NIH's new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically using ASSIST or an institutional system-to-system solution; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

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

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This Funding Opportunity Announcement (FOA) is one of six FOAs 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 FOAs indicated below:

NCTN - Network Group Operations Centers under RFA-CA-17-056 (U10)

NCTN - Network Group Statistics & Data Management Centers under RFA-CA-17-057 (U10) - this FOA

NCTN - Canadian Collaborating Clinical Trials Network under RFA-CA-17-058 (U10)

NCTN - Network Lead Academic Participating Sites under RFA-CA-17-059 (UG1)

NCTN - Network Radiotherapy & Imaging Core Services Center under RFA-CA-17-060 (U24)

NCTN - Network Group Integrated Translational Science Centers under RFA-CA-17-061 (UG1)

The purpose of this funding opportunity announcement (FOA) is to solicit 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.

On March 1, 2014, after several years of extensive consultation and coordination with numerous stakeholders, the NCI transformed its longstanding Cooperative Group Clinical Trials infrastructure program into the new NCI National Clinical Trials Network (NCTN) 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 immunotherapies, 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 implements and completes trials far more rapidly than in the past. 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 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 as evidenced by the large number of biotechnology and pharmaceutical companies that collaborate on NCTN 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 has also continued to promote the evaluation of multi-modality treatments, including surgery and radiotherapy in combination with novel agents, and has maintained a commitment to the conduct of trials in special populations (e.g., children, adolescents, young adults, and underserved populations) and involving patients with rare tumors. 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 now 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 Division of Cancer Treatment and Diagnosis (NCI/DCTD) approved, multi-center phase 2 and phase 3 trials originating outside the Network Groups.
• Network Group Statistics and Data Management Centers - this RFA: 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 Network Groups as well as substantial accrual to clinical trials conducted across the entire NCTN.
• Network Radiotherapy and Imaging Core Services Centers: This institution/organization provides scientific and technical expertise for incorporation of appropriate, integrated quality assurance and image data management for applicable clinical trials conducted by the NCTN that require specialized quality assurance or imaging data management and/or assessment for radiotherapy and imaging interventions. In addition, the Center also provides similar services for other approved NCI-supported clinical trials network programs (e.g., NCI/DCTD early phase clinical trial network program, NCI Division of Cancer Prevention (NCI/DCP) NCI Community Oncology Research Program).
• 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. 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 each U.S. Network Operations Center.

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.

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.

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

Only the current Network Statistics and Data Management Center awardees, supported under RFA-CA-12-011, are eligible to apply.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.

System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

o NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.

eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.

Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

An individual who is designated as a PD/PI on the application for this FOA 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-17-056);

Canadian Collaborating Clinical Trials Network (RFA-CA-17-058);

Network Lead Academic Participating Sites (RFA-CA-17-059); and

Network Radiotherapy and Imaging Core Services Centers (RFA-CA-17-060).

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 and/or the application for the Network Radiotherapy and Imaging Core Services Centers (RFA-CA-17-060), but not on applications for the other RFAs listed above and not on applications for other Network Group Operations Centers.

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

Each organization may submit only 1 application in response to this FOA.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

A button to access the online ASSIST system is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

Most applicants will use NIH's ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

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

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

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

The letter of intent should be sent to:

Meg Mooney, M.D.
National Cancer Institute
Telephone: 240-276-6086
Email: [email protected]

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	30
Admin Core	12
Core (Use for Statistics Core and Data Management Core)	12

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required; maximum of one
• Statistics Core: required; maximum of one
• Data Management Core: required; maximum of one

When preparing your application in ASSIST, use Component Type 'Overall'.

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

Complete entire form.

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

Follow standard instructions.

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.

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

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.

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, 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, 2014, through August 31, 2017 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 SF424 (R&R) Application Guide, with the following modifications:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide, with the following modification: No appendix materials are allowable for this component (Overall).

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

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

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

Complete only the following fields:

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

Enter Human Embryonic Stem Cells in each relevant component.

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.

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.

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

Budget forms appropriate for the specific component will be included in the application package. The following additional instructions apply to the Administrative Core in this FOA.

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 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 and an in-annual in-person meeting for special NCTN 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.

