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: Transdisciplinary Research in Energetics and Cancer (U54)

Announcement Type
This is a reissue of RFA-CA-05-010.

Request For Applications (RFA) Number: RFA-CA-10-006

Catalog of Federal Domestic Assistance Number(s)
93.393, 93.399

Key Dates
Release Date: November 24, 2009
Letters of Intent Receipt Date: January 26, 2010
Application Receipt Date: February 26, 2010
Peer Review Date: May/June 2010
Council Review Date: August 2010
Earliest Anticipated Start Date: September 2010
Additional Information To Be Available Date (URL Activation Date): Not Applicable
Expiration Date: February 27, 2010

Due Dates for E.O. 12372

Not Applicable

PRE-APPLICATION CONFERENCE CALL

The NCI anticipates holding a pre-application conference call on Monday, January 8, 2010 at 2 PM EST to which all interested prospective applicants are invited. NCI Program and review staff members will explain the goals and objectives for TREC, discuss the application peer review process, and to answer questions. Information about this Pre-Application Conference Call will be available at URL: http://cancercontrol.cancer.gov/trec/index.html

Additional Overview Content

Executive Summary

• Purpose. Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) solicits applications for the centers for Transdisciplinary Research on Energetics and Cancer (TREC) in nutrition, physical activity, energy balance, obesity, and cancer. The TREC initiative (http://cancercontrol.cancer.gov/trec/) is designed to foster collaboration across multiple disciplines and encompasses projects that cover the biology, genomics, and genetics of energy balance to behavioral, socio-cultural, and environmental influences upon nutrition, physical activity, weight, energetics, and cancer risk. This initiative is open to all qualified candidates regardless of whether or not they participated in the previous issuance of the TREC Program. Applicants responding to this FOA should establish transdisciplinary research teams with the appropriate breadth of expertise. TREC has two main goals, which are: (1) to enhance knowledge of the current mechanisms underlying the association between energy balance and carcinogenesis (from cellular, animal or human models to genetics and genomics and across the cancer continuum from causation and prevention); and (2) to explore and integrate the etiology of obesity behavior and relevant health behavior theories, with broad population impact at the social-environmental and policy levels for prevention and control of obesity. Special focus on children, groups at high risk for obesity, and cancer survivors is encouraged.
• Mechanism of Support. This FOA will utilize the NIH Cooperative Agreement Specialized Centers (U54) funding mechanism. This FOA is accompanied by a separate limited competition U01 FOA (RFA-CA-10-501), which solicits renewal application for a TREC Coordination Center.
• Funds Available and Anticipated Number of Awards. For this TREC FOA, the NCI has committed $15M in total costs for FY2010 and $75M in total costs over a 5-year period. Approximately six awards are expected in connection with this FOA.
• Budget and Project Period. Total direct costs requested or awarded for a single site may not exceed $1.5M per year, plus NIH-approved indirect rates in effect at the time of the award. It is anticipated that each award will not exceed $ 2.5M per year in total cost over a 5-year period.
• 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 always encouraged to apply for NIH support.
• Number of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs) may be designated on the application.
• Number of Applications. Applicant institutions may submit more than one TREC U54 application in response to this FOA, provided that each application is scientifically distinct and proposed by a separate team of investigators (i.e., with different PDs/PIs and other key personnel).
• Resubmissions. Resubmission applications are not permitted in response to this FOA.
• Renewals. Renewal applications are permitted in response to this FOA.
• Special Date(s). This FOA uses non-standard due dates. See Receipt, Review, and Anticipated Start Dates.
• Application Materials. See Section IV.1 for application materials. All applications, including resubmission, revision and renewal, submitted for due dates January 25, 2010 and beyond, must utilize the current forms and instructions.
• 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)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Purpose

This funding opportunity announcement (FOA) issued by the National Cancer Institute is a component of the Transdisciplinary Research on Energetics and Cancer (TREC) program. The overall purpose of the reissued TREC program is to foster transdisciplinary research in nutrition, physical activity, energy balance, obesity, and cancer. To address this goal, this FOA solicits applications for TREC Research Centers.

This FOA is open to all qualified applicants regardless of whether or not they participated in the previous TREC issuance.

The TREC initiative also includes a companion, limited competition FOA (http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-10-501.html) for the continuation of TREC Coordination Center.

Overall Goals of the TREC Program. This reissuance of the TREC Program takes advantage of the great progress made in recent years in the field of energetics in cancer research. The original TREC Program, started in 2005, has established a transdisciplinary infrastructure to promote research collaborations in this area. This FOA expands the TREC Program into other research areas including cancer survivorship, childhood obesity, genomics, and environmental aspects of obesity that include use of tools such as geospatial analysis.

Through this FOA, the NCI intends to expand the TREC research model in energetics and cancer with additional emphasis on testing and integrating behavior change theories, challenges in survivor populations, systems analysis (to address challenges across multiple levels), accelerating capacity using animal and human studies in diverse research designs (biological and physiological), and expansion of the application of biological markers to inform behavioral based-research.

TREC as a Collaborative Network of Transdiciplinary Research Centers. The FOA will support a network of research centers that will facilitate new collaborative endeavors and addresses knowledge gaps. Research using a transdisciplinary approach to energy balance and carcinogenesis throughout the lifecycle that involves integrating the areas of obesity, exercise physiology, behavioral sciences, nutrition, genetics, genomics, and molecular carcinogenesis to accelerate progress toward understanding mechanisms linking energy balance and carcinogenesis is desired. Transdisciplinary studies that integrate social, behavioral, and biological sciences into comprehensive study designs at an accelerated rate are highly desired. TREC applicants must be oriented to generate outcomes that will inform and enhance behavioral research and have public health significance.

TREC applicants are encouraged to take advantage of common resources, expertise, and relevant methodologies or technologies. It is expected that all of the awarded TREC sites will work together to minimize effort duplication and utilize existing resources available, available public use assessment tools and methodologies, and established data sets, patients/participants cohorts, and clinical centers or clinical care networks.

To build transdisciplinary teams necessary to meet the goals of this FOA, the proposed TREC Research Centers must have the ability to provide leadership in a variety of disciplines. Investigators from cancer centers, schools of public health, and academic departments will be challenged to build and strengthen bridges across diverse disciplines, such as molecular biology, genetics, oncology, psychology, anthropology, urban planning, communications and informatics, and behavioral and social sciences. Therefore, applicants may take advantage of the multiple Program Director/Principal Investigators (PDs/PIs) option. Each proposed TREC Research Center is expected to have a leadership structure in which one senior investigator (PD/PI) is identified to lead the overall team.

