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.

IMPORTANT: Per NOT-OD-24-086 updated application forms (FORMS-I) will be used for this opportunity. The updated forms are not yet available and will be posted 30 calendar days or more prior to the first application due date. Once posted, you will be able to access the forms using one of the following submission options:

1. NIH ASSIST
2. An institutional system-to-system (S2S) solution
3. Grants.gov Workspace

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

This is a limited competition Notice of Funding Opportunity Announcement (NOFO) and only the current award recipients under RFA-CA-17-057 are eligible to submit applications in response to this NOFO. This NOFO is one of six NOFOs that support the comprehensive effort by the National Cancer Institute (NCI) to provide the infrastructure for the conduct of national clinical trials through the National Clinical Trials Network (NCTN). The primary goal of the NCTN is the conduct of multi-center, late-phase, clinical treatment trials (i.e., randomized phase 2 and phase 3 trials) and advanced imaging trials across a broad range of cancers, modalities, and diverse patient populations as part of the NCI's overall clinical research program for adults, adolescents and young adults, and children with cancer. The NCTN also conducts, as necessary, preliminary studies needed for development of definitive trials, especially umbrella/basket trials and rare tumor trials, when an extensive, national patient catchment area is required.

The NCTN Program supports the following clinical trials infrastructure components through individual awards made under the respective NOFOs indicated below:

NCTN - Network Group Operations Centers under RFA-CA-24-030 (U10)

NCTN - Network Group Statistics and Data Management Centers under RFA-CA-24-031 (U10) - this NOFO

NCTN - Canadian Collaborating Clinical Trials Network under RFA-CA-24-032 (U10)

NCTN - Network Lead Academic Participating Sites under RFA-CA-24-033 (UG1)

NCTN - Network Radiotherapy & Imaging Core Services Center under RFA-CA-24-034 (U24

NCTN - Network Group Integrated Translational Science Centers under RFA-CA-24-035 (UG1)

Through this Notice of Funding Opportunity (NOFO), the National Cancer Institute (NCI) solicits applications from institutions/organizations that propose to maintain Network Group Statistics and Data Management Centers for the NCI National Clinical Trials Network (NCTN). The NCTN Network Group Statistics and Data Management Centers will provide statistical expertise for effective scientific design, conduct, and data management of clinical trials led by the associated NCTN Network Group Operations Center.

Background

The NCI National Clinical Trials Network (NCTN) was established for the conduct of large-scale, national, oncology treatment and advanced imaging clinical trials in an era of precision medicine.

Recent advances in deciphering the cancer genome, along with the emergence of successful targeted agents, immunotherapies, and cellular therapies, have fundamentally changed our approach to cancer treatment and have introduced new challenges to performing clinical trials. Due to the low incidence of certain molecular abnormalities, the development of targeted therapies often requires an infrastructure for the conduct of clinical trials that can screen large numbers of patients with the same or different cancer type to identify those patients whose tumors contain the distinct molecular targets of the therapies being tested. Immunotherapeutic approaches also present a similar challenge in that not all tumor types respond to this approach, and selecting the cancer types most likely to respond is critical for success.

The NCTN's integrated and collaborative network infrastructure has allowed the Program to meet the challenges of evaluating emerging therapies within its broad investigator base drawn from NCI-designated Cancer Centers, the NCI Community Oncology Research Program (NCORP), Minority/Underserved NCORPs, and other academic and community hospitals and private practitioners across the U.S. and internationally. The primary focus of the NCTN is the conduct of multi-center, late-phase, clinical treatment trials (i.e., randomized phase 2 and phase 3 trials) and investigation of new advanced imaging techniques; however, appropriate preliminary studies needed for development of potential definitive trials, especially umbrella/basket trials and rare tumor trials oriented to discovery, are also conducted when an extensive, national patient catchment area is required. With its state-of-the-art clinical trials infrastructure, the NCTN can implement and completes trials rapidly. The NCTN has streamlined trial registration, data management, and tumor banking processes. It has a Cancer Trials Support Unit (CTSU) to provide online access to all necessary study materials and a Central Institutional Review Board (CIRB) to make ethics review easier and less redundant across the country. The NCTN also has appeal for industry partners such as biotechnology and pharmaceutical companies that collaborate on NCTN trials, including precision medicine trials harnessing next generation DNA and RNA sequencing methods to inform treatment choices. NCTN's resources are ideal for screening large numbers of patients to identify patients whose tumors exhibit the molecular features that may be responsive to new, targeted treatments and/or immunotherapy approaches. In addition, biospecimens collected from patients on NCTN trials are available to help determine the underlying biological reasons for response and resistance to therapy.

The NCTN also promotes the evaluation of multi-modality treatments, including surgery and radiotherapy in combination with novel agents, and has a commitment to the conduct of trials in special populations (e.g., children, adolescents, young adults, and underserved populations) as well as in rare tumor types. This focus allows the NCTN Program to complement, rather than duplicate, research conducted by the private sector. Annual accrual to NCTN trials has remained in the 17,500 to 22,000 patient range in mostly large phase 2 and phase 3 trials, but with a larger number of patients screened on study to determine whether they might benefit from the therapy under evaluation.

