Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Cancer Institute (NCI)
Funding Opportunity Title	Childhood Cancer Survivor Study (Limited Competition U24)
Activity Code	U24 Resource-Related Research Projects Cooperative Agreements
Announcement Type	New
Related Notices	September 14, 2015 - This RFA has been reissued as RFA-CA-15-502.
Funding Opportunity Announcement (FOA) Number	RFA-CA-11-501
Companion FOA	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.395
FOA Purpose	The purpose of this Funding Opportunity Announcement (FOA) is to continue support for Childhood Cancer Survivor Study (CCSS) as a resource enabling broad studies on the long-term effects of cancer and its associated therapies on survivors of pediatric cancers. CCSS (originally funded as an investigator initiated program) serves the overall goal to quantify and better understand the effects of pediatric cancer and its treatment on later health of cancer survivors, including behavioral and sociodemographic outcomes. For these goals, CCSS has been designed as a comprehensive multicenter effort to comprehensively manage large cohorts of survivors of childhood cancer. The original cohort of study participants included 14,370 pediatric cancer survivors diagnosed between 1970 and 1986 as well as 3,737 siblings. Enrollment of a second cohort of survivors consisting of a similar number of subjects diagnosed between 1987 and 1999 is expected to be completed by the end of the current award period. The current CCSS structure includes 27 institutions, mostly in the U.S. but also in Canada.

Posted Date	February 17, 2011
Letter of Intent Due Date	Not Applicable
Application Due Date(s)	April 21, 2011
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	June-July 2011
Advisory Council Review	October, 2011
Earliest Start Date(s)	December, 2011
Expiration Date	April 22, 2011
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS398 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. While some links are provided, 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 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

Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to continue the Childhood Cancer Survivor Study (CCSS). CCSS, originally funded as an investigator initiated program, is a multi-institutional collaborative endeavor that consists of a cohort of over 14,000 five-year survivors of childhood cancer diagnosed between 1970-1986 and a similar number of five year survivors diagnosed between 1987 and 1999, and over 3,700 sibling controls.

The continued support for the CCSS as a research resource is expected to facilitate the following important research directions and specific objectives:

• Identification of high risk cancer survivorship populations for latent effects and to quantify the magnitude of the risk 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 conceptualizing, developing, and testing interventions to prevent or minimize latent effects;
• Enhance the CCSS resource by increasing the capacity 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;
• Continued follow-up of the initial population cohort (i.e., patients diagnosed between 1970-86);
• Complete recruitment to the expansion cohort (i.e., patients diagnosed between 1987-99) and conduct the first follow-up on that cohort;
• Formally merging the initial and expanded cohorts into a single resource to be maintained with periodic follow-ups;
• Expand collection and analysis of biological samples from the participating survivors; and
• Promote and facilitate the use of the CCSS resource by non-CCSS investigators.

Today, cure is the likely outcome for most children diagnosed with cancer. Improvements in therapy have increased the 5 year relative survival rate from less than 30% in 1960 to 79% in 2006. It has been shown that long-term survivors are at risk of developing a spectrum of adverse outcomes including early death, second neoplasms, organ dysfunction, impaired growth and development, decreased fertility, neurocognitive abnormalities, and overall reduction in quality or life. Because of the young age of childhood cancer survivors and thus the potential longevity of survivorship, the delayed consequences of therapy will likely have a substantial impact on their lives, their families, and society at large.

The Childhood Cancer Survivor Study has been funded by the NCI since 1993 as an investigator-initiated endeavor when a group of investigators recognized the need for a long-term follow-up study of survivors of childhood cancer. The results of the CCSS have greatly advanced knowledge of late effects among survivors of pediatric cancer. In particular, CCSS has shown that long-term survivors are at risk of developing a variety of adverse outcomes which include early death, second malignancies, organ dysfunction (eg cardiac, pulmonary, gonadal), impaired growth and development, impaired cognitive function, difficulties obtaining employment and insurance, and compromises in the quality of life. Unfortunately, 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.

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.

