Part I Overview Information

Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH) (http://www.nih.gov/)

Components of Participating Organizations
National Cancer Institute (NCI) (http://www.cancer.gov/)

Title: Early Detection Research Network: Data Management and Coordinating Center and Statistics and Biomarker Resource Center (U24)

Announcement Type
Reissuance of RFA-CA-05-501

Update: The following update relating to this announcement has been issued:

• November 06, 2014 - This RFA has been reissued as RFA-CA-14-017.
• August 19, 2009 - See Notice NOT-CA-09-033 The NCI will hold a pre-application meeting.

Request For Applications (FOA) Number: RFA-CA-09-020

Catalog of Federal Domestic Assistance Number(s)
93.393, 93.394

Key Dates
Release Date: July 24, 2009
Letters of Intent Receipt Date: September 29, 2009
Application Receipt Date: October 29, 2009
Peer Review Date: February/March 2010
Council Review Date: May 2010
Earliest Anticipated Start Date: July 2010
Additional Information To Be Available Date (URL Activation Date): Not applicable
Expiration Date: October 30, 2009

Due Dates for E.O. 12372

Not Applicable

PRE-APPLICATION MEETING

The NCI anticipates holding a pre-application meeting on September 29, 2009 at 9:00 AM - noon EDT to which all interested prospective applicants are invited. NCI program and review staff members will make presentations to explain the goals and objectives for the NCI Early Detection Research Network and its components, including the Data Management and Coordinating Center and the Statistics and Biomarker Resource Center. The discussion will also cover the preparation of applications and the peer review process. An NCI Grants Management Specialist will be available to answer financial questions. The meeting will be videocast with an opportunity for internet viewers to submit questions by e-mail.

Additional Overview Content

Executive Summary

• Purpose. This funding opportunity announcement (FOA) solicits cooperative agreement applications for a Data Management and Coordinating Center (DMCC) and a Statistics and Biomarker Resource Center (SBRC) as components of the Early Detection Research Network (EDRN). EDRN is a national consortium funded to discover, develop, and validate biomarkers for early cancer detection, risk assessment and the molecular diagnosis and prognosis of early cancer. Statistical and informatics activities for the EDRN are divided between the DMCC and the SBRC, as follows. The DMCC supports statistical and computational analysis, data management and protocol development, and informatics infrastructure and coordinates network-wide meetings and conferences. Its responsibilities are: (1) Network Coordination, (2) Data Management and Protocol Development, (3) Theoretical and Applied Statistical Research, and (4) Validation Infrastructure and Services. The SBRC is responsible for providing statistical services and consultation to EDRN investigators on study design and protocol development of individual EDRN studies and functions as the content management center for the EDRN biomarker knowledgebase. The other three main components of the EDRN are the Biomarker Developmental Laboratories (BDLs), the Clinical Validation Centers (CVCs), and the Biomarker Reference Laboratories (BRLs).
• Mechanism of Support. This FOA utilizes the NIH Cooperative Agreement (U24) award mechanism. Parallel FOAs for other EDRN components include RFA-CA-09-017 (U01) for BDLs, RFA-CA-09-018 (U01) for CVCs, and RFA-CA-09-019 (U24) for BRLs.
• Funds Available and Anticipated Number of Awards. The NCI expects to commit approximately $2 million per year to fund one DMCC award and approximately $500,000 per year to fund one SBRC award.
• Budget and Project Period. Applicants for the DMCC award may request a project period of up to 5 years at budget of up to $1.3 million per year (direct costs). Applicants for the SBRC award may request a project period of up to 5 years at a budget of up to $300,000 per year (direct costs).
• Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
• Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are encouraged to apply for NIH support.
• Number of PDs/PIs. Only one PD/PI may be designated on the application.
• Number of Applications. Applicant institutions may submit more than one application, provided they are scientifically distinct. Note that the same applicant or group of applicants cannot be awarded both the U24 award for the DMCC and the U24 award for the SBRC. Applicants must also be aware that a given PD/PI may serve in that role on only one EDRN award.
• Resubmissions. Resubmission applications are not permitted in response to this FOA.
• Renewals. Only the current DMCC awardees may submit a renewal application in response to this FOA.
• Special Date(s). This FOA uses non-standard receipt and other dates. See Receipt, Review and Anticipated Start Dates.
• Application Materials. See Section IV.1 for application materials.
• Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY 301-451-5936.

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2. Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Receipt, Review and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
D. Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
A. Cooperative Agreement Terms and Conditions of Award
1. Principal Investigator Rights and Responsibilities
2. NIH Responsibilities
3. Collaborative Responsibilities
4. Arbitration Process
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)
4. Intellectual Property Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Purpose

In this Funding Opportunity Announcement (FOA), the Division of Cancer Prevention (DCP), National Cancer Institute (NCI), solicits new and competing renewal applications for a Data Management and Coordinating Center (DMCC) award and new applications for a Statistics and Biomarker Resource Center (SBRC) award. DMCC and SBRC are important components of the national Early Detection Research Network (EDRN or Network , http://edrn.nci.nih.gov/). DMCC supports statistical and computational analysis, data management and protocol development, and informatics infrastructure and coordinates network-wide meetings and conferences. The SBRC provides statistical advice and consultation to EDRN investigators on study design and protocol development of individual EDRN studies and functions as the content management center for the EDRN biomarker knowledgebase. The mission of EDRN is the development, evaluation, and validation of biomarkers for early cancer detection, risk assessment and the molecular diagnosis and prognosis of early cancer. Each of the four scientific components of EDRN is covered by a parallel FOA.

These main EDRN components include:

1. Data Management and Coordinating Center (DMCC) and Statistics and Biomarker Resource Center (SBRC) (this RFA-CA-09-020);

2. Biomarker Developmental Laboratories (BDLs) (RFA-CA-09-017), which will discover, develop, and characterize new or refine existing biomarkers and assays;

3. Clinical Validation Centers (CVCs); formerly known as Clinical Epidemiology and Validation Centers) (RFA-CA-09-018), which will conduct clinical research on the validation of biomarkers in early cancer detection and risk assessment and serve as clinical resource centers for the EDRN; and

4. Biomarker Reference Laboratories (BRLs) (RFA-CA-09-019), which will serve as a Network resource for clinical and laboratory validation of biomarkers, including technological development and refinement.

All EDRN-related FOAs are open to all qualified applicants, NOT only to the current EDRN awardees.

Biomarkers-Definition. Biomarkers are defined as cellular, biochemical, and molecular (including genetic and epigenetic) characteristics by which normal and/or abnormal processes can be recognized and/or monitored. Biomarkers are measurable in biological materials, such as in tissues, cells, and/or bodily fluids.

Background

Overall Goals of the Early Detection Research Network. The EDRN program is established to: (a) promote translational research to identify biomarkers for cancer risk, early detection, and molecular diagnosis and prognosis of early cancer; and (b) coordinate biomarker research and therapeutic strategies in order to reduce cancer morbidity and mortality. These goals are to be achieved through strategic and systematic, evidence-based discovery, development, and validation of biomarkers (for details, see the EDRN Objectives in the Guidelines document on the EDRN web site at http://edrn.nci.nih.gov/FOA-guidelines).