Applications submitted in response to this FOA must adhere to the following definitions:

Transdisciplinary research is defined as research efforts conducted by investigators from different disciplines working jointly to create new conceptual, theoretical, methodological, and translational innovations that integrate and moves beyond discipline-specific approaches to address a common problem.

Energetics in the context of this FOA is defined as the study of the flow and transformation of energy through living systems (i.e., bioenergetics).

Non-responsive: Projects with the following attributes are non-responsive to this FOA and will not be considered:

• Projects that fail to consider several of the following aspects in the study design: Testing and integrating health theories, challenges in survivor populations, systems analysis (to address challenges across multiple levels), accelerating capacity using animal and human studies in diverse research designs (biological and physiological), and expansion of the application of biological markers to inform behavioral based-research.
• Projects that propose the establishment of new large subject cohorts for clinical/population studies.

Background

When the TREC initiative was first conceptualized in 2004, obesity and overweight occurred in over two-thirds of the adult United States (U.S.) population, and physical inactivity and poor diets were common. Since that time, weight gain, overweight and obesity rates have stabilized for some adults but continue to rise for children in the U.S. At the same time, levels of physical activity have decreased. Racial and ethnic differences in obesity rates remain, with the highest rates in non-Hispanic black men and women. An estimated 17% of children and adolescents 2-19 years of age are overweight according to the 2003-2004 NHANES. Among children 6 to 11 years of age, the percentage of those considered overweight increased from 4.2% to 18.8% (a 34.8% increase) between 1963-1965 and 2003 2004. Populations at high risk for developing obesity continue to be children and specific racial and ethnic groups. The costs of obesity are high in the U.S. According to the U.S. Centers for Disease Control and Prevention, medical costs of obesity in the U.S. were estimated at more than $92 billion in 2002, and the total treatment cost for obesity and ancillary chronic diseases is anticipated to top $586 billion in 2009.

Obesity due to unhealthy lifestyle (e.g., poor diet, sedentary behavior) has an adverse public health impact, is associated with shortened life expectancy similar in scope to that associated with tobacco use, and is perhaps the most important morbidity and mortality risk factor among non-smokers. Recent reviews and meta-analyses provide strong evidence from a number of research designs that overweight/obesity and fat distribution are associated with risk for many cancers. Similar evidence exists that increased physical activity is associated with a reduced risk of a number of cancers. The evidence is extensive for major cancers and expanding for more rare cancers that healthy weight, physical activity, and some characteristics of diet are associated with beneficial changes in a number of outcomes for cancer survivors, including quality of life, comorbid conditions, lymphedema, and, now emerging, survival. Basic science and small randomized controlled trials among both high-risk populations and cancer survivors in the areas of diet, physical activity, and intentional weight loss indicate that these health behaviors result in beneficial changes in a number of mechanisms and pathways that are thought to influence risk and prognosis. Further, for a number of cancers, evidence suggests that a combination of physical activity, beneficial diet, and healthy weight is associated with greater benefits than one of these behaviors or outcomes alone. The synergistic relationship between genes, behavior, and the environment continue to come to light, which necessitates our further understanding of these complex relationships.

The relationship between overweight/obesity, physical activity, and sedentary lifestyle and cancer risk are complex. Obesity may increase cancer risk by several mechanisms. For example, increased estrogens and testosterone levels increase risk of breast and endometrial cancers. Hyperinsulinemia and insulin resistance promote chronic inflammation and depressed immune function, leading to increased risks of colon, breast, and pancreatic cancers.

Evaluation of biomarkers has enabled investigators to assess the biological factors thought to be involved in the causal pathway between exposure and carcinogenesis. The proposed biomarkers for the observed associations among physical activity, overweight/obesity, and cancer have focused upon sex steroid hormones (estrogens/androgens). Additional biomarkers under investigation include hyperinsulinemia and insulin resistance, other metabolic hormones (i.e., leptin, adipokines), increased inflammation (i.e., prostaglandin, C-reactive protein), depressed immune function (i.e., natural killer cells, leukocytes, T helper cells) and oxidative stress. Physical activity, diet, and energy balance potentially affect all of these biomarkers.

Evidence continues to accumulate that increased physical activity can exert cancer-preventive effects. Exercise may alter tumor initiation events by modifying carcinogen activation, specifically by enhancing the cytochrome P450 system and enhancing selective enzymes in the carcinogenic detoxification pathway, including but not limited to, glutathione-S-transferases. Exercise may reduce oxidative damage by increasing a variety of anti-oxidative enzymes, enhancing DNA repair systems, and improving intracellular protein repair systems. It may exert a cancer protective effect by dampening the processes involved in the promotion and progression stages of carcinogenesis.

Considering the difficulty in reversing obesity and that obesity has been related to the development and course of many cancers, research on obesity prevention and healthy weight maintenance is sorely needed. As noted, children may be particularly at risk, as the obesity rate among children has steadily risen and evidence suggests that a majority of overweight children will continue to be obese in adulthood. Similarly, weight gain among survivors of many cancers is common and is associated with poor prognosis. Among high-risk populations for obesity (e.g., non-Hispanic blacks), these populations also experience greater morbidity rates from cancers of the breast and other cancers for which obesity, lack of physical activity, and poor diet are risk factors. Investigators have focused on the etiologic factors in the development of obesity and youth with special emphasis on ethnic differences during critical periods of adolescent growth. Available evidence suggests that factors at the biological, individual, and social-contextual and environmental levels may all play a role in obesity development, and as such, research is needed that furthers our understanding of mechanisms operating at each level as well as research paradigms that consider a multi-level approach, or a systems approach, to obesity prevention.

Obesity links with diet and physical activity are established, but current research is exploring more complex relationships that have come to light. In the early 2000s, research expanded rapidly on the adverse effect of inadequate sleep and sleep habits on obesity, hyperinsulinemia, hypertension, and a number of other chronic diseases. Limited evidence at that time suggested that inadequate sleep might have adverse effects on cancer outcomes. For example, sleep and the disruption of associated circadian patterns of hormones, such as cortisol and melatonin, has pervasive effects on the body, ranging from fatigue and depression, to increases in the rate of cancer progression and risk of cancer incidence. There is evidence that abnormal circadian clock gene expression is associated with cancer (i.e., breast, ovarian). Loss of normal circadian variation in cortisol predicts earlier mortality among metastatic breast cancer patients, independent of other known risk factors including estrogen/progesterone receptor status, age at diagnosis, and disease-free survival. Therefore, research on the influence of sleep, or lack thereof, on obesity, health habits, and cancer was a novel aspect of the first TREC initiative.