The emphasis of the CCSS is on approaches to ensure the functioning of CCSS as a strong and productive resource for the initial cohort of survivors diagnosed between 1970 -1986 and merge it with the second cohort consisting of childhood cancer survivors diagnosed between 1987-1999 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 and resources. In this regards, it is expected that the renewed CCSS will serve:

• Internal research (i.e., by CCSS investigators involved with CCSS Working Groups directed to answer research questions in prioritized areas of interest to CCSS); and
• Research by external investigators (i.e., non-CCSS investigators who may be interested in utilizing the CCSS resources to enrich their externally funded research projects).

Secondary goals/areas of emphasis for the program include the following aspects:

• Build 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);
• Development of strategies to improve the understanding of late effects on survivor health by specific organ system;
• Identification and collaboration with other childhood cancer survivor groups internationally; and
• Successful training/mentorship of junior investigators.

To address the goals and priorities of CCSS, applicants are expected to propose three interconnected Research Programs:

1. Program for Cohort Integration and Basic Functions;

2. Internal Research Program; and

3. Outreach and External Research Program

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:

Applicants are strongly encouraged to take advantage of the multiple PD/PI option and designate a lead PD/PI and a second PD/PI, who would share the responsibilities but would also be capable of leading the entire CCSS (e.g., in case the lead PD/PI is unable to continue serving in this role). PD/PI(s) are expected to work closely with the Steering Committee as a governing body for the CCSS (for details see Terms and Conditions of Cooperative Agreement). If multiple PD/PI option is not used, an appropriate qualified individual from the key personnel must be identified as a potential PD/PI substitute.

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

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.

Specialized Infrastructure/Support Cores:

It is expected that CCSS will include Administrative Core and specialized infrastructure Support Core as outlined below.

CCSS Administrative Core must be organized to provide overall administrative and organizational infrastructure for the entire CCSS. The CCSS Administrative Unit is expected to function as a central office, located at the lead PD/PI s institution. The Administrative Unit must provide appropriate infrastructure to serve internal needs of CCSS as well as the interactions between CCSS investigators and the Steering Committee and the NCI. It must have appropriate capabilities to provide: data management, finance and regulatory staff and other administrative staff, as needed (e.g., to administer surveys, informed consent, requests for medical record release and follow up).

Infrastructure/Support Core is expected to provide support in specific areas listed below (to be covered by dedicated sub-units).

Radiation Physics Unit must be capable of reviewing all relevant radiation therapy records for survivors who received radiation therapy. The Radiation Physics Unit 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 individuals's radiation treatment. Appropriate quality-control techniques must be used to ensure correctness of dosimetry.

Biopathology Unit will be responsible for collecting tissue on all secondary malignant neoplasms occurring in participants in the CCSS in order to identify, confirm, and analyze the neoplasms. In addition the Biopathology Unit will collect retrospectively paraffin embedded tumor material to create an archive for future studies.

Bio-repository Unit (Molecular Genetic Bank) must be organized to collect and bank the genomic DNA obtained from buccal cell or saliva samples of survivors and siblings, plus peripheral-blood samples from survivors with a second or subsequent neoplasm. The Unit must have the capability to establish lymphoblastoid cell lines from the peripheral-blood samples from study participants. Biologic material collection and distribution to individual investigators requires informed consent of CCSS study participants that is coordinated with the CCSS Administrative Unit.

Data and Statistics Unit must be able to ensure accuracy in collection and management of the data in the CCSS study. The Data and Statistics Unit will provide biostatistical support to the majority of CCSS data-analysis projects. The Data and Statistics Unit will review all research proposals involving CCSS data to ensure sound statistical design and analysis consistent with the overall design of CCSS. The Data and Statistics Unit is also expected to review all manuscripts (internal and external) generated using CCSS data for accuracy, consistency, and appropriateness of method descriptions and data interpretation. Members of the Data and Statistics Unit will meet regularly with the CCSS Coordinating Unit and Radiation and Physics Unit to discuss emerging issues associated with the data collection/management as well as study design and analytic issues relevant to ongoing data-analysis projects.