EDRN s goals include but are not limited to the following:

• Improve the screening processes for major epithelial cancers with national recommendations for cancer screening, such as for cancers of the colon, breast, cervix, and prostate;
• Develop biomarkers for the early detection of cancers that are major causes of cancer-related morbidity and mortality (e.g. those of the ovary, pancreas, liver, esophagus and stomach),;
• Facilitate the co-development of diagnostics with prevention or therapeutic interventions (theranostics);
• Integrate the state-of-the-science knowledge of genetic, cell signaling, and biochemical pathways with biomarker discovery efforts to have a broader applicability across different tumor types;
• Determine the potential of novel, network- and pathway-based biomarkers to detect and diagnose cancer (noting that pathway biomarkers would allow a systems biology-based approach to diagnosis, prevention, and therapy);
• Develop new serum- and tissue-related methods for early detection and diagnosis;
• Identify clinically significant disease and predictions of clinical outcome, with or without conventional tissue examination, and identify currently available biomarker tests;
• Expand collaborative efforts and shared resources to improve the capacity to conduct biomarker development and validation trials;
• Establish a biomarker database to capture and share methods and pre-competitive data on the validation and qualification of biomarkers;
• Employ cost-effectiveness measuring tools to evaluate biomarker discovery, development, and validation, and collaborate with the NCI’s CISNET (Cancer Intervention and Surveillance Modeling Network) on integrating cost-benefit effect models in the biomarker discovery and development processes; and
• Create well-defined standards and guidelines for biomarker development, validation, and qualification using the NCI-led Translational Research Working Group (TRWG)-developed Device Pathway to reduce uncertainty in discovery and development of biomarkers.

Since its inception in 1999, the EDRN has followed a "vertical" approach to biomarker research - that is, through the development, use, and support of an established, integrated, multidisciplinary research environment, which facilitates collaborations and hand-offs among technology developers, basic scientists, clinicians, epidemiologists, biostatisticians, and other health professionals, and, therefore, one that expedites efficacious clinical applications of the molecular knowledge that has burgeoned in recent years.

EDRN Phases of Biomarker Development. EDRN has produced a system for evaluating biomarkers as tools to clinically detect cancer before symptoms appear, and to identify people at risk (http://edrn.nci.nih.gov/). A five-phase approach has been established as a standard and a roadmap for successfully translating research on biomarker applications from the laboratory to the bedside:

Phase 1: the pre-clinical exploratory phase;

Phase 2: the validation phase (case/control);

Phase 3: the retrospective longitudinal phase;

Phase 4: the prospective screening study phase; and

Phase 5: the cancer control phase.

For more details, see Biomarker Development Plan in the FOA Guidelines, Section I: http://edrn.nci.nih.gov/FOA-guidelines.

In addition to the establishment of the five-phase approach for biomarker development, a coherent and comprehensive set of guidelines for study design for the discovery and evaluation of biomarkers for use in screening and early cancer detection, diagnosis, or prognosis has been delineated. A prospective-specimen collection, retrospective-blinded-evaluation (PRoBE) design for biomarker development is proposed. A set of rigorous study design standards and guidelines are described, which further address issues regarding the rate of false discovery due to the use of samples of convenience and introduction of bias and data over-fitting. The PRoBE study design includes four key components, which relate to: 1) the clinical context and outcomes; 2) criteria for measuring biomarker performance; 3) the biomarker itself; and 4) the sample size included in the study (see Biomarker Development Plan in the FOA Guidelines, Section I: http://edrn.nci.nih.gov/FOA-guidelines).

EDRN Administrative Structures

EDRN Organization: Structured around four main scientific components, EDRN currently includes 24 Biomarker Developmental Laboratories (BDLs), six Biomarker Reference Laboratories (BRLs), 10 Clinical Epidemiology and Validation Centers (CEVCs), and a Data Management and Coordinating Center (DMCC) (see The Early Detection Research Network: Investing in Translational Research on Biomarkers of Early Cancer and Cancer Risk, Fourth Report; NIH Publication No. 07-6135, January 2008 at http://edrn.nci.nih.gov/docs).

Steering Committee: The Steering Committee (SC) is the governing body of EDRN and is comprised of all EDRN Principal Investigators (PIs), including the PDs/PIs of Multi-PI awards, and the NCI-designated Program Coordinator. The SC has responsibility for the scientific management and oversight of all Network activities, including monitoring the activities of the DMCC. For the administrative structure and responsibilities of the Steering Committee, see "Collaborative Responsibilities."

The Network Consulting Team (NCT) is composed of a Chairperson and non-EDRN members appointed by NCI. The NCT reviews the progress of the EDRN, recommends new research initiatives, and ensures that the Network is responsive to promising opportunities in early detection research and risk assessment. The NCT can recommend new research projects to the SC or to NCI. Members of the NCT can serve on ad-hoc Committees of the EDRN, internal review groups, and as consultants to subcommittees.

The DMCC provides logistic support for the conduct of the SC and NCT meetings.

Headquarters: The institution of the Chair of the SC serves as the Headquarters of the EDRN. The Chairperson of the SC is a Principal Investigator (PI) of an EDRN cooperative agreement award and is elected by the SC. The Chairperson serves as the PI of the Headquarters and implements the scientific, operational, and organizational policies of the Network. The SC Chairperson provides executive leadership, scientific direction, and management for the Network. The Headquarters serve as a center for dissemination of information to investigators and institutions in EDRN, as well as to others outside the Network.

Funds: Funds will reside with: 1) the individually funded U01/U24 awardees in EDRN; and 2) the Headquarters.

The Principal Investigators (PIs) will have funds available through the individual EDRN U01/U24 awards to support the development of the scientific program and clinical protocols (30% of the funds for each BDL and CVC will be restricted for collaborative research projects). All investigators will be encouraged to seek supplemental funding through the Small Business Innovation awards (SBIR, R43 and/or R44), Small Business Technology Transfer awards (STTR, R41 and/or R42), Exploratory/Developmental grants (R21 and/or R33), and other research support mechanisms.

Core Funds will be available to the institution of the Chair of the SC. Applicants cannot apply for the Core Funds in their U01 or U24 applications submitted in response to this FOA. Core Funds are reserved for post-award collaborative research and for a variety of other functions. Release of these Core Funds will be based on the recommendations of the SC.

Core funds are used to:

1. Support EDRN multisite biomarker validation trials (see Process of Biomarker Validation in Section I of the EDRN FOA Guidelines document at http://edrn.nci.nih.gov/FOA-guidelines);

2. Expand participation in EDRN through supplemental funding to an investigator, who is not part of the Network (however, receipt of these supplemental funds does not, in and of itself, imply membership on the SC);

3. Provide support for the development of new biomarker tests to the point at which they can be validated at multiple centers and in larger populations. If test reagents are required to scale-up at this point, the SC may provide funding to contract commercial laboratories or companies that can scale up production and maintain the quality of the reagents (e.g., monoclonal antibodies, labels, etc.), and to CVCs for subject accrual; and

4. Support data management, travel, meetings, and other EDRN collaborative activities, including participation in the EDRN Associate Membership Program (see EDRN Administrative Structures in the EDRN FOA Guidelines document at http://edrn.nci.nih.gov/FOA-guidelines).

Semi-annual financial reports from the Headquarters will be required to report Core funds.

