Required Application Instructions

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

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

The purpose of this limited competition Funding Opportunity Announcement (FOA) is to continue the Childhood Cancer Survivor Study (CCSS). CCSS is a multi-institutional collaborative endeavor to assemble and maintain a research cohort of over 24,000 five-year survivors of childhood cancer (14,000 diagnosed between 1970-1986 and 10,000 diagnosed between 1987 and 1999) and over 3,700 sibling control subjects. CCSS has established itself as the national resource for research on late effects and ongoing risks in survivors of childhood cancer.

The CCSS awardees seeking renewal of this research resource are expected to address the following important research directions and specific objectives:

• Identification of high risk cancer survivorship populations for latent effects and to quantify the magnitudes of the risks that they face;
• Generate data to inform the development of risk-based screening guidelines;
• Identification of aspects of survivorship research that have potential for translation into intervention based research and increase the testing of interventions in this population to reduce later life morbidity and premature mortality;
• Utilize the CCSS resource to refine the relationship between therapeutic exposure and adverse outcome and developing an understanding of the role of genetic susceptibility in development of treatment-related adverse outcomes;
• Validate genetic studies and risk prediction models through collaboration with international colleagues and other late effects cohort studies (e.g., St. Jude's LIFE study);
• Continued follow-up of the merged population cohort (i.e., patients diagnosed between 1970-86 and between 1987-99);
• Evaluate the feasibility of direct assessment of childhood cancer survivors and compare to self-reported outcomes, and identification of subgroups who would benefit from this approach;
• Identify novel approaches for monitoring certain late effects and engagement of the cohort;
• Expand collection and analysis of biological samples from the participating survivors;
• Use of this cohort to address questions of the impact of factors such as ethnic/racial diversity, adolescent age at cancer diagnosis and changes in treatment on survivor outcome; and
• Promote and facilitate the use of the CCSS resource by non-CCSS investigators.

As a result of improvements in childhood cancer therapy over the past 5 decades, more than 80% of children diagnosed with cancer will experience long-term survival into adulthood. Through the CCSS, which has been funded by the NCI since 1993, investigators have identified and characterized the spectrum of adverse outcomes that long-term survivors are at risk of developing. The results of the CCSS have greatly advanced knowledge of late effects among survivors of pediatric cancer. Researchers have demonstrated that 60-90% of adults treated for cancer during childhood develop one or more chronic health conditions. They have also shown that by age 50 years, the cumulative incidence of self-reported severe, disabling, life-threatening, or fatal health condition was 53.6% among survivors compared with 19.8% among sibling control group. Among childhood cancer survivors who reach age 35 years without a previous severe, disabling, life-threatening, or fatal health condition, 25.9% will experience a new severe, disabling, life-threatening or fatal condition within 10 years as compared to 6% of healthy siblings. In addition to the findings related to an increased risk of increased morbidity and mortality, CCSS has shown that long-term survivors are at risk of developing a variety of adverse outcomes which include second malignancies, organ dysfunction (e.g., cardiac, pulmonary, gonadal), impaired growth and development, impaired cognitive function, difficulties obtaining employment and insurance, and compromises in the quality of life. Many of these long-term effects and how they affect survivors are poorly understood. Identification of individuals predisposed to develop these long-term effects and interventions designed to ameliorate these negative consequences of cancer treatment are being developed and tested. CCSS provides the foundation for these additional investigations. Based on the successful establishment of the unique CCSS cohort and its contributions to the area of cancer survivorship, CCSS has become an important resource to the cancer research community. Recognizing the CCSS research contributions, the NCI intends to continue supporting this program as defined by this FOA.

Continuing the research activities of the Childhood Cancer Survivor Study will provide essential data on the late effects of treatment for the longest followed cohort of survivors of cancer and specifically childhood cancer in order for cancer survivors to have the optimal quality of life and their physicians to provide the highest quality of care. In addition, these findings serve to inform and modify current treatment approaches for children with cancer.

The overall objectives of CCSS are to quantify and better understand the effects of pediatric cancer and its treatment on later health, including behavioral and sociodemographic outcomes and relationships with genetic factors.

The emphasis of the CCSS is on approaches to ensure the functioning of CCSS as a strong and productive resource for researchers studying pediatric cancer survivors diagnosed between 1970 -1999 and their siblings.