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities, The applicant will be solely responsible for planning, directing and executing th proposed project.
Application Types Allowed	Renewal only the renewal application for the current CCSS award is allowed for this FOA. The OER Glossary and the PHS398 Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The NCI intends to commit an estimated total of $4,380, 000 per year for 5 years to fund 1 CCSS award..
Award Budget	Budget request must not exceed $4,380, 000/year (total cost) and $21.9 million (total costs) over 5 yearsl.
Award Project Period	5 years

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.

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

Only the institution that is the current recipient of the CCSS award is eligible to apply. Consortium members (affiliated under subcontractual arrangments) are generally expected to be Domestic institutions although Canadian institutions are also eligible as application components. Other Foreign (non-U.S. and non-Canadian) instituions are NOT allowed to participate on the application submitted in response to this FOA.

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.

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) 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.

More than one PD/PI (i.e., multiple PDs/PIs) may be designated on the application.

Applicants are encouraged to designate a lead 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.

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 PHS398 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.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Only the current CCSS awardee institution is eligible to apply and may submit one application.

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

It is critical that applicants follow the instructions in the PHS398 Application Guide, 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.

Not Applicable

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission, two additional paper copies of the application and all copies of the appendix files must be sent to:

Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301)-496-3428
FAX: (301) 402-0275
Email: [email protected]

All page limitations described in the PHS398 Application Guide must be followed, with the following exceptions or additional requirements:

• Specific Aims is limited to 1 page.
• Research Strategy, including tables, graphs, figures, diagrams, and charts is limited to: 12 pages for CCSS Overview and Progress Report; 6 pages for Leadership and Administrative Core; 6 pages for Specialized Infrastructure/Support Core; 6 pages for Program for Cohort Integration and Basic Functions; 6 pages for Internal Research Program, and 6 pages for Outreach and External Research Program.

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:

Table of Contents (PHS 398 Form Page 3): Modify Form Page 3 of the PHS 398 to include in Section 3 "Research Strategy" the following sub-sections A-F:

A. CCSS Overview and Progress Report

B. Leadership and Administrative Structure (Administrative Core)

C. Specialized Infrastructure/Support Core

D. Program for Cohort Integration and Basic Functions

E. Internal Research Program

F. Outreach and External Research Program

BUDGET

This FOA uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html).

Budget (PHS 398 Form Pages 4 and 5): Follow the current PHS 398 instructions to provide a detailed budget (direct costs) for the entire application for the first 12-month period (Form page 4) and the entire proposed project period (Form page 5). Include appropriate budget pages for any sub-contractual arrangements proposed.

After the overall budget pages, use additional Form Pages 4 and 5 to provide detailed separate budget information (first year and cumulative budgets for the entire project period) for the individual application components. This part must include:

• Budget pages for Administrative Core;
• Budget pages separately for Specialized Infrastructure/Support Core;
• Budget pages separately for Program for Cohort Integration and Basic Functions
• Budget pages separately for Internal Research Program; and
• Budget pages for Outreach and External Research Program.

Research Strategy

Standard sub-sections of Section 3. Research Strategy of the PHS 398 Research Plan are replaced by the sub-sections A-F (see details below); and

The PHS 398 standard page limit for Research Strategy is replaced by individual limits indicated below for the sub-sections A-F.

Other sections of the PHS398 Research Plan remain unmodified and should be completed following standard instructions.

A. CCSS Overview and Progress Report (up to 12 pages)

In this section, address the following aspects.

• Background and Experience: Describe the group's history and experience in designing and implementing the CCSS. Outline the scientific rationale underpinning the need for the cohort.
• 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 new cohort, including identification and recruitment of study subjects and expanded sibling population
• CCSS Significance and Overall Goals: Describe the need for 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.

B. Leadership and Administrative Structure (Administrative Core) (up to 6 pages)

In this section, address the following aspects.