Recipients of Core Funds, such as commercial laboratories or manufacturing companies and institutions of outside investigators, participating, for example, in validation studies, will be subjected to the resource sharing and intellectual property requirements set forth in Section IV.6 of the corresponding EDRN FOA for Other Submission Requirements and Information. Awardees must advise Core Funds recipients and outside investigators of these requirements.

Specific Research Objectives and Requirements of this FOA:

Scope. To establish and enhance both the EDRN Data Management and Coordinating Center (DMCC) and the EDRN Statistics and Biomarker Resource Center (SBRC) as important scientific components of the Early Detection Research Network (EDRN). Separate applications are solicited for these two components.

The same applicant or group of applicants cannot be awarded both the U24 award for the DMCC and the U24 award for the SBRC.

It is essential that both DMCC applicants and SBRC applicants familiarize themselves with the companion FOAs for the other EDRN components with which the DMCC and SBRC must work: Biomarker Developmental Laboratories (BDL, RFA-CA-09-017), Clinical Validation Centers (CVC, RFA-CA-09-018), and Biomarker Reference Laboratories (BRL, RFA-CA-09-019).

Part A. Data Management and Coordinating Center (DMCC) Applications

The DMCC supports statistical and computational analysis, data management, protocol development, and informatics infrastructure and provides logistical support for network-wide meetings and conferences. The DMCC must have expertise and capabilities in biostatistics, information technology, data management, protocol development, and logistical support. As the number and types of Network validation studies will vary during the five year funding period, the number and identity of DMCC personnel should change in response to the scientific opportunities. These changes must be approved by the NCI Program Coordinator. Qualified investigators in the DMCC should assume responsibility in a flexible manner as the need arises.

Specifically, the DMCC will work closely with the NCI Program Coordinator and be responsible for four major activities: (1) Network Coordination, (2) Data Management and Protocol Development, (3) Theoretical and Applied Statistical Research, and (4) Validation Infrastructure and Services.

1. Network Coordination: The DMCC will;

• Provide logistical and administrative assistance in arranging meetings of the SC, the Executive Committee of the SC, and NCT (e.g. preparing, distributing and maintaining minutes of meetings) there will be two face to face Steering Committee Meetings per year, one NCT meeting per year, and monthly Executive Committee conference calls;
• Provide logistical and administrative assistance in arranging workshops there will be one scientific workshop every 18 months;
• Provide other operational support for the Network (e.g., communications, subcommittee meetings, telephone conference calls);
• Produce and maintain all documents, including Manual of Operations and procedures manuals;
• Develop and maintain an interactive web page to publicize the EDRN and to announce the availability of EDRN-supported resources and receive input from investigators;
• Develop and maintain a "listserv" interactive email system for communication within the Network;
• Work with the NCI Program Coordinator on the online review of applications/proposal submitted to the EDRN Steering Committee.

2. Data Management and Protocol Development: The DMCC under the direction of the Steering Committee will:

• Support the development, coordination, implementation, and conduct of EDRN-collaborative research protocols, including EDRN-sponsored multi-center biomarker validation studies;
• Provide statistical analysis of EDRN-collaborative validation studies;
• Assist in preparing data analysis for manuscripts on EDRN collaborative validation studies;
• Develop worksheets and information management systems for collection of data in multi-center biomarker validation studies, verify all data, develop tests, and maintain software for within-form edit checks at data entry;
• Monitor Network protocol adherence, data collection and data submission, and report violations to the Steering Committee;
• Assist in the collection of epidemiologic information, data analysis, study designs, quality assurance for a central database, statistical analyses of pooled data, and distribution of specimens stored at sites participating in the Network;
• Develop uniform investigative protocols for data and specimen collection;
• Support the formation and distribution of EDRN biospecimen reference sets and analyze data that result from the use of these specimens;
• Develop and maintain a computerized data system for data management and statistical analysis;
• Ensure that data are collected to determine the benefits and risks that follow from positive or negative test results;
• Provide support services for the production of data forms and reports, graphics, and other materials as required;
• Provide a mechanism for rapid and routine (to be decided by the Steering Committee) transmittal of materials (e.g. computer output, reports, etc.) among the network participants and the NCI Program Coordinator and other NCI staff;
• Provide advice and consultation to EDRN investigators in study design and protocol development of EDRN-collaborative validation studies, after the study has been approved by the EDRN Steering Committee.

3. Theoretical and Applied Statistical Research: There is a need for better statistical tools for data deriving from high throughput assays. The DMCC will survey the need for such tools, consult with the Steering Committee to establish priorities, and seek approval from NCI for the development of statistical methodologies and computational tools for use by the EDRN investigator.

It is expected that the DMCC will conduct research on the development of statistical and computational tools. Areas of interest include, but are not limited to:

• Preprocessing of high dimensional data deriving from proteomic-, genomic-, epigenomic-based assays;
• Development of analytical tools for analyzing expression data (from DNA, RNA, or protein array expression) with respect to clinical endpoints;
• Development of new analytical software to extract novel, relevant information on potential biomarkers from in silico data.

4. Validation Information System and Services:

The NCI has an Interagency Agreement with the NASA Jet Propulsion Laboratory (JPL) to assist the EDRN in building IT infrastructures for distributed data and tools. The DMCC will work closely with NCI and JPL in the specification and design of software for the Network-wide enterprise development. While the DMCC will take the lead in maintaining and developing resources for EDRN Secure Website for data security, data warehouse with interfaces, and data analysis for the Network-specific validation studies, JPL will take the lead in implementing the distributed network-based data warehouse, tools and interfaces for publicly-accessible information. DMCC and JPL will work closely with NCI staff and the NCI Center for Bioinformatics.

It is also the intention of the NCI to move all publicly accessible resources and tools to an NCI-designated portal. Such resources and tools include, but are not limited to Common Data Elements (CDE) linked to specific protocols, CDE Mapping Tools, Form Generating Tool, EDRN Research Network Exchange (ERNE), Validation Study Information Management System (VSIMS), Online protocols, Online Manual of Operation, Online Data Entry Tools, Issue tracking system, Documentation of the flow of specimens, List of Biomarkers and their development within EDRN, and the storage of data from studies. See the following reference for data sharing: http://grants1.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html. DMCC will closely work with JPL in expanding and/or updating these resources to meet the growing needs of EDRN in the future.

NOTE: Investigators interested in applying for the DMCC award may request access to information on current EDRN architecture and bioinformatics tools by contacting the NCI Program Coordinator for the EDRN (Email: [email protected]).