Finally, various research efforts begin to integrate diverse aspects, including those related to health services, economics, urban planning, geography, informatics, and communications. This integration is expected to facilitate progress in identifying effective population-level interventions to prevent obesity among high-risk populations at local, state, and federal levels. The results of such studies may inform obesity-related policymaking and promote critical policy changes counteracting obesity-promoting factors.

References to the issues discussed above are available at http://cancercontrol.cancer.gov/trec/.

In summary, the research that has resulted from the initial TREC initiative contributes to the understanding of energy balance at the molecular, cellular, organismal, and population levels as it relates to cancer prevention. The continuation of the TREC program is expected to accelerate research in promising directions and have a greater impact. As in the first TREC initiative, the reissued program continues to emphasize the collaboration across diverse disciplines: behavior science, physiology and metabolism, sociology, communications, geography, psychology, kinesiology, nutrition, biostatistics, biochemistry, molecular biology along with other diverse disciplines.

Specific Research Objectives and Scope of Applications for TREC Research Centers

Overall goals for TREC Research Centers:

Research programs of TREC Research Centers (to be proposed in response to this FOA) are expected to build bridges across various disciplines, and will require strong leadership, insight, and capacity to bring diverse teams together to contribute to the understanding of energetics at the molecular, cellular, organismal, and population levels as it relates to cancer prevention and control. The efforts of individual Research Centers will be integrated and facilitated by TREC Coordinating Center (to be funded as a result of a companion FOA http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-10-501.html).

TREC Research Center applicants must address the following research objectives:

a) Enhance knowledge of the current mechanisms, from cellular, animal or human models to genetics and genomics, underlying the association between energy balance and carcinogenesis across a range of cancer-relevant areas from causation to prevention throughout the human life cycle.

b) Explore and integrate the etiology of obesity behavior and relevant health behavior theories, with broad population impact at the social-environmental and policy levels for prevention and control of obesity, focusing on children, groups at high risk for obesity, and cancer survivors.

Types of research and experimental approaches that should be included to achieve the objectives

1. Foster a transdisciplinary approach to the research model.

It is important that applicants do not simply propose a collection of independent research projects that are loosely related. Each individual research project is expected to be systematically related to other projects and to the administrative core infrastructure.

2. Propose research projects to strengthen the understanding of how obesity affects cancer prevention and control, especially in high-risk populations.

In the context of examining mechanisms by which obesity, physical inactivity or poor diet may influence cancer outcomes, the proposed TREC Research Centers should focus their research on individuals at high risk of cancer, including cancer survivors. In the context of research exploring factors that influence the adoption of health behaviors relevant to the prevention of obesity, applicants may elect to focus on these groups as well as groups at high risk of developing obesity.

3. Propose innovative research projects to explore the relationship between energetics and carcinogenesis.

Apply and expand current mechanisms underlying the association between energetics and carcinogenesis. Proposed research topics are expected to span a range of cancer-relevant areas from causation to prevention. Approaches may vary from cellular, animal, or human models to genetics and genomics.

4. Propose innovative and relevant health behavior theory research projects to explore the relationship between obesity behavior and cancer.

Develop effective and innovative research to explore the etiology of obesity behavior, or relevant health behavior theory, with broad population impact at the social-environmental and policy levels for prevention of obesity, focusing on children, high-risk population groups, and cancer survivors. Efforts to test, refine, and integrate theories related to energy balance should be made when appropriate.

5. Integrate central resources with technical cores.

All TREC Research Centers will work collaboratively with the TREC Coordination Center and NCI to establish virtual cores and centralized resource centers that support the funded research and scientific needs across the initiative.

Specific areas of research that may be appropriate as relevant projects include, but are not limited to, the following examples

Energy Balance and Carcinogenesis throughout the Human Life Cycle

• Exploring energy balance and carcinogenesis throughout the life cycle (that involves obesity, exercise physiology, nutrition, genetics, genomics, or molecular carcinogenesis) to continue accelerated progress towards understanding mechanisms linking energy balance and carcinogenesis.
• Preventative and therapeutic approaches with translational potential to reduce cancer incidence in obese populations and relevance to cancer survivorship.

Ecological Models of Human Health Behavior

• Research that advances behavioral theory, intervention, and policy to address the prevention and control of obesity among cancer survivors and groups at high risk for obesity across the life course.
• Characterization at the individual level of the basic affective, cognitive, and physiological mechanisms that may underpin behavior change theory and interventions targeting diet, physical activity, and sedentary behavior.
• Mechanistic studies of behavior change that integrates emotional and decision-making processes and link laboratory and field studies.
• At the larger social ecological level, research that not only explores but attempts to integrate the interrelationships between environmental, social, cultural, and biological influences on obesity-related health behavior.

Social and Cultural Determinants of Human Behavior

• Characterization of the differences in energy balance among different racial and ethnic groups throughout the life course to understand better the complexity associated with developing overweight and obesity (for example, how inequities in the neighborhood and community environment contribute to disparities in energy balance and how these inequities may influence biology and behavior over the life course).
• Exploring the association and relevance of cultural factors and the acculturation process on physical activity and obesogenic behaviors (for example, transdisciplinary collaboration between biologists, epidemiologists, and behavioral scientists to further understand the causes and consequences of disparities in energy balance-related health behaviors in order to develop appropriate interventions).

Methodologies

• Utilizing recent advances in psychometric and statistical methods, technologies for coding self-report and objective measures of activity, and new biological markers, research opportunities exist to assess current state of the art methodologies in dietary, physical activity and anthropometric assessment, along with methods of assessing sedentary behavior and its impact on obesity and cancer. Studies that integrate data obtained from devices capturing emotional and decision-making processes in both laboratory and field study settings are especially needed.
• Evaluate how state of the art methodologies can be utilized in assessment of diet, physical activity, and body composition in different population and age groups. For example, research that builds upon and takes advantage of methodological advances (e.g., real-time data capture, neuroimaging, behavioral genetics, and ambulatory physiological assessments) in obesity-related research is particularly encouraged.

Synergistic Relationships among Genes, Behavior, Environment and Cancer Risk in Humans

• Evaluate how genes can determine obesity phenotypes by regulating energy expenditure, macronutrient intakes, and response to dietary and exercise regimens. For example, are specific macronutrient compositions or an exercise regimen more effective for weight loss in some persons depending upon their genotype?
• Research is needed to understand the genetic contributions to inter-individual differences in response to changes in energy balance in order to elucidate pathways through which obesity is modulated.
• Data on gene-behavior interactions are needed to help improve psychosocial theories and inform behavioral change interventions focused on obesity prevention. Transdisciplinary teams focused on gene-diet and gene-physical activity interactions aimed at preventing childhood and adulthood obesity are encouraged.