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. 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). 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 FOA), 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 FOA. 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 SF424 (R&R) Application Guide, with the following modification:

Resource Sharing Plans are expected for all applications but should be provided only under the Overall Component.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide, with the following modification:

• No appendix materials are allowable for the Administrative Core.

PHS Inclusion Enrollment Report (Administrative Core)

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

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

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

SF424 (R&R) Cover (Statistics Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant's Core
• 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, 2014, through August 31, 2017. 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, 2014 through August 31, 2017).

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

Budget (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)

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.

Data Safety Monitoring Plans: Data Safety Monitoring Plans are expected for all applications but should be provided only under the Administrative Core.

Resource Sharing Plan:

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

• 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.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide., with the following modification:

• No appendix materials are allowable for the Clinical Trials Development & Member Site Core.

PHS Inclusion Enrollment Report:

PHS Inclusion Enrollment Report are expected for all applications but should be provided only under the Administrative Core.

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

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

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant's Core
• 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, 2014, through August 31, 2017. 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 4th 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, 2014 through August 31, 2017).

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, 2014, through August 31, 2017. 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 4th 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, 2014 through August 31, 2017).

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

Budget (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 studies. 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 (currently and via the Navigator Project in the future).

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.

Data Safety Monitoring Plans: Data Safety Monitoring Plans are expected for all applications but should be provided only under the Administrative Core.

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

• 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.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide., with the following modification:

• No appendix materials are allowable for the Clinical Trials Development & Member Site Core.

PHS Inclusion Enrollment Report:

PHS Inclusion Enrollment Report are expected for all applications but should be provided only under the Administrative Core.

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

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

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) 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 Policy on Late Application Submission.

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

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

This initiative is not subject to intergovernmental review.

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

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

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

For information on how your application will be automatically assembled for review and funding consideration after submission go 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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

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

See more tips for avoiding common errors.

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

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

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this FOA, note the following:

Reviewers will provide an overall impact score for the entire Statistics and Data Management Center (Overall component). In addition, assigned reviewers will provide individual "criterion scores" for the Overall criteria but not for the other components.

All other components of the SDMC [i.e., Administrative Core, Statistics Core, and Data Management Core] will be evaluated but each will receive only one overall adjectival (not numerical) rating.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Statistics and Data Management Center (SDMC) 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 SDMC 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 SDMC that by its nature is not innovative may be essential to advance a field.

Does the SDMC address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the SDMC 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 PD(s)/PI(s), collaborators, and other researchers well suited to the SDMC? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

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

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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 project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the SDMCinvolves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Reviewers will provide only one overall adjectival rating for the Administrative Core (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining scientific and technical merit of this component:

• 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?

Reviewers will provide only one overall adjectival rating for the Statistics Core (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining scientific and technical merit of this component:

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?

Reviewers will provide only one overall adjectival rating for the Data Management Core (criterion scoring is not used for this component). Reviewers will consider the following aspects while determining scientific and technical merit of this component:

• 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)?

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

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

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

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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

Not Applicable

For Renewals, the committee will consider the progress made in the last funding period covering the period of March 1, 2014, through August 31, 2017.

Not Applicable

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

Not Applicable

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

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

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

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

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

As part of the scientific peer review, all applications:

• Will receive a written critique.

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the 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.
• Compliance with resource sharing policies and Data Safety and Monitoring policies.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee's business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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

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

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

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement - an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibilities 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.
• Awardees 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, Community Clinical Oncology Program (CCOP)/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.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

Designated NCI Program Director(s) will have substantial involvement as a Project Scientist(s).

Additionally, an NCI Program Director, acting as Program Official will be responsible for the normal,

scientific and programmatic stewardship of the award and will be named in the award notice. A

Program Official may also have substantial programmatic involvement (as a Project Scientist).

• 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 awardees 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 of data and safety monitoring plans and boards for NCTN clinical trials.
• 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 review and approval of final 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 awardees concerning mechanisms established by the awardees 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

Dispute Resolution

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting; one NIH designee; and a third designee with expertise in the relevant area who is chosen by the other two. In the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

General Research Programmatic Information and Administrative Information:

Meg Mooney, M.D.
National Cancer Institute
Telephone: 240-276-6086
Email: [email protected]

Information on Scientific Program - Adult US Network Group Statistics/Data Mgt Center Applicants:

Ed Korn, Ph.D.
National Cancer Institute
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]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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