Each of the key components of the NCTN Program is described briefly below.

• Network Group Operations Centers: The Operations Centers provide scientific leadership for developing and implementing multi-disciplinary, multi-institutional trials in a range of diseases and special populations with specific scientific strategy and goals. The Operations Centers' scientific goals may include strategic innovation in advanced technology for specific research areas (e.g., advanced imaging methods/agents, radiotherapy) and the testing of innovative concepts and tools in prospective, multi-institutional clinical trials. Operations Centers are responsible for trial operations including timely protocol development and management, compliance with the Food and Drug Administration (FDA) and the Office for Human Research Protections (OHRP) regulatory and patient protection requirements, audits, training, quality assurance, and site support. The Operations Centers are expected to be closely integrated with their corresponding Statistics and Data Management Center in all aspects of trial operations through jointly developed policies and procedures for clinical trial development and conduct. The Operations Centers are also responsible for Network Group administration, including financial management, monitoring of member institution/site performance, coordination of biospecimen collection from patients on clinical trials, and adherence to all applicable NIH/NCI policies and regulations. Network Group Operations Centers may also provide trial operations for NCI Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment and Diagnosis (NCI/DCTD, approved, multi-center phase 2 and phase 3 trials originating outside the Network Groups in special situations.
• Network Group Statistics and Data Management Centers: These Centers are responsible for providing the statistical expertise required to ensure effective scientific design and conduct of clinical trials as well as leadership in innovation in statistical methodology. These Centers are also responsible for data management, data analysis, and statistical analysis for NCTN trials led by their affiliated Network Group Operations Center as well as for translational and other ancillary studies associated with the trials.
• Network Group Integrated Translational Science Centers - These awards provide support for leadership and expertise to facilitate incorporating translational science into Network Group clinical trials.
• Network Lead Academic Participating Sites: These academic institutions/sites provide scientific leadership in development and conduct of clinical trials in association with one or more adult U.S. Network Groups as well as substantial accrual to clinical trials conducted across the entire NCTN.
• Network Radiotherapy and Imaging Core Services Center: This institution/organization provides scientific and technical expertise for incorporation of appropriate, integrated quality assurance/control and image data management for applicable clinical trials conducted by the NCTN that require specialized quality assurance/control or imaging data management and/or assessment for radiotherapy and imaging interventions. In addition, the Center may also provide similar services for other approved NCI-supported clinical trials network programs (e.g., NCI/DCTD/CTEP early phase clinical trial network program and the NCI Division of Cancer Prevention (NCI/DCP) NCI Community Oncology Research Program (NCORP).
• Canadian Collaborating Clinical Trials Network: This Canadian organization is a non-profit clinical trials organization capable of being a full partner with the U.S. Network in the conduct of large-scale, multi-site clinical trials that have relevance for U.S. cancer patient populations. Incorporation of a Canadian Clinical Trials Network as a collaborating partner brings an additional advantage as U.S. Network Groups are anticipated to have Canadian member sites. A Canadian network is able to help reduce duplicative regulatory staff at U.S. NCTN Group Operations Centers.

Interactions with Other NCI-supported Programs. In addition to the six key components of the NCTN that are described above that are directly funded by the NCTN Program, other NCI grant and contract-supported Programs and their awardees as well as NCI Advisory Committees have important supporting roles in carrying out the research objectives of the NCTN Program. Thus, the NCTN awardees are expected to interact as appropriate with such entities/programs as the NCI Clinical Trials Tumor Banks, the NCI Community Oncology Research Program (NCORP) and Minority/Underserved NCORPs, the NCI Cancer Trials Support Unit, the pediatric and adult NCI Central Institutional Review Boards, and NCI Advisory and Scientific Committees, including the NCI Scientific Steering Committees.

Main Components of Network Group Statistics and Data Management Center Applications

1. Administrative Core

The Administrative Core is the principal component for the organizational, administrative, and scientific management of the Statistics and Data Management Center (SDMC) for an associated Network Group Operations Center. This Core provides integration between the statistics and data management components, support for participation in the collective management of the NCTN Program, and facilitates collaborations with other NCTN Groups, NCI-sponsored programs, and clinical trials organizations.

2. Statistics Core

This functional component should provide robust statistical analysis plans for clinical trials and trial monitoring to ensure appropriate trial conduct and outcomes validity.

3. Data Management Core

This functional component should provide support for data management (collection and monitoring) processes and procedures for all phases of clinical trials to ensure appropriate trial conduct, serious adverse event reporting, timely trial completion, and data validity.

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

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

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

Only the current award recipients under RFA-CA-17-057 are eligible to submit applications in response to this NOFO.

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

Only the current Network Statistics and Data Management Center recipients supported under RFA-CA-17-057 are eligible to apply.

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 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.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • 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. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019. 

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.