Additional priorities are to enhance the CCSS resource by increasing the capacity to conduct hypothesis-testing genetic-based research and to enhance the use of CCSS data, expertise, and tissue samples. In this context, it is expected that the renewed CCSS will serve:

• Investigators involved with CCSS Working Groups formed to focus on specific research topics and directed to answer research questions in prioritized areas of interest to CCSS; and
• Investigators interested in utilizing the CCSS resources for their externally funded research projects.
• Secondary goals/areas of emphasis for the program include:
• Building the capacity to facilitate translation of CCSS findings and identify the opportunities for intervention strategies (however, the actual conduct of intervention studies remain beyond the scope of this FOA);
• Developing strategies to improve the understanding of late effects on survivor health by specific organ system;
• Identifying and collaborating with other childhood cancer survivor groups internationally; and
• Enhancing research experience and mentorship for CCSS junior investigators;

To address the stated goals and priorities, CCSS will be expected to have appropriate leadership, organization, and capabilities to ensure a smooth integration of the cohort-related functions, as specified in Section IV of this FOA, under Research Strategy).

Organizational Requirements and Expectations:

To conduct the indicated Research Programs of CCSS, the applicant is expected to assemble (or continue) a consortium of multiple collaborating institutions and researchers with appropriate expertise and interest in childhood cancer survivorship, who provide the access to the needed patient populations as appropriate to support the goals of the CCSS.

Leadership Structure:

It is expected that the scientific leadership will reflect the scientific disciplines of the CCSS and will continue to use Working Groups consisting of CCSS investigators to prioritize research areas of particular interest to CCSS.

Required Functionalities

The CCSS must provide appropriate functionalities (referred to as "support units") in specific areas as outlined below.

Administrative support must be organized to serve overall administrative and organizational needs of the entire CCSS. The CCSS administrative support is expected to function as a central office, located at the lead PD/PI s institution. In addition to internal CCSS administration, the administrative support must serve the interactions between CCSS investigators and the Steering Committee and the NCI.

Radiation physicists must be capable of reviewing all relevant radiation therapy records for survivors who received radiation therapy.

Biopathology group will be responsible for collecting the tissue from all secondary malignant neoplasms occurring in participants in the CCSS in order to identify, confirm, and analyze the neoplasms.

Biorepository group (Molecular Genetic Bank) must be organized to continue to collect and bank the genomic DNA obtained from peripheral blood, buccal cell or saliva samples of survivors and siblings, plus peripheral-blood samples from survivors with a second or subsequent neoplasm.

Data and Statistics services must be able to ensure accuracy in collection and management of the data in the CCSS study. This group will provide biostatistical support to the majority of CCSS data-analysis projects.

Overall governance of the CCSS program. The Steering Committee will serve as the main governing board for CCSS. For details see Section VI.2. Cooperative Agreement Terms and Conditions of Award of this FOA.

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 recipients of the CCSS award are eligible to apply.

It is expected that the subcontracting institutions on the current award will continue their participation in CCSS. However, it is up to the applicant team to determine the final composition of the collaborating institutions.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed but only if they are Canadian institutions.

Applicant Organizations

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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

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

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

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

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

• 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).

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

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

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

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:

Nita L. Seibel, M.D.,
National Cancer Institute (NCI)
Division of Cancer Treatment and Diagnosis
NCI-Shady Grove
9609 Medical Center Dr. Rm 5W410
Rockville MD 20850
Telephone: 240-276-6078
Fax: 301-276-7892
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

• For this specific FOA, the Research Strategy section is limited to 30 pages.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

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

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

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

Other Attachments: Provide the following materials listed below as Other Attachments. Upload these items as indicated attachments using file names provided (these file names will become bookmarks in the application).

• Attachment 1 (filename Cohort & Research Highlights):
• A summary table(s) of the main characteristics of the CCSS cohort including subgroup representation (e.g. minorities, adolescents etc.);
• A figure(s) or table(s) showing the changes in treatment modalities over time for the CCSS cohort;
• A summary of surveys and investigator initiated grants, e.g., a figure(s) showing the timing of the CCSS surveys and the investigator initiated projects with grant support using CCSS;
• Characteristics of CCSS genetic resource (in tabular format);
• A summary of research impact of CCSS, e.g., a table(s) showing selective examples of innovative, high impact research using CCSS; and
• Impact on clinical practice (a table listing examples of CCSS publications informing most recent COG Late Effect Guidelines).
• Attachment 2 (filename Organizational Structure):
• A chart illustrating the organizational and leadership structure of CCSS;
• Attachment 3 (filename Biospecimens Distribution):
• A list of research projects using CCSS banked biological specimens;
• A table listing subsequent neoplasms reported from the CCSS cohort and specimen collection; and
• A table listing the datasets distributed for the past 5 years to investigators (include information (columns) on whether the datasets needed revision or clean up and response time to investigators for receipt of dataset from project approval date).
• Attachment 4: (filename Home Sampling):
• Data (in tabular format) for the pilot sampling of key outcomes in patients homes and remotely through mobile technologies and applicable sample size considerations.
• Attachment 5 (filename Timeline):
• The timeline for future objectives/benchmarks for CCSS (a figure or a diagram)