Impact of Public Policies

• Public policy-relevant studies include those that assess the impact of the environment at the community-level (e.g., availability of supermarkets, multi-use trails, and parks and recreation facilities) and the macro-level (e.g., media, food supply, healthcare, federal regulations) on individual dietary and physical activity behavior. This research could include naturalistic studies that evaluate federal, state, local, or organizational policies; economic studies that assess and evaluate environmental changes and their effects on energy balance behavior, (such as benefit-cost and cost-effectiveness analyses and research on the effect of subsidies for healthy foods and price on dietary behavior); as well as other such types of studies in the policy area.

Required Structure and Main Components of the TREC Research Centers

All TREC applicants must address the following main aspects (for details, see Section IV. Content and Form of Application Submission):

1. Overall Research Focus. Each proposed Center must be focused on a well articulated, coherent transdisciplinary research program comprising 3-5 defined research projects. The ability of applicants to articulate a coherent transdisciplinary research agenda that will accelerate progress towards understanding the links between energy balance and obesity, and the impact on cancer risk is a key evaluation criterion for this FOA.

2. Research Team. Each team must represent appropriately diversified backgrounds as needed for the scientific profile of the proposed Center. The team must provide full expertise necessary to complete the proposed research projects. Applicants are encouraged to include the breadth of expertise relevant to support the science. For example, teams should include basic and clinical scientists, epidemiologists, and experts in genetics, urban planning, transportation, sociology, health behavior, and psychology, as appropriate, even if such an individual may not have a specific record in cancer research. The team members must be willing and able to work jointly in and across the required/represented disciplines (i.e., in a transdisciplinary fashion) to ensure the successful conduct and completion of the proposed studies.

3. Leadership and Organization of the Proposed Research Center (Administrative Core). Applicants are encouraged to consider multiple Program Directors/Principal Investigators (PDs/PIs). However, if this option is used, a well-thought out leadership structure should be described, in which one PD/PI is identified as lead PD/PI for the overall Center. Each TREC will be a virtual center, i.e., its laboratories and/or research facilities may be physically located at various institutions and geographical sites. Participating institutions/organizations may be a mix of academic, other non-profit, and/or for-profit entities, as needed. The NCI recommends limiting the number of separate institutions involved as participants in one TREC Research Center to no more than three entities. To facilitate effort coordination within the proposed center and across the TREC Network, each individual Center must organize an Administrative Core as a shared resource.

4. Research Program. A well-developed research program design should include up to three of the specific Research Areas or Themes provided as examples above to form the core of the application. Each area or theme should be integrated with the other components. Thus, each applicant team proposing a TREC Research Center needs to demonstrate in-depth expertise in all relevant scientific aspects of the proposed research activities. Applicants must clearly describe in their applications how the newly developed projects will address significant existing problems of obesity, energetics and cancer, and complement, but not duplicate, existing work. Emphasis should be placed on demonstrating why the proposed concepts and approaches are revolutionary within the context of related research and how the expected product/results will overcome currently existing barriers and knowledge gaps. The proposed research program should have the following attributes.

Individual Research Projects. A set of three to five individual (albeit connected) research projects must be proposed. Preferably, these projects should be highly interactive and synergistic to represent an integrated research program and supporting an overarching prospective goal to address cancer.

Shared Resources (Cores). An Administrative Core, plus a Bioinformatics Core, is recommended as a component of all TREC Research Centers to facilitate data sharing and results dissemination. Other Shared Research Resources Cores may also be proposed as appropriate. Total number of Shared Resources Cores supporting Research Projects should not exceed three (not counting the Administrative Core). In addition, core resources should include the centralized collection and provision of TREC-developed measures and data (e.g., behavioral, anthropometric, biomarkers) to the TREC Coordination Center. Tasks include the coordination of data collection and analyses of common measures, and archiving of data or biological specimens (as appropriate) for future data sharing.

5. Education/Training and Outreach Programs. A training program dedicated to the development of a new cadre of transdisciplinary scientists and a program to disseminate research findings and data sharing are mandatory components for all TREC Research Centers.

6. Developmental Pilot Projects and Cross TREC Projects. Each TREC Research Center application must include plans for the development of Pilot Projects (that can be conducted within the TREC Research Centers), cross-TREC projects (involving collaborations with other TREC awardees), or other cross-TREC activities that may involve outside organizations. Cross-TREC projects are expected to capitalize on unique strengths and expertise available to TREC.

7. Dissemination Plan: Connect to, and Become a Resource for, the Larger Community.

Applicants should propose to and awardees must actively synthesize and disseminate results to the larger medical, public health, policy, and cancer research community. TREC investigators are encouraged to link with other relevant research initiatives or clinical trial groups outside of TREC as applicable. These linkages can be supported in the form of workshops, conferences, publications, and transdisciplinary research collaborations.

Governance of the TREC Network

The TREC Network (i.e., the TREC Research Centers and Coordinating Center) will be governed by the TREC Steering Committee. The TREC Steering Committee (working with the Sub-committee of Experts) will oversee and coordinate the activities of all TREC awardees.

Steering Committee will also be responsible for the identification of appropriate opportunities for transdisciplinary research and selection of specific projects for development. This aspect pertains to both developmental Pilot Projects and cross-TREC Pilot Projects defined above.

Details on the composition and functions of TREC Steering Committee are provided in Section VI.2.A.3, Terms and Conditions of Cooperative Agreement Collaborative Responsibilities.

Self-evaluation of TRAC Awardees and External Evaluation of the Program

As the efficiency of the funded research is an increasing priority for NCI, TREC awardees will be expected to participate in TREC self-evaluation activities as well as cooperate with an external evaluation process.

The purpose of self-evaluation activities (to be coordinated by the TREC Coordination Center) is to monitor the performance and provide feedback to individual TREC awardees. It is expected that such feedback will facilitate optimization of various aspects and corrective actions if needed.

Outcomes to be assessed will include peer-reviewed publications, educational and outreach programs, and effectiveness of a collaborative research development model. This component includes evaluating the quality and innovation of the research conducted at the TREC Research Centers and Coordinating Center, as well as assessing critical antecedents and intermediate determinants of the overall success. Aspects to be assessed include development of infrastructure and research capacity, career development, efficiency of resource and data sharing arrangements within and among TREC Research Centers. The overall focus is on identifying and implementing optimal ways to conduct highly collaborative transdisciplinary nature research and, thereby, increase the likelihood for making significant scientific advances.