An individual who is designated as a PD/PI on the application for this NOFO for the Network Group Statistics and Data Management Center must not be designated as a PD/PI on an application for any of the NCTN key components listed below:

• Network Group Operations Centers (RFA-CA-24-030)
• Canadian Collaborating Clinical Trials Network (RFA-CA-24-032)
• Network Lead Academic Participating Sites (RFA-CA-24-033) and
• Network Radiotherapy and Imaging Core Services Centers (RFA-CA-24-034).                                                                                                                

However, an individual who is designated as a PD/PI on the application for a Network Group Statistics and Data Management Center can, if appropriate, be listed as key personnel in the application for its associated Network Group Operations Center (RFA-CA-24-030) and/or the application for the Network Radiotherapy and Imaging Core Services Centers (RFA-CA-24-034), but not on applications for the other RFAs listed above and not on applications for other Network Group Operations Centers.

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 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.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Margaret Mooney, M.D.
National Cancer Institute (NCI)
Telephone: 240-276-6006
Email: [email protected]
 

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.

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)

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Research & Related Other Project Information (Overall)

Follow standard instructions.

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 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)

Specific Aims: Describe succinctly the specific objectives and goals of the Network Group Statistics and Data Management Center (SDMC) as a whole, including the impact that the SDMC will have on appropriate design, conduct, and monitoring of clinical trials in the associated NCTN Network Group Operations Center's current and future trial portfolio and the impact on the field of oncology.

Research Strategy: Organize the Overall Research Strategy section with sub-sections in the specified order and using the instructions provided below. Start each sub-section with the appropriate sub-section heading: Sub-section A. Overall Significance; Sub-section B. Overall Innovation; Sub-section C. Overall Approach; and Sub-section D. Overall Progress Report.

Sub-section A. Overall Significance: Explain the importance of the SDMC's goals, including the overarching problems or critical barriers to ensuring the appropriate design and conduct of clinical trials with respect to statistical analysis and data management. Explain how the SDMC as a whole will improve scientific knowledge, technical capability, and/or clinical practice in clinical trial design, conduct, analysis, monitoring, and data collection and management. Also, explain how the SDMC incorporates and improves the use of NCTN tools in these aspects of clinical trials and how it participates in the collective management of the NCTN and collaborations with other NCTN Groups and NCI-sponsored programs.

Sub-section B. Overall Innovation: Explain how the SDMC seeks to shift current clinical trial design, conduct, monitoring, and data collection and management paradigms. Describe any novel (or refinements/improvements) in concepts, approaches, or methodologies that are being developed or used and any advantage that may have over existing methodologies.

Sub-section C. Overall Approach: Describe the overall strategy, methodology, and analyses to be used to accomplish the specific aims of the SDMC. Describe the experimental and/or refinements in trial design and monitoring & collection methods being proposed and how they will achieve robust and unbiased results and discuss potential problems, alternative strategies, and benchmarks for success anticipated to achieve the aims. Explain how relevant biological variables (e.g., sex, race, ethnicity, age, biomarkers) are factored into research designs and analyses for clinical trials.

Sub-section D. Overall Progress Report: This Progress Report should cover the period of March 1, 2019, through August 31, 2024 and should include a summary of the most significant achievements of the SDMC in terms of support for clinical trials designed and activated over this period and final analyses of major trials. This Progress Report should summarize how the SDMC has integrated and centralized functions to form an efficient operational unit and how it has incorporated applicable NCTN tools and processes. This Progress Report should highlight the SDMC's major contributions to the collective management of the NCTN Program and significant collaborations with other NCTN Groups and other NCI-sponsored programs.

Letters of Support: Provide a general Institutional Letter of Support (i.e., Letter of Support from the primary applicant institution or organization supporting the SDMC application). Also, include a Letter of Support from the applicant PD(s)/PI(s) of the associated NCTN Network Group Operations Center supporting the SDMC application.

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:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan in the Overall component only.

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)

Enter Human Embryonic Stem Cells in each relevant component.

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.

Other Attachments: Applicants must provide the following additional materials specified below for the Administrative Core. Each attachment should be uploaded as a separate PDF using the indicated filenames (which will serve as application bookmarks).

Attachment 1. Auditing Policy (use filename AdminCoreAuditing).

In this attachment, provide documentation of the auditing policy for the SDMC, including how patient cases are selected for auditing and how data is validated at site and in associated clinical trial databases.

Attachment 2. Conflict of Interest Policy (use filename AdminCoreCOI).

In this attachment, provide documentation of the Conflict of Interest Policy used by the SDMC to ensure that staff working design, monitoring, and analysis of specific trials do not have any conflicts of interest with respect to the trials. In this attachment, the SDMC should also describe the policies it has in place to ensure that outcome data for appropriate trials is guarded/blinded from other investigators on the study team (e.g., clinical investigators/study PIs) prior to the study's final analysis in avoid investigator bias in oversight/conduct of the trial.

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)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project 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.

a) PD/PI Effort Commitment. The minimal effort commitment for the Contact PD/PI must be 1.8 person-months per year. The effort commitment for the other PDs/PIs (if multiple) must be a minimum of 1.8 person-months per year. These effort commitments cannot be reduced in later years of the award.

b) Travel Expenses. Applicants must budget travel funds for two persons (two PDs/PIs or one PD/PI and an additional senior investigator) to attend one NCTN Leadership Management Committee in-person meeting or other NCTN-affiliated meeting or other NCTN Group-affiliated meeting per year in addition to other travel expenses. Applicants should also budget travel funds for one to two persons to attend an annual in-person meeting on NCTN SDMCs or an annual in-person meeting for special NCTN or NCI initiatives related to statistics and/or data management.

c) Other Expenses. Applicants must include in the budget appropriate expenses to cover support for the Data Safety Monitoring Board (meetings, member honorariums, and staff), auditing activities, preparation of data sets for applicable trials for the NCTN/NCORP Data Archive, and coordination activities with the associated NCTN Group Operations Center and tumor bank(s) to support linking of biospecimens and clinical data for the NCTN Navigator project and NCI/Cancer Therapy Evaluation Program (CTEP) approved integral and integrated correlative studies for ongoing trials as well as NCI/CTEP approved correlative studies using banked specimens.