Part B. Statistics and Biomarker Resource Center (SBRC) Applications

The SBRC will provide to EDRN investigators, primarily EDRN BDL Principal Investigators, statistical advice and consultation on study design and protocol development of individual EDRN studies and potential EDRN validation studies prior to their initial review by the EDRN Steering Committee (SC). When asked by the NCI Program Coordinator, the SBRC will provide similar services to non-EDRN investigators who are planning to submit a proposal to the EDRN SC for Core Funds to support a biomarker validation trial. After the proposed validation trial is approved by the EDRN SC, the DMCC will assume responsibility, oversight and management of studies supported by EDRN Core Funds. The NCI anticipates funding approximately 20 BDLs and it should be expected that typically two PIs will consult with the SBRC per month. The SBRC will provide support services that include, but are not limited to, the following aspects:

a. Statistical Services

• Develop and implement standard procedures for data collection by the EDRN BDLs.
• Perform manual data editing and conduct analysis of the biomarkers proposed by the BDLs and build classifiers or algorithms for discriminating between cancer and non-cancer.
• Develop instruction manuals for data collection from biomarker discovery work and interact with the participating institutions to resolve data errors. A significant portion of this support may require the creation of subset data files for statistical analysis and the generation of descriptive statistics through the use of existing analysis packages such as SAS. These studies could require only one data collection per subject or might be longitudinal studies.
• Develop programs to assist with or provide the following: screening of prognostic factors, survival analysis and curve graphing, covariate modeling of survival, descriptive statistics, least-squares regression analysis, power and sample size calculations, table making, data subsetting, two variable scatter plots and analysis of time dependent covariates.
• In response to requests from the NCI Program Coordinator, design interfacing modules with commercially available software necessary to support the biomarker discovery related research activities. An example of such software could be a generalized user-oriented interactive recode and statistical analysis system suitable for the analysis of high-dimensional data, e.g., microarray data from genomic, proteomic or epigenomic studies. Software designs developed by the statistical Center will be implemented at the direction of EDRN SC.
• Support other statistical services for the Network as directed by the EDRN SC.

b. Biomarker Knowledgebase

The SBRC will also function as the content manager for the EDRN biomarker knowledgebase. EDRN is proposing to develop a biomarker database, for which expertise in clinical epidemiology is crucial. SBRC will prepare a list of potential biomarkers from the literature and EDRN-supported studies and work with the relevant organ-specific EDRN Collaborative Groups to develop criteria for inclusion of published biomarkers into the biomarker database. SBRC will lead discussions with the relevant EDRN Collaborative Group on supporting biological, clinical and epidemiologic data to assess the relevancy for the inclusion of these biomarkers in the database. The final lists for all organ sites will be presented to the NCI-appointed Biomarker Expert Group, which will evaluate the supporting data and recommend to the NCI for their inclusion in the database. Some specific responsibilities of the SBRC are, but are not limited to, the following:

• Prepare and produce data collection forms on biomarkers in collaboration with the EDRN Informatics Center [currently the NASA Jet Propulsion Laboratory (JPL)], which is assisting the EDRN in building a biomarker database.
• Prepare procedural manuals for abstracting biomarker information from published data and from EDRN investigators, as needed.
• Obtain necessary information on each biomarker to determine its suitability in light of experimental, clinical and epidemiologic data.
• Develop quality control procedures for the handling of biomarker data and update files with error corrections, etc. as directed by the EDRN SC.
• Enter biomarker information into the database. In this regard, the SBRC may have to edit data and correct computer files as necessary.
• Specify, capture and annotate EDRN scientific data from selected studies. Data for description and/or capture are at two levels: instrument (specific instruments at bench or in clinic, which generate EDRN biomarker data), and biomedical and clinical data at the database level.
• Feed specifications back for integration into ontology models. Specifically, work on the development of metadata and review the ontology for the data captured at all levels of processing from the bench to the database to clinical work.
• Collaborate with the Informatics Center to modify ontology models as needed.
• Arrange for communications and meetings as needed with the relevant EDRN Collaborative Groups and, at least twice a year, with the Biomarker Expert Committee.
• Attend and participate in above meetings, provide required background materials, keep minutes of these meetings and take appropriate actions on recommendations as applicable.
• Work closely with the EDRN DMCC and Informatics Center on these responsibilities.
• Implement the goals, priorities, common protocols, procedures, and policies agreed upon by the NCI, Informatics Center and whenever necessary with the DMCC.
• Ensure that the Project Management Team (NCI, Informatics Center, and DMCC) reviews and approves the protocols, concepts, final protocol documents, informed consents, and study amendments, and advise NCI of changes in protocol status.
• Collaborate on common system designs or protocols with the Informatics Center and NCI, including methods and requirements for populating the databases and handling of data, including appropriate sharing of methods and data among collaborating organizations.

NOTE: Investigators interested in applying for the SBRC award may request access to information on current EDRN architecture and bioinformatics tools by contacting the NCI Program Coordinator for the EDRN (Email: [email protected]).

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

1. Mechanism of Support

This funding opportunity uses the NIH U24 cooperative agreement award mechanism(s).The Project Directors/Principal Investigators (PDs/PIs) will be solely responsible for planning, directing, and executing the proposed project.

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

This funding opportunity uses a cooperative agreement award mechanism. In the cooperative agreement mechanism, the PD/PI or PDs/PIs retain(s) the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the PD(s)/PI(s), as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award."

2. Funds Available

The estimated amount of funds available for the support of one DMCC and one SBRC awarded as a result of this announcement is $3.0 million for fiscal year 2010. Future year amounts will depend on annual appropriations.

Applicants for the DMCC award may request a project period of up to 5 years at budget of up to $ 1.3 million per year (direct costs).

Applicants for the SBRC award may request a project period of up to 5 years at a budget of up to $300,000 per year (direct costs).

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the NCI provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

Facilities and administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation; see NOT-OD-05-004.

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.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

• Public/State Controlled Institutions of Higher Education;
• Private 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);
• Small Businesses;
• For-Profit Organizations (Other than Small Businesses);
• US Territories or Possessions
• Other(s):
  • Eligible Agencies of the Federal Government.

Non-Domestic (i.e., Foreign) organizations are NOT eligible for application submission but may participate (under subcontractual arrangements) proposed by an eligible Domestic applicant institution.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her institution 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.

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

Resubmissions. Resubmission applications are not permitted in response to this FOA.

Renewal. The current DMCC awardees may submit a renewal application for the DMCC.

Number of Applications. Applicants may submit more than one application, provided each application is scientifically distinct. Note that the same applicant or group of applicants cannot be awarded both the U24 award for the DMCC and the U24 award for the SBRC.

Section IV. Application and Submission Information

1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance, contact GrantsInfo -- Telephone: (301) 710-0267; Email: [email protected].

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Applications must be prepared using the current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed in item (box) 2 only of the face page of the application form and the YES box must be checked.

The exceptions from the PHS398 instructions and detailed information on the application structure and components are provided in Section IV.6. Other Submission Requirements. All applicants must follow the specific instructions in that section.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review, and Anticipated Start Dates
Letters of Intent Receipt Date: September 29, 2009
Application Receipt Date: October 29, 2009
Peer Review Date: February/March 2010
Council Review Date: May 2010
Earliest Anticipated Start Date: July 2010

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

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

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 NCI staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

Sudhir Srivastava, Ph.D., M.P.H.
Program Coordinator
Division of Cancer Prevention
National Cancer Institute
6130 Executive Boulevard, EPN Room 3142
Bethesda, MD 20892-7362
Telephone: (301) 435-1594
FAX: (301) 402-8990
Email: [email protected]

3.B. Sending an Application to the NIH

Applications must be prepared using the forms found in the PHS 398 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 (for U.S. Postal Service express or regular mail)
Bethesda, MD 20817 (for express/courier delivery; non-USPS service)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all copies of the appendix material 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]

3.C. Application Processing

Applications must be received on or before the application receipt date described above (Section IV.3.A.). If an application is received after that date, the application may be delayed in the review process or not reviewed. Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute. Incomplete and/or non-responsive applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

Information on the status of an application should be checked by the PI in the eRA Commons at https://commons.era.nih.gov/commons/.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or renewal award if such costs: 1) are necessary to conduct the project; and 2) would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or renewal award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project (see the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm).

