and the overall aim of testing in clinical trials in the 5-year grant period. If support from a biotechnology company or large pharma company is planned, provide letters of support describing planned resources and the timeline for providing them.
• Discuss plans for collaborations with other Research Project(s) in the U19, Shared Research Cores, contractors, and/or industry.

Progress Reports for Renewal Projects:

• If Project(s) in this renewal application are extensions of or are closely related to those from the previous grant period, then a progress section should be included in this "Research Project" section.
• The Progress Report should discuss the accomplishments of the Project during the previous funding period, and the rationale for continuation.
• Progress for Projects from the previous grant period that will not be continued should be included in the Overall Section.
• Do not include a progress section for new Projects.

Non-clinical Research:

Development Candidates, i.e., drug-like small molecules or biological therapeutics at or beyond the "preclinical development" or "animal testing" stages, are preferred for this NOFO. Applicants may refer here for descriptions of drug discovery and development stages.

• For Projects pursuing agents that have not completed activities of the "lead optimization" stage, describe how an optimal Development Candidate will be identified within one year of the start of the U19.
• For all proposed Development Candidates (novel or repurposed agents), provide published or preliminary data demonstrating  validation of the target/pathway addressed by the agent(s) for GBM pathogenesis; the process of Development Candidate selection: e.g., structure-activity relationship (SAR) data and chemical structure (small molecules only); exploratory PK, metabolism and toxicology; in vivo testing in at least one model of GBM; and for small molecules only: potency, selectivity (vs. normal cells and analogous targets), solubility.
• For biologics only, describe: qualification of assays for identity, purity, potency; genetic optimization; and production of adequate material to support product characterization and animal efficacy studies from a single batch or from batches shown to be equivalent.
• In addition, for biologics, provide data or plans for the following as appropriate for the type of agent: generation of master cell and/or virus banks; generation of reference standard material; accelerated stability studies; range finding studies; and tissue cross-reactivity studies.
• For all proposed Development Candidates (novel or repurposed agents), provide preliminary data and/or a plan to address  scale-up and formulation; PK, particularly penetration of the BBB; ADME and GLP toxicology (testing of effects on cognition is encouraged); efficacy studies with agent delivered by the clinically intended route; a feasible path to the clinic; and generation and filing of the IND.
• If preclinical model(s) are included, present the rationale for the models that are chosen, and the relevance of the proposed model(s) to human adult GBM. For animal models, address methods for measuring adequate delivery through the blood-brain-barrier. Describe how the design of the animal studies may lead to design of clinical studies in human adult GBM. Applicants must not propose extensive model development.
• Describe how potential chemical, biological, or drug development pitfalls will be addressed, and effects of these obstacles on timely achievement of U19 milestones.

Clinical Trials:

Provide a clinical study synopsis keeping the relevant review criteria in mind, but do not duplicate information in the required clinical trial documents (e.g., PHS Human Subjects and Clinical Trials Information Form or IRB-approved clinical trial protocol):

• Describe the role(s) of the U19 institutions in the proposed clinical trial(s).
• Describe the scientific rationale/premise of the study(s) that is/are based on previously well-designed preclinical and/or clinical research.
• Describe the planned analyses, PK and PD assessments and statistical approach for the proposed study design.
• Demonstrate that the eligible population of patients is available within the institutions for study.
• Address potential ethical issues.
• Describe how the recruitment timelines are feasible for adequate accrual.
• Address the differences, if applicable, in the intervention effect due to sex/gender and race/ethnicity.
• Describe the plans to standardize, assure quality of, and monitor adherence to, the clinical protocol and data collection or distribution guidelines.
• Describe the plan to obtain required study agent(s), if not within one or more of the applicant institutions.
• Describe how existing available resources, as applicable, will be used.
• Describe the procedures for data management and quality control of data at clinical site(s) or at U19 laboratories, as applicable.
• Describe the methods for standardization of procedures for data management to assess the effect of the intervention and quality control.
• Describe the plan to complete data analysis within the proposed period of the award.
• Include information on preliminary studies, data, and/or experience of the co-leaders of the Project that are pertinent to the Project.

Letters of Support: Provide letters of support from collaborators detailing nature and extent of participation including letters for functions not supported by the U19 budget. If support from a biotechnology company or large pharma company is planned, provide letters of support describing planned resources and the timeline for providing them.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide, with the following modification:

Other Plan(s):

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions: 

• Do not include a Data Management and Sharing (DMS) Plan within this Component. If a DMS Plan is required for this NOFO, it must be included within the Overall Component. 