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 (Administrative Core)

Specific Aims: State concisely the goals of the SDMC Administrative Core in terms of providing integration between the statistics and data management components, contributing to the collective management of the NCTN Program, and facilitating collaborations with other NCTN Groups, NCI-sponsored programs, and clinical trials organizations.

Research Strategy: Organize the Administrative Core Research Strategy section with sub-sections in the specified order and using the instructions provided below. Start each sub-section with the appropriate sub-section heading: Sub-section A. Administrative Core Organizational Leadership and Structure; Sub-section B. Administrative Core Collective Management; and Sub-section C. Administrative Core Collaborative Research.

Sub-section A. Administrative Core Organizational Leadership and Structure: Describe the senior administrative leadership team and organizational structure of the SDMC and its key governance policies. The applicant should also provide a diagram illustrating the organizational structure of the SDMC. Explain how the SDMC sets priorities for development of clinical trial designs, monitoring, and data management. Describe the chain of responsibility for decision making and conflict resolution at the SDMC as well as how the SDMC addresses succession planning for senior leadership positions in the Center.

Sub-section B. Administrative Core Collective Management Explain how the SDMC contributes to the collective management of the NCTN Program through examples of participation in the NCI Scientific Steering Committees (SSC) and associated Task Forces and Working Groups, NCI Central IRB, NCTN Core Correlative Sciences Committee, the NCTN Central Auditing Project, NCTN General Auditing, Risk-based Central Monitoring, NCTN Data Quality Portal Project and other NCTN initiatives such as Streamlining Clinical Trials. Describe how the SDMC ensures that clinical data is provided in a timely and user-friendly format for public access to data from completed clinical trials (NCTN/NCORP Data Archive and any other ways access is provided). Describe how the SDMC also provides clinical data for studies approved for use of banked biospecimens and the NCTN Tumor Banking Navigator project. Describe how the SDMC implements new initiatives standards for clinical trial conduct and data management in a timely fashion.

Sub-section C. Administrative Core Collaborative Research: Describe the SDMC's current collaborations and future plans for collaborations/initiatives with other NCTN Network Groups and clinical trials organizations on the statistical design and analysis of clinical trials as well as with other NCI-sponsored programs and investigators on ancillary studies (e.g., translational research, laboratory studies, use of banked biospecimens) associated with clinical trials. While independent statistical research is not required (or funded directly under this NOFO), involvement in research related to the design, conduct, and analysis of cancer clinical trials is considered a strength, and the applicant should therefore describe research being conducted by the SDMC statisticians using Network Group SDMC and Operations Center resources, including their clinical databases.

Data Safety Monitoring Plans: Data Safety Monitoring Plans (including a Data Safety Monitoring plan/policy for early phase trials and a Data Safety and Monitoring Board plan/policy for all randomized phase 2 trials and all phase 3 trials) are required for this NOFO. Reviewers will comment on whether the plans/policies are reasonable. Although these plans are required in the application; prior to funding of an award, all plans will also need to be reviewed and approved by NCI/DCTD program staff prior to any award in to ensure that the plans are in compliance with the NIH/NCI regulations and Terms of Award for this key component of the NCTN Program.

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.

NOTE: The Data Management and Sharing Plan as applicable to this section should be attached in the Other Plan(s) attachment in the Overall component above.

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.

Statistics Core

When preparing your application, use Component Type ‘Statistics Core.’

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

SF424 (R&R) Cover (Statistics 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 (Statistics Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Statistics 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.

Other Attachments: Applicants must provide the following additional materials specified below for the Statistics Core. Each attachment should be uploaded as a separate PDF using the indicated filenames (which will serve as application bookmarks).

Attachment 1. Key Standard Operating Procedures (use filename StatsCoreKeySOP).

In this attachment, provide documentation for key procedures for statistical analysis (e.g., guidelines for interim monitoring, general procedures for sample size estimation, accrual rate estimation, and choice of testing and estimation procedures).

Attachment 2. Model Statistical Analysis Template (use filename StatsCoreTemp).

In this attachment, provide documentation/example of the SDMC's standard template used for generating statistical analysis plans for clinical trials as well as the SDMC's standard "Report of Studies" template for providing information related to ongoing and recently closed trials to the members of its associated Network Group Operations Center.

Attachment 3. Current Trials Supported in the NCTN (use filename StatsCoreTrials).