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

Applicants are encouraged to designate a contact PD/PI (based in the application submitting institution) and a second PD/PI, who would share the responsibilities but would also be capable of leading the entire CCSS (in case the lead PD/PI is unable to continue serving in this role). If only one PD/PI is designated, applicants must identify a PD/PI potential replacement candidate, i.e., a senior investigator who will be qualified to take over the PD s/PI’s responsibility for the entire CCSS if such need arises.

All instructions in the SF424 (R&R) Application Guide must be followed. In addition, up to

$100,000 per year should be set aside for pilot projects to be initiated post-award. These reserved funds can be used only for the pilot projects that are approved for funding by the CCSS Steering Committee.

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

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

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

Research Strategy: The Research Strategy must consist of sub-sections A-F as defined below.

Sub-section A. CCSS Overview

In this section, address the following aspects.

Describe the history and experience of the applicants' team in designing and implementing the CCSS. Outline the scientific rationale underpinning the need for the cohort. Address the following specific aspects.

• Cohort Characteristics: Summarize the main characteristics of the initial and expanded cohort, including a breakdown by gender and racial/ethnic subpopulations. Update on the progress with the merged cohort, including identification and recruitment of study subjects and expanded sibling population
• CCSS Significance and Overall Goals: Summarize the main scientific and public health-related benefits anticipated from the continuation of the CCSS resource, justification for recent expansion cohort and significance of CCSS in terms of risk identification for cancer survivorship and impact of CCSS on survivorship research. Summarize the CCSS's role and potential relative to mortality, morbidity, and quality of life of long-term survivors of childhood cancer with illustrative examples.
• Progress Report: Summarize the main accomplishments of the CCSS during the current funding period; include information on establishment, maintenance, and enhancement of the resource; salient contributions to peer-reviewed literature; and CCSS functioning as a resource for investigator-initiated research supported by external grants.
  

Note: Supplementary data in support of this subsection are requested under Other Attachments as Attachment 1.

Sub-section B. Leadership and Administrative Functions

In this sub-section, address the following aspects.

• Senior Leadership: Outline the proposed leadership structure (avoiding duplication with the "Multiple PD/PI Leadership Plan", if multiple PD/PI option is used). In addition to an overall PD/PI (expected to be designated as contact PD/PI at the application-submitting institution), identify another PD/PI (or a substitute PD/PI candidate) to assure program continuity. Without repeating information in respective biosketches, explain how the qualifications and experience of both persons would be advantageous for organizing and managing the CCSS and related activities as multi-institutional collaborative efforts. Describe the strategy to divide leadership responsibilities among key/senior individuals. List specific topical areas expected to be covered by CCSS Working Groups and individuals who will provide scientific leaderships for these Working Groups. Outline the roles and proposed duties of other key individuals in the leadership besides the PD(s)/PI(s) (for example, individuals who would lead support units defined below).
• Administrative Functions: Explain the roles and responsibilities of a unit, which will be providing administrative services to CCSS and logistic support for the interactions among CCSS investigators, the Steering Committee, and the NCI. Identify an individual who will be primarily responsible for the administrative support. The administrative support must have appropriate capabilities to manage cohort communications as well as regulatory staff and other administrative staff, as needed (e.g., to administer surveys, informed consent, requests for medical record release and follow-up).

Note: Supplementary data in support of this subsection are requested under Other Attachments as Attachment 2.

Sub-section C. Specialized Functional Support Groups

Provide details on the specialized groups needed to support the basic functions of CCSS. For each of these groups, identify the group leader(s) (if applicable) and outline how the group (or its prior equivalent) has contributed to the CCSS past performance. Outline planned activities of these groups using the guidelines provided below. When appropriate, address quality control issues.

It is expected that the following functional groups will be included.