• Senior Leadership: The use of the multiple PDs/PIs option is encouraged. Outline the proposed leadership structure (avoiding duplication with the "Leadership Structure" Section of PHS 398 Research Plan, which is required if the multiple PDs/PIs option is used). In addition to an overall PD/PI (expected to be designated as contact PD/PI at the application-submitting institution), identify a substitute PD/PI candidate to assure program continuity. The qualifications and experience of both persons must be described, specifically documenting their respective abilities to organize and manage the CCSS and related activities as multiinstitutional collaborative efforts. Describe the strategy to divide leadership responsibilities among key/senior individuals. Outline the qualifications, experience, and proposed duties of other key individuals in the leadership besides the PD(s)/PI(s) (for example, Directors of Administrative Units and Infrastructure/Support Units).

CCSS overall organizational structure and supporting facilities including the proposed organizational structure.The Steering Committee will be described including composition, duties and any subcommittees. One of the subcommittees of the Steering Committee should include a group of external experts to advise the PD(s)/PI(s) and Steering Committee. Details should be provided including how this subcommittee works with the PD(s )/PI(s) and Steering Committee. An organizational chart showing how the group will function must be included. The availability of key facilities must be described. Note: Applicants are reminded that it is the responsibility of all participating institutions to ensure 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. For this goal, applicants are encouraged to implement appropriate policy and procedures on financial Conflict of Interest (COI).

• Administrative Core: provide details pertaining to roles, tasks, and organization of the Adminstrative Core as an infrastructure serving CCSS as well as the interactions between CCSS investigators and the Steering Committee and the NCI. Identify the Core director.

C. Specialized Infrastructure/Support Core (up to 6 pages total for all subunits)

In this section, provide details on the organization and functioning of Specialized Infrastructure/Support Core. It is expected that the following functional subunits will be included.

• Radiation Physics;
• Biopathology;
• Bio-repository (Molecular Genetic Bank); and
• Data and Statistics.

For each of these subunits, identify the subunit leader(s) and outline how the unit (or its equivalent) has contributed to the CCSS, past performance, future plans and quality control (when appropriate). For the Biopathology subunit and Biorepository subunit, the description should also include an update on collection, processing and storage of biological specimens including sample management procedures.

D. Program for Cohort Integration and Basic Functions (up to 6 pages)

In this section, address the following aspects.

• Identify the Program leader(s) and Specific Aims;
• Describe plans for surveillance and maintenance of the initial cohort including validation and quality control;
• Provide estimates of the accrual for the second cohort from member institutions which will be used in the future for metrics of performance;
• Provide detailed plans and timing for merging the two cohorts and maintaining the merged cohort as an integrated resource;
• 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 maintaining contacts with the study participants;
• Outline approaches to protecting subject privacy and confidentiality for study particpants; 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 6 "Protection of Human Subjects" of Research Plan).

E. Internal Research Program (including Methodologic Research, if applicable) (up to 6 pages)

• Identify the Program leader(s) and Specific Aims;
• Describe plans for methodologic research aimed at developing, testing, and validating new methods and approaches to improve the proposed cohort infrastructure.
• The applicant team is expected to continue the current structure for internal research and review, which includes Working Groups. Describe the Working Groups, role within CCSS and address priorities and focus areas for research initiated from Working Groups and recommendations to Steering Committee;
• Outline a strategy to use CCSS data to improve the understanding of late effects on survivor health by specific organ system;
• Outline plans how the resource and its investigators can stimulate and facilitate hypothesis-generating and hypothesis testing molecular genetic studies. The goal is to use the resource to generate preliminary data and develop molecular genetics projects for which an independent funding will be sought (e.g., through R01 grants). Up to $100,000 per year may be set aside for such pilot projects. No specific projects need to be described in the application. However, applicants should provide details on how such pilot projects will be generated, evaluated, and selected for execution.
• Describe activities oriented on training junior investigators at participating institutions in pediatric cancer survivorship research. As one possible approach, consider using the instrument of the above-mentioned pilot research projects.