The external evaluation will be coordinated by involved NCI program staff members. This evaluation will be largely based on information available through the TREC self-evaluation process but with the emphasis on assessing the overall progress in achieving the scientific goals of the entire TREC Program.

Other Related Funding Opportunities

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 will use the NIH U54 Cooperative Agreement award mechanism.
The Project Director(s)/Principal Investigator(s) (PD/PI or 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 will use a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains 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 Principal Investigator, 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 support for up to six projects awarded as a result of this announcement is $15M for fiscal year 2010, and $75M over 5 years.

Applicants may request a project period up to 5 years, and a budget (in direct cost) up to $1.5M per year.

Future year amounts will depend on annual appropriations.

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 IC(s) 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 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);
• State Governments;
• Eligible Agencies of the Federal Government; and
• Units of Local Governments.

Foreign institutions may not submit applications for this FOA, but are allowed to participate under consortium/subcontractual arrangements on applications submitted by eligible Domestic (U.S.) 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.

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a team science approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans, policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations, and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills, and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

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. Renewal applications are permitted in response to this FOA.

Number of Applications. Applicants may submit more than one TREC U54 application, provided each application is scientifically distinct and led by an separate team of scientists (e.g., with different PDs/PIs and other key personnel).

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 most 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 standard 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.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PD/PIs are proposed, use the Face Page-Continued page to provide Items 3a 3h for all PD/PIs. NIH requires one PD/PI be designated as the contact PD/PI for all communications between the PD/PIs and the agency. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PD/PIs, but has no special roles or responsibilities within the project team beyond those mentioned above. The contact PD/PI may be changed during the project period. The contact PD/PI should be listed in Block 3 of Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page 1-Continued. When inserting the name of the PD/PI in the header of each application page, use the name of the Contact PD/PI, et. al. The contact PD/PI must be from the applicant organization if PD/PIs are from more than one institution.

All individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system (other roles such as SO or IAR will not give the PD/PI the appropriate access to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the Research Plan, entitled Multiple PD/PI Leadership Plan must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

Additional information is available in the PHS 398 grant application instructions.

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: January 26, 2010
Application Receipt Date: February 26, 2010
Peer Review Date: May/June 2010
Council Review Date: August 2010
Earliest Anticipated Start Date: September 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/PI (or PDs/PIs);
• 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 IC 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:

Yvonne F. Grant
Behavioral Research Program
Division of Cancer Control and Population Sciences
National Cancer Institute
6130 Executive Boulevard, MSC 7335
Executive Plaza North, Room 4056
Bethesda, Maryland 20892-7335 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
(301) 435-2838
(301) 435-7547
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 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; 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 PD/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

TREC Research Center (U54) applicants must demonstrate in the application their ability to meet:

• Research Objectives defined in Section I of the FOA;
• Data sharing requirements as outlined in this Section IV. 6. Other Submission Requirements (see below); and
• All investigator responsibilities described in Section VI.2.A Cooperative Agreement Terms and Conditions of Award.

For the TREC Research Center applications submitted in response to this FOA, the standard PHS 398 Research instructions for application preparation are altered as follows:

Table of Contents (PHS 398 Form Page 3): Modify Form Page 3 of the PHS 398 to replace standard sub-sections of Section 3 Research Strategy of the PHS 398 Research Plan with the following new sub-sections A-F:

A. Overview of the Proposed TREC and Its Area of Focus

B. Research Team, Center Organization and Infrastructure (Administrative Core)

C. Research Projects

D. Shared Research Support Resources (Cores)

E. Education/Training and Outreach Core

F. Developmental Pilot Projects and Cross-TREC Pilot Projects (Developmental Core)

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

Core resources should be budgeted to include centralized data collection and archive to the TREC Coordination Center.

Use additional Form Pages 4 and 5 to provide detailed separate budget information (first year and cumulative budgets for the entire project period) for the following individual application components:

• Budget pages for Administrative Core;
• Budget pages for separately for each proposed Research Project;
• Budget pages for separately for each proposed Research-Support Resource (Core);
• Budget pages for Education/Training and Outreach Core; and
• Budget pages for Developmental Core.

RESEARCH PLAN: The standard PHS398 Research Plan is altered as follows:

• Standard sub-sections of Section 3. Research Strategy of the PHS 398 Research Plan are replaced by the new sub-sections A-F (corresponding to individual application components, see details below); and
• The PHS 398 standard page limit for Research Strategy is replaced by individual limits indicated below for the new sub-sections A-F.

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

A. Overview of the Proposed TREC Research Center and Its Area of Focus (up to 12 pages)

Present the overall vision for the proposed TREC including the following segments:

• The proposed overarching organizing framework for the Center. The Center area of focus must be selected from the three thematic areas defined in Section I.1 Research Objectives.

• Outline the proposed research program with emphasis on project integration and goals. Describe how the Center and the team will collectively support the development of a transdisciplinary approach to address the link between obesity and cancer and desirable public health impact.

• Outline the overall vision (beyond the TREC award) for translation and future application.

• For renewal applications only, describe progress of TREC Research Center to date.

B. Research Team and Research Capabilities, Center Organization and Infrastructure (Administrative Core) (up to 12 pages).

In this section, describe the following aspects of the proposed TREC.

• Research Team:
• Outline the major strength of the team and specific senior investigators in the context of the proposed area of focus; Characterize the relevant expertise of team members (e.g., epidemiology, nutrition, physical activity, endocrinology, psychology, sociology, urban planning, transportation, or medical and clinical oncology) and the advantages of their respective research environments (e.g., academic or research centers of public health);
• Outline how each of these investigator groups will be directly involved with and actively contribute to the Center projects (such a relationship is required for each proposed project, but does not need to be unique for each); and
• Indicate the effort distribution across all the participating institutions (number of distinct institutions that can be supported by the TREC award is expected to be limited, not to exceed three entities, i.e., institution submitting application plus up to two institutions participating on a subcontractual basis).

• Leadership and Center Organization:
• Describe the organization of the leadership structure and overall Center structure (provide respective organizational diagrams);Outline the responsibilities of multiple PDs/PIs [avoid duplication with the standard required item 14 Multiple PD/PI Leadership Plan (see below)]; and
• Describe the overall plans for the participation in TREC Steering Committee, TREC advisory committees, and cross-TREC activities.