• Radiation physics group: This group will be expected to document absorbed radiation doses, specific to organs or anatomic sites for each individual included in a specific study, by merging basic dosimetry data and data concerning the individual's radiation treatment. Appropriate quality control techniques must be used to ensure correctness of dosimetry.
• Biopathology group: In addition to collecting and reviewing the subsequent neoplasms, the biopathology group should plan to collect retrospectively paraffin-embedded tumor material to create an archive for future studies. The description should include an update on collection, processing, and storage of biological specimens including sample management procedures.
• Bio-repository group (Molecular Genetic Bank): Provide an update on collection, processing, and storage of biological specimens including sample management procedures. Since this is such a unique, valuable resource, the investigators should identify the strategies to protect and maintain the resource and perform quality control (including sample receipt and storage, verification of specimen identification, and appropriate de-identification of accompanying data, etc.). Personnel training in these areas should be outlined, as appropriate.
• Data and Statistics group: CCSS statisticians should be involved in reviewing all requests for access to CCSS data to ensure sound statistical design and analysis consistent with the overall design of CCSS. The CCSS statisticians are also expected to review all manuscripts of scientific publications generated using CCSS data for accuracy, consistency, and appropriateness of method descriptions and data interpretation. This expectation applies to manuscripts authored by internal CCSS investigators as well as by external investigators using CCSS data. CCSS statisticians and ancillary personnel will be expected to interact regularly with the CCSS leadership to discuss emerging issues associated with the data collection/management as well as study design and analytic issues relevant to ongoing data-analysis projects. Outline the priorities in these areas and explain rules and general procedures for curating datasets for release to external investigators (including data cleaning/editing and quality control for such actions).

Note: Supplementary data in support of this subsection are requested under Other Attachments as Attachment 3.

Sub-section D. Program for Cohort Integration and Basic Resource Functions

In this section, address the following aspects.

• Define the overall goals for cohort integration and basic functions;
• Describe plans for surveillance and maintenance of the merged cohort including validation and quality control;
• Outline long-range strategy for the use of CCSS data to facilitate conception, development, implementation, and conduct of future intervention studies (beyond the scope of this FOA);
• Indicate specific opportunities/directions for such intervention studies inspired by CCSS findings;
• Characterize approaches to communication, education, and maintenance of contacts with the study participants;
• Although innovation is not essential for CCSS research, indicate any concepts, methodologies, and/or intervention options proposed that are novel to field of cancer survivorship;
• Outline approaches to protecting subject privacy and confidentiality for study participants; and
• Outline procedures to ensure that all participating clinical sites fully comply with all NIH and Federal Regulations in terms of protection of human subjects including IRB approvals, informed consent, and other required regulatory approval documents (avoid repetitions with the separate required Section of Research Plan, "Protection of Human Subjects").

Note: Supplementary data in support of this subsection are requested under Other Attachments as Attachment 4.

Sub-section E. Internal Research (including Methodologic Research, if applicable)

• Identify the investigators expected to lead the internal research.
• Define the current overall research goals.
• If methodologic research is proposed, it should be aimed at developing, testing, and validating new methods and approaches to improve the proposed cohort infrastructure.
• Describe the general focus areas/research directions for research by CCSS investigators.
• Describe how new research directions/projects will be initiated, reviewed, and prioritized for the final approval by the Steering Committee.
• Describe how the genetic resources (data, biospecimens) accumulated through the Molecular Genetic Bank will be made available for external investigators.
• Outline a strategy to use CCSS data to improve the understanding of late effects on survivors health by specific organ system.
• Pilot projects for junior investigators: Explain the anticipated role of pilot projects in helping junior investigators in hypothesis-generating and hypothesis-testing studies. The goal is to facilitate generation of preliminary data that junior investigators could use to further develop competitive research directions for which, ultimately, an independent funding (e.g., R01 grants) would be sought. Do NOT propose any specific pilot projects in the application. Rather, provide details on how such pilot projects will be generated, evaluated, and prioritized. The plans should incorporate the expectation that the Steering Committee will be involved in the final approval of pilot projects for execution. A "junior" investigator is defined as an investigator at the level of Assistant Professor or lower when the pilot project funding begins.
• Describe other activities oriented on engaging junior investigators at all CCSS-affiliated institutions in pediatric cancer survivorship research.

Note: Supplementary data in support of this subsection are requested under Other Attachments as Attachment 5.