F. Outreach and External Research Program(up to 6 pages). In this section, describe how the resource will function to facilitate research by outside investigators and outreach strategies to make the resource and resulting findings available to scientific and broad communities

• Identify the Program leader(s) and Specific Aims;
• Address priorities and focus areas that might be of interest to non-CCSS investigators. Outline the plans for facilitation of biospecimen and data sharing with non-CCSS investigators and/or public (if applicable).
• Describe the role of Working Groups and role in review of research proposed from outside investigators to CCSS and recommendations to Steering Committee.
• Address approaches to increase the visibility of the CCSS findings in 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 (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS) as provided in the PHS398 Application Guide, with the following modifications:

• Regardless of the amount of direct costs requested for any one year, Data Sharing Plan must be addressed.
• Whenever appropriate and feasible, the proposed data types and outputs for sharing are expected to comply with data standards of the Cancer Biomedical Informatics Grid (caBIG , https://cabig.nci.nih.gov) as a unified platform for sharing and disseminating cancer-related information.

Appendix

Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 Application Guide.

Part I. Overview Information contains information about Key Dates.

Information on the process of receipt and determining if your application is considered on-time is described in detail in the PHS398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

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 received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by the NCI. Applications that are incomplete and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

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:

This FOA underscores the role of CCSS as a resource to the cancer research community to provide insight and strategies for alleviating late effects of treatment for childhood cancer and ultimately improving the quality of life for cancer survivors. Therefore, in evaluating the CCSS application it is particularly important to assess how well the plans address these goals and maximize the use of this resource.

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the proposed Program 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 Program 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 resource that by its nature is not innovative may be essential to advance a field.

Significance

Does the proposed CCSS continuation address an important problem or a critical barrier to progress in the field? If the aims of the proposed CCSS continuation 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?

Investigator(s)

Are the PD/PIs, collaborators, and other researchers well suited to the proposed CCSS continuation? 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 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?

Innovation

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

Specific to this FOA:

Although not essential for the CCSS function, are concepts, methodologies, or intervention options proposed novel to field of cancer survivorship?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the proposed CCSS continuation? 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 proposed CCSS continuation involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA:

Are the CCSS design and methods adequate to achieve the stated objectives and to support the stated overall research agenda? How well will the applicants leverage other resources to achieve some of the goals (eg intervention studies, molecular genetic studies etc) beyond the scope of the funding for the cohort? Will the applicants take optimal advantage of other resources to achieve some of the short-term goals of the program as well as facilitate long-term objectives that are beyond the scope of this FOA (e.g., future intervention studies, molecular genetic studies, etc)?

Environment

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

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

Leadership and Administrative Structure (Administrative Core)

• What is the likelihood that the proposed leadership will be successful in achieving the overall scientific agenda and the goals of the program outlined in this FOA?
• Are the leadership and organizational infrastructure optimal in terms of enhancing the use of the CCSS cohort for internal and external scientific projects?
• How adequate are the administrative and communication structures of the Administrative Unit in terms of efficiently supporting CCSS activities across multiple participating institutions?
• How adequate are the infrastructure and tasks for the Administrative Unit in terms of ensuring protection of subject confidentiality and obtaining informed consent? Is the proposed coordination of these aspects by the Administrative Unit sufficient?

Infrastructure Support Core

• Are the structure, organization, personnel, and procedures proposed for the specific Units of Support Core appropriate and well optimized?
• Are all the individual units (such as Radiation Physics Unit, Biopathology Unit, Data and Statistics Unit, Bio-repository Unit) essential? Will they adequately contribute to the objectives of the CCSS?
• Are there appropriate plans for the rigorous management (including quality control) of data and biospecimens collected by the CCSS?

Cohort Integration and Basic 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?
• How appropriate are the approach and timing to complete the merger of the two current cohorts? Are the plans to maintain the merged cohort well thought out and sufficiently detailed? Are the length of follow-up and age characteristics of the cohort optimal?
• How well do the proposed plans cover outcome variables that are critical for the goals of this FOA? Is the tracking of specific outcome variables optimal in terms of providing the most complete and useful information?
• To what degree have the applicants taken advantage of the resource in identifying important opportunities for intervention studies?
• Are the plans for activities related to contacts with study participants appropriate and well developed?