• Administrative Core:
• Outline the organization and functioning of the Administrative Core;
• Outline plans for specific administrative activities of the TREC including, but not limited to, progress reports, site visits, travel for the PD/PI and team leaders to semiannual TREC scientific meetings, monthly meetings (when appropriate) and teleconferences, and participation in any coordinating and advisory sub-committees; and
• Describe institutional commitment, include any relationships to other affiliates, clinical or medical centers at the Center as appropriate.

Note: All TREC awardees will be expected to apply proper process management methods for planning, monitoring, and managing the workload over the award period and will be expected to share specific details of these aspects with NCI Program Staff members upon request.

C. Individual Research Projects (up to 12 pages per each Project).

Each application must include three, but not more than five, research projects closely pertinent to the research objectives (outlined in Section I of the FOA).

Describe each research project in sufficient detail to enable reviewers to judge its scientific merit.

The description must contain the following elements:

• A project title page containing project title, name of Project Leader, Project Summary, and a list of Key Personnel (listing calendar month effort for each individual);
• Research Plan to include the following items (analogous to standard sub-sections of Research Strategy section defined in the PHS 398 instructions):

a. Significance
b. Innovation
c. Preliminary Studies
d. Approach

D. Shared Resources (Cores) to Support Research Projects (up to 6 pages/Core)

Applicants may propose, as needed, appropriate shared technical resources, or Cores. These shared resources must not duplicate analogous NIH-funded resources already established in the applicant institutions (although supplemental funding to such existing resources may be requested).

No more than three Shared Resources Cores may be proposed to support Research Projects (in addition to the required Administrative Core).

For all proposed TREC Research Centers, it is recommended that, one Core is dedicated to bioinformatics and data sharing. Plans for such Bioinformatics Core must include timely sharing of data and their submission for centralized data collection at the Coordinating Center.

For each proposed Research Support Shared Resource Core include:

• A core title page containing Core title, name of Core Director, Core Summary, and a list of Key Personnel (listing calendar month effort for each individual);
• Brief description of the Core and its operations (indicate how the proposed core will facilitate the TREC research projects).
• For the Bioinformatics Core: Describe bioinformatics capabilities to support proposed projects and data sharing and the capacity to link with the TREC Coordination Center.

E. Education/Training and Outreach Core (up to 6 pages)

In this section, describe the following:

• Plans to create/expand local and remote modules for integrative training that may include graduate programs, fellowships, certifications, courses, and internal seminar series to develop transdisciplinary trainees that can tackle obesity and cancer-related research challenges.
• Mechanisms to exchange graduate and postdoctoral trainees, junior and senior investigators, as needed among participating TREC sites.
• Outreach activities (e.g., external seminar series and workshops) to disseminate information to cancer, obesity and behavioral sciences communities of TREC capabilities and results.

Note: a minimum of $50,000 in direct costs must be allocated to these activities in the budgetary request.

F. Developmental Pilot Projects, Cross-TREC Pilot Projects, and Other Cross-TREC Activities (Developmental Core, up to 6 pages)

Within the characteristics specified below, outline your vision on strategies and mechanisms for developing Pilot Projects and cross-TREC Projects and their evaluation/approval. (As specific Developmental Pilot Projects or cross-TREC Pilot Projects will be developed and selected post-award, no such specific projects are to be listed in the application).

• Briefly describe how the ideas for these projects should be solicited and prioritized. Summarize key scientific and translational capabilities, which the applicant TREC can provide to support such projects.
• Describe plans for outreach interactions to bring in expertise from outside of the individual TREC to enhance specific efforts.

Expected characteristics of Developmental Pilot Projects and cross-TREC Pilot Projects are as follows:

a) Developmental Pilot Projects. Each TREC applicant team must plan for developing Pilot Projects to be conducted within the Center. These projects are intended for the exploration of new ideas and emerging opportunities that may contribute to existing Center projects. A specific mechanism for the selection and approval of the Pilot Projects should be established by the leadership of the proposed TREC in consultation with Project and Core Leaders. In general, the Pilot Projects should be short term (8-12 months). Potentially, pilot projects should lead to larger research activities through seeking of separate funding in their later stages. All TREC applicants must allocate a minimum of $50,000 and a maximum of $150,000 in direct costs, for up to 2 Pilot Projects to start in funding year 02 through 05 (direct costs per project shall not exceed $75,000) Final approval for all Pilot Projects will be the responsibility of the TREC Steering Committee.

b) Cross-TREC Pilot Projects. Each TREC applicant team must plan for the participation in Cross-TREC Pilot Projects involving collaborations with other TREC awardees. TREC awardees will take part in formulating overarching projects involving more than one center, through participation in the TREC Steering Committee and the Sub-committee of Experts. Final approval for cross-TREC Pilot Projects is the responsibility of the TREC Steering Committee. All TREC applicants must allocate a minimum of $100,000 in direct costs, but shall not exceed $150,000 in direct costs per project for up to 3 cross-TREC projects starting in funding year 02 05.

All pilot projects shall be designed and scheduled to start at the beginning of the funding year.

c) Other cross-TREC Activities.

Describe your vision for any other activities that could have a synergistic effect on the outcomes of the TREC Program. In this section, also describe how the proposed TREC Research Center may interact with other non-TREC entities to increase the impact of the TREC program. Such interactions may involve, for example, other research organizations, public or non-profit organizations, relevant clinical centers or care networks, research programs/networks or public domain scientific data and information resources.

OTHER REQUIREMENTS

Awardees must agree to the award administration information detailed in Section VI.2.A, Cooperative Agreement Terms and Conditions of Award.

Site Visits and Annual TREC Scientific Meetings. Because of the complexity of the TREC, NIH/NCI program staff members will conduct at least one administrative site visit. TREC applicants must agree to participate in this process and should plan for one visit (with appropriate budget, including travel for collaborators and other necessary costs).

Applicants must plan appropriate travel funds for the PD(s)/PI(s) and team leaders to participate in the biannual TREC scientific meetings. They should also plan such funds for travel of key administrative staff, and of new/junior investigators of their institutions to these meetings.

Appendix Materials

All paper PHS 398 applications must provide appendix material on CD 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. 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: Investigators seeking $500,000 or more in direct costs in any year 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 at NIH Guide NOT-OD-07-088 and http://grants.nih.gov/grants/gwas/.

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

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

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.

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, or preventative interventions that drive this field?

Investigator(s). Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

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

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?

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

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.

(A) Review Criteria for the Overall TREC Research Center application

1) Overall Significance: Does the proposed TREC Research Center address an important cancer-obesity problem? Will the proposed TREC Research Center have a significant impact on the broader field of obesity and cancer research?