Sharing of genomic data should be consistent with respective NIH and NCI policies (see https://datascience.cancer.gov/data-sharing/genomic-data-sharing).

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

• Draft or IRB approved protocols can be attached to the appendix.

PHS Human Subjects and Clinical Trials Information (Research Projects)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions:

If you answered "Yes" to the question "Are Human Subjects Involved?" on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply- Application Guide must be followed.

Delayed Onset Study

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 How to Apply- Application Guide must be followed.

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

See Part 2. 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. contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH's electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply- 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 Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.

For information on how applications will be automatically assembled for review and funding consideration after submission, refer to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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

For assistance with your electronic application or for more information on the electronic submission process, visit 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) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization's profile in the eRA Commons and for the System for Award Management. Additional information may be found in How to Apply - 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. 

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov.

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. Applications submitted to 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 for the entire GTN U19 application. In addition, reviewers will also provide individual "criterion scores" for the Overall application. The Administrative Core and Shared Resource Core will be evaluated, but each will receive only one overall numerical rating. For Research Projects, reviewers will consider each of the review criteria listed under the "Scored Review Criteria - Research Projects" in determining the scientific merit and give a separate score for each. Reviewers will be assigned to evaluate the entire application.

For the evaluation of the U19 application, the Research Projects will be assessed as the scientific basis of each with additional components enhancing and integrating the overall research program. The overall Impact Score will reflect the synergy and integration provided by inclusion of each component. 

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

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?

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

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 NOFO: How well experienced are the Overall PD(s)/PI(s) in leading multi-institutional, multi-disciplinary research program(s) that may predict success of the U19?

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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?

Specific to this NOFO: How well does the application propose to test therapeutic agent(s), repurposed drugs, and/or drug combinations that are new to the treatment of GBM? If similar agent(s) or combinations were previously tested in GBM, how clear is the rationale for pursuing the agents and/or combinations proposed in the U19? 

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

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, 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?

Specific to this NOFO: How adequate is the approach of the U19 to move the novel therapeutic agent(s) and/or combination(s) from drug development to preclinical testing and into Phase I clinical trials? How likely is it that the U19 will, as an integrated effort, achieve the stated Overall Aims and meet proposed milestones? 

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, sex, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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?

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Additional Review Criteria - Overall

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.

Study Timeline

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

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 Human Subjects Policies

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for inclusion. 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 three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the American Veterinary Medicine Association (AVMA) Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals 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

For Resubmissions (as applicable), the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

For Renewals (as applicable), the committee will consider the progress made in the last funding period.

Revisions

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

Additional Review Considerations - Overall

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 Resource Sharing Plan(s) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

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.

Review Criteria for Administrative Core

Reviewers will assign one numerical score based on the following criteria (these criteria do not receive separate scores).

Leadership

Assess the scientific qualifications, involvement, leadership and time commitment of the Leader(s) and other key personnel sufficient for the requirements of the proposed Administrative Core.

Administrative Management

1. Evaluate the following:

• How well the plan for the Administrative Core addresses administrative management including fiscal and data operations and total integration of the U19.
• Whether the administrative and organizational structure is clearly defined and appropriate to support the U19.
• Whether there is an adequate succession plan for U19 leadership.
• The sufficiency of the conflict management plan.

Planning and evaluation

• Assess the proposed functions and intended areas of expertise of a required internal advisory board.
• Comment on plans for internal project evaluations during the project period, for milestone assessments, and for decisions to initiate changes.
• Evaluate whether the Administrative Core's plans to handle potential problems and provide alternative strategies in case of milestone delay or failure are reasonable.

Integration of U19 components

Evaluate whether the Administrative Core will adequately facilitate communication and integration across all Projects and Shared Resources Cores.