6. Other Submission Requirements

Special Instructions for Preparation of DMCC (Part A) SBRC and (Part B) Applications

Instructions for the Preparation of EDRN DMCC Applications RESEARCH PLAN: The standard PHS398 Research Plan (Items 2-5 as per Revision 11/07 of the PHS 398 Table of Contents) is altered as follows:

Part A: Instructions for the Preparation of EDRN DMCC Applications RESEARCH PLAN: The standard PHS398 Research Plan (Items 2-5 as per Revision 11/07 of the PHS 398 Table of Contents) is altered as follows:

Standard Items 2-5 of the PHS 398 Research Plan are replaced by the following three sections; 1) Investigators Capabilities and Experience; 2) Plans for The Required Areas of Responsibility, and 3) Compliance with EDRN Cooperative Agreement Terms. The incumbent DMCC must provide a transition plan if the incumbent is not recommended for continuation.

• The PHS 398 standard page limit for Items 2-5 is replaced by a new limit of 50 pages for the new Sections 1-3. Note: Applicants are encouraged to use the minimum number of pages necessary to describe the research plan clearly and succinctly.
• Other items of the PHS398 Research Plan remain unmodified.
• Specific Sections to be included in Research Plan are described below. (Table of Content should be modified accordingly).

The responsibilities of the EDRN DMCC are diverse. Each of the responsibilities described in the section "Section I. Funding Opportunity Description: 1. Research Objectives is relevant to the overall performance of the Network.

DMCC Section 1. Investigators Capabilities and Experience (up to 15 pages suggested)

• Describe the applicant organization's facilities, resources, and how the staff's strengths in biostatistics, data management, data analysis, and project management skills have been used in previous, successful large-scale collaborative research;
• Describe the knowledge and experience of the Principal Investigator and other staff in research on cancer and technologies used in detection;
• Describe the experience of the key personnel in assisting protocol design, data entry procedures and manual preparation, and in data collection and data quality control for previous large-scale, complex research projects;
• Present the applicant's record in generating reports on data collection and performance in previous large-scale collaborative projects, including preparation of manuscripts;
• Describe how logistical services and organizational support have been utilized in managing resources and monitoring performance in previous large-scale, collaborative research;
• Describe the applicants experience and accomplishments in the development of statistical and computational tools and present a plan to develop a theoretical and applied research project that is relevant to early detection.

DMCC Section 2. Plans for the Required Areas of Responsibility (up to 25 pages suggested)

Applicants must describe in detail the development, implementation, and maintenance plans for each required area of responsibility (defined in Section I. Research Objectives of this FOA). These main areas of responsibility to address include:

(1) Network Coordination,

(2) Data Management and Protocol Development,

(3) Theoretical and Applied Statistical Research, and

(4) Validation Information System and Services.

These plans should include description of design, personnel requirements, and infrastructure (hardware, software, other). Applicants are encouraged to describe in their application the cost-efficient use of existing technologies.

For a competing renewal application, the applicants should describe their participation in EDRN activities, their accomplishments in the five areas of responsibility during the previous funding period, and their contributions in meeting the EDRN missions (see EDRN Fourth Report, http://edrn.nci.nih.gov/docs).

DMCC Section 3. Compliance with EDRN Cooperative Agreement Terms (up to 5 pages suggested):

Specific issues related to the cooperative agreement must be addressed. Applicants must include their specific plans for responding to the "Cooperative Agreement Terms and Conditions of Award" section. These are described in detail in Section VI, Part 2A Cooperative agreement Terms and Conditions of Award of this FOA. Applicants should state their willingness to collaborate and share data freely with the other Network components, to participate in planning and attending workshops and symposia, to serve on the SC and be bound by its decisions, particularly those that relate to setting priorities for quality control and validation of new or existing biomarkers, and willingness to interact other EDRN investigators and the NCI in an Internet environment. Applicants must describe computer, Internet, and other communication resources for this type of interaction.

Transition Plan (only applicable to the incumbent EDRN DMCC renewal application) (up to 5 pages suggested)

The incumbent DMCC institution must provide a detailed transition plan and the cost involved in transferring data, software for IT infrastructures, databases, analytical tools, and other relevant documents concerned with the EDRN activities, e.g., Steering Committees, Workshops, Subcommittees, etc., to the NCI and to the new DMCC awardee. This transition plan will only be implemented if the incumbent is not recommended for continuation, and it should include, but is not limited to:

1. Convening a transition team.

2. Inventory of the materials to be transferred.

3. A time-line for the transfer.

4. A post-transfer meeting for closing out the transfer.

DMCC Additional Budget-related Information

Budget for personnel services directly involved in the activities of the DMCC should be clearly identified. Applicants should budget to cover the four types of services listed below. The workload in each category will vary as the needs and priorities of the EDRN change during the funding period. The applicant’s staffing plan must allow for the flexibility needed to adapt to these changes.

1) Administrative Services

• PI and senior co-investigators time to administer the center and EDRN projects
• Logistical arrangements and support for one SC meetings, one NCT meeting, and one scientific workshop every 18 months. Applicants must budget $50,000 (direct cost only) each year for reserving a site for the SC and NCT meetings and other related expenses. The place and dates for the meetings will be decided by the NCI Program Coordinator in consultation with the SC. The use of these funds is restricted and must be reviewed and approved by the SC and NCI. The SC meetings are three days for approximately 200 persons. The NCT meeting is a one day meeting for approximately 20 persons.
• onthly EC conference calls (arrange and keep minutes)
• Online review of applications submitted to EDRN (approximately 6 applications, three times per year)
• Travel and per diem expenses for SC meetings; applicants should plan for the PI, an additional senior investigator, a Meeting Coordinator, and up to two other DMCC staff, if needed for organizational activities, to attend EDRN-wide meetings.
• Travel and per diem expenses for participation by the PI and one additional senior investigator in one Network workshop or symposia per year

2) Informatics Services

• Maintain and develop secure website to allow for communication between EDRN members and posting of study results
• Develop tools for biomarker validation in collaboration with the Jet Propulsion Laboratory
• Transfer of data bases and informatics programs or tools to an NCI designated portal when requested to do so by the NCI Program Coordinator

3) Statistical Analysis and Protocol Development

• Assist in the design of network collaborative validation studies (data collection and entry, sample tracking, calculation of populations and power analysis) and perform statistical analysis on data
• Assist in the design of network specimen reference set collections (data collection and entry, sample tracking, calculation of populations and power analysis)

4) Validation Trials Services

• Perform data management and protocol maintenance (e.g., data entry and tracking, monitoring patient accrual, distribution of study manuals and materials) for EDRN validation trials and EDRN reference set collections.