Sub-Section F. Outreach and External Research

• Describe the approaches to facilitate research by "outside investigators" (i.e., investigators not affiliated with any of the institutions forming the CCSS) and outreach strategies to make the resource optimally available to interested scientists and efficiently disseminate the resulting findings to broad communities;
• Identify the individual(s) primarily responsible for these activities;
• Address priorities and focus areas that might be of interest to non-CCSS investigators. Define the anticipated role of Working Groups in review of research proposed by outside investigators to CCSS.
• Address approaches to increase the scientific and public visibility of the CCSS findings (notably including their impact on the Children's Oncology Group Late Effects Guidelines, http://www.childrensoncologygroup.org/disc/le/).
• Outline existing and planned international collaborations with other childhood cancer survivor groups.

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.

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• Applicants are expected to outline the plans for facilitation of biospecimen and data sharing with non-CCSS investigators and/or sharing the findings based on CCSS with the general public consistent with achieving the goals of the program.

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.

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

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

See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about Key Dates. 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.

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit 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.

Important reminders:

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

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

See more tips for avoiding common errors.

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

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Important Update: See NOT-OD-16-006 for updated review language for applications for due dates on or after January 25, 2016.

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 particular announcement, note the following:

Merit assessment of the CCSS application will particularly emphasize the usefulness of this resource to the scientific community in terms of the ability to provide rigorous insights into late effects of treatment for childhood cancer and inspire strategies for alleviating these late effects. The overall impact of the entire CCSS will be assessed based on the likelihood that the resource will contribute significantly to the improvements in quality of life for pediatric cancer survivors.

Individual aspects identified under the five criteria below will be assessed collectively in the context of their optimization for this overarching goal.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the CCSS to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

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

Does the CCSS application address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA: As proposed, will the CCSS provide the anticipated benefits in terms of meaningful scientific insights that would be able to inspire strategies for alleviating the late effects of treatment for childhood cancer? Can the proposed CCSS maximize the usefulness of this resource to scientific community? What is the likelihood that the activities under the CCSS award will inspire the investigators and facilitate their attempts to leverage other resources towards additional goals (exceeding the required scope) that would enhance the potential impact of the resource (e.g., intervention studies, molecular genetic studies, etc.)?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the CCSS ? If Early Stage Investigators or New Investigators, or 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 CCSS 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 CCSS?

Specific to this FOA: What is the likelihood that the proposed leadership will be successful in achieving the overall scientific agenda and the CCSS goals? Are the investigators leading CCSS functional units optimal in terms of enhancing the use of the CCSS cohort for internal and external scientific projects?

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 CCSS? 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?

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

Specific to this FOA:

Are the CCSS design and plans for administrative functions sufficient in terms of efficient support of CCSS activities across multiple participating institutions?

Are the organization, personnel, and procedures proposed for the specific Functional Support groups appropriate and well optimized? Are there appropriate plans for the sufficiently rigorous management (including quality control) of data and biospecimens collected by the CCSS?

Cohort Integration and Basic Resource Functions: Are the current CCSS cohorts adequate for the overall goals of the program? If the cohorts are not sufficiently representative, do the applicants address this issue and propose approaches to ameliorate the problem? Are the plans to maintain the merged cohort well thought out and sufficiently specific (e.g., with regard to maintaining contact with study participants, collecting outcome data, etc.)? How well do the proposed plans cover and track outcome variables that are critical for the goals of this FOA? Are the proposed approaches optimal and conductive to identifying important opportunities for future intervention studies?

Internal Research: Is the internal research agenda for CCSS well developed and responsive to the needs and expectations (e.g., in terms of sufficient focus on specific organ system, hypothesis-testing molecular genetic studies, engaging junior investigators, etc.)?

Outreach and External Research: Will external investigators have sufficient and easy access to the resource? Are appropriate measures proposed to ensure that outside investigators utilizing the CCSS resources comply with the access/usage policies and rules? How valuable for the resource are external collaborations (e.g., with other childhood cancer survivor groups)? How likely are the proposed outreach activities to increase the role of the CCSS-based research findings in the updates of cancer survivor guidelines?

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 CCSS benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

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

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

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

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.

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 Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

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:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the National Cancer Advisory Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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.