Network Coordinating Subgroup

Evaluate the following:

• The statement of commitment to work in partnership with NCSs from other U19 Centers to flexibly manage the necessary network-wide functions of the GTN.
• Whether the NCS Leader(s) and other personnel are experienced in managing translational research and coordinating collaborative basic or clinical research in the setting of a multi-component grant.
• Whether expertise of the NCS includes bioinformatics, biostatistics, and data management relevant to the support of GBM research and clinical trials.
• The feasibility of plans for the NCS, in partnership with NCSs from other U19 Centers, to:
  • Administer GTN meetings including Steering Committee, Executive Committee, annual face-to-face meeting, and others as defined by the newly formed GTN.
  • Develop standard operating procedures for GTN functions and data management
  • Coordinate collaborations between U19 Centers [termed "Collaborative Pilot Projects (CPPs)], and provide leadership in identifying and executing collaborations with scientists outside the GTN using restricted funds.
  • Design and maintain a GTN website.

Review Criteria for Shared Resources Core(s)

Reviewers will assign one numerical score based on the following criteria (these criteria do not receive separate scores).

Investigators

Assess the qualifications, experience, and commitment of the Shared Resources Core Director(s) and other key personnel to provide the proposed facilities or services.

Approach

Assess the following:

• Integration of the Core with Projects to meet Project objectives
• Quality of Core services including quality control processes
• The plan for prioritization of Shared Resources Core products and/or services
• The plan for data and/or sample transfer and communication if the Core is in a different geographic location.
• Plans to augment and/or complement resources supported by an NCI cancer Center Support grant (P30), if applicable.

Environment

Evaluate whether the Shared Resources Core is appropriate to support the program as proposed.

Scored Review Criteria - Research Projects

Overall Impact - Research Projects

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

Scored Review Criteria for Research Projects

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

Significance

Does the Research 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 Research 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 NOFO: In projects including preclinical models, assess whether the models are supported by rigorous published and/or preliminary data that substantiates their relevance to treatment of GBM.

Investigators

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Research 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 NOFO:

• Evaluate the plan for co-leadership of the project by basic and applied/clinical investigators in the conception, design, and proposed implementation of the project.

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?   

Specific to this NOFO: If similar agent(s) or combinations were previously tested in GBM, evaluate the rationale for how the proposed agents and/or combinations are new to GBM.

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Research Project? Have 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 Research 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?

Specific to this NOFO:

For Projects proposing non-clinical research:

If the Development Candidate has not yet been selected (i.e., activities in the "lead optimization" stage are in progress), assess the feasibility of identifying a Development Candidate within a year.

Evaluate assays, advancement criteria and/or data presented that for the stage(s) of drug development, toward the goal of IND filing and transition to the clinic, considering:

• Strength of plans for scale-up, formulation, pharmacokinetics (including penetration of the blood-brain barrier), ADME, GLP toxicology, and efficacy by the clinically intended route
• If preclinical model(s) is/are included, assess the relevance of the proposed model(s) to human adult GBM.

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?

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by CSR, in accordance with NIH peer review policies and practices, 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.

Requests for reconsideration of initial peer review will not be accepted for applications submitted in response to this NOFO.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. 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.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant's federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov.  NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant's integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 "Federal awarding agency review of risk posed by applicants."  This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access their 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 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient's business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain "applicable clinical trials" on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient organizations must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

Prior Approval of Pilot Projects

Recipient-selected projects that involve clinical trials or studies involving greater than minimal risk to human subjects require prior approval by NIH prior to initiation.

• The recipient institution will comply with the NIH Guidance on Changes That Involve Human Subjects in Active Awards and That Will Require Prior NIH Approval.
• The recipient institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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, Recipients, and Activities.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

By applying for or accepting federal funds from HHS, recipients certify compliance with all federal antidiscrimination laws and these requirements and that complying with those laws is a material condition of receiving federal funding streams. Recipients are responsible for ensuring subrecipients, contractors, and partners also comply.

Applicants and recipients are strongly encouraged to refer to the NIH Director's Statement of Priorities, entitled "Advancing NIH's Mission Through a Unified Strategy." 

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations. Pursuant to 2 CFR 200.340, by accepting an NIH award, the recipient agrees that continued funding for the award is contingent upon the availability of appropriated funds, recipient satisfactory performance, compliance with the Terms and Conditions of the award, and may also otherwise be terminated, to the extent authorized by law, if the agency determines that the award no longer effectuates the program goals or agency priorities, in line with 2 CFR 200.340(a)(4).