Currently, EDRN has ongoing network collaborative validation studies, biospecimen reference set collections, and NCI anticipates that in the future that in any given year the DMCC will coordinate approximately four network trials involving on average 10 study sites and biospecimen reference set collections. Applicants must set aside 30 percent of their total annual budgets for these network validation trials and reference set collections. In the case of the incumbent, this set aside should include the amount of funds already approved by NCI program staff for ongoing validation studies. The use of these set aside funds will be restricted and must be reviewed by the SC and approved by the NCI for release. If the number of network trials exceeds these estimates, additional funding may be allocated from the core funds. Direct plus for any year may not exceed $1.3 million, which includes the 30% set-aside funds.

Part B: Instructions for the Preparation of EDRN SBRC Applications RESEARCH PLAN: The standard PHS398 Research Plan (Items 2-5 as per Revision 11/07 of the PHS 398 Table of Contents) is altered as follows:

• Standard Items 2-5 of the PHS 398 Research Plan are replaced by the following three sections; 1) Investigators Capabilities and Experience; 2) Plans for the Required Areas of Responsibility, and 3) Compliance with EDRN Cooperative Agreement Terms.
• The PHS 398 standard page limit for Items 2-5 is replaced by a new limit of 20 pages for the new Sections 1-3. Note: Applicants are encouraged to use the minimum number of pages necessary to describe the research plan clearly and succinctly.
• Other items of the PHS398 Research Plan remain unmodified.

Specific Sections 1-3 to be included in Research Plan are described below. (Table of Content should be modified accordingly).

SBRC Section 1. Investigators Capabilities and Experience (up to 8 pages suggested)

Applicants should concisely describe the group’s expertise, specialized and/or unique facilities, shared core resources, and services that are available. The description should document the applicants ability to provide statistical advice and consultation to EDRN investigators in study design and protocol development and to function as the content management center for the EDRN biomarker database. The roles and expertise of all key personnel, collaborators, and consultants who are associated with the application should be described. Letters from collaborators and consultants should be included in the appendix.

Applicants should describe any ongoing grant-supported, institutional, or private sector resources that may augment or complement resources for which funding from this FOA is sought.

If the proposed collaborations involve a for-profit entity (entities), it is the applicant’s responsibility to ensure that the industrial partner freely shares protocols and study designs with NCI staff members and collaborating investigators. NCI will help establish Confidential Disclosure Agreements with all parties involved.

SBRC Section 2. Plans for the Required Areas of Responsibility (up to 10 pages suggested)

Applicants must describe in detail the development, implementation, and maintenance plans for the following required main areas of responsibility: (1) Statistical Services and (2) Biomarker Knowledgebase (described in Section I. Research Objectives of this FOA). These plans should include description of design, personnel requirements, and infrastructure (hardware, software, other). Applicants are encouraged to describe in their application the cost-efficient use of existing technologies.

a) Statistical Services: Applicants should describe their plans to provide statistical advice and consultation to EDRN investigators on study design and protocol development of individual EDRN studies and potential EDRN validation studies prior to their initial review by the EDRN SC. These requests will be primarily from the Principal Investigators of the EDRN BDLs. Applicants should also state their willingness, when asked by the NCI Program Coordinator, to provide similar services and consultation to non-EDRN investigators who are planning to submit a proposal to the EDRN SC for Core Funds to support a biomarker validation trial. The applicants should acknowledge that after the proposed validation trial is approved by the EDRN SC, the EDRN DMCC will assume responsibility, oversight and management of studies supported by EDRN Core Funds.

b) Biomarker Knowledgebase: Applicants should describe their plans to function as the content manager of EDRN biomarker knowledgebase and to perform related activities (defined earlier in Section I. Research Objectives of this FOA). The applicants should state their willingness to work closely with the NCI Program Coordinator, the EDRN DMCC, the EDRN Informatics Center (currently, the NASA Jet Propulsion Laboratory), and EDRN BDLs and CVCs on developing and maintaining the EDRN biomarker knowledgebase.

SBRC Section 3. Compliance with EDRN Cooperative Agreement Terms (up to 3 pages suggested)

Applicants must include their specific plans for responding to the "Cooperative Agreement Terms and Conditions of Award" (Section VI, 2A of this FOA). Applicants should state their willingness to collaborate and share data freely with the other EDRN components, to participate in planning and attending workshops and symposia, to serve on the SC and be bound by its decisions. Particular emphasis is on the adherence to those decisions of SC that relate to setting priorities for quality control and validation of new or existing biomarkers and willingness to interact with other EDRN investigators and the NCI in an Internet environment. Applicants should state their willingness to adapt their computer, internet, and other communication resources, if needed for compatibility with the EDRN environment and infrastructures.

SBRC Additional Budget-related Information

a) Applicants must adhere to the overall budget limits as defined in Section II. Funds Available.

b) Applicants must budget for travel and per diem expenses for SC meetings. In the first year, applicants should plan for the PI and an additional senior investigator to attend a Planning Meeting and two SC meetings. In the second and subsequent years, applicants should plan for the PI and another investigator to attend two SC meetings per year.

c) Applicants must budget for travel and per diem expenses for participation in Network workshops and symposia. Applicants should plan that at least two investigators will attend a Network workshop or symposium every 18 months.

d) Applicants must budget to arrange and attend two meetings per year of the Biomarker Expert Committee. NCI will pay travel expenses for the Expert Committee Members.

Appendix Materials

All paper PHS 398 applications must provide appendix material on CDs only, and include five identical CDs in the same package with the application (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html).

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible. See Sharing Model Organisms Policy and NIH Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight) or the presence or absence of a disease or condition. For further information, see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088 and http://grants.nih.gov/grants/gwas/.

In addition to the standard NIH rules, the following EDRN-specific requirements apply:

(d) Intellectual Property: NIH recognizes that certain research activities may result in inventions and that grantees are entitled to protect such inventions through patenting and licensing activities in accordance with the Bayh-Dole Act, 35 USC 200 et seq. and the implementing regulations, 37 CFR Part 401 ("Bayh-Dole Act"). However, the EDRN's core mission of collaboration both between Network members and between Network members and third party industry partners necessarily anticipates the sharing of intellectual property arising out of research resources developed in Network-related activities.

Since it is the policy of the NIH to make available to the public the results and accomplishments of the activities which it funds, applicants who respond to an EDRN FOA are expected to submit an Intellectual Property Management Plan (IPMP), which addresses the strategy to be followed for both solely or jointly owned inventions (including patents and licensing issues) and how these resources will be made available to the broader scientific community, consistent with the EDRN initiative. This plan should be included in the program description of the application and any approved IPMP will become a condition of the grant award. For more details on the preparation of an IPMP can be found at http://ttb.nci.nih.gov/ipplans.html. For further Licensing and IP issues related to Biomarker Discovery, Development, and Validation, see Section III of the FOA Guidelines document, at http://edrn.nci.nih.gov/FOA-guidelines.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NCI and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

• 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 a impact/priority score;
• Receive a written critique; and
• Receive a second level of review by National Cancer Advisory Board.

The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by peer review;
• Availability of funds;
• Relevance of the proposed project to program priorities; and
• Compliance with resource and data sharing policies.

The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability. As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

A. Review Criteria for DMCC Applications

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

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

Significance. Does the project address an important problem or a critical barrier to progress in the field? 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, and/or preventative interventions that drive this field?

In addition, specific to this FOA: How well do the proposed theoretical and applied research projects address an important need for statistical/analytical tools for earlier cancer detection and risk assessment? Over the project period, is there potential for the applicant to develop statistical and analytical approaches other than those specified in the application?