2) Overall Approach: How well does the proposed TREC Research Center take advantage of transdisciplinary approaches to promote and advance both discovery and application of innovative research to enhance our understanding of the mechanisms and behaviors underlying the association between energy balance, obesity and cancer across the cancer continuum, from causation to prevention and survival? Are the overall research goals, experimental design, methods, and capabilities sound and well developed? Are effective mechanisms in place to foster strong collaborative interactions and promote cross-fertilization among investigators (and participating institutions)?

3) Leadership and Research Teams: Is there adequate evidence for the managerial and collaborative capabilities of the proposed TREC Research Center’s leadership? How appropriate is the leadership structure of the proposed TREC Research Center in terms of: (a) the overall goals of the TREC Program; (b) the coordination of efforts of multiple institutions participating in a given TREC Research Center; and (c) the participation in and coordination of cross-TREC activities? Are the backgrounds, expertise, and commitments of the PD(s)/PI(s) and other key personnel sufficient for the proposed scope of activities and in line with the overall goals for the TREC Program? For applications involving multiple PDs/PIs, are their designated roles and responsibilities well defined, adequate, and appropriate for achieving the goals of the proposed TREC Research Center?

4) Organizational Framework and Integration: How well do all the proposed efforts take advantage of the infrastructure of the proposed TREC Research Center and existing resources of the participating institutions? Will the proposed Administrative Core effectively coordinate the efforts of the participating institutions and outside interactions at the cross-TREC level? Do they have capacity and budgeted resources to work with the TREC Coordination Center effectively? Is there evidence of sufficient institutional support for the proposed TREC Research Center across the participating institutions? Is there evidence of ongoing productive interactions among participating investigators/institutions? Will the Shared Resource Cores enhance the capabilities of individual research projects?

5. Progress (for renewal applications only). How significant is the contribution of the applicants currently funded TREC Research Center to scientific knowledge in the field of energy balance and cancer? How well have the applicants accomplished the specific objectives proposed in the original TREC Research Center application?

(B) Review Criteria for Individual Research Projects

1) Significance: Does this study address an important problem in energy balance, obesity and cancer? If the aims and milestones of the project are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods important to the field?

2) Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the project proposed appropriate to the experience and expertise of the project leader and other researchers and team members?

3) Innovation: Does the applicant provide the best innovative method to solve the problem stated in the study? Does the proposed project employ novel concepts, approaches, or methods? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies, health behavior theories, or technologies?

4) Approach: Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternatives, as appropriate?

5) Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments benefit from unique features of the scientific environment or employ useful collaborative arrangements?

C. Review Criteria for the Shared Resources Core(s)

How well the proposed cores fit in the overall goals for the proposed TREC Research Center without overlaps or unaddressed needs? Will the cores allow the proposed center, as a whole, to be responsive to the technical and scientific challenges that each of the individual projects may face? Are the functions of the cores appropriately described? How will the shared resources help the center meet requirements for the scientific research objectives and scope?

D. Review Criteria for Education/Training and Outreach Core

How appropriate and balanced are the proposed training and education activities in the context of the specific research goals proposed? Is the Education/Training Program well justified, and does it describe a program that will successfully train investigators capable of establishing independent multi- /transdisciplinary research on energetic and cancer? Are the proposed mentors experienced in the types of training proposed?

E. Review Criteria for Developmental Pilot Projects, Cross-TREC Pilot Projects and other Cross-TREC Activities (Developmental Core).

Are the plans to propose, identify, and frame pilot projects adequately described and appropriate for the goals of the TREC Research Center? Are the plans for the participation in the cross-TREC projects adequately described and appropriate for the goals of TREC Program? Are the conceptual frameworks adequately developed, well integrated, and appropriate? Does the applicant acknowledge potential problem areas? Does the applicant provide plans for future outreach and dissemination to a broader audience?

Additional Review Criteria

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 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 Agents 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).

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

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).

Selection Process

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
• Relevance to programmatic priorities

NIH considers the following in evaluating Center grant applications:

• The scientific and technical merit of the proposed program;
• The qualifications and experience of the center director and other key personnel;
• The statutory and program purposes to be accomplished;
• The extent to which the various components of the proposed program would be coordinated into one multi-disciplinary effort within the center;
• The extent to which the center's activities would be coordinated with similar efforts by other organizations;
• The administrative and managerial capability of the applicant; and
• Other factors which the awarding NCI considers appropriate in light of its particular statutory mission include the transdisciplinary approach to science.

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.

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 OMB administrative guidelines, 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. Principal Investigator Rights and Responsibilities

The PD(s)/PI(s) will have the primary authority and responsibility to define objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of studies conducted. The PD/PI(s) assume(s) responsibility and accountability to the awardee organization and to the NCI for the performance and proper conduct of TREC research in accordance with terms and conditions of the award.

The PD(s)/PI(s) of the TREC Research Centers will have the primary responsibility for:

• Determining directions and coordinating research approaches and procedures, and overseeing the analyses and interpretation of research data;
• Overseeing the timely release of data according to the approved plans;
• Coordinating and encouraging cross-TREC collaborations to cross-test novel projects proposed by fellow TREC investigators;
• Interacting with any advisory sub-committee(s);
• Participating in the semi-annual TREC PD/PI s scientific meetings, and monthly committee calls organized by the TREC Coordination Center, as relevant;
• Cooperating with the NCI representatives in the program evaluation process;
• Accepting and implementing all scientific, practical, and policy decisions approved by the TREC Steering Committee to the extent consistent with applicable grant regulations;
• Participating in the development and evaluation of Pilot Projects, cross-TREC Projects, and cross-TREC activities;
• Participating in the development of Working Groups that support discussions and exchange of the ideas across the TREC initiative;
• Providing information to the NCI Program Directors and NCI Project Scientists concerning progress by submitting annual progress reports in a standard format;
• Providing information to the NCI Program Directors and NCI Project Scientists concerning the TREC Steering Committee and scientific meetings and their outcomes; and
• Being prepared for administrative site visits by NCI staff.

Lead PD/PIs responsible for the TREC Research Centers will have, as appropriate, the following additional responsibilities:

• Participating in the development of TREC Steering Committee and other TREC advisory sub-committees as warranted;
• Serving on the TREC Steering Committee, i.e., one member of each awarded TREC (one of the PDs/PIs) is required to serve as member of the TREC Steering Committee (for details see Section II.A.3. Collaborative Responsibilities);
• Interacting with the Sub-committee of Experts and any other advisory committees; and
• Participating in the semiannual PDs/PIs scientific meetings, and monthly committee calls organized by the TREC Coordination Center.