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

• ongoing and consistent access to HHS owned or operated information or operational technology systems; and
• receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Cybersecurity plans and procedures must at minimum include the following:

• Develop cybersecurity plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data:
  • Identify:
    • Develop an inventory of all assets and accounts with access to HHS owned and operated information or operational technology systems or which obtain PII or PHI for the purposes of the award.
  • Protect:
    • Limit access to HHS owned and operated systems to only those in need of access to complete reward activities.
    • Require all staff to complete annual cybersecurity and privacy awareness training. Visit 405(d): Knowledge on Demand (hhs.gov) to obtain free trainings, if needed.
    • Enable multifactor authentication for all employees, subrecipients, and third-party entities to access HHS owned and operated information or operational technology systems.
    • Regularly backup sensitive data and test backups.
  • Detect:
    • Install anti-virus or anti-malware software on all devices, servers, and accounts used to connect to HHS owned and operated systems.
  • Respond:
    • Develop an incident response plan. See Incident-Response-Plan-Basics_508c.pdf (cisa.gov) to learn about developing incident response plans.
    • Have cybersecurity incident reporting procedures that ensure the relevant HHS awarding agencies are notified of a cybersecurity incident within 48 hours of discovery. A cybersecurity incident is defined as an unplanned interruption to a technology service or reduction in the quality of a technology service, or an occurrence that actually or potentially jeopardizes the confidentiality, integrity, or availability of an information system or the information the system processes, stores, or transmits.
  • Recover:
    • Investigate incidents and plug any security gaps identified. 

All activities proposed in your application and budget narrative must align with applicable law, including but not limited to statutes, executive orders, federal regulations and applicable judicial holdings.  Accordingly, discretionary awards shall not be used to fund, promote, encourage, subsidize, or facilitate; racial preferences or other forms of racial discrimination by the recipient, including activities where race or intentional proxies for race will be used as a selection criterion for employment or program participation; denial by the recipient of the sex binary in humans, or the belief that sex is a chosen or mutable characteristic; illegal immigration; or any other initiatives that compromise public safety.  If an application does not align, the application will not receive funding to the extent permitted by law and applicable court orders.

For applications involving substance abuse, the application must not support harm reduction. Please see Updated Funding Guidance for Recipients on Supplies and Services.

For applications involving funding Medication-Assisted Treatment (MAT) or medications for opioid use disorder (MOUD), this funding should be used to provide comprehensive treatment and recovery support services rather than medication-only models for opioid use disorder. Services should include medications, where clinically indicated, in conjunction with psychosocial and other treatment and recovery support services. Funding can also be used to support individualized tapering and discontinuation of medications when clinically indicated. Please see Updated Funding Guidance for Recipients on  MAT/MOUD.

As of October 1, 2025, HHS has adopted 2 CFR Part 200, with some modifications included in 2 CFR Part 300. These regulations replace those in 45 CFR Part 75. However, for NIH, under the Consolidated Appropriations Act for FY 2026, (P.L. 119-75, Division B, Title II, Sec. 224), the provisions relating to indirect costs in 45 CFR 75 continue to apply to NIH awards. Consistent with the statute, NIH will not apply updated thresholds outlined within 2 CFR Part 200, at this time.

In administering programs under this and all funding announcements, NIH prioritizes: 

• Research involving rigorous scientific methods, including for studies related to children and adolescents, where NIH is committed to approaches that reflect the highest standards of clinical care and child safety. 
• Biological and physiological integrity: Recognizing the relevance of biological sex to health outcomes, NIH encourages applicants to account for sex-based health factors in program design, data collection, and service delivery where scientifically appropriate.
• NIH will implement these priorities consistent with applicable laws, regulations, court orders, and all required administrative procedures. Applicants are encouraged to describe how their proposed programs align with these priorities in their project narratives. Funded activities must advance NIH's vision of protecting and improving the health and well-being of Americans. The particular focus is on those who are medically vulnerable, or live in areas with limited access to care. NIH's duty is to serve wisely, effectively, and with measurable results that justify every taxpayer dollar invested. 