Investigator(s). Are the PDs/PIs, collaborators, and/or other researchers well suited to the project? If Early Stage Investigators or New Investigators are involved, do they have appropriate experience and training? If established investigators are involved, 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 and are their leadership approach(es), governance plan(s), and organizational structure appropriate for the project?

In addition, specific to this FOA: Are the PD/PI and his/her collaborators appropriately trained and well in the area of statistical, mathematical and computational biology? Will this team of investigators contribute unique skills to the overall EDRN Network? How likely are the applicants to engage in collaborations, sharing information, and work towards the priorities and goals agreed upon by the Steering Committee for Network collaborative studies? Are the PD/PI and support personnel adequately trained and qualified for participating and managing multi-institutional collaboration?

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, methodologies, instrumentation, and/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, methodologies, instrumentation, and/or interventions proposed?

In addition, specific to this FOA Does the proposed approach/methodology challenge existing paradigms or develop new computational/statistical approaches? Will the approaches advance the field of cancer detection and risk assessment?

Approach. Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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 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?

In addition, specific to this FOA: Does the application adequately address how each of the goals set for the four required areas responsibility will be accomplished? Are relevant technical problems and their timely and effective solutions adequately addressed? Are the conceptual framework, design, methods, and analyses adequately developed and appropriate to the aims of the proposed research? Does the applicant acknowledge potential problem areas and consider alternative tactics? Will the proposed approaches be generally applicable to statistical analysis of data related to all biomarkers/reagents?

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, and/or collaborative arrangements?

In addition, specific to this FOA: Are facilities and equipment for data storage, data security and data analysis appropriate to support the objectives of the FOA? Has the applicant demonstrated adequacy of proposed infrastructure, commitment and documented evidence of institutional support for proposed endeavor, and institutional support for computer services?

In addition to the above review criteria, the following criteria will be applied to applications in the determination of scientific merit and the impact/ priority score.

For Competing Renewal DMCC Application: Did the incumbent DMCC successfully carry out during the previous funding period their responsibilities for Network Coordination, Data Management and Protocol Development, Theoretical and Applied Statistical Research, and Validation Information System and Services? Did they actively participate in EDRN activities? Did they make significant contributions to meeting the EDRN mission?

Collaborative Strengths: Are there adequate plans for effective interaction and coordination with the other Network components, the SC, and the NCI? Do the investigators state their willingness to collaborate and share information? Do the investigators state their willingness to abide by the priorities and policies agreed upon by the SC for collaborative studies?

B. Review Criteria for SBRC Applications

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

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

Significance. Does the project address an important problem or a critical barrier to progress in the field? 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, and/or preventative interventions that drive this field?

Investigator(s). Are the PDs/PIs, collaborators, and/or other researchers well suited to the project? If Early Stage Investigators or New Investigators are involved, do they have appropriate experience and training? If established investigators are involved, 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 and are their leadership approach(es), governance plan(s), and organizational structure appropriate for the project?

In addition, specific to this FOA: Do the PD/PI and collaborators have the expertise to advice and consult EDRN PIs on statistics and study design? Are they experienced in database development? Do they have expertise on cancer biomarkers? Are they experienced in working on collaborative research projects?

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, methodologies, instrumentation, and/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, methodologies, instrumentation, and/or interventions proposed?

Approach. Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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 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?

In addition, specific to this FOA: Will the proposed approaches be generally applicable to statistical analysis of data related to cancer biomarkers? Are the plans to respond to requests from EDRN Principal Investigators and NCI Program Coordinator reasonable and well developed? Is the role of content manager for the EDRN clearly described?

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, and/or collaborative arrangements?

In addition to the above review criteria, the following criteria will be applied to applications in the determination of scientific merit and the impact/ priority score.

Collaborative Strengths: Are there adequate plans for effective interaction and coordination with the other Network components, the SC, and the NCI? Do the investigators state their willingness to collaborate and share information? Do the investigators state their willingness to abide by the priorities and policies agreed upon by the SC for collaborative studies?

Additional Review Criteria applicable to both DMCC and SBRC Applications. As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, but will not give separate scores for these items.

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.

Inclusion of Women, Minorities, and Children. When the proposed project 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.

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 American Veterinary Medical Association (AVMA) Guidelines on Euthanasia.

Renewal Applications. When reviewing a Renewal application (formerly called a competing continuation application), the committee will consider the progress made in the last funding period.

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

Additional Review Considerations. As applicable for the project proposed, reviewers will address 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.

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

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 (http://grants.nih/gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

3. Anticipated Announcement and Award Dates

Not applicable

Section VI. Award Administration Information

1. Award Notices

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.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in Item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

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. See also Section IV.5. Funding Restrictions.

2. Administrative and National Policy Requirements

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 (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. 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 (HHS) 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.

2. A.1. Awardee and Principal Investigator Rights and Responsibilities

The PD/PI or PDs/PIs will have the primary responsibility and accountability to the applicant organization officials and to the NCI for the performance and the proper conduct of the research supported by the U24 mechanism in accordance with the terms and conditions that are stated in the FOA. The PI will be a voting member of the Steering Committee (SC) and, together with an additional senior investigator, will attend a Planning Meeting and two SC meetings in the first year, two SC meetings in each of the subsequent years of the award, and one EDRN-sponsored scientific workshop every 18 months (this usually coincides with one of the SC meetings). Attendance at these meetings are required as part of this cooperative agreement.

PD/PI of the DMCC will:

Oversee the DMCC activities to ensure that its four areas of responsibility are fulfilled.

Collaborate with other EDRN components to advance promising biomarkers towards EDRN validation studies.

Accept and implement the goals, priorities, common protocols, procedures, and policies agreed upon by the SC for the individual and Network collaborative studies.

Ensure Network and NCI review and approval of protocols, concepts, final protocol documents, informed consents, and study amendments, and advise NCI of changes in protocol status.

Collaborate on common research designs or protocols, including methods and requirements for joint participation and collaboration as recommended by the SC, and handling of data, including appropriate sharing of methods and data among collaborating organizations.

Define objectives and approaches, including the logistic support for the Steering and Executive Committees, organization of workshops, and provide assistance for other activities of the Network.

DMCC awardees whose award will be discontinued/not renewed will be required to: (a) submit to the NCI a specific Transition Plan and (b) cooperate as needed in the transition period with a new awardee.

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 HHS, PHS, and NIH policies.

PD/PI of the SBRC will:

Provide statistical advice and consultation to EDRN investigators on study design and protocol development of individual EDRN studies and potential EDRN validation studies prior to their initial review the EDRN SC.

Oversee content management activities for the biomarker knowledgebase.

The PI will collaborate with other EDRN components to advance promising biomarkers towards EDRN validation studies.

Accept and implement the goals, priorities, common protocols, procedures, and policies agreed upon by the SC for the individual and Network collaborative studies.

Ensure Network and NCI review and approval of protocols, concepts, final protocol documents, informed consents, and study amendments, and advise NCI of changes in protocol status.

Collaborate on common research designs or protocols, including methods and requirements for joint participation and collaboration as recommended by the SC, and handling of data, including appropriate sharing of methods and data among collaborating organizations.

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 HHS, PHS, and NIH policies.