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.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

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

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

• Defining the research plan and goals;
• Overseeing the execution of the program as a whole;
• Coordinating/overseeing research design, the development of a common study protocols for involvement of participants, and other research activities;
• Ensuring compliance of the CCSS with the mandatory regulations (including protection of human subjects);
• Overseeing the preparation of key study documents, including questionnaires, medical record abstract forms, and field procedures manuals;
• Overseeing establishment and maintenance of quality control in all data and materials collection and management procedures;
• Chairing the CCSS Steering Committee;
• Cooperating with NCI programmatic, technical and administrative staff;
• Implementing the recommendations of the CCSS Steering Committee to the extent consistent with the applicable grant regulations; and
• Administratively managing the U24 award.

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.

Awardee institution and all participating institutions will be responsible for ensuring that the design, conduct, and/or reporting of research conducted by CCSS are not biased by any conflicting financial conflict of interests of an investigator. Awardees will be expected to implement appropriate policy and procedures on financial Conflict of Interest (COI).

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

A designated NCI Program Director(s) acting as a Project Scientist(s) will have the following responsibilities:

• Participating in the activities of CCSS Steering Committee;
• Providing technical assistance and advice to the awardees as appropriate (e.g., assisting in the development of the research protocols and/or interpretation and reporting of the collected information);
• Monitoring progress of the resource as a whole and specific studies conducted.
• Conducting periodic site visits for discussions with awardee research teams, observation of field data collection and management techniques, other matters;
• Coordinating interactions, as appropriate and needed, with the NCI-supported Children's Oncology Group especially in data retrieval from exiting databases;
• Facilitating interactions/collaborations between the awardees and other NCI-sponsored programs, investigators, or organizations that may contribute to the CCSS goals;
• Serving as a liaison between the CCSS awardees and NCI staff members and investigators that may provide addition expertise and/or resources to the program;
• Monitoring the adherence of the awardees to the approved data sharing plans.
• Approve changes in the institutional membership based on recommendations from the CCSS PD(s)/PI(s).

The NCI reserves the right to adjust funding, withhold, suspend, or terminate the support to the awardee if the team is unable to meet the performance requirements set forth in these Terms and Conditions of Award, or significantly lower the level of performance.

Additional NCI staff members may be designated to have substantial involvement.

In addition, an NCI Program Director acting as the Program Official will be responsible for the normal scientific and programmatic stewardship and programmatic stewardship of the award, and will be named in the award notice.

Areas of Joint Responsibility include:

The Steering Committee will serve as the main governing board for CCSS. The CCSS Steering Committee will consist of the following voting members:

• PD/PI and a designated senior investigator [or two PD(s)/PI(s) if multiple PDs/PIs option is used];
• 1 or 2 Working Group chairs;
• 1 or 2 representatives of the support functional groups and other members as deemed necessary by the Chair of the Steering Committee; and
• Two NCI representatives.

Each voting member will have one vote, except for the NCI representatives, who will collectively have one vote. The Steering Committee will be chaired by the CCSS contact PD/PI. In the absence of the contact PD/PI, the second CCSS PD/PI (or a designated senior investigator) will chair Steering Committee meeting.

The Steering Committee may include additional individuals as non-voting members and may also form subcommittees as needed. One subcommittee should consist of external (non-affiliated with CCSS) researchers, who are experts in the field to advise the PD(s)/PI(s) and Steering Committee. Steering Committee may decide to continue with the current structure of committees or subcommittees or change this structure to better fit CCSS needs.

The Steering Committee will conduct one face to face meeting a year with additional teleconferences or meetings as needed.

The Steering Committee will be responsible for any changes to the CCSS organizational structure and Standard Operating Procedures. The Steering Committee will have primary responsibility to establish priorities, and to develop and provide preliminary approval of projects (including young pilot projects) and or protocols.

The Steering Committee will review on a regular basis:

• the overall performance of the CCSS;
• the performance of specific functional support groups; and
• the performance of investigator/teams at institutions participating in the Consortium.

The CCSS Steering Committee will have the authority to place on probation and to suspend participating institutions and add new institutions as participants, if appropriate. The CCSS Steering Committee will evaluate and approve all potential treatment (intervention) concepts as well as correlative science proposals, formally presented either by members of CCSS (internal investigators) or by outside investigators using CCSS resources.

Dispute Resolution:

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

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

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

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

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

eRA Commons Help Desk (Questions regarding 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 CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Nita L. Seibel, MD
National Cancer Institute (NCI)
Telephone: 240-276-6078
Email: [email protected]

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

Esther L. Young
National Cancer Institute (NCI)
Telephone: 240-276-6325
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.