All institutions/organizations participating in a given TREC Research Center will be expected to share with each other knowledge, data, research materials, and any other resources necessary and relevant to the TREC Research Center award.

All TREC awardees (Coordinating Center and TREC Research Centers) will be responsible for ensuring that Informatics and data sharing approaches used are appropriate to seek compatibility with caBIG.

Each TREC Research Center and the entire TREC program initiative will be subject to periodic self-evaluation (coordinated by TREC Coordinating Center) and external evaluation (coordinated by the NIH). TREC Research Center Awardees will be expected to participate in such evaluations.

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

A designated NCI Program Director, acting as a Project Scientist, will have substantial programmatic involvement that is above and beyond normal stewardship role in awards, as described below. The NCI Project Scientist may invite, as needed, additional NCI scientific staff as members with relevant expertise to have substantial involvement in the conduct of the TREC’s scientific activities.

All NCI staff members who may be involved in the scientific activities of TREC, including the Project Scientist, 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 interest.

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

Main NCI responsibilities to TREC awardees (both Research Centers and Coordinating Center) include:

• One NCI Project Scientist (possibly) having substantial programmatic involvement as the lead Scientific Program Director, and will be designated as NCI voting member on the TREC Steering Committee (for details see section 2.A.3. Collaborative Responsibilities);
• Assisting in avoiding unwarranted duplications of effort across TREC network;
• Helping coordinate collaborative research efforts that involve multiple Research Centers;
• Monitoring the operations of TREC Coordinating Center and Research Centers and making recommendations on overall project directions and allocations of project funds;
• Reviewing the progress of individual Research Centers and specific activities shared among the Research Centers and Coordinating Center;
• Participating in the development and evaluation of cross-TREC Projects;
• Participating in the semiannual PD/PI s meeting organized by the TREC Coordination Center and NCI;
• Participating as Collaborators to the TREC investigators in some shared activities, if appropriate;
• Assisting the TREC awardees as a liaison in stimulating their broader interactions with other NCI and NIH programs to disseminate results and outcomes from the TREC program and effectively leverage existing NIH/NCI resources and infrastructures; and
• Evaluating the adherence of TREC awardees to the approved data sharing plans and intellectual property plans.

The NCI reserves the right to adjust funding, withhold, suspend, or terminate the support to those TREC awardee institutions that are unable to meet the performance requirements set forth in these Terms and Conditions of Award, or significantly change the level of performance.

The NCI Staff members will coordinate an external evaluation of the TREC Program.

2.A.3. Collaborative Responsibilities

The TREC Steering Committee will serve as the main governing board for the TREC initiative.

The committee will consist of the following voting members:

• Two representatives of each TREC Research Center (the Center PDs/PIs or a lead PD/PI and a designated senior investigator) who will collectively have one vote;
• Two representatives of TREC Coordinating Center (the Center PDs/PIs or a lead PD/PI and a designated senior investigator) who will collectively have one vote; and
• Two NCI Project Scientists who will collectively have one vote for the NCI.

Additional NIH staff members may participate in Steering Committee meeting as non-voting members.

The TREC Steering Committee will meet two times per year (in person at the semiannual scientific PD/PI meetings). Two co-chairs of the TREC Steering Committee will be selected for every 12 months by the committee to coordinate its operation. The TREC Steering Committee co-chairs will meet with NCI Project Scientists members of TREC, one to two times per month by telephone conference.

In addition, the designated NCI Program Official will participate in the activities of the TREC Steering Committee as a non-voting member. Additional non-voting members to serve in an advisory capacity may be added to the TREC Steering Committee as needed by a decision of the existing voting committee members. These additional non-voting members may include other NCI and NIH Program Staff members and/or Program Staff members from other Federal agencies (e.g., Centers for Disease Control and Prevention).

The TREC Steering Committee will have primary responsibility for:

• Overseeing the overall organization of the TREC initiative and for reviewing its research goals;
• Developing the appropriate structure of Working Groups to promote the exchange of experiences, protocols, and ideas across the TREC;
• Establishing advisory committees and subcommittees, as necessary, to ensure the progress of the individual TREC as well as of the overall TREC initiative;
• Reviewing the potential of shared support infrastructure(s) at individual TREC Research Centers to serve the needs of other TREC Research Centers or the entire initiative;
• Developing (jointly with Working Groups) the TREC-wide requests for Pilot Projects and cross-TREC Pilot Projects, and conducting their evaluation and selection;
• Developing and recommending progress report formats for individual TREC pilot and cross-TREC projects.
• Ensuring that the TREC Research Projects and the Coordinating Center take advantage of existing NCI and NIH resources and programs;
• Making recommendation for re-directing or termination of TREC pilot projects that become unpromising or unproductive; and
• Scheduling semiannual PD/PI’s meeting at which all TREC investigators will present their scientific progress and future plans.
• Overseeing and coordinating the activities of TREC awardees towards compatibility of TREC informatics and data sharing with caBIG.

The TREC Steering Committee will establish a scientific advisory panel (a subcommittee) to serve the TREC Steering Committee and the TREC awardees.

The Advisory Panel Subcommittee will comprise scientific experts from outside the TREC initiative and will be charged with the following activities:

• Reviewing on a once-per-year schedule the overall progress of the TREC and making appropriate recommendations to strengthen activities in certain areas; and
• Developing and recommending to Steering Committee criteria for evaluation of pilot project proposals and the performance of the selected pilot projects.

TREC Steering Committee is also expected to form topic-specific working groups, which will be a resource of cross-TREC expertise. Representatives from the NCI organizational units (DCCPS, DCP, DCB), as well as other NIH institutes (e.g., NHLBI, NIDDK), or other Federal agencies (e.g., CDC) will participate in working groups as appropriate (but will not serve as chairs of these working groups).

Members of the TREC network (i.e., TREC Research Center awardees and TREC Coordinating Center awardee) will be required to accept and implement policies approved by the TREC 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 composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 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:

Dr. Linda Nebeling
Behavioral Research Program
Division of Cancer Control and Population Sciences
National Cancer Institute
6130 Executive Boulevard, MSC 7335
Executive Plaza North, Room 4056
Bethesda, MD 20892-7335 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 435-2841
FAX: (301) 435-7547
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:

Crystal Wolfrey
Team Leader, Biology and Population Sciences Section
Office of Grants Administration
National Cancer Institute
National Institutes of Health
6120 Executive Boulevard, EPS Suite 243
Bethesda, MD 20892-7150 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-8634
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); 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 IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule.

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-09-116.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.