In this attachment, provide documentation of the trials developed with design support by the statisticians in the Statistics Core since the inception of the NCTN on March 1, 2019, through August 31, 2024. Two tables should be provided - one table for all trials activated since the inception of the NCTN and one table for all trials still in development that have received final approval by NCI/CTEP as a Letter of Intent or Concept but that have not yet been activated, since the inception of the NCTN. The column headings for each table should include trial #, trial name, trial phase, major disease category (e.g., "breast cancer"), and name of the lead study statistician. The table should be sorted in the order listed: by trial phase and then by major disease category, and then by trial #. The timeframe for the period of services should be provided as a sub-heading for each table (e.g., March 1, 2019, through August 31, 2024).

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

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project 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 (Statistics 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.

PHS 398 Research Plan (Statistics Core)

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component.

Specific Aims: State concisely the goals of the SDMC Statistics Core in terms of providing robust statistical analysis plans for clinical trials and trial monitoring, including the impact of these plans on ensuring appropriate trial conduct and outcomes validity.

Research Strategy: Organize the Statistics Core Research Strategy section with sub-sections in the specified order and using the instructions provided below. Start each sub-section with the appropriate sub-section heading: Sub-section A. Statistics Core Structure; and Sub-section B. Statistics Core Approach.

Sub-section A. Statistics Core Structure: Describe the organizational structure of the Statistics Core of the SDMC and its key governance and standard operating procedures in order to demonstrate the applicant's capability to design, monitor, and analyze clinical trials in a timely manner. Describe how the leadership of the Statistics Core interacts with the Director of Operations position for the associated Network Group Operations Center and describe the SDMC's succession planning for key leadership positions in the statistical program.

Sub-section B. Statistics Core Approach: From the statistics perspective, describe the general approach to trial design and analysis plans for multi-institutional clinical trials, including guidelines for interim monitoring and general procedures for sample size estimation and choice of testing and estimation procedures as well as risk-based central monitoring for applicable NCTN trials. Describe how the Statistics Core provides statistical leadership in design and analysis, including incorporating new, integral and integrated, molecular and imaging biomarkers and laboratory studies into the overall evaluation of NCTN trials. Describe how the Statistics Core ensures that final study analyses are performed in a manner to provide timely publication of study results and results reporting per NIH/NCI, NCTN, and federal regulations.

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.

NOTE: The Data Management and Sharing Plan as applicable to this section should be attached in the Other Plan(s) attachment in the Overall component above.

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 (Statistics 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.

Data Management Core

When preparing your application, use Component Type ‘Data Management Core.’

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

SF424 (R&R) Cover (Data Management 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 (Data Management Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data Management 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.

Other Attachments: Applicants must provide the following additional materials specified below for the Data Management Core. Each attachment should be uploaded as a separate PDF using the indicated filenames (which will serve as application bookmarks).

Attachment 1. Key Data Management and Monitoring Policies & Procedures for Clinical Trials (use filename DataMgtCoreKeySOP).

In this attachment, provide documentation of key procedures for data management and monitoring policies for clinical trials, including risk-based central monitoring.

Attachment 2. Key Procedures to Ensure Security and Confidentiality of Patient Data (use filename DataMgtCoreSecurity).

In this attachment, provide documentation of key procedures for ensuring the security and confidentiality of patient data, including protected health information.

Attachment 3. General Data Quality and Timeliness for NCTN Trials (use filename DataMgtCoreTimeliness).

In this attachment, provide documentation of general data timeliness and quality for all data from all NCTN clinical trials led by the associated NCTN Group Operations Center since the inception of the NCTN on March 1, 2019, through August 31, 2024. A table should be provided detailing general data timeliness and quality by trial phase (pilot, other, phase 1, phase 2 (including phase 1/2), and phase 3 (including phase 2/3) on a yearly basis over that time period - with the 6th year consisting of only 6 months of data. The column headings for table should include Trial Phase, Reporting Year, % Eligible Patients, Eligibility Case Report Form (CRF) Reporting % Timeliness, Eligibility CRF Reporting % Accuracy, Treatment Cycle # or Equivalent CRF % Timeliness, Treatment Cycle # or Equivalent CRF % Accuracy, Off-Study CRF Reporting % Timeliness, and Off-Study CRF Reporting % Accuracy. The applicant team can select other major CRF categories that it believes represents the best measures of the timeliness of general data submission to its trials. In all cases, however, the report must include all the data submitted by sites participating in the trials led by the associated NCTN Group Operations Center regardless of whether the site is a member of that Group or another NCTN Group or a non-member collaborator. The timeframe for the period of services should be provided as a sub-heading for each table (e.g., March 1, 2019, through August 31, 2024).

Attachment 4. Summary of Data Quality and Data Timeliness for Serious Adverse Events on All NCTN Treatment/Imaging Trials Led by the Associated NCTN Group Operations Center (use filename DataMgtCoreSAES).

In this attachment, provide documentation of data timeliness and quality for Serious Adverse Event Reporting from all NCTN clinical trials led by the associated NCTN Group Operations Center since the inception of the NCTN on March 1, 2019, through August 31, 2024. A table should be provided detailing general data timeliness and quality by year for all treatment/imaging trials (regardless of phase) over that time-period - with the 6th year consisting of only 6 months of data. The column headings for table should include Total Accrual, % Eligible Patients, Serious Adverse Event (SAE) Reporting % Timeliness, SAE Reporting % Accuracy, and % Follow-up Forms Submitted on Time. The timeframe for the period of services should be provided as a sub-heading for each table (e.g., March 1, 2019, through August 31, 2024).