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 2 CFR Part 200, 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 recipients 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 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

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

 The PD(s)/PI(s) will have primary authority and responsibility to define objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of studies conducted under this program. The PD(s)/PI(s) assume responsibility and accountability to the applicant organization officials and to the NCI for the performance and proper conduct of the research supported by the U19 award. Specific responsibilities and rights include:

• Developing novel drugs and/or combinations for testing in clinical trials.
• Working with the Network Coordinating Subgroups (NCSs) to collaborate with other U19 teams to conduct clinical trials with appropriate target enrollment; and to share data, models, specimens, and agents.
• Participation in Executive Committee or other GTN meetings, working groups, and/or teleconferences as needed.
• Implementation of the data sharing plan; Institutions/organizations participating in the GTN will be expected to share knowledge, data, research materials, and any other resources necessary and relevant to the GTN.
• Serving as a voting member of the GTN Steering Committee.
• Adhering to the Steering Committee and GTN Coordinating Working Group recommendations and policies (to the extent consistent with applicable grants regulation) to ensure that the preclinical and clinical goals of the network are accomplished.

In addition, GTN Coordinating Working Group (the "GTN CWG," i.e. the combined Network Coordinating Subgroups from each U19) will have responsibility for:

• Planning of the GTN CWG operating structure and activities within a month after U19 funding.
• Administrative management of the GTN CWG.
• High quality, timely execution of all GTN CWG services to the GTN.
• Assisting in establishing Standard Operating Procedures together with the Steering Committee.
• Communicating with the NCI-designated government representatives; and
• Ensuring that the tools developed within the each U19 under this NOFO are freely available to all GTN members.
• Recipients 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 HHS, PHS, and NIH policies.

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

Designated NCI Program Staff member(s), acting as Project Scientist(s), will participate in the following activities:

• Assisting in avoiding unwarranted duplications of effort across the GTN.
• Helping to coordinate collaborative research efforts that involve multiple U19 recipients.
• Aiding in directing U19 recipients to NCI resources which may be helpful to the goals of the U19.
• Monitoring the operations of the U19s and making recommendations on overall project activities.
• Reviewing the progress of individual U19s and making recommendations on overall project strategies.
• Participating in establishing Standard Operating Procedures, with the Steering Committee.
• Participating in the development and evaluation of cross-U19 activities; and
• Assisting the GTN recipients 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).

Additionally, an agency program official or IC program director 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:

Steering Committee (SC)

A Steering Committee (SC) will be the governing body of the GTN and will be formed during the first year of the GTN. The SC will be responsible for establishing criteria required to move an agent into clinical trials. They will serve as advisors on the readiness of GBM therapeutic candidates from the GTN, from Associate Members of the GTN, or from other NIH programs (such as NExT) to enter clinical studies. The SC will serve as a hub for a broader outreach to the entire extramural research community investigating GBM. 

The Steering Committee will be composed of the following members:

• One representative (an Overall PD/PI or a designated U19 senior investigator) from each U19 award;
• One representative from each NCS.
• NCI Project Scientist(s). The NCI Project Scientist will have voting membership on the Steering Committee, and as appropriate, its subcommittees. The NCI Project Scientist's vote will represent NIH, as all NIH staff members will share one vote in support of the project.
• Additional members of the SC may include other NCI extramural staff; GBM investigators from the NCI intramural program; NCI SPORE or other NIH grant recipients  not part of the GTN; radiation oncologists with GBM expertise; and industrial partners. Decisions on administration and leadership of the Steering Committee will be made at the initial meeting.

The Chair of the Steering Committee will be selected by a vote of the Steering Committee. The NCI Project Scientist(s) or other NIH staff may not serve as Chairperson.

The Steering Committee will meet as needed by videoconference, teleconference, or in person (if warranted). The Steering Committee Chair will be responsible for scheduling SC meetings, in coordination with NCI Project Scientists and the GTN Coordinating Working Group.

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

Executive Committee (EC): EC members include GTN PIs, a representative from each NCS, and NCI staff. The EC is responsible for making operational decisions, including those regarding internal and external collaborations. The EC will also participate in the discussion on approval of collaborative pilot projects.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: 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 recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

3. Data Management and Sharing

A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format. Where the DMS Plan Format Page requires a "Yes or No" response, no additional narrative is allowed. The Data Management and Sharing (DMS) Plan must be provided in the Overall component.

• When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

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 Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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.

Grants.gov Support Center - Questions regarding Grants.gov registration and services (e.g., Workspace, subscriptions).

NCI GTN Program
National Cancer Institute (NCI)
Telephone: 240-276-5922 Email: GTN-contacts@nih.gov 

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date)

Office of Grants Administration
National Cancer Institute (NCI)
Telephone: 240-276-6291 Email: NCIFinancialContact@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.

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 2 CFR Part 200.