2. A.2. NIH Responsibilities

An NIH Project Scientist [and/or Project Coordinator, or Project Collaborator, or Intramural Scientist ] will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

The NCI Program Coordinator will have substantial scientific programmatic involvement during conduct of this activity, through technical assistance, initiation of Network collaborative projects, data sharing and analysis, composition of reports, advice and coordination. There will be only one NCI Program Coordinator for the Network. However, the Program Coordinator may be assisted by other NCI Program Directors and staff members on specific scientific issues as needed.

Because of the Network’s diverse research agenda and the number of tasks that have to be accomplished to achieve its goals, a number of NCI staff members may interact with the Network as needed. The NCI Program Coordinator (who is and will be a staff member in the Division of Cancer Prevention) will assist the Network on scientific and programmatic issues, and advise the Network on the availability of other resources. A member from the Chemoprevention Branch, DCP, NCI, will be available to assist the Network on intermediate endpoints and on any ongoing chemoprevention trials relevant to the Network studies. A member from the Biometry Branch, DCP, NCI, will be available to assist the Network on the issues of study design, sample size, and other statistical computations. The other NCI staff may assist and advise the Network on relevant programmatic and scientific issues through the NCI Program Coordinator.

The NCI Program Coordinator will convene the initial meeting of the SC, have voting membership on the Steering Committee, and, as determined by that committee, its subcommittees.

Although the PD(s)/PI(s) will have lead responsibilities in all collaborative tasks and activities, it is anticipated that the NCI Program Coordinator will have lead responsibilities in managing and sharing the broad programmatic issues among awardees.

The NCI reserves the right to adjust funding, withhold support, suspend, terminate, or curtail the study or an individual award in the event of a failure to comply with the Terms and Conditions of Award, data reporting, quality control, or other major breach of the protocol, or human subject ethical issues, whenever applicable.

The NCI Project Scientists/Coordinators/Collaborators and other substantially involved NIH staff members will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications. If such participation is essential, these individuals will seek NCI waiver according to the NCI procedures for management of conflict of interest.

Additionally, an NCI Program Director acting as the Program Official will be responsible for the normal scientific and programmatic stewardship of the awards and will be named in the award notice. A Program Official may also have substantial programmatic involvement (e.g., as a Project Scientist). In that case, the individual involved will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications, or will seek NCI waiver.

2.A.3. Collaborative Responsibilities

1. Steering Committee (SC):

The SC will be a governing body of the EDRN. It will provide overall scientific management oversight and will be responsible for developing collaborative research designs, protocols, and manuals, facilitating the conduct and monitoring of studies, and reporting study results. The SC will be composed of: (a) the PD(s)/PI(s) representing EDRN awardees (one representative per each EDRN award); and (b) the NCI Program Coordinator. Each voting member will have one vote.

The Chair (non-NIH person) will be selected by the SC. The awardee institution represented by the Chair of the SC will serve as the Headquarters (for definition, see Network Organization). Subcommittees, including the existing ones, will be established and maintained by the SC, as it deems appropriate; the NCI Program Coordinator will serve on subcommittees, as he/she deems appropriate.

After all the Network components have been funded, the SC will convene. Responsibilities of the SC include, but are not limited to (investigators are encouraged to review the EDRN Manual of Operations at http://edrn.nci.nih.gov/about-edrn/edrn-mo-v3-1-0.pdf/download), the following activities:

• Updating and refining established Network policies and procedures;
• Updating and refining established policies and procedures for collaborative projects, protocols, and Network-defined projects;
• Updating and refining established policies and procedures for reviewing changes in projects not showing translational significance at the request of the laboratories/centers, and making recommendations to the NCI for replacing the project with more promising ones with revised scope and adjusted budget (increase in the budget will not be permitted);
• Updating and refining established standards or decision criteria for validating biomarkers/reagents for further clinical studies, such as testing early detection strategies, or as risk factors; and
• Updating and refining established policies and procedures for accepting, reviewing, and recommending proposals from investigators outside the Network for supplemental funding and expanding the Network participation.

The SC will establish a Data and Safety Monitoring Committee (DSMC) for clinical trials as appropriate to ensure protection of human subjects.

The SC will review patient accrual, follow-up, protocol compliance, results of audits, and regulatory requirements at the participating Centers and formally report the results of its reviews to the NCI.

The SC will promote and foster the inclusion of women and ethnic minorities in clinical studies and assure the completeness of informed consent.

The SC will track the Network research progress and assure that the results of laboratory research and clinical studies are published in peer-reviewed journals in a timely manner and in accordance with the publication policies of the Network.

At any time during a Network project (i.e., collaborative research using Core Funds), the SC may ask a BDL or CVC to serve as a BRL on an as needed basis with appropriate compensation from Core Funds. The SC may also examine the validation data for biomarkers/reagents developed by the Network, and decide when a biomarker is sufficiently validated, or recommend when to stop non-productive experiments relating to biomarkers validation.

The SC will discuss collaborative projects to be pursued jointly with the funds set aside from the Headquarters and from individual U01 awardees.

Collaborative studies/protocols will be approved by the SC. Data will be submitted centrally to the DMCC. The SC will define the rules regarding access to data and publications consistent with NCI policies.

The SC will plan one of several Workshops during the Network project period to inform the scientific community and relevant advocacy groups of the progress made toward development and clinical application of biomarkers developed through the Network. The NCI Program Coordinator, members of the Network Consulting Team, and other NCI staff will provide the SC with advice on participants for the workshops and symposia. The DMCC will manage the logistics for these meetings.

The SC in consultation with the NCI will determine the PI of the Network-wide validation study.

For additional information on PD(s)/PI(s) responsibilities for the SC, see the EDRN Manual of Operations posted at http://edrn.nci.nih.gov/about-edrn/

All EDRN PDs/PIs and their awardee institutions will be required to accept and implement policies approved by the Steering Committee.

2.A.4. 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 arbitration. A Dispute Resolution Panel 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 rights in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

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.

Section VII. Agency Contacts

We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research; peer review; and financial or grants management issues.

1. Scientific/Research Contacts:

Sudhir Srivastava, Ph.D., M.P.H.
Program Coordinator
Division of Cancer Prevention
National Cancer Institute
6130 Executive Boulevard, EPN Room 3142
Bethesda, MD 20892-7362 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 435-1594
FAX: (301) 402-8990
Email: [email protected]

2. Peer Review Contacts:

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]

3. Financial or Grants Management Contacts:

Funmi Elesinmogun
Office of Grants Administration
National Cancer Institute
6120 Executive Boulevard, Suite 243
Bethesda, MD 20892(for regular mail)
Rockville, MD 20852(for non-USPS delivery)
Telephone: 301-496-7245
FAX: 301-496-8601
EMAIL: [email protected]

Section VIII. Other Information

Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (Phase I); efficacy studies (Phase II); and efficacy, effectiveness, and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local institutional review board (IRB) rules, as well as local, State, and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html) investigators must submit or have submitted for them their final, peer-reviewed manuscripts that arise from NIH funds and are accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available no later than 12 months after publication. As of May 27, 2008, investigators must include the PubMed Central reference number when citing an article in NIH applications, proposals, and progress reports that fall under the policy, and was authored or co-authored by the investigator or arose from the investigator’s NIH award. For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372. 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 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.