• For this table, SAE Reporting refers to reporting through the Cancer Therapy Evaluation Program Adverse Event Reporting System (CTEP-AERS) and/or the CTEP Adverse Event Expedited Reporting (AdEERS).
• Accuracy percentage for SAE Reporting is the percent of SAE forms amended for a change in toxicity Grade or addition of a toxicity Grade 3+. For example, if the total number of SAE forms received during the time-period covered by the report is 1,000, and out of those 1,000 SAE reports, 45 of them required a change in toxicity Grade or the addition of a grade 3+ or higher AE, then the accuracy percentage would be calculated as: ((1000 45) / 1000) = 95.5%.
• SDMCs should provide the exact definition that they use to calculate their accuracy percentage with this report in a brief paragraph note below the table.
• Timeliness percentage for SAE Reporting is the percent of follow-up data submitted as of February 28th of the project year with a 6-month grace period.
• Disciplinary actions imposed by the Group during the current funding period should be described and explained in a brief paragraph note below the table (e.g., # of sites placed on probation for auditing or other issues).

Project /Performance Site Location(s) (Data Management 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 (Data Management Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project 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 (Data Management 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.

PHS 398 Research Plan (Data Management Core)

Specific Aims: State concisely the goals of the SDMC Data Management Core in terms of providing appropriate data management (collection and monitoring) processes and procedures for clinical trials (all phases), including the impact of these plans on ensuring appropriate trial conduct, serious adverse event reporting, timely trial completion, and data validity.

Research Strategy: Organize the Data Management Core Research Strategy section with sub-sections in the specified order and using the instructions provided below. Start each sub-section with the appropriate sub-section heading: Sub-section A. Data Management Core Structure; Sub-section B. Data Management Core Approach; and Sub-section C. Data Management Core Training.

Sub-section A. Data Management Core Structure: Describe the organizational structure of the Data Management Core of the SDMC and its key governance and standard operating procedures in order to demonstrate the applicant's capability to provide accurate and timely data collection including appropriate SAE reporting. Describe how the Data Management Core leadership interacts with the Director of Operations position for the associated Network Group Operations Center as well as succession planning for key leadership positions in the data management program.

Sub-section B. Data Management Core Approach: Describe the data management and study monitoring practices of the Data Management Core, including the flow and review of data following submission from individual institutions/sites and investigators. The applicant should describe the data management systems employed and how the Core uses standard NCTN tools including the NCTN Common Data Management System (CDMS), the NCTN Regulatory Support System (RSS), the NCTN Oncology Patient Enrollment Network (OPEN), the NCI/DCTD Clinical Data Update Systems (CDUS/CDS) or the new CTEP AERS System, the NCI Common Terminology Criteria for Adverse Events (CTCAE) for data management for NCTN trials, and trial registration in the NCI National Clinical Trials Reporting Program (CTRP) and in the U.S. National Library of Medicine (NLM) (www.clinicaltrials.gov) along with results reporting, as applicable.

Describe how the SDMC facilities and equipment (including computer hardware and software) available as well as the information technology (IT) support for central storage, security, analysis and retrieval of clinical data for the SDMC appear adequate for clinical trial research.

Describe procedures for study monitoring as well for data quality control and accuracy verification, including how the Data Management Core works with the Statistics Core and the associated Network Group Operations Center on risk-based central monitoring and auditing activities. The applicant's method for active trial monitoring, including procedures for accrual and biospecimen collection tracking, assessing case, eligibility and evaluability, ensuring timely medical review and assessment of patient data, monitoring of data timeliness, and facilitating SDMC staff interactions with study chairs should be described. Explain the Data Management Core's guidelines for institutions/sites for data timelines, including a summary of data quality and timeliness as an indication of its potential to provide timely, high-quality data on trials in an efficient manner. Describe the information technology (IT) support for central storage, security, analysis and retrieval of clinical data in the Data Management Core.

Describe how the Data Management Core complies with the Constitution & By-laws of the associated Network Group Operations Center as well as its conflict of interest policy and guidelines for good clinical practice. The applicant should also describe how it complies with NCI/DCTD's Intellectual Property (IP) Option and NCI/DCTD's collaborative binding agreements for NCI/DCTD IND and IDE studies and studies conducted under a Network Group IND or IDE. Describe how the Data Management Core coordinates with the associated Network Group Operations Center to ensure that data and biospecimens can be made available to the public for future research (via the Navigator Project and other procedures).

Sub-section C. Data Management Core Training: Describe Data Management Core training for investigators, Clinical Research Associates, and study chairs related to data management and study monitoring for NCTN clinical trials.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

• Consistent with achieving the goals of the program, Resource Sharing Plans are expected for all applications but should be provided only under the Overall Component.

NOTE: The Data Management and Sharing Plan as applicable to this section should be attached in the Other Plan(s) attachment in the Overall component above. The Data Safety and Monitoring Plan is expected for all applications but should be provided only under the Administrative Core.

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 (Core or Project Name)

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 NCI, 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 [email protected].