Internal Research Program

• How well is the internal research agenda for CCSS developed? Is the process appropriate and meeting the needs?
• How appropriate are the strategies proposed to improve the understanding of late effects on survivor health by specific organ system? Are these strategies comprehensive enough?
• Is there sufficient attention to stimulating the development and conduct of hypothesis-testing molecular genetic studies?
• Are the scope and quality of methodologic research proposed adequate to the needs and characteristics of the resource?
• How well do the plans for pilot projects in molecular genetics take advantage of the resource?
• How appropriate for the needs are the plans for training junior investigators?

Resource Functions to Facilitate Research by Outside Investigators and Outreach

• Is the CCSS agenda to reach outside investigators well developed and sufficient? Are the processes for providing access to the resource and interactions with the ouside investigators appropriate and meeting the needs in this area?
• How well is the CCSS oversight set up to ensure that outside investigators utilizing the CCSS resources comply with the regulations stipulating resource/data sharing?
• How well developed and appropriate are the plans for international collaborations with other childhood cancer survivor groups?
• How likely are the proposed outreach activities to increase the contribution of the CCSS-based research findings in the updates of cancer survivor guidelines such as those by the Children's Oncology Group (http://www.childrensoncologygroup.org/disc/le/)?

Protections for Human Subjects

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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed Childhood Cancer Survivor Studyt involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

For Renewals, the committee will consider the progress made in the last funding period, including the following specific aspects:

• How successful has the applicant been in completing CCSS aims and activities for the current funding period?
• How well has the CCSS organizational structure supported the objectives of CCSS in the current funding period? How well have the CCSS Working Groups contributed to formulating the research agenda?
• How efficient has the CCSS been in terms of supporting scientific projects by outside investigators (as measured e.g., by publications and new grants resulting from such projects)?
• How successful has CCSS been in providing public access to the CCSS dataset and specimens? Has this access been sufficiently broad and effectively encouraged and publicized?

Revisions

Not Applicable

As applicable for the CCSI continuation 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/priority score.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the 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) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

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

As part of the scientific peer review, all applications:

• Will receive a written critique.

Application will be reviewed by an appropriate expert panel convened by the NCI.to the NCI . Following initial peer review, recommended application 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 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 the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants 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.

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 and the development of a common study protocol for involvement of participants;
• 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;
• Overseeing final data analysis and interpretation and preparation of publications of the study findings;
• 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.

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 managment techniques, other matters;
• Coordinating future activities, if any, with the 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 liason 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 membership based on recommendations from the 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. The substantially involved NCI staff members will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications. If such participation is deemed essential, these individuals will seek NCI waivers according to the NCI procedures for management of conflict of interest.

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. If this individual is substantially involved in the CCSS activities, he/she will not attend peer review meetings of renewal and /or supplemental applications or will seek NCI waiver if such participation is essential.

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 directors of the support units 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 PD/PI. In the absence of 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 external subcommittee could 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 and or protocols.

The Steering Committee will review on a regular basis:

• the overall performance of the CCSS;
• the performance of specific support units; and
• the performance of Member Sites.

The CCSS Steering Committee will have the authority to place on probation and to suspend participating Member sites and add new Members. Evaluating and approving 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 Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

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.

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: [email protected]

Nita L. Seibel, MD
Clinical Investigations Branch
Cancer Therapy Evaluation Program
National Cancer Institute
6130 Executive Blvd. Rm 7025, MSC 7436
Bethesda, MD 20892
Telephone: 301-435-9204
Email: [email protected]

Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-3428
FAX: (301) 402-0275
Email: [email protected]

Gerard B. Mc Cann
Office of Grants Administration
National Cancer Institute
6120 Executive Boulevard, EPS 243, MSC 7150
Bethesda, MD 20892-7150 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: 301-496-3183
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 Parts 74 and 92.