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.

For this NOFO, note the following:

Scoring: Reviewers will provide an overall impact score for the entire application. In addition, reviewers will also provide individual "criterion scores" for the Overall application but not for the other components.

All other components of the Network [i.e., Administrative Core, Statistical Core, and Data Management Core] will be evaluated but each will receive only an overall adjectival rating.

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?

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?

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 SDMC? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed SDMC? 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 SDMC 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 SDMC 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?

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, gender, 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/gender 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 Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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 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

Not Applicable

Renewals

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

Revisions

Not Applicable

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.

Scored Review Criteria – Cores

For each of the Network's components below (i.e., Administrative Core, Statistical Core, Data Management Core), reviewers will provide an overall adjectival rating. Reviewers will consider the following aspects while determining scientific and technical merit of each component. Criterion scores will not be provided for the Cores.

Review Criteria for Administrative Core

• How sufficient are the scientific qualifications, involvement of Core leadership?
• How appropriate are the plans for organizational and administrative management, including scientific and fiscal management, for the SDMC?
• How adequate are the plans for coordination and communication for accomplishing the objectives of the SDMC and for the SDMC to participate in the Collective Management of the NCTN Program, including the auditing program?
• Are sufficient methods in place to monitor progress in the services of all the Cores and to determine whether the resources in all the Cores are being utilized effectively?
• Is there a clearly described chain of responsibility for decision-making, and a succession plan should the need arise?

Review Criteria for Statistics Core

How comprehensive is the expertise of the statisticians in the Statistics Core and is the expertise appropriate for the types and phases of trials being designed and conducted (early phase and especially late phase, definitive, multi-institutional clinical trials in oncology, including integral and integrated biomarker/correlative science studies in both rare and common cancers and in special populations)? Will these investigators be able to work as a cohesive research team to efficiently and expeditiously develop the statistical analysis plans for NCTN clinical trials as well as analyze results from completed trials?

• Does the Core have a well-defined organizational structure and clearly defined roles and responsibilities for its staff? Does the applicant have appropriate and clearly defined succession and transition plans for the senior statistical leadership of the Core?
• Does it appear that the Statistics Core has the necessary expertise and experience to incorporate new molecular and imaging biomarkers into the overall evaluation of NCTN trials appropriately?
• Are the procedures for sample size estimation, end point selection and monitoring plans (including risk-based central monitoring for applicable NCTN trials) adequately described and justified? Are analytical techniques, procedures, and policies adequate, appropriate, and consistent with accepted standards?
• Is there evidence that past publications by the SDMC demonstrate thorough and state-of-the-art methodology, awareness of problems of multiple analyses, and sufficient independence and lack of bias of statistical collaborators?

Review Criteria for Data Management Core

• How comprehensive is the expertise of the data management staff in the Core and is it appropriate for the types and phases of NCTN trials the Network Group leads? How comprehensive and appropriate are the applicant's policies and procedures for active trial monitoring, including assessing case, eligibility and evaluability, ensuring timely medical review and assessment of patient data, monitoring of data timeliness, and facilitating SDMC staff interactions with study chairs?
• How robust are the Core's policies and procedures for risk-based central monitoring for NCTN trials as well for on-site auditing with the Administrative Core?
• How appropriate is the Core's training for investigators, Clinical Research Associates, and study chairs related to data management and study monitoring for clinical trials (as well as for statistics for non-statistical staff and investigators, if offered)?
• Does the Core have clear guidelines for institutions/sites related to data timeliness and metrics for data quality and timely reporting to the institutions/sites of this information/metrics?
• How well do the data management systems employed by the Core use standard NCTN tools and integrate with required results reporting systems?
• Does the Core have appropriate procedures in place to ensure compliance with respect to NCI/DCTD's IP Option and NCI/DCTD's collaborative binding agreements for NCI/DCTD IND studies?
• Do the facilities and equipment of the Core (including computer hardware and software) available as well as the information technology (IT) support for central storage, security, analysis and retrieval of clinical data for the Core appear adequate for clinical trial research?
• How able is the applicant to coordinate with the associated Network Group Operations Center to ensure that clinical data can be linked to biospecimens that can be made available to the public for future research (via the NCTN Navigator Project or other collaborations?

Additional Review Criteria - Cores

As applicable for the Cores and Projects proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall adjectival rating, but will not give separate scores for these items.

Study Timeline

Specific to applications involving clinical trials

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 Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Additional Review Considerations - Cores

As applicable for the Cores and Projects 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 adjectival rating.

Applications from Foreign Organizations

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

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the 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.

2. Review and Selection Process

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

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or 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: Grantee institutions 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).

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.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
  • HHS recognizes that NIH research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

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

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support.

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:

• Development of an overall strategy to provide statistical expertise for effective scientific design, conduct, and data management of clinical trials led by the associated NCTN Network Group Operations Center.
• Provision of standard operating procedures covering all aspects of clinical trial design, trial conduct (including compliance with Good Clinical Practice (GCP) guidelines including risk-based central monitoring for applicable NCTN IND trials), data management, study monitoring, data analysis, development and compliance with data safety/monitoring plans and Data Safety Monitoring Board policy for applicable trials, and training for Clinical Research Associates (CRAs) at member participating sites and Study Chairs/Teams about their responsibilities for study monitoring and data management.
• Participation in the collective management of the Network, including participation in appropriate NCTN Program activities and initiatives (e.g., NCI Scientific Steering Committees, NCI CIRBs, NCTN Core Correlative Science Committee).
• Compliance with NCTN Program/NCI/NIH timelines and policies for registration of trials in clinicaltrials.gov and Clinical Trials Reporting Program (CTRP), publication, and trial data deposit in the NCTN/NCORP Data Archive and the NCTN Navigator System.
• Provision of clinical trial data for NCI/DCTD-approved correlative science studies using banked biospecimens from NCTN trials.
• Evaluation of member site performance and auditing per NCTN Program/CTMB Guidelines.
• Use of NCTN Program's common data management system including use of NCTN reporting tools for adverse event reporting and risk-based central monitoring.
• Compliance with Part 1 of the NCI National Clinical Trials Network (NCTN) Program Guidelines/Handbook dated December 15, 2012 (https://ctep.cancer.gov/initiativesPrograms/docs/NCTN_Program_Guidelines.pdf) and any subsequent updated versions of the Guidelines/Handbook.
• Recipients will comply with the Handbook for Clinical Investigators Conducting Therapeutic Clinical Trials Supported by CTEP, DCTD, NCI at (https://ctep.cancer.gov/investigatorResources/investigators_handbook.htm), the NCI Guidelines for Auditing Clinical Trials for the National Clinical Trials Network (NCTN) Program including NCI Community Oncology Research Program (NCORP) and Research Bases at (https://ctep.cancer.gov/branches/ctmb/clinicalTrials/monitoring_coop_ccop_ctsu.htm), NCI/DCTD CRADA agreements, and the Intellectual Property Option to Collaborators at (https://ctep.cancer.gov/branches/rab/intellectual_property_option_to_collaborators.htm) for NCTN trials.
• 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 and within the limits of any accepted binding NCI/NIH collaborative agreements with biotechnology and as governed by NCI-approved Data Management and Sharing Plans and NCI-approved review for use of biospecimens collected in association with NCTN trials.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, with specific responsibilities that will include but are not limited to those described below:

• Responsibilities as a drug sponsor for investigational agent or device development for NCI-sponsored or co-sponsored IND and/or Investigational Device Exemption (IDE) clinical trials.
• Serving as scientific liaisons to recipients of this key component of the NCTN Program and participation in scientific meetings of the key components.
• Informing Network investigators of scientific opportunities resulting from NCI-supported clinical research programs.
• Oversight and clinical stewardship of data and safety monitoring plans and boards for NCTN clinical trials and implementation of accepted DSMB recommendations as well as the implementation of study closure.
• Oversight of data management and monitoring programs for NCTN trials as well as onsite auditing programs and quality assurance programs for the NCTN Program, including oversight of core services for radiotherapy and imaging supporting NCTN trial.
• Facilitating coordination of the clinical trial activities and collaborations between the Network and other NCI-sponsored programs and investigators.
• Facilitating the evaluation of clinical trial concepts and protocol development as well as responsibility for the final review and approval of trial protocols, including statistical analysis plans.
• Final review and approval of requests for use of any biospecimens collected in association with NCTN trials and associate statistical analysis plans, and oversight of the NCTN Core Correlative Sciences Committee.
• Ensuring compliance with FDA requirements for investigational agents and ensuring compliance with OHRP and other federal requirements and regulations for research involving human research subjects including compliance with Good Clinical Practice (GCP) guidelines for applicable NCTN IND trials.
• Advising recipients concerning mechanisms established by the recipients for quality control of therapeutic and diagnostic modalities.
• Monitoring the progress and performance of this key component of the NCTN Program.
• The NCI will have access to all data (including imaging data) collected and/or generated under this Cooperative Agreement and may periodically review the data. 

Areas of Joint Responsibility include:

• General aspects of collaboration on study development and conduct especially with respect to compliance with federal regulations for clinical trial research (and with respect to ensuring that when new avenues of cancer therapy involving investigational drugs are pursued, trials are designed, when appropriate, such that the clinical information obtained would be acceptable to the FDA for inclusion in a potential licensing application), conduct of Data and Safety Monitoring Boards for Phase 3 trials and randomized Phase 2 trials, development of collaborative trials and international trials, collective management of the NCTN including participating in the NCTN Leadership Management Committee that makes recommendations to NCI for modifications to the Program as well as to standard NCTN common tools and services.
• Review of recommendations from the NCI Clinical Trials and Translational Research Advisory Committee (CTAC) on strategic directions for the NCTN Program.

3. Data Management and Sharing

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described. 

• 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)

Finding Help Online: https://www.era.nih.gov/need-help  (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

General Research Programmatic Information and Administrative Information: 

Margaret Mooney, M.D.
National Cancer Institute (NCI)
Telephone: 240-276-6006
Email: [email protected]
 

Information on Scientific Program for Statistics and Data Management: 

Edward Korn, Ph.D.
National Cancer Institute (NCI) 
Telephone: 240-276-6029
Email: [email protected]
 

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

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email: [email protected]
 

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.